Multi-nuclear platinum complexes encapsulated in cucurbit[n]uril as an approach to reduce toxicity in cancer treatment

The use of cisplatin in the treatment of human cancers is limited by a number of factors, including high toxicity.1 One technique for lowering toxicity is the replacement of the chloro leaving groups with the slow ring opening oxalate ligand or by replacing one ammine ligand with a sterically bulky ligand.2 Carboplatin and ZD 0473 are examples of complexes developed using these approaches. The lower toxicity of these drugs is attributed to their slower reaction rates, both with water and thiol containing proteins.3,4 Platinum drug resistance in human cancers has been shown to be overcome by the use of multi-nuclear platinum complexes,5 however, these complexes are limited by high toxicity. Molecular encapsulation of these drugs provides a potential for reducing their toxicity through two mechanisms: 1) by decreasing the reactivity of the multi-nuclear platinum complex through hindered access and/or 2) to act as a slow release mechanism thereby limiting undesirable bio-reactions. n this communication we report the preparation of two multi-nuclear platinum complexes encapsulated within cucurbit[7]uril Q[7] (Fig. 1), a relatively new molecular host.6 The subsequent effect on reaction rates, DNA binding and cytotoxicity are discussed.