HOST-GUEST CHEMISTRY BETWEEN CUCURBITURIL AND CATIONIC AND NEUTRAL GUESTS
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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 cucurbituril (CB) 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 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 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 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-benzylammonium guests, while the strength of binding of the neutral hydrophobic group results from efficient packing within the inner CB cavity. Each of the biguanidinium guests was shown to form strong 1:1 host-guest complexes with CB. Metformin proved to be small enough to form 1:2 host-guest complexes at low concentrations of CB, while chlorhexidine and alexidine were shown to be large enough to form sequential 2:1 and 3:1 host-guest complexes with CB. UV-visible pH titrations showed that CB 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, indicating that this host could potentially act as carrier for these drug molecules. CB catalyzes the acid decomposition of berenil and each of the decomposition products, 4-hydroxy- and 4-aminobenzamidinium, bind to CB with increases in their pKa values in the presence of CB. The three flavylium dyes, with cationic oxonium centers, were shown to complex strongly with CB, resulting in a stabilization of the flavylium cation, with respect to the ring-opened 2-hydroxychalcones in neutral solutions.