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Mass Spectrometry and Theoretical Studies on N-C Bond Cleavages in the N-Sulfonylamidino Thymine Derivatives.
- Source :
-
Journal of the American Society for Mass Spectrometry . May2015, Vol. 26 Issue 5, p833-842. 10p. - Publication Year :
- 2015
-
Abstract
- 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 H proton shift to one of the neighboring oxygen atoms in a 1,5-fashion inducing N1(N3)-C 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. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10440305
- Volume :
- 26
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of the American Society for Mass Spectrometry
- Publication Type :
- Academic Journal
- Accession number :
- 102103901
- Full Text :
- https://doi.org/10.1007/s13361-014-1068-8