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(NH₃)₂}₂(µ-NH₂(CH₂)₈NH₂)]²⁺ (CT008) and [{Ru(phen)₂}₂(µ-bb₅)]⁴⁺ {phen = 1,10-phenanthroline; bb₅ = 1,5-bis[4(4′-methyl-2,2′-bipyridyl)]pentane} (Rubb₅) to Q[10] was studied by ¹H NMR and luminescence spectroscopy, cyclic voltammetry and molecular modelling. The ¹H NMR resonances of the methylene protons in the bridging ligands of CT008 and Rubb₅ 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. ¹H NMR-based kinetics experiments with Rubb₅ 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 Rubb₅ 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 ¹H NMR and biological timescales. This result was consistent with molecular modelling simulations. Cyclic voltammetry showed that the Ru(III/II) couple of free Rubb₅ appeared at +1.058 V (vs Ag/AgCl), with the first ligand reduction observed as a shoulder (≈−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 Rubb₅ to Q[10] yielded an approximate binding constant of 1.9 × 10⁹ 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.