caa a22 4500 605507619 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00775-015-1312-0 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1312-0 Oxidation of 5′-dGMP, 5′-dGDP, and 5′-dGTP by a platinum(IV) complex [Elektronische Daten] [Ioannis Kipouros, Sebastian Fica-Contreras, Gregory Bowe, Sunhee Choi] We previously reported that a Pt(IV) complex, [PtIV(dach)Cl4] [trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum(IV)] binds to the N7 of 5′-dGMP (deoxyguanosine-5′-monophosphate) at a relatively fast rate and oxidizes it to 8-oxo-5′-dGMP. Here, we further studied the kinetics of the oxidation of 5′-dGMP by the PtIV complex. The electron transfer rate constants between 5′-dGMP and PtIV in [H8-5′-dGMP-PtIV] and [D8-5′-dGMP-PtIV] were similar, giving a small value of the kinetic isotope effect (KIE: 1.2±0.2). This small KIE indicates that the deprotonation of H8 in [H8-5′-dGMP-PtIV] is not involved in the rate-determining step in the electron transfer between guanine (G) and PtIV. We also studied the reaction of 5′-dGDP (deoxyguanosine-5′-diphosphate) and 5′-dGTP (deoxyguanosine-5′-triphosphate) with the PtIV complex. Our results showed that [PtIV(dach)Cl4] oxidized 5′-dGDP and 5′-dGTP to 8-oxo-5′-dGDP and 8-oxo-5′-dGTP, respectively, by the same mechanism and kinetics as for 5′-dGMP. The PtIV complex binds to N7 followed by a two-electron inner sphere electron transfer from G to PtIV. The reaction was catalyzed by PtII and occurred faster at higher pH. The electron transfer was initiated by either an intramolecular nucleophilic attack by any of the phosphate groups or an intermolecular nucleophilic attack by free OH− in the solution. The rates of reactions for the three nucleotides followed the order: 5′-dGMP>5′-dGDP>5′-dGTP, indicating that the bulkier the phosphate groups are, the slower the reaction is, due to the larger steric hindrance and rotational barrier of the phosphate groups. SBIC, 2015 Oxidation nationallicence 5′-dGMP nationallicence 5′-dGDP nationallicence 5′-dGTP nationallicence Platinum(IV) complex nationallicence Kipouros Ioannis Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut Fica-Contreras Sebastian Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut Bowe Gregory Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut Choi Sunhee Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1327-1341 0949-8257 20:8<1327 2015 20 775 https://doi.org/10.1007/s00775-015-1312-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1312-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kipouros Ioannis Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut NATIONALLICENCE 700 1- Fica-Contreras Sebastian Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut NATIONALLICENCE 700 1- Bowe Gregory Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut NATIONALLICENCE 700 1- Choi Sunhee Department of Chemistry and Biochemistry, Middlebury College, 05753, Middlebury, VT, USA aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1327-1341 0949-8257 20:8<1327 2015 20 775