Chloride-Anion-Templated Synthesis of a Strapped-Porphyrin-Containing Catenane Host System

The synthesis, structure and anion-recognition properties of a new strapped-porphyrin-containing [2]catenane anion host system are described. The assembly of the catenane is directed by discrete chloride anion templation acting in synergy with secondary aromatic donor–acceptor and coordinative pyridine–zinc interactions. The [2]catenane incorporates a three-dimensional, hydrogen-bond-donating anion-binding pocket; solid-state structural analysis of the catenane⋅chloride complex reveals that the chloride anion is encapsulated within the catenane’s interlocked binding cavity through six convergent CH⋅⋅⋅⋅Cl and NH⋅⋅⋅Cl hydrogen-bonding interactions and solution-phase 1H NMR titration experiments demonstrate that this complementary hydrogen-bonding arrangement facilitates the selective recognition of chloride over larger halide anions in DMSO solution.


Introduction
[n]Catenanes, ac lass of mechanicallyb ondedm olecules comprising n interlocked ring components, [1] have received evergrowinga ttention over recent decades on account of their interesting topologies and aesthetic appeal, in addition to their potential applicationsa sm olecular machines, [2] imaging agents, [3] host systems [4] and functional nanomaterials. [5] However,d espite the widespread interest in catenane compounds, their synthesis remains challenging, usually relyingo nt he use of interweavingt emplating interactions to organise the molecular precursor componentsi na no rthogonal manner,b efore performing the final ring-closing step. Since Sauvage'sp ioneering use of aC u I -directed orthogonal assembly strategy, [6] much synthetic effort hasb een devoted to the development of new and efficient template-directedp rotocols for the preparation of catenanes. Although coordinate metal-ligand bonds remain the most widely exploited templatingi nteractions, [7] av ariety of alternativen oncovalent interactions, including p-p interactions, [8] hydrogen bonding, [8c, 9] radical-radical interactions, [10] halogen bonding, [11] and solvatophobic effects, [12] have been successfully appliedt ocatenane synthesis.
Our group [13] and others [14] have demonstrated that anions can also be effectively employed as discrete interweaving templates during catenane synthesis, and that the preorganised three-dimensional binding pockets contained within the resultant interlocked architectures can subsequently be exploited for selective anion-recognition purposes. [15] Incorporation of as uitable optical or redox-active reporter group can give rise to systems that produce as ignalling responseu pon complexation of the target guest species. However, despite the promise of this approach, anion-templation strategies remain underdeveloped and examples of catenane-based host systemst hat are capable of optically or electrochemically sensingt he presence of an anionic guest species are rare. [16] Herein we describet he synthesis and solid-state structure of an ew strapped-porphyrin-containing [2]catenane anion host system,w hich is assembled by using chloride anion templation in combination with aromatic donor-acceptor interactions and pyridine-zinc ligation. [17] After removal of the templating anion,t he catenane'sh alide anion-recognition and sensing properties were probedb y 1 HNMR, UV/Vis and fluorescence titration experiments.

