Enantioselective synthesis of chiral porphyrin macrocyclic hosts and kinetic enantiorecognition of viologen guests

The construction of macromolecular hosts that are able to thread chiral guests in a stereoselective fashion is a big challenge. We herein describe the asymmetric synthesis of two enantiomeric C₂-symmetric porphyrin macrocyclic hosts that thread and bind different viologen guests. Time-resolved fluorescence studies show that these hosts display a factor 3 kinetic preference (ΔΔG^‡_on = 3 kJ mol⁻¹) for threading onto the different enantiomers of a viologen guest appended with bulky chiral 1-phenylethoxy termini. A smaller kinetic selectivity (ΔΔG^‡_on = 1 kJ mol⁻¹) is observed for viologens equipped with small chiral sec-butoxy termini. Kinetic selectivity is absent when the C₂-symmetric hosts are threaded onto chiral viologens appended with chiral tails in which the chiral moieties are located in the centers of the chains, rather than at the chain termini. The reason is that the termini of the latter guests, which engage in the initial stages of the threading process (entron effect), cannot discriminate because they are achiral, in contrast to the chiral termini of the former guests. Finally, our experiments show that the threading and de-threading rates are balanced in such a way that the observed binding constants are highly similar for all the investigated host–guest complexes, i.e. there is no thermodynamic selectivity.

Chiral guests display kinetic stereoselective threading through chiral porphyrin cages if their chirality is located at the chain ends and not in the centers, supporting the previously reported entron effect of threading.     

A new twist in anion binding: metallo-helicate hosts for anionic guests

The condensation of 5-chlorocarbonyl-2,2'-bipyridine with a variety of rigid aromatic diamines, L, gave a series of new bisamido-2,2'-bipyridine based ligands (L = 4,4'-methylenediamine, L1; L = 1,1-bis(4-aminophenyl)cyclohexane, L2; L = 1,1-bis(4-amino-3,5-dimethylphenyl)cyclohexane, L3) capable of forming dinuclear triple helicate complexes on coordination to Fe(II). The reaction of various Fe(II) salts with gave: {[Fe2(L1)3](BF4)4, 1; [Fe2(L1)3](ClO4)4, 2; [Fe2(L1)3]Cl4, 3; [Fe2(L1)3](SO4)2, 4; [Fe2(L2)3](BF4)4, 5; [Fe2(L2)3]Cl4, 6; [Fe2(L3)3](BF4)4; 7; [Fe2(L3)3]Cl4, 8; and [Fe2(L3)3](SO4)2, 9, as determined by UV-Vis, IR and 1H NMR spectroscopy, electrospray mass spectrometry (ESMS) and elemental analyses. A UV-Vis complexometric titration experiment between L3 and Fe(BF4)2 established conclusively a [Fe2(L3)3]4+ product species. 1H NMR spectroscopy showed that the complexes exist as both rac-(helical) and meso-(non-helical) isomers in DMSO-d6 solution at 298 K. L1-L3 were designed such that following complexation, six amide hydrogen atoms would line an inter-strand intrahelical cavity of sufficient size to facilitate the binding of guest species within it. Indeed, ESMS studies showed characteristic peaks typical of complex-anion species in solution. Furthermore, 1H NMR titration experiments showed that anions bind within the intrahelical cavity as titration of 1, 5 and 7 with Bu4NCl showed significant downfield shifts in the amide and bipyridyl H6 proton resonances to yield a species of 1 : 2 host to guest stoichiometry. Moreover, addition of Bu4NCl to 1, 5 and 7 shifted the rac-/meso-species distribution from 1 : 2 in favour of the meso- to 100% in favour of the rac-isomer, showing that Cl- ions favour the formation of the triple helicate species in DMSO-d6 solution.     

