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Density functional theory studies on the oxidation of 5'-dGMP and 5'-dAMP by a platinum(IV) complex

journal contribution
posted on 2023-05-17, 15:05 authored by Alireza AriafardAlireza Ariafard, Tabatabaie, ES, Aghmasheh, S, Najaflo, S, Brian YatesBrian Yates
Density functional theory has been used to investigate the oxidation of a guanine nucleotide by platinum(IV), a process that can be important in the degradation of DNA. For the first time, we have provided a comprehensive mechanism for all of the steps in this process. A number of intermediates are predicted to occur but with short lifetimes that would make them difficult to observe experimentally. A key step in the mechanism is electron transfer from guanine to platinum(IV), and we show that this is driven by the loss of a chloride ligand from the platinum complex after nucleophilic attack of 5'-phosphate to C8 of guanine. We have investigated several different initial platinum(IV) guanine adducts and shown that the adduct formed from replacement of an axial chlorine ligand in the platinum(IV) complex undergoes oxidation more easily. We have studied adenine versus guanine adducts, and our results show that oxidation of the former is more difficult because of disruption of the aromatic π system that occurs during the process. Finally, our results show that the acidic hydrolysis step to form the final oxidized product occurs readily via an initial protonation of N7 of the guanine.

History

Publication title

Inorganic Chemistry

Volume

51

Issue

15

Pagination

8002-8013

ISSN

0020-1669

Department/School

School of Natural Sciences

Publisher

Amer Chemical Soc

Place of publication

1155 16Th St, Nw, Washington, USA, Dc, 20036

Rights statement

Copyright 2012 American Chemical Society

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the chemical sciences

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