Orientation-dependent quenching of the triplet excited 6-thiopurine by nucleobases

Wenska, G.; Filipiak, Piotr; Taras-Goślińska, Katarzyna; Sobierajska, A.; Gdaniec, Zofia

doi:10.1016/j.jphotochem.2010.09.018

Cited by 9 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The self-quenching constants depend on the viscosity of the solvent, suggesting they are close to the diffusion-controlled limit [195]. Similar results were obtained more recently for 6-thiopurine [208] and 9-propyl-6-thiopurine [21] upon nanosecond laser excitation at 355 nm in aqueous buffer solution at pH 5.8. Attempts to determine the intersystem crossing rate constant of 6-thiopurine by using picosecond transient absorption spectroscopy (35 ps pulse duration) were unsuccessful [195] and the authors concluded that it must have a value greater than 1.3 Â 10 10 s À1 .…”

Section: Excited-state Deactivation Mechanism In 6-thiopurine Derivatsupporting

confidence: 87%

Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution

Pollum

Martínez‐Fernández

Crespo‐Hernández

2014

Topics in Current Chemistry

114

200

View full text Add to dashboard Cite

The steady-state and time-resolved photochemistry of the natural nucleic acid bases and their sulfur- and nitrogen-substituted analogues in solution is reviewed. Emphasis is given to the experimental studies performed over the last 3-5 years that showcase topical areas of scientific inquiry and those that require further scrutiny. Significant progress has been made toward mapping the radiative and nonradiative decay pathways of nucleic acid bases. There is a consensus that ultrafast internal conversion to the ground state is the primary relaxation pathway in the nucleic acid bases, whereas the mechanism of this relaxation and the level of participation of the (1)πσ*, (1) nπ*, and (3)ππ* states are still matters of debate. Although impressive research has been performed in recent years, the microscopic mechanism(s) by which the nucleic acid bases dissipate excess vibrational energy to their environment, and the role of the N-glycosidic group in this and in other nonradiative decay pathways, are still poorly understood. The simple replacement of a single atom in a nucleobase with a sulfur or nitrogen atom severely restricts access to the conical intersections responsible for the intrinsic internal conversion pathways to the ground state in the nucleic acid bases. It also enhances access to ultrafast and efficient inter-system crossing pathways that populate the triplet manifold in yields close to unity. Determining the coupled nuclear and electronic pathways responsible for the significantly different photochemistry in these nucleic acid base analogues serves as a convenient platform to examine the current state of knowledge regarding the photodynamic properties of the DNA and RNA bases from both experimental and computational perspectives. Further investigations should also aid in forecasting the prospective use of sulfur- and nitrogen-substituted base analogues in photochemotherapeutic applications.

show abstract

Section: Excited-state Deactivation Mechanism In 6-thiopurine Derivatsupporting

confidence: 87%

Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution

Pollum

Martínez‐Fernández

Crespo‐Hernández

2014

Topics in Current Chemistry

114

200

View full text Add to dashboard Cite

show abstract

“…It is currently thought that 6‐thio‐2′‐deoxyguanosine incorporated into DNA is most responsible for inducing oxidatively generated damage within the cell following thiopurine treatment , but the mechanism by which 6‐thio‐2′‐deoxyguanosine induces damage is still debated . Earlier investigations reported singlet oxygen quantum yields of ca.…”

Section: Clinical Relevance and Applications Of Thiobasesmentioning

confidence: 99%

“…These side effects are due to a slow buildup of thiopurine prodrugs within the DNA of normal, nonmalignant cells during long-term treatments, and to the similar UVA-photosensitizing properties of the thiopurine derivatives as those of the thiopyrimidine derivatives, resulting in DNA damage. Currently, however, the primary photosensitization mechanism of the thiopurine derivatives is a matter of debate (6,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). It is necessary to understand whether the observed photoinduced side effects are due primarily to photocrosslinking and photocycloaddition reactions or to the generation of reactive oxygen species in order to mitigate the damage.…”

Section: Introductionmentioning

confidence: 99%

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Ashwood

Pollum

Crespo‐Hernández

2018

Photochem & Photobiology

115

132

View full text Add to dashboard Cite

Sulfur-substituted nucleobases (a.k.a., thiobases) are among the world's leading prescriptions for chemotherapy and immunosuppression. Long-term treatment with azathioprine, 6-mercaptopurine and 6-thioguanine has been correlated with the photoinduced formation of carcinomas. Establishing an in-depth understanding of the photochemical properties of these prodrugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, a basis for developing effective compounds for targeted phototherapy. In this review, a broad examination is undertaken, surveying the basic photochemical properties and excited-state dynamics of sulfur-substituted analogs of the canonical DNA and RNA nucleobases. A molecular-level understanding of how sulfur substitution so remarkably perturbs the photochemical properties of the nucleobases is presented by combining experimental results with quantum-chemical calculations. Structure-property relationships demonstrate the impact of site-specific sulfur substitution on the photochemical properties, particularly on the population of the reactive triplet state. The value of fundamental photochemical investigations for driving the development of ultraviolet-A chemotherapeutics is showcased. The most promising photodynamic agents identified thus far have been investigated in various carcinoma cell lines and shown to decrease cell proliferation upon exposure to ultraviolet-A radiation. Overarching principles have been elucidated for the impact that sulfur substitution of the carbonyl oxygen has on the photochemical properties of the nucleobases.

show abstract

“…2). Experiments with model mercaptopurine‐containing compounds indicate that UVA can induce covalent attachment between the thionucleobase and thymine or uracil (30,31). Interestingly, UVA irradiation of aqueous thioinosine in the presence or absence of an excess of adenosine generates substituted formylaminopyrimidine photoaddition products in which one of the imidazole rings is cleaved (32) (Fig.…”

Section: ‐Tg/uva‐induced Lesionsmentioning

confidence: 99%

“…Plausible mechanisms exist for the formation of ICL between 6‐TG and a nearby thymine or adenine on the opposite strand (Fig. 2; 30–32). ICL formation may involve the generation of thiyl radicals in a Type I photosensitization and subsequent reactions with nucleobase amino groups as observed for guanine radical cations (34).…”

Section: ‐Tg/uva‐induced Lesionsmentioning

confidence: 99%

Multiple forms of DNA Damage Caused by UVA Photoactivation of DNA 6‐Thioguanine

Brem

Karran

2011

Photochem & Photobiology

View full text Add to dashboard Cite

Thiopurines are prescribed frequently as medication for cancer and for inflammatory disorders. One of them, azathioprine, has been the immunosuppressant of choice for organ transplant recipients for many years. Thiopurine use is associated with elevated sun sensitivity and skin cancer risk. Skin sensitization is selective for UVA. 6-TG integrates into DNA and unlike the canonical DNA bases, it is a strong UVA chromophore with an absorbance maximum at 342 nm. DNA 6-TG is a photosensitizer and a source of reactive oxygen species. Reactive oxygen that is generated from the photochemical activation of DNA 6-TG causes extensive damage to DNA and proteins. This damage is mutagenic and extremely toxic to cultured human cells. Here we describe some of the lesions that are known to be generated from UVA irradiation of DNA 6-TG. We discuss how this photochemical damage might contribute to the toxic effect of thiopurine ⁄ UVA treatment on cultured cells and to the high risk of skin cancer in thiopurine-treated patients.

show abstract

Orientation-dependent quenching of the triplet excited 6-thiopurine by nucleobases

Cited by 9 publications

References 26 publications

Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution

Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Multiple forms of DNA Damage Caused by UVA Photoactivation of DNA 6‐Thioguanine

Contact Info

Product

Resources

About