A chemical preformulation study of a host–guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery

Abstract

Single crystal and powder X-ray diffraction have been used to examine the host–guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt, dpzm= 4,4′-dipyrazolylmethane). The single crystal structure shows that the host–guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host–guest complex crystallises with two chloride counterions and 5.5 water molecules. The unit cell comprises four asymmetric units, each of which contains three crystallographically independent CB[7]–di-Pt moieties. X-Ray powder diffraction demonstrated structural consistency of the bulk crystals with a single polycrystalline phase that is identical with the single crystal structure. Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the CB[7]–di-Pt complex lose 11 and 3.5% of their mass respectively, through the loss of water molecules, upon heating to 160 °C. The DSC results showed that the free dpzm ligand melts between 186 and 199 °C, with a standard enthalpy of fusion of 27.92 kJ mol−1. As a 2+ inorganic salt the metal complex does not melt but undergoes several decomposition events between 140 and 290 °C. Encapsulation by CB[7] completely stabilises di-Pt with no decomposition of either the macrocycle or metal complex at temperatures up to 290 °C.