Uncharged water-soluble amide derivatives of pillar[5]arene: synthesis and supramolecular self-assembly with tetrazole-containing polymers

© 2020, Springer Science+Business Media, Inc. New uncharged water-soluble pillar[5]arene derivatives bearing 2-hydroxyethylamide and 2-hydroxypropylamide moieties have been for the fi rst time synthesized via aminolysis. A detailed analysis performed for the spectral data (UV, IR; and 1H, 13C, NOESY, and HSQC NMR) allowed us to determine the spatial structure of the synthesized macrocycles. Aggregation properties of the obtained compounds with water-soluble tetrazole-containing polymers, viz. poly-5-vinyltetrazole (PVT) and polyvinyl(tetrazolyl)ethyl ether (PVTE), were evaluated. Pillar[5]-arene containing 2-hydroxyethylamide moieties formed monodisperse nanoscale aggregates with an average hydrodynamic diameter of 117 nm in the presence of PVTE in aqueous solution. The morphology of resulting particles was determined by scanning electron microscopy

Towards universal stimuli-responsive drug delivery systems: Pillar[5]arenes synthesis and self-assembly into nanocontainers with tetrazole polymers

In this work, we have proposed a novel universal stimulus-sensitive nanosized polymer system based on decasubstituted macrocyclic structures—pillar[5]arenes and tetrazole-containing polymers. Decasubstituted pillar[5]arenes containing a large, good leaving tosylate, and phthalimide groups were first synthesized and characterized. Pillar[5]arenes containing primary and tertiary amino groups, capable of interacting with tetrazole-containing polymers, were obtained with high yield by removing the tosylate and phthalimide protection. According to the fluorescence spectroscopy data, a dramatic fluorescence enhancement in the pillar[5]arene/fluorescein/polymer system was observed with decreasing pH from neutral (pH = 7) to acidic (pH = 5). This indicates the destruction of associates and the release of the dye at a pH close to 5. The presented results open a broad range of opportunities for the development of new universal stimulus-sensitive drug delivery systems containing macrocycles and nontoxic tetrazole-based polymers