Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects.
Martin SojkaJan ChybaShib Shankar PaulKarolina WawrockaKateřina HönigováBen Joseph R CuyacotAbril C CastroTomáš VaculovičJaromír MarekMichal RepiskyMichal MasaříkJan NovotnýRadek MarekPublished in: Inorganic chemistry (2021)
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-[PtII(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 β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.
Keyphrases
- density functional theory
- water soluble
- molecular dynamics
- high resolution
- ionic liquid
- oxidative stress
- molecular dynamics simulations
- room temperature
- mass spectrometry
- magnetic resonance
- crystal structure
- nk cells
- magnetic resonance imaging
- multiple sclerosis
- computed tomography
- emergency department
- monte carlo
- binding protein
- oxide nanoparticles
- dual energy
- capillary electrophoresis