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

Nitrosamines are well-known for their toxic and carcinogenic properties. The metabolic activation of nitrosamines occurs 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 1239−1271 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)FeII precursors.