Cucurbit[10]uril binding of dinuclear platinum(II) and ruthenium(II) complexes: association/dissociation rates from seconds to hours

Abstract

A simpler method for the purification of cucurbit[10]uril (Q[10]) from the Q[10].Q[5] inclusion complex is reported. 1,12-Diaminododecane was used to displace Q[5], as opposed to the synthetic melamine derivative currently used. The binding of trans-[{PtCl(NH(3))(2)}(2)(micro-NH(2)(CH(2))(8)NH(2))](2+) (CT008) and [{Ru(phen)(2)}(2)(micro-bb(5))](4+) {phen = 1,10-phenanthroline; bb(5) = 1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane} (Rubb(5)) to Q[10] was studied by (1)H NMR and luminescence spectroscopy, cyclic voltammetry and molecular modelling. The (1)H NMR resonances of the methylene protons in the bridging ligands of CT008 and Rubb(5) exhibited large upfield chemical shift changes upon addition of Q[10]. These shifts are indicative of encapsulation of the bridging ligand within the Q[10] cavity, with the metal centres positioned outside the portals. (1)H NMR-based kinetics experiments with Rubb(5) show the presence of a portal-bound intermediate which progresses to a completely encapsulated inclusion complex only after many hours. The large metal centres of Rubb(5) provide a restriction to the movement of the complex in and out of the cavity and result in binding kinetics that are slow on both the (1)H NMR and biological timescales. This result was consistent with molecular modelling simulations. Cyclic voltammetry showed that the Ru(III/II) couple of free Rubb(5) appeared at +1.058 V (vs Ag/AgCl), with the first ligand reduction observed as a shoulder ( approximately -1.38 V) on the edge of the solvent (water) front. The Q[10]-bound complex exhibited an anodic shift of 48 mV compared to the free metal complex. Luminescence spectroscopy of the binding of Rubb(5) to Q[10] yielded an approximate binding constant of 1.9 x 10(9) M(-1). Although CT008 was encapsulated within Q[10], the inclusion complex was not soluble in several buffers at pH 7.0. These results indicate that Q[10] is not an effective delivery vehicle for dinuclear platinum(II) anti-cancer drugs; however, due to the strong binding affinity and slow exchange rates, Q[10] does show considerable promise as a delivery mechanism for controlled slow release of large dinuclear ruthenium(II) complexes.