Exploring conformational energy landscape of glassy disaccharides by CPMAS 13C NMR and DFT/GIAO simulations. I. Methodological aspects

TL;DR

This paper evaluates the use of chemical shift surfaces combined with DFT/GIAO simulations to accurately characterize the conformational distributions of disaccharides in glassy states, emphasizing methodological considerations for reliable spectral interpretation.

Contribution

It introduces a detailed methodological framework for simulating inhomogeneous 13C chemical shift distributions, accounting for extrema and saddle points, to interpret solid-state NMR spectra of disaccharides.

Findings

Proper consideration of extrema and saddle points explains spectral discontinuities.

DFT/GIAO maps on relaxed conformations accurately reproduce experimental lineshapes.

The approach identifies dominant conformations in glassy trehalose.

Abstract

The aim of this article is to assess the ability of chemical shift surfaces to provide structural information on conformational distributions of disaccharides in glassy solid state. The validity of the general method leading to a simulation of inhomogeneous 13C chemical shift distributions is discussed in detail. In particular, a proper consideration of extrema and saddle points of the chemical shift map correctly accounts for the observed discontinuities in the experimental CPMAS spectra. Provided that these basic requirements are met, DFT/GIAO chemical shift maps calculated on relaxed conformations lead to a very satisfactory description of the experimental lineshapes. On solid-state trehalose as a model of amorphous disaccharide, this simulation approach defines unambiguously the most populated sugar conformation in the glass, and can help in discriminating the validity of different models of intramolecular energy landscape. Application to other molecular systems with broad conformational populations is foreseen to produce a larger dependence of the calculated chemical shift distribution on the conformational map.