Improved Synthesis, Anticancer Activity and Electrochemical Characterization of Unusual Zwitterionic Palladium Compounds with a Ten-Term Coordinative Ring.

Graphical Abstract

A new improved synthetic protocol for the preparation of uncommon zwitterionic palladium(II) complexes with a ten-term coordinative ring is reported. The antiproliferative activity of the synthesized complexes was tested toward eight different cancer cell lines. The mesityl derivative showed potent and selective cytotoxicity toward several types of cancer cell lines, with IC₅₀ values lower than cisplatin. Aiming to easily determine these promising metallo-drugs, a voltammetric study of their electrochemical fingerprint was first carried out.

Abstract

A new improved synthetic protocol for the preparation of uncommon zwitterionic palladium(II) complexes with a ten-term coordinative ring is reported. A suitable combination of reaction solvent and temperature allows to drastically reduce the reaction time and increase the yield. A detailed kinetic study, implemented by theoretical DFT calculations, clarifies and quantifies this solvent effect. The antiproliferative activity of the synthesized complexes was tested toward eight different cancer cell lines. The mesityl derivative showed potent and selective cytotoxicity toward several types of cancer cell lines, with IC₅₀ values lower than cisplatin. Additionaly, the anticancer activity against cisplatin-sensitive and cisplatin-resistant ovarian cancer cells suggested a different mechanism of action with respect to traditional platinum chemotherapeutics. Aiming to easily determine these promising metallo-drugs, a voltammetric study of their electrochemical fingerprint was carried out. For both compounds a suitable signal, ascribed to the reduction of the metallic center from palladium(II) to palladium(0), was identified and further investigated by Differential Pulse Voltammetry.