Synthesis of partially substituted Cucurbit[6-7]uril derivatives and binding studies for tuned supramolecular constructions

Classical cucurbit[n]uril (Q[n], n = 5 to 10) are macrocyclic structures resembling a hollow pumpkin shape or an open ended empty barrel. The synthesis of substituted Q[n] has been developed to introduce new substituents, especially those carrying reactive functional groups. However, its further development has been limited by the challenge of achieving higher homologues, where n = 6-8.In this thesis, as an extension to these results, the binding study has been evaluated for a range of neutral and cationic guests toward Me4Q[6] and CyP6Q[6], and these are compared to classical Q[6]. The guests were chosen that differed in shape and in the number of cations carried on them. The types of guests include various cyclopentyl ammonium salts, dioxane, and the gases isobutane and isobutylene. Two different competition methods were used in this study. These involved either two guests competing for one host, or two hosts competing for one guest. The findings are discussed, which show the importance of the equatorial alkyl substitution upon the portal-dipole interaction and the cavity interaction with guests with different molecular shapes. It also shows that equatorial alkyl substitution provides a potential to ‘tune’ guest binding. This was demonstrated in the synthesis of a pseudorotax[4]ane, where the thread is a cyclopentyl tetra-ammonium derivative, and Q[7] and two CyP6Q[6] are threaded on to it. This study displays the ‘tuning’ of binding constants and a demonstration of hetero-Q[n] supramolecular construction. The ability to ‘tune’ binding also suggests a potential for drug delivery applications.Studies toward the preparation of substituted Q[n] (SQ[n]), α,δ-Me4Q[7] and α,δ-AcidCyP2Q[6] using glycoluril dimer as a building block are discussed. This method opens the way to a general procedure to obtain significant proportions of the SQ[n] higher homologues. A study into overcoming high binding constants, and an equilibrium shift towards a lower binding sacrificial guest is discussed in order to vacate the cavity of α,δ-Me4Q[7], to remove a AdaNH3+ guest which was used in the purification process. The sacrificial guest was then removed by oxidation and decomposition. A new functionalised α,δ-AcidCyP2Q[6] was synthesised using a similar block method and it provided functional groups such as a CO2H group in two positions. This functionality creates an opportunity for further chemical elaboration. A secondary study was undertaken to better understanding the possible separation of enantiomers by using Q[n] and tartrate molecules as auxiliaries. This involved optical rotation dispersion (ORD) and circular dichroism (CD) spectral analysis of the formed chiral supramolecular structures. The results clearly show the domination of the tartrate anion, which controls the chiral centre and the inclusion complex. This study demonstrates a significant potential of Q[n] as another supramolecular way to identify and perhaps separate the enantiomers