Water structure and solvation of osmolytes at high hydrostatic pressure: pure water and TMAO solutions at 10 kbar versus 1 bar

Abstract

Trimethylamine N-oxide (TMAO) is a protecting osmolyte that stabilizes proteins against both temperature and pressure denaturation. Yet, even the solvation of TMAO itself is not well understood beyond ambient conditions. Here, using ab initio molecular dynamics, we analyze how its solvation structure changes upon compressing its ≈0.5 M aqueous solution from 1 bar to 10 kbar. The neat solvent, liquid water compressed to 10 kbar, is analyzed in detail to provide a meaningful gauge for the pressure-induced solvation changes of the solute. Pure water is shown to prefer to keep four H-bonded water molecules in a locally tetrahedral arrangement up to 10 kbar. The eye-catching shape changes of its oxygen-oxygen radial distribution function, where apparently the entire second peak is shifted into the first one, are traced back to about two more water molecules which are squeezed into the tetrahedral voids that are formed in the first shell by the H-bonded water molecules. These additional molecules increase the coordination number of pure water at 10 kbar significantly, but they are definitely not H-bonded to the central water molecule; rather they are its topological second to fourth H-bonded neighbors. The pressure response of TMAO(aq) is distinctly different, although its radial distribution functions do not change much. Under ambient conditions, the negatively charged oxygen site of the solute, which is strongly hydrophilic, predominantly accepts three H-bonds, whereas a roughly equal population of threefold and square-planar fourfold H-bonding is observed at 10 kbar. Moreover, only a negligible contribution of non-H-bonded water molecules is found in the first-shell region of TMAO even at 10 kbar, in contrast to the pressure response of water itself. In the hydrophobic region of TMAO, the solvating water molecules are found to straddle the three methyl groups at ambient pressure, which remains virtually unchanged upon compressing the solution to 10 kbar. Here, the pressure response is an increase from about 17 to 21 water molecules that solvate the methyl groups despite a sizable radial compression of the hydrophobic solvation shell.

Toward Extreme Biophysics: Deciphering the Infrared Response of Biomolecular Solutions at High Pressures

“…In a thrust to push forward extreme biophysics, we focus herein on Fourier transform infrared (FTIR) spectroscopy as a probe to reveal the molecular response of piezolytes in water and—only at a later stage—their interactions with biomolecules at high pressures . Information obtained by direct structural probes, for example, by measurement of the structure factors of a solution by X‐ray and neutron scattering, may not be sensitive enough at extreme conditions . However, in stark contrast to the increasing number of high‐pressure FTIR studies on biomolecules, truly quantitative FTIR spectroscopic studies on cosolvents effects lag behind, but are mandatory to fully explore the effect of pressure on the spectral properties of complex multicomponent solutions of biomolecules in future studies.…”

“…The molecular‐level picture was provided by AIMD of one TMAO and 107 H 2 O molecules in a cubic supercell by using the RPBE‐D3 functional as implemented in CP2k . This approach has been shown to provide an excellent description of the pressure response of pure water at 300 K up to 10 kbar. The reported mid‐IR spectra were obtained from 32 independent NVE trajectories of 20 ps in length with initial conditions sampled from a 250 ps NVT trajectory at 300 K by using massive Nosé–Hoover chains (see the Supporting Information).…”

How van der Waals interactions determine the unique properties of water

“…VDOS spectrum. Vibrational density of state (VDOS) computed from velocity autocorrelation functions obtained from RPBE-D3-based NNP simulations at T = 300 K and ρ = 1 g/cm 3 compared to results from ab initio simulations [77]. The hydrogen bond (HB) autocorrelation functions c(t) and n(t), shown in Fig.…”

Hydration structure of trimethylamine N-oxide in aqueous solutions revealed by soft X-ray emission spectroscopy and chemometric analysis

“…A theoretical study by means of Monte Carlo simulations coupled with an ab initio molecular orbital method 54 shows a complex of TMAO with 12 water molecules as a representative hydration structure. A more recent computational study 55 exhibits that the average numbers of hydrogen bonds per TMAO oxygen and of water molecules around the methyl groups are 3.1 and 17, respectively, at 1 bar. (Similar spatial distribution functions of water around the TMAO molecule are shown by another computational technique.…”