Iron(II) complexes of sterically bulky alpha-ketocarboxylates. structural models for alpha-ketoacid-dependent nonheme iron halogenases

Reaction of the sterically hindered alpha-ketocarboxylate 2,6-di(mesityl)benzoylformate (MesBF) with the iron(II) complexes LFeCl 2 L = N, N, N', N'-tetramethylpropylenediamine (Me 4pda) or 6,6'-dimethyl-2,2'-bipyridine (dmby)] yielded LFe(Cl)(MesBF) ( 1 or 2). X-ray crystal structures of these complexes showed that they closely model the active site structure of the nonheme iron halogenase enzyme SyrB2. A similar synthetic procedure using benzoylformate with L = dmby yielded (dmby)Fe(O 2CC(O)Ph)] 2 ( 3) instead, demonstrating the need for the sterically hindered alpha-ketocarboxylate to assemble the halogenase model compounds. In order to make reactivity comparisons among the structurally related iron(II) complexes of benzoylformates of varying steric properties, the complexes LFe(O 2CC(O)Ar)] n ( 4- 6) were prepared, where L' = tris(pyridylmethyl)amine (tpa) and Ar = 2,6-dimesitylphenyl, 2,6-di p-tolylphenyl, or 2,4,6-trimethylphenyl, respectively. X-ray structures for the latter two cases ( 5 and 6) revealed dinuclear topologies ( n = 2), but UV-vis and (1)H NMR spectroscopy indicated that all three complexes dissociated in varying degrees to monomers in CH 2Cl 2 solution. Although compounds 1- 6 were oxidized by O 2, oxidative decarboxylation of the alpha-ketocarboxylate ligand(s) only occurred for 3. These results indicate that the steric hindrance useful for structural modeling of the halogenase active site prohibits functional mimicry of the enzyme.