Density functional theory calculations and vibrational circular dichroism of aromatic foldamers

Ab initio calculations together with vibrational circular dichroism (VCD) have been used for studying the conformations of a quinoline-derived oligoamide bearing a terminal chiral residue. Three helically folded conformers of the dimer, trimer, and tetramer forms of the oligomer were optimized at the density functional theory (DFT) level using the B3LYP functional and the 6-31G* basis set. For each form, the three conformers differ in their helical handedness and in the conformation of the chiral end group. The calculated structures of the tetramer and also the proportions predicted between them based on their calculated Gibbs free energies differences match remarkably well with experimental data collected on an octamer. Specifically, a R-phenethyl terminal group gives rise to a 91:9 ratio between left handed and right handed helices. The predicted VCD spectrum calculated from the Boltzmann population of the individual conformer reproduces very well the experimental VCD spectrum of the tetramer in CDCl3 solution. The DFT calculations performed for the trimer also allow one to assess the preferred handedness of the helix and the conformation of the chiral end group, but the calculated relative populations differ slightly from experimental data. Finally, this study shows that the dimer fragment is not sufficient to obtain valuable information on the conformation of this aromatic oligoamide foldamer.     

Helical Mesoporous Tantalum Oxide Nanotubes: Formation,Optical Activity,and Applications

Nanomaterials with helical morphologies have attracted much attention owing to their potential applications as nanosprings, chirality sensors and in chiral optics. Single‐handed helical Ta₂O₅ nanotubes prepared through a supramolecular templating approach are described. The handedness is controlled by that of the organic self‐assemblies of chiral low‐molecular‐weight gelators (LMWGs). The chiral LMWGs self‐assemble into single‐handed twisted nanoribbons through H‐bonding, hydrophobic association, and π‐π stacking. The Ta₂O₅ nanotubes are formed by the adsorption and polycondensation of Ta₂O₅ oligomers on the surfaces and edges of the twisted organic nanoribbons followed by removal of the template. The optical activity of the nanotubes is proposed to originate from the chiral defects on the inner surfaces of the tubular structures. Single‐handed twisted LiTaO₃ nanotubes can also be prepared using Ta₂O₅ nanotubes.     

The N‐Terminal Nonapeptide of Cephaibols A and C: A Naturally Occurring Example of Mismatched Helical Screw‐Sense Control

The N‐terminal nonapeptide domain of the fungal nonribosomal peptide antibiotics cephaibol A and cephaibol C (AcPheAib₄LeuIvaGly‐ Aib) is reported to adopt a right‐handed helical conformation in the crystalline state. However, this conformation is at odds with the left‐handed helicity observed in solution in related synthetic oligomers capped with Ac‐L ‐PheAib₄ fragments. We report the synthesis of four diastereoisomers of the cephaibol N‐terminal nonapeptide, and show by NMR and CD spectroscopy that the peptide containing the chiral amino acids Phe and Leu in the naturally occurring relative configuration exists in solution as an interconverting mixture of helical screw‐sense conformers. In contrast, the nonapeptide containing the unnatural relative configuration at Phe and Leu adopts a single, stable helical screw‐sense, which is left handed when the N‐terminal Phe residue is L and right‐handed when the N‐terminal Phe residue is D .     

Three‐Way‐Switchable (Right/Left/OFF) Selective Reflection of Circularly Polarized Light on Solid Thin Films of Helical Polymer Blends

Two poly(quinoxaline‐2,3‐diyl) copolymers bearing miscibility‐enhancing 8‐chlorooctyloxy and (S)‐2‐methylbutoxy or n‐butoxy side chains were synthesized. After annealing in CHCl₃ vapor, a polymer‐blend film of these copolymers exhibited selective reflection of right‐handed circularly polarized light (CPL) in the visible region. The handedness of the CPL reflected was completely inverted upon annealing of the film in THF vapor. Annealing in n‐hexane vapor resulted in the phase separation of the polymer blend, which turned the selective reflection off. This three‐way‐switchable reflection, that is, reflection of right‐handed or left‐handed CPL, together with an OFF state, could be observed visually through right‐ and left‐handed CPL filters.     

