Chiral Dicopper Complexes with a Doubly Asymmetric Ligand as Models for the Tyrosinase Active Site: Synthesis, Structure, O-2-Reactivity and Comparison with Their Symmetric Analogs

In order to model the asymmetric active site of the type-3 copper enzyme tyrosinase the doubly asymmetric binucleating ligand 1-[bis-N,N-(pyrid-2-ylmethyl)aminomethyl]-3-[N-(pyrid-2-ylmethyl)-N-(2-pyrid-2-ylethyl)aminomethyl]benzene (unsDMPA) is synthesized and coordinated to copper(I). The O-2-reactivity of the Cu-I(unsDMPA) complex and its analog derived from the symmetric counterpiece of unsDMPA, DMPA, is investigated. Oxygenation in methanol leads to dicopper(II) bis(mu-hydroxo) and bis(mu-methanolato) complexes; the dicopper(II) bis(mu-hydroxo) complex of the unsDN1PA ligand is chiral. Oxygenation in dichloromethane leads to oxidative N-dealkylation. This is attributed to a tendency of DMPA and unsDMPA complexes to form dicopper bis(mu-oxo) intermediates, as evidenced by DFT The implications of these results with respect to the design of tyrosinase model systerms are discussed.