Calix[4]arene Polyamine Triazoles: Synthesis, Aggregation and DNA Binding

Abstract

Artificial gene delivery systems are in great demand from both scientific and practical biomedical points of view. In this paper, we present the synthesis of a new click chemistry calix[4]arene precursor with free lower rim and new water-soluble calixarene triazoles with 12 amino-groups on the upper rim (one with free phenol hydroxyl groups and two another containing four butyl or tetradecyl fragments). Aggregation in the series of amino-triazole calixarenes of different lipophilicity (calixarene with free phenol hydroxyl groups or butyl and tetradecyl fragments on the lower rim) was studied using dynamic light scattering and fluorescent pyrene probe. It was found that calix[4]arene with a free lower rim, like alkyl-substituted butyl calix[4]arene, forms stable submicron aggregates 150–200 nm in size, while the more lipophilic tetradecyl –substituted calix[4]arene forms micellar aggregates19 nm in size. Using UV-Vis spectroscopy, fluorimetry and CD, it was shown that amino-triazole calix[4]arenes bind to calf thymus DNA by classical intercalation. According to DLS and TEM data, all studied macrocycles cause significant DNA compaction, forming stable nanoparticles 50–20 nm in size. Among all studied calix[4]arenes the most lipophilic tetradecyl one proved to be the best for both binding and compaction of DNA.

Aggregation, Cytotoxicity and DNA Binding in a Series of Calix[4]arene Amphiphile Containing Aminotriazole Groups

“…The addition of calixarenes 3 , 4 and 8 to DNA at a calixarene concentration of 5 μM led to the compactization of DNA from 562 nm to 150–100 nm and low values of the polydispersity index ( Figure S6 ). Previously [ 24 ], it was shown that the addition of calixarenes 3 and 4 to DNA does not cause changes in the native DNA structure, according to the circular dichroism (CD) method. The addition of calixarene 7 to DNA did not significantly decrease the average hydrodynamic diameter of the calixarene–DNA double system, even at an equimolar ratio of 1:1 (50 μM) ( Figure 5 a).…”

“…Solvents were purified according to standard methods. 3-Bis[2-(tertbutoxycarbonylamino)ethyl]propargylamine, 25,26,27,28-tetrahydroxycalix[4]arene, 5,11,17,23-tetraazo-25,26,27,28-tetrahydroxycalix[4]arene, 5,11,17,23-tetraamino-25,26,27,28-tetrahydroxycalix[4]arene [ 33 , 34 , 35 ] and 5,11,17,23-tetraazido-25,26,27,28-tetrahydroxycalix[4]arene, 5,11,17,23-tetraazido-25,26,27,28-tetratetradecyloxycalix[4]arene [ 23 , 24 ] were prepared following procedures in the literature.…”

“…Fluorescence emissions were registered in the range of 535–750 nm with excitation at 525 nm and a 3 nm slit. The CAC values were measured according to the method presented in [ 24 ].…”

“…TEM was performed on a Hitachi HT7700 ExaLens (Hitachi High-Tech Corporation, Tokyo, Japan). Sample preparation was performed using a previously developed method [ 24 ].…”

“…Previously, our research group developed a strategy for the synthesis of tetra-azide derivatives of calix [4]arenes with tetradecyl alkyl chain substitutes 1 and free hydroxyl groups on the lower rim 2 (Scheme 1), and triazole-containing macrocycles with diethylenetriammonium fragments 3 and 4 were obtained [23,24]. als 2023, 16, x FOR PEER REVIEW 2 of 15 excellent host macrocyclic compounds.…”