Theoretical Models on the Cu₂O₂ Torture Track:  Mechanistic Implications for Oxytyrosinase and Small-Molecule Analogues

Accurately describing the relative energetics of alternative bis(μ-oxo) and μ-η²:η² peroxo isomers of Cu₂O₂ cores supported by 0, 2, 4, and 6 ammonia ligands is remarkably challenging for a wide variety of theoretical models, primarily owing to the difficulty of maintaining a balanced description of rapidly changing dynamical and nondynamical electron correlation effects and a varying degree of biradical character along the isomerization coordinate. The completely renormalized coupled-cluster level of theory including triple excitations and extremely efficient pure density functional levels of theory quantitatively agree with one another and also agree qualitatively with experimental results for Cu₂O₂ cores supported by analogous but larger ligands. Standard coupled-cluster methods, such as CCSD(T), are in most cases considerably less accurate and exhibit poor convergence in predicted relative energies. Hybrid density functionals significantly underestimate the stability of the bis(μ-oxo) form, with the magnitude of the error being directly proportional to the percentage Hartree−Fock exchange in the functional. Single-root CASPT2 multireference second-order perturbation theory, by contrast, significantly overestimates the stability of bis(μ-oxo) isomers. Implications of these results for modeling the mechanism of C−H bond activation by supported Cu₂O₂ cores, like that found in the active site of oxytyrosinase, are discussed.