Binuclear copper complex model of tyrosinase

Abstract

The synthesis is reported of a binuclear copper(1) complex 2 which exhibits the catalytic phenolase and catecholase activity of tyrosinase.

Oxidation Catalysis; A Dinuclear Approach

“…1c, 16,17 This is even more surprising if one realizes that selective oxidations of organic substrates mediated by copper complexes have been known over a century. 18 For instance the Glaser oxidative coupling of acetylenes, 19 the oxidative dimerization of naphthols 20 and the formation of poly(phenylene ethers) from 2,6-disubstituted phenols 21 are all based on copper-amine complexes and molecular oxygen.…”

“…This knowledge has been successfully applied by the groups of Waegell and Casella in the design of dinuclear copper complexes for the hydroxylation of exogenous phenols. 16,17 In order to get more insight into the reactivity of the Cu(I) complexes and in particular in the dependency of the arene hydroxylation on the substituent pattern different X-substituents (alkoxy, halogen, alkyl) were placed at the arene-1-position in 11 which is most vulnerable to oxygenation (vide infra). Furthermore preliminary investigations show that both O 2 -binding and hydroxylation are sensitive to the electronic effects of para-substituents (11, Y = OCH 3 , CH 3 , CO 2 CH 3 , NO 2 ).…”

Designer ligands: The search for metal ion selectivity

“…Tyrosinase, a polyphenol oxidase metalloenzyme, catalyses the ortho-hydroxylation of phenolic systems to catechols (phenolase activity) and their subsequent oxidation to quinones (catecholase activity) 2 − a process responsible for the browning of injured fruit and vegetables. The active site is believed to contain two appropriately coordinated copper(I) atoms 3 approximately 3.55 Å apart 4 and is activated, following binding of molecular oxygen, with the formation of a dioxygenbridged dicopper(II) complex (Figure 1).…”

“…30 These factors were taken into account and nickel(II)-selective bidentate ligands were designed to contain: (1) pyridyl and amino nitrogen donors, located to permit the formation of five-membered metal chelates; (2) substituents to fine-tune donor capacity and steric demand; and (3) a vinyl group for co-polymerisation to generate MIPs (Figure 8). The ligands 25a-g, which incorporate these features, were obtained following the general synthetic pathway outlined in Scheme 6.…”

Designer ligands. Part 9.1 Catalytic activity of biomimetic cobalt(II) and copper(II) complexes of multidentate ligands

“…[2][3][4][5][6] Some time ago, Reglier et al 7 described the synthesis and phenolase activity of a dinuclear Cu (I) complex, designed to model the enzyme tyrosinase, while very recently, Comba and co-workers 8 reported the X-ray crystal structures of three Cu(II) complexes which exhibit catecholase activity. Progress towards the elucidation of tyrosinase structures has been reviewed by van Gelder et al, 9 and it is apparent that the active sites contain a pair of suitably spaced copper atoms capable of accommodating a bridged dioxygen molecule.…”