Cucurbit[n]uril binding of platinum anticancer complexes

Abstract

The encapsulation of cisplatin by cucurbit [7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4 -dipyrazolylmethane (dpzm) ligand by Q [7] and cucurbit [8] 4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes.

Use of Cucurbit [6] Uril as a Modifier in the Electrochemical Determination of Antitumor Platinum (II) Complex: <i>Trans</i>-[PtCl<sub>2</sub>(Dimethylamine) (Isopropylamine)]. Application to Biological Samples

“…Similar shielding/deshielding movements are also observed for platinum resonances in 195 Pt NMR spectra [30,31].…”

“…Protons within a CB [n] cavity are highly shielded and can shift upfield (lower ppm/frequency) by up to 1.5ppp [30]. Protons that are located outside, but close to, the portals are slightly deshieded and move downfield, whilst protons far away from the CB[n] do not change chemical shift [30].…”

A chemical preformulation study of a host–guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery

“…The only large difference between the model and the crystal structure is seen in the structure of the CB [7] molecule. The portals of CB [7] are normally symmetrical with a van der Waals radius of 5.4 Å and this symmetry is observed in the molecular model of CB [7] and di-Pt; 31 however, from the single X-ray crystal structure the binding of di-Pt distorts the CB [7] into an ellipsoid shape, with one long van der Waals axis of~5.9 Å and one shorter axis of 4.8 Å .…”

Encapsulation of alkyl and aryl derivatives of quaternary ammonium cations within cucurbit[n]uril (n = 6,7) and their inverted diastereomers: density functional investigations

“…3003 (1) 2989 (2) 3009 (2) 2991 (1) 3013 (2) 2997 (1) 3008(4) 3000 (2) 3004 (80) 2982 (2) 2990 (2) (22) C-C N 1319 (12) 1499 (34) 1327 (1) 1314 (5) 1310(6) 1169 (38) 1166(3) Table 6 Electron density in anti-bonding orbital (σ* in au), Bond Distances (r in Å), and frequency of vibration (ν in cm −1 ) in host and their complexes. …”

“…A family of cucurbit[n]uril, CB [n], hosts comprising of methylene-bridged glycouril units have attracted considerable attention owing to their potential applications in organic synthesis [1][2][3][4], molecular recognition [5,6], nanoscience [7,8], catalysis [9][10][11], drug delivery vehicles [12] and separation technology [13,14]. The number of glycouril units in cucucrbituril homologues renders varying size to their hydrophobic cavity while portal carbonyl groups on portals provide hydrophilic exterior to these macrocycles.…”