Specific versus Nonspecific Solvent Interactions of a Biomolecule in Water

[Image: see text] Solvent interactions, particularly hydration, are vital in chemical and biochemical systems. Model systems reveal microscopic details of such interactions. We uncover a specific hydrogen-bonding motif of the biomolecular building block indole (C(8)H(7)N), tryptophan’s chromophore, in water: a strong localized N–H···OH(2) hydrogen bond, alongside unstructured solvent interactions. This insight is revealed from a combined experimental and theoretical analysis of the electronic structure of indole in aqueous solution. We recorded the complete X-ray photoemission and Auger spectrum of aqueous-phase indole, quantitatively explaining all peaks through ab initio modeling. The efficient and accurate technique for modeling valence and core photoemission spectra involves the maximum-overlap method and the nonequilibrium polarizable-continuum model. A two-hole electron-population analysis quantitatively describes the Auger spectra. Core–electron binding energies for nitrogen and carbon highlight the specific interaction with a hydrogen-bonded water molecule at the N–H group and otherwise nonspecific solvent interactions.