Intrastrand Photolesion Formation in Thio-Substituted DNA: A Case Study Including Single-Reference and Multireference Methods
| Autor: | Laura Gagliardi, Thais R. Scott, Eva Vos, Donald G. Truhlar, Inés Corral, Jesús González-Vázquez |
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| Rok vydání: | 2020 |
| Předmět: |
Thio
DNA Nucleobase chemistry.chemical_compound Cross-Linking Reagents chemistry Structural biology Pyrimidine Dimers Computational chemistry Excited state Potential energy surface Quantum Theory Density functional theory Sulfhydryl Compounds Complete active space Physical and Theoretical Chemistry DNA Damage |
| Zdroj: | The Journal of Physical Chemistry A. 124:10422-10433 |
| ISSN: | 1520-5215 1089-5639 |
| Popis: | The substitution of canonical nucleobases by thiated analogues in natural DNA has been exploited in pharmacology, photochemotherapy, and structural biology. Thionucleobases react with adjacent thymines leading to 6-4 pyrimidine-pyrimidone photoproducts (6-4PPs), which are a major source of DNA photodamage, in particular intrastrand cross-linked photolesions. Here, we study the mechanism responsible for the formation of 6-4PPs in thionucleobases by employing quantum-mechanical calculations. We use multiconfiguration pair-density functional theory, complete active space second-order perturbation theory, and Kohn-Sham density functional theory. Scrutinizing the photochemistry of thionucleobases can elucidate the reaction mechanism of these prodrugs and identify the role that triplet excited states play in the generation of photolesions in the natural biopolymer. Three different possible mechanisms to generate the 6-4PPs are presented, and we conclude that the use of multireference approaches is indispensable to capture important features of the potential energy surface. |
| Databáze: | OpenAIRE |
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