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The protolytic and complexing properties of phosphorylated derivatives of calix[4]resorcinolarenes were studied by pH-metric titration at 298 K in water-2-propanol (80 vol % 2-propanol). It was shown that calix[4]resorcinolarene containing the propylphosphonic acid fragment at the C atom linking the aryl groups exists in solution mainly as tetramer. At pH > 4, the anions of tetrameric, dimeric, and monomeric forms of this compound are formed. The neutral form of aminomethylated calix[4]resorcinolarene contaning, along with the propylphosphonic acid fragment, the CH2NEt2 group on the opposite side of the molecule is monomeric. It exists as a zwitterion and contains four betaine protons. Three dimeric species of this compound, one protonated and two deprotonated, were revealed. The dissociation constants of the phosphonate groups and two betaine protons were evaluated. The other two betaine protons and the protons of hydroxy groups do not dissociate. The equilibrium constants of the complex formation with lanthanum(III) and in some cases the stability constants of the complexes were calculated. Probable modes of coordination of calix[4]resorcinolarenes are discussed. Depending on the acidity of the medium, the competition between the phosphonic group and the phenolate ions takes place, and complexes with the coordination via phosphonic groups can rearrange into complexes with the coordination via phenolate groups. [ABSTRACT FROM AUTHOR]

The problem of low efficiency of nanotherapeutic drugs challenges the creation of new alternative biomedical nanosystems known as robotic nanodevices. In addition to encapsulating properties, nanodevices can perform different biomedical functions, such as precision surgery, in vivo detection and imaging, biosensing, targeted delivery, and, more recently, detoxification of endogenous and xenobiotic compounds. Nanodevices for detoxification are aimed at removing toxic molecules from biological tissues, using a chemical- and/or enzyme-containing nanocarrier for the toxicant to diffuse inside the nanobody. This strategy is opposite to drug delivery systems that focus on encapsulating drugs and releasing them under the influence of external factors. The review describes various kinds of nanodevices intended for detoxification that differ by the type of poisoning treatment they provide, as well as the type of materials and toxicants. The final part of the review is devoted to enzyme nanosystems, an emerging area of research that provides fast and effective neutralization of toxins in vivo., (Copyright ® 2023 National Research University Higher School of Economics.)

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.2]octane with four charges and two hydrophobic chains (n-Dabco-s-Dabco-n, where s = 2, 6, 12 and n = 12, 14, 16, 18) were synthesized. A linear dependence of the CMC decrease, with the increase of the number of carbon atoms in alkyl groups (slope 0.23) was shown. The aggregation numbers of n-Dabco-2-Dabco-n are smaller than 30 and they decrease with increasing alkyl chain length. This is in compliance with the larger surface area per n-Dabco-2-Dabco-n molecule. New liposomal formulations loading Rhodamine B phosphatidylcholine (with mean size about 100 nm and increased zeta potential from -7 ± 2 mV to +55 ± 2 mV) have been successfully stabilized by n-Dabco-s-Dabco-n surfactants. These formulations were designed to improve the bioavailability and skin permeation of loaded compound. The antibacterial activity of Dabco-surfactants was shown to be strongly affected by their structure (alkyl chain length and number of charged nitrogen). 12-Dabco-2-Dabco-12 was the most active (MIC = 0.48, 0.98 and 15.6 µg/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 µg/mL concentration. PC/14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC = 7.8 μg‧mL -1 ) and lowest cytotoxicity (IC 50  > 125). The modification of liposomes by Dabco-surfactants stabilizes the membrane of the vesicles, preventing the release of rhodamine B and impairing the penetration of the dye across Strat-M® membrane. Cellular uptake of rhodamine B-loaded PC/12-Dabco-2-Dabco-12-liposomes was also reported. This is the first example of cationic mixed liposomes containing Dabco-surfactants of potential interest for transdermal drug delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Multitarget ligands (MTL) based on sterically hindered phenol and containing a quaternary ammonium moiety (SHP-n-Q) were synthesized. These compounds are inhibitors of cholinesterases with antioxidant properties. The inhibitory selectivity is 10-fold potent for BChE than for AChE. IC 50 of SHP-n-Q for BChE is 20 μM. SHP-n-Q and their nanosystems exhibit more pronounced antioxidant properties than the synthetic antioxidant (hindered phenol, butylated hydroxytoluene). These compounds display a low hemolytic activity against human red blood cells. The nanotechnological approach was used to increase the bioavailability of SHP-n-Q derivatives. For water soluble SHP-n-Q derivative, the self-assembled structures have a size close to 100 nm at critical association concentration (0.01 M). Mixed cationic liposomes based on l-α-phosphatidylcholine and SHP-n-Q of 100 nm diameter were prepared. The stability, encapsulation efficacy and release from liposomes of a model drug, Rhodamine B, depend on the structure of SHP-n-Q. Cationic liposomes based on l-α-phosphatidylcholine and SHP-3-Q show a good stability in time (1year) and a sustained release (>65 h). They are promising templates for the development of anti-Alzheimer MT-drug delivery systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)