For the first time, a series of catechol-containing Schiff bases, tetrasubstituted at the lower rim thiacalix[4]arene derivatives in three stereoisomeric forms, cone, partial cone, and 1,3-alternate, were synthesized. The structure of the obtained compounds was proved by modern physical methods, such as NMR, IR spectroscopy, and HRMS. Selective recognition (K_b difference by three orders of magnitude) of copper (II) cation in the series of d-metal cations (Cu²⁺, Ni²⁺, Co²⁺, Zn²⁺) was shown by UV-vis spectroscopy. Copper (II) ions are coordinated at the nitrogen atom of the imine group and the nearest oxygen atom of the catechol fragment in the thiacalixarene derivatives. High thermal stable organic-inorganic copper-based materials were obtained on the base of 1,3-alternate + Cu (II) complexes.

A convenient method for the synthesis of the first generation PAMAM dendrimers based on the thiacalix[4]arene has been developed for the first time. Three new PAMAM-calix-dendrimers with the macrocyclic core in cone, partial cone, and 1,3-alternate conformations were obtained with high yields. The interaction of the obtained compounds with salmon sperm DNA resulted in the formation of the associates of the size up to 200 nm, as shown by the UV-Vis spectroscopy, DLS, and TEM. It was demonstrated by the CD method that the structure of the DNA did not undergo significant changes upon binding. The PAMAM-calix-dendrimer based on the macrocycle in cone conformation stabilized DNA and prevented its degradation.

Cancer is one of the most common diseases in developed countries. Recently, gene therapy has emerged as a promising approach to cancer treatment and has already entered clinical practice worldwide. RNA interference-based therapy is a promising method for cancer treatment. However, there are a number of limitations that require vectors to deliver therapeutic nucleic acids to target tissues and organs. Active research is currently underway to find highly effective, low-toxic nanomaterials capable of acting as nanocarriers. In this study, we demonstrated for the first time the ability of symmetrical polyamidoamine dendronized thiacalix[4]arenes (PAMAM-calix-dendrimers) to form stable positively charged complexes with siRNAs, protect them from enzymatic degradation, and efficiently deliver gene material to HeLa cells. A distinctive feature of PAMAM-calix-dendrimers was the unusual decrease in hemo- and cytotoxicity with increasing generation, while these compounds did not cause toxic effects at concentrations required for siRNA binding and delivery. A comparative analysis of the efficiency of complex formation of PAMAM-calix-dendrimers and classical PAMAM dendrimers with siRNAs was also performed. The findings may facilitate the creation of novel unique gene delivery systems for cancer nanomedicine development.

In this work, we investigated aggregation of native DNA and thiacalix[4]arene derivative bearing eight terminal amino groups in cone configuration using various redox probes on the glassy carbon electrode. It was shown that sorption transfer of the aggregates on the surface of the electrode covered with carbon black resulted in changes in electrostatic interactions and diffusional permeability of the surface layer. Such changes alter the signals of ferricyanide ion, methylene green and hydroquinone as redox probes to a degree depending on their specific interactions with DNA and own charge. Inclusion of DNA in the surface layer was independently confirmed by scanning electron microscopy, electrochemical impedance spectroscopy and experiments with doxorubicin as a model intercalator. Thermal denaturing of DNA affected the charge separation on the electrode interface and the signals of redox probes. Using hydroquinone, less sensitive to electrostatic interactions, made it possible to determine from 10 pM to 1.0 nM doxorubicin (limit of detection 3 pM) after 10 min incubation. Stabilizers present in the commercial medications did not alter the signal. The DNA sensors developed can find future application in the assessment of the complexes formed by DNA and macrocycles as delivery agents for small chemical species.