Building Block Synthesis and Recognition Properties of Cucurbit[n]uril (n = 7, 8) Derivatives

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Molecular containers have been a topic of interest for chemists since the discovery of crown ethers and their molecular recognition properties in the late 1960’s. Since then, the field of molecular containers has expanded rapidly to include many high affinity and highly selective host molecules. Chapter 1 introduces common molecular containers and goes on to discuss the CB[n] family of molecular containers. The CB[n] family are an exemplary group of hosts because they exhibit extremely high affinities (Ka values up to 1017 M-1) and high selectivity towards their guests which make them excellent candidates for many supramolecular applications. In order to maximize the use of CB[n], it became important to access specialized and functionalized derivatives to cater to various applications and chemistry. Early functionalization routes were limited by a lack of mechanistic understanding, but the mechanistic work of the Isaacs, Kim, and Day groups led to more successful syntheses.

Chapter 2 discusses a building block synthesis towards water-soluble CB[7] derivatives Me2CB[7] and CyCB[7]. The recognition properties of Me2CB[7] are investigated as well as its use in drug solubilization. It is found that Me2CB[7], though 10 times more water soluble than CB[7], is able to solubilize drugs only as well as CB[7].  Additionally, a route towards a monofunctionalized CB[7] derivative, Cl-CB[7], bearing a primary chloride which is able to undergo further functionalization to a clickable azide by SN2 chemistry is presented. A click reaction with a small alkyne is performed resulting in a self-associating host whose self-assembly process is further investigated.

Chapter 3 discusses a building block synthesis towards the first water-soluble CB[8] hosts Me4CB[8] and Cy2CB[8]. Mechanistic details of the CB[8] formation are elucidated from contrasting experiments and the recognition properties of the CB[8] derivatives are investigated by 1H NMR spectroscopy and X-ray crystallography. The CB[8] derivatives are investigated as potential drug solubilizing agents and it is found that they are able to solubilize several larger pharmaceutical molecules whereas CB[8] is water insoluble.