Interactions of Trimethylamine N−Oxide and Water with cyclo-Alanylglycine

Abstract

The osmolyte trimethylamine N-oxide (TMAO) is one of a family of compounds found in living systems that can stabilize biomolecular tertiary structures. As a step in exploring the interactions between this material and polyamino acids, we have determined intermolecular 1H{1H} nuclear Overhauser effects (NOEs) between the protons of cyclo-alanylglycine and protons of solvent components in TMAO-water solutions. Comparison of the results to effects predicted on the basis of the molecular shape of the dipeptide and experimental translational diffusion coefficients suggests that both water and TMAO molecules have properties in the vicinity of the dipeptide that are different from those in the bulk solution. Changes of local concentrations of water and TMAO and changes in the diffusive behavior of these components near the dipeptide are rejected as possible explanations of the discrepancies between observed and calculated Overhauser effects. Rather, it is concluded that TMAO molecules, and the water molecules associated with them, participate to some extent in the formation of long-lived solute-solvent complexes. The aliphatic alcohol tert-butyl alcohol is structurally similar to TMAO. Overhauser effect studies of its interaction with cyclo-alanylglycine in tert-butyl alcohol-water suggest similar kinds of interactions are present in this system but that they are significantly weaker, presumably because of the lower polarity of this alcohol compared to TMAO.