Electrochemical and Spectroscopic Effects of Mixed Substituents in Bis(phenolate)–Copper(II) Galactose Oxidase Model Complexes

Nonsymmetric substitution of salen (1 R1,R2 ) and reduced salen (2 R1,R2 ) CuII–phenoxyl complexes with a combination of - t Bu, -S i Pr, and -OMe substituents leads to dramatic differences in their redox and spectroscopic properties, providing insight into the influence of the cysteine-modified tyrosine cofactor in the enzyme galactose oxidase (GO). Using a modified Marcus–Hush analysis, the oxidized copper complexes are characterized as Class II mixed-valent due to the electronic differentiation between the two substituted phenolates. Sulfur K-edge X-ray absorption spectroscopy (XAS) assesses the degree of radical delocalization onto the single sulfur atom of nonsymmetric [1 t Bu,SMe]+ at 7%, consistent with other spectroscopic and electrochemical results that suggest preferential oxidation of the -SMe bearing phenolate. Estimates of the thermodynamic free-energy difference between the two localized states (ΔG o) and reorganizational energies (λR1R2 ) of [1 R1,R2 ]+ and [2 R1,R2 ]+ lead to accurate predictions of the spectroscopically observed IVCT transition energies. Application of the modified Marcus–Hush analysis to GO using parameters determined for [2 R1,R2 ]+ predicts a νmax of ∼13600 cm–1, well within the energy range of the broad Vis–NIR band displayed by the enzyme.