The activation of dioxygen by metalloenzymes is a subject of great current interest. The paradigm for high-valent oxidizing species has been the iron(IV)-oxo porphyrin radical species which has been identified in the reaction of heme peroxidases and is believed to be the key oxidant for cytochrome P450. The absence of the porphyrin ligand in nonheme diiron enzymes such as methane monooxygenase, ribonucleotide reductase, and fatty acid desaturases requires somewhat different chemistry. Our recent synthetic efforts involving the remarkably versatile ligand tris(2-pyridylmethyl)amine (TPA) have produced the first examples of complexes with a high-valent Fe 2 (μ-O) 2 diamond-shaped core. Examples of complexes with high valent M 2 (μ-O) 2 cores can also be found in the chemistry of Mn (quite common) and Cu (only recently characterized). Spectroscopic signatures for the Fe 2 (μ-O) 2 core include a short (ca. 2.7(2) 9) Fe-Fe distance readily discernible from EXAFS and a Raman vibration near 650 cm - 1 assigned to a centrosymmetric deformation of the diamond core. We have proposed the Fe 2 (μ-O) 2 core as an attractive structure for high-valent intermediates in the reactions of O 2 with nonheme diiron enzymes. In support of this hypothesis are reactivity studies showing that the synthetic high-valent Fe 2 (μ-O) 2 complexes can carry out oxidation reactions analogous to those associated with these enzymes, including hydrogen abstraction from aliphatic C-H bonds and EXAFS studies demonstrating the presence of a short Fe-Fe distance in intermediate Q of methane monooxygenase. The Fe 2 (μ-O) 2 diamond core thus represents a new paradigm for the oxygen activation mechanisms of nonheme diiron enzymes.