Mechanistic Insights Into Copper Aggregates With Unsymmetrical Coordination Environments: From Biomimetic Copper–Oxygen Model Complexes to Copper–Alkynyl Clusters

ABSTRACT Copper is one of the most abundant and less toxic transition metals in nature, which exhibits rich oxidation states and versatile catalytic activity using O 2 as an oxidant. To date, enormous efforts in crystallographic and spectroscopic analyses have explicitly disclosed the pivotal role of polynuclear copper aggregates in the biological and organocatalytic redox processes. Notably, most biological Cu–O active sites often have unsymmetrical coordination environments for each copper ion, which finally account for the differentiated redox properties and biological functions. Inspired by the structural biology advances, numerous synthetic model complexes as enzyme mimics and organocatalytic active species have been established to identify enzymatic reaction intermediates and clarify the catalytic mechanisms. However, those synthetic models often show identical or similar coordination environments for individual copper ions because of the extensive application of synthetically accessible symmetrical ligands. In this Perspective, we endeavor to summarize the composition and structural details of Cu–O active species in several important copper‐containing enzymes and pay special attention to the coordination environments of individual copper ions therein. Mechanistic studies on the biased functions of individual copper centers and the cooperative effect among them have been comprehensively surveyed. Recent progress of the synthetic Cu–O model complexes with unsymmetrical coordination environments, including the distinctive bi‐cluster alkynyl–copper–oxygen aggregate, is discussed in detail to clarify the distinctive structure–property relationship of nonequivalent copper ions. We hope that this Perspective reiterates the unsymmetrical structural features of polynuclear copper aggregates in copper‐catalytic systems and highlights the unique effect of coordination unequivalence in redox process, and provides new inspiration for the rational design of novel multimetallic catalysts.