Towards nanomaterials with tubular pores: synthesis and self-assembly of bis-pillar[5]arene

Recently, materials obtained using supramolecular chemistry approaches, and, in particular, spatially preorganized macrocyclic compounds, have attracted close attention of the researchers. Pillar[n]arenes are of special interest due to their tubular spatial structure and macrocyclic cavity. A similar tubular structure is retained in the supramolecular packaging of pillar[5]arene crystals, forming pores. In this study, we developed a block synthetic approach for the preparation of bis-pillar[5]arene containing amide groups. The ability of the synthesized bis-pillar[5]arene to form stable self-associates in solvents of different polarity (CHCl3 and CH3OH) was demonstrated by the DLS method. In trichloromethane at concentration of 1·10–3 M, monodisperse associates with average hydrodynamic diameter of 227 nm (PDI = 0.28) are formed; in methanol, stable associates (1·10–6 M) have an average hydrodynamic diameter of 136 nm (PDI = 0.21). The results obtained can be used to create new supramolecular systems, molecular machines, or capture and detect various organic molecules.

Fluorescein-Labeled Thiacalix[4]arenes as Potential Theranostic Molecules: Synthesis, Self-Association, and Antitumor Activity

In this paper, a series of thiacalix[4]arenes were synthesized as potential theranostic molecules for antitumor therapy. We propose an original strategy for the regioselective functionalization of thiacalix[4]arene with a fluorescent label to obtain antiangiogenic agent mimetics. The aggregation properties of the synthesized compounds were determined using the dynamic light scattering. The average hydrodynamic diameter of self-associates formed by the macrocycles in 1,3-alternate conformation is larger (277–323 nm) than that of the similar macrocycle in cone conformation (185–262 nm). The cytotoxic action mechanism of the obtained compounds and their ability to penetrate into of human lung adenocarcinoma and human duodenal adenocarcinoma cells were established using the MTT-test and flow cytometry. thiacalix[4]arenes in 1,3-alternate conformation did not have a strong toxic effect. The toxicity of macrocycles in cone conformations on HuTu-80 and A549 cells (IC50 = 21.83–49.11 µg/mL) is shown. The resulting macrocycles are potential theranostic molecules that combine both the pharmacophore fragment for neoplasmas treatment and the fluorescent fragment for monitoring the delivery and biodistribution of nanomedicines

Supramolecular Amphiphiles Based on Pillar[5]arene and Meroterpenoids: Synthesis, Self-Association and Interaction with Floxuridine

In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2′-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy