Issue 41, 2015

Increase in the photoreactivity of uracil derivatives by doubling thionation

Abstract

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.

Graphical abstract: Increase in the photoreactivity of uracil derivatives by doubling thionation

Supplementary files

Article information

Article type
Paper
Submitted
13 Aug 2015
Accepted
28 Sep 2015
First published
28 Sep 2015

Phys. Chem. Chem. Phys., 2015,17, 27851-27861

Author version available

Increase in the photoreactivity of uracil derivatives by doubling thionation

M. Pollum, S. Jockusch and C. E. Crespo-Hernández, Phys. Chem. Chem. Phys., 2015, 17, 27851 DOI: 10.1039/C5CP04822B

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