Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

Abstract

The synthesis, characterization, and cytotoxicity of eight new platinum(IV) complexes having the general formula cis,cis,trans-[Pt(NH[subscript 3)[subscript 2]Cl[subscript 2](O[subscript 2]CNHR)[subscript 2]] are reported, where R = tert-butyl (4), cyclopentyl (5), cyclohexyl (6), phenyl (7), p-tolyl (8), p-anisole (9), 4-fluorophenyl (10), or 1-naphthyl (11). These compounds were synthesized by reacting organic isocyanates with the platinum(IV) complex cis,cis,trans-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](OH)[subscript 2]]. The electrochemistry of the compounds was investigated by cyclic voltammetry. The aryl carbamate complexes 7−11 exhibit reduction peak potentials near −720 mV vs Ag/AgCl, whereas the alkyl carbamate complexes display reduction peak potentials between −820 and −850 mV vs Ag/AgCl. The cyclic voltammograms of cis,cis,trans-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](O[subscript 2]CCH[subscript 3])[subscript 2]] (1), cis,cis,trans-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](O[subscript 2]CCF[subscript 3])[subscript 2]] (2), and cis-[Pt(NH3)[subscript 2]Cl[subscript 4]] (3) were measured for comparison. Density functional theory studies were undertaken to investigate the electronic structures of 1−11 and to determine their adiabatic electron affinities. A linear correlation (R2 = 0.887) between computed adiabatic electron affinities and measured reduction peak potentials was discovered. The biological activity of 4−11 and, for comparison, cisplatin was evaluated in human lung cancer A549 and normal MRC-5 cells by the MTT assay. The compounds exhibit comparable or slightly better activity than cisplatin against the A549 cells. In MRC-5 cells, all are equally or slightly less cytotoxic than cisplatin, except for 4 and 5, which are more toxic.