Document Type
Article
Publication Date
7-25-2023
Abstract
All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen, and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4-d]pyrimidin-4(1H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(3H)-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions. It is demonstrated that thieno[3,4-d]pyrimidin-4(3H)-thione efficiently populates the long-lived and reactive triplet state generating singlet oxygen with a quantum yield of about 80% independent of solvent. It is further shown that thieno[3,4-d]pyrimidin-4(3H)-thione exhibits high photodynamic efficacy against monolayer melanoma cells and cervical cancer cells both under normoxic and hypoxic conditions. Our combined spectroscopic, computational, and in vitro data demonstrate the excellent potential of thieno[3,4-d]pyrimidin-4(1H)-thione as a heavy-atom-free PDT agent and paves the way for further development of photosensitizers based on the thionation of thieno[3,4-d]pyrimidine derivatives. Collectively, the experimental and computational results demonstrate that thieno[3,4-d]pyrimidine-4(3H)-thione stands out as the most promising thiobase photosensitizer developed to this date.
Language
English
Publication Title
Chemical Science
Grant
CHE-1800052
Rights
© The Author(s). This is an open access work distributed under the terms of the Creative Commons Attribution-Non-Commercial (https://creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Recommended Citation
Ortiz-Rodríguez, L. A., Fang, Y. G., Niogret, G., Hadidi, K., Hoehn, S. J., Folkwein, H. J., ... & Crespo-Hernández, C. E. (2023). Thieno [3, 4-d] pyrimidin-4 (3 H)-thione: an effective, oxygenation independent, heavy-atom-free photosensitizer for cancer cells. Chem. Sci., 2023,14, 8831-8841
Manuscript Version
Final Publisher Version