Chiral Liquid Crystalline Solvent Research Articles

Investigation of Solute-Fiber Affinity and Orientational Ordering of Norbornadiene Interacting with Two-Polypeptide Chiral Liquid Crystalline Solvents by Natural Abundance Deuterium (NAD) NMR.

A prochiral bridged compound of C2v symmetry, the norbornadiene (NBD), oriented in a chiral liquid crystal composed of various mixtures of poly-γ-benzyl-l-glutamate (PBLG) and poly-ε-carboxy-l-lysine (PCBLL), two chiral homopolypeptides, is investigated using natural abundance deuterium 2D-NMR (NAD 2D-NMR) spectroscopy. In such chiral oriented solvents, enantiotopic directions are spectrally nonequivalent, and two distinct (2)H quadrupolar doublets associated with enantioisotopomeric pairs of NBD are detected. As the two homopolypeptides have the same absolute configuration but distinct chemical functions in their side chains, the variation of residual quadrupolar couplings (RQC's) allows the determination of the relative solute-fiber affinities toward the two polypeptides in these lyotropic bipolymeric systems. Besides the experimental measurement of RQC's and the determination of their signs at each inequivalent (2)H site, the elements of the second-rank order tensor, Sαβ, are calculated by assuming a modeled structure. The variations of RQC's and diagonalized order parameters, Sα'α', are followed versus the relative proportion of two polypeptides in the chiral oriented mixture. The influence of the solute mass fraction in the two-homopolypeptide oriented samples is also examined as well as the case of homogeneous and uniform achiral mesophases "PBG-PCBL" made of two pairs of mirror-image homopolypeptides (PBLG/PBDG and PCBLL/PCBDL). In the latter, the solute ordering is modulated by the proportion of each type of homopolypeptide (chemical nature and absolute configuration), leading to eliminate the enantiodiscrimination mechanisms on the average. In the frame of a model, new insights on the solute-homopolypeptide fiber interactions are discussed.

The use of exchangeable nuclei to observe enantiomers through deuterium NMR in chiral liquid crystalline solvents

It is demonstrated that (2)H NMR in chiral liquid crystalline solvents can be used to measure enantiomeric excesses using exchangeable deuterons in alcohols. This is performed in a trivial way at low temperature (260-270 K) where a slow exchange regime was reached. Among the various alcohols used to explore the possibilities of this technique, an unusually large isotopic effect on molecular orientation between two isotopomers has been observed.

Application of z-COSY experiment and its variant for accurate chiral discrimination by 1H NMR

We report the application of z-COSY experiment and a band selected version of it by employing a selective 90 degrees pulse entitled BASE-z-COSY for precise chiral discrimination, quantification of enantiomeric excess and the analyses of the (1)H NMR spectra of chiral molecules aligned in the chiral liquid crystalline solvent poly-gamma-benzyl-l-glutamate (PBLG). We have demonstrated their applicability for obtaining very high resolution in the (1)H NMR spectra of small organic molecules. It is well known that the commonly employed z-COSY experiment disentangles the spectral complexity, provides pure phase spectra with high resolution, aids in the complete spectral analyses, in addition to yielding information on relative signs of the couplings. The BASE-z-COSY experiment possesses all these properties, permits the measure of enantiomeric excess, in addition to large saving of instrument time.

Band selective small flip angle COSY: A simple experiment for the analyses of 1H NMR spectra of small chiral molecules

The NMR spectroscopic discrimination of enantiomers in the chiral liquid crystalline solvent is more often carried out using 2H detection in its natural abundance. The employment of 1H detection for such a purpose is severely hampered due to significant loss of resolution in addition to indistinguishable overlap of the spectra from the two enantiomers. This study demonstrates that the band selected small flip angle homonuclear correlation experiment is a simple and robust technique that provides unambiguous discrimination, very high spectral resolution, reduced multiplicity of transitions, relative signs of the couplings and enormous saving of instrument time.

