Helleberg, H; Westerholm, R; Ehrenberg, L; Tornqvist, M
The reactive diol epoxides of fluoranthene and benzo[a]pyrene, (±)-anti-c-1,c-10b-epoxy-1,2,3,10b-tetrahydrofluoranthene-r-2,t-3-diol (1) and (±)-anti-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-r-7,t-8-diol (4), respectively, are known genotoxic agents and effective alkylators of nucleophilic sites in DNA and proteins. As models of in vivo N-alkylation at the N-termini of hemoglobin (Hb), N-L-valine methylamide (VMA) products of 1 and 4 were synthesised, N-(r-1,c-2,t-3-trihydroxy-1,2,3,10b-tetrahydrofluoranthen-t-10b-yl)-L-valine methylamide (2a,b) and N-(r-7,t-8,t-9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyren-c-10-yl)-L-valine methylamide (5a,b), respectively. For isolation of the reaction products from the alkylation of VMA two reversed-phase HPLC systems were developed. From each diol epoxide two diastereoisomeric products were isolated in separate fractions. The products were characterised by 1H NMR spectroscopy as well as by thermospray (TSP) tandem quadrupole mass spectrometry (MS and MS/MS) and fluorescence. When analysed by TSP-MS/MS the quasimolecular ions, [M+H]+, have a neutral loss of either the VMA or the 1 and 4 adduct moieties, respectively. The major daughter ion from 5a,b is the adduct moiety and the corresponding ion from 2a,b is the VMA moiety. Minor daughter ions are, in both cases, [(M-VMA)+H]+ ions with additional loss of H2O or H2O+CO. The higher the number of hydroxy groups in the 2a,b ions, the more easily is the C10b-amino bond disrupted in collision-induced dissociation. © Acta Chemica Scandinavica 1998.