Catalytic Models of Tyrosinase: Reactivity Differences between Systems Based on Mono- and Binucleating Ligands

A new tyrosinase model based on the binucleating ligand L(py)2 is synthesized and characterized. The ligand L(py)2 contains a combination of an imine and a pyridine function in the sidearms, which are bridged by a flexible alkyl spacer. As shown by UV/Vis and NMR spectroscopy, the Cu(2)L(py)2 complex catalyzed the conversion of the monophenol 2,4-ditert- butylphenol (DTBP-H) into the o-quinone 3,5-di-tert-butylquinone (DTBQ) with a turnover number (TON) of 18. The dicopper complex of L(py)2 thus shows monophenolase activity that is comparable to that of the recently developed L(py)1 model of tyrosinase, which is based on a known mono-nucleating ligand (M. Rolff, J. Schottenheim, G. Peters, F. Tuczek, Angew. Chem. Int. Ed. 2010, 122, 6583). The electron-poor substrate 4-hydroxybenzoic acid methyl ester (MeBA-OH), in contrast, is converted by Cu(2)L(py)2 into the semiquinone. For both substrates, the oxygenation reactions were also conducted in a stoichiometric fashion to obtain information on the intermediates involved. For the substrate MeBA-OH, we detected a binuclear mu-catecholato copper(II) complex by high-resolution ESI mass spectrometry. These studies were complemented by investigations of deactivation mechanisms that could be invoked to explain the limitation of the TON. To this end, a bis-mu-hydroxido L(py)2 dicopper(II) complex as well as a semiquinone L(py)2 complex were prepared. Both complexes may represent decay products of the catalyst.