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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]

Two series of new dicyclopalladated complexes {(DMF)PdCl(μ-R(1)C6H3N═NC6H3R(2))PdCl(DMF)} of 4,4'-functionalized azobenzenes with substituents of varying electron-donating or electron-withdrawing strength (R(1) = H, NMe2; R(2) = H, Cl, Br, I, OMe, PhNH, CO2H, SO3Na, or NO2) have been synthesized and fully characterized. (1)H NMR spectroscopy along with the ESI mass spectrometry unambiguously identified the new complexes in the solution, and their solid-state structures were determined by X-ray crystallography. The presence of easily exchangeable solvent ligands was confirmed by (1)H NMR spectroscopy, X-ray experiments, and ESI mass spectrometry. The complexes were additionally characterized by UV-vis and fluorescence spectroscopies. The effect of different 4,4'-substituents on the formation rate of mono- and dicyclopalladated azobenzenes was studied by UV-vis spectroscopy. The experimental results are complemented by the quantum-chemical (DFT) calculations in order to rationalize the kinetic results as well as substituent effects on the reaction rates. It was found that the mono- and dicyclopalladation reactions of azobenzenes proceed in two consecutive processes, adduct formation and palladation steps. The rate-determining step in both palladations is the breaking of the ortho C-H bond, which has been confirmed as an electrophilic substitution process by Hammett correlations and DFT calculations.