An Acrylonitrile-Based Copolymer Gel as an NMR Alignment Medium for Extraction of Residual Dipolar Couplings of Small Molecules in Aqueous Solution

An NMR weakly-aligning polymer gel has been prepared by copolymerization of acrylonitrile and 2-acrylamide-2-methyl-1-propanesulfonic acid in the presence of 1,4-butanediol diacrylate as a cross-linker. The polymer readily swells in water in a large range of temperatures, although the swelling ratio is decreased in saline solutions. The swollen gel can be mechanically compressed, in a reversible way, generating anisotropy, as easily shown in H-2 NMR experiments, and allowing measurement of D-1(CH) residual dipolar couplings (RDCs) through F1-coupled HSQC experiments. The performance of this gel as a NMR alignment medium was evaluated in several water-soluble organic molecules and, while it provided RDCs of proper size for sucrose and even such as small molecule as 5-norbornen-2-ol, in the case of azidothymidine and cefuroxime sodium salt the strong interaction of these molecules with the gel prevented successful extraction of the RDCs.

Automated summary

An NMR weakly-aligning polymer gel was prepared by copolymerization of acrylonitrile and 2-acrylamide-2-methyl-1-propanesulfonic acid with 1,4-butanediol diacrylate as a cross-linker. The gel swells in water over a wide range of temperatures, but its swelling ratio is reduced in saline solutions. The gel can undergo reversible mechanical compression, generating anisotropy, which is easily observed in H-2 NMR experiments and allows for measurement of D-1(CH) residual dipolar couplings (RDCs) through F1-coupled HSQC experiments. The gel's performance as an NMR alignment medium was evaluated for various water-soluble organic molecules, providing proper-sized RDCs for sucrose and even small molecules such as 5-norbornen-2-ol, but strong interaction between the gel and molecules like azidothymidine and cefuroxime sodium salt prevented successful extraction of RDCs.