²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

Abstract

The analytical potential and enantioselective properties of lyotropic mesophases made by mixing two chemically different chiral polypeptides are described. Here we examine the case of a mixture of poly-gamma-benzyl-L-glutamate (PBLG) and poly-epsilon-carbobenzyloxy-L-lysine (PCBLL). We demonstrate that 2H NMR spectroscopy on these chiral oriented mixtures can discriminate both enantiomers and enantiotopic directions in prochiral molecules. Moreover, in such systems, degree of enantiodiscrimination, resolution, and sensitivity can be conjointly optimized by changing the relative proportion of the two polypeptides. Therefore, these new enantiodiscriminating media provide a favorable alternative to single-polypeptide mesophases with respect to stereochemical applications. At a more fundamental level, the present work points out that solute distribution in the vicinity of each polypeptide partly governs the degree of enantiodiscrimination and NMR relaxation rates. To this end, the experimental trends of solute NMR observables (Delta nu Q, T1) versus the fraction of peptide units of each polymer were analyzed by using a "mean-field" model derived from that proposed for mixtures of thermotropic nematic solvents, and based on the separation of intermolecular interactions between the solute and both polypeptides. This approach allows the relative solute-fiber affinities in these lyotropic systems to be determined. To identify the factors controlling solute-polypeptide affinities, we investigated various solutes (polar/apolar, rigid/flexible, achiral/prochiral/chiral molecules) using 2H NMR at natural abundance or on isotopically enriched solutes.

Analysis of NAD 2D‐NMR Spectra of Saturated Fatty Acids in Polypeptide Aligning Media by Experimental and Modeling Approaches

“…In calculations, the area per polymer (a p ) in Equation (4) ) estimated from the polymer concentration in solutions. [45] We verified that the general shape of the splitting profiles is not very sensitive to small variations (up to the order of 0.5 kJ mol…”

How different are diastereomorphous orientations of enantiomers in the liquid crystalline phases of PBLG and PBDG: a case study

“…If one diastereomorphous interaction is clearly favored, the resulting value of the RDCs should be shifted toward the value of the corresponding neat LC phase. Hence the passage from one neat LC phase to the other should proceed in a nonlinear effect fashion, as was shown for two chemically different orienting media by Lesot et al [42] All RDCs (see Fig. 2 and Supporting Information), which differ in value for the neat PBLG and PBDG LC phases show either a linear or a slightly s-shaped dependence on the molar fraction of PBLG.…”

“…1b). This was initiated by the very recent results of Lesot et al [42] who reported that when mixing PBLG and poly-ε-carbobenzyloxy-L-lysine (PCBLL), solutes exhibited different affinities toward the fibers of the two different LC phases. We were thus interested whether such a difference in affinities would also be detectable for the diastereomorphous interactions of the two enantiomers of the solute with the two enantiomers of the liquid crystal (PBLG and PBDG).…”

Analytical contribution of NAD 2D‐NMR spectroscopy in polypeptide mesophases to the investigation of triglycerides

“…The analytical potential of NMR in polypeptide chiral‐oriented media (organic solutions of poly‐ γ ‐benzyl‐ L ‐glutamate (PBLG), poly‐ ε ‐carbobenzyl‐ L ‐lysine, poly‐ γ ‐ethyl‐ L ‐glutamate, or a mixture of polypeptides) mainly lies in the efficiency of shape recognition phenomena of the mesophase that lead to orient differently pairs of enantiotopic directions in prochiral compounds or enantiomers in average at NMR time scale . When the enantiorecognition mechanisms are efficient enough, two distinct spectral signatures are expected to be observed, one for each R / S enantiomer or each pro‐ R /pro‐ S enantiotopic element .…”

“…The power of this emerging approach for biochemical studies has been nicely demonstrated recently . Compared with the SNIF‐NMR® technique developed by Martin and co‐workers in 1980s that uses isotropic liquids as NMR solvent, NAD NMR spectroscopy in polypeptide‐oriented solvents has three advantages: (i) the 2 H quadrupolar interaction is no longer averaged to zero as in liquids, and hence each inequivalent deuterium site gives rise to a quadrupolar doublet (QD) whose splitting, Δν Q , is proportional to the order parameter of the C–D bond, S C–D , (where ); (ii) the distribution of doublets on NAD 2D maps allows to reduce the peak overlapping for small‐to‐middle size molecules and generally provides different QDs for fortuitously isochronous deuterons unlike to isotropic NMR for which resonances are located at the same 2 H chemical shift; and (iii) the spectral discrimination of enantiotopic elements in prochiral molecules or enantiomers is possible when the mesophase is chiral …”