2024

Pamula, Malgorzata

The following thesis investigates the synthesis, structural behavior, and host-guest binding characteristics of two distinct classes of macrocyclic compounds: calix[4]resorcinarenes and calix[4]pyrroles, which belong to the broader family of calixarenes. The first part of the thesis gives an overview of the evolution of calixpyrrole and resorcinarene chemistry from its roots to modern advancements. The text explores their synthesis and binding properties with different types of substrates such as anions, cations, and small organic molecules, emphasizing the importance of synthetic strategies and functionalization in enhancing anion-binding properties and selectivity with potential applications in controlled recognition or transmembrane transport. Additionally, the text highlights the ability of calix[4]pyrrole and resorcinarene units to controlled assembly into supramolecular dimeric capsules showcasing their potential in creating dynamic and reversible encapsulation systems with diverse functionalities. The first part of the experimental section highlights the synthesis and conformational dynamics of two calix[4]resorcinarene derivatives. Notably, podand 5, containing a sulfonyl group attached to its 1,2-dioxyethane chain, adopts a distinctive boat conformation with an aromatic cavity filled through intramolecular self-inclusion driven by C−H⋅⋅⋅π interactions. Conversely, podand 6, lacking hydrogen bond acceptor groups, shows a reduced aromatic cavity due to different arm conformations. Variable-temperature 1H NMR experiments revealed the dynamics of the boat-to-boat exchanges and self-inclusion phenomena in solution, with similar energy barriers for both podands. The second part focuses on the synthesis of aryl-extended meso-p-hydroxylphenylcalix[4]pyrrole via the condensation of pyrrole with p-hydroxyacetophenone, where the αααα-isomer was selectively separated. Results obtained via X-ray crystallography and spectroscopic techniques revealed diverse supramolecular structures upon co-crystallization with various anions and neutral polar guests. NMR titrations indicated strong hydrogen bonding interactions with anions, supported by computational studies emphasizing the role of the dispersive interactions and the exo-cavity configurations. The final section explores the synthesis and characterization of two-armed calix[4]pyrroles, with a focus on their anion-binding properties. Binding studies supported with mass spectrometry revealed selective complexation and broader binding tendencies towards chloride ions by cis-13 appended with urea groups. Chloride transport activity, assessed via lucigenin assay, demonstrated efficient Cl-/NO3- antiport mechanisms in model lipid vesicles for cis-13, while cis-10 lacking the urea groups showed minimal activity. Reduced transport efficiency with SO42- confirmed the proposed mechanism.