Evidence for the Formation of an Iron(III)-Indolenylperoxo Intermediate During Indole Dioxygenation: Similarities with Heme Dioxygenases.

Evidence for an iron(III)-indolenylperoxo (OOIn-) complex, [FeIII(OOIn)(TPP)(OCH3)]- (TPP = 5,10,15,20-tetraphenylporphyrinato2-) trapped at -78 °C, was obtained. The formation of this species was initiated by reaction of either FeIII(TPP)(Cl) in the presence of excess O2, OCH3- as axial ligand and base, and 3-methylindole, or from reaction of preformed [FeIII(O2•-)(TPP)(OCH3)]- with 3-methylindole under the same basic conditions. The new species was characterized by UV-vis, X-band EPR, and Mössbauer spectroscopies. Interestingly, the EPR spectra of [FeIII(OOIn)(TPP)(OCH3)]- exhibited two overlapping low-spin (S = 1/2) rhombic signals (A: g = [2.31, 2.20, 1.93]; B: g = [2.24, 2.15, 1.96]), whose ratios are sensitive to the amount of MeOH in the solvent mixture MeOH/toluene. The two sets of EPR signals (A and B) were assigned as arising from the presence or absence of hydrogen bonding between the OCH3- axial ligand and the solvent MeOH. This assignment was supported by analysis of ligand field splitting parameters derived from the EPR data. Addition of 1-methylimidazole (1-MeIm) to [FeIII(OOIn)(TPP)(OCH3)]- at -78 °C leads to conversion of the two overlapping rhombic EPR signals into a new, single S = 1/2 rhombic spectrum with g = [2.31, 2.18, 1.94] and a sharper Mössbauer spectrum. These data are consistent with substitution of OCH3- axial ligand by 1-MeIm to give FeIII(OOIn)(TPP)(1-MeIm). Thermal decay of the iron(III)-indolenylperoxo complex gives the ring-opened, dioxygenated product N-(2-acetylphenyl)formamide (75% by GC-MS). The capability of [FeIII(OOIn)(TPP)(OCH3)]- to convert into dioxygenated product indicates that iron indolenylperoxide is a possible intermediate of the indole dioxygenation process. This work has implications for the proposed mechanisms of tryptophan/indoleamine 2,3-dioxygenase (TDO/IDO) and demonstrates a feasible pathway for dioxygenation mediated by a single iron porphyrin complex.