Synthetic, Spectroscopic and DFT Studies of Iron Complexes with Iminobenzo(semi)quinone Ligands: Implications for o-Aminophenol Dioxygenases

Abstract

The oxidative CC bond cleavage of o-aminophenols by nonheme Fe dioxygenases is a critical step in both human metabolism (the kynurenine pathway) and the microbial degradation of nitroaromatic pollutants. The catalytic cycle of o-aminophenol dioxygenases (APDOs) has been proposed to involve formation of an FeII/O2/iminobenzosemiquinone complex, although the presence of a substrate radical has been called into question by studies of related ring-cleaving dioxygenases. Recently, we reported the first synthesis of an iron(II) complex coordinated to an iminobenzosemiquinone (ISQ) ligand, namely, [Fe(Tp)(tBuISQ)] (2 a; where Tp=hydrotris(3,5-diphenylpyrazol-1-yl)borate and tBuISQ is the radical anion derived from 2-amino-4,6-di-tert-butylphenol). In the current manuscript, density functional theory (DFT) calculations and a wide variety of spectroscopic methods (electronic absorption, Mössbauer, magnetic circular dichroism, and resonance Raman) were employed to obtain detailed electronic-structure descriptions of 2 a and its one-electron oxidized derivative [3 a]+. In addition, we describe the synthesis and characterization of a parallel series of complexes featuring the neutral supporting ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (TIP). The isomer shifts of about 0.97 mm s−1 obtained through Mössbauer experiments confirm that 2 a (and its TIP-based analogue [2 b]+) contain FeII centers, and the presence of an ISQ radical was verified by analysis of the absorption spectra in light of time-dependent DFT calculations. The collective spectroscopic data indicate that one-electron oxidation of the FeII–ISQ complexes yields complexes ([3 a]+ and [3 b]2+) with electronic configurations between the FeIII–ISQ and FeII–IBQ limits (IBQ=iminobenzoquinone), highlighting the ability of o-amidophenolates to access multiple oxidation states. The implications of these results for the mechanism of APDOs and other ring-cleaving dioxygenases are discussed