Results and Discussion
Design and synthetic strategy We have previouslye mployed ac hloride-anion-templated, amide-condensation-based clippings trategy to assemble [2]catenane architectures in which bidentate hydrogen-bonddonorg roups from each of the interlocked macrocyclic components converge towards ac entral, three-dimensional binding cavity,w here the halide anion template is encapsulated.
Upon removal of the template, the [2]catenanes were shown to recognise halide anionss electively over oxoanionsi n1:1 CDCl 3 /CD 3 OD, which is primarily attributedt ot he optimal size-and shape-complementarity between the halide anions and the hosts' interlocked binding domains. [13d] In the currents tudy we have modified our previousc atenane design by incorporating az inc(II) metalloporphyrin unit into one of the interlocked macrocyclic components,a nd a3 ,5-pyridine bis(amide) motif into the second macrocycle component, in order to introduce an intercomponent pyridine-zinc interaction into the final interlocked structure (Figure 1).
We anticipated that this coordinativei nteraction could be exploited in severalw ays: as well as providing an auxiliary templating interaction during catenane assembly,t he pyridine-zinc ligationp rocess was predicted to enhancet he anion recognition properties of the [2]catenane host system by increasing both the overall preorganisationo ft he host system and the acidity of the 3,5-pyridine bis(amide) hydrogen-bond-donor groups;i t was also envisaged that the pyridine-zinc bond would create ad irect through-bond communication pathway betweent he anion recognition site and the porphyrin chromophore, which could potentially enable the [2]catenane host system to optically sense the presenceo fa nencapsulated guest anion.
The assignment of the atropisomers was confirmed by solidstate structural characterisation of compounds Zn·3a and 3b ( Figure 2). In both structures, the meso-aryl substituents are ar- Figure 1. Cartoon representation of the intended synthetic route to the target strapped-porphyrin-containing [2]catenane, which incorporates an intercomponent pyridine-zinc coordinative bond.
Having isolatedt he a,a-bis(amino)porphyrin precursor Zn·3a,t he strap component of the porphyrin-containing macrocycle was constructed in ten steps from commercially available4 -(benzyloxy)phenol. Reaction of this precursor with bromooacetonitrile, followedb yc yano-groupr eduction, Boc-protection of the amino group and hydrogenative debenzylation afforded the phenol derivative 7, [13a] which was condensed with ethyl bromoacetate to providec ompound 8. Cleavage of the N-Boc protectingg roup by bubbling HCl (g) through as olution of compound 8 in Et 2 Oy ielded the corresponding amine as its hydrochloride salt, 9·HCl. This wasc ondensed with 0.5 equivalents of the bis-acid chloride 10 to produce the bis-esteri ntermediate 11,w hich was subsequently converted into the bis-acid-functionalised strap precursor 12 in 88 %y ield by base-mediated hydrolysiso ft he ester groups. An EDC-promoted coupling reaction[ EDC = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide,w hich was added to the reaction as ah ydrochloride salt] between this bis-acid derivativea nd the a,a-bis(amino)porphyrin Zn·3a in DMFa fforded the pyridine-strapped macrocycle 13 in 44 %y ield. [26] Finally,a lkylation of the pyridine group by treatment of macrocycle 13 with MeI in the presence of NaHCO 3 [27] in DMF, followed by repeated extraction with NH 4 Cl (aq) ,a fforded the chloride salt of the target pyridinium-strapped porphyrin macrocycle, 14·Cl, in 99 %y ield (Scheme 2).
Both of the new macrocycles 13 and 14·Cl werec haracterised by X-ray crystallography in the solid state. The crystal structureo ft he pyridine-strapped macrocycle 13 ( Figure 3) reveals the existence of an intramolecular coordinative interaction between the pyridyl nitrogen atom and the zinc(II) cation (ZnÀN pyr distance:2 .222(3) ), which causes the strap to fold inwards,i nducingaparallel stacking arrangement between the 1,4-hydroquinone and 3,5-pyridine bis(amide) moieties. A saddle distortion of the porphyrin unit is also apparent. For the N-methylpyridinium-strapped macrocycle 14·Cl, it is not possible for an analogous intramolecular pyridine-zinci nteraction to occur,a nd the axial coordination site is instead occupied by ap yridine solvate molecule, which ligatest ot he outer face of the porphyrin unit (ZnÀN pyr distance:2 .136(4) ; Figure 4). The macrocycle's 3,5-pyridiniumb is(amide) group adopts a syn-syn conformation and the chloride counteranion is held within the resultant binding cleftb yt hree short NH···Cl and CH···Cl contacts (N···Cl distances:3 .348(1) and 3.233(1) ; C···Cl distance:3 .231(2) ). Examination of the crystal packing reveals that the pyridinium macrocycle 14·Cl forms ah ead-totail dimer in the solid state. Each dimeric unit appearst ob e stabilised by two complementary intermolecular aromatic stacking interactions between the pyridinium and porphyrin groups,i na ddition to four NH···O amide-amide hydrogen bonds.
Ad ramatic > 6ppm upfield shift in the signal for the aromatic ortho pyridine proton ai sobserved upon incorporation of macrocycle 17 into the [2]catenane, withc oncomitant 0.3-1.2 ppm upfield shifts in the signals corresponding to the para pyridine proton ba nd aliphatic CH 2 protons da nd e. This indicates that the pyridyl group is located within the shielding region createdb yt he porphyrin ring currents,a nd therefore strongly suggestst hat the [2]catenane is stabilised by an intercomponent pyridine-zinc interaction in solution. In contrast, the resonance fora mide protonc shifts downfield, which is consistentw ith the pyridine bis(amide) group participating in NH···Cl hydrogen-bonding interactions with the chloride anion, since these interactions would be expectedt op olarise the amide NH bonds. The pronouncedu pfield shift and splittingo f the resonances for hydroquinone protons fa nd gi sd iagnostic of secondary aromatic-donor-acceptor interactions between the electron-richh ydroquinone groups in the neutral macrocycle and the electron-deficient pyridinium component of the chargedm acrocycle. [30] In addition, an umber of through-space interactions between the two interlocked macrocyclic components of the catenane were observed by 2D 1 HNMR ROESY spectroscopy in CD 2 Cl 2 and [D 6 ]DMSO, which provided further supportive evidence for the interlocked nature and proposed solution conformation of the [2]catenane( see the Supporting Information, FiguresS20 and S24).
Single crystals of the [2]catenanes 16·Cl and 16·PF 6 that were suitable for X-ray structural determination were grown by layered diffusion of hexane into aC H 2 Cl 2 /MeOH solution of the chlorides alt 16·Cl, andb yl ayered diffusion of diisopropyl ether into an acetones olution of the hexafluorophosphate salt 16·PF 6 .I nb oth cases, the crystalsw ere small and weakly diffracting, and X-ray diffraction dataw ere collectedb yu sing synchrotron radiation.
The crystal structure of the chloride-complexedc atenane 16·Cl( Figure 6) confirms the existence of an intercomponent pyridine-zinc coordinativeb ond in the solid state (ZnÀN pyr distance:2 .138 (2) ). The chloride anion is encapsulated within the pseudo-octahedral interlocked binding cavity defined by the orthogonally disposed 3,5-pyridinium bis(amide) and 3,5pyridine bis(amide) moieties. The hydrogen atoms from each of the sixa romatic CH and amide NH hydrogen-bond-donor groups are directed towards the encapsulated chloride anion, and six short X···Cl (X = C, N) contacts are observed, with X···Cl distances ranging from 3.285 to 3.353(2) a nd XÀH···Cl angles ranging from 159 to 1808.Ap arallel donor-acceptor-donor aromatic stacking arrangement between the electron-rich 1,4-  www.chemeurj.org hydroquinone and electron-deficient pyridiniumm otifs is also observed, with centroid-to-centroid distances of 3.493 and 3.822 .
The diffractiond ata obtained for the hexafluorophosphate catenane 16·PF 6 were unusually weak and the structure was found to incorporate as ignificant degree of disorder, necessitating the use of extensive restraints during minimisation. Nevertheless, it is evident from the structure that the conformation of the hexafluorophosphate catenane 16·PF 6 is largely unchanged fromt hat of the chloride catenane 16·Cl in the solid state ( Figure 6). In the absence of an encapsulatedc hloride anion, the pyridine-zinc coordinativeb ond and approximate interlocked co-conformation of the two macrocyclesa re preserved, but the 3,5-pyridinium bis(amide) and 3,5-pyridine bis(amide) groups adopt a syn-anti conformation, which is stabilised by two intercomponent NH···O amide-amide hydrogen bonds. The hexafluorophosphate counteranion is not involved in short contacts with the hydrogen-bond-donor groups from either of the bis(amide) motifs,w hichi si na ccordance with its assumedn on-coordinating role. [31] Halide recognition and sensingexperiments Encouraged by the crystallographic evidencet hat the chloride counteranion is encapsulated within the interlocked binding cavity of the [2]catenane 16·Cl in the solid state, we employed 1 HNMR, UV/Vis and fluorescencespectroscopictitration experiments to investigate the ability of the [2]catenane host system to recognise and sense halide anions in solution. 1

