Heteroditopic receptor flexibility – an important design principle for effective ion pair extractants based on carboxylate studies

Despite the continuous development of heteroditopic molecular receptors with the ability to transfer salts from the aqueous to the organic phase as a symporter, the factors contributing to the effectiveness of these extractants are still unclear. One of those interplaying factors is the conformational freedom of the heteroditopic receptor. This receptor feature is traditionally thought to decrease the association energy due to energy expenditure of conformational changes during the complexation process. Herein we describe a series of heteroditopic carboxylate salt receptors that vary in the distances between the ion binding domains. Those receptors are based on α-ε-amino acids equipped with a 4-nitrophenyl urea group (anion binding domain) andN-(3-aminobenzyl)-aza-18-crown-6 (cation binding domain). The1H NMR titrations (3% H2O/CD3CN) revealed high binding affinity and cooperativity for carboxylate potassium salts for receptors1and2whereas for more flexible receptors3-5weaker binding was observed. Under liquid-liquid extraction conditions the receptor2proved to be the most efficient extractant of highly hydrophilic KOAc salt. Unexpectedly, the receptor4weakly associating with KOAc under titration conditions proved to be only 18% less effective than2in an extraction process. The solution structures of ternary2·KOAc and4·KOAc complexes after an extraction process were studied by 2D ROESY experiments. Those studies suggest that the receptor2adopts a closed conformation while the receptor4displays a more open conformation. The compact structure of the2·KOAc complex creates low polar entity, which is better stabilized in organic solvents and accelerates the extraction process. However, the open conformation of the4·KOAc complex is still suitable for salt extraction. Thus the conformational freedom of heteroditopic receptors may lower the salt affinities but under extraction conditions it is compensated by the capability of better adapting to interphase conditions.