Conformation‐Specific Circular Dichroism Spectroscopy of Cold,Isolated Chiral Molecules

The CD spectroscopy of a chiral compound in solution yields an average CD value derived from all of the conformations of a chiral molecule. By contrast, CD spectroscopy of cold chiral molecules in the gas phase distinguishes specific conformers of a chiral molecule, but the weak CD effect has limited the practical application of this technique. Reported herein is the first resonant two‐photon ionization CD spectra of ephedrines in a supersonic jet using circularly polarized laser pulses, which were generated by synchronizing the oscillation of the photoelastic modulator with the laser firing. The spectra exhibited well‐resolved CD bands which were specific for the conformations and vibrational modes of each enantiomer. The CD signs and magnitudes of the jet‐cooled chiral molecules were very sensitive to their conformations and thus offered crucial information for determining the three‐dimensional structures of chiral species, as conducted in combination with quantum chemical calculations.     

Laser Mass Spectrometry with Circularly Polarized Light: Circular Dichroism of Cold Molecules in a Supersonic Gas Beam

An experiment on chiral molecules that combines circular dichroism (CD) spectroscopy, mass‐selective detection by laser mass spectrometry (MS), and cooling of molecules by using a supersonic beam is presented. The combination of the former two techniques (CD–laser‐MS) is a new method to investigate chiral molecules and is now used by several research groups. Cooling in a supersonic beam supplies a substantial increase in spectroscopic resolution, a feature that has not yet been used in CD spectroscopy. In the experiments reported herein, a large variation in the electronic CD of carbonyl 3‐methylcyclopentanone was observed depending on the excited vibrational modes in the n→π* transition. This finding should be of interest for the detection of chiral molecules and for the theoretical understanding of the CD of vibronic bands. It is expected that this effect will show up in other chiral carbonyls because the n→π* transition is typical for the carbonyl group.     

Supramolecular helical columns from the self-assembly of chiral rods

Chiral-bridged rod molecules (CBRs) that consisted of bis(penta-p-phenylene) conjugated to an opened or closed chiral bridging group as a rigid segment and oligoether dendrons as flexible segments were synthesized and characterized. In the bulk state, both molecules self-assemble into a hexagonal columnar structure, as confirmed by X-ray scatterings and transmission electron microscopy (TEM) observations. Interestingly, these structures display opposite Cotton effects in the chromophore of the aromatic unit in spite of the same chirality (R,R) of the chiral bridging groups. The molecules were observed to self-assemble into cylindrical micellar aggregates in aqueous solution, as confirmed by light scattering and TEM investigations, and exhibit intense signals in the circular dichroism (CD) spectra, which are indicative of one-handed helical conformations. The CD spectra of each molecule showed opposite signals to each other, which were similar to those in the bulk. Notably, when the opened CBR was added to a solution of closed CBRs up to a certain concentration, the CD signal of the closed CBR was amplified. This implies that both molecules co-assemble into a one-handed helical structure because the opened chiral bridge is conformationally flexible, which is inverted to co-assemble with the closed CBR. These results demonstrate that small structural modifications of the chiral moiety can transfer the chiral information to a supramolecular assembly in the opposite way.     

Time dependent density functional theory calculations for electronic circular dichroism spectra and optical rotations of conformationally flexible chiral donor-acceptor dyad

Twelve conformations of a chiral donor-acceptor (charge-transfer) dyad and six conformations of its dimer complex were structurally optimized by using the Kohn-Sham density functional theory (BLYP/TZV2P) incorporating a recently developed empirical correction scheme that uses C6/R6 potentials for van der Waals interactions (DFT-D). Subsequent time-dependent DFT calculations with BH-LYP and B3-LYP functionals (with triple-zeta basis set) were performed to obtain theoretical circular dichroism (CD) spectra. The experimental CD spectra obtained independently were properly reproduced by averaging the calculated spectra of individual conformers according to a Boltzmann population derived from single-point SCS-MP2 energies. The optical rotations of the monomer were also calculated by using the same functionals with an aug-cc-pVDZ basis set. Dielectric continuum solvation models (COSMO) applied to correct the relative energies from the isolated molecule calculations resulted in conformer distributions that piled the same or even poorer level of agreement with the experimental CD spectrum. Our results clearly show the advantage of the DFT-D method for the geometry optimization of large systems with donor-acceptor interactions and the TD-DFT/BH-LYP calculations for reproducing the experimental CD spectra. As compared with the calculated optical rotations, the wealthy information embedded in the experimental/calculated CD spectra is requisite for the configurational and/or conformational analyses of relatively large and flexible chiral organic molecules in solution.     

