Comparative macrocycle binding of the anticancer drug phenanthriplatin by cucurbit[n]urils, β-cyclodextrin and para-sulfonatocalix[4]arene: a ¹H NMR and molecular modelling study

The potential anticancer drug phenanthriplatin, [cis-(NH₃)₂(phenanthridine)Cl]⁺, forms supramolecular complexes with cucurbit[n]urils (CB[n], n = 7 or 8), β-cyclodextrin and para-sulfonatocalix[4]arene (sCX[4]) as determined by ¹H NMR spectroscopy and molecular modeling. The results show that cucurbit[7]uril binds over the long arm of the drug, where hydrophobic effects and two hydrogen bonds stabilise binding. For cucurbit[8]uril, two phenanthriplatin molecules can bind simultaneously within the macrocycle’s cavity. Unfortunately, Na⁺ was able to displace the drug from both CB[7] and CB[8] making the macrocycles unsuitable as delivery vehicles for phenanthriplatin. Drug binding to β-cyclodextrin occurs at the portal of the macrocycle with no part of the phenanthriplatin located within the cavity. Phenanthriplatin binding to sCX[4] occurs in a 2-to-1, macrocycle-to-drug, ratio with the formation of a capsule-like complex where each sCX[4] binds over opposing ends of the drug. The results indicate that para-sulfonatocalix[4]arene is the only suitable macrocycle of the four studied for further research into phenanthriplatin drug delivery.