L. Ya. Zakharova

Supramolecular systems based on dicationic pyrimidine-containing surfactants and polyethyleneimine

Aggregates based on a novel pyrimidine-containing amphiphile containing three uracil fragments were quantitatively characterized. The critical micelle concentration (CMC) is 2 mmol L–1 and the degree of binding of counterions is β = 0.95, which is consistent with the low zeta potential of the micelles equal to +5 mV. Aggregates with a diameter of 45 nm are formed in the CMC region, and in the region of higher concentrations the aggregates are rearranged to micelle-like particles. In the presence of hydrophilic polymer polyethyleneimine, the CMC significantly decreases (to 0.2 mmol L–1), the degree of binding of counterions decreases, and the electrokinetic potential increases. The size of the aggregates in the binary system is 6—7 nm.

Alkylated 1,4-diazabicyclo[2.2.2]octanes: self-association, catalytic properties, and biological activity

Aggregation of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide in the presence of diethyl 4-nitrophenyl phosphate was studied using 1H NMR spectroscopy. The quantitative characteristics of the aggregation were determined. The data obtained were used to explain the catalytic effect of micelles on the hydrolysis of the phosphate. It was found that the aggregation properties and biological activity of alkylated mono- and dicationic 1,4-diazabicyclo-[2.2.2]octanes are correlated.

Catalysis of nucleophilic substitution reactions in supramolecular systems

The factors determining the catalytic effect of supramolecular systems on the nucleophilic substitution reactions are analyzed. The role of the structural and phase transitions of nanoaggregates in the catalytic mechanism are determined. The substrate specificity is shown for different structures of the supramolecular composition.

Catalytic properties of micellar systems based on 4-aza-1-alkyl-1-azoniabicyclo[2.2.2]octane bromides

The catalytic effect of micellar systems based on alkylated 1,4-diazabicyclo[2.2.2]octanes on the alkaline hydrolysis of butyl chloromethyl 4-nitrophenyl phosphonate is reported. The catalytic effect is due to the reactants concentrating in the micellar phase. It increases with an increase in the hydrophobicity of the surfactant. The bicyclic surfactant manifests the higher efficiency than its cyclic and noncyclic analogues. The micellization properties of alkylated 1,4-diazabicyclo[2.2.2]octanes in aqueous solutions have been investigated by the NMR method. An increase in the hydrophobicity of the surfactant decreases the critical micelle concentration and increases the hydrodynamic radius and aggregation numbers of the micelles.

Gemini surfactant-nonionic polymer mixed micellar systems

Tensiometry, dynamic light scattering, and optical spectrophotometry are employed to quantitatively characterize the aggregation behavior of a gemini (dicationic) surfactant in aqueous solutions in the presence of poly(ethylene glycol) with a molecular mass of 20000 Da or a Pluronic F127 block copolymer with a molecular mass of 12600 Da. It is shown that the formation of surfactant-polymer mixed aggregates decreases the positive surface potential of gemini surfactant micelles and is one of the main reasons for weakening of the micellar catalytic effect in hydrolysis of carboxylic acid esters.

Catalytic properties of polymer-colloid complexes based on polyethyleneimines and mono- and diquaternized 1,4-diazabicyclo[2.2.2]octane derivatives in the hydrolysis of phosphorus acids esters

It is established by spectrophotometry that polyethyleneimines, mono- (MQD) and diquaternized (DQD) hexadecyl derivatives of 1,4-diazabicyclo[2.2.2]octane, and mixed polymercolloid systems based thereon catalyze the hydrolysis of p-nitrophenyl alkyl chloromethylphosphonates. The catalysis efficiency depends on the structures of substrate, 1,4-diazabicyclo-[2.2.2]octane derivatives, and polyethyleneimine, pH of the medium, and the temperature. In the case of MQD, the catalytic effect changes from 20 to 80-fold with an increase in the length of phosphonate alkyl radical from R = OEt to R = OC6H13; the DQDs exhibit lower catalytic activity compared to the MQD. The most efficient catalysis (up to 90-fold acceleration) is observed for a mixed polyethylene—dicationic surfactant system where the surfactant contains the hydroxyethyl fragment in the head group, which is due to a favorable effect of the micellar microenvironment of reagents.