Matrix Isolation‐Vibrational Circular Dichroism Spectroscopy of 3‐Butyn‐2‐ol and its Binary Aggregates

Vibrational circular dichroism (VCD) spectroscopy has a unique specificity to chirality and is highly sensitive to the conformational equilibria of chiral molecules. On the other hand, the matrix‐isolation (MI) technique allows substantial control over sample compositions, such as the sample(s)/matrix ratio and the ratio among different samples, and yields spectra with very narrow bandwidths. We combined VCD spectroscopy with the MI technique to record MI‐VCD and MI‐vibrational absorption spectra of 3‐butyn‐2‐ol at different MI temperatures, which allowed us to investigate the conformational distributions of its monomeric and binary species. Good mirror‐imaged MI‐VCD spectra of opposite enantiomers were achieved. The related conformational searches were performed for the monomer and the binary aggregate and their vibrational absorption and VCD spectra were simulated. The well‐resolved experimental MI‐VCD bands provide the essential mean to assign the associated vibrational absorption spectral features correctly to a particular conformation in case of closely spaced bands. By varying the matrix temperature, we show that one can follow the self‐aggregation process of 3‐butyn‐2‐ol and confidently correlate the MI‐VCD spectral features with those obtained for a 0.1 M CCl₄ solution and as a neat liquid at room temperature. Comparison of the aforementioned experimental VCD spectra shows conclusively that there is a substantial contribution from the 3‐butyn‐2‐ol aggregate even at 0.1 M concentration. This spectroscopic combination will be powerful for studying self‐aggregation of chiral molecules, and chirality transfer from a chiral molecule to an interacting achiral molecule and in electron donor–acceptor chiral complexes.     

DFT study of vibrational circular dichroism spectra of D-lactic acid-water complexes

This paper presents a discussion of the interaction energies, conformations, vibrational absorption (VA, harmonic and anharmonic) and vibrational circular dichroism (VCD) spectra for conformers of monomeric chiral d(-)-lactic acid and their complexes with water at the DFT(B3LYP)/aug-cc-pVDZ and DFT(B3LYP)/aug-cc-pVTZ levels. A detailed analysis has been performed principally for the two most stable complexes with water, differing by lactic acid conformation. The VCD spectra were found to be sensitive to conformational changes of both free and complexed molecules, and to be especially useful for discriminating between different chiral forms of intermolecular hydrogen bonding complexes. In particular, we show that the VCD modes of an achiral water molecule after complex formation acquire significant rotational strengths whose signs change in line with the geometry of the complex. Using the theoretical prediction, we demonstrate that the VCD technique can be used as a powerful tool for structural investigation of intermolecular interactions of chiral molecules and can yield information complementary to data obtained through other molecular spectroscopy methods.     

Pillararene Host–Guest Complexation Induced Chirality Amplification: A New Way to Detect Cryptochiral Compounds

The contradiction between the rising demands of optical chirality sensing and the failure in chiral detection of cryptochiral compounds encourages researchers to find new methods for chirality amplification. Inspired by planar chirality and the host–guest recognition of pillararenes, we establish a new concept for amplifying CD signals of cryptochiral molecules by pillararene host–guest complexation induced chirality amplification. The planar chirality of pillararenes is induced and stabilized in the presence of the chiral guest, which makes the cryptochiral molecule detectable by CD spectroscopy. Several chiral guests are selected in these experiments and the mechanism of chiral amplification is studied with a non‐rotatable pillararene derivative and density functional theory calculations. We believe this work affords deeper understanding of chirality and provides a new perspective for chiral sensing.     