Structural design criteria for anion hosts: strategies for achieving anion shape recognition through the complementary placement of urea donor groups

The arrangement of urea ligands about different shaped anions has been evaluated with electronic structure calculations. Geometries and binding energies are reported for urea complexes with Cl-, NO(3)-, and ClO(4)-. The results yield new insight into the nature of urea-anion interactions and provide structural criteria for the deliberate design of anion selective receptors containing two or more urea donor groups.     

Protonated macrobicyclic hosts containing pyridine head units for anion recognition

In this paper, we report two macrobicyclic receptors containing pyridine head units derived from 1,10-diaza-15-crown[5] (L1) or 4,13-diaza-18-crown[6] (L2) that can be protonated in MeCN and used for anion recognition. The interaction of these protonated lateral macrobicycles with different anions has been investigated by means of spectrophotometric titrations in MeCN. The association constants for the complexes of halide anions with the protonated macrobicycles follow the sequences Cl(-)>Br(-)>I(-)>F(-) (L1) and Cl(-)>F(-)>I(-)>Br(-) (L2), whereby an increase of more than two logarithmic units is observed from F(-) to Cl(-) for the binding constants of the receptor derived from L1. The association constants also indicate an important degree of selectivity of these macrobicyclic receptors for Cl(-) over Br(-) or I(-). The X-ray crystal structure analyses of the chloride and bromide complexes confirms the formation of the envisaged supramolecular complexes. Moreover, the binding constants indicate that these receptors present a high sulfate-to-nitrate binding selectivity. The stability trend observed for the recognition of halide anions by the macrobicycles presented herein as well as the sulfate-to-nitrate binding selectivity have been rationalised by means of DFT calculations at the B3LYP/LanL2DZ level. These studies indicate that the especially high binding selectivity for Cl(-) is the result of the optimum fit between the protonated macrobicyclic cavity and the size of the anion, whereas the sulfate-to-nitrate selectivity results from shape complementarity between the hydrogen-binding acceptor sites on sulfate and the hydrogen-bond donors of the macrobicycle.     

Orientation of pyrylium guests in cucurbituril hosts

According to recent reports, supramolecular complexes of the pyrylium cation with cucurbit[x]urils (CB[x], x = 7, 8) show promising photoluminescence suitable for electroluminescent devices. In turn, photoluminescence seems to be related to the stereochemistry of the complexes; however, that has been controversial. Here, we report that in H(2)O, 2,6-disubsituted-4-phenyl pyryliums (Pylm) form dimers quantitatively (equilibrium constants >10(4) M(-1)), but they enter as such only in the larger CB[8]. In terms of orientation, (1)H NMR shows that Me-Pylm, Ph-Pylm, and t-Bu-Pylm insert their 4-phenyl groups in either the CB[7] or CB[8] cavity. The orientation of iPr-Pylm in the iPr-Pylm@CB[7] complex is similar. Experimental conclusions are supported by DFT calculations using the M062X functional and the 6-31G(d) basis set. In the case of (iPr-Pylm)(2)@CB[8], (1)H NMR of both the guest and the host indicates that both guests might enter CB[8] from the same side with their iPr groups in the cavity, but DFT calculations leave room for ambiguity. In addition to the size and hydrophobicity of the 2,6-substituents of the guests, as well as the size and flexibility of the hosts, theory reveals the importance of explicit solvation (H(2)O) and finite temperature effects (particularly for (1)H NMR shielding calculations) in the determination of the stereochemistry of those complexes.     

Recognition of guests by water-stabilized cavitand hosts

Water stabilized, deep cavitands with three walls and an open side are shown to be receptors for amines and ammonium cations bearing bulky aliphatic groups. The missing wall allows the binding of guests not accommodated by the four-walled counterparts.     

