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 macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization 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 endowed with anti-cancer activity, namely Glabrescione B (GlaB). 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 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.
Highlights
Published: 29 October 2021A wide range of biologically active compounds suffers from poor aqueous solubility impairing their bioavailability and, as a result, their preclinical and clinical development
We demonstrated that physical descriptors, namely the aggregation polarity index (API), the cavitation Gibbs free-energy change (∆∆Gcav), and the decrease of the molecular surface (A) after the exposure of solute to the solvent upon aggregation
The self-assembled molecules of R2 show a strong surfactant action, as evidenced by the formation of a thick layer of foam (Figure 7). These results suggest that, in such an experimental condition, the resorc[4]arene R2 might act as an effective molecular shuttle of hydrophobic structures
Summary
Published: 29 October 2021A wide range of biologically active compounds suffers from poor aqueous solubility impairing their bioavailability and, as a result, their preclinical and clinical development. The self-assembly process of well-defined structures from various chemical building blocks have found exponential growth in the development of drug delivery and bio-nanotechnology systems [1]. These assemblies give the possibility to encapsulate pharmaceutically active compounds in their core (or at their surface) and to cargo them to the therapeutic targets [2]. Among the large pool of macrocycles available, calixarene-based macrocycles are one of the most ubiquitous host molecules in supramolecular chemistry These macrocycles are cyclic oligomers characterized by a unique three-dimensional surface, featuring several phenolic units bound with methylene
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