Angewandte Chemie International Edition

The tight regulation of bacterial resitance against the antiobiotic tetracycline (Tc) has been studied by crystallographic methods in atomic detail. In the resistant bacterial cell, homodimeric tetracycline repressor (TetR)₂ binds with high specificity to operator DNA (K_ass≈10¹¹ M⁻¹; see picture) and inhibits transcription of the gene tetA, which codes for the resistance protein TetA. If Tc enters the bacterial cell, it forms a complex with (TetR)₂ and induces conformational changes in the dimer that are partly stabilized by the cooperative binding of water molecules. This releases operator DNA, which is associated with the biosynthesis of protein TetA so that the bacterial cell becomes resistant to Tc.

Conformation is the mediator between structure and function in all flexible active molecules. Since the function of many (biologically) active molecules is controlled by conformation, that is reason enough to try to decode the conformation design found in nature. The next step is to apply the insights gained to the synthesis of large molecular skeletons with a predetermined conformation. The present view shows how far this is possible regarding substituted and functionalized alkane chains, for example 1, in which the preferred conformation (right) may be deduced from the structural formula (left) by use of the principles put forward in this review.

The bridged structure of diborane B₂H₂ does not conform to the usual Lewis-bonding scheme. The establishment of the correct diborane structure took time and required persuasion. A significant scene from the Schlessinger–Pauling correspondence is highlighted.

Conformational constraints are the keys for the efficient synthesis of medium-sized rings by ring-closing olefin metathesis (RCM). While the RCM reaction has already proved itself in the synthesis of the larger macrocycles, like that found in epothilone, only recently has this reaction been increasingly used in the construction of eight- to ten-membered carbo- and heterocycles. In the picture, a cyclopentane ring ensures the conformational constraints necessary for a successful cyclization.

New traceless linkers based on sulfur and selenium mediate useful chemical transformations of substrates during their attachment to solid supports. Also, the cleavage from the support can now be performed with simultaneous C−C bond formation. A cyclization on selenium-functionalized polystyrene (Pol) is shown.

An astonishing amount of methane is reversibly adsorbed in pores of [{CuSiF₆(4,4′-bipyridine)₂}_n], which exists as a stable 3D microporous network (see picture). The approximate channel sizes of this material is 8×8 Ų along its c axis and 6×2 Ų along the a and b axes. At 36 atm, the density of methane adsorbed in micropore volume is 0.21 g mL⁻¹, which is superior to that of any reported zeolites.

Hydrolyses with complete retention of configuration are reported for the first time for nonnatural Cinchona alkaloids, both the quinidine and quinine series. This is attributed to the favourable syn, open conformation of the substrates as well as molecular recognition by solvation. Naturally configured C9 derivatives, however, are hydrolysed with complete inversion (see scheme). Ms=Methanesulfonyl.

The replacement of sp²C−R fragments by isolobal phosphorus atoms may cause a reversal of the order of the frontier orbitals on metallocenes (see scheme). Hexaphosphamanganocene 1 is a good example to demonstrate this effect, as it exhibits the ground state ²A, not previously observed for manganocene derivatives. The spin-density distribution of 1 mainly resembles a manganese d orbital. In contrast to decamethylmanganocene, 1 is not Jahn–Teller active!

Isolated spin doublets and not quartets are identified by EPR spectroscopy and SQUID magnetometer measurements in the title compound, the first well-characterized molecular complex with C₆₀ trianions. As shown in the X-ray structure (see picture for a section), the fullerene trianions are ordered and stacked in a slightly distorted hexagonal primitive arrangement; the distances between the spherical fullerenes and also some of the K−C bond lengths are surprisingly short.

In the potential energy hypersurface (see picture) of (CH)₈ isomers lies a bifurcation point (valley–ridge inflection, VRI), which plays a crucial role in the interconversion of cyclooctatetraene (COT) to semibullvalene (SBV). This VRI point connects the transition structure for the valence isomerization from COT to SBV (TS1) with the transition structure for the Cope rearrangement for SBV (TS2) and provides a concerted, one-step reaction path for the valence isomerization.

With no prior knowledge of the identity of single components, a complete assignment of a bioactive ligand from a mixture of 15 carbohydrate ligands can be accomplished by utilizing NMR spectroscopy. A 3D-TOCSY-(transfer)NOESY experiment delivered essential information for the critical assignment of the glycosidic linkage type of the bioactive disaccharide (see scheme).

Replacement of the butyrolactone unit of the natural products with a quinone subunit has resulted in the synthesis of natural-product hybrids of quinone–mucocin (1). These compounds, which are combined from partial structures of annonaceous acetogenins and ubiquinone, are very potent inhibitors of complex I (an NADH ubiquinone oxidoreductase) from mitochondrial membranes.