“Helix‐in‐Helix” Superstructure Formation through Encapsulation of Fullerene‐Bound Helical Peptides within a Helical Poly(methyl methacrylate) Cavity

A one‐handed 3₁₀‐helical hexapeptide is efficiently encapsulated within the helical cavity of st‐PMMA when a fullerene (C₆₀) derivative is introduced at the C‐terminal end of the peptide. The encapsulation is accompanied by induction of a preferred‐handed helical conformation in the st‐PMMA backbone with the same‐handedness as that of the hexapeptide to form a crystalline st‐PMMA/peptide‐C₆₀ inclusion complex with a unique optically active helix‐in‐helix structure. Although the st‐PMMA is unable to encapsulate the 3₁₀‐helical peptide without the terminal C₆₀ unit, the helical hollow space of the st‐PMMA is almost filled by the C₆₀‐bound peptides. This result suggests that the C₆₀ moiety can serve as a versatile molecular carrier of specific molecules and polymers in the helical cavity of the st‐PMMA for the formation of an inclusion complex, thus producing unique supramolecular soft materials that cannot be prepared by other methods.     

Chirality and Template‐Mediated Induction of Helical Preferences in Achiral β‐Peptides

This study describes chirality‐ or template‐mediated helical induction in achiral β‐peptides for the first time. A strategy of end capping β‐peptides derived from β‐hGly (the smallest achiral β‐amino acid) with a chiral β‐amino acid that possesses a carbohydrate side chain (β‐Caa; C‐linked carbo β‐amino acid) or a small, robust helical template derived from β‐Caas, was adopted to investigate folding propensity. A single chiral (R)‐β‐Caa residue at the C‐ or N‐terminus in these oligomers led to a preponderance of right‐handed 12/10‐helical folds, which was reiterated more strongly in peptides capped at both the C‐ and N‐terminus. Likewise, the presence of a template (a 12/10‐helical trimer) at both the C‐ and N‐terminus resulted in a very robust helix. The propagation of the helical fold and its sustenance was found in a homo‐oligomeric sequence with as many as seven β‐hGly residues. In both cases, the induction of helicity was stronger from the N terminus, whereas an anchor at the C terminus resulted in reduced helical propensity. Although these oligomers have been theoretically predicted to favor a 12/10‐mixed helix in apolar solvents, this study provides the first experimental evidence for their existence. Diastereotopicity was found in both the methylene groups of the β‐hGly moieties due to chirality. Additionally, the β‐hGly units have shown split behavior in the conformational space to accommodate the 12/10‐helix. Thus, end capping to assist chiralty‐ or template‐mediated helical induction and stabilization in achiral β‐peptides is a very attractive strategy.     

Homo‐double helix formation of an optically active conjugated polymer bearing carboxy groups and amplification of the helicity upon complexation with achiral and chiral amines

An optically active, m‐terphenyl‐based π‐conjugated polymer bearing carboxy groups was synthesized by the copolymerization of the diethynyl monomer bearing a carboxy group with (S,S)‐2,5‐bis(2‐methylbutoxy)‐1,4‐dibromobenzene using Sonogashira reaction. The copolymer showed a weak circular dichroism (CD) in the main‐chain chromophore region due to a homo‐double helix formation with an excess helical handedness biased by the chiral alkoxy substituents through self‐association. However, upon complexation with achiral amines, such as piperidine, the CD intensity of the polymer significantly increased resulting in the formation of a greater excess one‐handed homo‐double helix via hydrogen‐bonded inclusion complexation with the achiral amines between each strand, leading to the amplification of the helicity. A preferred‐handed homo‐double helix was also induced in the polymer in the presence of nonracemic amines. The effect of the achiral and chiral amines on the homo‐double helix formation was investigated by comparing the CD spectra of the polymer to those of its model dimer. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 990–999     

Remote Control of the Planar Chirality in Peptide‐Bound Metallomacrocycles and Dynamic‐to‐Static Planar Chirality Control Triggered by Solvent‐Induced 310‐to‐α‐Helix Transitions

