The Ultraviolet Absorption Spectra of Thiouracils1

Elion, Gertrude B.; Ide, Walter S.; Hitchings, George H.

doi:10.1021/ja01215a004

Cited by 32 publications

(14 citation statements)

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“…These observations are in agreement with those reported in the early literature. 43,44 Measurement of intersystem crossing rates, triplet yields, and rates of triplet-state decay Femtosecond to microsecond broadband transient absorption spectroscopy was used to measure the rates of intersystem crossing to the triplet manifold, the triplet yields, and the rates of triplet-state decay back to the ground state. The triplet state of the thiouracil derivatives can be selectively probed at wavelengths longer than 600 nm without the interference of other transient absorption species.…”

Section: Steady-state Absorption Spectramentioning

confidence: 99%

Increase in the photoreactivity of uracil derivatives by doubling thionation

Pollum

Jockusch

Crespo‐Hernández

2015

Phys. Chem. Chem. Phys.

101

193

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The ability of 4-thiouracil to strongly absorb UVA radiation and to populate a reactive triplet state in high yield has enabled its use as a versatile photocrosslinker for nearly 50 years. In this contribution, we present a detailed spectroscopic and photochemical investigation of the 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil series in an effort to further advance this chemistry and to scrutinize the photoreactivity of 2,4-dithiouracil. Our results reveal that excitation of 2,4-dithiouracil leads to intersystem crossing to the triplet manifold in 220 ± 40 fs, which enables the population of the reactive triplet state with near unity yield (ΦT = 0.90 ± 0.15) and ultimately leads to a ca. 50% singlet oxygen generation (ΦΔ = 0.49 ± 0.02)-one of the highest singlet oxygen yields reported to date for a photoexcited thiobase. In addition, the long-lived triplet state of 2,4-dithiouracil reacts efficiently with the nucleic acid base adenine 5'-monophosphate through a direct, oxygen-independent photocycloaddition mechanism and at a rate that is at least 3-fold faster than that of 4-thiouracil under equal conditions. The new physico-chemical insights reported for these RNA-thiobase derivatives are compared to those of the DNA and RNA bases and the DNA-thiobase derivatives. Furthermore, the strong near-visible absorption and increased photoreactivity measured for 2,4-dithiouracil lays a solid foundation for developing RNA-targeted photocrosslinking and phototherapeutic agents that are more effective than those currently available.

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Section: Steady-state Absorption Spectramentioning

confidence: 99%

Increase in the photoreactivity of uracil derivatives by doubling thionation

Pollum

Jockusch

Crespo‐Hernández

2015

Phys. Chem. Chem. Phys.

101

193

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“…Interestingly, one of these naturally occurring tRNA thiopyrimidine derivatives, 4‐thiouracil, was found to be responsible for the photo‐induced growth delay of E. coli by ultraviolet‐A radiation (UVA: 320–400 nm) . Sulfur substitution of uridine to generate 4‐thiouridine drastically shifts the absorption spectrum causing 4‐thiouridine to efficiently absorb UVA radiation (Scheme 2), contrary to the canonical uridine that only absorbs efficiently in the UVC (100–280 nm) and UVB (280–320 nm) regions of the electromagnetic spectrum . More importantly, sulfur substitution also makes 4‐thiouridine significantly more photoreactive than the canonical nucleosides (Scheme 3), readily initiating crosslinking reactions or generating Type I and Type II reactive oxygen species following light activation .…”

Section: Introductionmentioning

confidence: 99%

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

Ashwood

Pollum

Crespo‐Hernández

2018

Photochem & Photobiology

115

132

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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.

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“…The structure was determined by comparing the ultraviolet absorption spectrum of the thiation product with that reported for 4-mercapto-2(1H)-pyrimidinone. 18…”

Section: Thiation Of Uracilmentioning

confidence: 99%