A high formaldehyde feed concentration and a low reaction temperature are among the advantages of using heteropolyacids (phosphotungstic acid and silicotungstic acid) as catalysts in the formation of trioxane; this cyclic trimer of formaldehyde (see scheme) is used in the industrial production of acetal resins. Compared to reactions with a conventional catalyst, like sulfuric acid, trioxane can be produced in higher yield and with higher selectivity.

Monocarbocyclic nine-membered rings can be enantioselectively accessed by deprotonation of (Z,Z)-dienyl carbamates 1 and subsequent intramolecular α,α′-coupling to furnish the cyclononadienols 2 (R=H: 73% yield, e.r.=96:4; R=OSiPh₂tBu: 79% yield, e.r.=100:0, d.r.=94:6). Cby=2,2,4,4-Tetramethyl-1,3-oxazolidin-3-ylcarbonyl, Cb=diisopropylaminocarbonyl.

A six-fold coordinated As atom was shown to be the first structurally characterized As^V azide [PPh₄]⁺[As(N₃)₆]⁻. The anion (see picture) has idealized S₂ symmetry.

Up to three reporter groups are covalently bound to a protein in one step by an Ugi reaction. Thus, protein conjugates can be prepared which bear up to three low molecular weight reporter groups in an equimolar ratio.

The thermally stable μ₄-peroxo complex 1 and its analogous bis(μ₂-hydroxo) complex 2 have been structurally characterized. Complex 1 offers new insights into the binding of O₂ at multinuclear copper sites and 2 provides an indication of where the reduction of O₂ on a Cu₄ core might eventually lead.

By using porous silica gel as a solid support, template molecules can be immobilized to give a novel approach to molecular imprinting in polymers. Polymerizable, functional monomers assemble around a template (such as theophylline, see picture). Following polymerization, this support is sacrificed by dissolving in HF. The remaining polymer shows a specific binding capacity for theophylline, but not for related compounds, such as theobromine and caffeine. All binding sites are uniformly oriented and located at the surface of the polymer.

The starlike anion [{(CO)₅Cr}₃Pb]²⁻ (1) with its trigonal-planar coordination at the central metal Pb and its short Pb−Cr bonds (273 pm; left-hand structure) is an organometallic equivalent of CO₃²⁻. The conjugated Pb-p_π–Cr-d_π bonding system in 1 corresponds to the conjungated p_π–p_π bonding system of the carbonate ion. The unsaturated character of 1 is revealed in the formation of the PMe₃ adduct [{(CO)₅Cr}₃PbP(CH₃)₃]²⁻ (2) (d(Cr−Pb)=282 pm; right-hand structure).

Nitric oxide reacts selectively with the O₂ stable, weakly fluorescent complex [Co(DATI-4)] in dichloromethane solution to dissociate a fluorophore-substituted arm of the aminotroponiminate ligand DATI-4. The resulting cobalt–dinitrosyl adduct (see picture) effects a positive fluorescence response. The detection limit of 2 is 50–100 μM for NO.

Nitric oxide in solitary confinement: Conformationally mobile p-tert-butylcalix[4]arene methyl ether captures nitric oxide (NO) with unprecedented efficiency (K>5×10⁸ M⁻¹) upon oxidative activation. X-ray crystallographic and NMR spectroscopic studies confirm that NO penetrates deep into the interior of the quasi-cylindrical cavity of the 1,3-alternate conformer (see picture).

The transition state during the highly enantioselective abstraction (see picture) of the pro-S atom of N-Boc-pyrrolidine 1 by the alkyllithium reagent iPrLi/(−)-sparteine was investigated using ab initio molecular orbital calculations. The stability of the transition states was found to be controlled by steric parameters.

Achiral building blocks form nonracemic, chiral capsular hosts with enantioselective molecular recognition properties. The chirality is imprinted by a chiral guest template, and persists for hours in organic solvents after the guest has been removed. The exchange equilibria are depicted, with the guest exchanges shown by the horizontal equilibria and monomer exchanges by the vertical equilibria.

A topochemical polymerization of a triacetylene has been achieved by the synthesis of a host molecule specifically designed to preorganize a triacetylene dicarboxylic acid guest in accordance with the exacting structural requirements needed for the reaction. Irradiation of the resulting host–guest complex using γ-rays yields a base-soluble polytriacetylene polycarboxylic acid (see picture). This study demonstrates the power of supramolecular synthesis as a preparative tool.

Novel peripherally heterogeneous dendrimers in which both ferrocene and cobaltocenium units are attached to the surface of poly(propylene imine) dendritic frameworks (see picture) were prepared. The presence of the two redox-active moieties allows the heterometallic dendrimers to be used as novel types of mediator in amperometric biosensors.

