Acireductone dioxygenase (ARD) is an essential enzyme in the methionine salvage pathway in animals, plants and bacteria. The human form has been linked to cellular pathogenic behavior in in-vitro studies. Many questions remain about ARD’s unique oxidative mechanism of substrate activation modulated simply by the metal’s identity at the active site. This leads to the so-called on and off pathways. The on-pathway is facilitated exclusively by iron, while the off-pathway has been shown to occur with nickel in bacteria and the mammalian relevant metals cobalt and manganese. The metal active site consists of a less common 3His-1Glu motif. A novel Ni(II)N3O model complex of ARD was reported by our laboratory. This compound is capable of direct O2 activation at the nickel center leading to the formation of a putative high-valent Ni(III) complex as the proposed active oxidant species, based on spectroscopic and computational evidence.1 Subsequent studies have led us to the synthesis of the entire family of ARD models using iron, cobalt, and manganese. This talk will discuss the structural, spectroscopic, redox, and biomimetic reactivity of this family of complexes. Key insights about the biomimetic, metal dependent, carbon-carbon oxidative cleavage reactivity of these compounds will be discussed in the context of the enzyme and its implications for other relevant dioxygenases.