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

Abstract

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) and N-(3-aminobenzyl)-aza-18-crown-6 (cation binding domain). The ¹H NMR titrations (3% H₂O/CD₃CN) revealed high binding affinity and cooperativity for carboxylate potassium salts for receptors 1 and 2 whereas for more flexible receptors 3–5 weaker binding was observed. Under liquid–liquid extraction conditions the receptor 2 proved to be the most efficient extractant of highly hydrophilic KOAc salt. Unexpectedly, the receptor 4 weakly associating with KOAc under titration conditions proved to be only 18% less effective than 2 in an extraction process. The solution structures of ternary 2·KOAc and 4·KOAc complexes after an extraction process were studied by 2D ROESY experiments. Those studies suggest that the receptor 2 adopts a closed conformation while the receptor 4 displays a more open conformation. The compact structure of the 2·KOAc complex creates low polar entity, which is better stabilized in organic solvents and accelerates the extraction process. However, the open conformation of the 4·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.