“Black belt” S_Ni and S_Ni′: Deuterium labeling revealed an inherent preference of N- and C-metalated nitriles for S_Ni, rather than S_Ni′ displacement. The fundamental reactivity preferences are harnessed in a series of cyclizations to cis- and trans-decalins that install contiguous quaternary–tertiary and quaternary–quaternary stereocenters (see scheme).

Tantalizingly simple: The common organometallic starting material TaMe₃Cl₂ can be used for the catalytic CH functionalization reaction, hydroaminoalkylation. The substrate scope for this readily accessed compound includes unactivated terminal and internal alkenes, styrene derivatives, and both alkylaryl- and dialkyl secondary amines (see scheme).

Facet-selective growth: Regular ZnO/TiO₂ heterojunctions have been successfully synthesized using a facile hydrothermal technique (see figure). Due to the interfacial lattice matching, wurtzite ZnO can only grow on the eight {101} facets of the anatase TiO₂ single crystals, while the other two {001} facets are untouched. The as-prepared regular ZnO/TiO₂ heterojunctions exhibited enhanced photocatalytic generation of ^.OH radicals and enhanced photodegradation of methyl orange when irradiated with UV light.

The thermal and photochemical reactions of a newly synthesized complex, [Ru^II(TPA)(tpphz)]²⁺ (1; TPA=tris(2-pyridylmethyl)amine, tpphz=tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h: 2′′′,3′′′-j]phenazine), and its derivatives have been investigated. Heating a solution of complex 1 (closed form) and its derivatives in MeCN caused the partial dissociation of one pyridylmethyl moiety of the TPA ligand and the resulting vacant site on the Ru^II center was occupied by a molecule of MeCN from the solvent to give a dissociated complex, [Ru^II(η³-TPA)(tpphz)(MeCN)]²⁺ (1′, open form), and its derivatives, respectively, in quantitative yields. The thermal dissociation reactions were investigated on the basis of kinetics analysis, which indicated that the reactions proceeded through a seven-coordinate transition state. Although the backwards reaction was induced by photoirradiation of the MLCT absorption bands, the photoreaction of complex 1′ reached a photostationary state between complexes 1 and 1′ and, hence, the recovery of complex 1 from complex 1′ was 67 %. Upon protonation of complex 1 at the vacant site of the tpphz ligand, the efficiency of the photoinduced recovery of complex 1+H⁺ from complex 1′+H⁺ improved to 83 %. In contrast, dinuclear μ-tpphz complexes 2 and 3, which contained the Ru^II(TPA)(tpphz) unit and either a Ru^II(bpy)₂ or Pd^IICl₂ moiety on the other coordination edge of the tpphz ligand, exhibited 100 % photoconversion from their open forms into their closed forms (2′→2 and 3′→3). These results are the first examples of the complete photochromic structural change of a transition-metal complex, as represented by complete interconversion between its open and closed forms. Scrutinization by performing optical and electrochemical measurements allowed us to propose a rationale for how metal coordination at the vacant site of the tpphz ligand improves the efficiency of photoconversion from the open form into the closed form. It is essential to lower the energy level of the triplet metal-to-ligand charge-transfer excited state (³MLCT*) of the closed form relative to that of the triplet metal-centered excited state (³MC*) by metal coordination. This energy-level manipulation hinders the transition from the ³MLCT* state into the ³MC* state in the closed form to block the partial photodissociation of the TPA ligand.

Ru being served? Photochromic structural changes of Ru^II/TPA (TPA=tris(2-pyridylmethyl)amine) complexes that contain a diimine ligand are reported. Further metal coordination to the diimine ligand allows interconversion between its open/closed forms (see scheme).

The reactions of MCl₅ or MOCl₃ with imidazole-based pro-ligand L¹H, 3,5-tBu₂-2-OH-C₆H₂-(4,5-Ph₂-1H-)imidazole, or oxazole-based ligand L²H, 3,5-tBu₂-2-OH-C₆H₂(1H-phenanthro[9,10-d])oxazole, following work-up, afforded octahedral complexes [MX(L^1, 2)], where MX=NbCl₄ (L¹, 1 a; L², 2 a), [NbOCl₂(NCMe)] (L¹, 1 b; L², 2 b), TaCl₄ (L¹, 1 c; L², 2 c), or [TaOCl₂(NCMe)] (L¹, 1 d). The treatment of α-diimine ligand L³, (2,6-iPr₂C₆H₃NCH)₂, with [MCl₄(thf)₂] (M=Nb, Ta) afforded [MCl₄(L³)] (M=Nb, 3 a; Ta, 3 b). The reaction of [MCl₃(dme)] (dme=1,2-dimethoxyethane; M=Nb, Ta) with bis(imino)pyridine ligand L⁴, 2,6-[2,6-iPr₂C₆H₃N(Me)C]₂C₅H₃N, afforded known complexes of the type [MCl₃(L⁴)] (M=Nb, 4 a; Ta, 4 b), whereas the reaction of 2-acetyl-6-iminopyridine ligand L⁵, 2-[2,6-iPr₂C₆H₃N(Me)C]-6-Ac-C₅H₃N, with the niobium precursor afforded the coupled product [({2-Ac-6-(2,6-iPr₂C₆H₃N(Me)C)C₅H₃N}NbOCl₂)₂] (5). The reaction of MCl₅ with Schiff-base pro-ligands L⁶H–L¹⁰H, 3,5-(R¹)₂-2-OH-C₆H₂CHN(2-OR²-C₆H₄), (L⁶H: R¹=tBu, R²=Ph; L⁷H: R¹=tBu, R²=Me; L⁸H: R¹=Cl, R²=Ph; L⁹H: R¹=Cl, R²=Me; L¹⁰H: R¹=Cl, R²=CF₃) afforded [MCl₄(L^6–10)] complexes (M=Nb, 6 a–10 a; M=Ta, 6 b–9 b). In the case of compound 8 b, the corresponding zwitterion was also synthesised, namely [Ta⁻Cl₅(L⁸H)⁺]⋅MeCN (8 c). Unexpectedly, the reaction of L⁷H with TaCl₅ at reflux in toluene led to the removal of the methyl group and the formation of trichloride 7 c [TaCl₃(L^7-Me)]; conducting the reaction at room temperature led to the formation of the expected methoxy compound (7 b). Upon activation with methylaluminoxane (MAO), these complexes displayed poor activities for the homogeneous polymerisation of ethylene. However, the use of chloroalkylaluminium reagents, such as dimethylaluminium chloride (DMAC) and methylaluminium dichloride (MADC), as co-catalysts in the presence of the reactivator ethyl trichloroacetate (ETA) generated thermally stable catalysts with, in the case of niobium, catalytic activities that were two orders of magnitude higher than those previously observed. The effects of steric hindrance and electronic configuration on the polymerisation activity of these tantalum and niobium pre-catalysts were investigated. Spectroscopic studies (¹H NMR, ¹³C NMR and ¹H¹H and ¹H¹³C correlations) on the reactions of compounds 4 a/4 b with either MAO(50) or AlMe₃/[CPh₃]⁺[B(C₆F₅)₄]⁻ were consistent with the formation of a diamagnetic cation of the form [L⁴AlMe₂]⁺ (MAO(50) is the product of the vacuum distillation of commercial MAO at +50 °C and contains only 1 mol % of Al in the form of free AlMe₃). In the presence of MAO, this cationic aluminium complex was not capable of initiating the ROMP (ring opening metathesis polymerisation) of norbornene, whereas the 4 a/4 b systems with MAO(50) were active. A parallel pressure reactor (PPR)-based homogeneous polymerisation screening by using pre-catalysts 1 b, 1 c, 2 a, 3 a and 6 a, in combination with MAO, revealed only moderate-to-good activities for the homo-polymerisation of ethylene and the co-polymerisation of ethylene/1-hexene. The molecular structures are reported for complexes 1 a–1 c, 2 b, 5, 6 a, 6 b, 7 a, 8 a and 8 c.

Ta very much: The combination of a niobium or tantalum pre-catalyst that contained an imine-based ligand set and a MeAlCl₂ (MADC) co-catalyst is capable, in the presence of ethyl trichloroacetate (ETA), of polymerising ethylene with activities in excess of 11 000 g mmol⁻¹ h⁻¹ bar⁻¹ for niobium and 20 000 g mmol⁻¹ h⁻¹ bar⁻¹ for tantalum. These systems produced essentially linear, high-molecular-weight polyethylene.

The stereospecificity of an enzymatic reaction depends on the way in which a substrate and its enantiomer bind to the active site. These binding modes cannot be easily predicted. We have studied the stereospecificity and stereoselectivity of the ketoreductase domain Tyl-KR1 of the tylactone polyketide synthase from Streptomyces fradiae by analysing the stereochemical outcome of the reduction of five different keto ester substrates. The absolute configuration of the Tyl-KR1 reduction products was determined by using vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. The conversion of only one of the tested substrates, 2-methyl-3-oxovaleric acid N-acetylcysteamine thioester, afforded the expected anti-(2R,3R) configuration of the α-methyl-β-hydroxyl ester product, representing the stereochemistry observed for the physiological polyketide product tylactone. For all other substrates, which were modified with respect to the type of ester and/or the chain length (C₄ instead of C₅), the opposite configuration (anti-(2S,3S)) was obtained with significant enantio- and diastereoselectivity. Inversion of both stereocentres suggests completely different binding modes invoked by only minor modifications of the substrate structure.

Substrate dependence: The stereospecificity of an enzymatic reduction depends on the way a substrate binds to the active site. By using vibrational circular dichroism, it was shown that the stereospecificity and stereoselectivity of the ketoreductase Tyl-KR1 from a polyketide synthase complex in Streptomyces fradiae are inverted for different surrogates of polyketide-like substrates (see figure).

The total synthesis of the pentacyclic tetrahydroisoquinoline alkaloid quinocarcin, which possesses intriguing structural and biological features, has been achieved through a gold(I)-catalyzed regioselective hydroamination reaction. It is noteworthy that the regioselectivity of the intramolecular hydroamination of an unsymmetrical alkyne could be completely switched through substrate control. Other key features of this synthesis include the highly stereoselective synthesis of 2,5-cis-pyrrolidine through the intramolecular amination of the bromoallene and the Lewis acid mediated ring opening of dihydrobenzofuran.

Golden(I): A convergent asymmetric total synthesis of quinocarcin employed Sonogashira and Au-catalyzed hydroamination reactions (see scheme). The regioselectivity of the intramolecular hydroamination of an unsymmetrical alkyne was switched by substrate control.

1,3-Dichloro-2-nitro-2-azapropane is an excellent precursor to dense energetic functionalized dipyrazolyl-N-nitromethanamines. This new family of energetic compounds was fully characterized by using ¹H, ¹³C, and ¹⁵N NMR and IR spectroscopy, differential scanning calorimetry, elemental analysis, and impact sensitivity tests. Additionally, single-crystal X-ray structuring was done for 3 and 5⋅CH₃CN, which gave insight into structural characteristics. The experimentally determined densities of 2–9 fall between 1.69 and 1.90 g cm⁻³. Heats of formation and detonation properties were calculated by using Gaussian 03 and EXPLO5 programs, respectively. The influence of different energetic moieties on the structural and energetic properties was established theoretically.

Energize your chemistry! 1,3-Dichloro-2-nitro-2-azapropane is the precursor to energetic dense functionalized dipyrazolyl-N-nitromethanamines (see figure). The new compounds exhibit high thermal stability, high performance, and moderate to low sensitivities.

We describe the coupling of anilines with aryl boronic acids, under ligand-, base-, and salt-free conditions at room temperature. This new reaction proceeds through the formation of an aryl palladium alkoxo complex, which allows the transmetalation step with aryl boronic acids without any external base. Importantly, this sustainable procedure generates only environmentally friendly byproducts such as tBuOH, H₂O, N₂, and B(OH)₃. The reaction mechanism has been deeply investigated through experimental and theoretical studies.

Eco-couple: The cross-coupling of anilines with aryl boronic acids has been achieved under ligand-, base-, and salt-free conditions at room temperature (see scheme). The reaction mechanism, investigated through experimental and theoretical studies, proceeds through the formation of an aryl palladium alkoxo complex, which enables the transmetalation step without any external base, and gives only environmentally friendly byproducts.

The development of molecular frameworks derived from binuclear platinum(II) aromatic Schiff base (salphen) complexes and their supramolecular chemistry have been undertaken. A series of axially rotating (Pt-salphen)₂ luminophores, tethered in a cofacial manner by a rigid linker (xanthene, 1; dibenzofuran, 2; biphenylene, 3), was synthesized in which the O(salphen) groups are potentially amenable for guest-binding. The molecular structures of 1 and 3 have been determined by X-ray crystallography, revealing intra- and intermolecular π-stacking interactions, as well as contrasting syn (1) and anti (3) configurations, for the (Pt-salphen)₂ moiety. All complexes are luminescent in solution at room temperature. Their photophysical and solvatochromic properties have been examined, and the emissions are assigned to mixed triplet O(p)/Pt(d)→π*(diimine) excited states. The red-shifted fluid emissions and lower quantum yields of 1 and 3, relative to 2, are ascribed to enhanced intramolecular π-stacking interactions. Photophysical changes and selective responses to metal ions (particularly Pb²⁺) have been investigated by using various spectroscopic methods and DFT calculations, and through comparative studies with control complexes. A plausible binding mechanism is proposed based on occupation of the O(salphen)-binding cavity, which induces perturbation of intramolecular π–π interactions, and hence the self-quenching and emission properties, of the (Pt-salphen)₂ unit.

To π or not to π? The ratiometric phosphorescent ion-selective responses of axially rotating binuclear assemblies have been investigated by using X-ray crystallography, DFT calculations, and various spectroscopic techniques to provide an insight into the binding mechanism (see figure). These results may carry important implications for stimuli-responsive luminescent host complexes that engage in intramolecular interactions.

Chasing the active impurity: In the validation of a screening hit it was discovered that a polymeric trace impurity was responsible for the biological activity. Such a side product can be formed with similar compounds. During the investigations it was discovered that the negatively charged macromolecule interacts very efficiently with the protein surface of E. coli RNAP via electrostatic interactions.

Two-in-one fluorescent compounds: Blending the strong emitter, diquinaldinato aluminum, and the good electron transporter, tetraphenyl silole, resulted in highly fluorescent compounds that are promising candidates for light-emitting devices without the need of dopants (see figure).

Molecular assemblies (MAs) of oligofurans and oligothiophenes were formed from solutions on various substrates. These films were obtained by alternating deposition of organic chromophores (oligofurans or oligothiophenes) and a palladium salt. These coordination-based MAs were characterized by UV/Vis spectroscopy, spectroscopic ellipsometry, atomic force microscopy (AFM), X-ray reflectivity (XRR), X-ray photoelectron spectroscopy (XPS), and electrochemistry. The MAs exhibit similar electrochemical behavior and their growth and structure are apparently not affected when different organic template layers are used. The density of the MAs is a function of the structure of the molecular component. The oligothiophene density is approximately 50 % higher than that observed for the oligofuran-based assemblies. The optical and electrochemical properties of the MAs scale linearly with their thickness. The UV/Vis data indicate that upon increasing the film thickness, there is no significant conjugation between the metal-separated organic chromophores. DFT calculations confirmed that the HOMO–LUMO gap of the surface-bound oligofuran and oligothiophene metal oligomers do not change significantly upon increasing their chain length. However, electrochemical measurements indicate that the susceptibility of the MAs towards oxidation is dependent on the number of chromophore units.

Coming to the surface: Surface-bound molecular assemblies (MA-1 to MA-3) were constructed by an iterative solution deposition approach. The formed MAs consist of either oligofuran or oligothiophene chromophores coordinated to a palladium salt.

A one-pot wonder: 1,2,3,4-Tetrahydroisoquinolines with a C4 stereocenter can be formed by using a one-pot multicomponent chiral-phosphoric-acid-catalyzed transformation of a mixture of oxetane-tethered benzaldehydes, amines, and the dimethyl ester derivative of the Hantzsch ester (see scheme). This transformation can be used to prepare the spermidine alkaloid, (+)-(8S,13R)-cyclocelabenzine.

The lithiation of N-tert-butoxycarbonyl (N-Boc)-1,2,3,4-tetrahydroisoquinoline was optimized by in situ IR (ReactIR) spectroscopy. Optimum conditions were found by using n-butyllithium in THF at −50 °C for less than 5 min. The intermediate organolithium was quenched with electrophiles to give 1-substituted 1,2,3,4-tetrahydroisoquinolines. Monitoring the lithiation by IR or NMR spectroscopy showed that one rotamer reacts quickly and the barrier to rotation of the Boc group was determined by variable-temperature NMR spectroscopy and found to be about 60.8 kJ mol⁻¹, equating to a half-life for rotation of approximately 30 s at −50 °C. The use of (−)-sparteine as a ligand led to low levels of enantioselectivity after electrophilic quenching and the “poor man’s Hoffmann test” indicated that the organolithium was configurationally unstable. The chemistry was applied to N-Boc-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and led to the efficient synthesis of the racemic alkaloids salsolidine, carnegine, norlaudanosine and laudanosine.

Spectroscopic optimization: Optimum conditions for the lithiation of tetrahydroisoquinolines were established by in situ IR and NMR spectroscopy. The use of n-butyllithium in THF at −50 °C for less than 5 min is preferable to the reaction at −78 °C. The organolithium was quenched with electrophiles to give 1-substituted tetrahydroisoquinoline products (see scheme).

We herein report detailed investigations into the interaction of Lewis acidic fluoroboranes, for example BF₂Pf (Pf=perfluorophenyl) and BF₂Ar^F (Ar^F=3,5-bis(trifluoromethyl)phenyl), with Lewis basic platinum complexes such as [Pt(PEt₃)₃] and [Pt(PCy₃)₂] (Cy=cyclohexyl). Two presumed Lewis adducts could be identified in solution and corresponding secondary products of these Lewis adducts were characterized in the solid state. Furthermore, the concept of frustrated Lewis pairs (FLP) was applied to the activation of ethene in the system [Pt(BPf₃)(CH₂CH₂)(dcpp)] (dcpp=1,3-bis(dicyclohexylphosphino)propane; Pf=perfluorophenyl). Finally, DFT calculations were performed to determine the interaction between the platinum-centered Lewis bases and the boron-centered Lewis acids. Additionally, several possible mechanisms for the oxidative addition of the boranes BF₃, BCl_3, and BF₂Ar^F to the model complex [Pt(PMe₃)₂] are presented.

Still elusive: Several attempts to yield the elusive, unsupported Lewis adduct between a Lewis basic transition-metal complex and a Lewis acidic borane are presented, including NMR spectroscopic characterization at low temperatures, isolation of secondary products and detailed DFT calculations (see figure).

In situ transformations of selenidostannate frameworks in ionic liquids (ILs) were initiated by treatment of the starting phase K₂[Sn₂Se₅] and the consecutive reaction products by means of temperature increase and/or amine addition. Along the reaction pathway, the framework dimensionalities of the five involved selenidostannate anions develop from 3D to 1D and back, both in top-down and bottom-up style. Addition of ethane-1,2-diamine (en) led to the reversion of the 2D→1D step from 2D-{[Sn₂₄Se₅₆]¹⁶⁻} to 1D-{[Sn₆Se₁₄]⁴⁻}. As rationalized by DFT investigations, the 2D anion is thermodynamically favored. Photoconductivity measurements reveal that all samples show Schottky contact behavior with absolute thresholds below 10 V. One of the samples exhibits conductive states within the energy range of visible photons.

New dimensions: Three selenidostannate phases yielded from complex transformation pathways in ionic liquids include (in part reversible) dimensionality changes of the anionic Sn/Se substructures (see figure). As rationalized by DFT investigations, the transformations are provoked by competing influences of temperature and amine addition (DMMP=2,6-dimethylmorpholine, en=ethane-1,2-diamine).

Three ferrocenyl-functionalized tripodal hexaurea anion receptors with ortho- (L²), meta- (L³), and para-phenylene (L⁴) bridges, which showed strong binding affinities toward sulfate ions, have been designed and synthesized. In particular, meta-phenylene-bridged ligand L³, owing to its trigonal bipyramidal structure, can encapsulate two SO₄²⁻ ions in its “inner” and “outer” tripodal clefts, respectively, as supported by their clearly distinct NMR resonances and by molecular modeling. The sulfate complex of ortho-ligand L², (TBA)₂[SO₄⊂L²]⋅2 H₂O (1), displays a caged tetrahedral structure with an encapsulated sulfate ion that is hydrogen bonded by the six urea groups of ligand L². CV studies showed two types of electrochemical response of the ferrocene/ferrocenium redox couple upon anion binding, that is, a shift of the wave and the appearance of a new peak. Quantitative binding data were obtained from the NMR and CV titrations.

The time capsule: Three ferrocenyl-functionalized tripodal hexaurea anion receptors were designed for sulfate recognition. Owing to its trigonal-bipyramidal shape, a meta-phenylene-bridged ligand can encapsulate two SO₄²⁻ ions in two distinct steps. CV studies showed two types of electrochemical response of the Fc/Fc⁺ redox couple upon anion binding, that is, a shift of the wave and the appearance of a new peak.

Suggesting novel disconnections: A powerful Ni-catalyzed cascade reaction involving cyclization followed by cross-coupling allows the formation of up to three alkyl–alkyl bonds in a single operation by using alkene-containing alkyl iodides and Grignard reagents (see scheme; acac=acetylacetonate; TMEDA=N,N′,N′-tetramethyl ethylenediamine). Mechanistic experimental and computational studies suggest a Ni^I–Ni^II–Ni^III catalytic cycle and the intermediacy of radicals.

Herein, we report a “threading followed by shrinking” approach for the synthesis of rotaxanes by using an “oxygen-deficient” macrocycle that contained two arylmethyl sulfone units and the dumbbell-shaped salt bis(3,5-dimethylbenzyl)ammonium tetrakis(3,5-trifluoromethylphenyl)borate as the host and guest components, respectively. The extrusion of SO₂ from both of the arylmethyl sulfone units of the macrocyclic component in the corresponding [2]pseudorotaxane resulted in a [2]rotaxane that was sufficiently stable to maintain its molecular integrity in CD₃SOCD₃ at 393 K for at least 5 h.

Shrink wrap: A “threading followed by shrinking” method, which was used to extrude both arylmethyl sulfone motifs from the macrocyclic components of dialkylammonium-ion-based [2]pseudorotaxanes, afforded robust [2]rotaxanes that were sufficiently stable to maintain their molecular integrity in CD₃SOCD₃ at 393 K for at least 5 h (see figure).

The development of novel Brønsted acids featuring the hexacoordinate phosphorus(V) anion [TRISPHAT]⁻ {[1]⁻=[P(1,2-O₂C₆Cl₄)₃]⁻} are reported. The title compound, H(OEt₂)₂[1], was synthesized from 1,2-(HO)₂C₆Cl₄ (3 equiv) and PCl₅ in the presence of diethyl ether. This compound was fully characterized by ¹H, ³¹P and ¹³C NMR spectroscopy, X-ray crystallography and elemental microanalysis. Dissolution of H(OEt₂)₂[1] in acetonitrile results in the slow precipitation of crystalline H(OEt₂)(NCMe)[1], which was characterized by X-ray diffraction; however, in CD₂Cl₂ solution the [TRISPHAT]⁻ anion protonated and ring-opened. The weighable, solid H(OEt₂)₂ [1] was found to be a competent initiator for the polymerization of n-butyl vinyl ether, α-methylstyrene, styrene and isoprene at a variety of temperatures and monomer-to-initiator ratios. At low temperatures, polymers with M_n>10⁵ were obtained for n-butyl vinyl ether and α-methylstyrene whereas slightly lower molecular weights were obtained with styrene and isoprene (10⁴<M_n<10⁵). The poly(α-methylstyrene) synthesized at −78 °C is syndiotactic-rich (ca. 87 % rr) whereas the polystyrene obtained at −50 °C is atactic. The polyisoprene obtained possessed all possible modes of enchainment as well as branched and/or cyclic structures that are often observed in polyisoprene.

Lining ′em up: Strong Brønsted acids, H(OEt₂)[1] and H(OEt₂)(NCMe)[1] ([1]⁻=[TRISPHAT]⁻=P(1,2-O₂C₆Cl₄)₃]), were prepared and characterized. It is shown that H(OEt₂)₂[1] is a very effective weighable single-component initiator for the cationic polymerization of vinyl ether, α-methylstyrene, styrene, and isoprene at reduced temperatures (<−50 °C) to afford moderate- to high-molecular weight polymers (see figure).

Although metal ion homeostasis in cells is often mediated through metallochaperones, there are opportunities for toxic metals to be sequestered through the existing transport apparatus. Proper trafficking of Cu^I in human cells is partially achieved through complexation by HAH1, the human metallochaperone responsible for copper delivery to the Wilson and Menkes ATPase located in the trans-Golgi apparatus. In addition to binding copper, HAH1 strongly complexes Hg^II, with the X-ray structure of this complex previously described. It is important to clarify the solution behavior of these systems and, therefore, the binding of Hg^II to HAH1 was probed over the pH range 7.5 to 9.4 using ¹⁹⁹Hg NMR, ^199mHg PAC and UV–visible spectroscopies. The metal-dependent protein association over this pH range was examined using analytical gel-filtration. It can be concluded that at pH 7.5, Hg^II is bound to a monomeric HAH1 as a two coordinate, linear complex (HgS₂), like the Hg^II–Atx1 X-ray structure (PDB ID: 1CC8). At pH 9.4, Hg^II promotes HAH1 association, leading to formation of HgS₃ and HgS₄ complexes, which are in exchange on the μs–ns time scale. Thus, structures that may represent central intermediates in the process of metal ion transfer, as well as their exchange kinetics have been characterized.

HAH1, the Hg^II carrier? Trafficking of Cu^I in human cells is achieved through complexation by the metallochaperone, HAH1. In addition, HAH1 strongly binds Hg^II; the solution behavior of Hg^II–HAH1 complexation (see figure) has remained obscure, but is elucidated in this work. We report structures which may represent central intermediates in the processing of Hg^II ion.

The design and preparation of an asymmetrically substituted and bulky phosphinine was achieved by introducing sterically demanding substituents into specific positions of a rigid phosphorus-heterocyclic framework. Compound 5 shows, at the same time, axial chirality and a sufficiently high energy barrier for internal rotation to prevent enantiomerization. Both enantiomers of 5 were isolated by means of chiral analytical HPLC, and their absolute configurations could be assigned by combining experimental data and DFT calculations. Despite its substitution pattern, 5 can still coordinate to transition-metal centers through the lone pair of electrons on the phosphorus atom. Rapid CH activation on the adjacent aryl substituent at the 2-position of the phosphorus heterocycle was achieved by using [{Cp*IrCl₂}₂] (Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) as a metal precursor. A racemic mixture of 5 was applied as a π-accepting low-coordinate phosphorus ligand in the Rh-catalyzed hydroformylation of trans-2-octene, which showed a clear preference for the formation of 2-methyloctanal.

Bulky phosphinines: An asymmetrically substituted, bulky, and atropisomeric phosphinine has been prepared and characterized (see figure). Rapid CH activation on the 2-aryl substituent of the phosphorus heterocycle was achieved with [{Cp*IrCl₂}₂] (Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) as a metal precursor. A racemic mixture of the phosphinine acted as a π-accepting low-coordinate phosphorus ligand in the Rh-catalyzed hydroformylation of 2-octene.

In this work it is shown that iron(III) and gold(I) triflimide efficiently catalyze the hydroaddition of a wide array of nucleophiles including water, alcohols, thiols, amines, alkynes, and alkenes to multiple CC bonds. The study of the catalytic activity and selectivity of iron(III), gold(I), and Brønsted triflimides has unveiled that iron(III) triflimide [Fe(NTf₂)₃] is a robust catalyst under heating conditions, whereas gold(I) triflimide, even stabilized by PPh₃, readily decomposes at 80 °C and releases triflimidic acid (HNTf₂) that can catalyze the corresponding reaction, as shown by in situ ¹⁹F, ¹⁵N, and ³¹P NMR spectroscopy. The results presented here demonstrate that each of the two catalyst types has weaknesses and strengths and complement each other. Iron(III) triflimide can act as a substitute of gold(I) triflimide as a catalyst for hydroaddition reactions to unsaturated carbon–carbon bonds.

Lewis and Brønsted catalysis: In this work it is shown that iron(III) catalyses as efficiently as gold(I) the hydroaddition of a wide array of nucleophiles including water, alcohols, thiols, amines, alkynes, and alkenes to multiple CC bonds (see scheme).

A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N⁺Me₃Br⁻) have been synthesized. The substituent effects on their reactivity with H₂O₂ and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron-withdrawing substituents, such as aromatic F, NO₂, or benzylic N⁺Me₃Br⁻, whereas electron-donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH₃ or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation.

Tunable quinone methide formation: Aromatic substituents and the benzylic leaving group strongly affect the H₂O₂-induced formation of quinone methides (QMs) from arylboronic esters (see scheme). The reactivity of arylboronic esters can be predictably adjusted by varying substituents.

The reactions of bis(borohydride) complexes [(RN)Mo(BH₄)₂(PMe₃)₂] (4: R=2,6-Me₂C₆H₃; 5: R=2,6-iPr₂C₆H₃) with hydrosilanes afford new silyl hydride derivatives [(RN)Mo(H)(SiR′₃)(PMe₃)₃] (3: R=Ar, R′₃=H₂Ph; 8: R=Ar′, R′₃=H₂Ph; 9: R=Ar, R′₃=(OEt)₃; 10: R=Ar, R′₃=HMePh). These compounds can also be conveniently prepared by reacting [(RN)Mo(H)(Cl)(PMe₃)₃] with one equivalent of LiBH₄ in the presence of a silane. Complex 3 undergoes intramolecular and intermolecular phosphine exchange, as well as exchange between the silyl ligand and the free silane. Kinetic and DFT studies show that the intermolecular phosphine exchange occurs through the predissociation of a PMe₃ group, which, surprisingly, is facilitated by the silane. The intramolecular exchange proceeds through a new non-Bailar-twist pathway. The silyl/silane exchange proceeds through an unusual Mo^VI intermediate, [(ArN)Mo(H)₂(SiH₂Ph)₂(PMe₃)₂] (19). Complex 3 was found to be the catalyst of a variety of hydrosilylation reactions of carbonyl compounds (aldehydes and ketones) and nitriles, as well as of silane alcoholysis. Stoichiometric mechanistic studies of the hydrosilylation of acetone, supported by DFT calculations, suggest the operation of an unexpected mechanism, in that the silyl ligand of compound 3 plays an unusual role as a spectator ligand. The addition of acetone to compound 3 leads to the formation of [trans-(ArN)Mo(OiPr)(SiH₂Ph)(PMe₃)₂] (18). This latter species does not undergo the elimination of a SiO group (which corresponds to the conventional Ojima′s mechanism of hydrosilylation). Rather, complex 18 undergoes unusual reversible β-CH activation of the isopropoxy ligand. In the hydrosilylation of benzaldehyde, the reaction proceeds through the formation of a new intermediate bis(benzaldehyde) adduct, [(ArN)Mo(η²-PhC(O)H)₂(PMe₃)], which reacts further with hydrosilane through a η¹-silane complex, as studied by DFT calculations.

Rule breakers: Silyl hydride complex [(ArN)Mo(H)(SiH₂Ph)(PMe₃)₃] undergoes a silane-assisted exchange of coordinated and free phosphines and catalyzes the hydrosilylation of carbonyl groups through an unexpected mechanism (see scheme), as studied by using DFT.

A remarkable solvent-controlled enantiodivergence is seen in the hydroquinidine 1,4-phthalazinediyl diether ((DHQD)₂PHAL)-catalyzed chlorocyclization of unsaturated carbamates. Eyring plot analyses of this previously unreported reaction are used to probe and compare the R- and S-selective pathways. In the CHCl₃/hexanes solvent system, the pro-R process shows a surprising increase in selectivity with increasing temperature. These studies point to a strongly solvent-dependent entropy–enthalpy balance between the pro-R and pro-S pathways.

Two solvents, two enantiomers: Enantiodivergent hydroquinidine 1,4-phthalazinediyl diether ((DHQD)₂PHAL)-catalyzed chlorocyclization of unsaturated carbamates, controlled solely by the choice of solvent, yields oxazolidinones in high enantioselectivity (see scheme; DCDMH=1,3-dichloro-5,5-dimethyl hydantoin). The origin of the observed enantiodivergence is traced back to a solvent-selected entropy–enthalpy balance between pro-R and pro-S pathways that dictates the course of the reaction.

The photophysical properties of a series of para-substituted donor–acceptor cruciform fluorophores (p1–4) were investigated and compared with their meta and ortho isomers (m1–4 and o1–4). The structural variations were found to have a significant effect on the solvatochromism, fluorescence quantum yields (Φ_fl), fluorescence lifetimes (τ_fl), and response upon addition of trifluoroacetic acid. The observed spectral shifts in absorption and emission caused by protonation of the cruciforms make them promising candidates as chemosensors. Additional computational studies provided more insight into the electronic structure of the systems.

Position is everything: The position of the nitrogen atoms and groups of cruciforms containing both pyridine and N,N-dimethylaniline moieties has a profound effect on the photophysical properties (solvatochromism, fluorescence quantum yields, fluorescence lifetimes, and their response to a change in the pH of the environment) of these compounds. This effect is in part due to the meta-positioned nitrogen atoms and groups of the excited states having surprisingly large orbital coefficients in the HOMO (see picture). Additionally, these compounds show promise as pH sensors.

Cascade reactions: A variety of novel cascade reactions can be performed when the known and well-studied radical 5- or 6-exo-cyclization of an aryl diazonium salt is conducted in the presence of alkenes and further optional scavengers (see scheme).

Get asymmetric! Asymmetric [4+1] annulation of sulfur ylides and N-(ortho-chloromethyl)aryl amides allowed the formation of the desired cycloadduct with moderate to high yields and enantioselectivities (see scheme). The described strategy, taking advantage of chiral sulfur ylides, represents a direct procedure to access chiral 2-substituted indolines.

Two is better than one! Dual activation of isatins and formaldehyde tert-butyl hydrazone by 2,2′-diamino-1,1′-binaphthalene (BINAM)-derived bis(ureas) is the key to achieve high reactivity and excellent enantioselectivities in the synthesis of azo and azoxy-functionalized 3-hydroxy-2-oxindoles (see scheme).

As the demand for probes suitable for sensor development increases, investigation of approaches that utilize known successful receptors gains in general importance. This study describes a two-prong approach that can be used as a guide to developing sensors from known receptors. First, the conversion of a simple receptor, calix[4]pyrrole, into a fluorescent probe to establish a ratiometric signal is described. Secondly, the sensors that employ an output from a single ratiometric calix[4]pyrrole probe are fabricated by using poly(ether-urethane) hydrogel copolymers. These hydrogels are designed to absorb, internalize and transport aqueous electrolytes. A sensor array of ten different poly(ether-urethane) matrices with varying comonomer proportions were doped with a single probe and were exposed to eight different anions: acetate, benzoate, fluoride, chloride, phosphate, pyrophosphate, hydrogen sulfide, and cyanide, eight urine samples and anti-inflammatory drugs (NSAIDs). The poly(ether-urethane) matrices comprise different proportions of anion-binding urethane moieties and different hydrophilicity given by the ratio between ethylene glycol ether and butylene glycol ether. This diversity in the hydration behavior provides different environment polarity, in which the recognition and self-assembly processes display enough diverse behavior to allow for unique response of the probe to the analytes. Furthermore, a single probe is shown to recognize eight different aqueous anions and eight urine samples when embedded in ten different polyurethanes in an array that displays 100 % classification accuracy. To demonstrate the potential of the concept for quantitative studies, an estimation of non-steroidal anti-inflammatory drugs ibuprofen and diclofenac in water and in saliva was performed. A limit of detection of 0.1 ppm and a dynamic range of 0.1–0.6 and 0.05–60 ppm was observed, respectively. Given the general difficulty of chemosensors to recognize aqueous anions, the fact that one probe recognizes eight different analytes attests to an enormous effect of the polymer environment on the recognition process. This method could be used to generate a variety of sensor arrays for various analyses including species that are difficult to recognize, such as small-molecule- and inorganic anions.

One for all, all for one: A single fluorescent probe is shown to recognize eight different aqueous anions and eight urine samples when embedded in ten different polyurethanes in an array that displays 100 % classification accuracy (see figure). To demonstrate the potential of the concept for quantitative studies, an estimation of non-steroidal anti-inflammatory drugs ibuprofen and diclofenac in water and in saliva was performed.

Materials of supramolecular nature have attracted much attention owing to their interesting features, such as self-reparability and material robustness, that are imparted by noncovalent interactions to synthetic materials. Among the various structures and synthetic methodologies that may be considered for this purpose, the introduction of extensive arrays of multiple hydrogen bonds allows for the formation of supramolecular materials that may, in principle, present self-healing behavior. Hydrogen bonded networks implement dynamic noncovalent interactions. Suitable selection of structural units gives access to novel dynamic self-repairing materials by incrementing the number of hydrogen-bonding sites present within a molecular framework. Herein, we describe the formation of a tris-urea based motif giving access to six hydrogen-bonding sites, easily accessible through reaction of carbohydrazide with an isocyanate derivative. Extension towards the synthesis of multiply hydrogen-bonded supramolecular materials has been achieved by polycondensation of carbohydrazide with a bis-isocyanate component derived from poly-dimethylsiloxane chains. Such materials underwent self-repair at a mechanically cut surface. This approach gives access to a broad spectrum of materials of varying flexibility by appropriate selection of the bis-isocyanate component that forms the polymer backbone.

Healing power: Easy access to a tris-urea motif, with the possibility of forming six H-bonds, has been demonstrated. This concept was further extended to the formation of soft functional materials based on polydimethylsiloxane moieties amenable to self-repair (see figure).

A bicyclic ligand platform for iron(II), which allows total control over the complex’s magnetic properties in aqueous solution simply by varying one of the six coordination sites of the bispidine ligand, is reported. To achieve this, an efficient synthetic route to an N5 bispidine framework (ligand L4) that features an unsubstituted N-7 site is established. Then, by choosing appropriate N-7-coordinating substituents, the spin state of choice can be imposed on the corresponding ferrous complexes under environmentally relevant conditions in water and near-room temperature. Importantly, the first low-spin and diamagnetic iron(II) chelates in the bispidine series, both in the solid state and in aqueous solution, are reported. The eradication of head-on steric clashes between pendent coordinating arms is at the origin of this success. A new pair of constitutionally similar ferrous coordination compounds of a multidentate ligand system is obtained, which exhibits a distinctly binary (off–on) magnetic relationship. The new synthetic intermediate L4 may be substituted in just one step by any desired pendent arm, thus allowing access to complexes with finely tuned magnetic properties.

All under control: Structural variation of bispidines allows for the preparation of ferrous complexes that adopt magnetic properties of choice under environmentally benign conditions in water at room temperature. Pairs of constitutionally similar, robust chelates with a binary off–on magnetic relationship are obtained (see figure).

Aequorea victoria is a type of jellyfish that is known by its famous protein, green fluorescent protein (GFP), which has been widely used as a probe in many fields. Aequorea has another important protein, aequorin, which is one of the members of the EF-hand calcium-binding protein family. Aequorin has been used for intracellular calcium measurements for three decades, but its bioluminescence mechanism remains largely unknown. One of the important reasons is the lack of clear and reliable knowledge about the light emitters, which are complex. Several neutral and anionic forms exist in chemiexcited, bioluminescent, and fluorescent states and are connected with the H-bond network of the binding cavity in the protein. We first theoretically investigated aequorin chemiluminescence, bioluminescence, and fluorescence in real proteins by performing hybrid quantum mechanics and molecular mechanics methods combined with a molecular dynamics method. For the first time, this study reported the origin and clear differences in the chemiluminescence, bioluminescence and fluorescence of aequorin, which is important for understanding the bioluminescence not only of jellyfish, but also of many other marine organisms (that have the same coelenterazine caved in different coelenterazine-type luciferases).

See jellyfish in a new light: The origin and differences in the chemiluminescence, bioluminescence, and fluorescence of the proteins of the aequorin jellyfish were theoretically investigated by performing hybrid quantum mechanics and molecular mechanics methods combined with a molecular dynamics method. The findings are important for understanding the bioluminescence of jellyfish and other marine organisms (see figure).

A green way to amino acids: α-Tetrasubstituted α-amino-acid derivatives are formed in high yield and enantioselectivity by using a Rh-catalyzed enantioselective alkynylation of α-ketiminoesters. This reaction, which involves a proton transfer and can be conducted at room temperature, has high substrate scope (see scheme; Cbz=benzyloxycarbonyl, Fmoc=9-fluorenylmethyloxycarbonyl).

5-(Tetrazol-1-yl)-2H-tetrazole (1), or 1,5′-bistetrazole, was synthesized by the cyclization of 5-amino-1H-tetrazole, sodium azide and triethyl orthoformate in glacial acetic acid. A derivative of 1, 2-methyl-5-(tetrazol-1-yl)tetrazole (2) can be obtained by this method starting from 5-amino-2-methyl-tetrazole. Furthermore, selected salts of 1 with nitrogen-rich and metal (alkali and transition metal) cations, including hydroxylammonium (4), triaminoguanidinium (5), copper(I) (8) and silver (9), as well as copper(II) complexes of both 1 and 2 were prepared. An intensive characterization of the compounds is given, including vibrational (IR, Raman) and multinuclear NMR spectroscopy, mass spectrometry, DSC and single-crystal X-ray diffraction. Their sensitivities towards physical stimuli (impact, friction, electrostatic) were determined according to Bundesamt für Materialforschung (BAM) standard methods. Energetic performance (detonation velocity, pressure, etc.) parameters were calculated with the EXPLO5 program, based on predicted heats of formation derived from enthalpies computed at the CBS-4M level of theory and utilizing the atomization energy method. From the analytical and calculated data, their potential as energetic materials in different applications was evaluated and discussed.

A Bigger Bang! 5-(Tetrazol-1-yl)-2H-tetrazole (1,5′-bistetrazole) was prepared according to a modified literature procedure and its chemistry was investigated by the preparation of several new salts with various metal and nitrogen-rich cations, as well as complexes with copper(II). The compounds were characterized and investigated as potential new energetic materials for various applications like primary and secondary explosives or pyrotechnic colorants.

Within the past decade photochromic materials, specifically dithienylethenes (DTEs), have received increased interest because of their ability to function as potential photoswitchable molecular devices and optical memory storage systems. Current research in this area has focused on incorporating organic architectures to functionalize the DTE framework and alter the resulting photophysical properties; however, their syntheses are often not trivial. In this context, we have designed a simple and versatile diimine (2) containing adjacent 2,5-dimethyl(thienyl) rings in the backbone. This redox active diimine (2) acts as a precursor to a novel photochromic ligand and has been used to coordinate to both boron and phosphorus elements, along with the synthesis of a phosphorane-side-chain functionalized polymer without further functionalization to the parent DTE framework. A study of the resulting photochromic properties of these compounds revealed that 1) the UV-visible absorption spectra of the closed-ring isomer were dependent of the element present in the N,N′-chelating pocket and 2) incorporating the dithienylethene into a side-functionalized phosphorane polymer greatly increased the closed-/open-ring reversibility and decreased the formation of by-products.

Switching it up! A versatile redox-active diazabutadiene (DAB) ligand containing photochromic dithienylethene rings in the backbone has been synthesized. The coordination of both B^III and P^III has been demonstrated, along with the facile functionalization of the P^III heterocycle with a polymerizable group and the synthesis of a photochromic side-chain functionalizable polymer (see figure).

The cathodic reactions in Li–S batteries can be divided into two steps. Firstly, elemental sulfur is transformed into long-chain polysulfides (S₈↔Li₂S₄), which are highly soluble in the electrolyte. Next, long-chain polysulfides undergo nucleation reaction and convert into solid-state Li₂S₂ and Li₂S (Li₂S₄↔Li₂S) by slow processes. As a result, the second-step of the electrochemical reaction hinders the high-rate application of Li–S batteries. In this report, the kinetics of the sulfur/long-chain-polysulfide redox couple (theoretical capacity=419 mA h g⁻¹) are experimentally demonstrated to be very fast in the Li–S system. A Li–S cell with a blended carbon interlayer retains excellent cycle stability and possesses a high percentage of active material utilization over 250 cycles at high C rates. The meso-/micropores in the interlayer are responsible for accommodating the shuttling polysulfides and offering sufficient electrolyte accessibility. Therefore, utilizing the sulfur/long-chain polysulfide redox couple with an efficient interlayer configuration in Li–S batteries may be a promising choice for high-power applications.

More Juice: The kinetics of the sulfur/long-chain polysulfide redox couple (S₈↔Li₂S₄; theoretical capacity= 419 mA h g⁻¹) are experimentally demonstrated to be very fast in the Li–S system. A Li–S battery with a blended-carbon interlayer retains excellent cycle stability and high discharge capacity over 250 cycles at 10 C and 15 C rate. The meso-/micropores in the interlayer are responsible for storing the migrating polysulfides and offering sufficient electrolyte accessibility.

The highly Z-selective asymmetric conjugate addition of 3-substituted oxindoles to alkynyl carbonyl compounds has been developed by using scandium complexes of chiral N,N′-dioxides under mild conditions. The thermodynamically unstable Z-olefin derivatives were obtained in excellent yields and high enantiomeric and geometric control. The catalyst was also found to be effective in the asymmetric acetylenic substitution reaction of 3-substituted oxindoles, giving excellent enantioselectivities.

A highly Z-selective asymmetric conjugate addition of alkynyl carbonyl compounds with 3-substituted oxindoles has been developed by using scandium complexes of chiral N,N′-dioxides (L) under mild conditions. The products were obtained in excellent yields and high enantiomeric and geometric control. The catalyst was also found to be effective in the asymmetric acetylenic substitution reaction of 3-substituted oxindoles, giving excellent enantioselectivities (see scheme).

Sweetening up jadomycin A: The first total synthesis of jadomycins B, S, T, and ILEVS1080 has been achieved, featuring construction of the unique 8H-benz[b]oxazolo[3,3-f]phenanthridine skeleton by biomimetic condensation of a quinone aldehyde with amino acid sodium salts and elaboration of the glycosides by Mitsunobu condensation (see figure).

Cerium and nanocubes: CeO₂-supported Pd–Cu-alloy nanocubes (Pd–Cu NCs/CeO₂) with high content and good dispersion of the Pd–Cu NCs were prepared in high yields by heating a solution containing Pd, Cu, and Ce precursors (see figure). The prepared Pd–Cu NCs/CeO₂ has excellent catalytic activity and stability toward formic acid electro-oxidation due to the synergism between the Pd–Cu-alloy catalysts and the CeO₂ support.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with a high degree of structural diversity and a wide variety of bioactivities. Understanding the biosynthetic machinery of these RiPPs will benefit the discovery and development of new molecules with potential pharmaceutical applications. In this Concept article, we discuss the features of the biosynthetic pathways to different RiPP classes, and propose mechanisms regarding recognition of the precursor peptide by the post-translational modification enzymes. We propose that the leader peptides function as allosteric regulators that bind the active form of the biosynthetic enzymes in a conformational selection process. We also speculate how enzymes that generate polycyclic products of defined topologies may have been selected for during evolution.

It follows the leader: In this article, the biosynthesis of different ribosomally synthesized and post-translationally modified peptides (RiPPs) is discussed. Mechanisms for recognition of the precursor peptide by post-translational modification enzymes are proposed; it is suggested that the leader peptides function as allosteric regulators, and speculations on how enzymes that generate polycyclic products may have been selected for during evolution are discussed.

Aligned Ca₂Ge₇O₁₆ nanowire arrays were successfully grown on carbon textiles to form hierarchical 3D structures by using a facile hydrothermal method on a large scale. Typical Ca₂Ge₇O₁₆ nanowires are single crystals that show preferred growth along the [001] direction. The 3D hierarchical structures were used as binder-free anodes for lithium-ion batteries, which showed the features of highly reversible capacity (900–1100 mA h g⁻¹ at a current density of 300 mA g⁻¹), remarkable cycling stability, even over 100 cycles, and good rate capability, with a capacity of about 500 mA h g⁻¹ at 3 A g⁻¹. Furthermore, highly bendable full cells were also fabricated, which showed high flexibility, with little voltage change after bending 600 times, and superior temperature tolerance within the range 4–60 °C, thus demonstrating their promising potential for applications in high-performance lithium-ion batteries.

Batteries not included: A hierarchical flexible electrode that consisted of aligned Ca₂Ge₇O₁₆ nanowire arrays on carbon textile exhibited a highly reversible capacity, remarkable cycling stability, and good rate capability (see figure).

A new tetranuclear magnesium hydride cluster, [{NN-(MgH)₂}₂], which was based on a NN-coupled bis-β-diketiminate ligand (NN²⁻), was obtained from the reaction of [{NN-(MgnBu)₂}₂] with PhSiH₃. Its crystal structure reveals an almost-tetrahedral arrangement of Mg atoms and two different sets of hydride ions, which give rise to a coupling in the NMR spectrum (J=8.5 Hz). To shed light on the relationship between the cluster size and H₂ release, the thermal decomposition of [{NN-(MgH)₂}₂] and two closely related systems that were based on similar ligands, that is, an octanuclear magnesium hydride cluster and a dimeric magnesium hydride species, have been investigated in detail. A lowering of the H₂-desorption temperature with decreasing cluster size is observed, in line with previously reported theoretical predictions on (MgH₂)_n model systems. Deuterium-labeling studies further demonstrate that the released H₂ solely originates from the oxidative coupling of two hydride ligands and not from other hydrogen sources, such as the β-diketiminate ligands. Analysis of the DFT-computed electron density in [{NN-(MgH)₂}₂] reveals a counterintuitive interaction between two formally closed-shell H⁻ ligands that are separated by 3.106 Å. This weak interaction could play an important role in H₂ desorption. Although the molecular product after H₂ release could not be characterized experimentally, DFT calculations on the proposed decomposition product, that is, the low-valence tetranuclear Mg(I) cluster [(NN-Mg₂)₂], predict a structure with two almost-parallel, localized MgMg bonds. As in a previously reported β-diketiminate Mg^I dimer, the MgMg bond is not characterized by a bond critical point, but instead displays a local maximum of electron density midway between the atoms, that is, a non-nuclear attractor (NNA). Interestingly, both of the NNAs in [(NN-Mg₂)₂] are connected through a bond path that suggests that there is bonding between all four Mg^I atoms.

Size matters: The temperature that is required for the elimination of H₂ in magnesium hydride clusters is dependent on the cluster size (see scheme). Detailed experimental and/or theoretical data of magnesium hydride and magnesium(I) clusters are reported.

Recent progress in the RNA therapeutics has increased demand for the synthesis of large quantities of oligoribonucleotides. The assembly of RNA oligomers relies mainly on solid-phase approaches. These allow rapid product purification and the ability to drive a target reaction to completion through the use of excess reagents. Despite the known advantages of solid-phase synthesis, some issues in the process remain to be addressed, such as low and limited scale, reagent accessibility, and the use of a very large excess of reagents. Herein, we report a highly efficient and practical method of liquid-phase synthesis of RNA oligomers by using alkyl-chain-soluble support. We demonstrate the utility of the liquid-phase method through 21-mer RNA synthesis on a gram scale.

The assembly of RNA oligomers relies principally on solid-phase approaches, although some alternative methods have been developed to date. A highly efficient and practical method of liquid-phase synthesis for RNA oligomers by using alkyl-chain-type soluble support is reported. The utility of the liquid-phase method through 21-mer RNA synthesis on a gram scale is described (see scheme).

How much should we switch? Two Fe^II₄L₄ tetrahedral capsules were shown to undergo thermally induced spin crossover (SCO). Guest binding to one of these capsules was observed to affect the thermodynamics of its SCO in solution, leading to different spin transition temperatures between the empty host (blue) and the host–guest complex (red). HS: high spin; LS: low spin.

Chiral amino acid- and amino alcohol-oxalamides are well-known as versatile and efficient gelators of various lipophilic and polar organic solvents and water. To further explore the capacity of the amino acid/oxalamide structural fragment as a gelation-generating motif, the dioxalamide dimethyl esters 1₆Me and 1₉Me, and dicarboxylic acid 2₆OH/2₉OH derivatives containing flexible methylene bridges with odd (9; n=7) and even (6; n=4) numbers of methylene groups were prepared. Their self-assembly motifs and gelation properties were studied by using a number of methods (FTIR, ¹H NMR spectroscopy, CD, TEM, DSC, XRPD, molecular modeling, MMFF94, and DFT). In contrast to the previously studied chiral bis(amino acid or amino alcohol) oxalamide gelators, in which no chiral morphology was ever observed in the gels, the conformationally more flexible 1₆Me, 1₉Me, 2₆OH, and 2₉OH provide gelators that are capable of forming diverse aggregates of achiral and chiral morphologies, such as helical fibers, twisted tapes, nanotubules, straight fibers, and tapes, in some cases coexisting in the same gel sample. It is shown that the differential scanning calorimetry (DSC)-determined gelation enthalpies could not be correlated with gelator and solvent clogP values. Spectroscopic results show that intermolecular hydrogen-bonding between the oxalamide units provides the major and self-assembly directing intermolecular interaction in the aggregates. Molecular modeling studies reveal that molecular flexibility of gelators due to the presence of the polymethylene bridges gives three conformations (zz, p1, and p2) close in energy, which could form oxalamide hydrogen-bonded layers. The aggregates of the p1 and p2 conformations tend to twist due to steric repulsion between neighboring iBu groups at chiral centers. The X-ray powder diffraction (XRPD) results of 1₆Me and 1₉Me xerogels prove the formation of p1 and p2 gel aggregates, respectively. The latter results explain the formation of gel aggregates with chiral morphology and also the simultaneous presence of aggregates of diverse morphology in the same gel system.

Mix/morph gelators: Chiral dioxalamide dimethyl esters and dicarboxylic acid derivatives (containing flexible methylene bridges with an odd (n=7) and even (n=4) number of methylene groups) are good gelators of polar and lipophilic organic solvents, which are capable of forming diverse gel aggregates of chiral and achiral morphologies sometimes simultaneously present in the same gel system.

We report the gold-catalyzed synthesis of highly functionalized iodofulvenes from iododialkynes under mild conditions. The catalytic cycle involves the formation of gold acetylides and vinylgold intermediates. These intermediates can then undergo an unprecedented iodine/gold exchange. This new pathway for catalyst transfer in dual gold catalysis opens up the possibility of highly regioselective transformations directed by the gold in the organogold intermediates. The resulting products are well suited for further metal-mediated coupling reactions, allowing the synthesis of extended π-systems.

Iodine/gold exchange: A gold-catalyzed iodine transfer allows the efficient synthesis of benzofulvenes with iodo substituents on the fulvene core (see scheme). The new dual-activation catalysts are efficient catalysts for this new type of cycloisomerization.

Hydrogen liberation: An attractive approach to reversible hydrogen storage applications is based on the decomposition of formic acid. The efficient and selective hydrogen liberation from formic acid is catalyzed by an iron-pincer complex in the presence of trialkylamine (see scheme). Turnover frequencies up to 836 h⁻¹ and turnover numbers up to 100 000 were achieved at 40 °C. A mechanism including well-defined intermediates is suggested on the basis of experimental and computational data.

Adding value: The direct vinylogous Michael addition of γ-substituted butenolides with a series of 3-aroyl acrylates and 1,2-diaroylethylenes has been demonstrated. This organocatalytic method delivers highly enantio- and diastereomerically pure γ,γ-disubstituted butenolides with adjacent quaternary and tertiary stereocenters (see scheme).

Star quality: Goniopectenoside B, a minor asterosaponin from starfish Goniopecten demonstrans with antifouling activity, has been synthesized in a convergent 21 steps and in 4.3 % overall yield starting from adrenosterone. This represents the first synthesis of a complex asterosaponin, which are ubiquitous and characteristic in starfish as defense chemicals (see figure).

Subsequent mild cyclization of aromatic substrates by Pictet–Spengler condensation to stereoselectively gave new tricyclic compounds. Examples are described in decent yield over two steps in one pot, and a crystal structure is also presented to support the proposed structures (see figure).

Ironing out the details: Proline and pyrrolidine derivatives (Hayashi–Jørgensen catalysts) are considered “work horses” in organocatalysis. This report describes a new effective ferrocenyl pyrrolidine catalyst able to perform well in benchmark organocatalytic reactions (see figure). The ferrocene moiety controls the conformational space and a simple alkyl group effectively covers a face of the derived enamine. This new framework can find applications in organocatalysis, and in general, in new ligand design.

Composites of electrospun poly(ethylene oxide) (PEO) fibers and silver nanoparticles (Ag NPs) were used as a soft template for coating with TiO₂ by atomic layer deposition (ALD). Whereas the as-deposited TiO₂ layers on PEO fibers and Ag NPs were completely amorphous, the TiO₂ layers were transformed into polycrystalline TiO₂ nanotubes (NTs) with embedded Ag NPs after calcination. Their plasmonic effect can be controlled by varying the thickness of the dielectric Al₂O₃ spacer between Ag NPs and dye molecules by means of the ALD process. Electronic and spectroscopic analyses demonstrated enhanced photocurrent generation and solar-cell performance due to the intense electromagnetic field of the dye resulting from the surface plasmon effect of the Ag NPs.

Plasmon-enhanced solar cells were fabricated by using polycrystalline TiO₂ nanotubes (NTs) with embedded Ag nanoparticles (NPs), obtained by coating composites of electrospun poly(ethylene oxide) and Ag NPs with TiO₂ by atomic layer deposition (ALD), as the photoanode. Their plasmon effect can be controlled by varying the thickness of a dielectric Al₂O₃ spacer between the Ag NPs and dye molecules by means of the ALD process (see figure).

We report the synthesis of two [2]catenane-containing struts that are composed of a tetracationic cyclophane (TC⁴⁺) encircling a 1,5-dioxynaphthalene (DNP)-based crown ether, which bears two terphenylene arms. The TC⁴⁺ rings comprise either 1) two bipyridinium (BIPY²⁺) units or 2) a BIPY²⁺ and a diazapyrenium (DAP²⁺) unit. These degenerate and nondegenerate catenanes were reacted in the presence of Cu(NO₃)₂⋅2.5 H₂O to yield Cu-paddlewheel-based MOF-1050 and MOF-1051. The solid-state structures of these MOFs reveal that the metal clusters serve to join the heptaphenylene struts into grid-like 2D networks. These 2D sheets are then held together by infinite donor–acceptor stacks involving the [2]catenanes to produce interpenetrated 3D architectures. As a consequence of the planar chirality associated with both the DNP and hydroquinone (HQ) units present in the crown ether, each catenane can exist as four stereoisomers. In the case of the nondegenerate (bistable) catenane, the situation is further complicated by the presence of translational isomers. Upon crystallization, however, only two of the four possible stereoisomers—namely, the enantiomeric RR and SS forms—are observed in the crystals. An additional element of co-conformational selectivity is present in MOF-1051 as a consequence of the substitution of one of the BIPY²⁺ units by a DAP²⁺ unit: only the translational isomer in which the DAP²⁺ unit is encircled by the crown ether is observed. The overall topologies of MOF-1050 and MOF-1051, and the selective formation of stereoisomers and translational isomers during the kinetically driven crystallization, provide evidence that weak noncovalent bonding interactions play a significant role in the assembly of these extended (super)structures.

Playing the hand-stacking game: The reaction of [2]catenane-containing struts with Cu(NO₃)₂ produces extended frameworks, from whence both co-conformational selection and diastereoselection are observed following crystallization. Solid-state structures reveal the selective formation of stereoregular π–π stacks of enantiomeric pairs of donor–acceptor catenanes, despite the presence in solution of up to eight co-conformational and stereoisomers exhibiting planar chirality (see figure).

Novel Janus nanoparticles with Au and mesoporous silica faces on opposite sides were prepared using a Pickering emulsion template with paraffin wax as the oil phase. These anisotropic colloids were employed as integrated sensing–actuating nanomachines for enzyme-controlled stimuli-responsive cargo delivery. As a proof of concept, we demonstrated the successful use of the Janus colloids for controlled delivery of tris(2,2’-bipyridyl) ruthenium(II) chloride from the mesoporous silica face, which was grafted with pH-sensitive gatelike scaffoldings. The release was mediated by the on-demand catalytic decomposition of urea by urease, which was covalently immobilized on the Au face.

Janus-nanoparticle-based nanomachine: This article reports an integrated sensing–actuating nanomachine based on Janus Au–mesoporous silica nanoparticles with gatelike scaffolding for enzyme-controlled cargo release (see figure).

Sieve and take: A biomimetic strategy was designed to fabricate two-dimensional silica sieve plates (SSP) by use of catanionic surfactants as a composite template and L-tartrate with hydroxyl and carboxyl groups as a regulator. Tartrate was found to combine two capabilities in the formation of SSP structures: the connection of adjacent silica structures through H bonding and the separation of adjacent structures through electrostatic repulsion.

A selective iron-based catalyst system for the hydrogenation of α,β-unsaturated aldehydes to allylic alcohols is presented. Applying the defined iron–tetraphos complex [FeF(L)][BF₄] (L=P(PhPPh₂)₃) in the presence of trifluoroacetic acid a broad range of aldehydes are reduced in high yields using low catalyst loadings (0.05–1 mol %). Excellent chemoselectivity for the reduction of aldehydes in the presence of other reducible moieties, for example, ketones, olefins, esters, etc. is achieved. Based on the in situ detected hydride species [FeH(H₂)(L)]⁺ a catalytic cycle is proposed that is supported by computational calculations.

Go catalytic! A selective iron-based catalyst system for the hydrogenation of α,β-unsaturated aldehydes to allylic alcohols is presented (see scheme). By applying the defined iron–tetraphos complex [FeF(L)][BF₄] (L=P(PhPPh₂)₃) in the presence of trifluoroacetic acid, a broad range of aldehydes were reduced in high yields using low catalyst loadings.

Pt–CeO₂: Flowerlike Pt–CeO₂ hybrids on reduced graphene oxide (RGO) can be prepared by treating Pt cubes with Ce(NO₃)₃ in the presence of graphene oxide. The density of the CeO₂ coating around the Pt cubes depends on the amount of Ce(NO₃)₃ used. The as-obtained samples exhibit high stability and activity for the catalytic hydrolysis of ammonia borane (AB).

Shining a nanobeacon: Single-label nanobeacon sensors were constructed by using graphitic carbon nanoparticles (CNPs) and their oxides as energy acceptors (see figure). Excellent sensing performances were achieved with simplified operation and lowered cost.

The catalytic, deactivation, and regeneration characteristics of large coffin-shaped H-ZSM-5 crystals were investigated during the methanol-to-hydrocarbons (MTH) reaction at 350 and 500 °C. Online gas-phase effluent analysis and examination of retained material thereof were used to explore the bulk properties of large coffin-shaped zeolite H-ZSM-5 crystals in a fixed-bed reactor to introduce them as model catalysts for the MTH reaction. These findings were related to observations made at the individual particle level by using polarization-dependent UV-visible microspectroscopy and mass spectrometric techniques after reaction in an in situ microspectroscopy reaction cell. Excellent agreement between the spectroscopic measurements and the analysis of hydrocarbon deposits by means of retained hydrocarbon analysis and time-of-flight secondary-ion mass spectrometry of spent catalyst materials was observed. The obtained data reveal a shift towards more condensed coke deposits on the outer zeolite surface at higher reaction temperatures. Zeolites in the fixed-bed reactor setup underwent more coke deposition than those reacted in the in situ microspectroscopy reaction cell. Regeneration studies of the large zeolite crystals were performed by oxidation in O₂/inert gas mixtures at 550 °C. UV-visible microspectroscopic measurements using the oligomerization of styrene derivatives as probe reaction indicated that the fraction of strong acid sites decreased during regeneration. This change was accompanied by a slight decrease in the initial conversion obtained after regeneration. H-ZSM-5 deactivated more rapidly at higher reaction temperature.

Death of the coffins: Large coffin-shaped H-ZSM-5 zeolite crystals were used as model catalysts for the methanol-to-hydrocarbons reaction (see figure). Their activity and deactivation behavior were tested by the combined use of fixed-bed reactor and optical microspectroscopy experiments. Deactivation by carbonaceous deposit formation was studied by an integral approach to result in a comprehensive coking model.

The structural determination of small organic molecules is mainly undertaken by using NMR techniques, although it is increasingly supplemented by using computational methods. NMR parameters, such as chemical shifts and coupling constants, are extremely sensitive indicators of local molecular conformation and are a source of structural evidence. However, their interpretation is fairly challenging in many circumstances, such as the case of the new polyether squalene derivative nivariol, the structure of which was elucidated by means of NMR spectroscopy and DFT calculations. The potential flexibility of this molecule and the high number of quaternary carbon atoms that it contains make its configurational assignment very difficult. Moreover, the relative configuration of four separated stereoclusters was established and subsequently connected by using NOE and J-based analysis, as well as by a comparison of its experimental ¹³C NMR chemical shifts with the corresponding population-weighted values, as calculated by using DFT methods. Limitations of these used approaches became apparent but were overcome by combining the two methods.

Never say nivariol again: The interpretation of NMR coupling constants and chemical shifts with the aid of DFT calculations allowed the structural determination of a complex polyether triterpene (see figure). This approach is of particular importance when studying chiral quaternary carbon centers or distant stereoclusters.

A new approach to obtain green-emitting iridium(III) complexes is described. The synthetic approach consists of introducing a methylsulfone electron-withdrawing substituent into a 4-phenylpyrazole cyclometalating ligand in order to stabilize the highest-occupied molecular orbital (HOMO). Six new complexes have been synthesized incorporating the conjugate base of 1-(4-(methylsulfonyl)phenyl)-1 H-pyrazole as the cyclometalating ligand. The complexes show green emission and very high photoluminescence quantum yields in both diluted and concentrated films. When used as the main active component in light-emitting electrochemical cells (LECs), green electroluminance is observed. High efficiencies and luminances are obtained at low driving voltages. This approach for green emitters is an alternative to the widely used fluorine-based substituents in the cyclometalating ligands and opens new design possibilities for the synthesis of green emitters for LECs.

Green enlightenment: Electron-withdrawing sulfone groups introduced into the cyclometalating phenylpyrazole ligands lead to very efficient green-emitting ionic iridium complexes. Green electroluminescence from efficient light-emitting chemical cells is obtained (see figure).

The total syntheses of four fawcettimine-related Lycopodium alkaloids, (±)-fawcettimine, (±)-fawcettidine, (±)-lycoposerramine-Q, and (±)-lycoflexine, were completed in a highly stereoselective manner. The Pauson–Khand reaction of 4-methylidene-6-siloxyoct-1-en-7-yne followed by regio- and stereoselective hydrogenation led to the short-step preparation of the bicyclo[4.3.0]nonenone intermediate bearing a methyl group with the required stereochemistry. The subsequent chemical manipulation of the bicyclic compound afforded the 6-5-9-membered tricyclic dioxo compound, which was then transformed into the four targeted alkaloids in an alternative and more efficient fashion.

Fawcettimine alkaloids: The total syntheses of four fawcettimine-related Lycopodium alkaloids, (±)-fawcettimine, (±)-fawcettidine, (±)-lycoposerramine-Q, and (±)-lycoflexine, are described. The key steps in these syntheses are the Pauson–Khand reaction of 4-methylidene-6-siloxyoct-1-en-7-yne followed by regio- and stereoselective hydrogenation to provide the bicyclo[4.3.0]nonenone intermediate bearing a methyl group with the required stereochemistry (see scheme).

The large-scale preparation of graphene is of great importance due to its potential applications in various fields. We report herein a simple method for the simultaneous exfoliation and reduction of graphene oxide (GO) to reduced GO (rGO) by using alkynyl-terminated dopamine as the reducing agent. The reaction was performed under mild conditions to yield rGO functionalized with the dopamine derivative. The chemical reactivity of the alkynyl function was demonstrated by post-functionalization with two thiolated precursors, namely 6-(ferrocenyl)hexanethiol and 1H,1H,2H,2H-perfluorodecanethiol. X-ray photoelectron spectroscopy, UV/Vis spectrophotometry, Raman spectroscopy, conductivity measurements, and cyclic voltammetry were used to characterize the resulting surfaces.

Modified graphene oxide: A simple method has been developed for the simultaneous exfoliation and reduction of graphene oxide (GO) to reduced GO (rGO) by using alkynyl-terminated dopamine as the reducing agent. The reaction was performed under mild conditions to yield rGO functionalized with the dopamine derivative (see figure). The chemical reactivity of the alkynyl function was demonstrated and the surfaces of the rGO characterized by a variety of techniques.

Here we report a novel family of crystalline, supermicroporous iron(III) phosphonate nanomaterials (HFeP-1-3, HFeP-1-2, and HFeP-1-4) with different Fe^III-to-organophosphonate ligand mole ratios. The materials were synthesized by using a hydrothermal reaction between benzene-1,3,5-triphosphonic acid and iron(III) chloride under acidic conditions (pH≈4.0). Powder X-ray diffraction, N₂ sorption, transmission and scanning electron microscopy (TEM and SEM) image analysis, thermogravimetric and differential thermal analysis (TGA-DTA), and FTIR spectroscopic tools were used to characterize the materials. The triclinic crystal phase [P1¯(2) space group] of the hybrid iron phosphonate was established by a Rietveld refinement of the PXRD analysis of HFeP-1-3 by using the MAUD program. The unit cell parameters are a=8.749(1), b=8.578(1), c=17.725(3) Å; α=104.47(3), β=97.64(1), γ=113.56(3)°; and V=1013.41 ų. With these crystal parameters, we proposed an 24-membered-ring open framework structure for HFeP-1. Compound HFeP-1-3, with an starting Fe/ligand molar ratio of 3.0, shows the highest Brunauer–Emmett–Telller (BET) surface area of 556 m²g⁻¹ and uniform supermicropores of approximately 1.1 nm. The acidic surface of the porous iron(III) phosphonate nanoparticles was used in a highly efficient and recyclable catalytic transesterification reaction for the synthesis of biofuels under mild reaction conditions.

Iron brews biofuels: Highly crystalline, supermicroporous iron(III) phosphonate nanoparticles have been synthesized through a hydrothermal reaction between benzene-1,3,5-triphosphonic acid and FeCl₃. The resulting material was used as an efficient and recyclable catalyst for the synthesis of biofuels under mild reaction conditions (see scheme).

Tris(pentafluorophenyl)borane (TPFPB) was found to be an efficient catalyst for rapid superoxide (O₂⁻) disproportionation. The kinetics for the catalytic disproportionation reaction is much faster than the reaction between O₂⁻ and propylene carbonate. Therefore, the negative impact of the reaction between the electrolyte and O₂⁻ produced by the O₂ reduction is minimized. The cathodic current for O₂ reduction can be doubled in the presence of TPFPB. The high reduction current resulted from the pseudo two-electron O₂-reduction reaction due to the replenishment of O₂ at the electrode surface. This discovery could lead to a new avenue for the development of high-capacity, high-rate, rechargeable Li–air batteries.

Rechargeable Li–air battery: An efficient catalyst for rapid superoxide (O₂⁻) disproportionation is reported. The negative impact of the reaction between the electrolyte and O₂⁻ produced by the O₂ reduction was minimized (see scheme).

The amide bond is a versatile functional group and its directional hydrogen-bonding capabilities are widely applied in, for example, supramolecular chemistry. The potential of the thioamide bond, in contrast, is virtually unexplored as a structuring moiety in hydrogen-bonding-based self-assembling systems. We report herein the synthesis and characterisation of a new self-assembling motif comprising thioamides to induce directional hydrogen bonding. N,N′,N′′-Trialkylbenzene-1,3,5-tris(carbothioamide)s (thioBTAs) with either achiral or chiral side-chains have been readily obtained by treating their amide-based precursors with P₂S₅. The thioBTAs showed thermotropic liquid crystalline behaviour and a columnar mesophase was assigned. IR spectroscopy revealed that strong, three-fold, intermolecular hydrogen-bonding interactions stabilise the columnar structures. In apolar alkane solutions, thioBTAs self-assemble into one-dimensional, helical supramolecular polymers stabilised by three-fold hydrogen bonding. Concentration- and temperature-dependent self-assembly studies performed by using a combination of UV and CD spectroscopy demonstrated a cooperative supramolecular polymerisation mechanism and a strong amplification of supramolecular chirality. The high dipole moment of the thioamide bond in combination with the anisotropic shape of the resulting cylindrical aggregate gives rise to sufficiently strong depolarised light scattering to enable depolarised dynamic light scattering (DDLS) experiments in dilute alkane solution. The rotational and translational diffusion coefficients, D_trans and D_rot, were obtained from the DDLS measurements, and the average length, L, and diameter, d, of the thioBTA aggregates were derived (L=490 nm and d=3.6 nm). These measured values are in good agreement with the value L_w=755 nm obtained from fitting the temperature-dependent CD data by using a recently developed equilibrium model. This experimental verification validates our common practice for determining the length of BTA-based supramolecular polymers from model fits to experimental CD data. The ability of thioamides to induce cooperative supramolecular polymerisation makes them effective and broadly applicable in supramolecular chemistry.

Thioamide bonds: The polymerisation of a thioamide-based supramolecular motif is elucidated by combining depolarised dynamic light scattering and temperature-dependent spectroscopic measurements (see figure). A cooperative polymerisation mechanism and strong amplification of chirality makes this a highly versatile structuring motif.

Molecular (photo)switch: A WCo photomagnetic discrete complex has been prepared through the self-assembly of preformed building blocks. [Co(bik)₃][{W(CN)₈}₃{Co(bik)₂}₃]⋅2 H₂O⋅13 CH₃CN (see figure) exhibits a thermally-induced electron-transfer-coupled spin transition between the two states: W^V↔W^IV. It also shows photomagnetic effects at low temperature.

Blennolide A can be synthesized through an enantioselective domino-Wacker/carbonylation/methoxylation reaction of 7 a with 96 % ee and an enantioselective Wacker oxidation of 7 b with 89 % ee. Further transformations led to the α,β-unsaturated ester (E)-17, which was subjected to a highly selective Michael addition, introducing a methyl group to give 18 a. After a threefold oxidation and an intramolecular acylation, the tetrahydroxanthenone 4 was obtained, which could be transformed into (−)-blennolide A (ent-1) in a few steps.

Domino effect: An enantioselective domino-Wacker/carbonylation/methoxylation process and an enantioselective Wacker oxidation are the key steps in the first total synthesis of the fungal metabolite blennolide A (see scheme).

Redox chemistry: Redox active europium complexes based on a new tris(2-pyridyl)plumbate ligand are described. Reactions of [LiPb(2-py^R)₃(thf)] (py^R = C₅H₃-6-OtBu) with tri- or divalent lanthanoid metals resulted in the first stable Pb–Ln-bonded complexes or unprecedented redox reactions, involving, for example, the pentametallic complex depicted.

Organocatalysis: A concise synthesis of L-pyrrolysine has been accomplished in six steps from simple starting materials. The facile synthetic strategy relies on an organocatalytic Michael addition, an efficient amide coupling, and a challenging method for the imine-bond construction (see scheme).

For the first time, the adaptability of the CC double bond as a versatile precursor for the postsynthetic modification (PSM) of microporous materials was extensively investigated and evaluated. Therefore, an olefin-tagged 4,4′-bipyridine linker was synthesized and successfully introduced as pillar linker within a 9,10-triptycenedicarboxylate (TDC) zinc paddle-wheel metal-organic framework (MOF) through microwave-assisted synthesis. Different reactions, predominately used in organic chemistry, were tested, leading to the development of new postsynthetic reactions for the functionalization of solid materials. The postsynthetic oxidation of the olefin side groups applying osmium tetroxide (OsO₄) as a catalyst led to the formation of a microporous material with free vicinal diol functionalities. The epoxidation with dimethyldioxirane (DMDO) enabled the synthesis of epoxy-functionalized MOFs. In addition to that, reaction procedures for a postsynthetic hydroboration with borane dimethyl sulfide as well as a photoinduced thiol-ene click reaction with ethyl mercaptan were developed. For all of these PSMs, yields of more than 90 % were obtained, entirely maintaining the crystallinity of the MOFs. Since the direct introduction of the corresponding groups by means of pre-synthetic approaches is hardly possible, these new PSMs are useful tools for the functionalization of porous solids towards applications such as selective adsorption, separation, and catalysis.

One MOF, many modifications: The postsynthetic transformation of CC double bonds is a versatile synthetic strategy for the introduction of functional groups in metal-organic frameworks (MOFs). A zinc-based, olefin-tagged MOF was applied to develop the epoxidation, dihydroxylation, hydroboration, and thiol-ene click reaction as new postsynthetic modifications (PSM). The discussed PSMs are high yielding, maintaining the crystallinity and porosity of the frameworks (see scheme).

1,2,3,4-Tetrasubstituted cyclopentadienes and indene derivatives with identical or different substituents were obtained in good to excellent isolated yields through a zirconocene- and CuCl-mediated intermolecular coupling process. This synthetic procedure involved three organic partners, including one CH₂I₂, and two different or identical alkynes. Two alkynes or one diyne undergo Cp₂Zr^II-mediated (Cp=η⁵-C₅H₅) pair-selective reductive coupling to afford the corresponding zirconacyclopentadiene derivatives, which react, in the presence of CuCl and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU), with CH₂I₂ through intermolecular followed by intramolecular coupling to afford the cyclopentadiene derivatives. An application of the prepared tetrasubstituted cyclopentadiene derivatives was demonstrated by the facile synthesis of the corresponding zirconocene complexes [(^4RCp)₂ZrCl₂] and [(^4RCp)₂ZrR′₂] (R′=Me, Et, or nBu). The unique 1,2,3,4-tetrasubstituted cyclopentadiene ligands and the corresponding metallocenes are expected to have further applications in organometallic chemistry and organic synthesis.

Ringing in the changes: A one-pot synthesis of 1,2,3,4-tetrasubstituted cyclopentadienes by zirconocene- and CuCl-mediated intermolecular coupling of two alkynes and diiodomethane (see scheme; Cp=η⁵-C₅H₅; DMPU=1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone) gave products that were successfully applied for the synthesis of corresponding zirconocene derivatives.

A simple bifunctional surface-enhanced Raman scattering (SERS) assay based on primer self-generation strand-displacement polymerization (PS-SDP) is developed to detect small molecules or proteins in parallel. Triphosphate (ATP) and lysozyme are used as the models of small molecules and proteins. Compared to traditional bifunctional methods, the method possesses some remarkable features as follows: 1) by virtue of the simple PS-SDP reaction, a bifunctional aptamer assembly binding of trigger 1 and trigger 2 was used as a functional structure for the simultaneous sensing of ATP or lysozyme. 2) The concept of isothermal amplification bifunctional detection has been first introduced into SERS biosensing applications as a signal-amplification tool. 3) The problem of high background induced by excess bio-barcodes is circumvented by using magnetic beads (MBs) as the carrier of signal-output products and massive of hairpin DNA binding with SERS active bio-barcodes relied on Au nanoparticles (Au NPs), SERS signal is significantly enhanced. Overall, with multiple amplification steps and one magnetic-separation procedure, this flexible biosensing system exhibited not only high sensitivity and specificity, with the detection limits of ATP and lysozyme of 0.05 nM and 10 fM, respectively.

A simple bifunctional surface-enhanced Raman scattering assay based on primer self-generation strand-displacement polymerization (PS-SDP) can be applied to sensitive SERS assays of either ATP or lysozyme in parallel to using a DNA cycle amplification signal technique (see scheme).

Fluorescent nanoparticles (FNPs) are obtained in water by self-assembly from a polymeric ionic liquid, fluorescent carboxylate moiety, and a surfactant through two main supramolecular interactions, that is, ionic bonds and hydrophobic/hydrophilic interactions. The hydrophobicity of the surfactant is tunable and a highly hydrophobic surfactant increases the fluorescence intensity and stability of the FNPs. The fluorescence of the FNPs is sensitive to a quenching effect by various ions with high selectivity, and consequently, they may be used as sensors. The self-assembly approach used to generate the FNPs is considerably simpler than other methods based on more challenging synthetic methods and the flexibility of the approach should allow a wide and diverse range of FNPs to be prepared with specific sensor applications.

Self-assembly makes good sense: Fluorescent nanoparticles were prepared by two main supramolecular interactions: ionic bonding and hydrophobic/hydrophilic interactions. The fluorescence of the nanoparticles is sensitive to a quenching effect by various ions with high selectivity (see figure).

Nickel HAS it: A Ni(cod)₂/dppp catalyst system promotes the direct alkylation of electron-rich heterocycles with α-bromo carbonyl compounds and involves an alkyl radical intermediate (see scheme; cod=1,5-cyclooctadiene, dppp=1,3-bis(diphenylphosphino)propane). This homolytic radical aromatic substitution (HAS)-type reaction enables the C3-selective direct functionalization of 2-pyridones.

Get selective! Enantioselective allylation of ketimines derived from isatins by using chiral 1,3-bis(imidazolin-2-yl)benzene (Phebim)–Pd^II complexes afforded products with good enantioselectivity (see scheme). The reaction was applied to a wide variety of ketimines. The obtained product can be converted to homoallylic amines and a spirocyclic amine without the loss of enantiopurity.

Synthetic methods: An asymmetric catalytic, desulfonylative Mannich reaction of α-keto imines with aldehydes, which is catalyzed by diarylprolinol silyl ether 1, was developed. It gave the Mannich product in good yield with excellent anti and enantioselectivity (see scheme).

Reactions templated by cellular nucleic acids are attractive for nucleic acid sensing or responsive systems. Herein we report the use of a photocatalyzed reductive cleavage of an immolative linker to unmask a rhodamine fluorophore, and its application to miRNA imaging. The reaction was found to proceed with a very high turnover (>4000) and provided reliable detection down to 5 pM of template by using γ-serine-modified peptide nucleic acid (PNA) probes. The reaction was used for the selective detection of miR-21 in BT474 cells and miR-31 in HeLa cells following irradiation for 30 min. The probes were introduced by using reversible permeation with streptolysin-O (SLO) or a transfection technique.

Seeing is believing: Different miRNAs were used as templates for the photoreduction of an azide-based immolative linker by Ru^II-peptide nucleic acid (PNA) conjugates to uncage rhodamine (see figure). The method was validated by using two sets of γ-serine-modified PNA derivatives with varying affinities to their target (perfect match and mismatch).

Boron–phenylpyrrin dyes: In the presence of BF₃⋅OEt₂, 4-(diethylamino)salicylaldehyde reacts with substituted pyrroles to give boron–phenylpyrrin dyes, which contain a central boron-containing seven-membered ring. Upon protonation in acidic solution, the complexes with a large Stokes shift, exhibit a color change, and a unique red shift in both the electronic absorption and fluorescence emission spectra (see picture), thus rendering them new analogues of boron–dipyrrin dyes that can be used as pH sensors.

A highly stereocontrolled synthesis of (+)-chamuvarinin has been completed in 1.5 % overall yield over 20 steps. The key fragment coupling reactions were the addition of alkyne 8 to aldehyde 7 (under Felkin–Anh control), followed by the two step activation/cyclization to close the C20–C23 2,5-cis-substituted tetrahydrofuran ring and a Julia–Kocienski olefination at C8–C9 to introduce the terminal butenolide. The inherent flexibility of our coupling strategy led to a streamlined synthesis with 17 steps in the longest sequence (2.2 % overall yield), in which the key bond couplings are reversed. In addition, a series of structural analogues of chamuvarinin have been prepared and screened for activity against HeLa cancer cell lines and both the bloodstream and insect forms of Trypanosoma brucei, the parasitic agent responsible for African sleeping sickness.

A hive of activity: The total synthesis of the tetrahydropyran-containing acetogenin (+)-chamuvarinin has been completed through a modular coupling strategy utilizing key bond couplings at C8–C9 and C20–C21 (see figure). This enabled the unambiguous stereochemical assignment of the natural product. A revised synthetic approach provided material for biological studies and enabled access to analogue structures that displayed selective trypanocidal activity.

Borate not graphene: The [B₆O₁₂]_∞⁶⁻ single borate layer is a graphene-like layer (see figure). The weak Na⁺Br(Cl)⁻ ionic connection between the layers leads to the layer cleavage, and difficulty of the block crystal growth.

The supramolecular self-assembly of the core-substituted naphthalene diimide bearing pyridyl motifs leads to the formation of a variety of nanostructures with pH and solvent control. The detection of HCl can be monitored by UV/Vis and fluorescence spectroscopy, as well as the naked eye, with a change in colour (blue to red, see figure). The cycle is fully reversed by the addition of triethylamine (TEA).

The asymmetric total synthesis of the diastereomers of stylopsal establishes the absolute configuration of the first reported sex pheromone of the twisted-wing parasite Stylops muelleri as (3R,5R,9R)-trimethyldodecanal. The key steps for the diastereo- and enantiodivergent introduction of the methyl groups are two different types of asymmetric conjugate addition reactions of organocopper reagents to α,β-unsaturated esters, whereas the dodecanal skeleton is assembled by Wittig reactions. The structure of the natural product was confirmed by chiral gas chromatography (GC) techniques, GC/MS and GC/electroantennography (EAD) as well as field tests. An investigation into the biosynthesis of the pheromone revealed that it is likely to be produced by decarboxylation of a 4,6,10-trimethyltridecanoic acid derivative, which was found in substantial amounts in the fat body of the female, but not in the host bee Andrena vaga. This triple-branched fatty acid precursor thus seems to be biosynthesized de novo through a polyketide pathway with two consecutive propionate-propionate-acetate assemblies to form the complete skeleton. The simplified, motionless and fully host-dependent female exploits a remarkable strategy to maximize its reproductive success by employing a relatively complex and potent sex pheromone.

Love at first…smell: An asymmetric total synthesis, gas chromatographic analyses, and field tests confirm the structure of the first isolated sex pheromone of a twisted-wing parasite Stylops muelleri (see figure). Its biosynthetic origin and complexity demonstrate the considerable efforts undertaken by the motionless and fully host-dependant female to attract the very short-lived free-living male, thus securing success in the perpetuation of the species.

Graphene, a class of two-dimensional carbon nanomaterial, has attracted extensive interest in recent years, with a significant amount of research focusing on graphene oxides (GOs). They have been primed as potential candidates for biomedical applications such as cell labeling and drug delivery, thus the toxicity and behavior of graphene oxides in biological systems are fundamental issues that need urgent attention. The production of GO is generally achieved through a top-down route, which includes the usage of concentrated H₂SO₄ along with: 1) concentrated nitric acid and KClO₃ oxidant (Hoffmann); 2) fuming nitric acid and KClO₃ oxidant (Staudenmaier); 3) concentrated phosphoric acid with KMnO₄ (Tour); or 4) sodium nitrate for in-situ production of nitric acid in the presence of KMnO₄ (Hummers). It has been widely assumed that the properties of these four GOs produced by using the above different methods are roughly similar, so the methods have been used interchangeably. However, several studies have reported that the toxicity of graphene-related nanomaterials in biological systems may be influenced by their physiochemical properties, such as surface functional groups and structural defects. In addition, considering how GOs are increasingly used in the field of biomedicine, we are interested to see how the oxygen content/functional groups of GOs can impact their toxicological profiles. Since in-vitro testing is a common first step in assessing the health risks related with engineered nanomaterials, the cytotoxicity of the GOs prepared by the four different oxidative treatments was investigated by measuring the mitochondrial activity in adherent lung epithelial cells (A549) by using commercially available viability assays. The dose–response data was generated by using two assays, the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and the water-soluble tetrazolium salt (WST-8). From the viability data, it is evident that there is a strong dose-dependent cytotoxic response resulting from the four GO nanomaterials tested after a 24 h exposure, and it is suggested that there is a correlation between the amounts of oxygen content/functional groups of GOs with their toxicological behavior towards the A549 cells.

GO get ‘em: The toxicity of graphene is governed by the amount and type of oxygen-containing groups on its surface and is important for practical applications. The influence of differing oxidative treatments (Staudenmaier, Hofmann, Hummers, and Tour) on the toxicological behavior of graphene oxides have been investigated in adherent lung epithelial cells (see figure)

We describe the synthesis of a series of interlocked structures from porphyrin–glycoluril cage compounds and bis(olefin)-terminated viologens by an olefin-metathesis protocol. The length of the chain connecting the olefin substituents with the viologen has a marked effect on the products of the ring-closure reaction. Long chains give [2]- and [3]catenane structures, whereas short chains give a mixture of [3]-, [4]-, and [5]catenanes. For comparison several [2]rotaxane compounds were prepared. The interlocked catenane and rotaxane structures display switching behavior, which can be controlled by the addition of acid and base. The kinetic and thermodynamic parameters of the switching processes have been determined by NMR spectroscopy.

Olefin metathesis is used as an elegant method to construct a series of catenanes and rotaxanes based on olefin-containing viologen threads and cavity-containing porphyrin macrocycles. By varying the olefin substituents of the viologens, the outcome of the metathesis reactions can be controlled. The interlocked porphyrin structures show acid/base-controlled switching behavior (see figure).

Despite the rapid developments in recent nanocrystal research and their expanding applications, the evolution mechanism of nanocrystals remains veiled for the most part due to the lack of appropriate analytical techniques. Here we demonstrate one promising multi-spectroscopic approach for the in situ investigation of nanocrystal evolution. That is, the formation of nanocrystalline cerium dioxide (NC-CeO₂) has been probed by dynamic light scattering (DLS), X-ray absorption spectroscopy (XAS) and high-energy X-ray scattering (HEXS). The obtained results indicate that the fine colloidal particles of NC-CeO₂ are formed in an acidic aqueous solution simply through the hydrolysis of the initial precursor of small oligomer Ce^IV species. This information on how NC-CeO₂ evolves is fundamental to simplifying and alleviating the synthetic strategy for NC-CeO₂ production.

Nanocrystal evolution: A multi-spectroscopic approach has revealed that the hydrolysis of tetravalent cerium (Ce^IV) produces a colloidal solution of fine cerium dioxide (CeO₂) nanocrystals (see figure). A simple synthetic concept of nanocrystalline metal oxides is proposed based on the obtained results.

Not one, but two: Metalation of a mono-Pd^II hexaphyrin (1) with [Pd(OCOCF₃)₂] gave a bis-Pd^II complex (2), which possesses a characteristic 26 π-aromatic circuit with two outer amino-pyrroles within a rectangular molecular framework. Complex 2 was readily deprotonated to afford dianion, which was regioselectively methylated to give a methyl derivative. Similar methylation reaction of 1 produced skeletal rearranged product that contained an N-confused pyrrole.

Follow that dream: By combining a reversible transesterification between benzylic alcohols and dialkyl oxalates with catalytic decarboxylation of the resulting esters, a regiospecific CC-bond-forming reaction to give α-arylacetates was achieved. In the overall process, CO₂ and a volatile alcohol are the only byproducts. Various α-arylacetates were thus synthesized in high yields from easily accessible starting materials in the presence of catalytic amounts of Pd(OAc)₂, dppp, and DABCO (see scheme).

A new zeolitic–imidazolate framework (ZIF), [Zn(imidazolate)_2−x(benzimidazolate)_x], that has the zeolite A (LTA) framework topology and contains relatively inexpensive organic linkers has been revealed using in situ atomic force microscopy. The new material was grown on the structure-directing surface of [Zn(imidazolate)_1.5(5-chlorobenzimidazolate)_0.5] (ZIF-76) crystals, a metal–organic framework (MOF) that also possesses the LTA framework topology. The crystal growth processes for both [Zn(imidazolate)_2−x(benzimidazolate)_x] and ZIF-76 were observed using in situ atomic force microscopy; it is the first time the growth process of a nanoporous material with the complex zeolite A (LTA) framework topology has been monitored temporally at the nanoscale. The results reveal the crystal growth mechanisms and possible surface terminations on the {100} and {111} facets of the materials under low supersaturation conditions. Surface growth of these structurally complex materials was found to proceed through both “birth-and-spread” and spiral crystal-growth mechanisms, with the former occurring through the nucleation and spreading of metastable and stable sub-layers reliant on the presence of non-framework species to bridge the framework during formation. These results support the notion that the latter process may be a general mechanism of surface crystal growth applicable to numerous crystalline nanoporous materials of differing complexity and demonstrate that the methodology of seeded crystal growth can be used to discover previously unobtainable ZIFs and MOFs with desirable framework compositions.

Surface inspired: A new zeolitic–imidazolate framework that has the zeolite A framework topology and contains relatively inexpensive organic linkers has been grown on the structure-directing surface of ZIF-76 ([Zn(imidazolate)_1.5(5-chlorobenzimidazolate)_0.5]) crystals (see figure). Structural aspects, crystal growth mechanisms and possible surface terminations of both materials are revealed using in situ atomic force microscopy. The work exemplifies the use of this methodology to discover new MOFs with desirable frameworks.

Channel tunneling: We have prepared functional biomimetic nanochannels in polyethylene terephthalate (PET) polymer films (see illustration). We used p-sulfonatocalix[4]arene to modify the channel surface by flexible layer-by-layer electrostatic assembly. Using this method we were able to detect acetylcholine with high sensitivity.

A family of iridium(I)-hydroxides of the form [Ir(cod)(NHC)(OH)] (cod=1,5-cyclooctadiene, NHC=N-heterocyclic carbene) is reported. Single-crystal X-ray analyses and computational methods were used to explore the structural characteristics and steric properties of these new complexes. The model complex [Ir(cod)(IiPr)(OH)] (IiPr=1,3-(diisopropyl)imidazol-2-ylidene) undergoes reaction with a wide variety of substrates including boronic acids and silicon compounds. In addition, OH, NH and CH bond activation was achieved with alcohols, carboxylic acids, amines and various sp-, sp²- and sp³-hybridised carbon centres, giving access to a wide range of new Ir^I complexes. These studies have allowed us to explore the exciting reactivity of this motif, revealing a versatile and useful synthon capable of activating important chemical bonds under mild (typically room temperature) conditions. No additives were required and, in the case of XH bond activation, water was the only waste product, rendering this an atom efficient procedure for bond activation. This system has great potential for the construction of new catalytic cycles for organic synthesis and small-molecule activation.

Reagents of change: General methods are reported for the preparation of a family of (NHC)-iridium(I)-hydroxides and their structural characteristics are explored. The Ir-hydroxide motif was shown to be a valuable synthon for bond activation and its activity towards various organic substrates was explored. The Ir-hydroxide (see figure) is able to deprotonate NH, OH and CH bonds to afford valuable organometallic species.

An efficient catalytic system for Sonogashira–Hagihara-type reactions displaying ligand acceleration in the copper-catalyzed formation of C(sp²)C(sp) bonds is described. The structure of the ligand plays a key role for the coupling efficiency. Various copper sources show excellent catalytic activity, even in sub-mol % quantities. A wide variety of substituents is tolerated in the substrates. Mechanistic details have been revealed by kinetic measurements and DFT calculations.

Just a pinch of copper! An efficient system for the formation of C(sp²)C(sp) bonds has been developed. In sub-mol % quantities various copper sources showed excellent catalytic activity. Different combinations of aryl(hetero) iodides and terminal aryl(hetero) alkynes were applied, leading to the desired products in moderate to excellent yields (see scheme). Mechanistic details of this process have been revealed by kinetic measurements and DFT calculations.

A new class of rare-earth-metal alkynyl complexes has been prepared. The reactions of the tris(tetramethylaluminate)s of lanthanum, praseodymium, samarium, yttrium, holmium, and thulium, [Ln(AlMe₄)₃], with phenylacetylene afforded compounds [Ln{(μ-CCPh)₂AlMe₂}₃] (Ln=La (1), Pr (2), Sm (3), Y (4), Ho (5), Tm (6)). All of these compounds have been characterized by NMR spectroscopy, X-ray crystallography, and by elemental analysis. NMR spectroscopic studies of the series of para- magnetic compounds [Ln(AlMe₄)₃] and [Ln{(μ-CCPh)₂AlMe₂}₃] have also been performed.

A rare sight: A family of rare-earth-metalalkynyl/alkyl complexes was accessed from their tetramethylaluminates, [Ln(AlMe₄)₃], and phenylacetylene. These structures feature new acetylide binding modes and interesting paramagnetic behavior (see figure).

The chromophore of the photoactive yellow protein (PYP), the photoreceptor in the photomotility of the bacterium Halorhodospira halophila, is a deprotonated para-coumaric thioester linked to the side residue of a cysteine residue. The photophysics of the PYP chromophore is conveniently modeled with para-hydroxycinnamic thiophenyl esters. Herein, we report the first direct evidence, obtained with X-ray diffraction, of photodimerization of a para-hydroxycinnamic thiophenyl ester in single crystalline state. This result represents the first direct observation of [2+2] dimerization of a model PYP chromophore, and demonstrates that even very weak light in the visible region is capable of inducing parallel radical reactions in PYP from the excited state of the chromophore, in addition to the main reaction pathway (trans–cis isomerization). This PYP model system adds an interesting example to the known solid-state photodimerizations, because unlike the anhydrous crystal (which is not capable of sustaining the stress and disintegrates in the course of photodimerization), a single water molecule “dilutes” the structure to the extent sufficient for single-crystal-to-single-crystal reaction.

Model under the spotlight: The first X-ray diffraction study of a model for the photoactive yellow protein (PYP) provided direct evidence for the single-crystal-to-single-crystal dimerization of the chromophore under weak visible light (see figure).

CH activation: The ruthenium-catalyzed direct sp² CH amidation of arenes by using sulfonyl azides as the amino source is presented (see scheme). A wide range of substrates were readily amidated including arenes bearing weakly coordinating groups. Synthetic utility of the thus obtained products was demonstrated in the preparation of biologically active heterocycles.

Multi-component organic nanocrystals that are comprised of two or more supramolecular building blocks can be used to extend the design and assembly scope of solid molecular materials. Herein, we report the use of ultrasonication to prepare halogen-bonded stilbene-based nano-cocrystals that exhibit different photoemission properties, including one- and two-phonon emission and fluorescence lifetimes, relative to those of macrodimensional crystals. The structural transformation from nano-cocrystals into nanocrystals upon heating results in a luminescence red-shift from greenish blue to yellow. The temperature-dependent ratiometric luminescence may allow such nano-cocrystals to be used as fluorescent sensors and thermosensitive materials.

Ultrasound as a pound: Halogen-bonding assembled nano-cocrystals that were prepared by using a sonochemical method showed sensitive temperature-dependent luminescence, owing to a transformation from nano-cocrystals into nanocrystals (see figure).

We have prepared a new borazine derivative that bears mesityl substituents at the boron centers and displays exceptional chemical stability. Detailed crystallographic and solid-state fluorescence characterizations revealed the existence of several polymorphs, each of which showed different emission profiles. In particular, a bathochromic shift is observed when going from the lower- to the higher-density crystal. Computational investigations of the conformational dynamics of borazine 1 in both the gas phase and in the solid state using molecular dynamics (MD) simulations showed that the conformation of the peripheral aryl groups significantly varies when going from an isolated molecule (in which the rings are able to flip over the 90° barrier at RT) to the crystals (in which the rotation is locked by packing effects), thus generating specific nonsymmetric intermolecular interactions in the different polymorphs. To investigate the optoelectronic properties of these materials by fabrication and characterization of light-emitting diodes (LEDs) and light-emitting electrochemical cells (LECs), borazine 1 was incorporated as the active material in the emissive layer. The current and radiance versus voltage characteristics, as well as the electroluminescence spectra reported here for the first time are encouraging prospects for the engineering of future borazine-based devices.

Polymorphism power rangers: A new borazine derivative that bears mesityl substituents at the boron centers and displays exceptional chemical stability has been prepared (see figure). Detailed crystallographic and solid-state fluorescence characterizations revealed the existence of several polymorphs, each of which shows different emission profiles.

Two types of 4f–3d thiostannates with general formula [Hen]₂[Ln(en)₄(CuSn₃S₉)]⋅0.5 en (Ln1; Ln=La, 1; Ce, 2) and [Hen]₄[Ln(en)₄]₂[Cu₆Sn₆S₂₀]⋅3 en (Ln2; Ln=Nd, 3; Gd, 4; Er, 5) were prepared by reactions of Ln₂O₃, Cu, Sn, and S in ethylenediamine (en) under solvothermal conditions between 160 and 190 °C. However, reactions performed in the range from 120 to 140 °C resulted in crystallization of [Sn₂S₆]⁴⁻ compounds and CuS powder. In 1 and 2, three SnS₄ tetrahedra and one CuS₃ triangle are joined by sharing sulfur atoms to form a novel [CuSn₃S₉]⁵⁻ cluster that coordinates to the Ln³⁺ ion of [Ln(en)₄]³⁺ (Ln=La, Ce) as a monodentate ligand. The [CuSn₃S₉]⁵⁻ unit is the first thio-based heterometallic adamantane-like cluster coordinating to a lanthanide center. In 3–5, six SnS₄ tetrahedra and six CuS₃ triangles are connected by sharing common sulfur atoms to form the ternary [Cu₆Sn₆S₂₀]¹⁰⁻ cluster, in which a Cu₆ core is enclosed by two Sn₃S₁₀ fragments. The topological structure of the novel Cu₆ core can be regarded as two Cu₄ tetrahedra joined by a common edge. The Ln³⁺ ions in Ln1 and Ln2 are in nine- and eightfold coordination, respectively, which leads to the formation of the [CuSn₃S₉]⁵⁻ and [Cu₆Sn₆S₂₀]¹⁰⁻ clusters under identical synthetic conditions. The syntheses of Ln1 and Ln2 show the influence of the lanthanide contraction on the quaternary Ln/Cu/Sn/S system in ethylenediamine. Compounds 1–5 exhibit bandgaps in the range of 2.09–2.48 eV depending on the two different types of clusters in the compounds. Compounds 1, 3, and 4 lost their organic components in the temperature range of 110–350 °C by multistep processes.

Heterometallic adamantane ligand [CuSn₃S₉]⁵⁻ is coordinated to a lanthanide center in [Hen]₂[Ln(en)₄(CuSn₃S₉)]⋅0.5 en (Ln=La, Ce), while [Hen]₄[Ln(en)₄]₂[Cu₆Sn₆S₂₀]⋅3 en (Ln=Nd, Gd, Er) contain [Cu₆Sn₆S₂₀]¹⁰⁻ cluster anions (see figure). Both compound types were obtained by solvothermal reactions of Ln₂O₃, Cu, Sn, and S in ethylenediamine (en) at 160–190 °C. Their formation reveals the influence of the lanthanide contraction on the quaternary Ln/Cu/Sn/S system.

A highly efficient method for the synthesis of fluorine-containing multisubstituted phenanthridines through Rh-catalyzed alkyne [2+2+2] cycloaddition reactions has been developed. This method exhibits excellent functional-group compatibility. When a bromodifluoromethyl group, rather than a trifluoromethyl group, was employed in the cycloaddition reaction, more-complicated polycyclic compounds were obtained through tandem Rh-catalyzed cycloaddition/CH difluoromethylenation. This route provides convenient access to fluorine-containing polycyclic compounds.

[2+2+2] Little boys: Fluorine-containing multisubstituted phenanthridines have been synthesized through Rh-catalyzed alkyne [2+2+2] cycloaddition reactions (see scheme; FG=functional group). Polycyclic compounds were also obtained through Rh-catalyzed CH difluoromethylenation.

Polyoxometalate (POM) complex (DODA)₂[Mo₆O₁₉] with a symmetrical linear structure was prepared conveniently by replacing the tetrabutylammonium (TBA) counterions of Lindquist-type cluster (TBA)₂[Mo₆O₁₉] with cationic surfactant dioctadecyldimethylammonium (DODA). A helical self-assembled structure of the complex was formed in dichloromethane/propanol. The dynamically reversible transformation between helical and spherical assemblies on alternate UV irradiation and H₂O₂ oxidation was characterized by SEM, TEM, and UV/Vis studies. The redox-controlled morphology change is modulated by variation of the electrostatic interactions between the inorganic polyanion and the organic cation DODA through controlling the redox properties of the POM component, as shown by the XRD, X-ray photoelectron spectroscopic, and ¹H NMR measurements. The strategy applied herein is a unique example of targeted smart and helical assembly of POM complexes.

Smart helical assembly: A symmetrical helical assembly was constructed from surfactant-enwrapped Lindqvist polyoxometalate (POM) complex (DODA)₂[Mo₆O₁₉] (DODA=dioctadecyldimethylammonium). Reversible smart transformation between helical and spherical assemblies associated with photochromism was achieved by controlling the redox properties of the POM component through UV irradiative reduction and H₂O₂ oxidation (see figure).

β1,6-GlcNAc-transferase (C2GnT) is an important controlling factor of biological functions for many glycoproteins and its activity has been found to be altered in breast, colon, and lung cancer cells, in leukemia cells, in the lymhomonocytes of multiple sclerosis patients, leukocytes from diabetes patients, and in conditions causing an immune deficiency. The result of the action of C2GnT is the core 2 structure that is essential for the further elongation of the carbohydrate chains of O-glycans. The catalytic mechanism of this metal-ion-independent glycosyltransferase is of paramount importance and is investigated here by using quantum mechanical (QM) (density functional theory (DFT))/molecular modeling (MM) methods with different levels of theory. The structural model of the reaction site used in this report is based on the crystal structures of C2GnT. The entire enzyme–substrate system was subdivided into two different subsystems: the QM subsystem containing 206 atoms and the MM region containing 5914 atoms. Three predefined reaction coordinates were employed to investigate the catalytic mechanism. The calculated potential energy surfaces discovered the existence of a concerted S_N2-like mechanism. In this mechanism, a nucleophilic attack by O6 facilitated by proton transfer to the catalytic base and the separation of the leaving group all occur almost simultaneously. The transition state for the proposed reaction mechanism at the M06-2X/6-31G** (with diffuse functions on the O1′, O5′, O_Glu, and O6 atoms) level was located at C1O6=1.74 Å and C1O1=2.86 Å. The activation energy for this mechanism was estimated to be between 20 and 29 kcal mol⁻¹, depending on the method used. These calculations also identified a low-barrier hydrogen bond between the nucleophile O6H and the catalytic base Glu320, and a hydrogen bond between the N-acetamino group and the glycosidic oxygen of the donor in the TS. It is proposed that these interactions contribute to a stabilization of TS and participate in the catalytic mechanism.

A model subject: The catalytic mechanism of the key enzyme in the biosynthesis of branched O-glycans, the metal-ion-independent β1,6-GlcNAc-transferase (C2GnT), was investigated by using quantum mechanical (QM) (density functional theory)/molecular modeling (MM) methods (see figure).

Peripheral expansion: A series of peripherally tetrathiafulvalene (TTF)-annulated subphthalocyanines was synthesized (see scheme). These compounds exhibited unique perturbed optical properties, such as a comparatively broad Q band absorption and gradual quenching of fluorescence upon increasing the number of the TTF units, while electrochemical measurements revealed TTF-centered oxidation processes.

Flustering oxindoles: An enantioselective synthesis of 3,3′-disubstituted oxindoles by conjugate addition of malonates to isatylidene-3-acetaldehydes in high yield and enantioselectivity is developed (see scheme). The synthetic utility of this reaction is demonstrated by the synthesis of three oxindole core structures and the asymmetric total synthesis of debromoflustramine E.

Viscoelastic vesicle gels were prepared by mixing a nonionic surfactant, tetraethylene glycol monododecyl ether (C₁₂EO₄), and an anionic dye, sodium 4-phenylazobenzoic acid (AzoNa). The gels, which were composed of multilamellar vesicles, were analyzed by cryogenic transmission electron microscopy (cryo-TEM), freeze–fracture transmission electron microscopy (FF-TEM), ²H NMR spectroscopy, and small-angle X-ray scattering (SAXS). The mechanism of vesicle-gel formation is explained by the influence of anionic molecules on the bilayer bending modulus. Interestingly, the vesicle gels were observed to be sensitive to temperature, pH, and light. The viscoelastic vesicle gels respond to heat; they thin at lower temperatures and become thicker at higher temperatures. The vesicle gels are only stable from pH 7 to 11, and the gels become thinner outside of this range. UV light can also trigger a structural phase transition from micelles to multilamellar vesicle gels.

Shape shifters: Viscoelastic vesicle gels were prepared by mixing C₁₂EO₄ and AzoNa. The vesicle gels were found to be sensitive to temperature, pH, and light. The vesicle gels thicken when heated and thin when cooled and are stable from pH 7 to 11. Outside of this range, the gels become thinner. UV irradiation can also trigger a transition from a micelle solution to multilamellar vesicle gels (see figure).

Spirocyclic azlactones are shown to be useful precursors of cyclic quaternary amino acids, such as the constrained cyclohexane analogues of phenylalanine. These compounds are of interest as building blocks for the synthesis of artificial peptide analogues with controlled folds in the peptide backbone. They were prepared in the present study by a step- and atom-economic catalytic asymmetric tandem approach, requiring two steps starting from N-benzoyl glycine and divinylketones. The key of this protocol is the enantioselective formation of the azlactone spirocycles, which involves a Pd^II-catalyzed double 1,4-addition of an in situ generated azlactone intermediate to the dienone (a formal [5+1] cycloaddition). As the catalyst, a planar chiral ferrocene bispalladacycle was used. Mechanistic studies suggest a monometallic reaction pathway. Although the diastereoselectivity was found to be moderate, the enantioselectivity is usually high for the formation of the azlactone spirocycles, which contain up to three contiguous stereocenters. Spectroscopic studies have shown that the spirocycles often prefer a twist over a chair conformation of the cyclohexanone moiety.

A formal [5+1] cycloaddition of divinylketones and an in situ-generated glycine-derived azlactone was catalyzed by a chiral bis-palladacycle and provided highly enantioenriched, spirocyclic, masked amino acid products. The latter were used to synthesize biologically interesting constrained cyclohexane analogues of phenylalanine in just two steps (see scheme).

The cyclen-based tetraphosphinate chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis[methylene(2-carboxyethyl)phosphinic acid] (DOTPI) comprises four additional carboxylic acid moieties for bioconjugation. The thermodynamic stability constants (logK_ML) of metal complexes, as determined by potentiometry, were 23.11 for Cu^II, 20.0 for Lu^III, 19.6 for Y^III, and 21.0 for Gd^III. DOTPI was functionalized with four cyclo(Arg-Gly-Asp-D-Phe-Lys) (RGD) peptides through polyethylene glycol (PEG₄) linkers. The resulting tetrameric conjugate DOTPI(RGD)₄ was radiolabeled with ¹⁷⁷Lu and ⁶⁴Cu and showed improved labeling efficiency compared with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The labeled compounds were fully stable in transchelation challenges against trisodium diethylenetriaminepentaacetate (DTPA) and disodium ethylenediaminetetraacetic acid (ETDA), in phosphate buffered saline (PBS), and human plasma. Integrin α_vβ₃ affinities of the non-radioactive Lu^III and Cu^II complexes of DOTPI(RGD)₄ were 18 times higher (both IC₅₀ about 70 picomolar) than that of the c(RGDfK) peptide (IC₅₀=1.3 nanomolar). Facile access to tetrameric conjugates and the possibility of radiolabeling with therapeutic and diagnostic radionuclides render DOTPI suitable for application in peptide receptor radionuclide imaging (PRRI) and therapy (PRRT).

Easy way to tetra-nostics: The chelator DOTPI (see figure) allows for the facile multimerization of targeting vectors, for example, peptides addressing cell-surface receptors. Subsequent radiolabeling with the positron-emitter ⁶⁴Cu or the beta-emitter ¹⁷⁷Lu yields a theranostic pair, that is, two nearly equivalent radiopharmaceuticals for nuclear imaging and therapy.

Human A₃ adenosine receptor (hA₃AR) is a membrane-bound G protein-coupled receptor implicated in a number of severe pathological conditions, including cancer, in which it acts as a potential therapeutic target. To derive structure–activity relationships on pyrazolo–triazolo–pyrimidine (PTP)-based A₃AR antagonists, we developed a new class of organometallic inhibitors through replacement of the triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA₃ receptor in the low micromolar range. The assembly of these complexes through a template-driven approach with selective ligand replacement at the metal center to control their steric and receptor-binding properties is discussed.

Scaffold design: A novel class of ruthenium(II)–arene complexes containing chelating N,N-pyrazolo–pyrimidine ligands was rationally developed to be selective antagonists of human A₃ adenosine receptors based on the proven pyrazolo–triazolo–pyrimidine design (see figure).

Improving the electrocatalytic activity and durability of Pt-based catalysts with low Pt content toward the oxygen reduction reaction (ORR) is one of the main challenges in advancing the performance of polymer electrolyte membrane fuel cells (PEMFCs). Herein, a designed synthesis of well-defined Pd@Pt core–shell nanoparticles (NPs) with a controlled Pt shell thickness of 0.4–1.2 nm by a facile wet chemical method and their electrocatalytic performances for ORR as a function of shell thickness are reported. Pd@Pt NPs with predetermined structural parameters were prepared by in situ heteroepitaxial growth of Pt on as-synthesized 6 nm Pd NPs without any sacrificial layers and intermediate workup processes, and thus the synthetic procedure for the production of Pd@Pt NPs with well-defined sizes and shell thicknesses is greatly simplified. The Pt shell thickness could be precisely controlled by adjusting the molar ratio of Pt to Pd. The ORR performance of the Pd@Pt NPs strongly depended on the thickness of their Pt shells. The Pd@Pt NPs with 0.94 nm Pt shells exhibited enhanced specific activity and higher durability compared to other Pd@Pt NPs and commercial Pt/C catalysts. Testing Pd@Pt NPs with 0.94 nm Pt shells in a membrane electrode assembly revealed a single-cell performance comparable with that of the Pt/C catalyst despite their lower Pt content, that is the present NP catalysts can facilitate low-cost and high-efficient applications of PEMFCs.

Thin-shelled catalysts: Well-defined Pd@Pt core–shell nanoparticles with sub-1 nm Pt shells have been synthesized through in situ heteroepitaxial growth of a Pt layer on a Pd nanoparticle core in a solution phase without the assistance of a sacrificial layer. These Pd@Pt_x (x=molar Pt/Pd ratio) nanoparticles showed shell-thickness-dependent catalytic activity toward the oxygen reduction reaction (see figure) and high durability.

Ru^II complexes incorporating both amide-linked bithiophene donor ancillary ligands and laminate acceptor ligands; dipyrido[3,2-a:2′,3′-c]phenazine (dppz), tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j]phenazine (tpphz), and 9,11,20,22-tetraazatetrapyrido[3,2-a:2′,3′-c:3′′,2′′-l:2′′′,3′′′]-pentacene (tatpp) exhibit long-lived charge separated (CS) states, which have been analyzed using time-resolved transient absorption (TA), fluorescence, and electronic absorption spectroscopy in addition to ground state electrochemical and spectroelectrochemical measurements. These complexes possess two electronically relevant ³MLCT states related to electron occupation of MOs localized predominantly on the proximal “bpy-like” portion and central (or distal) “phenazine-like” portion of the acceptor ligand as well as energetically similar ³LC and ³ILCT states. The unusually long excited state lifetimes (τ up to 7 μs) observed in these complexes reflect an equilibration of the ³MLCT_prox or ³MLCT_dist states with additional triplet states, including a ³LC state and a ³ILCT state that formally localizes a hole on the bithiophene moiety and an electron on the laminate acceptor ligand. Coordination of a Zn^II ion to the open coordination site of the laminate acceptor ligand is observed to significantly lower the energy of the ³MLCT_dist state by decreasing the magnitude of the excited state dipole and resulting in much shorter excited state lifetimes. The presence of the bithiophene donor group is reported to substantially extend the lifetime of these Zn adducts via formation of a ³ILCT state that can equilibrate with the ³MLCT_dist state. In tpphz complexes, Zn^II coordination can reorder the energy of the ³MLCT_prox and ³MLCT_dist states such that there is a distinct switch from one state to the other. The net result is a series of complexes that are capable of forming CS states with electron–hole spatial separation of up to 14 Å and possess exceptionally long lifetimes by equilibration with other triplet states.

Ru enlightened: Long-lived, directional photoinduced charge separation in Ru^II complexes with laminate polypyridyl ligands is demonstrated. Charge separated states are exhibited by complexes bearing laminate acceptor and bithienyl donor ligands (see scheme). Unusual excited state lifetimes reflect equilibration of ³MLCT_prox or ³MLCT_dist states with a ³LC state or a ³ILCT state that formally localizes a hole on the bithiophene and an electron on the laminate acceptor ligand.

Quantum mechanical tunneling of atoms allows chemical reactions to proceed through barriers too high for thermally activated processes. This causes hydroxycarbenes to decay rapidly and at a temperature-independent rate even at 11 K. In methylhydroxycarbene, tunneling causes decay through a mechanism that reveals a high but thin barrier rather than an alternative with a lower but broader barrier. No accurate estimates of the widths of such barriers and the lengths of tunneling paths were available. Herein, such a measure is provided by calculating the length of the tunneling paths by using instanton theory. Potential energies are provided by density functional theory verified by explicitly correlated coupled cluster CCSD(T) energies. Our results explain the decay efficiency in the known cases and suggest new substitutions to tune the effects of barrier widths and heights. Fluorination and replacement of the hydroxyl group by a thiol group change the qualitative character of the decay. Methylaminocarbene is predicted to be stable for thousands of years.

Through the tunnel: It is known that atomic quantum tunneling in chemical reactions may take a different path to classical reactions. A method is introduced that calculates the tunneling path. Information on the length of the path (the width of the barrier) is important to judge the probability of tunneling. This explains stability and decay in singlet carbenes (see figure).

A new approach for shaping Au nanostructures by tuning the molecular structure of biomolecules has been explored. Different molecules, such as catechol, rutin, and quercetin, which have structural similarity to the catechol ring, were used to induce Au nanostructures under similar conditions. The as-synthesized nanostructures are characterized by using TEM, XPS, XRD, and UV/Vis spectral measurements. The growth mechanism for the formation of these noble metal shapes and the role of the molecular structure of the stabilizing/reducing agent were investigated by using TEM and UV/Vis spectral measurements. The structure and functional groups of the reducing/stabilizing agent play a vital role in the shape evolution of nanostructures. The electrocatalytic activity of different nanostructures in the reduction of oxygen was investigated and was found to be shape-dependent.

Gold’s gotta catechol! A bioinspired approach for the facile synthesis of gold nanostructures of different shapes has been developed. The structure and functional groups of the reducing/stabilizing agent play a vital role for the shape evolution of nanostructures (see figure).

Herein, we report several examples of stereoselective aldol additions of aldehydes or ketones to Re^I tricarbonyl complexes to form monomeric derivatives in good yields. The metal-centered chirality defines the final stereochemistry of the carbon atom of the monomeric Re^I complex after the addition. However, it cannot control the resulting stereochemistry of the enolate part, and thus, if the α-carbon atom of the reagent is prochiral, a mixture of diastereoisomers is obtained. On the other hand, all of the monomeric complexes can be reversibly dimerized in basic media to form cis dimers, for which an epimerization of the metal-centered chirality is required in order to avoid steric congestion. All of these results are supported by exhaustive crystallographic analysis.

Facing up to Re: The stereochemical pathways of the stereoselective aldol addition of carbonyl compounds to Re^I complexes and pH-driven dimerizations of these adducts (see scheme; Tf=trifluoromethanesulfonyl) have been studied by crystallographic analysis. The aldol addition only occurs on one face of the carbonyl compound, whereas the dimerization occurs with a concomitant epimerization of the metal center.

The preparation of chiral alcohols and amines by using iridium catalysis is reviewed. The methods presented include the reduction of ketones or imines by using hydrogen (hydrogenations), isopropanol, formic acid, or formate (transfer hydrogenations). Also dynamic and oxidative kinetic resolutions leading to chiral alcohols and amines are included. Selected literature reports from early contributions to December 2012 are discussed.

Chemical building blocks: Enantiopure alcohols and amines are very important building blocks used in the pharmaceutical, flavors, and fragrances industry. In this review we focus on the preparation of these compounds by using iridium catalysis. The methods presented include the reduction of ketones or amines by using hydrogen (hydrogenations), isopropanol, formic acid, or formate (transfer hydrogenations; see scheme).

We describe herein a concise synthesis of (+)-neopeltolide, a marine macrolide natural product that elicits a highly potent antiproliferative activity against several human cancer cell lines. Our synthesis exploited the powerful bond-forming ability and high functional group compatibility of olefin metathesis and esterification reactions to minimize manipulations of oxygen functionalities and to maximize synthetic convergency. Our findings include a chemoselective olefin cross-metathesis reaction directed by H-bonding, and a ring-closing metathesis conducted under non-high dilution conditions. Moreover, we developed a 16-member stereoisomer library of 8,9-dehydroneopeltolide to systematically explore the stereostructure–activity relationships. Assessment of the antiproliferative activity of the stereoisomers against A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma, HT-1080 human fibrosarcoma, and P388 murine leukemia cell lines has revealed marked differences in potency between the stereoisomers. This study provides comprehensive insights into the structure–activity relationship of this important antiproliferative agent, leading to the identification of the pharmacophoric structural elements and the development of truncated analogues with nanomolar potency.

SAR of (+)-neopeltolide: A modular synthetic route to (+)-neopeltolide, a potent antiproliferative marine macrolide, was established by exploiting the esterification/olefin metathesis strategy, and a 16-member stereoisomer library of 8,9-dehydeoneopeltolide was developed to elucidate the stereostructure–activity relationships (see figure).

The synthesis of a putative biosynthetic precursor of psymberin including a formal synthesis of the natural product is described. The key step towards the densely functionalized tetrahydropyran core was an enantioselective catalytic Mukaiyama aldol reaction using a titanium(IV)–BINOL catalyst system. syn-Selective reduction followed by ozonolysis led to a rapid assembly of the tetrahydropyran ring. This flexible approach also allows the synthesis of similar fragments of other complex molecules such as bryostatins and pederins. The syn-selective coupling between the tetrahydropyran and the aromatic aldehyde was achieved using a boron-mediated aldol reaction which was followed by further transformations to complete the synthesis of the precursor as well as the formal synthesis of the natural product.

Paving the way: The synthesis towards 8-desmethoxy psymberin, a putative biosynthetic precursor of psymberin, was accomplished in 25 steps including a formal synthesis of the marine natural product itself. The key step towards the THP core was an enantioselective Mukaiyama aldol reaction paving the way for other related THP units. The target compound was submitted for further testing to evaluate its role in the biosynthesis of psymberin.

Peptide-derived protease inhibitors are an important class of compounds with the potential to treat a wide range of diseases. Herein, we describe the synthesis of a series of triazole-containing macrocyclic protease inhibitors pre-organized into a β-strand conformation and an evaluation of their activity against a panel of proteases. Acyclic azido–alkyne-based aldehydes are also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards calpain II, cathepsin L and S, and the 20S proteasome chymotrypsin-like activity. Some of the first examples of highly potent macrocyclic inhibitors of cathepsin S were identified. These adopt a well-defined β-strand geometry as shown by NMR spectroscopy, X-ray analysis, and molecular docking studies.

Clicked to fit: Macrocyclic protease inhibitors, constrained into a β-strand geometry by using Huisgen cycloaddition, are shown to inhibit a range of proteases. The geometries of the component peptide backbones were defined by NMR spectroscopy, X-ray crystallography, and docking studies (see scheme; Cbz=carbobenzyloxy).

The assembly of gold nanoparticles (AuNPs) on a hydrogenated Si(100) surface, mediated by a series of hierarchical and reversible complexation processes, is reported. The proposed multi-step sequence involves a redox-active ditopic guest and suitable calix[n]arene-based hosts, used as functional organic monolayers of the two inorganic components. Surface reactions and controlled release of AuNPs have been monitored by application of XPS, atomic force microscopy (AFM), field-emission scanning electron microscopy (FESEM) and electrochemistry.

Exploring the surface: The assembly of gold nanoparticles (AuNPs) on a hydrogenated Si surface is mediated by a series of hierarchical complexation processes. The multi-step sequence involves a redox-active ditopic guest and suitable functional organic monolayers of the two inorganic components (see figure). Surface reactions and controlled release of AuNPs were monitored.

A family of new chiral zwitterionic phosphorus-containing heterocycles (zPHC) have been derived from methylene-bridged bis(imidazolines). These structures were unambiguously determined, including single-crystal XRD analysis for two compounds. The stability, acid/base and electronic properties of these dipolar phosphorus heterocycles were subsequently investigated. zPHCs can be successfully employed as a new class of chiral solvating agents for the enantiodifferentiation of chiral carboxylic and sulfonic acids by NMR spectroscopy. The stoichiometry and binding constants for the donor–acceptor complexes formed were established by NMR titration methods.

A convenient synthetic approach to a new class of chiral zwitterionic phosphorus-containing heterocycles starting from methylene-bridged bis(imidazolines) was designed and executed. Stability and properties of the synthesized compounds were investigated. The applicability of the designed compounds as chiral solvating agents for the determination of the enantiomeric excesses of chiral acids was demonstrated.

An aluminum-rich MSE-type zeolite (Si/Al is as small as 7) has been successfully synthesized in a remarkably short crystallization period of only 3 days by the hydrothermal conversion of an FAU-type zeolite, presumably by the assembly of four-membered-ring (4-R) aluminosilicate oligomers supplied by the double 6-R (D6R) components of the FAU framework with the aid of the structure-directing agents and seed crystals. The dealuminated version of the aluminum-rich MSE-type zeolite showed a high level of coke durability in addition to a significant yield of propylene, which indicates that this novel zeolitic material is suitable for industrial applications as a highly selective and long-lived catalyst.

Aluminum-rich zeolites: An aluminum-rich MSE-type zeolite (Si/Al as small as 7) has been synthesized in a remarkably short crystallization period of only 3 d by the hydrothermal conversion of an FAU-type zeolite, presumably by the assembly of four-membered-ring (4-R) aluminosilicate oligomers supplied by the double 6-R (D6R) components of the FAU framework with the aid of structure-directing agents and seed crystals (see figure).

A series of soluble carbonyl-bridged heterotriangulenes, in which flexible n-dodecyl chains are attached through different spacers to the planar nitrogen-centered polycyclic core, have been synthesized. The introduction of triisopropylsilylethynyl moieties enabled, for the first time, the characterization of single-crystal columnar packing of a substituted heterotriangulene by X-ray crystallography. Electrochemical studies disclosed the carbonyl-bridged heterotriangulene core as a reasonably strong acceptor for a reversible two-electron transfer. The tendency of substituted heterotriangulenes to self-assemble in solution, on surfaces, and in the bulk appeared to sensitively depend on the nature of the lateral substituents, their steric demand, and the applied solution processing conditions. It can be concluded that 1) additional phenylene moieties between the heterotriangulene core and the n-dodecyl chains facilitate self-assembly by extending the π-conjugated polycyclic disc, 2) the rod-like ethynylene spacers introduce some additional flexibility and hence lower the overall aggregation tendency, and 3) the combination of both features in the phenylene–ethynylene moieties induces thermotropic liquid crystallinity.

Playing the triangle: A series of electron-deficient heterotriangulenes with pendant alkyl chains have been synthesized and their propensity for self-assembly in solution, on a surface, and in the bulk was studied (see figure). A pronounced dependence of the self-assembly behavior on the nature of the spacer between the rigid heterotriangulene core and the flexible alkyl chains was identified.

A new strategy for the fixation of redox-active dinickel(II) complexes with high-spin ground states to gold surfaces was developed. The dinickel(II) complex [Ni₂L(Cl)]ClO₄ (1ClO₄), in which L²⁻ represents a 24-membered macrocyclic hexaaza-dithiophenolate ligand, reacts with ambidentate 4-(diphenylphosphino)benzoate (dppba) to form the carboxylato-bridged complex [Ni₂L(dppba)]⁺, which can be isolated as an air-stable perchlorate [Ni₂L(dppba)]ClO₄ (2ClO₄) or tetraphenylborate [Ni₂L(dppba)]BPh₄ (2BPh₄) salt. The auration of 2ClO₄ was probed on a molecular level, by reaction with AuCl, which leads to the monoaurated Ni^II₂Au^I complex [Ni^II₂L(dppba)Au^ICl]ClO₄ (3ClO₄). Metathesis of 3ClO₄ with NaBPh₄ produces [Ni^II₂L(dppba)Au^IPh]BPh₄ (4BPh₄), in which the Cl⁻ is replaced by a Ph⁻ group. The complexes were fully characterized by ESI mass spectrometry, IR and UV/Vis spectroscopy, X-ray crystallography (2BPh₄ and 4BPh₄), cyclic voltammetry, SQUID magnetometry and HF-ESR spectroscopy. Temperature-dependent magnetic susceptibility measurements reveal a ferromagnetic coupling J=+15.9 and +17.9 cm⁻¹ between the two Ni^II ions in 2ClO₄ and 4BPh₄ (H=−2 JS₁S₂). HF-ESR measurements yield a negative axial magnetic anisotropy (D<0), which implies a bistable (easy axis) magnetic ground state. The binding of the [Ni₂L(dppba)]ClO₄ complex to gold was ascertained by four complementary surface analytical methods: contact angle measurements, atomic-force microscopy, X-ray photoelectron spectroscopy, and spectroscopic ellipsometry. The results indicate that the complexes are attached to the Au surface through coordinative AuP bonds in a monolayer.

Paved with gold: The chemisorption of exchange-coupled [Ni₂L(O₂C₆H₄PPh₂)]⁺ complexes on gold through the ambidentate 4-(diphenylphosphino)benzoate co-ligand is reported (see figure). The binding of the macrocyclic Ni₂ complexes was studied by water contact angle measurements, atomic-force microscopy, X-ray photoelectron spectroscopy, and ellipsometry, by using a discrete trinuclear Ni^II₂Au^I complex [Ni₂L(O₂CC₆H₄PPh₂)AuPPh₃]⁺ as a spectroscopic and structural probe.

Lactimidomycin (1) was described in the literature as an exquisitely potent cell migration inhibitor. Encouraged by this claim, we developed a concise and scalable synthesis of this bipartite glutarimide-macrolide antibiotic, which relies on the power of ring-closing alkyne metathesis (RCAM) for the formation of the unusually strained 12-membered head group. Subsequent deliberate digression from the successful path to 1 also brought the sister compound isomigrastatin (2) as well as a series of non-natural analogues of these macrolides into reach. A careful biological re-evaluation of this compound collection showed 1 and progeny to be potently cytotoxic against a panel of cancer cell lines, even after one day of compound exposure; therefore any potentially specific effects on tumor cell migration were indistinguishable from the acute effect of cell death. No significant cell migration inhibition was observed at sub-toxic doses. Although these findings cannot be reconciled with some reports in the literature, they are in accord with the notion that lactimidomycin is primarily a ribosome-binder able to effectively halt protein biosynthesis at the translation stage.

On the contrary! Alkyne metathesis powered a synthesis-driven (re)evaluation of bipartite glutarimide antibiotics, including lactimidomycin and isomigrastatin, which feature highly strained polyunsaturated macrolide head groups. Rather than being potent cell migration inhibitors as previously claimed, lactimidomycin and progeny was found acutely cytotoxic, causing cell death before any specific interference with cell motility could set in.

n-Heptyl α-D-mannoside (HM) has previously been identified as a nanomolar FimH antagonist able to prevent Escherichia coli adhesion. We have designed mono- and heptavalent glycoconjugates in which HM is tethered to β-cyclodextrin (β-CD) through short and long spacers. One-pot click or co-clicking procedures were developed to directly obtain the glycoconjugates from unprotected HM and β-CD precursors. These FimH antagonists were examined biophysically and in vivo. Reverse titrations by isothermal calorimetry led to trapping of the short-tethered heptavalent β-CD in a complex with three FimH lectins. Combined dynamic light scattering and small-angle X-ray solution scattering data allowed the construction of a model of the FimH trimer. The heptavalent β-CDs were shown to capture and aggregate living bacteria in solution and are therefore also able to aggregate FimH when attached to different bacteria pili. The first in vivo evaluation of multivalent FimH inhibitors has been performed. The heptavalent β-CDs proved to be much more effective anti-adhesive agents than monovalent references with doses of around 2 μg instilled in the mouse bladder leading to a significantly decreased E. coli load. Intravenously injected radiolabeled glycoconjugates can rapidly reach the mouse bladder and >2 μg concentrations can easily be retained over 24 h to prevent fluxing bacteria from rebinding.

Let’s stick together. One-pot click or co-clicking procedures have been developed to directly obtain mono- and heptavalent conjugates from unprotected alkynyl-armed heptyl mannoside (HM) and azido-β-cyclodextrin synthons (see figure). These anti-adhesives aggregate both FimH adhesin and uropathogenic bacteria in solution. The in vivo evaluation of synthetic multivalent FimH inhibitors showed the heptavalent β-CDs to be more effective anti-adhesive agents than the corresponding monovalent HM conjugates.

A method for the stereocontrolled synthesis of a bacterial phosphoglycolipid (PGL1) isolated from thermophilic bacteria is described. The key features of the synthesis include a highly α-selective glycosylation reaction between a trichloroacetimidate donor and a D-lyxose-derived primary alcohol acceptor and the late-stage incorporation of the phospholipid.

Glycolipids from bacteria: A method for the stereocontrolled synthesis of a bacterial phosphoglycolipid (PGL1) isolated from thermophilic bacteria is described. The key features of the synthesis include a highly α-selective glycosylation reaction between a trichloroacetimidate donor and a D-lyxose-derived primary alcohol acceptor and the late-stage incorporation of the phospholipid (see scheme; TBDMS=tert-butyldimethylsilyl).

A new strategy for fast fluorescent detection of cysteine (Cys), based on a response-assisted electrostatic attraction, is demonstrated. By utilizing this strategy, we designed and synthesized three fluorescent probes for the specific detection of Cys under actual physiological conditions. The probe m-CP, a coumarin fluorophore conjugated with a substituted methyl pyridinium group through an unsaturated ketone unit, showed highly selective and sensitive detection for cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). The kinetic analysis indicated that the sensing process was highly accelerated (a response time less than 1 min) by the response-assisted electrostatic attraction. More importantly, control experiments with isomeric probes first demonstrated that the spatial charge configuration of the probe played an important role in Cys-preferred selectivity and kinetic rate acceleration. Furthermore, the practical utility of the probe m-CP in the fluorescent labeling of Cys residues within proteins was demonstrated. Finally, these probes were employed in living cell imaging with HeLa cells, in which it displayed satisfactory cell permeability and enabled us to distinguish active thiols in the cytoplasm, nucleus, and mitochondria.

Cysteine grapple: A new strategy for the development of a cysteine (Cys)-specific probe, based on a response-assisted electrostatic attraction, is demonstrated. We constructed three fluorescent probes with isomeric structures (see scheme). We demonstrate that the spatial charge configuration plays an important role in the Cys-preferred selectivity and sensitivity.

The activation of the CH bond of 1-phenylpyrazole (2) and 2-phenyl-2-oxazoline (3) by [Ru(OAc)₂(p-cymene)] is an autocatalytic process catalyzed by the co-product HOAc. The reactions are indeed faster in the presence of acetic acid and water but slower in the presence of a base K₂CO₃. A reactivity order is established in the absence of additives: 2-phenylpyridine>2-phenyl-2-oxazoline>1-phenylpyrazole (at RT). The accelerating effect of added acetate ions reveals an intermolecular deprotonation after CH bond activation by a cationic Ru^II center (S_E3 mechanism). The reactions of 1-phenylpyrazole and 2-phenyl-2-oxazoline first lead to the neutral cyclometalated complexes A₂ and A₃ ligated by one acetate. The latter dissociate to the cationic complexes B₂⁺ and B₃⁺, respectively, and acetate. A slow incorporation of one or two D atoms into 2, 3, and 2-phenylpyridine (1) was observed in the presence of deuterated acetic acid. The “reversibility” of the CH bond activation/deprotonation takes place from the cationic complexes B_n⁺ (n=1–3). They are also involved in oxidative additions to PhI, which are rate-determining and lead to the mono- and bis-phenylated products at high temperatures. A general mechanism is proposed for the arylation of arenes 1–3 catalyzed by [Ru(OAc)₂(p-cymene)]. In contrast, the reaction of Pd(OAc)₂ with 2-phenylpyridine (1), is much faster: Pd(OAc)₂>[Ru(OAc)₂(p-cymene)]. Since the kinetics is not affected by added acetates, the reaction proceeds through a CMD mechanism assisted by a ligated acetate (intramolecular process) and is irreversible. A bis-cyclometalated Pd^II^Pd^II dimer D′₁ is formed whose bielectronic electrochemical oxidation leads to a [Pd^III^Pd^III]²⁺ dimer, in agreement with the result of a reported chemical oxidation used in arene functionalizations catalyzed by Pd(OAc)₂.

Acetate aid: The activation of the CH bond of 1-phenylpyrazole and 2-phenyl-2-oxazoline by [Ru(OAc)₂(p-cymene)] is an autocatalytic intermolecular process aided by free acetate (see figure). In contrast, activation by Pd(OAc)₂ proceeds through a concerted metalation–deprotonation (CMD) mechanism through an intramolecular and irreversible process that is assisted by ligated acetate. A cyclometalated dimeric Pd^II^Pd^II is formed whose bielectronic electrochemical oxidation leads to a dimeric [Pd^III^Pd^III]²⁺.

The intrinsic acid-base properties of the hexa-2′-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1⋅G2⋅G3⋅C4⋅C5⋅T6)=(HNPP)⁵⁻] have been determined by ¹H NMR shift experiments. The pK_a values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10 % D₂O, 47 °C, I=0.1 M, NaClO₄). These results quantify the release of H⁺ from the two (N7)H⁺ (G⋅G), the two (N3)H⁺ (C⋅C), and the (N1)H⁺ (A) units, as well as from the two (N1)H (G⋅G) and the (N3)H (T) sites. Based on measurements with 2′-deoxynucleosides at 25 °C and 47 °C, they were transferred to pK_a values valid in water at 25 °C and I=0.1 M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three pK_a clusters occur, that is those encompassing the pK_a values of 2.44, 2.97, and 3.71 of G2(N7)H⁺, G3(N7)H⁺, and A1(N1)H⁺, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H₅(HNPP)^±, the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4 %, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no “cost”. The eight pK_a values for H₅(HNPP)^± are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1⋅G2⋅G3⋅ C4⋅C5⋅U6), where U=uridine, were calculated. Finally, the effect of metal ions on the pK_a values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range.

Intrinsic pK_a shifts between 0 and 0.8 pK units of the eight N sites in the single-stranded DNA hexanucleoside pentaphosphate d(ApGpGpCpCpT) were determined by NMR spectroscopic analysis and comparison with the pK_a values of the individual nucleosides. Extensive neighboring effects are due to stacking and charge repulsion. The existing tautomeric equilibria are characterized in detail.

Here we report the direct comparison of a conventional batch mode synthesis of Meclinertant (SR48692, 1), a neurotensin receptor-1 antagonist, with its machine-assisted flow chemistry alternative. By using these enabling tools, combined with solid-supported reagents and scavengers, many process advantages were observed. Care, however, must be taken not to convert these techniques into expensive solutions to problems that do not exist.

Flow and pharmaceuticals? An investigation into whether machine-assisted technologies can be of true help in the multistep synthesis of a potent neurotensin receptor-1 probe, Meclinertant (SR48692; see structure), is reported.

A precise understanding of the mechanism-based inactivation of cytochrome P450 enzymes (P450s) at the quantum mechanical level should allow more reliable predictions of drug–drug interactions than those currently available. Hydrazines are among the molecules that act as mechanism-based inactivators to terminate the function of P450s, which are essential heme enzymes responsible for drug metabolism in the human body. Despite its importance, the mechanism explaining how a metabolic intermediate (MI) is formed from hydrazine is not fully understood. We used density functional theory (DFT) calculations to compare four possible mechanisms underlying the reaction between 1,1-dimethylhydrazine (or unsymmetrical dimethylhydrazine, UDMH) and the reactive compound I (Cpd I) intermediate of P450. Our DFT calculations provided a clear view on how an aminonitrene-type MI is formed from UDMH. In the most favorable pathway, hydrogen is spontaneously abstracted from the N2 atom of UDMH by Cpd I, followed by a second hydrogen abstraction from the N2 atom by Cpd II. Nitrogen oxidation of nitrogen atoms and hydrogen abstraction from the CH bond of the methyl group were found to be less favorable than the hydrogen abstraction from the NH bond. We also found that the reaction of protonated UDMH with Cpd I is rather sluggish. The aminonitrene-type MI binds to the ferric heme more strongly than a water molecule. This is consistent with the notion that the catalytic cycle of P450 is impeded when such an MI is produced through the P450-catalyzed reaction.

Interaction to inactivation: Hydrazines act as mechanism-based inactivators of cytochrome P450 enzymes, which are responsible for drug metabolism in the human body. A density functional theory study provides a clear view on how an aminonitrene-type metabolic intermediate is generated from 1,1-dimethylhydrazine through reaction with the reactive compound I intermediate of cytochrome P450 (see figure).

Endogenous vicinal-dithiol-containing proteins (VDPs) that have two thiol groups close to each other in space play a significant importance in maintaining the cellular redox microenvironment. Approaches to identify VDPs mainly rely on monitoring the different concentration of monothiol and total thiol groups or on indirect labeling of vicinal thiols by using p-aminophenylarsenoxide (PAO). Our previous work has reported the direct labeling of VDPs with a highly selective receptor PAO analogue, which could realize fluorescence detection of VDPs directly in living cells. Herein, we developed a conjugated approach to expand detectable tags to nitrobenzoxadiazole (NBD), fluorescein, naphthalimide, and biotin for the synthesis of a series of probes. Different linkers have also been introduced toward conjugation of VTA2 with these functional tags. These synthesized flexible probes with various features will offer new tools for the potential identification and visualization of vicinal dithiols existing in different regions of VDPs in living cells. These probes are convenient tools for proteomics studies of various disease-related VDPs and for the discovery of new drug targets.

Conjugation approaches were developed to expand a series of chemical probes by attachment of functional tags (nitrobenzoxadiazole (NBD), fluorescein, and biotin) to linkers attached to a stable and selective receptor (VTA2; see figure) for vicinal-dithiol-containing proteins (VDPs). These versatile probes will offer new tools for the potential labeling of various types of VDPs in different microenvironments in living cells.

Multicomponent reactions are attractive for assembling functionalized heterocyclic compounds. To this end, an efficient gold-catalyzed three-component domino reaction to form oxazoles directly from imines, alkynes, and acid chlorides is presented. The reaction proceeds in a single synthetic step by using a gold(III)–N,N′-ethylenebis(salicylimine) (salen) catalyst to give trisubstituted oxazoles in up to 96 % yield. The substrate scope, a mechanistic study exploring the role of the gold catalyst, and the synthetic applications of the oxazole products are discussed.

Crossing bridges: Oxazoles are generated in up to 96 % yield from readily available imines, acid chlorides, and alkynes by using a gold(III) catalyst (see scheme). The use of a sacrificial benzyl group enables the bridging of an imine–alkyne coupling and a cycloisomerization manifold to form the oxazole products in a single domino reaction.

Cationic, two-coordinate triphenylphosphine–gold(I)–π complexes of the form [(PPh₃)Au(π ligand)]⁺ SbF₆⁻ (π ligand=4-methylstyrene, 1⋅SbF₆), 2-methyl-2-butene (3⋅SbF₆), 3-hexyne (6⋅SbF₆), 1,3-cyclohexadiene (7⋅SbF₆), 3-methyl-1,2-butadiene (8⋅SbF₆), and 1,7-diphenyl-3,4-heptadiene (10⋅SbF₆) were generated in situ from reaction of [(PPh₃)AuCl], AgSbF₆, and π ligand at −78 °C and were characterized by low-temperature, multinuclear NMR spectroscopy without isolation. The π ligands of these complexes were both weakly bound and kinetically labile and underwent facile intermolecular exchange with free ligand (ΔG^≠≈9 kcal mol⁻¹ in the case of 6⋅SbF₆) and competitive displacement by weak σ donors, such as trifluoromethane sulfonate. Triphenylphosphine–gold(I)–π complexes were thermally unstable and decomposed above −20 °C to form the bis(triphenylphosphine) gold cation [(PPh₃)₂Au]⁺SbF₆⁻ (2⋅SbF₆).

Golden family: A family of cationic, two-coordinate gold complexes of the form [(PPh₃)Au(π ligand)]⁺SbF₆⁻ were generated in situ and characterized by low-temperature NMR spectroscopy (see scheme). The π ligands of these complexes underwent facile intermolecular exchange with free ligand (ΔG^≠≈9 kcal mol⁻¹) and competitive displacement by weak σ donors.

Electron diffraction offers advantages over X-ray based methods for crystal structure determination because it can be applied to sub-micron sized crystallites, and picogram quantities of material. For molecular organic species, however, crystal structure determination with electron diffraction is hindered by rapid crystal deterioration in the electron beam, limiting the amount of diffraction data that can be collected, and by the effect of dynamical scattering on reflection intensities. Automated electron diffraction tomography provides one possible solution. We demonstrate here, however, an alternative approach in which a set of putative crystal structures of the compound of interest is generated by crystal structure prediction methods and electron diffraction is used to determine which of these putative structures is experimentally observed. This approach enables the advantages of electron diffraction to be exploited, while avoiding the need to obtain large amounts of diffraction data or accurate reflection intensities. We demonstrate the application of the methodology to the pharmaceutical compounds paracetamol, scyllo-inositol and theophylline.

Electron diffraction and polymorphic forms: A new approach to the determination of organic crystal structures in which electron diffraction patterns from a single crystallite are used to identify the structure from a set of putative crystal structures (generated computationally by crystal structure prediction) is described. The approach can be applied to crystallites of sub-micron thickness and to samples in which the phase of interest is the minor component in a mixture of crystal forms.

A new approach to crystal structure determination, combining crystal structure prediction and transmission electron microscopy, was used to identify a potential new crystal phase of the pharmaceutical compound theophylline. The crystal structure was determined despite the new polymorph occurring as a minor component in a mixture with Form II of theophylline, at a concentration below the limits of detection of analytical methods routinely used for pharmaceutical characterisation. Detection and characterisation of crystallites of this new form were achieved with transmission electron microscopy, exploiting the combination of high magnification imaging and electron diffraction measurements. A plausible crystal structure was identified by indexing experimental electron-diffraction patterns from a single crystallite of the new polymorph against a reference set of putative crystal structures of theophylline generated by global lattice energy minimisation calculations.

Crystal structure of an organic picogram crystal: With a combination of electron diffraction and crystal structure prediction it was possible to propose the structure of a new crystal form of the pharmaceutical compound theophylline. This analysis was performed on a single crystallite (pictured), with a thickness of approximately 0.3 μm, present in a sample consisting predominantly of Form II of theophylline, a situation for which conventional X-ray based approaches to crystal structure determination would not be applicable.

DFT calculations have been used to probe the mechanism of the addition reaction of group 15 hydrides EH₃ (E=N, P, As) and H₂ to a N-heterocyclic silylene and its germylene homologue. Nitrogen lone pair donation into the vacant p-orbital of Si and Ge is the first step of ammonia activation, whereas silylene and germylene behave as nucleophiles toward dihydrogen, phosphane, and arsane. Formation of 1,4-addition products is kinetically favoured in all cases. In excess ammonia, the assistance of a second molecule drastically lowers the 1,1-addition energy barriers, enabling formation of 1,1-addition products. The participation of a second molecule in the PH bond activation of phosphane also lowers the 1,1-addition energy barriers, but not enough to cause inversion.

No metal required! Metal-free activation of small molecules such as NH₃, PH₃, AsH₃ and H₂ is an emergent topic in main-group compounds chemistry. Herein, we report the outcomes of a DFT analysis of both ammonia NH bond activation and dihydrogen cleavage occurring at the silicon and germanium centres of N-heterocyclic compounds (see figure). The elucidation of key mechanistic and thermodynamic aspects of the investigated reactions is expected to provide helpful information on similar processes.

The lichen-derived glycoconjugate gobienine A is structurally more complex than most glycolipids isolated from higher plants by virtue of the all-cis substituted γ-lactone substructure embedded into its macrocyclic frame. A concise entry into this very epimerization-prone and hence challenging structural motif is presented, which relies on an enantioselective cyanohydrin formation, an intramolecular Blaise reaction, a palladium-catalyzed alkoxycarbonylation, and a diastereoselective hydrogenation of the tetrasubstituted alkene in the resulting butenolide. This strategy, in combination with ring-closing olefin metathesis for the formation of the macrocyclic perimeter, allowed the proposed structure of gobienine A (1) to be formed in high overall yield. The recorded spectral data show that the structure originally attributed to gobienine A is incorrect and that it is not the epimerization-prone ester site on the butanolide ring that is the locus of misassignment; rather, the discrepancy must be more profound.

Enigmatic beauty: The putative lichen-derived glycolipid gobienine A is structurally rather unique, not least because of its thermodynamically unfavorable all-cis paraconic acid (4-carboxy-γ-butyrolactone) aglycone. A largely catalysis-based and broadly applicable entry into this unusual motif was developed, and the total synthesis of the target glycoconjugate completed, just to find out that the originally proposed structure must have been profoundly misassigned.

Pyridinylazolato (N–N′) ruthenium(II) complexes of the type [(N–N′)RuCl(PMe₃)₃] have been obtained in high yields by treating the corresponding functionalised azolylpyridines with [RuCl₂(PMe₃)₄] in the presence of a base. ¹⁵N NMR spectroscopy was used to elucidate the electronic influence of the substituents attached to the azolyl ring. The findings are in agreement with slight differences in the bond lengths of the ruthenium complexes. Furthermore, the electronic nature of the azolate moiety modulates the catalytic activity of the ruthenium complexes in the hydrogenation of carbon dioxide under supercritical conditions and in the transfer hydrogenation of acetophenone. DFT calculations were performed to shed light on the mechanism of the hydrogenation of carbon dioxide and to clarify the impact of the electronic nature of the pyridinylazolate ligands.

Ruthenium catalysis: Ruthenium complexes of the type [(N–N′)RuCl(PMe₃)₃] (see figure) have been synthesised from azolylpyridines possessing different substituents on the azolyl unit. These complexes show good activity in the catalytic hydrogenation of carbon dioxide to formates. The influence of the azolyl substituents on the catalytic activity was elucidated by spectroscopy and DFT calculations.

Reaction of the ligands 4,5-bis(propylthio)tetrathiafulvalene-2-(2-pyridyl)benzimidazole (L¹) and 4,5-bis(propylthio)tetrathiafulvalene-2-(2-pyridyl)-3-(2-pyridinylmethyl)benzimidazole (L²) with Dy(hfac)₃⋅2 H₂O (hfac=1,1,1,5,5,5-hexafluoroacetylacetonate) gave mononuclear complexes [Dy(hfac)₃(L¹)] (1) and [Dy(hfac)₃(L²)] (2). In both compounds the Dy^III ion is surrounded by six oxygen and two nitrogen atoms. Complex 1 displays single-ion magnet (SIM) behaviour only in solution (Δ=12(1) K and τ₀=1.9(4)×10⁻⁶ s), while complex 2 is a SIM in both solution (Δ=15(2) K and τ₀=1.5(3)×10⁻⁶ s) and solid state (Δ=17(2) K and τ₀=9.5(2)×10⁻⁶ s). The SIM behaviour is obtained if the hydrogen bond is broken by dissolution (1 in solution) or by alkylation (2). Multiple relaxation processes were identified for 2 with two competing processes: a fast one in zero field and a slow one for fields higher than 500 Oe. The two processes coexist for intermediate applied magnetic field. Magnetic-dilution and frozen-solution measurements led to the conclusion that the origin of these multiple relaxation processes is not due to the property of a single molecule.

Hydrogen-bond rupture in mononuclear dysprosium(III) complexes leads to single-ion magnet behaviour with a single relaxation process in frozen solution and magnetically diluted samples, but to multiple relaxation processes for bulk samples (see figure). The origin of these multiple relaxation processes is not attributed to the properties of single molecules.

The double benzannulation of bis-carbene complexes of chromium with α,ω-diynes generates [m.n]cyclophanes in which all three rings are generated in a single reaction. This triple annulation process is very flexible allowing for the construction of symmetrical [n.n]cyclophanes and unsymmetrical [m.n]cyclophanes as well as isomers in which the two benzene rings are both meta bridged or both para bridged, and isomers that contain both meta and para bridges. The connectivity patterns of the bridges in the cyclophanes can be controlled by regioselectivity transfer from the bis-vinyl carbene complexes in which the substitution pattern of the vinyl groups in the carbene complexes dictate the connectivity pattern in the [m.n]cyclophanes. This synthesis of [n.n]cyclophanes is quite flexible with regard to ring size and can be used with tether lengths ranging from n=2 to n=16 and thus to ring sizes with up to 40 member rings. The only limitation to regioselectivity transfer from the carbene complexes to the [m.n]cyclophanes was found in the synthesis of para,para-cyclophanes with four carbon tethers for which the loss of fidelity occurred with the unexpected formation of meta,para-cyclophanes.

Put a ring on it: Regiospecificity is the key in the control of the connectivity patterns in [m.n]cyclophanes. Bis-carbene complexes react with diynes to generate all three rings of [m.n]cyclophanes in a single reaction. The regiochemistry of the vinyl groups in the carbene complexes sets the stage for the nature of the linkages in the cyclophanes.

A small amphiphile that contains a coumarin unit and alkynyl groups, as a two-photon-cleavable segment and polymerizable groups, respectively, was designed and synthesized. The amphiphile showed a critical aggregation concentration of about 4.6×10⁻⁵ M and formed a vesicle-type assembly. The formed vesicles were stabilized by in situ “click” polymerization without altering their morphology. Hydrophobic and hydrophilic guests can be encapsulated within the vesicle membrane and inside the aqueous core of the vesicle, respectively. The loaded guests can be released from the vesicle by using UV or near-IR stimuli, through splitting up the amphiphilic structure of the amphiphile. Distinguished dose-controlled photorelease of the polymeric vesicle is achieved with the maintenance of vesicular integrity, which makes the guest release dependent on the amount of cleavage of the amphiphilic structure during irradiation. This study provides a potential strategy for the development of versatile and stable drug-delivery systems that offer sustained and photo-triggered release.

Light of my life: A robust and versatile vesicle, which was prepared from an amphiphile that contained a coumarin unit and two alkynyl groups, could encapsulate hydrophobic and hydrophilic guests and enable their controlled release by using a two-photon trigger. Dose-controlled photorelease, which was achieved by the polymerized membrane of the vesicles, was dependent on the cleavage amount of the amphiphilic structure during irradiation (see figure).

The heterogeneous proline-catalyzed aldol reaction was investigated under continuous-flow conditions by means of a packed-bed microreactor. Reaction-progress kinetic analysis (RPKA) was used in combination with nonlinear chromatography for the interpretation, under synthetically relevant conditions, of important mechanistic aspects of the heterogeneous catalytic process at a molecular level. The information gathered by RPKA and nonlinear chromatography proved to be highly complementary and allowed for the assessment of optimal operating variables. In particular, the determination of the rate-determining step was pivotal for optimizing the feed composition. On the other hand, the competitive product inhibition was responsible for the unexpected decrease in the reaction yield following an apparently obvious variation in the feed composition. The study was facilitated by a suitable 2D instrumental arrangement for simultaneous flow reaction and online flow-injection analysis.

A good synergy: Reaction-progress kinetic analysis and nonlinear chromatography are useful tools for investigating a model aldol reaction performed in continuous-flow microreactors packed with proline-functionalized silica gel (see figure). The study was facilitated by a suitable instrumental arrangement for online monitoring; it also assessed optimal operating and feed variables.

We present an in situ small- and wide-angle X-ray scattering (SAXS/WAXS) and quick-scanning extended X-ray absorption fine-structure (QEXAFS) spectroscopy study on the crystallization of the metal–organic framework ZIF-7. In combination with DFT calculations, the self-assembly and growth of ZIF-7 microrods together with the chemical function of the crystal growth modulator (diethylamine) are revealed at all relevant length scales, from the atomic to the full crystal size.

X-ray marks the spot: We present an in situ time-resolved small- and wide-angle X-ray scattering and quick-scanning extended X-ray absorption spectroscopy study on the crystallization of the metal–organic framework ZIF-7, along with density functional theory calculations (see figure).

In this work, we demonstrate the successful incorporation of pure fullerene from solution into two-dimensional layered aluminosilicate minerals. Pure fullerenes are insoluble in water and neutral in terms of charge, hence they cannot be introduced into the clay galleries by ion exchange or intercalation from water solution. To overcome this bottleneck, we organically modified the clay with quaternary amines by using well-established reactions in clay science in order to expand the interlayer space and render the galleries organophilic. During the reaction with the fullerene solution, the organic solvent could enter into the clay galleries, thus transferring along the fullerene molecules. Furthermore, we demonstrate that the surfactant molecules, can be selectively removed by either simple ion-exchange reaction (e.g., interaction with Al(NO₃)₃ solution to replace the surfactant molecules with Al³⁺ ions) or thermal treatment (heating at 350 °C) to obtain novel fullerene-pillared clay structures exhibiting enhanced surface area. The synthesized hybrid materials were characterized in detail by a combination of experimental techniques including powder X-ray diffraction, transmission electron microscopy, X-ray photoemission, and UV/Vis spectroscopy as well as thermal analysis and nitrogen adsorption–desorption measurements. The reported fullerene-pillared clay structures constitute a new hybrid system with very promising potential for the use in areas such as gas storage and/or gas separation due to their high surface area.

Fullerene-containing clays: The successful incorporation of pure fullerene from solution into two-dimensional layered aluminosilicate minerals (namely clays) is described. The approach involved the organic modification of the parent clay with quaternary amines by using well-established reactions, thereby achieving expansion of the clay interlayer space and rendering the galleries organophilic. The surfactant molecules can be selectively removed by either simple ion-exchange reactions or thermal treatment.

Three new patterns of reactivity of rare-earth metal methylidene complexes have been established and thus have resulted in access to a wide variety of imido rare-earth metal complexes [L₃Ln₃(μ₂-Me)₃(μ₃-Me)(μ-NR)] (L=[PhC(NC₆H₃iPr₂-2,6)₂]⁻; R=Ph, Ln=Y (2 a), Lu (2 b); R=2,6-Me₂C₆H₃, Ln=Y (3 a), Lu (3 b); R=p-ClC₆H₄, Ln=Y (4 a), Lu (4 b); R=p-MeOC₆H₄, Ln=Y (5 a), Lu (5 b); R=Me₂CHCH₂CH₂, Ln=Y (6 a), Lu (6 b)) and [{L₃Lu₃(μ₂-Me)₃(μ₃-Me)}₂(μ-NR′N)] (R′=(CH₂)₆ (7 b), (C₆H₄)₂ (8 b)). Complex 2 b was treated with an excess of CO₂ to give the corresponding carboxylate complex [L₃Lu₃(μ-η¹:η¹-O₂CCH₃)₃(μ-η¹:η²-O₂C-CH₃)(μ-η¹:η¹:η²-O₂CNPh)] (9 b) easily. Complex 2 a could undergo the selective μ₃-Me abstraction reaction with phenyl acetylene to give the mixed imido/alkynide complex [L₃Y₃(μ₂-Me)₃(μ₃-η¹:η¹:η³-NPh)(μ₃-CCPh)] (10 a) in high yield. Treatment of 2 with one equivalent of thiophenol gave the selective μ₃-methyl-abstracted products [L₃Ln₃(μ₂-Me)₃(μ₃-η¹:η¹:η³-NPh)(μ₃-SPh)] (Ln=Y (11 a); Lu (11 b). All new complexes have been characterized by elemental analysis, NMR spectroscopy, and most of the structures confirmed by X-ray diffraction.

New imido clusters: Three new routes for the synthesis of rare-earth metal imido clusters were established based on the reactions of rare-earth metal methylidene complexes with imines, azobenzenes, and amines, and resulted in access to a wide variety of imido rare-earth metal complexes (an example is shown in the figure). Primary reactivity studies on these imido clusters toward some small molecular substrates provide good options to the synthesis of their imido derivatives.

With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP=2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as commercial compounds, were cross-coupled under palladium catalysis (e.g., Suzuki coupling with 2,4-dimethoxy-5-pyrimidylboronic acid) to afford various representative biaryl compounds. Deprotometalation of the latter compounds was performed by using the lithium/zinc-TMP base and evaluated by subsequent iodolysis. The outcome of these reactions has been discussed in light of the CH acidities of these substrates, as determined in THF solution by using the DFT B3LYP method. Except for in the presence of decidedly lower pK_a values, the regioselectivities of the deprotometalation reactions tend to be governed by nearby coordinating atoms rather than by site acidities. In particular, azine and diazine nitrogen atoms have been shown to be efficient in inducing the reactions with the lithium/zinc-TMP base at adjacent sites (e.g., by using 1-(2-methoxyphenyl)isoquinoline, 4-(2,5-dimethoxyphenyl)-3-methoxypyridine, or 5-(2,5-dimethoxyphenyl)-2,4-dimethoxypyrimidine as the substrate), a behavior that has already been observed upon treatment with lithium amides under kinetic conditions. Finally, the iodinated biaryl derivatives were involved in palladium-catalyzed reactions.

Addicted to base: A series of biaryl compounds, including heterocycles, were deprotometalated by using a 2,2,6,6-tetramethylpiperidino-based mixed lithium/zinc base (see scheme). The obtained regioselectivities are discussed in light of the CH acidities of the substrates, as determined in THF by using the DFT B3LYP method.

Tantalum nitride (Ta₃N₅) modified with various O₂-evolution cocatalysts was employed as a photocatalyst for water oxidation under visible light (λ>420 nm) in an attempt to construct a redox-mediator-free Z-scheme water-splitting system. Ta₃N₅ was prepared by nitriding Ta₂O₅ powder under a flow of NH₃ at 1023–1223 K. The activity of Ta₃N₅ for water oxidation from an aqueous AgNO₃ solution as an electron acceptor without cocatalyst was dependent on the generation of a well-crystallized Ta₃N₅ phase with a low density of anionic defects. Modification of Ta₃N₅ with nanoparticulate metal oxides as cocatalysts for O₂ evolution improved water-oxidation activity. Of the cocatalysts examined, cobalt oxide (CoO_x) was found to be the most effective, improving the water-oxidation efficiency of Ta₃N₅ by six to seven times. Further modification of CoO_x/Ta₃N₅ with metallic Ir as an electron sink allowed one to achieve Z-scheme water splitting under simulated sunlight through interparticle electron transfer without the need for a shuttle redox mediator in combination with Ru-loaded SrTiO₃ doped with Rh as a H₂-evolution photocatalyst.

Split me! A redox-mediator-free Z-scheme water-splitting system capable of working under simulated sunlight was achieved by sing Ir/CoO_x/Ta₃N₅ in combination with the aid of Ru/SrTiO₃:Rh as a H₂-evolution photocatalyst.

Nitrogen (N)-, boron (B)-, and boron,nitrogen (B,N)-doped graphene (G) act as carbocatalysts, promoting the aerobic oxidation of the benzylic positions of aromatic hydrocarbons and cyclooctane to the corresponding alcohol/ketone mixture with more than 90 % selectivity. The most active material was the co-doped (B,N)G, which, in the absence of solvent and with a substrate/(B,N)G ratio of 200, achieved 50 % tetralin conversion in 24 h with a alcohol/ketone selectivity of 80 %. An FT-Raman spectroscopic study of a sample of (B,N)G heated at 100 °C in the presence of oxygen revealed new bands that disappeared upon evacuation and that have been attributed to hydroperoxide-like species formed on the G sheet based on the isotopic shift of the peak from 819 to 779 cm⁻¹ when ¹⁸O₂ was used as the oxidizing reagent. Furthermore, (B)G and (N)G exhibited high catalytic activity in the aerobic oxidation of styrene to benzaldehyde (BA) in 4 h. However, the product distribution changed over time and after 10 h a significant percentage of styrene oxide (SO) was observed under the same conditions. The use of doped G as catalyst appears to offer broad scope for the aerobic oxidation of benzylic compounds and styrene, for which low catalyst loading, mild reaction temperatures, and no additional solvents are required.

Oxidation at graphene: Boron- and nitrogen-doped graphenes are excellent catalysts for promoting the oxidation of benzylic hydrocarbons, cyclooctane, and styrene with molecular oxygen at 0.5 wt % under atmospheric pressure and solvent-free conditions (see figure).

The origin of the experimentally known preference for [6,6] over [5,6] bonds in cycloaddition reactions involving C₆₀ has been computationally explored. To this end, the Diels–Alder reaction between cyclopentadiene and C₆₀ has been analysed by means of the recently introduced activation strain model of reactivity in combination with the energy decomposition analysis method. Other issues, such as the aromaticity of the corresponding transition states, have also been considered. These results indicate that the major factor controlling the observed regioselectivity is the more stabilising interaction between the deformed reactants in the [6,6] reaction pathway along the entire reaction coordinate.

Why [6,6]? The preference for [6,6] over [5,6] bonds in cycloaddition reactions involving C₆₀ is experimentally well-established (see figure). However, the reasons (i.e., physical factors) behind this preference are so far completely unknown. By means of the recently introduced activation strain model of reactivity in combination with the energy decomposition analysis method, a definite answer to the question in the title is provided.

Hydroxyaryl alkyl tellurides are effective antioxidants both in organic solution and aqueous biphasic systems. They react by an unconventional mechanism with ROO^. radicals with rate constants as high as 10⁷ M⁻¹ s⁻¹ at 303 K, outperforming common phenols. The reactions proceed by oxygen atom transfer to tellurium followed by hydrogen atom transfer to the resulting RO^. radical from the phenolic OH. The reaction rates do not reflect the electronic properties of the ring substituents and, because the reactions occur in a solvent cage, quenching is more efficient when the OH and TeR groups have an ortho arrangement. In the presence of thiols, hydroxyaryl alkyl tellurides act as catalytic antioxidants towards both hydroperoxides (mimicking the glutathione peroxidases) and peroxyl radicals. The high efficiency of the quenching of the peroxyl radicals and hydroperoxides could be advantageous under normal cellular conditions, but pro-oxidative (thiol depletion) when thiol concentrations are low.

Anti- and pro-oxidants: Hydroxyaryl alkyl tellurides are unconventional antioxidants able to quench chain-carrying peroxyl radicals with rate constants as high as 10⁷ M⁻¹ s⁻¹ by a mechanism involving oxygen atom transfer to tellurium followed by reaction of the RO^. radical with the phenol (see figure). They can also catalytically decompose both the ROO^. radical and H₂O₂ in the presence of excess thiols.

Based on the different oxidation potentials of endohedral fullerenes Sc₃N@C₈₀ I_h and D_5h and Sc₃N@C₇₈, an efficient and useful method that avoids HPLC has been developed for their separation. Selective chemical oxidation of the Sc₃N@D_5h-C₈₀ isomer and Sc₃N@C₇₈ by using an acetylferrocenium salt [Fe(COCH₃C₅H₄)Cp]⁺ followed by column chromatographic separation and reduction with CH₃SNa resulted in the isolation of pure Sc₃N@I_h-C₈₀, Sc₃N@C₇₈, and a mixture of Sc₃N@D_5h-C₈₀ and Sc₃N@C₆₈.

Endohedral metallofullerenes: Sc₃N@C₈₀ I_h and D_5h isomers and Sc₃N@C₇₈ were selectively separated by using a chemical oxidation and reduction method based on their different oxidation potentials (see figure).

The intramolecular [2+2] photocycloaddition of four 4-(but-3-enyl)oxyquinolones (substitution pattern at the terminal alkene carbon atom: CH₂, Z-CHEt, E-CHEt, CMe₂) and two 3-(but-3-enyl)oxyquinolones (substitution pattern: CH₂, CMe₂) was studied. Upon direct irradiation at λ=300 nm, the respective cyclobutane products were formed in high yields (83–95 %) and for symmetrically substituted substrates with complete diastereoselectivity. Substrates with a Z- or E-substituted terminal double bond showed a stereoconvergent reaction course leading to mixtures of regio- and diastereomers with almost identical composition. The mechanistic course of the photocycloaddition was elucidated by transient absorption spectroscopy. A triplet intermediate was detected for the title compounds, which–in contrast to simple alkoxyquinolones such as 3-butyloxyquinolone and 4-methoxyquinolone–decayed rapidly (τ≈1 ns) through cyclization to a triplet 1,4-diradical. The diradical can evolve through two reaction channels, one leading to the photoproduct and the other leading back to the starting material. When the photocycloaddition was performed in the presence of a chiral sensitizer (10 mol %) upon irradiation at λ=366 nm in trifluorotoluene as the solvent, moderate to high enantioselectivities were achieved. The two 3-(but-3-enyl)oxyquinolones gave enantiomeric excesses (ees) of 60 and 64 % at −25 °C, presumably because a significant racemic background reaction occurred. The 4-substituted quinolones showed higher enantioselectivities (92–96 % ee at −25 °C) and, for the terminally Z- and E-substituted substrates, an improved regio- and diastereoselectivity.

Upon UV irradiation quinolones A undergo a rapid cyclization at the T₁ level (τ≈1 ns) through the respective 1,4-diradicals (e.g., 1), leading to the [2+2]-photocycloaddition products in high yields. Lifetimes and transient absorption spectra have been carefully measured. The high cyclization rate is one key element in the enantioselective formation of products, such as 3, when sensitized by catalyst (+)-2 (10 mol %)

Hybrid organic–inorganic solids represent an important class of engineering materials, usually prepared by sol–gel processes by cross-reaction between organic and inorganic precursors. The choice of the two components and control of the reaction conditions (especially pH value) allow the synthesis of hybrid materials with novel properties and functionalities. 3-Glycidoxypropyltrimethoxysilane (GPTMS) is one of the most commonly used organic silanes for hybrid-material fabrication. Herein, the reactivity of GPTMS in water at different pH values (pH 2–11) was deeply investigated for the first time by solution-state multinuclear NMR spectroscopic and mass spectrometric analysis. The extent of the different and competing reactions that take place as a function of the pH value was elucidated. The NMR spectroscopic and mass spectrometric data clearly indicate that the pH value determines the kinetics of epoxide hydrolysis versus silicon condensation. Under slighly acidic conditions, the epoxy-ring hydrolysis is kinetically more favourable than the formation of the silica network. In contrast, under basic conditions, silicon condensation is the main reaction that takes place. Full characterisation of the formed intermediates was carried out by using NMR spectroscopic and mass spectrometric analysis. These results indicate that strict control of the pH values allows tuning of the reactivity of the organic and inorganic moities, thus laying the foundations for the design and synthesis of sol–gel hybrid biomaterials with tuneable properties.

Tuning the reactivity through pH control: The reactivity of 3-glycidoxypropyltrimethoxysilane (GPTMS) in water at different pH values (pH 2–11) was investigated in detail for the first time by solution-state multinuclear NMR spectroscopic and mass spectrometric analysis (see picture). The extent of the different and competing reactions taking place as a function of the pH value was elucidated.

A total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine is reported. The tetrasubstituted dibenzofuran substructure was accessible either through a Pd-mediated ortho-metalation or by an Ir-catalyzed meta-borylation. The synthesis of the β,β,α-linked trisaccharide consisting of D-olivose, L-rhodinose, and L-rhamnose was challenged by the unprecedented β-linked rhodinose. A Pd-catalyzed β-selective glycosylation of a 4-epi-rhodinose and a subsequent Mitsunobu inversion provided selectively the β-linked L-rhodinose-L-rhamnose disaccharide. Comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product.

Natural product reassignment: Total synthesis of the proposed structures for fulicineroside and its aglycone fulicinerine has been achieved (see figure). Key issues were the tetrasubstituted dibenzofuran and the trisaccharide with its β-linkage between L-rhodinose and L-rhamnose. A comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product.

A new series of donor–bridge–acceptor (D–B–A) compounds consisting of π-conjugated oligofluorene (oFL) bridges between a ferrocene (Fc) electron-donor and a fullerene (C₆₀) electron-acceptor have been synthesized. In addition to varying the length of the bridge (i.e., mono- and bi-fluorene derivatives), four different ways of linking ferrocene to the bridge have been examined. The Fc moiety is linked to oFL: 1) directly without any spacer, 2) by an ethynyl linkage, 3) by a vinylene linkage, and 4) by a p-phenylene unit. The electronic interactions between the electroactive species have been characterized by cyclic voltammetry, absorption, fluorescence, and transient absorption spectroscopy in combination with quantum chemical calculations. The calculations reveal exceptionally close energy-matching between the Fc and the oFL units, which results in strong electronic-coupling. Hence, intramolecular charge-transfer may easily occur upon exciting either the oFLs or Fcs. Photoexcitation of Fc–oFL–C₆₀ conjugates results in transient radical-ion-pair states. The mode of linkage of the Fc and FL bridge has a profound effect on the photophysical properties. Whereas intramolecular charge-separation is found to occur rather independently of the distance, the linker between Fc and oFL acts (at least in oFL) as a bottleneck and significantly impacts the intramolecular charge-separation rates, resulting in beta values between β_CS 0.08 and 0.19 Å⁻¹. In contrast, charge recombination depends strongly on the electron-donor–acceptor distance, but not at all on the linker. A value of β_CR (0.35±0.01 Å⁻¹) was found for all the systems studied. Oligofluorenes prove, therefore, to be excellent bridges for probing how small structural variations affect charge transport in D–B–A systems.

Finely tuned transfer: Chemical modification of the oligo-fluorene linkers between Fc and C₆₀ units enables fine-tuning of photoinduced charge-transfer processes in new donor-bridge-acceptor conjugates (see illustration).

Proteins typically have nanoscale dimensions and multiple binding sites with inorganic ions, which facilitates the templated synthesis of nanoparticles to yield nanoparticle–protein hybrids with tailored functionality, water solubility, and tunable frameworks with well-defined structure. In this work, we report a protein-templated synthesis of Mn-doped ZnS quantum dots (QDs) by exploring bovine serum albumin (BSA) as the template. The obtained Mn-doped ZnS QDs give phosphorescence emission centered at 590 nm, with a decay time of about 1.9 ms. A dual-channel sensing system for two different proteins was developed through integration of the optical responses (phosphorescence emission and resonant light scattering (RLS)) of Mn-doped ZnS QDs and recognition of them by surface BSA phosphorescent sensing of trypsin and RLS sensing of lysozyme. Trypsin can digest BSA and remove BSA from the surface of Mn-doped ZnS QDs, thus quenching the phosphorescence of QDs, whereas lysozyme can assemble with BSA to lead to aggregation of QDs and enhanced RLS intensity. The detection limits for trypsin and lysozyme were 40 and 3 nM, respectively. The selectivity of the respective channel for trypsin and lysozyme was evaluated with a series of other proteins. Unlike other protein sensors based on nanobioconjugates, the proposed dual-channel sensor employs only one type of QDs but can detect two different proteins. Further, we found the RLS of QDs can also be useful for studying the BSA–lysozyme binding stoichiometry, which has not been reported in the literature. These successful biosensor applications clearly demonstrate that BSA not only serves as a template for growth of Mn-doped ZnS QDs, but also impacts the QDs for selective recognition of analyte proteins.

2 proteins, 1 sensor: Protein-directed synthesis of phosphorescent Mn-doped ZnS quantum dots (QDs) is reported. By exploring the phosphorescence and resonance light scattering (RLS) of the QDs, and the specific protein–protein interactions with bovine serum albumin (BSA) as the substrate, a dual-channel sensor was developed that employs only one type of QDs for the detection of two different proteins (see figure).

π-Conjugated thienylenephenylene oligomers with fluorinated and dialkoxylated phenylene fragments have been designed and prepared to understand the interactions in fragment orbitals, the influence of the substituents (F, OMe) on the HOMO–LUMO gap, and the role of intramolecular non-covalent cumulative interactions in the construction of π-conjugated nanostructures. Their strong conjugation was also evidenced in the gas phase by UV photoelectron spectroscopy and theoretical calculations. These results can be explained by the crucial role of the relative energetic positions of the π orbitals of the dimethoxyphenylene, which was used to model the dialkoxyphenylene entity, in determining the π/π^* orbital levels of the fluorinated phenylene entity. Dialkoxyphenylenes raise the HOMO orbitals, whereas fluorinated phenylenes lower the LUMO orbitals in the oligomers. In addition, the presence of S⋅⋅⋅F and H⋅⋅⋅F interactions in the fluorinated phenylenethienylene compounds add to the S⋅⋅⋅O interactions in the mixed targets and contribute to the full conjugation in the oligomer, inducing weak inter-ring angles between the involved aromatic cycles. These results, which showed extended conjugation of the π system, were corroborated by a narrow HOMO–LUMO gap (according to DFT calculations) and by a relatively strong maximum wavelength (as obtained by TD-DFT calculations and experimental UV/Vis measurements). The crystallographic data of two mixed thienylene(fluorinated and dialkoxylated phenylene) five-ring oligomers agree with the above results and show the formation of quasi-planar conformations with non-covalent S⋅⋅⋅O, H⋅⋅⋅F, and S⋅⋅⋅F interactions. These studies in the solid and gas phases show the relevance of associating dialkoxyphenylene and fluorinated phenylene fragments with thiophene to lead to oligomers with improved electronic delocalization for electronic or optoelectronic devices.

Des oligomères thiénylène-phénylène ont été conçus et préparés en incorporant dans l’enchaînement des motifs fluoro- et dialkoxyphényles afin de comprendre l’interaction des orbitales moléculaires entre les fragments, l’influence des substituants (F, OMe) sur l’écart HOMO–LUMO et le rôle d’interactions intramoléculaires cumulées non-covalentes afin d’élaborer des nanostructures fortement π-conjuguées. Leur forte conjugaison résultante a également pu être mise en évidence, en phase gazeuse, grâce à la confrontation des résultats de la spectroscopie photoélectronique à rayonnement UV et des calculs théoriques. Celle-ci peut s’expliquer par le rôle crucial de la position énergétique relative des orbitales π du diméthoxyphénylène, pris comme modèle du motif dialkoxyphénylène, par rapport à celle des orbitales π/π^* des entités fluorobenzène. Les sous-unités dialkoxyphénylène contribuent à élever le niveau de la plus haute orbitale occupée (HO) tandis que les fragments fluorobenzène diminuent le niveau énergétique de la plus basse orbitale vacante (BV) des oligomères. De plus, la présence des interactions S⋅⋅⋅F et H⋅⋅⋅F dans les oligomères thiénylène-fluorophenylène ajoutée à la présence de l’interaction S⋅⋅⋅O dans les nanostructures mixtes possédant des phenylènes fluorés et dialkoxylés contribuent à une conjugaison totale et induisent la diminution de l’angle de torsion entre les cycles aromatiques impliqués. Ces résultats démontrant une conjugaison étendue du système π ont été corroborés par un faible écart énergétique HOMO–LUMO mis en évidence par les calculs de DFT ainsi qu’une longueur d’onde maximale relativement importante obtenue par des calculs de TD-DFT et des mesures expérimentales en spectroscopie UV/Vis. Les données cristallographiques obtenues sur deux oligomères à cinq cycles thiénylène-(fluoro- et dialkoxyphénylène) corrèlent les résultats précédents et mettent en évidence des conformations quasi-planes avec des interactions non-covalentes S⋅⋅⋅O, H⋅⋅⋅F et S⋅⋅⋅F. Ces études réalisées à la fois à l’état solide et en phase gazeuse montrent bien la pertinence d’associer des fragments dialkoxyphénylène et fluorophénylène à du thiophène pour conduire à des oligomères présentant une très forte délocalisation électronique, pouvant être utilisés dans des dispositifs d’électronique ou d’opto-électronique.

π in the sky: Thienylenephenylene oligomers with fluorinated and dialkoxylated phenylene fragments have been designed and prepared. UV photoelectron spectroscopy and DFT calculations highlight how the resulting strong conjugation depends on the energetics of the π orbitals of the molecular fragments, which are related to the nature of the substituents (F, OMe) on the phenylene groups (see figure).

A general, organocatalytic inverse-electron-demand [3+2] cycloaddition reaction between a range of carbonyl compounds and diazoacetates has been developed. This reaction is catalyzed by secondary amines as a “green promoter” to generate substituted pyrazoles with high levels of regioselectivity. It is noteworthy that this [3+2] cycloaddition reaction proceeds efficiently at room temperature with a simple and inexpensive catalyst. Considering the large variety and ready availability of the starting materials (e.g. ketones, β-ketoesters, β-diketones, and aldehydes), as well as the operational simplicity of this process, a convenient, practical, and highly modular pyrazole synthesis has been developed. We believe that this work will arouse more research interest in the organocatalytic synthesis of other biologically active heterocycles. Such studies are currently underway in our laboratory.

Dipoles apart: In situ formed enamines react with diazoacetates under mild conditions to afford the corresponding polysubstituted pyrazoles in good-to-excellent yields through an inverse-electron-demand 1,3-dipolar cycloaddition process (see scheme).

An ultrasensitive surface enhanced Raman scattering (SERS) method has been designed to selectively and sensitively detect lysozyme. The gold chip as the detection substrate, the aptamer-based target-triggering cascade multiple cycle amplification, and gold nanoparticles (AuNPs) bio-barcode Raman probe enhancement on the gold substrate are employed to enhance the SERS signals. The cascade amplification process consists of the nicking enzyme signaling amplification (NESA), the strand displacement amplification (SDA), and the circular-hairpin-assisted exponential amplification reaction (HA-EXPAR). With the involvement of an aptamer-based probe, two amplification reaction templates, and a Raman probe, the whole circle amplification process is triggered by the target recognition of lysozyme. The products of the upstream cycle (NESA) could act as the “DNA trigger” of the downstream cycle (SDA and circular HA-EXPAR) to generate further signal amplification, resulting in the immobility of abundant AuNPs Raman probes on the gold substrate. “Hot spots” are produced between the Raman probe and the gold film, leading to significant SERS enhancement. This detection method exhibits excellent specificity and sensitivity towards lysozyme with a detection limit of 1.0×10⁻¹⁵ M. Moreover, the practical determination of lysozyme in human serum demonstrates the feasibility of this SERS approach in the analysis of a variety of biological specimens.

Target triggering: An ultrasensitive surface enhanced Raman scattering (SERS) method for the detection of lysozyme is reported. Based on aptamer-based target-triggering multiple cycle amplification and gold nanoparticles (AuNPs) bio-barcode Raman probe enhancement on the gold substrate (see figure), the SERS signals are significantly enhanced and concentrations of lysozyme as low as 1 fM could be detected.

A series of zinc–phthalocyanine sensitizers (PcS16–18) with different adsorption sites have been designed and synthesized in order to investigate the dependence of adsorption-site structures on the solar-cell performances in zinc–phthalocyanine based dye-sensitized solar cells. The change of adsorption site affected the electron injection efficiency from the photoexcited dye into the nanocrystalline TiO₂ semiconductor, as monitored by picosecond time-resolved fluorescence spectroscopy. The zinc–phthalocyanine sensitizer PcS18, possessing one carboxylic acid directly attached to the ZnPc ring and six 2,6-diisopropylphenoxy units, showed a record power conversion efficiency value of 5.9 % when used as a light-harvesting dye on a TiO₂ electrode under one simulated solar condition.

All dyed out! Zinc phthalocyanine dyes were designed and optimized in order to increase the absorption of red light in dye-sensitized solar cells (see figure). By optimizing the structure of the adsorption site and reducing the size of bulky substituents, a high power conversion efficiency of 5.9 % was obtained.

The development of novel nanostructured electrode materials with high performance and based on abundant elements is a key element in the societal pursuit of sustainable energy. Graphene-based structures with rich macroporosity and high conductive networks are promising components to develop novel electrode materials. Herein, we described a facile procedure to confine Ni(OH)₂ particles in a graphene film, leading to a new sandwich-like hybrid structure. The hybrid film offers simultaneously ordered ion diffusion channels and high electrical conductivity, which facilitate the improvement of both electrode kinetics and electrochemical stability, thus leading to high capacitance, fast rate capability, and stable cycle life as supercapacitor materials. This work provides a facile pathway for optimized structures for electrode materials, and represents a benefit for the global issues of energy shortage and environmental pollution.

Sandwich-like structures: Confinement of Ni(OH)₂ particles in a graphene film has resulted in a new sandwich-like structure with excellent electrode kinetics and electrochemical stability. This system is a promising candidate for supercapacitor materials (see figure).

The coordination chemistry of the doubly base-stabilised diborane(4), [HB(hpp)]₂ (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido-[1,2-a]pyrimidinate), was extended by the synthesis of new late transition-metal complexes containing Cu^I and Rh^I fragments. A detailed experimental study was conducted and quantum-chemical calculations on the metal–ligand bonding interactions for [HB(hpp)]₂ complexes of Group 6, 9, 11 and 12 metals revealed the dominant BHM interactions in the case of early transition-metal fragments, whereas the BBM bonding prevails in the case of the late d-block compounds. These findings support the experimental results as reflected by the IR and NMR spectroscopic parameters of the investigated compounds. DFT calculations on [MeB(hpp)]₂ and model reactions between [B₂H₄⋅2NMe₃] and [Rh(μ-Cl)(C₂H₄)₂] showed that the bicyclic guanidinate allows in principle for an oxidative addition of the BB bond. However, the formation of σ-complexes is thermodynamically favoured. The results point to the selective BH or BB bond-activation of diborane compounds by complexation, depending on the chosen transition-metal fragment.

Bond deal for diboranes: The synthesis of new diborane complexes combined with experimental and DFT investigations show how BH and BB bonds can be specifically activated depending on the chosen transition-metal fragment (see figure).

Fifteen iodo compounds and six iodyl compounds with an iodine content between 45.3 and 89.0 % were prepared. The mono, di, and triiodyl compounds were obtained from the corresponding iodo compound by employing Oxone. All the compounds were characterized by IR, ¹H and ¹³C NMR, elemental analysis, and differential scanning calorimetry (DSC). The impact sensitivity was measured by using BAM (Bundesamt für Materialforschung) methodology. Based on the calculated heats of formation and experimental densities, the detonation properties and detonation products were predicted by employing Cheetah 6.0. A total percentage of iodine-containing species in wt % (I₂, HI, and I in gas phase) ranged from 46.7 (21) to 88.94 % (11) was found in the detonation products. The high concentration and easy accessibility of iodine and/or iodine-containing species is very important in developing materials suitable as Agent Defeat Weapons (ADWs).

Agent Defeat Weapons: Fifteen iodo compounds and six iodyl compounds with an iodine content between 45.3 and 89.0 % were synthesized. The high concentration and easy accessibility of iodine and/or iodine-containing species is very important in developing materials suitable as agent defeat weapons (see figure).

The complex series [Ru(pap)(Q)₂]ⁿ ([1]ⁿ–[4]ⁿ; n=+2, +1, 0, −1, −2) contains four redox non-innocent entities: one ruthenium ion, 2-phenylazopyridine (pap), and two o-iminoquinone moieties, Q=3,5-di-tert-butyl-N-aryl-1,2-benzoquinonemonoimine (aryl=C₆H₅ (1⁺); m-(Cl)₂C₆H₃ (2⁺); m-(OCH₃)₂C₆H₃ (3⁺); m-(tBu)₂C₆H₃ (4⁺)). A crystal structure determination of the representative compound, [1]ClO₄, established the crystallization of the ctt-isomeric form, that is, cis and trans with respect to the mutual orientations of O and N donors of two Q ligands, and the coordinating azo N atom trans to the O donor of Q. The sensitive CO (average: 1.299(3) Å), CN (average: 1.346(4) Å) and intra-ring CC (meta; average: 1.373(4) Å) bond lengths of the coordinated iminoquinone moieties in corroboration with the NN length (1.292(3) Å) of pap in 1⁺ establish [Ru^III(pap⁰)(Q^.−)₂]⁺ as the most appropriate electronic structural form. The coupling of three spins from one low-spin ruthenium(III) (t_2g⁵) and two Q^.− radicals in 1⁺–4⁺ gives a ground state with one unpaired electron on Q^.−, as evident from g=1.995 radical-type EPR signals for 1⁺–4⁺. Accordingly, the DFT-calculated Mulliken spin densities of 1⁺ (1.152 for two Q, Ru: −0.179, pap: 0.031) confirm Q-based spin. Complex ions 1⁺–4⁺ exhibit two near-IR absorption bands at about λ=2000 and 920 nm in addition to intense multiple transitions covering the visible to UV regions; compounds [1]ClO₄–[4]ClO₄ undergo one oxidation and three separate reduction processes within ±2.0 V versus SCE. The crystal structure of the neutral (one-electron reduced) state (2) was determined to show metal-based reduction and an EPR signal at g=1.996. The electronic transitions of the complexes 1ⁿ–4ⁿ (n=+2, +1, 0, −1, −2) in the UV, visible, and NIR regions, as determined by using spectroelectrochemistry, have been analyzed by TD-DFT calculations and reveal significant low-energy absorbance (λ_max>1000 nm) for cations, anions, and neutral forms. The experimental studies in combination with DFT calculations suggest the dominant valence configurations of 1ⁿ–4ⁿ in the accessible redox states to be [Ru^III(pap⁰)(Q^.−)(Q⁰)]²⁺ (1²⁺–4²⁺)→[Ru^III(pap⁰)(Q^.−)₂]⁺ (1⁺–4⁺)→[Ru^II(pap⁰)(Q^.−)₂] (1–4)→[Ru^II(pap^.−)(Q^.−)₂]⁻ (1⁻–4⁻)→[Ru^III(pap^.−)(Q²⁻)₂]²⁻ (1²⁻–4²⁻).

Proven not innocent! All four redox-active components of [Ru(pap)(Q)₂]ⁿ behave non-innocently in not immediately predictable ways according to structural, spectroelectrochemical, and computational information for the accessible forms between n=2+ and n=2− (see figure). Cations, anions, and neutral forms are distinguished by significant near-infrared absorptions (λ_max>1000 nm).

