Substituent effects on OH bond strength and hyperfine properties of phenol, as model for modified tyrosyl radicals in proteins

Density functional theory is used to investigate the effects of a variety o f substituents (CH3, OH, OCH3, SH, SCH3, NH2, NMe2, NO2, F, Cl, CN, and imi dazole) on the phenol O-H bond dissociation energy (BDE) and phenoxyl radic al hyperfine properties. Substitutions are made at the ortho position to mo del modified tyrosine residues found in enzymes. The calculations show that besides the electronic effects of the substituents, intramolecular hydroge n bonds between OH and the substituents will contribute considerably to sta bilize the parent species. Substituent effects on anisole O-Me bond strengt hs can thus not correctly describe the effects on ortho-substituted phenol O-H bond strengths, as previously proposed. This fact is supported by a ser ies of calculations on o-substituted anisoles. The odd-alternant spin patte rn of the phenoxyl radical is conserved for most of the substitutions. In p articular, it is predicted that the cysteine crosslink to tyrosine, present in the radical enzyme galactose oxidase, and the histidine crosslink, pres ent in cytochrome-c oxidase, will only have minor effects on the BDE and th e radical hyperfine coupling constants and spin distribution of the tyrosyl radical. (C) 2000 John Wiley & Sons, Inc.