Density variations of TMAO solutions in the kilobar range: Experiments, PC-SAFT predictions, and molecular dynamics simulations

We present measurements, molecular dynamics (MD) simulations, and predictions using Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) of the density of aqueous solutions in a pressure range from 1 bar to 5000 bar, a pressure regime that is highly relevant for both biochemical applications and the fundamental understanding of solvation. The accurate determination of density data of pressurized solutions remains challenging. We determined relative density changes from the variations in X-ray absorption through the sample and developed a new water parameter set for PC-SAFT modeling that is appropriate for high pressure conditions in the kilobar regime. As a showcase, we studied trimethylamine N-oxide (TMAO) solutions and demonstrated that their compressibility decreases with the TMAO content. This result is linked to the stabilizing effect of TMAO on the local H-bond network of water. Experiments and calculations, which represent two independent methods, are in very good agreement and are in accordance with results of force field molecular dynamics simulations of the same systems. [Display omitted] •We determined the density of pressurized TMAO solutions by experiments and theory.•X-ray absorption is suitable to determine densities at pressure in the kbar range.•PC-SAFT allows predicting density of aqueous TMAO solutions at high pressure.•X-ray absorption, thermodynamic modeling, and MD simulations are in good agreement.•TMAO decreases the compressibility, reflecting a locally stabilized water structure.