Issue 1, 2015

Water-mediated interactions between trimethylamine-N-oxide and urea


The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in natural organisms, where it counteracts biochemical stress associated with urea in aqueous environments. Despite the important role of TMAO as osmoprotectant, the mechanism behind TMAO's action has remained elusive. Here, we study the interaction between urea, TMAO, and water in solution using broadband (100 MHz–1.6 THz) dielectric spectroscopy. We find that the previously reported tight hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of TMAO, remain intact at all investigated concentrations of urea, showing that no significant hydrogen bonding occurs between the two co-solutes. Despite the absence of direct TMAO–urea interactions, the solute reorientation times of urea and TMAO show an anomalous nonlinear increase with concentration, for ternary mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the reorientation correlates with changes in the viscosity, showing that the combination of TMAO and urea cooperatively enhances the hydrogen-bond structure of the ternary solutions. This nonlinear increase is indicative of water mediated interaction between the two solutes and is not observed if urea is combined with other amphiphilic solutes.

Graphical abstract: Water-mediated interactions between trimethylamine-N-oxide and urea

Supplementary files

Article information

Article type
20 Jun 2014
07 Aug 2014
First published
12 Aug 2014
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2015,17, 298-306

Author version available

Water-mediated interactions between trimethylamine-N-oxide and urea

J. Hunger, N. Ottosson, K. Mazur, M. Bonn and H. J. Bakker, Phys. Chem. Chem. Phys., 2015, 17, 298 DOI: 10.1039/C4CP02709D

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