FUNCTIONAL-MODELING OF TYROSINASE - MECHANISM OF PHENOL ORTHO-HYDROXYLATION BY DINUCLEAR COPPER-COMPLEXES

The copper-mediated oxygenation of methyl 4-hydroxybenzoate (1) in ace tonitrile has been investigated by employing a series of dinuclear cop per(I) complexes with polybenzimidazole ligands. The reaction mimics t he activity of the copper enzyme tyrosinase, since the initial product of the reaction is the o-catechol, methyl 3, 4-dihydroxybenzoate (2). The ligand systems investigated include alpha, -(1-methyl-2-benzimida zolyl)-ethyl]amino}-m-xylene (L-66) alpha, -(1-methyl-2-benzimidazolyl )methyl]amino}-m-xylene (L-55), alpha, 2-(1-methyl-2-benzimidazolyl)et hyl]amino}-m-xylene (L-56), and alpha, 2-(1-methyl-2-benzimidazolyl)et hyl]amino}-m-xylene (L-5p6). The most effective among the dicopper(I) complexes is that derived from L-66, while its mononuclear Cu(I) analo gue, with the ligand N, N-bis[2-(1-methyl-2-benzimidazolyl)ethyl]amine is inactive in the monooxygenase reaction. The catechol 2 is the only product of phenol hydroxylation when the reaction is carried out at l ow temperature (-40 degrees C). As the temperature is increased, methy l 2-[4-(carbomethoxy)phenoxy]-3, 4-dihydroxybenzoate (4), formally res ulting from Michael addition of the starting phenol to 4-carbomethoxy- 1, 2-benzoquinone (3) and probably resulting from the reaction between free phenolate and some intermediate copper-catecholate species, beco mes a major product of the reaction. In order to gain insight into the mechanism of the reaction, the dicopper(I)-phenolate adducts and dico pper(II)-catecholate adducts of the L-66, L-55, and L-6 complexes have been studied, In a few cases the adducts containing catecholate monoa nion or catecholate dianion have been isolated and spectrally characte rized. It has been shown that the final product of the monooxygenase r eaction corresponds to the dicopper(II)-catecholate dianion complex. A mechanism for the biomimetic phenol ortho-hydroxylation has been prop osed and its possible relevance for tyrosinase discussed.