Modeling tyrosinase monooxygenase activity. Spectroscopic and magnetic investigations of products due to reactions between copper(I) complexes of xylyl-based dinucleating ligands and dioxygen: aromatic ring hydroxylation and irreversible oxidation products

Abstract

A full account of a chemical system possessing features that mimic the reactivity aspects of tyrosinase is presented. Using dinucleating ligands with a m-xylyl spacer three new dicopper(I) complexes have been synthesized and their reactivity with dioxygen investigated. The six-membered chelate ring forming ligands provide only two nitrogen coordinations to each copper. The complexes [Cu^I₂L(CH₃CN)₂]X₂ (X = ClO₄^- (1a), SbF₆^- (1b)) and [Cu^I₂(L-NO₂)(CH₃CN)₂][SbF₆]₂ (1c) [L = α,α'-bis[N-methyl-N-(2-pyridylethyl)amino]-m-xylene; L-NO₂ = para-nitro derivative of L] have been characterized by IR and ¹H NMR spectroscopy. The reaction of O₂ with 1a-c in CH₂Cl₂ or THF is instantaneous and causes stoichiometric xylyl hydroxylation reactions producing phenol products. Thus 1a produces phenoxo-/hydroxo-bridged product [Cu^II₂(L-O)(OH)][ClO₄]₂ (2a). The existence of putative peroxo-dicopper(II) species could not be detected even at -80 °C. A trend is observed for the extent of aromatic ring hydroxylation (298 K): CH₃CN ~DMF > CH₃OH _» CH₂Cl₂. Cyclic voltammetric experiment of 1a in DMF reveals an appreciably low redox potential (E_½ = -0.26 V vs SCE) for the Cu^II₂/Cu^I₂ redox process. Variable-temperature (25-300 K) magnetic susceptibility measurements establish that the copper(II) centers in 2a and the dihydroxo-bridged complex [Cu^II₂L'(OH)₂][ClO₄]₂ (2b) [formed due to an impurity (L') present during the synthesis of L following Method A; L' = bis[α,α'-bis(N-methyl-N-(2-pyridylethyl)amino)-m-xylene]methylamine] are antiferromagnetically coupled, with 2a considerably more coupled than 2b. Reaction of 1a with O₂ in CH₂Cl₂ (298 K) produces an additional unhydroxylated product of composition [Cu^II₂L(OH)(OH₂)][ClO₄]₃·2H₂O·0.5HCl (3a). In agreement with its proposed hydroxo-/aquo-bridged structure, 3a is weakly antiferromagnetically coupled. In CH₃CN solution, 3a rearranges to generate a doubly hydroxo-bridged species [Cu^II₂L(OH)₂]²⁺. Using a solution-generated dicopper(I) complex of a closely similar ligand (L' ') providing five-membered chelate ring, the reactivity toward dioxygen was also investigated. It produces only an irreversibly oxidized product of composition Cu^II₂L' '(OH)(ClO₄)₃(H₂O)₂ (3b) (L' ' = α,α'-bis[N-methyl-N-(2-pyridylmethyl)amino]-m-xylene). For 3b the copper(II) centers are almost uncoupled.