Intramolecular Hydrogen-Bond Interactions Tune Reactivity in Biomimetic Bis(μ-hydroxo)dicobalt Complexes

Active site hydrogen-bond (H-bond) networks represent a key component by which metalloenzymes control the formation and deployment of high-valent transition metal-oxo intermediates. We report a series of dinuclear cobalt complexes that serve as structural models for the nonheme diiron enzyme family and feature a Co₂(μ-OH)₂ diamond core stabilized by intramolecular H-bond interactions. We define the conditions required for the kinetically controlled synthesis of these complexes: [Co₂(μ-OH)₂(μ-OAc)(κ¹-OAc)₂(py^R)₄][PF₆] (1), where OAc = acetate and py^R = pyridine with para-substituent R, and we describe a homologous series of 1 in which the para-R substituent on pyridine is modulated. The solid state X-ray diffraction (XRD) structures of 1 are similar across the series, but in solution, their ¹H NMR spectra reveal a linear free energy relationship (LFER) where, as R becomes increasingly electron-withdrawing, the intramolecular H-bond interaction between bridging μ-OH and κ¹-acetate ligands results in increasingly "oxo-like" μ-OH bridges. Deprotonation of the bridging μ-OH results in the quantitative conversion to corresponding cubane complexes: [Co₄(μ-O)₄(μ₃-OAc)₄(py^R)₄] (2), which represent the thermodynamic sink of self-assembly. These reactions are unusually slow for rate-limiting deprotonation events, but rapid-mixing experiments reveal a 6000-fold rate acceleration on going from R = OMe to R = CN. These results suggest that we can tune reactivity by modulating the μ-OH pK_a in the presence of intramolecular H-bond interactions to maintain stability as the octahedral d⁶ centers become increasingly acidic. Nature may similarly employ dynamic carboxylate-mediated H-bond interactions to control the reactivity of acidic transition metal-oxo intermediates.