Density functional theory studies on the oxidation of 5'-dGMP and 5'-dAMP by a platinum(IV) complex.
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.
Department of Chemistry, Faculty of Science, Central Tehran Branch, Islamic Azad University, Shahrak Gharb, Tehran, Iran. ariafard@yahoo.com
Alireza
A
Ariafard
Elham S
ES
Tabatabaie
Simin
S
Aghmasheh
Sahar
S
Najaflo
Brian F
BF
Yates
D053938:DNA Fragmentation; D003838:Deoxyadenine Nucleotides / Q000737:chemistry*; D003848:Deoxyguanine Nucleotides / Q000737:chemistry*; D004579:Electron Transport; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory
D003838:Deoxyadenine Nucleotides; D003848:Deoxyguanine Nucleotides; D008024:Ligands; D011522:Protons; D010984:Platinum; C012873:2'-deoxy-5'-adenosine monophosphate; C007257:2'-deoxyguanosine 5'-phosphate