Change in conformation upon complexation of double-armed terephthalamide hosts: dynamic molecular recognition of ditopic guests with strong CD signaling

Conformation of novel terephthalamide hosts 1 changes from anti to syn upon complexation with a bidentate guest (2 or 3). Chiral sense in the helical syn-form of the double-armed host molecules 1 is biased by the asymmetric centers on the chiral guest [(R,R)/(S,S)-2a], which can be detected by the drastic change in circular dichroism (CD) spectrum thanks to the exciton coupling of two chromophores (‘arms’) linked to the amide nitrogens. Asymmetric centers on the host molecule also exhibit preference for the twisting direction upon change in geometry from the anti- to syn-form. Thus, the achiral guests (2b or 3) can also be detected by modulation of CD spectrum upon complexation with the chiral host [(R,R)-1a].     

Reversible encapsulation of multiple,neutral guests in hexameric resorcinarene hosts

A variety of aromatic guest molecules are co-encapsulated with Bu4SbBr in an assembly of six resorcinarene subunits.     

Multiple recognition of barbiturate guests by Hamilton-receptor-functionalized dendrimers

The well-known unsubstituted "Hamilton receptor" was monofunctionalized with an amino group and attached at the periphery of poly(propyleneamine) dendrimers through the use of an activated ester. Four generations of Hamilton-receptor-functionalized dendrimers (HR-dendrimers) were synthesized and characterized by (1)H and (13)C NMR spectroscopy and MALDI-TOF mass spectrometry. The photophysical properties of the HR-dendrimers were investigated by UV/Vis as well as with steady-state and time-resolved fluorescence spectroscopy. The dendrimers were used as multivalent hosts for the barbiturate guests Barbital (7) and [Re(Br)(CO)(3)(barbi-bpy)] (8; barbi-bpy=5-[4-(4'-methyl)-2,2'-bipyridyl]methyl-2,4,6-(1 H,3 H,5 H)-pyrimidinetrione). The stable adducts formed between the dendritic architectures (the hosts) and the barbiturate guests 7 and 8 were investigated by (1)H NMR spectroscopy and photophysical methods. The binding constants of the barbiturate guests for binding to reference compound 2 (with a single receptor unit) in chloroform were found to be 1.4 x 10(3) M(-1) and 1.5 x 10(5) M(-1) for 7 and 8, respectively. Binding of 7 to the dendrimers enhances the weak emission of the Hamilton receptor. This increase in emission is also generation dependent; it was found to be most pronounced in the case of 2 and the least in the case of the fourth-generation dendrimer 6. The unexpected increase in the quantum yield of emission from the HR-dendrimers with increasing generation could be caused by the rather rigid conformation of the Hamilton receptors in later-generation compounds, which is a result of intramolecular aggregation and steric hindrance at the periphery of the dendrimer. The photoinduced energy transfer from the excited state of the HR-dendrimers to the lower-lying excited state of the guest 8 was used to probe the formation of host-guest complexes. The rate of energy transfer was calculated to be 3.6 x 10(10) s(-1). Energy transfer in 2 subset 8 only occurred in the presence of a strong base, which shows that the basic amine core in the HR-dendrimers is crucial for this photoinduced process. The binding of 8 to the dendrimers is completely reversible: 8 can be exchanged with a competitive guest such as 7 and the emission of the HR-dendrimer is restored.     

De novo structure-based design of bisurea hosts for tetrahedral oxoanion guests

This paper presents a computational approach to the deliberate design of improved host architectures. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential structures. The efficacy of this computer-aided design methodology is illustrated with a search for bisurea podands that are structurally organized for complexation with tetrahedral oxoanions.     

Chiral porphyrin dimer with a macrocyclic cavity for intercalation of aromatic guests

Chiral diporphyrin receptor 1, which has a macrocyclic cavity to sandwich aromatic guest molecules via double π-π stacking interactions, enabled the naked-eye detection of an aromatic explosive as well as chiral discrimination in NMR.     

