SYNTHESIS OF SULFATED PILLAR[N]ARENES: INFLUENCE OF CHARGE, SHAPE AND SIZE ON MOLECULAR RECOGNITION

Abstract

Supramolecular chemistry shifts focus from covalent bonds to non-covalent interactions, forming the foundation of functional systems at molecular level. Molecular containers like pillar[n]arenes provide unique, rigid cavities for selective molecular recognition. Water-soluble derivatives are vital for sensing and drug delivery, using principle of molecular recognition to bind specific guests in physiological environments. Gaining deeper insight into the structure-function relationships of water-soluble sulfated pillar[n]arenes will advance our understanding of their contributions to the broader field of host-guest chemistry.Chapter 2 presents the synthesis and extensive molecular recognition study of a series of partially sulfated pillar[5]arenes (P5Sn) that differ in the number of sulfate substituents. The series exhibits precise tuning of binding affinity towards positively charged guests in biologically relevant sodium phosphate buffer, pH 7.4. The study demonstrated that simple structural changes (e.g. degree of sulfation) modulate host•guest non-covalent interactions thereby enabling fine tuning of host•guest binding affinity of 7 orders of magnitude. Chapter 3 presents the synthesis of a water-soluble pillar[8]arene, P[8]S8 with a flexible “figure eight” shaped cavity. The macrocycle resists self aggregation and exhibits good aqueous solubility. Molecular recognition studies show that P[8]S8 exhibits adaptable, induced‑fit binding, forming moderately strong complexes with quaternary ammonium guests. Additionally, cationic cyclophanes bind to P[8]S8 with exceptionally high affinity, highlighting the critical role of electrostatic preorganization in designing versatile supramolecular hosts for effective molecular recognition in aqueous environments. Chapter 4 presents a series of linearly extended water-soluble sulfated pillar[6]arenes, Ex(n)-P[6]S8 (n = 0, 1, 2), incorporating phenyl, biphenyl, and terphenyl spacers. Comprehensive NMR, ITC, UV‑Vis, and fluorescence studies reveal strong yet tunable binding toward diverse (di)ammonium guests, governed by flexibility of host cavity and charge and size compatibility between host and guest. Overall, aromatic spacer extension in the host induces structural twisting and increased adaptability, enabling finely tailored supramolecular recognition. Chapter 5 presents a comprehensive summary of the thesis, and the overall significance of the research findings.