Galactose oxidase (GOase) is a type II copper protein (68 kDa) that catalyzes the oxidation of primary alcohols to aldehydes with the concomitant reduction of molecular oxygen. [1] Its crystal structure [2] reveals a unique mononuclear copper site with two nitrogen (from histidine imidazole groups) and two oxygen (from one axial and one equatorial tyrosine group) donor atoms, plus an exogenous water or acetate molecule in a distorted square-pyramidal coordination. The enzyme exists in three well-defined oxidation levels: the EPR-silent active form (cupric ion antiferromagnetically coupled to the equatorial tyrosyl radical), an intermediate form, and the reduced copper(i) form [Eq. ( 1)].
The axial tyrosine group is involved in protonation± deprotonation processes during the catalytic cycle (Scheme 1 b).
Among the structural models of the active site of GOase described, [3] only a few contain two phenolic arms and involve the [N 2 O 2 ] copper coordination sphere of the enzyme. [4] Some of the functional models of GOase involve salen-type ligands and exhibit interesting catalytic activity only with activated alcohols as substrates. [5] The best results have been obtained by Wieghardt et al. with a very nice set of complexes in which the redox chemistry during the catalytic cycle is ligandbased. [6±7] Another interesting model developed by Wieghardt and co-workers involves true GOase chemistry but is not, strictly speaking, a structural model. [8] We have previously described a model, unfortunately not functional, involving an axial phenoxyl radical associated with a Cu II center possessing a [N 2 O 2 ] coordination sphere. It was built from a tripodal ligand (Scheme 1 a). [9] With a model close to ours, the phenoxyl radical species was obtained spontaneously by disproportionation. [10] We present here a structural and functional model of galactose oxidase. Our strategy was based on the differentiation of the two phenolic arms in the tripodal ligand COMMUNICATIONS