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Formation of bifunctional cross-linked products due to reaction of NAMI-A with DNA bases – a DFT study

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Abstract

It is reported that NAMI-A and other Ru-anticancer complexes preferably bind with the N7 site of guanine and can also form DNA inter-strand cross-links. Therefore, in order to understand the DNA cross-link formation capability of NAMI-A, we have investigated here the structure and energetics of the reactions of the GN7-NAMI-A (a monofunctional adduct of NAMI-A with the N7 site of guanine) with the N3, N7, and O6 sites of guanine; the N1, N3, and N7 sites of adenine; the O2 and N3 sites of cytosine; and the O2 and O4 sites of thymine, using the M06-2X functional of density functional theory. It is found that the GN7-NAMI-A can form stable cross-linked products at all the sites studied here except at the N3 site of cytosine and O2 site of thymine. The calculated reaction free energies and reaction enthalpies indicate that the N3 site of adenine (AN3) and N7 site of guanine (GN7) are most exothermic among all the studied reactions. This study shows that NAMI-A would favorably form the cross-linked products involving the N7 site of guanine at one side and the N7 site of guanine or the N3 site of adenine at the other side.

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Acknowledgements

The authors acknowledge the general computational facility of the Department of Physics, Assam University, Silchar.

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  1. Department of Physics, Assam University, Silchar, Assam, 788 011, India

    Pramod Kumar Shah & Pradeep Kumar Shukla

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  1. Pramod Kumar Shah
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Contributions

P. K. Shah: performing simulation, data collection, and partial contribution to the first draft of the manuscript. P.K. Shukla: planning and supervision of the research work, analysis of the results, and writing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Pradeep Kumar Shukla.

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Shah, P.K., Shukla, P.K. Formation of bifunctional cross-linked products due to reaction of NAMI-A with DNA bases – a DFT study. Struct Chem 33, 807–814 (2022). https://doi.org/10.1007/s11224-022-01897-0

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