Studies in anion-responsive polymers and 6-shogaol as a chemopreventive of prostate cancer

The study of the binding and recognition of anions has emerged as a significant branch of supramolecular chemistry over the past 20 years. Of particular interest is the binding in aqueous media of industrially or biologically relevant anions including fluoride, pyrophosphate, and terephthalate. To date, most anion recognition using synthetic systems has been accomplished with small molecule receptors operating in organic media. We believe the challenge of sensing and binding anionic species in aqueous media could be addressed through polymers. This is due to their solubility, which can be tuned by judicious selection of the appropriate polymer backbone. Further, polymers can be cross-linked (forming interchain bonds) to produce insoluble materials that are attractive for use as filter materials for liquids and gases. The polymer network can also act as a net to strip away the solvent shell of the anions, leading to increased sensitivity toward hydrated analytes. In addition, the multi-valency due to multiple binding sites in a polymer can lead to increased affinities for analytes. This dissertation details the author’s work focused on the preparation of anion receptor-containing polymers and their subsequent evaluation as both sensors for the fluoride anion and as extractants for bisanions under conditions of liquid-liquid extraction.

Chapter 1 gives a brief review of the challenges of anion binding and a primer on the field of sensing and extracting anions using polymeric systems. Chapter 2 describes our work incorporating three quinoxaline-based anion receptors into poly(methyl methacrylate) polymers and their sensing of anionic targets. Chapter 3 describes our work incorporating calix[4]pyrrole anion receptors into poly(methyl methacrylate) polymers. These polymeric systems were found to undergo reversible crosslinking in organic media when combined with certain ditopic anions. Chapter 4 describes our work to investigate chemopreventives of prostate cancer based on the phytochemicals 6-gingerol and 6-shogaol. The mechanism of action was linked to the inhibition of inflammation pathways. Derivatives of 6-shogaol were synthesized and their ability to inhibit prostate cancer cell growth was evaluated. Chapter 5 details all the syntheses and characterization data of the compounds discussed in this dissertation, as well as spectra from titrations and extraction studies.