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)]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.
Xu
Nan
N
Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Norman, Oklahoma 73019, USA.
Goodrich
Lauren E
LE
Lehnert
Nicolai
N
Powell
Douglas R
DR
Richter-Addo
George B
GB
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
D009602:Nitrosamines; D006418:Heme; D003577:Cytochrome P-450 Enzyme System
J Am Chem Soc. 2008 Nov 19;130(46):15288-303
18942830
Adv Exp Med Biol. 1996;387:385-94
8794233
Inorg Chem. 1998 Sep 7;37(18):4677-4688
11670621
Chem Rev. 2002 Apr;102(4):1019-66
11942786
Biochem J. 1983 Jun 15;212(3):599-608
6882387
J Natl Cancer Inst. 1978 Feb;60(2):251-3
621744
J Org Chem. 2000 Oct 6;65(20):6729-35
11052125
Inorg Chem. 2008 Nov 17;47(22):10187-9
18928271
Carcinogenesis. 1983;4(3):315-9
6831636
Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369-73
2819872
Chem Rev. 2002 Apr;102(4):1091-134
11942788
Angew Chem Int Ed Engl. 1999 Feb 1;38(3):392-395
29711664
Inorg Chem. 2000 Oct 30;39(22):5102-10
11233208
Inorg Chem. 2005 Oct 17;44(21):7333-44
16212360
Chem Res Toxicol. 1998 Jun;11(6):559-603
9625726
Carcinogenesis. 1993 Jan;14(1):7-10
7678786
Carcinogenesis. 1991 Jul;12(7):1217-20
1712676
Carcinogenesis. 1982;3(2):161-5
7067044
Chem Pharm Bull (Tokyo). 1995 Dec;43(12):2173-6
8582020
Chem Biol Interact. 1979;28(1):17-33
227615
J Am Chem Soc. 2005 Mar 2;127(8):2696-708
15725027
J Inorg Biochem. 2004 Jul;98(7):1238-46
15219991