Excited-State Dynamics in 6-Thioguanosine from the Femtosecond to Microsecond Time Scale
Abstract
Patients treated with the immunosuppressant and anticancer drugs 6-thioguanine, azathioprine, or mercaptopurine can metabolize and incorporate them in DNA as 6-thioguanosine. The skin of these patients is sensitive to UVA radiation, and long-term treatment can result in extremely high incidence of sunlight-induced skin cancer. In this contribution the photophysics of 6-thioguanosine have been studied in aqueous buffer solution and in acetonitrile after excitation with UVA light to provide mechanistic insights about the origin of its phototoxicity. It is shown that most of the initial excited-state population in the S(2)(ππ*, L(a)) state decays by ultrafast intersystem crossing to the triplet manifold. A triplet quantum yield of 0.8 ± 0.2 is determined in aqueous buffer solution. A minor fraction of the S(2) population bifurcates on an ultrafast time scale to populate the S(1)(n(S)π*) state, which decays back to the ground state in tens of picoseconds. Quantum-chemical calculations that include solvent effects support the experimental results. The high triplet yield of 6-thioguanosine, which we argue can result in photosensitization of molecular oxygen and photooxidative DNA damage, is proposed to explain the high phototoxicity exhibited by these pro-drugs in patients upon sunlight exposure. Finally, the experimental and computational results for 6-thioguanosine are compared with those reported for the DNA/RNA guanine monomers.
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The singlet excited state of 6-TG is converted efficiently by very fast intersystem crossing into the triplet manifold.
“In agreement with quantum chemical calculations, it was found that the singlet excited state of the base was converted efficiently by very fast intersystem crossing into the triplet manifold.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [210]
The high triplet quantum yield of 6-TG (ΦT = 0.8 ± 0.2) likely favors energy transfer to O2 and generation of singlet oxygen.
“The high triplet quantum yield value (F T = 0.8 ± 0.2) is likely to favor energy transfer to O 2 and therefore the generation of 1 O 2 (210).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [210]
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Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup>
Cadet, J., Mouret, S., Ravanat, J., & Douki, T. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01200.x · Cited by 300 · see citing works
- Authors
- Reichardt, C., Guo, C., & Crespo-Hernández, C. E.
- Affiliations
- Case Western Reserve University (US)
- Department of Chemistry and the Center for Chemical Dynamics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States
- ORCID
- Reichardt, Christian
- Venue
- The Journal of Physical Chemistry B
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-03-08
- Volume
- 115
- Issue
- 12
- Pages
- 3263-3270
- ISSN
- 1520-5207 (ISSN-L)
- 1520-6106
- OpenAlex
- W2020640998
- Cited by
- 109
- References
- 67
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 12 · 2017: 16 · 2016: 11 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Physical Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Spectroscopy and Quantum Chemical Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- 6-thioguanosine, excited-state dynamics, intersystem crossing, triplet state, photodynamic DNA damage, photosensitization, molecular oxygen, 6-thioguanine, azathioprine, 6-mercaptopurine, photoproducts, solvent effects
- MeSH terms
- Absorption, Acetonitriles, Buffers, DNA, DNA Damage, Electrons, Guanosine, Models, Molecular, Molecular Conformation, Solutions, Thionucleosides, Time Factors, Ultraviolet Rays, Water, Cell Death, Photosensitizing Agents
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