Cosolvent Effects on Solute–Solvent Hydrogen-Bond Dynamics: Ultrafast 2D IR Investigations

Abstract

Cosolvents strongly influence the solute-solvent interactions of biomolecules in aqueous environments and have profound effects on the stability and activity of several proteins and enzymes. Experimental studies have previously reported on the hydrogen-bond dynamics of water molecules in the presence of a cosolvent, but understanding the effects from a solute's perspective could provide greater insight into protein stability. Because carbonyl groups are abundant in biomolecules, the current study used 2D IR spectroscopy and molecular dynamics simulations to compare the hydrogen-bond dynamics of the solute's carbonyl group in aqueous solution, with and without the presence of DMSO as a cosolvent. 2D IR spectroscopy was used to quantitatively estimate the time scales of the hydrogen-bond dynamics of the carbonyl group in neat water and 1:1 DMSO/water solution. The 2D IR results show spectral signatures of a chemical exchange process: The presence of the cosolvent was found to lower the hydrogen-bond exchange rate by a factor of 5. The measured exchange rates were 7.50 × 10(11) and 1.48 × 10(11) s(-1) in neat water and 1:1 DMSO/water, respectively. Molecular dynamics simulations predict a significantly shorter carbonyl hydrogen-bond lifetime in neat water than in 1:1 DMSO/water and provide molecular insights into the exchange mechanism. The binding of the cosolvent to the solute was found to be accompanied by the release of hydrogen-bonded water molecules to the bulk. The widely different hydrogen-bond lifetimes and exchange rates with and without DMSO indicate a significant change in the ultrafast hydrogen-bond dynamics in the presence of a cosolvent, which, in turn, might play an important role in the stability and activity of biomolecules.

Vibrational Stark Effects of Carbonyl Probes Applied to Reinterpret IR and Raman Data for Enzyme Inhibitors in Terms of Electric Fields at the Active Site

“…This observation is consistent with studies on similar alkyl acetates where the solvents exhibit altered conformations of the terminal methyl group, resulting in differences in the E/Z-rotamer populations, 77–79 or the presence of different H-bonding configurations as observed by MD simulations and 2D IR. 80–82 Consistent with multiple H-bonding configurations, post-processing of MD trajectories by Pazos et al . showed that the fields and frequencies of these 1- and 2-H-bonding configurations fall on the same field-frequency calibration line as other non-H-bonding solvents, consistent with a linear Stark effect.…”

Interfacial H-Bond Dynamics in Reverse Micelles: The Role of Surfactant Heterogeneity

“…The slowing of dynamics identified in heterogeneous micelles indicates that there is a greater amount of water trapped in the surfactant-water interfacial region of these systems. Water molecules penetrating deeper into the surfactant region have restricted access to the collective hydrogen-bond networks that facilitate HB switching in bulk water. − Previous work has shown that cosolvents slow HB fluctuations by preventing the instantaneous replacement of one HB for another . Therefore, as water penetration increases, a greater proportion of water molecules enter the crowded surfactant layer, which then lengthens the average HB fluctuation dynamics, as experimentally observed from the 2D IR CLS analysis.…”

Solvent-Independent Anharmonicity for Carbonyl Oscillators

“…Using the peak positions and anharmonic shift as determined by the 2D IR spectroscopic measurements and estimated T 1 population relaxation times of 1175, 2500, and 840 fs for acetophenone, methyl benzoate, and ethyl thioacetate, respectively, the time-dependent response functions for each of the rephasing and nonrephasing pathways were calculated and used to generate the simulated 2D IR spectra. The vibrational lifetimes ( T 2 ) were in the generally observed range for other simple carbonyl compounds (0.8–5.2 ps − ), though this has been tested predominately with amides. The relative intensities of the overtones were scaled in order to more closely match the experimental fits.…”