cis-[Ni(NCS)_2tren]的镜面对称性破缺: 螯环的特殊手性构象

为了探究cis-[Ni(NCS)2tren][tren:三(2-氨基乙基)胺]的手性来源,本文采用单晶X射线衍射、溶液紫外-可见-近红外(UV-Vis-NIR)光谱、固体紫外圆二色(CD)光谱和粉末X射线衍射(XRD)等对cis-[Ni(NCS)2tren]的一对手性晶体进行了表征.研究结果表明:该手性晶体由结晶过程中的镜面对称性破缺而形成;三角架型配体tren配位后的特殊手性构象(δδλ,λλδ)是cis-[Ni(NCS)2tren]的主要手性来源.络合物固体紫外CD谱所呈现的Cotton效应可能来自其螯环手性构象以及手性金属中心对NCS-配体的π-π*跃迁和荷移跃迁生色团的手性微扰.对20批次合成产物进行固体CD检测的统计结果表明:它们的对映体过量(ee)值在39%-100%之间.     

Stereochemistry of phenyl alpha-nitronyl nitroxide radicals

An extensive investigation of the conformations adopted by the family of phenyl alpha-nitronyl nitroxides has been carried out. A database containing 110 crystal structures was used in a statistical study of the solid-state geometries and conformations of these radicals. This study revealed that the favoured conformations involve a twisted distortion in the imidazolyl rings and a twist between the aromatic and heterocyclic rings in the molecules. As a consequence, these radicals show two types of preferred conformations in the solid state: the pseudo-anti enantiomeric pair and the pseudo-eclipsed pair, the latter type being the most statistically probable. A new chiral member of this group of radicals that bears a lactate moiety, (R)-1, and its corresponding racemic compound, (R,S)-1, have been prepared in order to study the influence of chiral induction from the stereogenic centre on the torsion angle between the aromatic and heterocyclic rings of the alpha-nitronyl nitroxides. The X-ray crystal structures of the enantiopure and racemic compounds, which both reveal chains of molecules sustained by strong O-H...O hydrogen bonds between the carboxylic acid group and the ON group of the radical in the solid, as well as their magnetic properties have been determined. Remarkably, the molecules with a given stereogenic centre have a single helical sense between their component rings, even in the racemic crystal. Chiral induction from the stereogenic centre to the radical unit has also been proved by CD spectroscopy in the solid state. The results of these experiments have been rationalised by ab initio calculations of the spectra.     

Effect of the Side‐Chain‐Distribution Density on the Single‐Conjugated‐Polymer‐Chain Conformation

The spatial arrangement of the side chains of conjugated polymer backbones has critical effects on the morphology and electronic and photophysical properties of the corresponding bulk films. The effect of the side‐chain‐distribution density on the conformation at the isolated single‐polymer‐chain level was investigated with regiorandom (rra‐) poly(3‐hexylthiophene) (P3HT) and poly(3‐hexyl‐2,5‐thienylene vinylene) (P3HTV). Although pure P3HTV films are known to have low fluorescence quantum efficiencies, we observed a considerable increase in fluorescence intensity by dispersing P3HTV in poly(methyl methacrylate) (PMMA), which enabled a single‐molecule spectroscopy investigation. With single‐molecule fluorescence excitation polarization spectroscopy, we found that rra‐P3HTV single molecules form highly ordered conformations. In contrast, rra‐P3HT single molecules, display a wide variety of different conformations from isotropic to highly ordered, were observed. The experimental results are supported by extensive molecular dynamics simulations, which reveal that the reduced side‐chain‐distribution density, that is, the spaced‐out side‐chain substitution pattern, in rra‐P3HTV favors more ordered conformations compared to rra‐P3HT. Our results demonstrate that the distribution of side chains strongly affects the polymer‐chain conformation, even at the single‐molecule level, an aspect that has important implications when interpreting the macroscopic interchain packing structure exhibited by bulk polymer films.     

