Towards Universal Stimuli-Responsive Drug Delivery Systems: Pillar[5]arenes Synthesis and Self-Assembly into Nanocontainers with Tetrazole Polymers

Abstract

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.

Crystal structure and supramolecular features of a bis-urea-functionalized pillar[5]arene

“…all ten functionalization sites are substituted with N-phenyl triazole (CECDAR; Deng et al, 2012), N-(naphthalen-2-ylmethyl)trizole (ACIYOC: Yu et al, 2012) or phthalimide (QUYCOF; Yuan, 2020) have also been reported. The crystal structures of 4,9,14,19,24,26,28,30,32,34-decakis[2-(morpholin-4-yl)ethoxy]pillar [5]arene in which pillararene is functionalized with ten morpholine fragments (CIZFID; Xia et al, 2018) and that of 4,8,14,18,23,26,28,31,32,35-deca-[2-(pyrrolidin-1yl)ethoxy]pillar [5]arene in which in which pillararene is functionalized with ten pyrrolidine fragments at their periphery (JAPGAM; Shurpik et al, 2021) have also been reported in the literature. Another structurally related macrocycle reported is 5,11,17,23,29-31,32,33,34,35-decakis{2-[2-(4-t-butylbenzoyl)hydrazinyl]-2-oxoethoxy}calix(5)arene tridecahydrate (KUYFAN; Hu et al, 2012).…”

Breaking the size constraint for nano cages using annular patchy particles

“…These structures will find applications in vaccine production, acting as nanoreactors, 3 drug delivery systems, etc. 1,2 In the biological world we know that the subunits of certain kinds of viruses aggregate together to form spherical closed structures with icosahedral symmetry. At very low temperature, the nucleation rates of these subunits are very high and the yield of the closed shells falls leading to partially open shells, as reported in the kinetic study of the shell growth of viral capsids 31 in solution.…”

“…With the advancement in our understanding of nanoscale phenomena, researchers have found ways to synthesize different types of nanocages. The possible uses of these cages are in targeted drug delivery, 1,2 nanoreactors, 3 nanocontainers 4 etc. Recently it was shown that using nanocages it is possible to trap viruses, thus giving us a new method of treatment for viral infections.…”

Self-Assembling Systems Based on Pillar[5]arenes and Surfactants for Encapsulation of Diagnostic Dye DAPI

“…The cooperative action of the cavity and substituents is particularly characteristic during the complexation of charged macrocycles and a substrate, for example, surfactant molecules [ 23 , 24 , 25 , 26 , 27 ]. As a result, 1:1 host–guest complexes are formed [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In addition, the ability of water-soluble macrocycles, by analogy with non-macrocyclic surfactants, to form various types of associates such as liposomes [ 36 , 37 , 38 ], micelles [ 39 , 40 , 41 ], and liquid crystals [ 42 , 43 ], etc., is well known.…”