Regioselective aliphatic carbon-carbon bond cleavage by a model system of relevance to iron-containing acireductone dioxygenase

Mononuclear Fe(II) complexes ([(6-Ph₂TPA)Fe(PhC(O)C(R)C(O)Ph)]X (3-X: R = OH, X = ClO₄ or OTf; 4: R = H, X = ClO₄)) supported by the 6-Ph₂TPA chelate ligand (6-Ph₂TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-(2-pyridylmethyl)amine) and containing a β-diketonate ligand bound via a six-membered chelate ring have been synthesized. The complexes have all been characterized by ¹H NMR, UV-vis, and infrared spectroscopy and variably by elemental analysis, mass spectrometry, and X-ray crystallography. Treatment of dry CH₃CN solutions of 3-OTf with O₂ leads to oxidative cleavage of the C(1)-C(2) and C(2)-C(3) bonds of the acireductone via a dioxygenase reaction, leading to formation of carbon monoxide and 2 equiv of benzoic acid as well as two other products not derived from dioxygenase reactivity: 2-oxo-2- phenylethylbenzoate and benzil. Treatment of CH₃CN/H₂O solutions of 3-X with O₂ leads to the formation of an additional product, benzoylformic acid, indicative of the operation of a new reaction pathway in which only the C(1)-C(2) bond is cleaved. Mechanistic studies show that the change in regioselectivity is due to the hydration of a vicinal triketone intermediate in the presence of both an iron center and water. This is the first structural and functional model of relevance to iron-containing acireductone dioxygenase (Fe-ARD′), an enzyme in the methionine salvage pathway that catalyzes the regiospecific oxidation of 1,2-dihydroxy-3-oxo-(S)- methylthiopentene to form 2-oxo-4-methylthiobutyrate. Importantly, this model system is found to control the regioselectivity of aliphatic carbon-carbon bond cleavage by changes involving an intermediate in the reaction pathway, rather than by the binding mode of the substrate, as had been proposed in studies of acireductone enzymes.