Abstract
Thione-containing nucleobases have attracted the attention of the scientific community for their application in oncology, virology, and transplantology. The detailed understanding of the reactivity of the purine derivative 8-thioguanosine (8-TG) with reactive oxygen species (ROS) and free radicals is crucial for its biological relevance. An extensive investigation on the fate of 8-TG under both reductive and oxidative conditions is here reported, and it was tested by employing steady-state photooxidation, laser flash photolysis, as well as γ-radiolysis in aqueous solutions. The characterization of the 8-TG T1 excited state by laser flash photolysis and the photooxidation experiments confirmed that singlet oxygen is a crucial intermediate in the formation of the unexpected reduced product guanosine, without the formation of the usual oxygenated sulfinic or sulfonic acids. Furthermore, a thorough screening of different radiolytic conditions upon γ-radiation afforded the reduced product. These results were rationalized by performing control experiments in the predominant presence of each reactive species formed by radiolysis of water, and the mechanistic pathway scenario was postulated on these bases.
Highlights
The search for new purine and pyrimidine derivatives of biological significance has been conducted by many research groups [1,2]
The characterization of the 8-TG T1 excited state by laser flash photolysis and the photooxidation experiments confirmed that singlet oxygen is a crucial intermediate in the formation of the unexpected reduced product guanosine, without the formation of the usual oxygenated sulfinic or sulfonic acids
Considering what has been previously described for 6-TG and the proposed mechanism hypothesized for thiourea in the presence of singlet oxygen [22], we propose that a similar [2 + 2] attack of 1 O2 on the thione moiety would lead to a thioperoxyl radical via
Summary
The search for new purine and pyrimidine derivatives of biological significance has been conducted by many research groups [1,2]. The analogues of purine bases of nucleic acids containing a sulfur atom, such as mercaptopurine, 6-thioguanine, or azathioprine, have been applied in medicine for many years in the treatments of cancer, in particular leukemia in children, viral diseases, and in transplantology [3,4,5]. A small structural modification involving the attachment of a thione group to the purine ring system results in a decrease in energy of the electronic excited states, leading to absorption of long-wavelength light, including the UV-A range [8]. Thio-derivatives of guanine present in the chains of nucleic acids can take part in photochemical transformations or at least can initiate them
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