Regioselective Aliphatic Carbon–Carbon Bond Cleavage by a Model System of Relevance to Iron-Containing Acireductone Dioxygenase

• Published in: Journal of the American Chemical Society Vol. 135; no. 2; pp. 659 - 668
• Main Authors: Allpress, Caleb J, Grubel, Katarzyna, Szajna-Fuller, Ewa, Arif, Atta M, Berreau, Lisa M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.01.2013
• Subjects: Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Crystallography, X-Ray; Dioxygenases - chemistry; Glyoxylates - chemistry; Iron - chemistry; Ligands; Magnetic Resonance Spectroscopy; Mandelic Acids - chemistry; Models, Molecular; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja3038189

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.