HN MR titration experiments
Additiono fa ni ncreasing concentrationo ft etrabutylammonium (TBA) chloride to a1 .5 mm solution of compound 16·PF 6 in [D 6 ]DMSO inducedp rogressive shifts in the 1 HNMR signals for protons14, 15 and c ( Figure 7), which is consistent with fast-exchange complexation of the chloride anion within the [2]catenane's interlocked binding domain. A1 :1 stoichiometric association constant of K = 2144(149) m À1 was determined by analysiso ft he chloride-concentration-dependents hifts of the externalp yridinium proton 16 with WinEQNMR2 [32] software ( Figure 8). In contrast, comparable titratione xperiments using TBAI and TBABr salts produced no convincing evidence of ab inding interaction between the larger halide anions and the catenane's interlocked cavity.A ddition of up to 10 equivalents of TBABra nd TBAI to a[ D 6 ]DMSO solutiono ft he catenaner esulted in only slight (Dd 0.11ppm) perturbationsi nt he 1 HNMR signals for the cavity protons 14, 15 and c ( Figure 8), which could not be definitively assigned to ab inding event. The [2]catenane host system 16·PF 6 therefore appears to display an impressives electivity for chloride over bromide and iodide anions in DMSO, whichm ay reflecta no ptimal host-guest complementarity relationship between the chloride anion and the catenane'sp reorganised hydrogen-bonddonating bindingp ocket. [33] UV/Vis and fluorescence experiments UV/Visand fluorescencespectroscopic titration experimentsr evealed that the [2]catenane exhibits modesto ptical chloridesensingc apabilities:u pon titration of TBACl into solutionso f the catenanei nD MSO ag radualhypsochromic shift of approximately 1nmw as observed in the Soret band absorbance, with the formation of as ingle isosbestic point at 418.5 nm, [34] along with approximately 9a nd 4% increases in the intensities of the emission maxima at 595 nm and 650 nm, respectively (Figure 9). Analysis of the UV/Vis titration data by using Specfit [35] software revealed a1 :1 stoichiometric association constant of log K = 3.38 AE 0.04 (K = 2396 m À1 ), which is in good agreement with the value determined by 1 HNMR spectroscopy.B yc omparison, addition of increasing concentrations of TBABr and TBAI to DMSO solutionso ft he catenane produced   Figures S27a nd S28), which corroborates the 1 HNMR evidencet hat these larger halidesd on ot significantly interact with the [2]catenane hostsystem in DMSO.

