Hydrazone- and imine-containing [PdPtL] cages: a comparative study of the stability and host-guest chemistry.

A new [PdPtL] heterobimetallic cage containing hydrazone linkages has been synthesised using the sub-component self-assembly approach. H and DOSY nuclear magnetic resonance (NMR) spectroscopy and electrospray ionisation mass spectrometry (ESIMS) data were consistent with the formation of the [PdPtL] architecture. The cage was stimulus-responsive and could be partially disassembled and reassembled by the addition of dimethylaminopyridine (DMAP) and -tolenesulfonic acid (TsOH), respectively. Additionally, the stability of the hydrazone cage against hydrolysis in the presence of water and nucleophilic decomposition in the presence of guest molecules was compared to a previously synthesised imine-containing [PdPtL] cage. It was established that the hydrazone linkage was more resistant to hydrolysis. Furthermore, the host-guest (HG) chemistry with a series of drug and drug-like molecules was examined. The hydrazone cage was shown to interact with cisplatin while the smaller imine cage was shown to interact with 5-fluorouracil and oxaliplatin in CDCN. No HG interactions were observed in the more polar -DMSO. antiproliferative activity studies demonstrated both cages were active against the cancer cell lines tested and displayed half-maximal inhibitory (IC) values in the range of 25-35 μM. Most [PdPtL]-drug mixtures tested had higher IC values than the hosts. However, the [PdPtL] cages, and [PdPtL]:drug mixtures were less cytotoxic than the well established anticancer drugs cisplatin, oxaliplatin and 5-fluorouracil.