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

A new improved synthetic protocol for the preparation of uncommon zwitterionic palladium(II) complexes with a tentermcoordinative ring is reported. A suitable combination of reaction solvent and temperature allows to drastically reducethe reaction time and increase the yield. A detailed kinetic study, implemented by theoretical DFT calculations, clarifiesand 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 anticanceractivity against cisplatin-sensitive and cisplatin-resistant ovarian cancer cells suggested a different mechanism of action withrespect to traditional platinum chemotherapeutics. Aiming to easily determine these promising metallo-drugs, a voltammetricstudy of their electrochemical fingerprint was carried out. For both compounds a suitable signal, ascribed to thereduction of the metallic center from palladium(II) to palladium (0), was identified and further investigated by Differential PulseVoltammetry.