Multinuclear NMR in polypeptide liquid crystals: Three fertile decades of methodological developments and analytical challenges

Abstract

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.

Deuterium Residual Quadrupolar Couplings: Crossing the Current Frontiers in the Relative Configuration Analysis of Natural Products

“…Deuterium possesses a small quadrupolar coupling constant ( 2 H-QCC), C Q , which makes the T 2 ( 2 H) relaxation times long enough to obtain isotropic or anisotropic 2 H spectra with narrow linewidths. [35][36][37][38][39] At first glance, the notably low sensitivity of the technique (relative receptivity 1 H/ 2 H is 1.7 × 10 6 : 1) caused by the low natural abundance of deuterium (NAD) and its poor magnetogyric ratio (γ( 1 H )/ (γ( 2 H ) = 6.515) appears as primary drawbacks. 40,41 However, in modern NMR instruments operating at high magnetic fields and equipped with modern electronics and, particularly, cryogenically cooled 2 H probes, 42,43 it is possible to collect 1D NAD-{ 1 H} spectra (and even 2D) for samples at moderate concentrations (~10 -4 -10 -5 mol with MW ~ 200-400), leading to a wide range of analytical applications.…”

“…35 Interestingly as 2 H-{ 1 H} NMR spectra can be recorded at the natural abundance level, no isotopic enrichment is necessary. [39][40][41][42] Moreover, because all monodeuterated isotopomers for a given molecule form independent dilute 2 H-spin systems, anisotropic NAD (denoted herein ANAD) measurements are not affected by all the cumbersome strong 1 H-1 H coupling effects that frequently hamper accurate determination of 1 D CH couplings in CH 2 groups. 48,49 Disregarding the obvious problem with sensitivity, NAD NMR determination also has some additional disadvantages: first, the experimental determination of the sign of the RQCs is not straightforward since there is no isotropic component involved in the 2 experiments for 2 H-RQCs.…”

Exploring the enantiomeric 13C position-specific isotope fractionation: challenges and anisotropic NMR-based analytical strategy

“…An alternative to these "isotropic" methods consists of using chiral aligning solvents such as chiral liquid crystals (CLC) that are able to orient enantiomers differently on average. This differential orientational order leads to distinct orderdependant NMR observables for each enantiomer as the residual dipolar coupling (RDC), the residual chemical shift anisotropy (RCSA) or the residual quadrupolar coupling (RQC) for spin I > 1/2 [45,46,47]. Obviously, each strategy possesses specific analytical advantages and drawbacks in terms of practicality and/or application ranges.…”

Light-Controlled Lyotropic Liquid Crystallinity of Polyaspartates

“…In a next step, we investigate the influence of this change on intermolecular interactions between probe molecules and the polymer. As the lyotropic liquid crystal is inherently chiral due to the one-handed helical backbone of the polypeptide, its enantiomer differentiation capabilities 38,39 were simultaneously tested. Therefore, either (+)-or (-)-IPC additionally dissolved in the NMR sample as probe molecules were investigated (Figure 4 enantiomers with respect to the NMR spectrometer's magnetic field.…”