Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[Pt-II(NH3)(2)(H2O)(NH2-R)](2+) compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its beta-cyclodextrin (beta-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@beta-CD, respectively, while maintaining a significantly lower toxicity profile.