Measurement of residual chemical shift anisotropies in compressed polymethylmethacrylate gels. Automatic compensation of gel isotropic shift contribution

Abstract

Mechanical compression of polymer gels provides a simple way for the measurement of residual chemical shift anisotropies, which then can be employed, on its own, or in combination with residual dipolar couplings, for structural elucidation purposes. Residual chemical shift anisotropies measured using compression devices needed a posteriori correction to account for the increase of the polymer to solvent ratio inside the swollen gel. This correction has been cast before in terms of a single-free parameter which, as shown here, can be simultaneously optimized along with the components of the alignment tensor while still retaining discriminating power of the different relative configurations as illustrated in the stereochemical analysis of α-santonin and 10-epi-8-deoxycumambrin B.

Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy

“…Although RDC applications date back to the sixties, there have been more reports in the past decade to determine the configuration of small molecules 12,[15][16][17][18][19] . In contrast, 13 C RCSA can be robustly measured, using conventional hardware, only since 2016 [20][21][22] . So far, there are only a few reports of temperature-based RCSA measurements for biomolecules 23,24 .…”

“…Recently, robust measurement of 13 C RCSAs was reported by using the compression and stretching of PMMA gels or by using liquid crystals [20][21][22][35][36][37] . These RCSAs delivered the relative configuration for a number of molecules with several stereogenic centers by cross validation of the experimental RCSAs against the theoretical ones derived from all possible other relative configurations 22 . However, 13 C RCSA measurements from 1D 13 C spectra are impossible due to the low sensitivity of carbon if the available sample is below a few 10's of micrograms at natural abundance.…”

Practical aspects of oligopeptide AAKLVFF as an alignment medium for the measurements of residual dipolar coupling of organic molecules

“…α‐Santonin (Figure ), as a historically important eudesmanolide, was previously employed by Hallwass et.al as a test molecule for the RDC and residual chemical shift anisotropy (RCSA)–based structure elucidation . In this study, we measured RDCs of α‐santonin at two different concentrations of the AAKLVFF phase (22.5 and 18.0 mg/mL, Table ).…”

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.…”