Five- and Six-Coordinate Adducts of Nitrosamines with Ferric Porphyrins: Structural Models for the Type II Interactions of Nitrosamines with Ferric Cytochrome P450

摘要

Nitrosamines are well known for their toxic and carcinogenic properties. The metabolic activation of nitrosamines occur via interaction with the heme-containing cytochrome P450 enzymes. We report the preparation and structural characterization of a number of nitrosamine adducts of synthetic iron porphyrins. The reactions of the cations [(por)Fe(THF)2]ClO4 (por = TPP, TTP, OEP) with dialkylnitrosamines (R2NNO; R2 = Me2, Et2, (cyclo-CH2)4, (cyclo-CH2)5, (PhCH2)2) in toluene generate the six-coordinate high-spin (S = 5/2) [(por)Fe(ONNR2)2]ClO4 compounds and a five-coordinate intermediate-spin (S = 3/2) [(OEP)Fe(ONNMe2)]ClO₄ derivative in 57–72% yields (TPP = 5,10,15,20-tetraphenylporphyrinato dianion, TTP = 5,10,15,20-tetra-p-tolylporphyrinato dianion, OEP = 2,3,7,8,12,13,17,18-octaethylporphyrinato dianion). The N–O and N–N vibrations of the coordinated nitrosamine groups in [(por)Fe(ONNR₂)₂]ClO₄ occur in the 1238–1285 cm⁻¹ range. Three of the six-coordinate [(por)Fe(ONNR₂)₂]ClO₄ compounds and one five-coordinate [(OEP)Fe(ONNMe₂)]ClO₄ compound have been characterized by single crystal X-ray crystallography. All the nitrosamine ligands in these complexes bind to the ferric centers via a sole η¹-O binding mode. No arylnitrosamine adducts were obtained from the reactions of the precursor compounds [(por)Fe(THF)₂]ClO₄ with three arylnitrosamines (Ph₂NNO, Ph(Me)NNO, Ph(Et)NNO). However, prolonged exposure of [(por)Fe(THF)₂]ClO₄ to these arylnitrosamines resulted in the formation of the known five-coordinate (por)Fe(NO) derivatives. The latter (por)Fe(NO) compounds were obtained more readily by the reactions of the three arylnitrosamines with the four-coordinate (por)Fe^II precursors.