A single methyl group drastically changes urea's hydration dynamics

The amphiphilicity and denaturation efficiency of urea can be tuned via alkylation. Although the interaction of alkylureas with water and proteins has been studied in detail, hydration of 1-methylurea has remained elusive, precluding the isolation of the effect of an individual methyl group. Here, we study water dynamics in the hydration shell of 1-methylurea (1-MU) using infrared absorption and ultrafast infrared spectroscopies. We find that 1-MU hardly affects the hydrogen-bond distribution of water as probed by the OD stretching vibration of HOD molecules. Polarization resolved infrared pump-probe experiments reveal that 1-MU slows down the rotational dynamics of up to 3 water molecules in its hydration shell. A comparison to earlier results for other alkylureas suggests that further alkylation does not necessarily slow down the rotational dynamics of additional water molecules. Two-dimensional infrared experiments show that 1-MU markedly slows down the hydrogen-bond fluctuation dynamics of water, yet similar to what has been found for urea and dimethylureas. Remarkably, (alkyl-) ureas that share a similar effect on water's hydrogen-bond fluctuation dynamics have a similar (modest) protein denaturation tendency. As such, not only the hydrophobicity but also hydration of hydrophilic fragments of alkylureas may be relevant to explain their function toward biomolecules. (C) 2022 Author(s).

Automated summary

The hydrophobicity and denaturation efficiency of urea can be modified by alkylation. In this study, the hydration of 1-methylurea was investigated using infrared spectroscopy. The results showed that 1-methylurea has little effect on the hydrogen-bond distribution of water but slows down the rotational dynamics and hydrogen-bond fluctuation dynamics of water molecules in its hydration shell. Further alkylation does not necessarily affect the rotational dynamics of additional water molecules. Ureas that have a similar effect on water's hydrogen-bond fluctuation dynamics exhibit a similar protein denaturation tendency.