Combined use of Overhauser spectroscopy and NMR diffusion experiments for mapping the hydration structure of nucleosides: structure and dynamics of uridine in water

Abstract

Complementary results from 13C intermolecular nuclear Overhauser effects (NOE), 1H-13C heteronuclear Overhauser spectroscopy (HOSEY) and 1H-NMR diffusion measurements were used for probing the structure of the first solvation shell of uridine in water. It is demonstrated that a cyclic dihydrate is formed. The two water molecules produce two hydrogen bonds with the two oxygen atoms from the pyrimidine ring and accept only one hydrogen bond from the amide proton. The dihydrate has only a short lifetime as compared with the rotational correlation time of the free nucleoside. The chemical exchange constant of the amide proton with water is then estimated by diffusion experiments. The results are consistent with previous data obtained for uracil in water and provide interesting information about water accessibility in nucleic acid bases.

Predicting the NMR spectra of nucleotides by DFT calculations: cyclic uridine monophosphate

“…[23,24] Indeed, whereas sugar carbon nuclei are relatively screened from the solvent, it is not necessarily so for the planar ring carbons as well as for all hydrogens. Nevertheless, it appears that such interactions are relatively weak and nonspecific (see also the very weak intermolecular NOE effects observed), so that a solvent reaction field is sufficient to model them.…”

“…Furthermore, the solvation shell of related molecules such as uracil and uridine has been investigated by intermolecular NOE spectroscopy. [23,24] Whereas solute-water interactions were detectable, they were interpreted as arising from weak, short-lived hydrates.…”

NMR diffusion measurements under chemical exchange between sites involving a large chemical shift difference

“…An interesting work concerns possible chemical shift modulations in diffusion decays (10). Several applications aimed at determining exchange rates or residence times can be found in the literature for medium-sized molecules (11)(12)(13)(14)(15) and also for large molecules such as proteins (16,17). All these latter works concern, however, slow exchange (at least with respect to chemical shift).…”

NH exchange in point mutants of human ubiquitin

“…There are hundreds of papers dealing with the NH exchange in amino acids, peptides and proteins and these have been reviewed by Englander and coworkers [1,2] Very recently such studies have even been obtained for the solid state [3]. There are several methods to record quantitative data of the NH exchange in proteins, such as H/D exchange measurements [4], saturation transfer methods [5], the MEXICO [6] and CLEANEX [7] experiments and the recently proposed diffusion technique [8,9].…”