The dynamic planar chirality in a peptide‐bound Ni^II‐salphen‐based macrocycle can be remotely controlled. First, a right‐handed (P)‐3₁₀‐helix is induced in the dynamic helical oligopeptides by a chiral amino acid residue far from the macrocyclic framework. The induced planar chirality remains dynamic in chloroform and acetonitrile, but is almost completely locked in fluoroalcohols as a result of the solvent‐induced transition of the peptide chains from a 3₁₀‐helix to a wider α‐helix, which freezes the rotation of the pendant peptide units around the macrocycle.     

Induction of Single‐Handed Helicity of Polyacetylenes Using Mechanically Chiral Rotaxanes as Chiral Sources

Effective induction of preferred‐handed helicity of polyacetylenes by pendant mechanically chiral rotaxanes is discussed. Polyacetylenes possessing optically active mechanically chiral rotaxanes in the side chains were synthesized by the polymerization of the corresponding enantiopure [2]rotaxane‐type ethynyl monomers prepared by the chiral‐phase HPLC separations. The CD Cotton effects revealed that the polyacetylenes took preferred‐handed helical conformations depending on the rotaxane chirality. The preferred‐handed helix was not disturbed by an additional chiral substituent on the rotaxane side chain. These results demonstrate the significance and utility of mechanically chiral rotaxanes for the effective construction of asymmetric fields.     

Glycosyl‐Templated Chiral Helix Stapling of Ethynylpyridine Oligomers by Alkene Metathesis between Inter‐Pitch Side Chains

Ethynylpyridine polymers and oligomers consisting of 4‐substituted pyridine rings linked by acetylene bonds at the 2‐ and 6‐positions have been investigated. Ethynylpyridine oligomers covalently linked with a glycosyl chiral template form chiral helical complexes by intramolecular hydrogen bonding, in which the chirality of the template is translated to the helix. With a view to fixation of the chiral architecture, D /L ‐galactosyl‐ and D /L ‐mannosyl‐linked ethynylpyridine oligomers have been developed with 4‐(3‐butenyloxy)pyridine units having alkene side chains. The helical structures are successfully stapled by alkene metathesis of the side chains. Subsequent removal of the chiral templates by acidolysis produces template‐free stapled oligomers. The chiral, template‐free, stapled oligomers show chiral helicity, which is resistant to polar solvents and heating.     

Ferrochirality: a simple theoretical model of interacting,dynamically invertible,helical polymers, 2. Molecular field approach: supports and the details

Using a molecular field approach, the effect of interaction between reversibly invertible, helical polymers is investigated theoretically. The helices are modelled by nearest-neighbour statistical thermodynamics. If the interaction energy between two helices of common handedness is lower than that of oppositely handed ones, a critical temperature T_c exists, below which the system spontaneously must leave the racemic state, though there is no contact to any chiral centre or force. This is analogous to the second-order phase transition of ferromagnets. The critical point increases with molecular weight and optical persistence of the helices. At the critical point the system is highly sensitive to any chiral influence. Doping with 1 ppb of a chiral additive leads to a relative optical rotation of order 10⁻³ at the critical point. This corresponds to an intrinsic energy difference of left- to right-handed monomeric units of only 10⁻⁸ J/mol. The cooperative effects in chirally doped nematic poly(hexyl isocyanate) (PHIC) can be easily described without using the improbable assumption that the supramolecular cholesteric arrangement with an axis-to-axis rotation of only 0,001° must be the reason for the collective helix sense preference in this system. On the other hand, if the chain-to-chain interaction is transmitted through this supermolecular twist, the structure of the equations is altered slightly only and critical behaviour must be expected as well.     

