Liquid-jet XPS and theoretical computations reveal solvation-driven shifts and deprotonation site in uracil

Solute-solvent interactions are fundamental to understanding the stability, reactivity, and biological function of molecules. Spectroscopic techniques allow gaining molecular-level insights into these interactions. Here we explore the hydration of uracil, a model system for the behavior of biomolecules in an aqueous environment. We combine experimental liquid-jet photoemission spectroscopy with different theoretical approaches to investigate the element-specific core-level binding energies of solvated uracil and what they reveal about solvation. The maximum overlap method (MOM) approach combined with density functional theory (DFT) is applied to calculate the binding energies of DFT-optimized micro-hydrated clusters with an additional non-equilibrium dielectric continuum modeling long-range solvent interactions. The latter proves to be crucial but sufficient to describe the case of neutral uracil. On the other hand, for deprotonated uracil, structures extracted from QM/MM molecular dynamics provide more accurate binding energies. Both cases highlight the need to go beyond micro-hydration and to describe the full solvation, although in different ways. The conjugation of experiment and theory also allowed us to clearly identify the site of deprotonation of uracil. The present findings represent quantitative experiment-theory benchmarks on representative solvated molecules.