Inclusion complexes of the antitumor metallocenes Cp 2 MCl 2 (M = Mo, Ti) with cucurbit[n]urils

Abstract

The encapsulation of the aquated forms of molybdocene dichloride and titanocene dichloride by cucurbit[n]uril (Q[n], where n = 7 and 8) at different pD values has been studied by 1H NMR spectroscopy and molecular modelling. 1H NMR titration experiments indicate that both metallocenes form 1:1 host-guest complexes with both Q[7] and Q[8]. In these complexes, both the cyclopentadienyl ligands and metal centre are positioned deep within the cucurbituril cavity. In vitro cell proliferation studies using the cancer cell lines MCF-7 and 2008 showed that the encapsulated molybdocene complex was more active than the corresponding free metallocene, with GI 50 values of 210 and 400 μM respectively. However, unexpectedly the encapsulation of Cp2MoCl2(aq)at pD 7 catalysed significant degradation of the cucurbituril framework in the presence of oxygen. Encapsulation of Cp2TiCl2(aq) by Q[7] greatly slowed the protonolysis of the cyclopentadienyl ligands in aqueous phosphate buffer (pD 7), while encapsulation in Q[8] only slightly retarded the hydrolytic degradation of the metallocene. This journal is Show more