Comprehensive Theoretical View of the [Cu₂ O₂ ] Side-on-Peroxo-/Bis-μ-Oxo Equilibria

Coupled binuclear copper (CBC) sites are employed by many metalloenzymes to catalyze a broad set of biochemical transformations. Typically, the CBC catalytic sites are activated by the O₂ molecule to form various [Cu₂ O₂ ] reactive species. This has also inspired synthesis and development of various biomimetic inorganic complexes featuring the CBC core. From theoretical perspective, the [Cu₂ O₂ ] reactivity often hinges on the side-on-peroxo-dicopper(II) (P) vs. bis-μ-oxo-dicopper(III) (O) isomerism - an equilibrium that has become almost iconic in theoretical bioinorganic chemistry. Herein, we present a comprehensive calibration and evaluation of the performance of various composite computational protocols available in contemporary computational chemistry, involving coupled-cluster and multireference (relativistic) wave function methods, popular density functionals and solvation models. Starting with the well-studied reference [Cu₂ O₂ (NH₃ )₆ ]²⁺ system, we compared the performance of electronic structure methods and discussed the relativistic effects. This allowed us to select several 'calibrated' DFT functionals that can be conveniently employed to study ten experimentally well-characterized [Cu₂ O₂ ] inorganic systems. We mostly predicted the lowest-energy structures (P vs. O) of the studied systems correctly. In addition, we present calibration of the used electronic structure methods for prediction of the spectroscopic features of the [Cu₂ O₂ ] core, mostly provided by the resonance Raman (rR) spectroscopy.