Host-Guest Chemistry Between Cucurbit[7]uril and Cationic and Neutral Guests

Abstract

This thesis describes the use of electrospray mass spectrometry, 1H NMR, and UV-visible spectroscopy, along with molecular modeling studies, to characterize the host-guest complexes that are formed between the cucurbit[7]uril (CB[7]) host molecule and a series of cationic alkylammonium (benzethonium), biguanidinium (metformin, phenformin, chlorhexidine and alexidine), amidinium (berenil, pentamidine, and 4-hydroxy- and 4-aminobenzamidines), and flavylium (4’- and 6-methoxyflavylium and 6,4’-dimethoxyflavylium) guests in aqueous solution. The stoichiometries and binding strengths of the CB[7] host-guest complexes with these series of drug and dye molecules were determined, and have been rationalized in terms of the specific ion-dipole interactions and hydrophobic effects involved. The potential uses of CB[7] as a slow-release drug delivery agent and molecular stabilizing agent are indicated from kinetic and spectroscopic studies on the reactivities of the host-guest complexes. CB[7] forms 1:1 and 2:1 host-guest complexes with the benzethonium cation by sequential binding to the hydrophilic benzyldimethylammonium group and the hydrophobic 2,4,4-trimethylpentyl group, respectively. The binding strength at the former site is consistent with data for other CB[7]-benzylammonium guests, while the strength of binding of the neutral hydrophobic group results from efficient packing within the inner CB[7] cavity. Each of the biguanidinium guests was shown to form strong 1:1 host-guest complexes with CB[7]. Metformin proved to be small enough to form 1:2 host-guest complexes at low concentrations of CB[7], while chlorhexidine and alexidine were shown to be large enough to form sequential 2:1 and 3:1 host-guest complexes with CB[7]. UV-visible pH titrations showed that CB[7] binds more strongly to mono-protonated metformin than the di-protonated form of this guest. Both pentamidine and berenil formed tightly bound complexes with CB[7], indicating that this host could potentially act as carrier for these drug molecules. CB[7] catalyzes the acid decomposition of berenil and each of the decomposition products, 4-hydroxy- and 4-aminobenzamidinium, bind to CB[7] with increases in their pKa values in the presence of CB[7]. The three flavylium dyes, with cationic oxonium centers, were shown to complex strongly with CB[7], resulting in a stabilization of the flavylium cation, with respect to the ring-opened 2-hydroxychalcones in neutral solutions.