Thioester hydrolysis reactivity of zinc hydroxide complexes: investigating reactivity relevant to glyoxalase II enzymes

Abstract

A recently reported binuclear zinc hydroxide complex [(L¹Zn₂)(µ-OH)](ClO₄)₂ (1, L¹ = 2,6-bis[(bis(2-pyridylmethyl)amino)methyl]-4-methylphenolate monoanion) containing a single bridging hydroxide was examined for thioester hydrolysis reactivity. Treatment of 1 with hydroxyphenylthioacetic acid S-methyl ester in dry CD₃CN results in no reaction after ∼65 h at 45(1) °C. Binuclear zinc hydroxide complexes of the N-methyl-N-((6-neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine (L²) and N-methyl-N-((6-neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)ethyl)amine (L³) chelate ligands were prepared by treatment of each ligand with molar equivalent amounts of Zn(ClO₄)₂·6H₂O and KOH in methanol. These complexes, [(L²Zn)₂(µ-OH)₂](ClO₄)₂ (2) and [(L³Zn)₂(µ-OH)₂](ClO₄)₂ (3), which have been structurally characterized by X-ray crystallography, behave as 1 : 1 electrolytes in acetonitrile, indicating that the binuclear cations dissociate into monomeric zinc hydroxide species in solution. Treatment of 2 or 3 with one equivalent of hydroxyphenylthioacetic acid S-methyl ester per zinc center in acetonitrile results in the formation of a zinc α-hydroxycarboxylate complex, [(L²)Zn(O₂CCH(OH)Ph)]ClO₄·1.5H₂O (4) or [(L³)Zn(O₂CCH(OH)Ph)]ClO₄·1.5H₂O (5), and CH₃SH. These reactions, to our knowledge, are the first reported examples of thioester hydrolysis mediated by zinc hydroxide complexes. The results of this study suggest that a terminal Zn–OH moiety may be required for hydrolysis reactivity with a thioester substrate.