Kinetics of the substitution reactions of some Pt(II) complexes with 5′-GMP and L -histidine

Abstract

The reactions of platinum(II) complexes, [PtCl 2 (dach)] (dach = (1R,2R)-1,2-diaminocyclohexane) and [PtCl 2 (en)] (en = ethylenediamine) with biologically relevant ligands such as 5 -GMP (guanosine-5 -monophosphate) and L-His (L-histidine) were studied by UVvis spectrophotometry, 1 H NMR spectroscopy, and high-performance liquid chromatography (HPLC). Spectrophotometrically, these reactions were investigated under pseudo-first-order conditions at 310 K in 25 mM Hepes buffer (pH 7.2) and 10 mM NaCl to prevent the hydrolysis of the complexes. The [PtCl 2 (en)] complex reacts faster than [PtCl 2 (dach)] in the reaction with studied nucleophiles. This confirms the fact that the reactivity of studied Pt(II) complexes depends on the structure of the inert bidentate ligand. Also, the substitution reactions with L-His are always faster than the reactions with nucleotide 5 -GMP. The reactions of [PtCl 2 (dach)] and [PtCl 2 (en)] complexes with L-histidine are studied by 1 H NMR spectroscopy. The obtained rate constants are in agreement with those obtained by UV-vis. The same reactions were studied by HPLC comparing the obtained chromatograms during the reaction. The changes in intensity of signals of the free and coordinated ligand show that after a few days there is only one dominant product in the system. C

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“…5′-GMP can coordinate to metal ions through N1 and N7 atoms, but only bind through the N7 position at pH 7.2 cause the N1 atom is protonated (pKa (N1) = 9.3) in this medium [35]. For our sample system, in which the pH had been adjusted to 7.3, the coordination of 5′-GMP to platinum occurred via N7 position.…”

“…To further understand the intrinsic reactivity of our synthesized sugar conjugated platinum complexes with DNA, the kinetic study of platinum complexes with 5′-Guanosine Monophosphate (5′-GMP) implementing 1 H NMR analysis was performed to mimic the platinum(II)-DNA adduct formation. 5′-GMP can coordinate to metal ions through N1 and N7 atoms, but only bind through the N7 position at pH 7.2 cause the N1 atom is protonated (pKa (N1) = 9.3) in this medium [ 35 ]. For our sample system, in which the pH had been adjusted to 7.3, the coordination of 5′-GMP to platinum occurred via N7 position.…”

“…It is well known that 5′-GMP can coordinate to metal ions through the N1 and N7 positions, but only bind through the N7 position in a neutral medium [35]. Therefore, nucleophilic substitution reaction with 5′-GMP occurs at the N7 atom of purine base.…”

“…With the aim to understand the intrinsic reactivity of the interactions of platinum complexes with N-bonding ligands, we investigated the complex-formation kinetics of 5a, 5b, 5c with nitrogen donor ligands 5′-GMP implementing 1 H NMR analysis to mimic the Pt(II)-DNA adduct formation and compared to that of oxaliplatin. It is well known that 5′-GMP can coordinate to metal ions through the N1 and N7 positions, but only bind through the N7 position in a neutral medium [ 35 ]. Therefore, nucleophilic substitution reaction with 5′-GMP occurs at the N7 atom of purine base.…”