SMALL MOLECULAR SCAFFOLDS FOR THE SELECTIVE RECOGNITION OF ANIONS

Abstract

Anions are ubiquitous in a myriad of chemical, biological and environmental processes. The ability to selectively recognise target anions in competitive solvents has potential uses in biomedical and environmental applications. Macrocyclic structures such as cyclic peptides in particular, provide excellent scaffolds for anionic recognition as they allow for a preorganised binding site; however, their synthesis is laborious and typically involves numerous purification steps. Therefore, the work described in this thesis focuses on the development of small molecular scaffolds for the selective recognition of anions. Chapter 2 describes the design of a family of novel linear peptide-based bis[zinc(II)– dipicolylamine] receptors and an investigation of their anion binding abilities. In order to maximise the effectiveness of the synthetic strategy, the solid phase peptide synthesis approach was employed. An investigation of the binding abilities of these receptors under mimicked physiological conditions was carried out using an indicator displacement assay approach with pyrocatechol violet as the indicator. Based on the results of the UV-Vis spectroscopic binding studies performed with these receptors, it was found that all receptors exhibit excellent affinity for the target anion, pyrophosphate, with observed selectivity over adenosine triphosphate and adenosine diphosphate. Chapter 3 describes the design of two new covalently linked receptors [a dipicolylamine–naphthalimide derivative and a bis(isoquinoline) derivative] and an investigation of their metal and anion sensing properties. Preliminary metal sensing studies under mimicked physiological conditions revealed that for both derivatives, coordination to different metal ions afforded different fluorescence outputs. Furthermore, anion sensing studies using the respective dipicolylamine–naphthalimide and bis(isoquinoline) metal complexes highlighted the potential of these two derivatives operating as multi anion probes upon complexation to different metal ions. Chapter 4 describes the design of a series of novel linear peptide-based receptors (decorated with either a thiourea group or a squaramide moiety) and an investigation of their anion binding abilities. In a similar manner to the synthetic strategy employed in Chapter 2, we have also utilised the solid phase peptide synthesis approach for the preparation of these linear peptide-based receptors. 1H NMR spectroscopic titrations performed in 0.5% v/v H2O/DMSO-d6 and in a more competitive media of 20% v/v H2O/DMSO-d6 indicated that all receptors demonstrate strong binding affinity and selectivity for the target anion, sulfate. Such remarkable binding to sulfate is proposed to arise from a synergistic interaction between the amide backbone and the thiourea/squaramide NH protons analogous to that observed in the sulfate binding protein. The final chapter, Chapter 5, describes the first study of a novel family of croconamides as anion receptors. Access to these compounds was achieved via a three-step route from croconic acid. 1H NMR titrations with these croconamides in both CD3CN-d3 and DMSO-d6 revealed a strong preference for the chloride anion. Interestingly, unique binding behaviours that are contrary to those reported for a structurally similar class of compounds (oxosquaramides) were observed.