Manganese-Oxygen Intermediates in O-O Bond Activation and Hydrogen-Atom Transfer Reactions

Biological systems capitalize on the redox versatility of manganese to perform reactions involving dioxygen and its derivatives superoxide, hydrogen peroxide, and water. The reactions of manganese enzymes influence both human health and the global energy cycle. Important examples include the detoxification of reactive oxygen species by manganese superoxide dismutase, biosynthesis by manganese ribonucleotide reductase and manganese lipoxygenase, and water splitting by the oxygen-evolving complex of photosystem II. Although these enzymes perform very different reactions and employ structurally distinct active sites, manganese intermediates with peroxo, hydroxo, and oxo ligation are commonly proposed in catalytic mechanisms. These intermediates are also postulated in mechanisms of synthetic manganese oxidation catalysts, which are of interest due to the earth abundance of manganese. In this Account, we describe our recent efforts toward understanding O-O bond activation pathways of Mn^III-peroxo adducts and hydrogen-atom transfer reactivity of Mn^IV-oxo and Mn^III-hydroxo complexes. In biological and synthetic catalysts, peroxomanganese intermediates are commonly proposed to decay by either Mn-O or O-O cleavage pathways, although it is often unclear how the local coordination environment influences the decay mechanism. To address this matter, we generated a variety of Mn^III-peroxo adducts with varied ligand environments. Using parallel-mode EPR and Mn K-edge X-ray absorption techniques, the decay pathway of one Mn^III-peroxo complex bearing a bulky macrocylic ligand was investigated. Unlike many Mn^III-peroxo model complexes that decay to oxo-bridged-Mn^IIIMn^IV dimers, decay of this Mn^III-peroxo adduct yielded mononuclear Mn^III-hydroxo and Mn^IV-oxo products, potentially resulting from O-O bond activation of the Mn^III-peroxo unit. These results highlight the role of ligand sterics in promoting the formation of mononuclear products and mark an important step in designing Mn^III-peroxo complexes that convert cleanly to high-valent Mn-oxo species. Although some synthetic Mn^IV-oxo complexes show great potential for oxidizing substrates with strong C-H bonds, most Mn^IV-oxo species are sluggish oxidants. Both two-state reactivity and thermodynamic arguments have been put forth to explain these observations. To address these issues, we generated a series of Mn^IV-oxo complexes supported by neutral, pentadentate ligands with systematically perturbed equatorial donation. Kinetic investigations of these complexes revealed a correlation between equatorial ligand-field strength and hydrogen-atom and oxygen-atom transfer reactivity. While this trend can be understood on the basis of the two-state reactivity model, the reactivity trend also correlates with variations in Mn^III/IV reduction potential caused by changes in the ligand field. This work demonstrates the dramatic influence simple ligand perturbations can have on reactivity but also illustrates the difficulties in understanding the precise basis for a change in reactivity. In the enzyme manganese lipoxygenase, an active-site Mn^III-hydroxo adduct initiates substrate oxidation by abstracting a hydrogen atom from a C-H bond. Precedent for this chemistry from synthetic Mn^III-hydroxo centers is rare. To better understand hydrogen-atom transfer by Mn^III centers, we developed a pair of Mn^III-hydroxo complexes, formed in high yield from dioxygen oxidation of Mn^II precursors, capable of attacking weak O-H and C-H bonds. Kinetic and computational studies show a delicate interplay between thermodynamic and steric influences in hydrogen-atom transfer reactivity, underscoring the potential of Mn^III-hydroxo units as mild oxidants.