title: Five- and six-coordinate adducts of nitrosamines with ferric porphyrins: structural models for the Type II interactions of nitrosamines with ferric cytochrome P450.
abstract: 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)]ClO(4) (por = TPP, TTP, OEP) with dialkylnitrosamines (R(2)NNO; R(2) = Me(2), Et(2), (cyclo-CH(2))(4), (cyclo-CH(2))(5), (PhCH(2))(2)) in toluene generate the six-coordinate high-spin (S = 5/2) [(por)Fe(ONNR(2))(2)]ClO(4) compounds and a five-coordinate intermediate-spin (S = 3/2) [(OEP)Fe(ONNMe(2))]ClO(4) 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(ONNR(2))(2)]ClO(4) occur in the 1239-1271 cm(-1) range. Three of the six-coordinate [(por)Fe(ONNR(2))(2)]ClO(4) compounds and one five-coordinate [(OEP)Fe(ONNMe(2))]ClO(4) 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 eta(1)-O binding mode. No arylnitrosamine adducts were obtained from the reactions of the precursor compounds [(por)Fe(THF)(2)]ClO(4) with three arylnitrosamines (Ph(2)NNO, Ph(Me)NNO, Ph(Et)NNO). However, prolonged exposure of [(por)Fe(THF)(2)]ClO(4) 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Norman, Oklahoma 73019, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Goodrich
authors.forename: Nicolai
authors.initials: N
authors.lastname: Lehnert
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Powell
authors.forename: George B
authors.initials: GB
authors.lastname: Richter-Addo
mesh_terms: D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005615:Freezing; D006418:Heme / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009602:Nitrosamines / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D013696:Temperature
chemical_list: D009602:Nitrosamines; D006418:Heme; D003577:Cytochrome P-450 Enzyme System
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