Helical Structures of Bicyclic α‐Amino Acid Homochiral Oligomers with the Stereogenic Centers at the Side‐Chain Fused‐Ring Junctions

Chiral bicyclic α‐amino acid (R,R)‐Ab_5,6=c with stereogenic centers at the γ‐position of fused‐ring junctions, and its enantiomer (S,S)‐Ab_5,6=c, were synthesized. The CD spectra of (R,R)‐Ab_5,6=c oligomers indicated that the (R,R)‐Ab_5,6=c hexapeptide formed a mixture of right‐handed (P)‐ and left‐handed (M)‐3₁₀‐helices, while, in the (R,R)‐Ab_5,6=c nonapeptide, a right‐handed (P)‐3₁₀‐helix slightly dominated over the (M)‐helix. X‐Ray crystallographic analyses of (S,S)‐tripeptide and (R,R)‐hexapeptide revealed that both the tripeptide and hexapeptide formed a mixture of (P)‐ and (M)‐3₁₀‐helices, respectively. These results indicated that the side‐chain environments around the stereogenic centers are particularly important to control the helical‐screw handedness of foldamers.     

Trismaleimide Dendrimers: Helix‐to‐Superhelix Supramolecular Transition Accompanied by White‐Light Emission

Reported here are unprecedented fluorescent superhelices composed of primary, supramolecular polymers of the opposite helical twist. A new class of functional dendrimers was synthesized by amino‐ene click reactions, and they demonstrate an alternating OFF/ON fluorescence with generation growth. A peripherally alkyl‐modified dendrimer displays helix‐sense‐selective supramolecular polymerization, which predominantly forms right‐handed (or left‐handed) helical supramolecular polymers in the solution containing chiral solvents. With increasing the concentration, these primary helical supramolecular polymers spontaneously twist around themselves in the opposite direction to form superhelical structures. Atomic force microscopy and circular dichroism measurements were used to directly observe the helix‐to‐superhelix transition occurring with a reversal in the helical direction. Exceptional white‐light emission was observed during superhelix formation.     

The Helix to Super‐Helix Transition in the Self‐Assembly of π‐Systems: Superseding of Molecular Chirality at Hierarchical Level

Higher‐order super‐helical structures derived from biological molecules are known to evolve through opposite coiling of the initial helical fibers, as seen in collagen protein. A similar phenomenon is observed in a π‐system self‐assembly of chiral oligo(phenyleneethylene) derivatives (S )‐ 1 and (R )‐ 1 that explains the unequal formation of both left‐ and right‐handed helices from molecule having a specific chiral center. Concentration‐ and temperature‐dependent circular dichroism (CD) and UV/Vis spectroscopic studies revealed that the initial formation of helical aggregates is in accordance with the molecular chirality. At the next level of hierarchical self‐assembly, coiling of the fibers occurs with opposite handedness, thereby superseding the command of the molecular chirality. This was confirmed by solvent‐dependent decoiling of super‐helical structures and concentration‐dependent morphological analysis.     

Helix twist inversion in ferroelectric liquid crystals with one chiral centre

The helix twist inversion in the chiral smectic C phase was studied for two new homologous series of lactic acid derivatives. The inversion phenomenon was attributed to a competition between spatial conformers leading to opposite helix handedness. The temperature of inversion was found to increase with increasing length of the chiral molecular tail. With all substances studied, high values of the spontaneous polarization P_s were found which did not reach saturation on cooling, in spite of a saturated tilt angle θ_s.     

Helical Folding Competing with Unfolded Aggregation in Phenylene Ethynylene Foldamers

The folding and aggregation behavior of a pair of oligo(phenylene ethynylene) (OPE) foldamers are investigated by means of UV/Vis absorption and circular dichroism spectroscopy. With identical OPE backbones, two foldamers, 1 with alkyl side groups and 2 with triethylene glycol side chains, manifest similar helical conformations in solutions in n‐hexane and methanol, respectively. However, disparate and competing folding and aggregation processes are observed in alternative solvents. In cyclohexane, oligomer 1 initially adopts the helical conformation, but the self‐aggregation of unfolded chains, as a minor component, gradually drives the folding–unfolding transition eventually to the unfolded aggregate state completely. In contrast, in aqueous solution (CH₃OH/H₂O) both folded and unfolded oligomer 2 appear to undergo self‐association; aggregates of the folded chains are thermodynamically more stable. In solutions with a high H₂O content, self‐aggregation among unfolded oligomers is kinetically favored; these oligomers very slowly transform into aggregates of helical structures with greater thermodynamic stability. The folded–unfolded conformational switch thus takes place with the free (nonaggregated) molecules, and the very slow folding transition is due to the low concentration of molecularly dispersed oligomers.     

