title: Identification of new DNA adducts of phenylnitrenium.
abstract: Phenylnitrenium ion (PhNH(+)) may bind to nucleophiles through nitrogen as well as through C2 or C4 carbons. However, only adducts of the former type have been hitherto reported after its reaction with purine nucleosides. In this study, reactions of N-acetoxyaniline (PhNHOAc), a precursor to PhNH(+), with 2'-deoxyadenosine (dA), 2'-deoxyguanosine (dG), and with DNA in vitro at physiological conditions are described. The reaction of PhNHOAc with dA followed by a hydrolytic deribosylation afforded 8-phenylaminoadenine (C8-PhNHA) together with a smaller amount of N(6)-(4-aminophenyl)adenine (N(6)-4APA). A similar reaction with dG afforded 8-phenylaminoguanine (C8-PhNHG) together with traces of 7-(4-aminophenyl)guanine (N7-4APG). The same adducts were found also in the DNA treated with PhNHOAc, and all of them were identified by comparison of their HPLC retention times and MS(2) spectra with a set of synthesized authentic adenine adducts at C2, C8, N7, and N(6) positions and guanine adducts at C8, N7, and N(2) positions. The newly identified minor adduct, N7-4APG, represents the first proof of arylnitrenium adduction at the N7 position of dG, which is the prominent site of attack by most C-electrophiles.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 1905, CZ-166 28 Prague, Czech Republic.
authors.forename: Antonín
authors.initials: A
authors.lastname: Králík
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 1905, CZ-166 28 Prague, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Linhart
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 1905, CZ-166 28 Prague, Czech Republic.
authors.forename: Lubomír
authors.initials: L
authors.lastname: Váňa
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 1905, CZ-166 28 Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Moulisová
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis*; D007094:Imides / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D001555:Benzene Derivatives; D018736:DNA Adducts; D007094:Imides; C523745:phenylnitrenium