title: Oxidation of a guanine derivative coordinated to a Pt(IV) complex initiated by intermolecular nucleophilic attacks.
abstract: In this study we report that fac-[Pt(IV)(dach)(9-EtG)Cl(3)](+) (dach = d,l-1,2-diaminocyclohexane, 9-EtG = 9-ethylguanine) in high pH (pH 12) or phosphate solution (pH 7.4) produces 8-oxo-9-EtG and Pt(II) species. The reaction in H(2)(18)O revealed that the oxygen atom in hydroxide or phosphate ends up at the C8 position of 8-oxo-G. The kinetics of the redox reaction was first order with respect to both Pt(IV)-G and free nucleophiles (OH(-) and phosphate). The oxidation of G initiated by hydroxide was approximately 30∼50 times faster than by phosphate in 100 mM NaCl solutions. The large entropy of activation of OH(-1) (ΔS(‡) = 26.6 ± 4.3 J mol(-1) K(-1)) due to the smaller size of OH(-) is interpreted to be responsible for the faster kinetics compared to phosphate (ΔS(‡) = -195.5 ± 11.1 J mol(-1) K(-1)). The enthalpy of activation for phosphate reaction is more favorable relative to the OH(-) reaction (ΔH(‡) = 35.4 ± 3.5 kJ mol(-1) for phosphate vs. 96.6 ± 11.4 kJ mol(-1) for OH(-1)). The kinetic isotope effect of H8 was determined to be 7.2 ± 0.2. The rate law, kinetic isotope effect, and isotopic labeling are consistent with a mechanism involving proton ionization at the C8 position as the rate determining step followed by two-electron transfer from G to Pt(IV).
authors.affiliation: Department of Chemistry and Biochemistry, Middlebury College, Middlebury, Vermont 05753, USA. choi@middlebury.edu
authors.forename: Sunhee
authors.initials: S
authors.lastname: Choi
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Personick
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bogart
authors.forename: DaWeon
authors.initials: D
authors.lastname: Ryu
authors.forename: Romany M
authors.initials: RM
authors.lastname: Redman
authors.forename: Edith
authors.initials: E
authors.lastname: Laryea-Walker
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
chemical_list: D056831:Coordination Complexes; D010984:Platinum; D006147:Guanine; C014542:9-ethylguanine; D010100:Oxygen