Light-driven reversible handedness inversion in self-organized helical superstructures

We report here a fast-photon-mode reversible handedness inversion of a self-organized helical superstructure (i.e., a cholesteric liquid crystal phase) using photoisomerizable chiral cyclic dopants. The two light-driven cyclic azobenzenophanes with axial chirality show photochemically reversible trans to cis isomerization in solution without undergoing thermal or photoinduced racemization. As chiral inducing agents, they exhibit good solubility, high helical twisting power, and a large change in helical twisting power due to photoisomerization in three commercially available, structurally different achiral liquid crystal hosts. Therefore, we were able to reversibly tune the reflection colors from blue to near-IR by light irradiation from the induced helical superstructure. More interestingly, the different switching states of the two chiral cyclic dopants were found to be able to induce a helical superstructure of opposite handedness. In order to unambiguously determine the helical switching, we employed a new method that allowed us to directly determine the handedness of the long-pitched self-organized cholesteric phase.     

Foldamer‐Mediated Remote Stereocontrol: >1,60 Asymmetric Induction

An N‐terminal L ‐α‐methylvaline dimer induces complete conformational control over the screw sense of an otherwise achiral helical peptide foldamer formed from the achiral quaternary amino acids Aib and Ac₆c. The persistent right‐handed screw‐sense preference of the helix enables remote reactive sites to fall under the influence of the terminal chiral residues, and permits diastereoselective reactions such as alkene hydrogenation or iminium ion addition to take place with 1,16‐, 1,31‐, 1,46‐ and even 1,61‐asymmetric induction. Stereochemical information may be communicated in this way over distances of up to 4 nm.     

Selective Dynamic Assembly of Disulfide Macrocyclic Helical Foldamers with Remote Communication of Handedness

Disulfide bridge formation was investigated in helical aromatic oligoamide foldamers. Depending on the position of thiol‐bearing side chains, exclusive intramolecular or intermolecular disulfide bridging may occur. The two processes are capable of self‐sorting, presumably by dynamic exchange. Quantitative assessment of helix handedness inversion rates showed that bridging stabilizes the folded structures. Intermolecular disulfide bridging serendipitously yielded a well‐defined, C₂‐symmetrical, two‐helix bundle‐like macrocyclic structure in which complete control over relative handedness, that is, helix–helix handedness communication, is mediated remotely by the disulfide bridged side chains in the absence of contacts between helices. MM calculations suggest that this phenomenon is specific to a given side chain length and requires disulfide functions     

Enantioselective noncovalent synthesis of hydrogen-bonded double-rosette assemblies

The noncovalent synthesis of enantiomerically pure hydrogen-bonded assemblies (M)- and (P)-1(3).(CA)(6) is described. These dynamic assemblies are of one single handedness (M or P), but do not contain any chiral components. They are prepared by using the "chiral memory" concept: the induction of supramolecular chirality is achieved through initial assembly with chiral barbiturates, which are subsequently replaced by achiral cyanurates. This exchange process occurs quantitatively and without loss of the M or P handedness of the assemblies. Racemization studies have been used to determine an activation energy for racemization of 105.9+/-6.4 kJ mol(-1) and a half-life time to racemization of 4.5 days in benzene at 18 degrees C. Kinetic studies have provided strong evidence that the rate-determining step in the racemization process is the dissociation of the first dimelamine component 1 from the assembly 1(3).(CA)(6). In addition to this, it was found that the expelled chiral barbiturate (RBAR or SBAR) acts as a catalyst in the racemization process. Blocking the dissociation process of dimelamines 1 from assembly 1(3).(CA)(6) by covalent capture through a ring-closing metathesis (RCM) reaction produces an increase of more than two orders of magnitude in the half-life time to racemization.