Enantiodiscrimination in Deuterium NMR Spectra of Flexible Chiral Molecules with Average Axial Symmetry Dissolved in Chiral Liquid Crystals: The Case of Tridioxyethylenetriphenylene

Flexible chiral molecules undergoing fast interconversion (on the NMR time scale) between different conformational enantiomers may yield "average" axial species with enantiotopically related sites. Contrary to the situation observed for rigid axial molecules, signals from these enantiotopic sites in NMR spectra recorded in chiral liquid-crystalline solvents can be resolved. In the present work, we studied the deuterium NMR spectra of tridioxyethylenetriphenylene (compound 4) statistically deuterated to 10% in the flexible side chains and dissolved in chiral and achiral lyotropic liquid crystals based on poly(gamma-benzylglutamate). The fast chair-chair flipping of the side chains in 4 on average renders the molecule axially symmetric ( D 3 h ) with pairs of enantiotopic ethylene deuterons. These deuterons exhibit unusually large enantiodiscrimination. To explain this observation, we first describe how the average symmetry of flexible molecules can be derived from the symmetry of the "frozen" conformers and the nature of the averaging process. The procedure is then applied to 4 and used to analyze the NMR results. It is shown that the large enantiodiscrimination in the present case reflects a large difference in the orientational ordering of the conformational enantiomers participating in the interconversion processes as well as a large geometrical factor due to the special shape of the dioxyethylene side groups. (1)H and (13)C NMR spectra of 4 in the same lyotropic liquid crystalline solvent are analyzed to determine its ordering characteristics. Several related cases are also discussed.

Separation and Complete Analyses of the Overlapped and Unresolved 1H NMR Spectra of Enantiomers by Spin Selected Correlation Experiments

NMR spectroscopic discrimination of optical enantiomers is most often carried out using (2)H and (13)C spectra of chiral molecules aligned in a chiral liquid crystalline solvent. The use of proton NMR for such a purpose is severely hindered due to the spectral complexity and the significant loss of resolution arising from numerous short- and long-distance couplings and the indistinguishable overlap of spectra from both R and S enantiomers. The determination of all the spectral parameters by the analyses of such intricate NMR spectra poses challenges, such as, unraveling of the resonances for each enantiomer, spectral resolution, and simplification of the multiplet pattern. The present study exploits the spin state selection achieved by the two-dimensional (1)H NMR correlation of selectively excited isolated coupled spins (Soft-COSY) of the molecules to overcome these problems. The experiment provides the relative signs and magnitudes of all of the proton-proton couplings, which are otherwise not possible to determine from the broad and featureless one-dimensional (1)H spectra. The utilization of the method for quantification of enantiomeric excess has been demonstrated. The studies on different chiral molecules, each having a chiral center, whose spectral complexity increases with the increasing number of interacting spins, and the advantages and limitations of the method over SERF and DQ-SERF experiments have been reported in this work.

Discrimination of enantiomers by means of NMR spectroscopy using chiral liquid crystalline solution: application to triazole fungicides, uniconazole and diniconazole

An NMR method for discriminating among enantiomers by using a chiral liquid crystalline solution was applied to chiral triazole compounds, uniconazole (1) and diniconazole (2), which exhibit antifungal and plant growth regulating activities. These chiral compounds were dissolved in PBLG (poly-gamma-benzyl-L-glutamate)--CDCl3 chiral liquid crystalline solvent for measurements of 13C NMR. The enantiomeric separations were primarily observed in the signals of aromatic carbons owing to differences in chemical shift anisotropies. The enantiomeric excess (ee) was determined from the integral scale of the separated peaks. The resulting ee values are in fair agreement with the actual values. The extrasplittings due to residual dipolar couplings were also measured using Het2DJ spectra for 1S and R, and 2R, and the results are discussed.

Exploring the Analytical Potential of NMR Spectroscopy in Chiral Anisotropic Media for the Study of the Natural Abundance Deuterium Distribution in Organic Molecules

The deuterium/hydrogen (D/H)(i) ratio measurement by quantitative (2)H NMR spectroscopy is a method of choice for the analysis of kinetic isotopic effects associated with enzyme-catalyzed reactions during a biosynthetic pathway. However, the efficiency of the current isotropic (2)H-[(1)H] NMR can be limited by the rather small chemical shift dispersion of deuterium nuclei. In addition, this method does not allow the enantiotopic deuterons in prochiral molecules to be spectrally discriminated, hence precluding the quantification of isotopic fractionation on methylene prostereogenic sites. In this work, we explore another analytical strategy able to circumvent these disadvantages. This approach is based on the use of natural abundance (2)H 2D NMR experiments on solutes embedded in polypeptidic, chiral liquid crystalline solvent. Thus, we show that NMR in these oriented phases is a powerful way to separate deuterium signals on the basis of the quadrupolar interactions, providing a promising alternative to overcrowded (2)H NMR spectra obtained in liquid state. To illustrate our purpose, we have experimentally investigated the case of 1,1'-bis(phenylthio)hexane derived by cleavage from methyl linoleate of safflower. The (2)H NMR results in chiral liquid crystals are presented and discussed. We show, for the first time, that (D/H)(pro-R) and (D/H)(pro-S) can be measured at the same methylene position of a fatty acid chain.

