Thermal Signature of Hydrophobic Hydration Dynamics

Abstract

Hydrophobic hydration, the perturbation of the aqueous solvent near an apolar solute or interface, is a fundamental ingredient in many chemical and biological processes. Both bulk water and aqueous solutions of apolar solutes behave anomalously at low temperatures for reasons that are not fully understood. Here, we use (2)H NMR relaxation to characterize the rotational dynamics in hydrophobic hydration shells over a wide temperature range, extending down to 243 K. We examine four partly hydrophobic solutes: the peptides N-acetyl-glycine-N'-methylamide and N-acetyl-leucine-N'-methylamide, and the osmolytes trimethylamine N-oxide and tetramethylurea. For all four solutes, we find that water rotates with lower activation energy in the hydration shell than in bulk water below 255 +/- 2 K. At still lower temperatures, water rotation is predicted to be faster in the shell than in bulk. We rationalize this behavior in terms of the geometric constraints imposed by the solute. These findings reverse the classical "iceberg" view of hydrophobic hydration by indicating that hydrophobic hydration water is less ice-like than bulk water. Our results also challenge the "structural temperature" concept. The two investigated osmolytes have opposite effects on protein stability but have virtually the same effect on water dynamics, suggesting that they do not act indirectly via solvent perturbations. The NMR-derived picture of hydrophobic hydration dynamics differs substantially from views emerging from recent quasielastic neutron scattering and pump-probe infrared spectroscopy studies of the same solutes. We discuss the possible reasons for these discrepancies.

Strong temperature dependence of water reorientation in hydrophobic hydration shells

“…These numbers are obtained from molecular dynamics simulations and amount to 25 and 32 water molecules for TBA and TMU, respectively. 9,11 A strong advantage of femtosecond midinfrared spectroscopy is that the bulk and the hydration shell contributions to the reorientation can be distinguished. Hence, the number of water molecules, or more precisely the number of water hydroxyl groups, that show a slowed down reorientation is directly measured.…”

“…In both NMR and femtosecond midinfrared spectroscopy measurements, it was observed that the solvating water molecules show much slower orientational dynamics than the molecules in bulk liquid water. [6][7][8][9][10][11][12][13] The thermodynamic properties of hydrophobic hydration are strongly temperature dependent. [14][15][16][17][18][19] For small hydrophobic solutes, the free energy change associated with the solvation reaches a maximum at an elevated temperature, which implies that at this temperature the change in excess entropy has become zero, and the enthalpy change has become positive.…”

How the hydrophobic factor drives protein folding

“…We suggest that the rapid rotations of water molecules in alkane hydration shells (17) can be explained by the very short (approximately picoseconds) lifetimes of C...O vdW interactions, because hydration shells that are stabilized importantly by these vdW interactions must be continually broken down and remade on a very fast timescale. The evidence for C...O vdW interactions stabilizing alkane hydration shells is given above and can be summarized as follows.…”

“…He implied that when these shells are found and studied, their role in driving folding will become obvious. Qvist and Halle (17) in 2008 looked for water cages by NMR. They expected H-bonded water cages to be semirigid and found that instead water molecules adjacent to nonpolar groups rotate rapidly, like bulk water molecules.…”

“…They expected H-bonded water cages to be semirigid and found that instead water molecules adjacent to nonpolar groups rotate rapidly, like bulk water molecules. One of the four partly hydrophobic solutes studied by Qvist and Halle (17) was N-acetyl-leucine-N-methylamide, which should have an alkane-like hydration shell. See also the recent NMR study of protein hydration shells by Zhong and coworkers (18).…”