Structural Differentiation of Diastereomeric Benzo[ghi]fluoranthene Adducts of Deoxyadenosine by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Postsource Decay
Date of Original Version
The product ion formation characteristics of four diastereomeric deoxyadenosine adducts formed by the reaction of the syn and anti diastereomers of trans-3,4-dihydroxy-5,5a-epoxy-3,4,5,5a-tetrahydrobenzo[ghi]fluoranthene are studied by matrix-assisted laser desorption ionization and postsource decay (PSD) to determine fragmentation pathways that may permit differentiation of their structures. The two adducts derived from each diol-epoxide with DNA differ in structure based on the cis/trans arrangement of the 3′-hydroxyl group on the benzo[ghi]fluoranthene (B[ghi]F) and the adenine base bound to the B[ghi]F 5a carbon. The two adduct diastereomers with the cis adenine-3′-hydroxyl configuration produce product ions at m/z 394 and m/z 510 formed by the loss of water that are not observed in the PSD spectra of the two trans isomers. The data suggest a mechanism of water loss that is initiated by a hydrogen-bonding interaction between the charge-bearing proton on the N1 atom and the 3′-hydroxyl oxygen on the polycyclic aromatic hydrocarbon (PAH). Fragmentation is initiated by the transfer of the adenine N1 proton from the nitrogen to the PAH 3′-hydroxyl oxygen and inductive cleavage of the C3-O3 bond to form a benzylic carbocation on B[ghi]F. The proposed mechanism is supported by semiempirical molecular modeling calculations.
Chemical Research in Toxicology
Chiarelli, M. P., Hui-Fang Chang, Kenneth W. Olsen, Damon Barbacci, and Bongsup P. Cho. "Structural Differentiation of Diastereomeric Benzo[ghi]fluoranthene Adducts of Deoxyadenosine by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Postsource Decay." Chemical Research in Toxicology 16, 10 (2003): 1236-1241. doi:10.1021/tx0340798.