Elena P. Zhiltsova

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.

Self-assembling systems based on quaternized derivatives of 1,4-diazabicyclo[2.2.2]octane in nutrient broth as antimicrobial agents and carriers for hydrophobic drugs.

Aggregation properties of mono (mono-CS) and dicationic (di-CS) surfactants, namely quaternised derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), have been evaluated in water and in nutrient broths of different pH, i.e. in Hottinger broth (рН=7.2) and Sabouraud dextrose broth (рН=5.6). Aggregation capacity of surfactants was shown to be responsible for the solubilization properties of a complex composed of a hydrophobic probe (Sudan I) and a selected drug (quercetin), contributing to the antimicrobial activity of this surfactant system. The effect of N-methyl-d-glucamine (NmDg) additive on the antimicrobial activity of mono-CS, and its aggregation and solubilization parameters, has also been evaluated. A substantial decrease in critical micelle concentration (CMC) of cationic surfactants in nutrient broths (up to 60 times) has been reported. Twofold dilution of monocationic surfactant by NmDg slightly changed the CMC of surfactant; however, it provided a remarkable increase in solubilization capacity (∼by 4 times) and decrease in its toxicity. The data anticipate the potential use of DABCO quaternized derivatives as innovative non-toxic delivery systems for hydrophobic drugs.

Amphiphilic O-functionalized calix[4]resocinarenes with tunable structural behavior

Novel amphiphilic calix[4]resorcinarenes oxyethylated at the upper rim and alkylated at the lower rim (CR–CnH2n+1, here n is the number of carbon atoms in the alkyl substituent; n = 2,5,7,8,9,11) were synthesized, and their association behavior in water-organic solvents was explored. Surface properties and the association behavior of CRs were shown to be strongly controlled by their structure and the nature of the co-solvent. Solely CR–C5H11 demonstrates surface activity in the mixed water–DMF and water–DMSO solutions, while no surface activity occurs in the water–THF mixture. The DLS measurements revealed a very low concentration threshold of the aggregation (around 0.01 mM) for the CR series including surface inactive compounds. In water–DMF and water–DMSO solutions the CRs of low hydrophobicity were shown to associate through an open model with the formation of large aggregates of 300–400 nm, while more hydrophobic CRs can associate through a closed model and form rather small micelle-like aggregates of 10 to 20 nm.

Phosphorylation of Polyethylene Imines in Chloroform in the Presence of Calix(4)resorcinarenes

Kinetics of the reaction of alkylated polyethylene imines with 4-nitrophenyl bis(chloromethyl)-phosphinate in chloroform in the absence and in the presence of substituted calix[4]resorcinarenes were studied by UV spectrophotometry. It was shown that calixarenes forming mixed aggregates with polyethylene imines have a catalytic effect on the polymer phosphorylation process. The catalytic effect depends on the structure of polyethylene imine and the component ratio in the system.

Supramolecular Systems Based on Aminomethylated Calix(4)resorcinarene and a Cationic Surfactant: Catalysts of the Hydrolysis of Esters of Phosphorus Acids

Kinetics of alkaline hydrolysis of 4-nitrophenyl esters of tetracoordinated phosphorus acids in micellar solutions of aminomethylated calix[4]resorcinarene containing sulfonatoethylene groups on the lower rim of the macrocycle, 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide and their mixtures was investigated spectrophotometrically. It is established that the catalytic effect of aggregates depends on the concentration of calixarene and surfactants, pH, presence of lanthanum salt and reaches more than two orders of magnitude. The parameters of the catalyzed reactions and their dependence on the composition are determined.

Complexation of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide with nickel nitrate in acetone

The complexation of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide with Ni(II) nitrate in acetone is studied by means of spectrophotometry (the Job–Ostromisslensky technique and molar ratios). The formation of 3: 1 and 1: 1 ligand: metal complexes is established and confirmed by mathematical modeling. The stability constants of the complexes and the change in the Gibbs free energy are determined.

Complexes of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide with transition metal nitrates. Micelle-forming, solubilizing, and adsorption properties

Amphiphilic complexes of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide (D-16) with nitrates of transition metals (La3+, