The splitting of signals in the NMR spectra originating from enantiotopic sites in prochiral molecules when dissolved in chiral solvents is referred to as spectral enantiotopic discrimination. This phenomenon is particularly noticeable in chiral liquid crystals (CLCs) due to the combined effect of the anisotropic magnetic interactions and the ordering of the solute in the mesophase. The enantiorecognition mechanisms are different for rigid and flexible solutes. For the former, discrimination results from symmetry breaking and is restricted to solutes whose point groups belong to one of the following four ("allowed") symmetries, Cs, C2v, D2d and S4. The nature of the symmetry breaking for each one of these groups is discussed and experimental examples, using mainly (2)H 1D/2D-NMR in chiral polypeptide lyotropic mesophases, are presented and analyzed. When flexible optically active solutes undergo fast racemization (on the NMR timescale) their spectrum corresponds to that of an average prochiral molecule and may exhibit enantiotopic sites. In CLCs, such sites will become discriminated, irrespective of their average (improper) symmetry. This enantiodiscrimination results mainly from the different ordering of the interchanging enantiomers. Several examples of such flexible molecules, including solutes with average axial and planar symmetries, are commented. Dynamic processes in solution that are not accompanied by the modulation of magnetic interactions remain "NMR blind". This is sometimes the case for interconversion of enantiomers (racemization) or exchange of enantiotopic sites in isotropic solvents. The limitation can be lifted by using CLCs. In such solvents, non-equivalence between enantiomers or between enantiotopic sites is induced by the chiral environment, thus providing the necessary interactions to be modulated by the dynamic processes. Illustrative examples involving exchange of both, enantiotopic sites and enantiomers are examined. In this comprehensive review, various important aspects of enantiodiscrimination by NMR are presented. Thus the possibility to reveal enantiotopic recognition using residual dipolar couplings or to determine the absolute configuration of enantiotopic NMR signals is discussed. The various kinds of chiral mesophases able to reveal enantiotopic discrimination in guest prochiral molecules are also described and compared with each other. Finally to illustrate the high analytical potentialities of NMR in CLCs, several and various applications involving the enantiodiscrimination phenomenon are described. A strategy for assigning the NMR signals of meso compound in a meso-threo mixture of cyclic molecules is first discussed. This is followed by a description of advantages of the method for the determination of (D/H) natural isotopic fractionation in biocompounds.

We report new and explicit experimental evidence of the differentiation of (1)H-(1)H, (13)C-(1)H, and (13)C-(2)H enantiotopic directions in prochiral molecules with C(s) and C(2v)symmetry dissolved in a chiral liquid-crystalline phase using (13)C and (2)H-[(1)H] NMR spectroscopy at the natural abundance level. The case of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, bicyclo[2.2.1]hepta-2,5-diene, and ethyl alcohol oriented in organic solutions of poly-gamma-benzyl-L-glutamate (PBLG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL) is investigated and discussed. Next, we describe the first NMR differentiation of enantiotopic directions in a C(2v) molecule with no prostereogenic carbon using malononitrile as a model. The various results presented in this work experimentally validate our recent theoretical arguments which predict that NMR spectra of nonplanar C(s) and C(2v) compounds embedded in a chiral oriented solvent should differ from those recorded in nonchiral oriented media, because their effective molecular symmetry point group (interacting molecule) is different from their molecular point group (isolated molecule). In addition, the differentiation of enantiotopic directions in C(2v) molecules exhibiting no prostereogenic tetrahedral center illustrates for the first time an old stereochemical hypothesis which speculates that "for molecules of the type CXXYY. the two X groups as well as the Y groups are equivalent and cannot be distinguished in chiral or achiral circumstances. However, the relationships between X and Y groups are not all equivalent. The four X-Y relationships may be ordered into two enantiotopic sets of two equivalent relationships" (Mislow, K.; Raban, M. Top. Stereochem. 1967, 1, 1) and validate the stereogenicity concepts proposed more recently by Fujita (Fujita, S. J. Am. Chem. Soc. 1990, 112, 3390).

NMR spectroscopy of oriented samples makes accessible residual anisotropic intramolecular NMR interactions, such as chemical shift anisotropy (RCSA), dipolar coupling (RDC), and quadrupolar coupling (RQC), while preserving high spectral resolution. In addition, in a chiral aligned environment, enantiomers of chiral molecules or enantiopic elements of prochiral compounds adopt different average orientations on the NMR timescale, and hence produce distinct NMR spectra or signals. NMR spectroscopy in chiral aligned media is a powerful analytical tool, and notably provides unique information on (pro)chirality analysis, natural isotopic fractionation, stereochemistry, as well as molecular conformation and configuration. Significant progress has been made in this area over the three last decades, particularly using polypeptide-based chiral liquid crystals (CLCs) made of organic solutions of helically chiral polymers (as PBLG) in organic solvents. This review presents an overview of NMR in polymeric LCs. In particular, we describe the theoretical tools and the major NMR methods that have been developed and applied to study (pro)chiral molecules dissolved in such oriented solvents. We also discuss the representative applications illustrating the analytical potential of this original NMR tool. This overview article is dedicated to thirty years of original contributions to the development of NMR spectroscopy in polypeptide-based chiral liquid crystals.

