Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated Raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution. Author summarySaccharides are an essential part of many biosystems. Not only their identification but also their structural characterization is crucial to understanding their role. For example, animal cells possess a surrounding aqueous layer rich in sugars. Although its sugar content is known, the structures formed by these sugars in such a flexible and mobile environment are lesser understood. A trustworthy characterization of their atomistic structure will foster our knowledge and contribute to drug development. This characterization is also crucial in developing accurate computer models needed to study such environments. Unfortunately, many available structure characterization techniques are inadequate when applied to flexible molecules such as saccharides. Therefore, new methods are welcomed. We use molecular dynamics simulations and quantum chemical calculations to extract structural data of sugars in solution when compared against experimental Raman/ROA/NMR spectra. This combination of techniques allows interpreting these spectra to extract structural features of saccharides. We get, for example, the molecular structure of sugar rings (puckering confirmation) or the preferred orientation of bonds connecting two sugar units (glycosidic bonds). We can determine the presence of different sugar moieties in solutions and their proportions. Overall, this technique should contribute to the understanding of sugars in their native aqueous environment.

Automated summary

Sugars play a crucial role in biosystems and industrial applications. Combining Raman/ROA spectroscopies with simulations allows for precise characterization of sugar structural features in solution, providing valuable insights for understanding their role and developing accurate computer models.