Unraveling Hydration Shell Dynamics and Viscosity Effects Around Cyanamide Probes via 2D IR Spectroscopy

Abstract

Hydration dynamics and solvent viscosity play critical roles in the structure and function of biomolecules. An overwhelming body of evidence suggests that protein and membrane fluctuations are closely linked to solvent fluctuations. While extensive research exists on the use of vibrational probes to detect local interactions and solvent dynamics, fewer studies have explored how the behavior of these reporters changes in response to bulk viscosity. To address this gap, two-dimensional infrared spectroscopy (2D IR) was employed in this study to investigate the ultrafast hydration dynamics around a cyanamide (NCN) probe attached to a nucleoside, deoxycytidine, in aqueous solutions with varying glycerol content. The use of a small vibrational probe on a targeted nucleic acid offers the potential to capture more localized hydration dynamics than alternative methods. The time scales for the frequency correlation decays were found to increase linearly with bulk viscosity, ranging from 0.9 to 11.4 ps over viscosities of 0.96–49.1 cP. Additionally, molecular dynamics (MD) simulations were performed to model the local hydration dynamics around the NCN probe. Interestingly, increasing the glycerol content did not significantly alter the hydration of the deoxycytidine. The MD simulations further suggested that the NCN probe’s frequency fluctuations were primarily influenced by the dynamics of water in the second solvation shell. Cage correlation functions, which measure the movement of water molecules in and out of the second solvation shell, exhibited decays that closely matched those of the frequency-fluctuation correlation function (FFCF). These findings offer new insights into hydration dynamics and the impact of viscosity on biological systems.