Cucurbit[n]urils (CB[n]) are potential stabilizing, solubilizing, activating, and delivering agents for drugs. The toxicity of the macrocyclic host molecules cucurbit[7]uril (CB[7]), the most water-soluble homologue, as well as cucurbit[8]uril (CB[8]) has been evaluated. In vitro studies on cell cultures revealed an IC₅₀ value of 0.53 ± 0.02 mM for CB[7], corresponding to around 620 mg of CB[7] per kg of cell material. Live-cell imaging studies performed on cells treated with subtoxic amounts of CB[7] showed no detrimental effects on the cellular integrity as assessed by mitochondrial activity. For CB[8], no significant cytotoxicity was observed within its solubility range. The bioadaptability of the compounds was further examined through in vivo studies on mice, where intravenous administration of CB[7] showed a maximum tolerated dosage of 250 mg kg⁻¹, while oral administration of a CB[7]/CB[8] mixture showed a tolerance of up to 600 mg kg⁻¹. The combined results indicate a sufficiently low toxicity to encourage further exploration of CB[n] as additives for medicinal and pharmaceutical use.

A novel approach to cucurbituril synthesis is described where partial substitution is introduced into cucurbit[n]uril. The identification of homologues (and their substitution) in reaction mixtures is achieved by a combination of ESMS and the use of the molecular probes (guests) 1,4-dioxane and 1,9-octanediamine. A unique symmetrical hexamethylcucurbit[3,3]uril, the major product, was isolated and characterized.

The aqueous solubilities of albendazole encapsulated in cucurbit[6, 7 and 8]urils (Q[6], Q[7] and Q[8]) have been determined by ¹H NMR spectroscopy, and the effect of encapsulation on their cytotoxicities evaluated. Encapsulation in Q[6] and Q[7] increased the aqueous solubility of albendazole by 2 000-fold, from 3 µM to 6 mM at pH 6.6, while Q[8]-encapsulation increased the solubility to over 2 mM. Encapsulation in Q[7] and Q[8] induced significant upfield shifts for the albendazole propyl and benzimidazole resonances, compared to those observed for Q[6]-binding and what would normally be expected for the respective functional groups. The upfield shifts indicate that the albendazole propyl and benzimidazole protons are located within the Q[7] and Q[8] cavity upon encapsulation. Alternatively, encapsulation in Q[6] only induced a large upfield shift for the albendazole carbamate methyl resonance, indicating that the drug associates with Q[6] at its portals, with only the carbamate group within the cavity. Simple molecular models based on the observed relative changes in chemical shift could be constructed that were consistent with the conclusions from the NMR experiments. Cytotoxicity assays against human colorectal cells (HT-29), human ovarian cancer cells (1A9) and the human T-cell acute lymphoblastic leukaemia cells (CEM) indicated that encapsulation in Q[7] did not significantly reduce the in vitro anti-cancer activity of albendazole.

p-Hydroxybenzoic acid acts as a template in the presence of KI for the self-assembly of cucurbit[5]uril, which arranges into 6-membered ring structures. These form hexagonal netting sheets, superimposed upon one another to create continuous channels. This solid material is absorbent to volatile organics, ranging in size from methanol to 1,4-dioxane.

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.