Solvation of the Guanidinium Ion in Pure Aqueous Environments. A Theoretical Study from an "Ab Initio"-based Polarizable Force Field.

We report simulation results regarding the hydration process of the guanidinium cation in water droplets and in bulk liquid water, at a low concentration of 0.03 M, performed using a polarizable approach to model both water/water and ion/water interactions. In line with earlier theoretical studies, our simulations show a preferential orientation of guanidinium at water-vacuum interfaces, i.e., a parallel orientation of the guanidinium plane to the aqueous surface. In an apparent contradiction with earlier simulation studies, we show also that guanidinium has a stronger propensity for the cores of aqueous systems than the ammonium cation. However, our bulk simulation conditions correspond to weaker cation concentrations than in earlier studies, by 2 orders of magnitude, and that the same simulations performed using a standard nonpolarizable force field leads to the same conclusion. From droplet data, we extrapolate the guanidinium single hydration enthalpy value to be -82.9 +/- 2.2 kcal mol(-1). That is about half as large as the sole experimental estimate reported to date, about -144 kcal mol(-1). Our result yields a guanidinium absolute bulk hydration free energy at ambiant conditions to be -78.4 +/- 2.6 kcal mol(-1), a value smaller by 3 kcal mol(-1) compared to ammonium. The relatively large magnitude of our guanidinium hydration free energy estimate suggests the Gdm(+) protein denaturing properties to result from a competition between the cation hydration effects and the cation/protein interactions, a competition that can be modulated by weak differences in the protein or in the cation chemical environment.