Surprising Radiolytic Stability of 8-Thiomethyladenine in an Aqueous Solution.

8-Thiomethyladenine (ASCH3), a potentially radiosensitizing modified nucleobase, has been synthesized in a reaction between 8-thioadenine and methyl iodide. Despite favorable dissociative electron attachment (DEA) characteristics, the radiolysis of an aqueous solution of ASCH3 with a dose of X-ray amounting to as much as 300 Gy leads to no effects. Nevertheless, crossed electron-molecule beam experiments in the gas phase on ASCH3 confirm the theoretical findings regarding the stability of its radical anion, namely, the most abundant reaction channel is related to the dissociation of the S-CH3 bond in the respective anion. Furthermore, electron-induced degradation of ASCH3 has been observed in aprotic acetonitrile, which is strong evidence for the involvement of proton transfer (PT) in stabilizing the radical anion in an aqueous solution. These findings demonstrate that PT in water can be the main player in deciding the radiosensitizing properties of modified nucleobases/nucleosides.

Dissociative Electron Attachment to 5-Iodo-4-thio-2'-deoxyuridine: A Potential Radiosensitizer of Hypoxic Cells.

In the search for effective radiosensitizers for tumor cells, halogenated uracils have attracted more attention due to their large cross section for dissociation upon the attachment of low-energy electrons. In this study, we investigated dissociative electron attachment (DEA) to 5-iodo-4-thio-2'-deoxyuridine, a potential radiosensitizer using a crossed electron-molecule beam experiment coupled with quadrupole mass spectrometry. The experimental results were supported by calculations on the threshold energies of formed anions and transition state calculations. We show that low-energy electrons with kinetic energies near 0 eV may effectively decompose the molecule upon DEA. The by far most abundant anion observed corresponds to the iodine anion (I-). Due to the associated bond cleavage, a radical site is formed at the C5 position, which may initiate strand break formation if the molecule is incorporated into a DNA strand. Our results reflect the conclusion from previous radiolysis studies with the title compound, suggesting its potential as a radiosensitizer.

Electron-Induced Decomposition of 5-Bromo-4-thiouracil and 5-Bromo-4-thio-2'-deoxyuridine: The Effect of the Deoxyribose Moiety on Dissociative Electron Attachment.

When modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-2'-deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry was used to detect the anionic products of dissociative electron attachment (DEA), and the experimental results were supported by quantum chemical calculations performed at the M062X/aug-cc-pVTZ level of theory. Experimentally, we found that BrSU predominantly captures low-energy electrons with kinetic energies near 0 eV, though the abundance of bromine anions was rather low compared to a similar experiment with bromouracil. We suggest that, for this reaction channel, proton-transfer reactions in the transient negative ions limit the release of bromine anions.

Reversed-phase pH gradient thin-layer chromatography of biologically active substances with controlled developing solvent velocity.

For the first time, stepwise pH gradient thin-layer chromatograms of biologically active substances with controlled developing solvent velocity are presented and described in the paper. Change in buffer pH of the mobile phase solution influences retardation, selectivity, and shape of the separated substances' spots. The conducted research has confirmed that the mobile phase's pH gradient could be an essential factor to optimize the conditions of the separation of substances in reversed-phase high-performance thin-layer chromatography. The reproducibility of the gradient retardation factor values of separated substance zones is satisfactory.