Perhydrolysis of a sterically congested multifunctional epoxide was achieved in ethereal H₂O₂ with the aid of a recently developed Mo catalyst. The resulting hydroperoxide cyclized to give a 1,2,4-trioxane, which could be readily elaborated into qinghaosu and a range of novel analogues. Some of the compounds with two such trioxane moieties showed in vitro antimalarial activity comparable to or even better than that of artesunate or chloroquine.

Molybdenum magic: Facile perhydrolysis of a highly hindered epoxide was achieved with the aid of a molybdenum catalyst. The resulting hydroperoxide was readily converted into a 1,2,4-trioxane, from which natural qinghaosu (QHS, or artemisinin; see scheme) and a range of analogues were constructed. Some of the newly accessed trioxanes showed in vitro antimalarial activity comparable to or even better than that of chloroquine and artesunate.

The asymmetric Kinugasa reaction was performed on pure water for the first time without the need for any organic co-solvents. In contrast to most asymmetric Kinugasa reactions, trans-β-lactams were obtained as the major products in good yields, enantioselectivities, and diastereoselectivities (up to 90 % yield, 98 % ee, and >99:1 d.r.). This reaction is atom-economical, environmentally friendly, and affords synthetically useful but challenging products.

Walking on water: Asymmetric Kinugasa reactions on pure water without any organic co-solvents afforded synthetically useful trans-β-lactams in good yields, enantioselectivities, and diastereoselectivities (up to 90 % yield, 98 % ee, and >99:1 d.r.).

Recently described and fully characterized trinuclear rhodium-hydride complexes [{Rh(PP*)H}₃(μ₂-H)₃(μ₃-H)][anion]₂ have been investigated with respect to their formation and role under the conditions of asymmetric hydrogenation. Catalyst–substrate complexes with mac (methyl (Z)- N-acetylaminocinnamate) ([Rh(tBu-BisP*)(mac)]BF₄, [Rh(Tangphos)(mac)]BF₄, [Rh(Me-BPE)(mac)]BF₄, [Rh(DCPE)(mac)]BF₄, [Rh(DCPB)(mac)]BF₄), as well as rhodium-hydride species, both mono-([Rh(Tangphos)- H₂(MeOH)₂]BF₄, [Rh(Me-BPE)H₂(MeOH)₂]BF₄), and dinuclear ([{Rh(DCPE)H}₂(μ₂-H)₃]BF₄, [{Rh(DCPB)H}₂(μ₂-H)₃]BF₄), are described. A plausible reaction sequence for the formation of the trinuclear rhodium-hydride complexes is discussed. Evidence is provided that the presence of multinuclear rhodium-hydride complexes should be taken into account when discussing the mechanism of rhodium-promoted asymmetric hydrogenation.

Catalyst–substrate complexes containing the ligands tBu-BisP*, Tangphos, Me-BPE, DCPE, DCPB, and mono- ([Rh(PP*)(MeOH)₂H₂]BF₄) or dinuclear ([{Rh(PP*)H}₂(μ₂-H)₃]BF₄) Rh-hydride species, are described (see figure). A sequence for the formation of the trinuclear Rh-hydride complexes is suggested. The presence of these complexes should be taken into account when discussing the mechanism of asymmetric hydrogenation.

Germanium has been a central feature in the renaissance of main-group inorganic chemistry. Herein, we present the stationary-point geometries of tetragermacyclobutadiene and its related isomers on the singlet potential energy surface at the CCSD(T)/cc-pVTZ level of theory. Three of these 12 structures are reported for the first time and one of them is predicted to lie only 0.4 kcal mol⁻¹ above the previously reported global minimum. Focal-point analyses has provided electronic energies at the CCSD(T) level of theory, which are extrapolated to the complete basis-set limit and demonstrate the convergence behavior of the electronic energies with improving levels of theory and increasing basis-set size. The lowest-energy structure is the bicyclic structure, which lies 35 kcal mol⁻¹ below the “all-Ge” cyclobutadiene structure. The reaction energies for the association of known Ge hydrides (e.g., digermene) to form Ge₄H₄ indicate that Ge₄H₄ could be observed experimentally. We investigate the bonding patterns by examining the frontier molecular orbitals. Our results demonstrate that: 1) the cyclic isomers of (GeH)₄ distort to maximize the mixing of the p orbitals that are involved in the π system of tetragermacyclobutadiene and 2) the lowest-energy isomers exhibit unusual bonding arrangements (e.g., bridging H bonds) that maximize the nonbonding electron density at the Ge centers.

Germaphobe: The structure and energetics of tetragermacyclobutadiene and its structural isomers were investigated by using coupled-cluster methods and focal-point analysis to extrapolate to the complete basis-set limit. The Ge₄H₄ isomers exhibited non-planar structures and less double bonding than in C₄H₄.

Boronic acids are important in the organic and biological arenas. Thus, their identification and characterization are important. ESI-MS is a well-known tool for such uses. Herein we report a systematic analysis of the chemical behavior of arylboronic acids under ESI-MS conditions. Such information will be very critical to understanding the gas-phase chemistry of boronic acids in an ESI mass spectrometer ion source in general and the MS analysis of boronic acids and their macromolecular conjugates in particular.

Mass-ive findings: A systematic analysis of the chemical behavior of arylboronic acids under ESI-MS conditions is reported (see scheme). Such information is critical to understanding the gas-phase chemistry of boronic acids in an ESI mass spectrometer chamber in general and the MS analysis of boronic acids and their macromolecular conjugates in particular.

We have fabricated a mixed-shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroELGroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co-assembly of block copolymers poly(lactide-b-poly(ethylene oxide) (PLA-b-PEG) and poly(lactide)-b-poly(N-isopropylacryamide) (PLA-b-PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone-like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more-complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM-based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.

Heroes in a mixed shell: Core–shell–corona polymeric micelles with a temperature-induced hydrophobic shell can act as an artificial chaperone in a process that involves the capture of thermally denatured proteins, thus preventing their aggregation, followed by assisted refolding during cooling (see figure).

A study of the coordination chemistry of different bis(diphenylphosphino)methanide ligands [Ph₂PC(X)PPh₂] (X=H, SiMe₃) with Group 4 metallocenes is presented. The paramagnetic complexes [Cp₂Ti{κ²-P,P-Ph₂PC(X)PPh₂}] (X=H (3 a), X=SiMe₃ (3 b)) have been prepared by the reactions of [(Cp₂TiCl)₂] with [Li{C(X)PPh₂}₂(thf)₃]. Complex 3 b could also be synthesized by reaction of the known titanocene alkyne complex [Cp₂Ti(η²-Me₃SiC₂SiMe₃)] with Ph₂PC(H)(SiMe₃)PPh₂ (2 b). The heterometallacyclic complex [Cp₂Zr(H){κ²-P,P-Ph₂PC(H)PPh₂}] (4 aH) has been prepared by reaction of the Schwartz reagent with [Li{C(H)PPh₂}₂(thf)₃]. Reactions of [Cp₂HfCl₂] with [Li{C(X)PPh₂}₂(thf)₃] gave the highly strained corresponding metallacycles [Cp₂M(Cl){κ²-P,P-Ph₂PC(X)PPh₂}] (5 aCl and 5 bCl) in very good yields. Complexes 3 a, 4 aH, and 5 aCl have been characterized by X-ray crystallography. Complex 3 a has also been characterized by EPR spectroscopy. The structure and bonding of the complexes has been investigated by DFT analysis. Reactions of complexes 4 aH, 5 aCl, and 5 bCl did not give the corresponding more unsaturated heterometallacyclobuta-2,3-dienes.

Strained metallacycles: Heterometallacyclic complexes of the type [Cp₂M(L)(κ²-P,P-Ph₂PC(X)PPh₂)] (M=Ti, X=H, SiMe₃, no L; M=Zr, X=H, L=H; M=Hf, X=H, SiMe₃, L=Cl) have been prepared through salt elimination pathways, from which the corresponding metallacycles have been obtained in very high yields. Analysis of the structure and bonding of these complexes has revealed that in-plane aromaticity plays an important role in their stabilization, especially in the case of paramagnetic Ti^III complexes (see figure).

A family of highly emissive dithiazolo[5,4-b:4′,5′-d]phospholes has been designed and synthesized. The structures of two trivalent P species, as well as their corresponding P oxides, have been confirmed by X-ray crystallography. The parent dithiazolo[5,4-b:4′,5′-d]phosphole oxide exhibits strong blue photoluminescence at λ_em=442 nm, with an excellent quantum yield efficiency of ϕ_PL=0.81. The photophysical properties of these compounds can be easily tuned by extension of the conjugation and modification of the phosphorus center. Compared with the established dithieno[3,2-b:2′,3′-d]phosphole system, the incorporation of electronegative nitrogen atoms leads to significantly lowered frontier orbital energy levels, as validated by both electrochemistry and theoretical calculations, thus suggesting that the dithiazolo[5,4-b:4′,5′-d]phospholes are valuable, air-stable, n-type conjugated materials. These new building blocks have been further applied to the construction of an extended oligomer with fluorene. Extension of the dithiazolophosphole core with triazole units through click reactions also provides a suitable N,N-chelating moiety for metal binding and a representative molecular species was successfully used as a selective colorimetric and fluorescent sensor for Cu^II ions.

Sliding down with a glow: Incorporation of nitrogen atoms into the dithienophosphole scaffold generates a new building block, dithiazolo[5,4-b:4′,5′-d]phosphole (see scheme), that combines intense luminescence with high electron affinity. A family of conjugated small molecules and a polymer based on this building block have been synthesized by a click reaction that also serves as selective colorimetric and fluorescent sensor for Cu^II.

Rh^III and Ir^III complexes based on the λ³-P,N hybrid ligand 2-(2′-pyridyl)-4,6-diphenylphosphinine (1) react selectively at the PC double bond to chiral coordination compounds of the type [(1H⋅OH)Cp*MCl]Cl (2,3), which can be deprotonated with triethylamine to eliminate HCl. By using different bases, the pK_a value of the POH group could be estimated. Whereas [(1H⋅O)Cp*IrCl] (4) is formed quantitatively upon treatment with NEt₃, the corresponding rhodium compound [(1H⋅O)Cp*RhCl] (5) undergoes tautomerization upon formation of the λ⁵σ⁴-phosphinine rhodium(III) complex [(1⋅OH)Cp*RhCl] (6) as confirmed by single-crystal X-ray diffraction. Blocking the acidic POH functionality in 3 by introducing a POCH₃ substituent leads directly to the λ⁵σ⁴-phosphinine iridium(III) complex (8) upon elimination of HCl. These new transformations in the coordination environment of Rh^III and Ir^III provide an easy and general access to new transition-metal complexes containing λ⁵σ⁴-phosphinine ligands.

Rh^III and Ir^III complexes based on the λ³-P,N hybrid ligand 2-(2′-pyridyl)-4,6-diphenylphosphinine (1) react selectively at the PC double bond to give chiral coordination compounds of the type [(1H⋅OH)Cp*MCl]Cl, which can be deprotonated to form [(1H⋅O)Cp*IrCl] and [(1⋅OH)Cp*RhCl] (see figure). These new transformations in the coordination environment of Rh^III and Ir^III provide an easy and general access to new transition-metal complexes containing λ⁵σ⁴-phosphinine ligands.

A series of oligovalent carbohydrate assemblies (ranging from mono- to pentavalent), derived from three structurally different β-linked or β-(1→2)-linked mannosides, has been chemically synthesized, and the respective compounds have been biologically evaluated in order to investigate their immunostimulatory properties. The Crich methodology for β-mannosylation was successfully utilized to introduce the β-linkages, and a click chemistry protocol was utilized to generate the oligovalent derivatives. A convenient protecting group strategy involving the simultaneous use of both p-methoxybenzyl and benzylidene groups was employed, which allowed a simple and cost-effective global deprotection step. The immunomodulatory properties of the synthesized multivalent mannosides were evaluated by assessing cytokine production in human white blood cell cultures. The Th2-type cytokines interleukin-4 and interleukin-5 (IL-4 and IL-5), the Th1 cytokine interferon-γ (IFN-γ), the Treg cytokine IL-10, and the pro-inflammatory cytokine tumor necrosis factor (TNF) were included in the screening. A single trivalent acetylated mannobiose derivative was identified as a potent inducer of Treg and Th1 immune response, resulting in strong IL-10 and moderate IFN-γ productions dose-dependently, while inducing no Th2 cytokine response. The immunomodulatory properties of this trivalent mannoside were further studied in vitro in allergen (Bet v)-stimulated human peripheral blood mononuclear cell cultures of birch pollen allergic subjects. Stimulation with birch pollen induced strong IL-4 and IL-5 responses, which could be suppressed by the trivalent acetylated mannobiose derivative. The IL-10 response was also suppressed, whereas the production of IFN-γ was strongly enhanced. The results suggest that the identified lead compound has suppressive effects on the Th2-type allergic inflammatory response and shows potential as a possible lead adjuvant for the specific immunotherapy of allergies.

A new direction! A series of oligovalent β-(1→2)-linked mannosides was synthesized by using click chemistry and biologically evaluated to test their immunostimulating properties (see scheme). An acetylated trivalent assembly of mannobioses was a potent inducer of Treg and Th1-type immune response and showed suppressive effects against the Th2-type allergic inflammatory response. This compound might prove useful as an adjuvant in the specific immunotherapy of allergies.

Compound I from cytochrome P450 119 prepared by the photooxidation method involving peroxynitrite oxidation of the resting enzyme to Compound II followed by photooxidation to Compound I was compared to Compound I generated by m-chloroperoxybenzoic acid (MCPBA) oxidation of the resting enzyme. The two methods gave the same UV/Visible spectra, the same products from oxidations of lauric acid and palmitic acid and their (ω-2,ω-2,ω-3,ω-3)-tetradeuterated analogues, and the same kinetics for oxidations of lauric acid and caprylic acid. The experimental identities between the transients produced by the two methods leave no doubt that the same Compound I species is formed by the two methods.

Much of a muchness: Cytochrome P450 119 Compounds I generated by chemical oxidation (black symbols and lines) and photooxidation (red symbols and lines) have the same UV/visible spectra, the same products for oxidations of fatty acids, and the same kinetics of reactions. Rate constants for reactions of Compound I with lauric acid at −5 °C and GC traces of products from oxidations of lauric acid are shown.

Stressing disulfide bonds! Nucleophilic thiol–disulfide exchange reactions within the I27 domain of titin were previously investigated with force clamp AFM. Here, all possible pathways associated with disulfide bond scission at constant tensile force are revealed in terms of end-to-end distances by using force clamp molecular dynamics. The simulations, together with experimental data unravel the competition between mechanochemical bond activation and solvent-mediated regiospecificity exhibited during SS bond cleavage due to the nucleophilic substitution mechanism within a stretched peptide (see figure).

The iron(III) spin-crossover compounds [Fe(Hthsa)(thsa)]⋅H₂O (1), [Fe(Hth5Clsa)(th5Clsa)₂]⋅H₂O (2), and [Fe(Hth5Brsa)(th5Brsa)₂]⋅H₂O (3) (H₂thsa=salicylaldehyde thiosemicarbazone, H₂th5Clsa=5-chlorosalicylaldehyde thiosemicarbazone, and H₂th5Brsa=5-bromosalicylaldehyde thiosemicarbazone) have been synthesized and their spin-transition properties investigated by magnetic susceptibility, Mössbauer spectroscopy, and differential scanning calorimetry measurements. The three compounds exhibit an abrupt spin transition with a thermal hysteresis effect. The more polarizable the substituent on the salicylaldehyde moiety, the more complete is the transition at room temperature with an increased degree of cooperativity. The molecular structures of 1 and 2 in the high-spin state are revealed. The occurrence of the light-induced excited-spin-state trapping phenomenon appears to be dependent on the substituent incorporated into the 5-position of the salicylaldehyde subunit. Whereas the compounds with an electron-withdrawing group (-Br or ‒Cl) exhibit light-induced trapped excited high-spin states with great longevity of metastability, the halogen-free compound does not, even though strong intermolecular interactions (such as hydrogen-bonding networks and π stacking) operate in the system. For compound 2, the surface level of photoconversion is less than 35 %. In contrast, compound 3 displays full photoexcitation.

Pssst—it’s LIESST: Strong intermolecular π–π stacking interactions (see figure) can lead to the light-induced excited-spin-state trapping (LIESST) effect, even for iron(III) spin-crossover (SCO) compounds. This condition, induced through a photoexcitation process, is necessary for trapping the high-spin metastable state of an iron(III) SCO complex.

Reaction of the potassium salt of amido ligand [Ph₂Si(NAr)₂]²⁻ (L, Ar=2,6-iPr₂C₆H₃) and LnI₂(thf)₂ (Ln=Sm, Yb) gives sandwich complexes [(L)₂Ln{K(Et₂O)}₂] (Ln=Sm (2), Yb (3)) with potassium–arene π interactions. Reaction of 2 with azobenzene gave the dimeric samarium cluster [(L)₂Sm₂(μ-η²:η²-N₂Ph₂)₂{K(thf)₂}₂] (4) and the tetrameric [(L)Sm₄ (μ-η²:η²-N₂Ph₂)₃ (μ₃-NPh)₂(thf)₃] (5). On the other hand, the reaction of 2 with α-diimines ligands ArNCRCRNAr (DAD, R=H, Me) gives two Sm^III complexes: polymeric [(L)Sm{(ArN)RCCR(NAr)}K]_n (R=H (6), Me (7)) assembled through cation–π interactions and byproduct [{(L)₂Sm}{K(thf)₆}] (8). Complexes 2–8 have been fully characterized by elemental analyses and X-ray crystallography. In particular, crystallographic analyses of 6 and 7 revealed that in both complexes samarium(III) is stabilized by dianionic DAD units.

Unusual sandwiches: Heterometallic sandwich complex 1 reacts with azobenzene to afford [(L)₂Sm₂(μ-η²:η²-N₂Ph₂)₂{K(thf)₂}₂] (2) and [(L)Sm₄(μ-η²:η²-N₂Ph₂)₃(μ₃-NPh)₂(thf)₃] (3), for which crystallographic studies showed that the alkali metal cation–arene π interactions help to stabilize the divalent metal centers. In addition, complex 1 reacts with diazabutadiene ligands to give Sm^III complexes that form one-dimensional networks through cation–arene π interactions.

To unravel the exact composition and structure of aggregates in an aqueous solution of 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]), we performed static and dynamic light-scattering measurements, as well as transmission electron microscopy (TEM). Results from this work show that the aggregates are vesicles and unstable; herein, we discuss the driving force behind the self-assembly. Apart from the van der Waals forces and repulsive electrostatic interactions between adjacent cation clusters, the hydrogen-bonding forces as well as counterion effects might also contribute to this driving force. The information obtained here is useful for a better understanding of the vital role that aggregation behavior plays in the field of ionic liquid recovery, and its potential use in controlled release, drug delivery, and petroleum recovery.

Deviant behavior: The structure of aggregates in an aqueous solution of [Bmim][BF₄] were examined and revealed to be vesicles (see graphic, white circles are H₂O) and unstable. This ultimately led to the conclusion that their aggregation behavior in water is somewhat different from that of surfactants, although both are surface-active agents.

The well-known Stöber method has been used to coat crosslinked polymers on inorganic nanomaterials. In their Communication on page 6942 ff., J. Liu, S. Z. Qiao, and co-workers report a procedure for the synthesis of Ag,AgBr@RF core–shell composites from a resorcinol–formaldehyde (RF) resin and their derivative core–and yolk–shell-structured carbon composites. Because of the adjustability and functionality of both cores and shells, these complex core–and yolk–shell spheres could have potential applications as nanocatalysts.

Nitrile reductase QueF catalyzes the reduction of a nitrile to its corresponding amine. In their Full Paper on page 7007 ff., N. Klempier et al. report on the investigation of active-site binding and the substrate scope of E. coli QueF by modeling, enzyme, and substrate engineering. The active-site residues and structural features of the substrates essential for catalysis were identified in spectrophotometric and HPLC-MS based screenings of active-site mutants and natural substrate analogues.

This review focuses on recent developments and growth potential in colorimetric and/or fluorimetric chemosensors based on rationally designed materials and suitable for use in highly selective and sensitive naked-eye detection of environmental and biological analytes.

From nanoparticles to quantum dots to polymers: A review of the synthesis, fabrication, mechanisms and development of materials-based sensors for various analytes is presented. The abundance of physical space in the nanostructured materials and the ease of selective functionalization allows efficient colorimetric sensing of different analytes.

Quick, but not dirty! Microwave heating was found to have a significant effect on the Ru-catalyzed hydrovinylations of alkynes. A broad range of different terminal alkynes were coupled to methyl acrylate within just 30 min in good to excellent yields (see scheme). This new protocol was transferred to the hydrovinylation of enynes as novel coupling partners in CH-activation chemistry giving different 1,3,5-trienes as the sole products.

Layer upon layer: A facile extended Stöber method has been developed for the synthesis of diverse metal–carbon spheres, which includes core–shell-structured Ag@carbon, rattle-type Ag,AgBr@meso-SiO₂, and yolk–shell-structured Ag@carbon@meso-SiO₂ (see figure).

Magnetic switch: An iron(II) complex with a diarylethene moiety was synthesized and its magnetic properties were investigated. The complex exhibited four unique electronic states based on high- and low-spin iron(II), as well as open- and closed-forms of the diarylethene moiety (see scheme). The complex showed switchable spin states based on light-induced excited-spin-state trapping in the solid state, as well as through photocyclization reactions in butyronitrile.

Metal-free cooperation: The cooperative combination of Eosin Y as a photoredox catalyst with organocatalytic thiourea allows for the highly diastereoselective construction of trans-1,2-cycloalkanes and heterocycles. This new efficient, cooperative organophotoredox/organocatalysis protocol presents a valuable alternative to metal-based photoredox approaches and is the first example of combining photoredox with hydrogen-bond catalysis (see scheme).

Covalent linkages: Zwitterion-based covalent linkages were observed in cyclic oligomers and in dispersed polymers based on monomers. Addition of acids and bases promoted transitions between monomeric species and the oligomeric and/or polymeric states. Exchange of constituent monomer units in the cyclic oligomers was observed in the solution state, whereas the polymers obtained as precipitates from CH₃CN were not converted to the cyclic oligomers (see scheme).

Golden gates: Conformational change of single-strand, duplex, and triplex structures triggered by Ag⁺ and Hg²⁺ has been used to construct electronic logic gates (AND, NAND, and NOR) by metal-ion-mediated base pairs (C-Ag⁺-C and T-Hg²⁺-T; see scheme).

Soak it up: A boron-imidazolate metal–organic framework composed of a mixed ligand system acts as a precursor for the synthesis of a high-surface-area borocarbonitride (BC₄N) with remarkable H₂ and CO₂ storage properties (see figure; ndc=naphthalenedicarboxylate). Furthermore, BC₄N has been exploited for the stabilisation of metal (Au and Pd) nanoparticles.

Photochromism: Functionalization of a diarylethene derivative with π-conjugated oligomers resulted in a higher aggregation capability in the open rather than the closed form due to tunable steric hindrance of methyl groups of the diarylethene core (see scheme). Distinct aggregation abilities of the open and the closed isomers in nonpolar solvent and phototunable energy transfer between the two functional units enabled visible-light-triggered formation of fluorescent organogels.

MDO rocks! Proline and (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid are both poor catalysts for the inverse-electron-demand hetero-Diels–Alder reactions between aldehydes and electron-deficient enones. However, forming modularly designed organocatalysts (MDOs) through their self-assembly with cinchona alkaloid-derived thioureas can dramatically improve the efficiency of these catalysts (see scheme; PCC=pyridinium chlorochromate).

Gd in silica: Noncovalent confinement of a monoaqua Gd chelate into biocompatible silica nanoparticles (NPs; see figure) by a sol-gel method affords a new example of nanosized contrast agents with very high per-Gd relaxivities. Such NPs provide a route to highly efficient multimodal contrast agents.

Golden opportunities: A redox-, atom-, and step-economical asymmetric cascade reaction for the synthesis of chiral spirocyclic architectures with two contiguous stereocenters in high yields and excellent enantioselectivities by using a gold/chiral Brønsted acid relay catalysis system is described (see scheme). The results suggest that the chiral Brønsted acid rather than the chiral gold phosphate complex serves as the real catalyst of the enantiodetermining step.

We present the synthesis of the isobicyclo-DNA building blocks with the nucleobases A, C, G and T, as well as biophysical and biological properties of oligonucleotides derived thereof. The synthesis of the sugar part was achieved in 5 steps starting from a known intermediate of the tricyclo-DNA synthesis. Dodecamers containing single isobicyclo-thymidine incorporations, fully modified A- and T-containing sequences, and fully modified oligonucleotides containing all four bases were synthesized and characterized. Isobicyclo-DNA forms stable duplexes with natural nucleic acids with a pronounced preference for DNA over RNA as complements. The most stable duplexes, however, arise by self-pairing. Isobicyclo-DNA forms preferentially B-DNA-like duplexes with DNA and A-like duplexes with complementary RNA as determined by circular dichroism (CD) spectroscopy. Self-paired duplexes show a yet unknown structure, as judged from CD spectroscopy. Biochemical tests revealed that isobicyclo-DNA is stable in fetal bovine serum and does not elicit RNaseH activity.

A twist to DNA structure: Moving the phosphodiester backbone from the natural C(5′) position into the C(6′) position, which is only available on the bicyclo-DNA skeleton, leads to isobicyclo-DNA (Isobc-DNA; see scheme). Isobc-DNA forms stable duplexes with DNA and discriminates RNA as a complement. In addition, it forms very stable antiparallel self-duplexes with a structure that is different from A-, B-, and Z-DNA.

Nitrile reductase QueF catalyzes the reduction of 2-amino-5-cyanopyrrolo[2,3-d]pyrimidin-4-one (preQ₀) to 2-amino-5-aminomethylpyrrolo[2,3-d]pyrimidin-4-one (preQ₁) in the biosynthetic pathway of the hypermodified nucleoside queuosine. It is the only enzyme known to catalyze a reduction of a nitrile to its corresponding primary amine and could therefore expand the toolbox of biocatalytic reactions of nitriles. To evaluate this new oxidoreductase for application in biocatalytic reactions, investigation of its substrate scope is prerequisite. We report here an investigation of the active site binding properties and the substrate scope of nitrile reductase QueF from Escherichia coli. Screenings with simple nitrile structures revealed high substrate specificity. Consequently, binding interactions of the substrate to the active site were identified based on a new homology model of E. coli QueF and modeled complex structures of the natural and non-natural substrates. Various structural analogues of the natural substrate preQ₀ were synthesized and screened with wild-type QueF from E. coli and several active site mutants. Two amino acid residues Cys190 and Asp197 were shown to play an essential role in the catalytic mechanism. Three non-natural substrates were identified and compared to the natural substrate regarding their specific activities by using wild-type and mutant nitrile reductase.

To pick a pocket: Nitrile reductase QueF is the only enzyme known to catalyze the reduction of a nitrile to its corresponding amine. The active site binding and the substrate scope of E. coli QueF (see figure) was investigated. Natural substrate analogues were synthesized and screened with wild-type and mutant QueF. Three non-natural substrates were found, and amino acid residues that are essential for the reduction were identified.