Ironcarbon bond formation during substrate activation by hemoproteins

Abstract

Recent results point to the existence of an important organometallic chemistry of certain hemoproteins, with the formation of ironcarbon bonds during substrate activation. Evidence for such ironcarbon bond formation comes both from spectroscopic studies on the hemoproteins themselves and from model studies on iron-porphyrins. These ironcarbon bonds are formed either upon reduction or oxidation of several substrates [1]. Reduction of benzylhalides, ArCH 2X, by microsomal cytochrome P450 leads to σ-alkyl complexes of this cytochrome involving a Fe(III)CH 2Ar bond. Reduction of halothane,CF 3CHClBr, leads also to a σ-alkyl cytochrome P450Fe(III)CHClCF 3 complexes, whereas microsomal reduction of other polyhalogenated compounds such as CCl 4 or CCl 3CN leads to ironcarbene complexes, cytochrome P450Fe(II) ← CCl 2 (or CClCN). Similar reactions occur upon reduction of the same compounds by iron-porphyrins, the corresponding σ-alkyl or carbene complexes having been isolated and characterized [2]: ▪ Cytochrome P450iron(II)carbene complexes are also formed upon metabolic oxidation of the methylene group of 1,3-benzodioxole derivatives, suggesting a mechanism for CH bond activation by cytochrome P450 that involves the intermediate formation of an ironcarbon bond [3]. Very recently, it has been indicated that σ-alkyl (or -aryl) iron(III) complexes of cytochrome P450 [4] or hemoglobin [4, 5] are formed upon metabolic oxidation of various monosubstituted hydrazines by these hemoproteins. Most often, iron(II)diazene complexes are involved as intermediates in this reaction: ▪ Similar diazene and σ-alkyl complexes are formed upon reaction of RNHNH 2 with ironporphyrins; they have been isolated and characterized [6]. A general scheme for ironcarbon bond formation will be given; it involves a reductive or oxidative activation of the substrate leading to an organic free radical, and the combination of this radical with the hemoproteiniron. Most of these hemoproteinσ-alkyl or carbene complexes have also been detected in vivo; their biological implications will be discussed.