Multipoint recognition of catecholamines by hydrindacene-based receptors accompanied by the complexation-induced conformational switching

The molecular recognition of catecholamines by hydrindacene-based receptors 1 and 2, as well as the durene-based receptor 3, and the guest-induced conformational changes are reported. These receptors selectively bind adrenaline and dopamine salts through the guests' ammonium group and 3-hydroxyl group on the aromatic ring. In the case of adrenaline, an additional hydrogen bond with a benzylic hydroxyl group is formed. In 2 % CD3CN/CDCl3, the association constants are of the order of 10(4) M(-1), which is much larger than with guests without the 3-hydroxyl groups (10(3) M(-1)). The two amide groups of receptor 1 can rotate freely around the C(aromatic)--C(amide) bond, whereas the tert-amide in 2 changes between two stable conformations at a slow enough rate to allow detection by (1)H NMR spectroscopy. In the absence of a guest molecule, the syn-conformer is less stable than the anti-conformer. On complex formation with adrenaline, the syn-conformer becomes dominant due to an intramolecular dipole-reversal effect in addition to multipoint hydrogen bonding.     

Supramolecular organization of light-harvesting porphyrin macrorings

Porphyrin‐based supramolecular nanostructures have been produced by the self‐assembly of porphyrin macrorings with three benzoic acid groups (Acid‐R) on each side of the rings through cooperative carboxyl–carboxyl hydrogen bonds. Structures of the organized Acid‐R were analyzed by AFM, and two clear distribution peaks were observed at 3 and 27 nm in the height‐distribution histogram. From the overall assessment, the higher objects are considered to be one‐dimensional structures standing vertically on the mica substrate. The height corresponds to an 11‐mer of a unit Acid‐R. Light‐harvesting functions were examined by using fluorescence titration, whereby an energy‐acceptor molecule (Tripod 2 ) was employed that strongly interacted with Acid‐R units (association constant: 2.0×10⁸ M ^?1), specifically from the inner pore. The titration results showed that the apparent stoichiometry [Tripod 2 ]/[Acid‐R] was <0.5, and that the value was concentration dependent. Titration results reasonably account for the scheme in which Tripod 2 only interacts with each terminal in the organized Acid‐R. The number of organization was fitted to a 10‐mer of Acid‐R in a 6.8×10^?7 M solution, and was consistent with that estimated from the AFM results. In the composites of organized Acid‐R/Tripod 2 , a singlet excitation energy transfer occurred among the Acid‐R units, and to Tripod 2 . The energy‐transfer rate constants were estimated by using the decamer model, which employed kinetic parameters obtained from steady‐state and time‐resolved fluorescence experiments.     

Lanthanide luminescent anion sensing: evidence of multiple anion recognition through hydrogen bonding and metal ion coordination

The delayed lanthanide luminescence of the terbium [Tb(III)] diaryl-urea complex 1xTb is significantly enhanced upon sensing of dihydrogenphosphate (H2PO4(-)) in CH3CN, which occurs through multiple anion binding through hydrogen bonding interactions and potential metal ion coordination to Tb(III).     

Supramolecular assemblies of tripodal porphyrin hosts and C60

The self-assembly of two tripodal porphyrin hosts in the presence of C(60), in the solid state, has been studied using synchrotron X-ray crystallography, and in solution by using (1)H NMR and fluorescence spectroscopies. The binding affinities, stoichiometries and geometries strongly depend on the size of the porphyrin host. Intramolecular and/or intermolecular porphyrin-fullerene interactions are observed in the co-crystallites and in each case, the trimer exhibits a "tweezers-like" structural motif. The solid-state structures of the trimer-fullerene co-crystallites reveal close fullerene-porphyrin and fullerene-fullerene contacts.     

Tripodal pyrrolotetrathiafulvalene receptors for recognition of electron-deficient molecular guests

We report the synthesis of tripodal receptors with monopyrrolo-tetrathiafulvalene arms 1a,b, based on 1,3,5-substituted 2,4,6-triethylbenzene scaffold. The three converging pyrrolotetrathiafulvalene groups form an electron rich cone-shaped binding site. Molecular hosts 1a,b are capable of binding neutral electron deficient guests in solution, as well as positively charged pyridinium species in the gas phase.