Solvent effects on the physicochemical properties of the cross-linked histidine-tyrosine ligand of cytochrome c oxidase.

Density functional theory was used to explore the effects of aqueous solvation on the structure, vibrational frequencies, and the electronic absorption spectrum of 2-(4-methylimidazol-1-yl)-phenol (Me-ImPhOH), a chemical analogue of the cross-linked histidine−tyrosine CuB ligand of cytochrome c oxidase. In addition, the phenolic−OH pKa, the anodic redox potential for the biring radical/anion couple, and the phenolic−OH bond dissociation energy were calculated relative to phenol using a series of isodesmic reactions. In the gas phase, the imidazole moiety stabilizes the biring anion for all the models and greatly decreases the phenolic−OH pKa relative to phenol. Moreover, the conductor−like polarizable continuum model (C-PCM)-water-solvated reactions predict ΔpKa values that are five times smaller than the gas-phase reactions, in agreement with the proposed role of the cross-linked histidine−tyrosine as a proton donor in the enzyme. For the neutral biring radical solvation models, the imidazole moiety indu...