苯丙氨酸桥联手性锌双卟啉受体对胺的分子识别

金属卟啉的分子识别研究是当今卟啉仿生化学的重要课题.手性金属卟啉作为光学活性分子的对映选择识别受体和手性核磁共振试剂^[1]尤为引人注目.     

Pillararene Host–Guest Complexation Induced Chirality Amplification: A New Way to Detect Cryptochiral Compounds

The contradiction between the rising demands of optical chirality sensing and the failure in chiral detection of cryptochiral compounds encourages researchers to find new methods for chirality amplification. Inspired by planar chirality and the host–guest recognition of pillararenes, we establish a new concept for amplifying CD signals of cryptochiral molecules by pillararene host–guest complexation induced chirality amplification. The planar chirality of pillararenes is induced and stabilized in the presence of the chiral guest, which makes the cryptochiral molecule detectable by CD spectroscopy. Several chiral guests are selected in these experiments and the mechanism of chiral amplification is studied with a non-rotatable pillararene derivative and density functional theory calculations. We believe this work affords deeper understanding of chirality and provides a new perspective for chiral sensing.     

Chirality transfer from chiral solvents and its memory in an azobenzene derivative exhibiting photo-switchable racemization

The transfer and dynamic fixation of chirality in cyclic azobenzenes using R-(+)-1-phenylethylalcohol (R-PEA) and S-(-)-1-phenylethylalcohol (S-PEA) as solvents or additives are investigated. The cyclic azobenzenes used in this study carry a 1,5-dioxynaphthalene moiety as rotating unit, connected to the photoisomerizing (E-Z) azobenzene unit with spacers of varying lengths. With suitable lengths of the spacers the molecules exhibit stable enantiomers originated from the element of planar chirality in the E form due to the stopped rotation of the rotor, while in the Z form the allowed rotation results in racemization. The CD spectra of racemic compounds in the E form in chiral solvents were inert or almost negligible before irradiation, while 366 nm irradiation causing E-Z photoisomerization resulted in induction of clear CD bands. The thermal or photochemical reverse Z-E isomerization causes a change in the CD spectra to new ones which are reasonably matching with the spectra of the pure enantiomers recorded in non-chiral solvents. The obtained new CD spectra are maintained even in a racemic solvent system attained by the dilution with an equal amount of chiral solvent of opposite stereostructure. These results indicate that the chirality is transferred from the chiral solvents or additives to the racemizing Z form of cyclic azobenzene and it is fixed in the non-racemizing E form. The molecule without racemization in both E and Z forms did not show any significant induced CD bands irrespective of E-Z isomerizations. The molecule showing racemization in E and Z forms just shows the non-fixed induced CD. The property of photo-switchable racemization is necessary for the effective transfer and temporal fixation of the chirality in this type of chirality sensors.     

Exploring the ability of frozen-density embedding to model induced circular dichroism

In this study, we present calculations of the circular dichroism (CD) spectra of complexes between achiral and chiral molecules. Nonzero rotational strengths for transitions of the nonchiral molecule are induced by interactions between the two molecules, which cause electronic and/or structural perturbations of the achiral molecule. We investigate if the chiral molecule (environment) can be represented only in terms of its frozen electron density, which is used to generate an effective embedding potential. The accuracy of these calculations is assessed in comparison to full supermolecular calculations. We can show that electronic effects arising from specific interactions between the two subsystems can reliably be modeled by the frozen-density representation of the chiral molecule. This is demonstrated for complexes of 2-benzoylbenzoic acid with (-)-(R)-amphetamine and for a nonchiral, artificial amino acid receptor system consisting of ferrocenecarboxylic acid bound to a crown ether, for which a complex with l-leucine is studied. Especially in the latter case, where multiple binding sites and interactions between receptor and target molecule exist, the frozen-density results compare very well with the full supermolecular calculation. We also study systems in which a cyclodextrin cavity serves as a chiral host system for a small, achiral molecule. Problems arise in that case because of the importance of excitonic couplings with excitations in the host system. The frozen-density embedding cannot describe such couplings but can only capture the direct effect of the host electron density on the electronic structure of the guest. If couplings play a role, frozen-density embedding can at best only partially describe the induced circular dichroism. To illustrate this problem, we finally construct a case in which excitonic coupling effects are much stronger than direct interactions of the subsystem densities. The frozen density embedding is then completely unsuitable.     

