Theoretical and Experimental Evaluation of the Electronic Relaxation Mechanisms of 2-Pyrimidinone: The Primary UVA Absorbing Moiety of the DNA and RNA (6–4) Photolesion

Authors

Sean J. Hoehn, Case Western Reserve University
Sarah E. Krul, Case Western Reserve University
Carlos E. Crespo-Hernández, Case Western Reserve UniversityFollow

Document Type

Article

Publication Date

7-1-2024

Abstract

The (6–4) photolesion is a key photodamage that occurs when two adjacent pyrimidine bases in a DNA strand bond together. To better understand how the absorption of UVB and UVA radiation by the 2-pyrimidinone moiety in a (6–4) lesion can damage DNA, it is important to study the electronic deactivation mechanism of its 2-pyrimidinone chromophore. This study employs theoretical (MS-CASPT2/cc-pVDZ level) and experimental (steady state and femtosecond broadband spectroscopic) methods to elucidate the photochemical relaxation mechanisms of 2-(1H)-pyrimidinone and 1-methyl-2-(1H)-pyrimidinone in aqueous solution (pH 7.4). In short, excitation at 320 nm leads to the population of the S1¹(ππ*) state with excess vibrational energy, which relaxes to the S1¹(ππ*) minimum in one picosecond or less. A trifurcation event in the S1¹(ππ*) minimum ensued, leading to radiative and nonradiative decay of the population to the ground state or the population of the long-lived and reactive T1³(ππ*) state in hundreds of picoseconds. Collectively, the theoretical and experimental results support the idea that in DNA and RNA, the T1³(ππ*) state of the 2-pyrimidinone moiety in the (6–4) lesion can further participate in photosensitized chemical reactions increasing DNA and RNA damage.

Keywords

(6–4) photolesion, DNA and RNA photodamage, excited state dynamics, modified nucleobases, multiconfigurational calculations

Language

English

Publication Title

Chemphotochem

Grant

MIS‐IMAGINE

Rights

© 2024 The Author(s). ChemPhotoChem published by Wiley-VCH GmbH. This is an open access work distributed under the terms of the Creative Commons Attribution-Non-Commercial (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

D. Valverde, S. J. Hoehn, E. D. Koyanagui, S. E. Krul, C. E. Crespo-Hernández, A. C. Borin. Theoretical and Experimental Evaluation of the Electronic Relaxation Mechanisms of 2-Pyrimidinone: The Primary UVA Absorbing Moiety of the DNA and RNA (6–4) Photolesion. ChemPhotoChem 2024, 8, e202400070. https://doi.org/10.1002/cptc.202400070