Thioether‐Containing Copper Complexes as PHM, DβM, and TβM Model Systems

Abstract

This minireview presents efforts of synthetic chemists to mimic the active site of the copper monooxygenase enzymes peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM), all of which feature copper-thioether ligation in their resting states. These monooxygenases are involved in the initial activation of O 2 to generate neurotransmitters by the selective activation of CÀ H bonds of their corresponding substrates, resulting in subsequent hydroxylation. Attempts to emulate the N 2 S donor set provided by the two histidines and the methionine residues that coordinate to copper in the active site employ N 2 S and N 3 S-type ligands, with the latter ones providing the best conditions for testing the reactivity of their Cu I complexes with dioxygen. Identification of Cu II -superoxos as capable agents for CÀ H activation has provided support for these species as the key reactive intermediates in the enzymatic systems. Synthetic end-on [Cu II -η 1 -O 2 * À ] and side-on [Cu II -η 2 -O 2 * À ] cupric superoxos are capable of such transformations, which is related to the open question of whether the methionine Sdonor may act as a hemilabile ligand in biological systems.

Ligand–Copper(I) Primary O2-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides

“…Castillo recently reviewed the coordination chemistry of copper with thioether ligands as relevant to the PHM and DβM enzyme Cu M . The presence of this RSR′ ligand has long puzzled (bio)­chemists and spurred experimental and computational investigations.…”