Molecular dynamics simulation of aqueous solutions of trimethylamine-N-oxide and tert-butyl alcohol

In this work we have investigated hydration properties of aqueous Solutions up to a solute molar fraction X-2 = 0.125 of two isosteric molecules - the bioprotectant trimethylamine-N-oxide (TMAO) and the denaturant tert-butyl alcohol (TBA) - using molecular dynamics simulation at 298 K. Statistical analyses of the trajectories show in particular that as the solute concentration increases the number of the water molecules in the first hydration shell decreases uniformly for TMAO, while for TBA it decreases more rapidly in a concentration range where experiments indicate that TBA starts to self-aggregate. No appreciable solute segregation occurs for TMAO even in the most concentrated solution, where on the average each water molecule is shared by two solutes. This result parallels what has been recently found for glycine betaine, an organic osmolyte closely related to TMAO.