Conclusions
An ew strapped-porphyrin-containing [ 2]catenane anion-host system was prepared through an amide-condensation-based clippingr eaction, which was directed by chloride anion templation in combination with pyridine-zinc ligation and aromatic donor-acceptor interactions. Uponr emovalo ft he halide template, the catenane wass hown to selectively recognise chloride( K = 2144(149) m À1 )o ver larger halide anions in the competitive solvent [D 6 ]DMSO. The [2]catenane also exhibits am odesta bility to optically sense chloride anionsi nD MSO through smallb ut detectable changes in the absorption and emission spectrao ft he porphyrin chromophore.

Experimental Section
All solvents and reagents were purchased from commercial suppliers and used as received, unless otherwise stated. Dry solvents were obtained by purging with N 2 and then passing through an MBraun MPSP-800 column. H 2 Ow as deionised and microfiltered by using aM illi-Q Millipore machine. Et 3 Nw as distilled and stored over KOH. TBA salts were stored in av acuum desiccator containing P 2 O 5 prior to use. 1 H, 13 C, 19 Fa nd 31 PNMR spectra were recorded on aV arian Mercury-VX 300, aV arian Unity Plus 500, aB ruker AVD500 or aB ruker AVII500 with cryoprobe at 293 K. Chemical shifts are quoted in parts per million relative to the residual solvent peak. Mass spectra were obtained by using aM icromass LCT (ESMS) instrument or aM ALDI Micro MX instrument. Electronic absorption spectra were recorded on aP Gi nstruments T60U spectrometer.

X-ray crystallography
Single crystal diffraction data for compounds 3b and Zn·3a were collected at 150(2) Ku sing graphite monochromated Mo Ka radiation (l = 0.71073 ) on aN onius Kappa CCD diffractometer. Cell parameter determination and refinement and raw frame data integration were carried out by using the DENZO-SMN package. [36] Diffraction data for compounds 13, 14·Cl, 16·Cl and 16·PF 6 were collected at 100(2) Kb yu sing silicon double crystal monochromated synchrotron radiation (l = 0.68890 ) at Diamond Light Source, beamline I19, [37] with ac ustom-built Rigaku diffractometer. [38] Cell parameter determination and refinement and raw frame data integration were carried out by using the CrysAlisPro [39] package. The structures were solved by charge-flipping methods using SUPER-FLIP [40] and refined by full matrix least squares on F 2 using the CRYSTALS [41] suite. All non-hydrogen atoms were refined with anisotropic displacement parameters. Where appropriate, disordered regions were modelled by using refined partial occupancies, geometric restraints were applied to ensure ap hysically reasonable model, and thermal and vibrational restraints were applied to maintain sensible ADPs;i na ddition, when present, diffuse disordered solvent and counteranions were modelled by treating the discrete Fourier transform of the void region as contributions to the calculated structure factors with PLATON/SQUEEZE. [42] Hydrogen atoms were generally visible in the difference map and were treated in the conventional manner. [43] CCDC 1412108-1412113 contain the supplementary crystallographic data (excluding structure factors) for this paper.T hese data are provided free of charge by The Cambridge Crystallographic Data Centre.