New Stretching Method for Aligning Gels: Its Application to the Measurement Residual Chemical Shift Anisotropies (RCSAs) without the Need for Isotropic Shift Correction

Abstract

An existing gel stretching device is modified, permitting the use of organic solvents for the study of small molecules. Different from the original device, gels are stretched into 4 mm open-ended NMR tubes and then inserted into regular 5 mm NMR tubes. No open-ended tubes are inserted in the NMR probe avoiding the risk of sample leaking. It is also shown that residual chemical shift anisotropies (RCSAs) measured with the device are free of isotropic shift interferences and corrections for them are not needed during the post-acquisition data analysis. Three internal references for chemical shift were evaluated (CCl , CBr and TMS), being CCl the most convenient one to measure RCSAs in CDCl . RCSAs measured with the modified stretching device using CCl as the internal chemical shift reference were enough to determine the relative configuration of three small molecules with an excellent degree of configuration discrimination.

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

“…Anisotropic NMR has contributed powerful complementary restraints to isotropic chemical shifts, NOEs and J-couplings 9,10 as implemented, for example, in the powerful DP4+ analysis tool 25 . Measurement of anisotropic NMR parameters requires partial ordering of the molecules in alignment media such as aligning gels and liquid crystals 9,[26][27][28][29][30][31][32][33] . Although one-bond 1 H- 13 C RDC measurement is the most common, the sensitivity of RDC measurement becomes problematic if the available sample is below a few hundred micrograms 34 .…”

Elucidating natural product structures using a robust measurement of carbon residual chemical shift anisotropy combined with DFT

“…In several reports, the highly upfield carbon signal of symmetric and tetrahedral TMS and CCl 4 , for which the RCSA effect vanishes, were used as reference signals. [35] However, some tetrahedral molecules can still show anisotropic behavior and might change the alignment tensor of the compound of interest. [45] In a very recent report, both the spectra were referenced at the solvent peaks.…”

“…[ 13,14,33 ] These developments render RCSA analysis a powerful tool in the structure elucidation process, and recently, they were used to determine configurations. [ 13,14,19,34–37 ]…”

“…[13,14,33] These developments render RCSA analysis a powerful tool in the structure elucidation process, and recently, they were used to determine configurations. [13,14,19,[34][35][36][37] As noted above, DFT-computed CSA tensors are required for the interpretation of RCSA data. [12,13] Because it is problematic to measure them employing solid-state NMR for carbons with smaller CSAs, alternate means of computing CSA tensors using computational chemistry becomes mandatory.…”

Stereochemical Elucidation of Natural Products from Residual Chemical Shift Anisotropies in a Liquid Crystalline Phase

“…Pioneering work in this field was performed in 2011 by Luy and co-workers using variable-angle NMR spectroscopy . Recently, more practical methods have been introduced in polymeric gels, which rely mainly on the usage of a specially designed two-stage NMR tube or a compression device. − Additionally, a method to acquire RCSAs with an enhanced alignment amplitude in poly-γ-(benzyl- l -glutamate) (PBLG) has been proposed using a first-order correction strategy for changes in PBLG concentration. , …”