Interaction with the zeolitic walls changes the structure of zeolite-encapsulated Cu^I(CO)₃ cations (see picture), which were synthesized in situ by treating Cu^I-ZSM-5 zeolite with CO at 80 K, from the planar D_3h form, typical of homogeneous analogues such as [Cu(CO)₃]⁺AsF₆⁻, to a C_3v-symmetric bent form. This conclusion was drawn on the basis of fine-structure and near-edge X-ray adsorption spectra, supported by IR spectroscopic data.

The secret behind the efficient formation of a Schiff base aluminum initiator for the controlled polymerization of methacrylates is a nickel catalyst. Bis(acetylacetonato) nickel(II), [Ni(acac)₂], in combination with a suitable alkylating agent, catalyzes the transformation of methylmethacrylate (MMA) monomer into the active aluminum centers (see scheme). Highly syndiotactic-enriched (84 %) poly(methylmethacrylate) (PMMA) can be prepared at −20 °C and block copolymers are readily accessible.

Selective and efficient transformation of a diazoketone monolayer on a Pt (110) metal surface has been achieved by irradiation using light with a wavelength of 300–400 nm. The monolayer loses nitrogen to give a remarkably stable ketene intermediate at the interface.

The incorporation of amino acids into proteins in vivo is controlled by the aminoacyl-tRNA synthetases. The successful incorporation of a nonnatural amino acid, trans-crotylglycine (Tcg), into a protein has now been achieved by increasing the methionyl-tRNA synthetase activity of a bacterial expression host (see scheme). The incorporation of Tcg into proteins creates new opportunities for macromolecular synthesis through genetic engineering, due to the rich chemistry of the olefinic side chain.

In a high yield photoreaction (90–99 %), enyne–carbodiimides (X=N) cyclize to indoloquinolines within a few minutes (see scheme). Analogously, enyne–ketenimines (X=CAr) photocyclize to benzocarbazoles, which paves the way to a simple synthesis of certain photoactive prodrugs.

The crucial intermediate A with a racemization barrier of 16 kcal mol⁻¹ at −78 °C is proposed for the asymmetric α-methylation of 1 to give 2 in 81 % ee and 96 % yield (see scheme). The asymmetric α-methylation occurs in other amino acid derivatives (Dopa, Val, Leu, Trp, His, Tyr) in 78–93 % ee.

Regioselective, double C−H activation of a variety of ether and amine substrates, as exemplified with an ether in [Eq. (1)], is effected by the Ir^I compound [Ir(κ³-Tp^Ph)(η⁴-isoprene)]). The formation of the corresponding Fischer-type carbenes follows the activation reaction. Tp^Ph=hydridotris(3-phenylpyrazol-1-yl)borate.

Purification and characterization of a new enzyme belonging to the amino sugar N,N-dimethyltransferase family has been achieved. DesVI catalyzes the successive transfer of two methyl groups in the biosynthetic pathway of desosamine (see scheme), an unusual sugar found in many macrolide antibiotics, including methymycin (R¹=OH, R²=H) and neomethymycin (R¹=H, R²=OH).

Mixtures of derivatives of coumarin-2 and coumarin-343 can self-assemble on silicon wafers to form monolayers in which light harvesting and energy transfer take place (see picture). Photophysical properties, such as donor quenching and fluorescence amplification, were tuned by varying the molar ratio of the donor and acceptor chromophores on the surface or by increasing the number of coumarin-2 chromophores on the donor adsorbate through the use of a dendritic linker.

Reversible intramolecular cyclization reactions to form crown ethers are possible with photoactive anthracene derivatives containing two binding sites (see scheme). Different chemical inputs in the form of HgCl₂ and Na⁺ ions result in changes in the efficiency and rate of the forward and reverse processes.

The base sets the rhythm for a mixed-valence Mn^III(Mn^IV)₃ complex which catalyzes the disproportionation of hydrogen peroxide. The presence of the base 1,4,7-trimethyl-1,4,7-triazacyclononane switches the catalysis kinetics from Michaelis–Menten type (Hill coefficient n=1.03) to cooperative (Hill coefficient n=1.58; see the figure). The cooperative catalytic behavior has the highest turnover constant reported to date for any synthetic manganese complex.

DBU-catalyzed Michael addition reactions were shown to occur at room temperature between a nickel(II) complex of the Schiff base of glycine 1 and (S)- or (R)-N-(E-enoyl)-4-phenyl-3-oxazolidin-2-ones (2, see scheme). This reaction, which has an almost completely stereoselective outcome, provides a practical and generalized approach to a family of glutamic/pyroglutamic acids. R=alkyl, aryl.

A Mannich-insertion strategy was employed in the synthesis of cytostatic 1. The synthesis allowed the absolute and relative stereochemistry to be confirmed and yielded quantities of 1 suitable for upcoming biological testing. Boc=tert-butoxycarbonyl.