Solubilizing and catalytic properties of supramolecular systems based on gemini surfactants

Quantitative parameters characterizing the aggregation behavior of dicationic surfactants of the 12-s-12 type in aqueous solutions were determined: critical micelle concentrations, aggregation numbers, and surface potentials. The effects of the spacer length of the surfactants on their solubilizing effect with respect to hydrophobic (dye Orange OT) and water-soluble (p-nitrophenol) spectral probes and on their ability to shift acid-base equilibria were studied. The kinetics of alkaline hydrolysis of p-nitrophenyl acetate and p-nitrophenyl caprinate in 12-s-12 solutions was studied by spectrophotometry. A correlation between the micellar catalytic effect and the surface potential of micelles was established. The pronounced substrate specificity was revealed: the maximum acceleration of hydrolysis is observed in solutions of 12-6-12, attaining 1760 times for p-nitrophenyl caprinate.

Solubility and hydrolytic stability of indomethacin in aqueous micellar solutions

The solubility of the indomethacin drug in aqueous micellar solutions of a series of dicationic surfactants was characterized by spectrophotometry. The use of these surfactants can significantly increase the indomethacin content in aqueous solutions without destruction of the drug. The increase in the solubility can be explained by the multifactorial mechanism of the influence of micelles involving the solubilization of the drug and its binding with surfactants due to electrostatic and specific interactions. The use of dicationic surfactants in alkaline solutions was shown to markedly accelerate the hydrolytic cleavage of indomethacin. The highest catalytic effect is observed for N,N´-(hexane-1,6-diyl)bis(2-hydroxyethyl)(methyl)(cetyl)ammonium dibromide: a 1200-fold increase in the reaction rate of alkaline hydrolysis of the drug.

Effect of surfactant micelles on solubility and spectral characteristics of 2,2’-bibenzimidazole

The solubilization capacity of surfactants of different types was quantitatively characterized by spectrophotometry toward 2,2’-bibenzimidazole (BBI), whose derivatives possess a wide range of pharmacological activity. 2,2’-Bibenzimidazole solubilized by sodium dodecyl sulfate micelles is characterized by a high molar absorption coefficient (9400 mol−1 L cm−1) at the absorbance maximum (342 nm at pH 4–10), which may serve as a basis for the development of procedures for analytical monitoring of the BBI content in aqueous solutions and biosystems. The ability of surfactants to enhance the solubility of BBI in water and, as a consequence, to increase its bioavailability in the series sodium dodecyl sulfate < cetyltrimethylammonium bromide < Tween-80.

Cationic gemini surfactants as new agents for plasmid DNA delivery into cells

197 Gene therapy has a great potential for treating many human diseases that are currently considered incurable. Viral vectors based on adenoviruses or rett roviruses are very effective in gene delivery. Neverthe less, in view of the problems associated with immunoo genicity and biosafety of viral vectors, there remains a need to develop nonviral vectors. As an alternative to viral vectors, cationic polymers [1–3] and liposomes [4], which bind to DNA through electrostatic interacc tions and form nanosized complexes, have been invess tigated [5, 6]. Cationic agents protect DNA from degg radation by nucleases and serve as mediators in the penetration into the cell and subsequent release from endosomes, which increases the efficiency of transfecc tion. The use of cationic surfactants as nonviral vectors was described in several papers [6, 7]. It is shown that they are effective agents that provide the compaction of DNA and recharging of the complex. Despite the obvious advantages (simplicity of synthesis and forr mulation, low concentration, availability, and high complexing ability), a significant drawback of synn thetic agents based on cationic surfactants is the low transfection efficiency. In view of this, the search for new cationic vector systems is a relevant problem. In this study, we investigated alkylammonium gemm ine surfactants (AGSs) with the formula , where m = 4–12, R = СН 3 , С 2 Н 4 ОН, R 1 = nC n Н 2n + 1 , where n = 10, 12, 14, and 16. Aqueous solutions of these compounds ensure efficient delivery of DNA into cells. Gemine surfactants (alkanedyllα,ω bis(methyldialkylammonium bromides)) were pree pared under laboratory conditions as described in [8]. The structure of the obtained compounds was conn firmed by elemental analysis as well as by IR and NMR spectroscopy data. Cell line 293T (human embryonic kidney epithee lium cells), which was used as a producer of pseudoo lentiviruses and as a model target cell line, was mainn tained by the standard procedure. We used the peGFPPN1 plasmid (Clontech, United States), which is 5100 bp in length and expresses the green fluoress cent protein, and the pCIINEO plasmiddbased vector (Promega, United States), which is 5000 bp in length and does not contain the green fluorescent protein gene. HEK293T cells were replated 40 thousand cells per well one day before transfection. To transfect HEK293T cells, 50–100 thousand cells per well of a 966well plate were used. One hour before transfection, …