Recognition of Anions via Squaramide H-bond Donors in Aqueous Media

Abstract

Anions are essential to many different biological and chemical processes, therefore the development of novel receptors for anions in aqueous media could have great potential utility in biological, medicinal, chemical, industrial and environmental applications. This thesis describes the synthesis and anion binding ability, as determined by spectroscopic methods, of receptors functionalised with hydrophilic squaramide moieties. Chapter two focusses on difunctionalised peptides and the effect side-chain length had on the binding affinity, monitored by 1H NMR spectroscopy, of the receptors to sulfate. Chapter three investigates the effect an additional squaramide unit and increased rigidity or flexibility has on the anion binding affinity of these peptidic receptors. Chapter four explores the effect pre-organisation, in the form of macrocyclisation of the peptidic scaffold, had on the anion binding affinity of the receptor. This was shown to induce more complex binding stoichiometries when the macrocycle contained flexible spacers. With the aim of producing a sensor for anions, Chapter five explores the anion binding ability of carbocationic fluorescent scaffolds functionalised with the hydrophilic squaramide moieties. This chapter focussed on binding to sulfate and dicarboxylates in particular, which was monitored via UV-Vis and fluorescence spectroscopy. Overall, it was shown that incorporation of the hydrophilic squaramide moiety onto peptidic and fluorescent scaffolds resulted in receptors with good selectivity and affinity for sulfate in aqueous DMSO and MeCN solvents. Structural changes such as shortening the distance between squaramide binding sites and increased pre-organisation via macrocyclization increased the receptors binding affinity to sulfate with measurable binding to sulfate observed with the peptidic based receptors in up to 75% H2O/DMSO-d6.