FROM MACROCYCLES TO MOLECULAR SHUTTLES: EXPLORING THE SUPRAMOLECULAR ASSEMBLY OF RESORC[4]ARENES

Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cycloligomers) with a good solubility profile can improve solubilization of hydrophobic drugs.[1,2] Herein, we explore the ability of resorc[4]arenes (BSK, R1, R2 and R3) to self-assembly in polar solutions and to act as molecular shuttles of a poorly water-soluble isoflavone endowed with anticancer activity, namely Glabrescione B (GlaB).[3] Accordingly, we synthesized several 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 phenomenon of the amphiphilic resorc[4]arenes has been investigated in 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]arenebased systems can be modulated at given pH values, and thus promoting the solubility of GlaB.