Gas Chromatography Electron Ionization Mass Spectral Analysis of Thio Analogues of Pyrimidine Bases: 5-Bromo-2,4-di-o-(m- and p-) chloro- (bromo-)benzylthiouracils and 6-methyluracils
Electron ionization (EI) mass spectral fragmentation routes of twelve 5-bromo-2,4-di-o-(m- and p-) chloro- (bromo-)benzyl-thiouracils and 6-methyluracils are investigated. The compounds studied are analyzed using gas chromatography/mass spectrometry (GC/MS). Fragmentation pathways, whose elucidation is assisted by accurate mass measurements and metastable transitions, are discussed. Correlation between the abundances of the selected fragment ions of the compounds investigated is discussed. The data obtained make grounds for distinction of structural isomers. 1. Introduction Thio derivatives of pyrimidine bases are of interest because of their biological and pharmacological activities, for example, as minor components of t-RNA or as antithyroidal and anticancer drugs as well as sedatives [1–7]. Essential role in biological systems play compounds, which contain 5-bromopyrimidine moiety, like 5-bromouracil and 5-bromouridine. It is well known that these compounds are mutagenic [8–10] and able to replace thymine residue in the DNA molecule. On the other hand, C-5 bromo group is a hydrophobic substituent having also electron-negative properties, very important for anaesthetic and anticonflict activities [11]. The presence of benzyl group also influences the activity of pyrimidine derivatives, for example, the pyrimidine thioethers with 2-benzylthio substituent have been reported as a novel nonnucleoside HIV-1 reverse transferase inhibitors (NNRTIs) with activity against BHAP-resistant HIV [12, 13]. Because of biological importance of the modified thio analogues of pyrimidine bases, much attention has been devoted to recognize their properties. Mass spectrometry continues to be a convenient and effective method for determination of nature of covalent modifications to thio analogues of nucleobases and for distinction of structural isomers [14–17]. The mass spectral behavior of modified derivatives of thionucleobases, for example, 2-benzylthio and 4-benzylthiouracils which may appear in the gas phase in various tautomeric forms has been studied previously. However, to the best of our knowledge, no work has been published about the mass spectrometric behavior of fully aromatic 2,4-dibenzylthio-5-bromouracils. The hereby presented study of mass fragmentation of the title compounds were undertaken to examine the influence of C-5 bromo substitution in pyrimidine ring on their EI mass fragmentation. Isomeric organic compounds discrimination is a challenging task for mass spectrometrists because of the identical molecular masses and similar fragmentation pathways of
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