Integrated Computational Protocol for the Analysis of Quadrupolar Splittings from Natural‐Abundance Deuterium NMR Spectra in (Chiral) Oriented Media

Abstract

Despite its low natural abundance, deuterium NMR spectroscopy in weakly oriented (chiral) solvents gives easy access to deuterium residual quadrupolar couplings ( H-RQCs). These are formally equivalent to one-bond residual dipolar couplings (( C- H)-RDCs) for calculation of the Saupe tensor, and provide similar information for the study of molecular structure and orientational behavior. Because the quadrupolar interaction is one order of magnitude larger than the dipolar one, H-RQC analysis is a much more sensitive tool for the detection of subtle structural differences and also tiny differences in molecular alignment, such as those observed for different enantiomers in chirally aligned media. To promote the analytical advantages of anisotropic, natural-abundance deuterium NMR (NAD NMR) spectroscopy in the organic chemistry community, we describe a H-RQC/DFT-based integrated computational protocol for the evaluation of the order parameters of aligned solutes by using singular-value decomposition. Several examples of H-RQC-assisted analysis of chiral and prochiral molecules dissolved in various polypeptide lyotropic chiral liquid crystals are reported. The role of the molecular shape in the ordering mechanism was investigated through the determination of intertensor angles between alignment tensors and inertia tensors by using the proposed protocol.

2H and 13C NMR‐Based Enantiodetection Using Polyacetylene versus Polypeptide Aligning Media: Versatile and Complementary Tools for Chemists

“…In PLA, seventeen QDs (out of the 20 expected if all sites were discriminated) are observed, and unexpected large differences of RQCs (up to 13 Hz, DOE=1.0) have been measured (Figure and Figure SI‐31). These first NAD NMR results in PLA aligning media open promising prospects in terms of analytical applications, especially for saturated hydrocarbons which are difficult to crystallize and derivatize, but also generally in the domain of the structural elucidation of small organic chiral molecules based on 2 H‐RQC measurements,, complementing or replacing the measurements of ( 13 C‐ 1 H)‐RDCs or 13 C‐RCSAs…”

Residual Dipolar Couplings in Structure Determination of Natural Products

“…RDCs will keep contributing to a variety of structure determination problems and will become an important tool for all NMR spectroscopists, or in combination with the measurement of residual chemical shift anisotropies (RCSAs) [ 100 ] and deuterium residual quadrupolar couplings ( 2 H-RQCs) [ 101 ] in weakly oriented (chiral) solvents. With the development of anisotropic NMR parameters, in the near future, this methodology will be routinely applicable for assigning the stereochemical correlation of spatially distant stereocenters in structurally complicated molecules.…”

Analytical contribution of deuterium 2D‐NMR in oriented media to 2H/1H isotopic characterization: the case of vanillin

“…From a structural viewpoint, depends on the angle between the C‐ 2 H i bond and the magnetic field axis, . Consequently, the magnitude of 2 H‐RQCs for a given 2 H site is structurally related to its position in a (rigid) molecule, and this property is very useful for the assignment of QDs (see below) . For instance, in planar molecules, two collinear C‐ 2 H internuclear directions show the same RQC values (see Figure A) .…”