Binding Between Cyclohexanohemicucurbit[n]urils and Polar Organic Guests

Abstract

Inherently chiral, barrel-shaped, macrocyclic hosts such as cyclohexanohemicucurbit[n]urils (cycHC[n]) bind zinc porphyrins and trifluoroacetic acid externally in halogenated solvents. In the current study, we tested a set of eighteen organic guests with various functional groups and polarity, namely, thiophenols, phenols, and carboxylic and sulfonic acids, to identify a preference toward hydrogen bond–donating molecules for homologous cycHC[6] and cycHC[8]. Guests were characterized by Hirshfeld partial charges on acidic hydrogens and their binding by ¹H and ¹⁹F NMR titrations. Evaluation of association constants revealed the complexity of the system and indirectly proved an external binding with stoichiometry over 2:1 for both homologs. It was found that overall binding strength is influenced by the stoichiometry of the formed complexes, the partial atomic charge on the hydrogen atom of the hydrogen bond donor, and the bulkiness of the guest. Additionally, a study on the formation of complexes with halogen anions (Cl⁻ and Br⁻) in methanol and chloroform, analyzed by ¹H NMR, did not confirm complexation. The current study widens the scope of potential applications for host molecules by demonstrating the formation of hydrogen-bonded complexes with multisite hydrogen bond acceptors such as cycHC[6] and cycHC[8].