Synthetic, spectroscopic, and DFT studies of iron complexes with iminobenzo(semi)quinone ligands: implications for o-aminophenol dioxygenases.

Abstract

The oxidative C-C 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 Fe(II)/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((Ph2)Tp)((tBu)ISQ)] (2a; where (Ph2)Tp=hydrotris(3,5-diphenylpyrazol-1-yl)borate and (tBu)ISQ 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 2a and its one-electron oxidized derivative [3a](+). 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 ((Ph2)TIP). The isomer shifts of about 0.97 mm s(-1) obtained through Mössbauer experiments confirm that 2a (and its (Ph2)TIP-based analogue [2b](+)) contain Fe(II) 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 Fe(II)-ISQ complexes yields complexes ([3a](+) and [3b](2+)) with electronic configurations between the Fe(III)-ISQ and Fe(II)-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.