Synthesis and binding study of thiourea Calix[4]arene derivatives

Abstract

Two novel macrocyclic heteroditopic receptors 14 and 15 which were comprised of calixarene scaffolds and bis-thiourea binding sites bearing two amide or ester moieties at the lower rim were synthesized. The proper synthetic pathway for the preparation of calix[4]arene amide 14 (3.7%) and ester 15 (15%) were different. Both macromolecule 14 and its analogous 15 existed in cone conformation in either chloroform or acetonitrile solution. The x-ray structure of 14 indicated the closed flattened cone conformation. The cations, anions (both basic anions and amino acid anions) as well as cooperative binding properties of both receptors were investigated. [superscript 1]H-NMR titration was employed to measure the stoichiometry of the complexes, binding constants and Gibbs free energy in acetonitrile-d[subscript 3]. Both receptors recognized alkali cations with highest selectivity towards sodium. Compared to 14, compound 15 was found to be a more efficiency and specific host for sodium. Despite their similar structures, macromolecule 14 can selectively bind Y-shaped carboxylate anions while analogous molecule 15 displayed a good selectivity with tetrahedral phosphate type anions. Moreover, the binding affinity of both receptors towards TBA salt of amino acids was affected by changing the amino acid side chain. Bis-thiourea 14 and 15 did not show a significant difference in binding affinity among various amino acids. However, receptor 14 showed a moderate selectivity for TBA salt of leucine whereas ester macromolecule 15 formed a remarkably strong complex with carboxylate salts of phenylalanine and asparagine. Both bis-thiourea derivatives were more selective for TBA salts of shorter amino acids (aspartic acid and asparagine) than those of longer amino acids (glutamic acid and glutamine). Additionally, ligand 14 preferentially recognized dicarboxylate amino anions (aspartic acid and glutamic acid) over monocarboxylate amino anions (asparagine and glutamine) whilethe inverse trend was observed for ligand 15. The binding efficiency of sodium bound 14 towards common carboxylate or phosphate anion could be evaluated only with diphenylphosphate as a negative allosterism. Unlike bound 14, the sequestering by ion-pairing effect in the case of bound 15 was not predominantly observed. Both free and sodium bound 15 preferentially recognized phosphate type anions, in which the latter system was controlled by synergistic effects. The strongest binding efficiency was found in the case of dihydrogen phosphate whereas the highest cooperativity factor was discovered in the case of acetate. On the other hand, the presence of sodium cation in the amide cavity of 14 displayed the positive allosterism in the case of dicarboxylate salt of aspartic acid and negative allosterism in the case of dicarboxylate anion of glutamic acid. On the contrary, the binding affinity of the sodium bound 15 towards bis-TBA salts of aspartic acid and glutamic acid were decreased.