A comparative study of hydrogen bonding structure and dynamics in aqueous urea solution of amides with varying hydrophobicity: Effect of addition of trimethylamine N-oxide (TMAO)

Abstract

A comparison of effects of addition of TMAO on the hydrogen bonding structure and dynamics in aqueous urea solution of three different amides (formamide-FA, N-methylformamide-NMF, N-methylacetamide-NMA), have been carried out with the help of classical molecular dynamics simulations. The interactions between amide-water, amide-urea and amide-TMAO in presence of concentrated urea/urea-TMAO solution are depicted here by different site-site radial distribution functions and the average interaction energies between these species in the solution. It is observed that the aqueous peptide hydrogen bond interaction is preferably stronger with increasing TMAO concentration in the solution, particularly for NMF and NMA, where hydrophobic solvation of CH3-groups increases significantly in TMAO solution. Upon increasing the size of hydrophobic groups of NMA, hydrogen bonding capacity decreases while interaction of hydrophobic groups with TMAO is seen to be favourable. The lifetimes of amide-water, water-water hydrogen bonds are found to increase with TMAO concentration in the solution. While all FA-water hydrogen bonds exhibit faster dynamics and reduced lifetimes, HNMF…OWAT hydrogen bonding is most persistent in terms of lifetime but shows faster reorganisation than that of NMA-water hydrogen bonds. Our calculated self-diffusion coefficients and orientational relaxation times shows slower dynamics of amide, water as well as solute molecules owing to strong inter-species hydrogen bonding at elevated TMAO concentrations.