Assay for the enantiomeric analysis of [2H1]-fluoroacetic acid: insight into the stereochemical course of fluorination during fluorometabolite biosynthesis in streptomyces cattleya.

A sensitive method for the configurational analysis of (R)- and (S)-[2H1]-fluoroacetate has been developed using 2H[1H]-NMR in a chiral liquid crystalline solvent. This has enabled biosynthetic experiments to be conducted which reveal stereochemical details on biological fluorination occurring during the biosynthesis of fluoroacetate and 4-fluorothreonine in the bacterium Streptomyces cattleya. In particular, feeding experiments to S. cattleya with isotopically labeled (1R, 2R)- and (1S, 2R)-[1-2H1]-glycerol 3d and 3e and [2,3-2H(4)]-succinate 4a gave rise to samples of enantiomerically enriched [2-2H1]-fluoroacetates 1a. The predominant enantiomer resulting from each experiment suggests that the stereochemical course of biological fluorination takes place with an overall retention of configuration between a glycolytic intermediate and fluoroacetate 1. Consequently, this outcome suggests that the stereochemical course of the recently identified fluorinase enzyme which mediates a reaction between fluoride ion and S-adenosyl-l-methionine (SAM), occurs with an inversion of configuration.

ChemInform Abstract: Achiral Deuterated Derivatizing Agent for Enantiomeric Analysis of Carboxylic Acids by NMR in a Chiral Liquid Crystalline Solvent.

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Achiral deuterated derivatizing agent for enantiomeric analysis of carboxylic acids by NMR in a chiral liquid crystalline solvent

The use of a deuterated ‘probe’ for the enantiomeric analysis of chiral carboxylic acids is proposed. The probe is the perdeuterobenzyl fragment which can be easily attached to the acid and removed from the corresponding ester. The analysis is performed through the measurement of the proton-decoupled deuterium NMR spectrum of the chiral benzyl ester dissolved in poly-γ-benzyl- l-glutamate/dimethylformamide liquid crystal. Enantiomeric discrimination was observed for all the studied compounds on the para and/or α deuterons. There is no need for the deuterons to be located close to the stereogenic centre. Thus enantiomers were correctly distinguished from the signal of a deuterium located 12 bonds away from the asymmetric carbon. The major interest of this general technique is that no kinetic resolution should occur during the derivatization process.

The relationship between molecular symmetry and second-rank orientational order parameters for molecules in chiral liquid crystalline solvents

From group theoretical arguments, we demonstrate that the effective molecular symmetry is reduced in a chiral liquid crystalline phase. This reduction changes the location of the principal axes of the orientational order matrices for four molecular point groups, namely Cs, C2v, S4, and D2d. These symmetries correspond to compounds which have prochiral faces, groups, or directions. The change in effective molecular symmetry can be detected by NMR spectroscopy, and this is illustrated by the example of acenaphthene dissolved in a chiral nematic solvent.

Diastereomeric Shape Recognition Using NMR Spectroscopy in a Chiral Liquid Crystalline Solvent.

Unambiguous assignment of the resonances of different diastereomers in a nonracemic mixture is possible with (1)H-decoupled (2)H NMR spectroscopy in a chiral liquid crystalline solvent. This is demonstrated with, for example, the alpha,alpha'-dideuterated diol shown in the picture. Even diastereomers with centers of chirality up to nine bonds apart can be discriminated.

Double diastereoselection in asymmetric [2+3] cycloaddition of chiral oxazoline N-oxides: application to the kinetic resolution of a racemic α,β-unsaturated δ-lactone

The asymmetric [2+3] cycloaddition reaction between chiral oxazoline N-oxide 1 and α,β-unsaturated lactone 2 was studied. A double diastereoselection was observed, (1 R)- 1 and ( R)- 2 gave a mismatched pair with almost no cycloadduct obtained. A transition state model is proposed, accounting for the destabilization of transition state in the cycloaddition reaction. This result has led to kinetic resolution studies, in which both enantiomers of 1 were reacted with racemic lactone 2. The enantiomeric excess of the recovered lactone 2 was determined to be up to 70% ee, by 13C-{ 1H} NMR analysis in a chiral liquid crystalline solvent. The experimental results are in agreement with predicted enantiomeric excesses and consistent with the transition state models.