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https://hdl.handle.net/1959.11/56016
Title: | A high-level quantum chemical study of the thermodynamics associated with chlorine transfer between N-chlorinated nucleobases |
Contributor(s): | O'Reilly, Robert J (author) ; Karton, Amir (author) |
Publication Date: | 2023-06 |
Early Online Version: | 2023-05-12 |
DOI: | 10.1088/2516-1075/acd234 |
Handle Link: | https://hdl.handle.net/1959.11/56016 |
Abstract: | | The relative free energies of the isomers formed upon N-chlorination of each nitrogen atom within the DNA nucleobases (adenine, guanine, and thymine) have been obtained using the high-level G4(MP2) composite ab initio method (the free energies of the N-chlorinated isomers of cytosine have been reported at the same level of theory previously). Having identified the lowest energy N-chlorinated derivatives for each nucleobase, we have computed the free energies associated with chlorine transfer from N-chlorinated nucleobases to other unsubstituted bases. Our results provide quantitative support pertaining to the results of previous experimental studies, which demonstrated that rapid chlorine transfer occurs from N-chlorothymidine to cytidine or adenosine. The results of our calculations in the gas-phase reveal that chlorine transfer from N-chlorothymine to either cytosine, adenine, or guanine proceed via exergonic processes with ∆Go values of −50.3 (cytosine), −28.0 (guanine), and −6.7 (adenine) kJ mol–1. Additionally, we consider the effect of aqueous solvation by augmenting our gas-phase G4(MP2) energies with solvation corrections obtained using the conductor-like polarizable continuum model. In aqueous solution, we obtain the following G4(MP2) free energies associated with chlorine transfer from N-chlorothymine to the three other nucleobases: −58.4 (cytosine), −26.4 (adenine), and −18.7 (guanine) kJ mol–1. Therefore, our calculations, whether in the gas phase or in aqueous solution, clearly indicate that chlorine transfer from any of the N-chlorinated nucleobases to cytosine provides a thermodynamic sink for the active chlorine. This thermodynamic preference for chlorine transfer to cytidine may be particularly deleterious since previous experimental studies have shown that nitrogen-centered radical formation (via N–Cl bond homolysis) is more easily achieved in N-chlorinated cytidine than in other N-chlorinated nucleosides.
Publication Type: | Journal Article |
Source of Publication: | Electronic Structure, 5(2), p. 1-12 |
Publisher: | Institute of Physics Publishing Ltd |
Place of Publication: | United Kingdom |
ISSN: | 2516-1075 |
Fields of Research (FoR) 2020: | 340701 Computational chemistry |
Socio-Economic Objective (SEO) 2020: | 280120 Expanding knowledge in the physical sciences |
Peer Reviewed: | Yes |
HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
Appears in Collections: | Journal Article School of Science and Technology
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