The Interplay of Methyl-Group Distribution and Hydration Pattern of Isomeric Amphiphilic Osmolytes

Abstract

The intermolecular interactions and dynamics of aqueous 1,1-dimethyurea (1,1-DMU) solutions were studied by examining the concentration dependence of the solvent and solute relaxations detected by dielectric spectroscopy. Molecular dynamics simulations were carried out to facilitate interpretation of the dielectric data and to get a deeper insight into the behavior of the system components at the microscopic level. In particular, the simulations allowed for explaining the main differences between the dielectric spectra of aqueous solutions of 1,1-DMU and of its structural isomer 1,3-DMU. Similar to the previously studied compounds urea and 1,3-DMU, 1,1-DMU forms rather stable hydrates. This is evidenced by an effective solute dipole moment that significantly exceeds the value of a neat 1,1-DMU molecule, indicating pronounced parallel alignment of the solute dipole with two to three HO moments. The MD simulations revealed that the involved water molecules form strong hydrogen bonds with the carbonyl group. However, in contrast to 1,3-DMU, it was not possible to resolve a "slow-water" mode in the dielectric spectra, suggesting rather different hydration-shell dynamics for 1,1-DMU as confirmed by the simulations. In contrast to aqueous urea and 1,3-DMU, addition of 1,1-DMU to water leads to a weak decrease of the static permittivity. This is explained by the emergence of antiparallel dipole-dipole correlations among 1,1-DMU hydrates with rising concentration.

Hydrophobic pattern of alkylated ureas markedly affects water rotation and hydrogen bond dynamics in aqueous solution

“…[6][7][8][9][10][11][12] Obviously, RUs amphiphilicity stems from the spatial variation of their interaction with water and the hydrophobic substitution pattern thus critically affects RUs function. 6 As such, the effect of amphiphilic solutes on water structure and dynamics has been intensively studied: ultrafast infrared (IR), [13][14][15][16][17][18][19][20] optical Kerr effect, 21 dielectric relaxation (DR), 15,[22][23][24][25] NMR relaxometry 26,27 and diffusometry experiments 28 as well as classical 23,24,29,30 and ab initio molecular dynamics (MD) simulations [31][32][33][34] have evidenced a slowdown of the water dynamics near hydrophobic moieties. In particular, comparison between aqueous solutions of 'hydrophilic' urea (U) and amphiphilic tetramethylurea (TMU) reveals a marked retardation of water dynamics in the presence of methyl groups.…”

“…For solutions of TMU, the latter has been suggested to prevail. 30 Different alkylation patterns of U [22][23][24]27 can be used to disentangle these scenarios and therefore relate hydration to RUs biological function: depending on the position and the length of the alkyl groups, the number of methyl(ene) groups at U can be kept constant, while the excluded volume of the adjacent hydrophobic groups may be non-additive due to partial intramolecular overlap for spatially close hydrophobic groups. Recent DR experiments have pointed at the importance of the alkylation pattern: only for solutions of 1,3-dimethylurea (1,3-DMU) a marked slow-down of water dynamics has been observed, while 1,1-dimethylurea (1,1-DMU) has been found to hardly perturb water.…”

“…Recent DR experiments have pointed at the importance of the alkylation pattern: only for solutions of 1,3-dimethylurea (1,3-DMU) a marked slow-down of water dynamics has been observed, while 1,1-dimethylurea (1,1-DMU) has been found to hardly perturb water. 23,24 Force-field MD simulations have suggested that shorter residence times of the water molecules in the vicinity of the methyl groups of 1,1-DMU and their lower hydration number are responsible for the very limited retardation of water dynamics, as measured with DR spectroscopy. 23 As DR probes the collective rotational dynamics, correlations between the dynamics of the solutes and water can be significant: indeed, the dwell times of water in the hydration shell of DMUs have been reported to be rather long.…”

“…23,24 Force-field MD simulations have suggested that shorter residence times of the water molecules in the vicinity of the methyl groups of 1,1-DMU and their lower hydration number are responsible for the very limited retardation of water dynamics, as measured with DR spectroscopy. 23 As DR probes the collective rotational dynamics, correlations between the dynamics of the solutes and water can be significant: indeed, the dwell times of water in the hydration shell of DMUs have been reported to be rather long. 23,24 The resulting correlated motion together with potential aggregation of RUs, 40 most pronounced for longer alkyl substituents, 22 makes it challenging to elucidate the inherent dynamics of water in the hydrophobic hydration shell.…”

“…23 As DR probes the collective rotational dynamics, correlations between the dynamics of the solutes and water can be significant: indeed, the dwell times of water in the hydration shell of DMUs have been reported to be rather long. 23,24 The resulting correlated motion together with potential aggregation of RUs, 40 most pronounced for longer alkyl substituents, 22 makes it challenging to elucidate the inherent dynamics of water in the hydrophobic hydration shell. 22 Here, we isolated the inherent water dynamics using the OD stretching vibration of trace HDO molecules in water as a probe.…”