The natural abundance deuterium 2D Q-COSY NMR spectra of two apolar bridged ring systems, norbornene (C s symmetry) and quadricyclane (C 2 v symmetry), oriented in a chiral liquid crystal made of an organic solution of poly-γ-benzyl-l-glutamate (PBLG), are analyzed. In such a chiral oriented solvent, enantiotopic nuclei or directions are nonequivalent. Consequently, it is possible to measure many more anisotropic interactions compared to those obtained from NMR spectra in nonchiral nematic solvents. From the measurement of all residual quadrupolar splittings, ΔνQ, and one-bond carbon−proton residual dipolar couplings, 1 D C - H, all the elements of the second rank order tensor, S αβ, were calculated. Knowledge of the S αβ values allows all deuterons and subsequently proton NMR resonances to be assigned unambiguously. The reason is that there exists a one-to-one mathematical relationship linking the orientational order parameters of a solute molecule, the molecular geometry, and the anisotropic interactions measured on oriented spectra. In the case of norbornene, it was possible to assign nuclei to each enantiotopic face in this prochiral molecule. Such an analytical approach yields original stereochemical information probing the diastereotopicity and/or enantiotopicity of molecules, and is revealed to be a very useful alternative to conventional 2D-NMR experiments in isotropic solvents.

A new NMR method to determine the relative configuration of asymmetric centres is presented. It proceeds through the use of a weakly ordered solvent and the measurement of orientational order parameters. The method is illustrated by using dihydropyridone derivatives for which the orientations and the relative configurations of the asymmetric carbon atoms are determined unambiguously.

This article begins with general considerations about enrichment of hydrogen gas into its para isomer (corresponding to nuclear spins in the singlet state); this is a necessary condition to obtain hyperpolarization from transfer of the relevant population excess. This transfer is generally mediated by a hydrogenation reaction such that the two protons become nonequivalent. The energy level populations of this new spin system can be calculated unambiguously using a density matrix formalism. This formalism is reviewed, and the authors propose a simple method that leads to the spin state after the hydrogenation reaction and the insertion of the sample in the NMR magnet. The effect of radiofrequency pulses is also considered.

The enantiotopic discrimination in the NMR spectrum of prochiral molecules dissolved in chiral liquid crystals (CLCs) is governed by the ordering of the solute molecules. The lifting of the spectral degeneracy of enantiotopic sites in such solvents stems from the nonequivalence in their effective ordering. This, in turn, is brought about by a change in the directions (or the equivalence) of the principal axes of their ordering tensor, relative to those in achiral liquid crystals. This discrimination mechanism can only occur for solute molecules belonging to a limited number of (“allowed”) improper point groups, viz., D2d, C2v, Cs, and S4 [D. Merlet, J. W. Emsley, P. Lesot, and J. Courtieu, J. Chem. Phys. 111, 6890 (1999)]. In this work it is shown that the ordering tensor of such prochiral solutes in CLC, SCLC, and likewise, the tensors, Tk, describing the anisotropic magnetic resonance interactions of enantiotopic pairs, can be partitioned into symmetric and antisymmetric (and irrelevant) parts. The NMR results in such solvents can be cast into separate sets of equations depending on either the symmetric or the antisymmetric parts of SCLC and Tk. The discrimination observed in such solvents depends only on the latter set of equation, while the former applies to the average splitting of enantiotopic pairs as well as to diasterotopic or homotopic sites in the prochiral molecules. The factorization procedure greatly facilitates the analysis of the ordering properties of prochiral solutes in CLC and provides new insight on the discrimination mechanism. In particular, it allows correlation between independent enantiotopic partners and the identification of NMR signals belonging to common prosterogenic faces in the molecule. Expressions relating NMR observables with the symmetric and antisymmetric parts of SCLC are derived for each of the four allowed groups. Model examples are presented and discussed.

The conformational dynamics and orientational behavior of two model cyclic molecules, cis-decalin (cis-dec) and tetrahydrofurane (THF), dissolved in weakly ordering, polypeptidic chiral liquid crystals (CLCs) are theoretically discussed and experimentally investigated using deuterium and carbon-13 NMR spectroscopies. The analysis of enantiomeric and enantiotopic discriminations in these compounds is shown to depend on the rate of conformational exchange regime, slow or fast. The slow exchange regime is illustrated through the case of cis-dec at low temperature (243 K). We show that the deuterium NMR spectra in this regime can be qualitatively and quantitatively interpreted by restricting the conformational pathway of cis-dec to two enantiomeric conformers of C(2)-symmetry. The orientational order parameters of these interconverting enantiomers are calculated by matching the (2)H quadrupolar splittings with calculated conformer structures. The fast exchange regime is investigated through the examples of cis-dec at high temperature (356 K) and THF at room temperature (300 K). The (2)H NMR spectra above the coalescence temperature are analyzed by introducing the concept of "average molecular structure". This fictitious structure allows easily identifying NMR equivalences of solutes dissolved in CLC. However, it cannot be applied to determine consistent orientational order parameters. This study emphasizes that enantiotopic discriminations observed for flexible molecules in the fast exchange regime can be quantitatively interpreted only by considering the orientational order of each conformer.