Low-Temperature Photosensitized Oxidation of a Guanosine Derivative and Formation of an Imidazole Ring-Opened Product
Abstract
An organic-soluble guanosine derivative, 2',3',5'-O-(tert-butyldimethylsilyl)guanosine (1), was prepared and its photosensitized oxidation was carried out in several solvents at various temperatures. Singlet oxygen is the reactive oxidizing agent responsible for this reaction. Neither an endoperoxide nor a dioxetane intermediate was detected by low-temperature NMR even at -78 degrees C. A product (A) with an oxidized imidazole ring was the only major product detected at room temperature; this compound could be isolated by low-temperature column chromatography and was characterized by (1)H and (13)C and mass spectroscopy. CO(2) was the other major product. A small amount of the corresponding 8-oxo-7,8-dihydroguanosine derivative B was detected during the initial stage of the photooxidation and was shown to be intermediate in the formation of two products of extensive degradation, C and D. Reaction of 1 with the singlet oxygen analogues 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) gave products consistent with a proposed mechanism involving the rearrangement of an initially formed endoperoxide to give A and B from reaction of 1 with singlet oxygen.
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The endoperoxide intermediate rearranges quantitatively within double-stranded DNA into 8-hydroxyperoxyguanine, which is further reduced to 8-oxoGua, the exclusive singlet oxygen oxidation product.
“The latter intermediate quantitatively rearranges within ds DNA into 8-hydroxyperoxyguanine (39,99) that is further reduced into 8-oxoGua (Fig. 5), the exclusive 1 O 2 oxidation product (39,100,101).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [99]
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- Authors
- Sheu, C., Kang, P., Khan, S., & Foote, C. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Foote, Christopher S.
- ORCID
- Khan, Saeed
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2002-03-22
- Volume
- 124
- Issue
- 15
- Pages
- 3905-3913
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2040546412
- Cited by
- 78
- References
- 48
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 6 · 2014: 4 · 2013: 2 · 2012: 6
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (8f31gm020081-04)
- National Institute of General Medical Sciences (GM-20081)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Chemical Reactions and Mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Oxidative Organic Chemistry Reactions
- Keywords
- photosensitized oxidation, guanosine derivatives, singlet oxygen, imidazole ring opening, 8-oxo-7,8-dihydroguanosine, low-temperature NMR, photooxidation mechanism
- MeSH terms
- Cold Temperature, Guanosine, Imidazoles, Kinetics, Models, Molecular, Oxidation-Reduction, Photochemistry, Stereoisomerism, Reactive Oxygen Species, Organosilicon Compounds, Nuclear Magnetic Resonance, Biomolecular
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