Laser Induced Fluorescence Spectroscopy of IrN

High resolution laser induced fluorescence, spectra of IrN in the spectral region between 394 and 520 nm were recorded using laser vaporization/reaction free jet expansion and laser induced fluorescence spectroscopy. Seven new vibronic transition bands were observed and analyzed. Two Ω=1 and five Ω=0 new states were identified. Least squares fit of rotationally resolved transition lines yielded accurate molecular constants for the upper states. Spectra of isotopic molecules were observed, which provided confirmation for the vibrational assignment. Comparison of the observed electronic states of IrB, IrC, and IrN provides a good understanding of the chemical bonding of this group of molecules.     

Phenyl‐(2‐pyridyl)‐(3‐pyridyl)‐(4‐pyridyl)methane: Synthesis,Chiroptical Properties,and Theoretical Calculation of Its Absolute Configuration

The title compound, a prototypical chiral molecule based on a tetraarylmethane framework, has been synthesized in five steps from (2‐pyridyl)‐(3‐pyridyl)ketone. X‐ray crystallographic analysis revealed the tetraarylmethane framework of the molecule but did not determine the positions of the nitrogen atoms because the crystal is a racemic compound and the aryl groups are disordered in the crystal. The optical resolution of the title compound was achieved by chiral HPLC with a Chiralcel OD column. The CD spectra of the two fractions in acetonitrile exhibited opposite signs as expected for a pair of enantiomers. Their CD spectra are changed in 2 M HCl due to protonation. The calculated CD curve for the target molecule based on time‐dependent density functional theory (TDDFT) reproduces the experimental result very well, thus suggesting that the first eluted fraction is the R isomer in terms of absolute configuration.     

A configurational and conformational study of aframodial and its diasteriomers via experimental and theoretical VA and VCD spectroscopies

In this work we present the experimental and theoretical vibrational absorption (VA) and the theoretical vibrational circular dichroism (VCD) spectra for aframodial. In addition, we present the theoretical VA and VCD spectra for the diasteriomers of aframodial. Aframodial has four chiral centers and hence has 2⁴ = 16 diasteriomers, which occur in eight pairs of enantiomers. In addition to the four chiral centers, there is an additional chirality due to the helicity of the entire molecule, which we show by presenting 12 configurations of the 5S,8S,9R,10S enantiomer of aframodial. The VCD spectra for the diasteriomers and the 12 configurations of one enantiomer are shown to be very sensitive not only to the local stereochemistry at each chiral center, but in addition, to the helicity of the entire molecule. Here one must be careful in analyzing the signs of the VCD bands due to the ‘non-chiral’ chromophores in the molecule, since one has two contributions; one due to the inherent chirality at the four chiral centers, and one due to the chirality of the side chain groups in specific conformers, that is, its helicity. Theoretical simulations for various levels of theory are compared to the experimental VA recorded to date. The VCD spectra simulations are presented, but no experimental VCD and Raman spectra have been reported to date, though some preliminary VCD measurements have been made in Stephens’ lab in Los Angeles. The flexible side chain is proposed to be responsible for the small size of the VCD spectra of this molecule, even though the chiral part of the molecule is very rigid and has four chiral centers. In addition to VCD and Raman measurements, Raman optical activity (ROA) measurements would be very enlightening, as in many cases bands which are weak in both the VA and VCD, may be large in the Raman and/or ROA spectra. The feasibility of using vibrational spectroscopy to monitor biological structure, function and activity is a worthy goal, but this work shows that a careful theoretical analysis is also required, if one is to fully utilize and understand the experimental results. The reliability, reproduceability and uniqueness of the vibrational spectroscopic experiments and the information which can be gained from them is discussed, as well as the details of the computation of VA, VCD and Raman (and ROA) spectroscopy for molecules of the complexity of aframodial, which have multiple chiral centers and flexible side chains. Festschrift in Honor of Philip J. Stephens’ 65th Birthday.     

