Naslov
Mass Spectrometry and Theoretical Studies on N-C Bond Cleavages in the N-sulfonylamidino Thymine Derivatives

Autori
Kobetić, Renata ; Kazazić, Snježana ; Kovačević, Borislav ; Glasovac, Zoran ; Krstulović, Luka ; Bajić, Miroslav ; Žinić, Biserka

Izvornik
Journal of the American Society for Mass Spectrometry (1044-0305) 26 (2015), 5; 833-842

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
N-sulfonylamidines; Thymine; retro-Michael addition; ESI-MS; DFT calculations

Sažetak
The reactivity of new biologically active thymine derivatives substituted with 2-(arylsulfonamidino)ethyl group at N1 and N3 position was investigated in the gas phase using CID experiments (ESI-MS/MS) and by density functional theory (DFT) calculations. Both derivatives show similar chemistry in the negative mode with a retro-Michael addition (Path A–) being the most abundant reaction channel, which correlate well with the fluoride induced retro-Michael addition observed in solution. The difference in the fragmentation of N-3 substituted thymine 5 and N-1 substituted thymine 1 in the positive mode relates to the preferred cleavage of the sulfonyl group (m/z 155, Path B) in N-3 isomer and the formation of the acryl sulfonamidine 3 (m/z 309) via Path A in N-1 isomer. Mechanistic studies of the cleavage reaction conducted by DFT calculations give the trend of the calculated activation energies that agree well with the experimental observations. A mechanism of the retro-Michael reaction was interpreted as a McLafferty type of fragmentation, which includes Hβ proton shift to one of the neighboring oxygen atoms in a 1, 5-fashion inducing N1(N3)–Cα bond scission. This mechanism was found to be kinetically favorable over other tested mechanisms. Significant difference in the observed fragmentation pattern of N-1 and N-3 isomers proves the ESI-MS/MS technique as an excellent method for tracking the fate of similar sulfonamidine drugs. Also, the observed N-1 and/or N-3 thymine alkylation with in situ formed reactive acryl sulfonamidine 3 as a Michael acceptor may open interesting possibilities for the preparation of other N-3 substituted pyrimidines.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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