Oxidation of the Platinum(II) Anticancer Agent [Pt{(p-BrC(6)F(4))NCH(2)CH(2)NEt(2)}Cl(py)] to Platinum(IV) Complexes by Hydrogen Peroxide

Pt(IV) coordination complexes are of interest as prodrugs of Pt(II) anticancer agents, as they can avoid deactivation pathways owing to their inert nature. Here, we report the oxidation of the antitumor agent [Pt(II)(p-BrC(6)F(4))NCH(2)CH(2)NEt(2)}Cl(py)], 1 (py = pyridine) to dihydroxidoplatinum(IV) solvate complexes [Pt(IV){(p-BrC(6)F(4))NCH(2)CH(2)NEt(2)}Cl(OH)(2)(py)].H(2)O, 2·H(2)O with hydrogen peroxide (H(2)O(2)) at room temperature. To optimize the yield, 1 was oxidized in the presence of added lithium chloride with H(2)O(2) in a 1:2 ratio of Pt: H(2)O(2,) in CH(2)Cl(2) producing complex 2·H(2)O in higher yields in both gold and red forms. Despite the color difference, red and yellow 2·H(2)O have the same structure as determined by single-crystal and X-ray powder diffraction, namely, an octahedral ligand array with a chelating organoamide, pyridine and chloride ligands in the equatorial plane, and axial hydroxido ligands. When tetrabutylammonium chloride was used as a chloride source, in CH(2)Cl(2), another solvate, [Pt(IV){(p-BrC(6)F(4))NCH(2)CH(2)NEt(2)}Cl(OH)(2)(py)].0.5CH(2)Cl(2,) 3·0.5CH(2)Cl(2), was obtained. These Pt(IV) compounds show reductive dehydration into Pt(II) [Pt{(p-BrC(6)F(4))NCH=CHNEt(2)}Cl(py)], 1H over time in the solid state, as determined by X-ray powder diffraction, and in solution, as determined by (1)H and (19)F NMR spectroscopy and mass spectrometry. 1H contains an oxidized coordinating ligand and was previously obtained by oxidation of 1 under more vigorous conditions. Experimental data suggest that oxidation of the ligand is favored in the presence of excess H(2)O(2) and elevated temperatures. In contrast, a smaller amount (1Pt:2H(2)O(2)) of H(2)O(2) at room temperature favors the oxidation of the metal and yields platinum(IV) complexes.