Transfer and Amplification of Chirality Within the “Ring of Fire” Observed in Resonance Raman Optical Activity Experiments

We report extremely strong chirality transfer from a chiral nickel complex to solvent molecules detected as Raman optical activity (ROA). Electronic energies of the complex were in resonance with the excitation‐laser light. The phenomenon was observed for a wide range of achiral and chiral solvents. For chiral 2‐butanol, the induced ROA was even stronger than the natural one. The observations were related to so‐called quantum (molecular) plasmons that enable a strong chiral Rayleigh scattering of the resonating complex. According to a model presented here, the maximal induced ROA intensity occurs at a certain distance from the solute, in a three‐dimensional “ring of fire”, even after rotational averaging. Most experimental ROA signs and relative intensities could be reproduced. The effect might significantly increase the potential of ROA spectroscopy in bioimaging and sensitive detection of chiral molecules.     

Enantiomer resolution of intrinsically chiral C21-alkylated N-confused porphyrin complexes

The resolution of stereoisomers of C21‐alkylated nickel(II) complexes of N‐confused porphyrin (NCP) was performed by means of chiral‐phase HPLC with an effectiveness of above 90 % molar ratio for each isomer. The reverse signs of the Cotton effects in the circular dichroism (CD) spectra of the separated fractions are indicative of the pair of enantiomers. The application of low‐temperature 2D NMR methods to the separated diastereomers of the system comprising a chiral 2‐(S)‐methylbutyl substituent, in connection with the CD spectra and relative HPLC migration rates, allowed the assignment of the absolute configuration of the chiral C21‐substituted complexes of NCP. The assignment was confirmed by time‐dependent DFT (TDDFT) calculations of CD spectra for the C21‐methylated nickel(II) complex. The system remains chiral after removal of the metal ion from the macrocyclic crevice, despite the fact that this demetalation is connected with a change of the C21 hybridization from pyramidal to trigonal. The retention of chirality was established by means of CD spectra and confirmed by TDDFT calculations for a C21‐methylated NCP free base. Stereoisomers were also separated for three covalently linked bis(NCP) systems with bridges involving one or two C21 carbon atoms. The occurrence of a pair of enantiomers was established for nonsymmetrical dimers comprising only one stereogenic center. In the case of the 21,21′‐(o‐xylene)‐linked dimer, three stereoisomers, that is, a pair of enantiomers and an optically inactive meso‐form, were separated and analyzed by CD and ¹H NMR spectroscopy. The stereoisomers of a diastereoselectively formed nonsymmetrical chloroplatinum(II)‐linked dimer, consisting of heterochiral C21‐alkylated NCP nickel(II) subunits, after separation displayed a strong optical activity, which can be ascribed to the rigid helical structure of the complex.     

Handedness inversion of chiral amphiphilic molecular assemblies evidenced by supramolecular chiral imprinting in mesoporous silica assemblies

Antipodal twisted helical ribbons with lamellar bilayer structure were obtained by self-assembly of chiral amphiphilic molecules in water and water/ethanol. The handedness inversion of the molecular arrangement in these antipodal helical ribbons was investigated by using chiroptical spectroscopy and molecular probes in their antipodal mesoporous silica assemblies synthesized through pairing interaction between the head group of the chiral amphiphilic molecules and a co-structure-directing agent. The supramolecular chirality is imprinted in the pore surface through the organic group of the co-structure-directing agent. The mirror-image diffuse-reflectance circular dichroism spectra of the conjugated discotic probing molecule introduced into their supramolecular chiral imprinted mesoporous silica demonstrated the origin of inverse chirality from the antipodal helical stacking of the molecules.