Exploring the assembly of resorc[4]arenes for the construction of supramolecular nano-aggregates

Abstract

Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocy-cles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubiliza-tion of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone en-dowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized sev-eral architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phe-nomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV– visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.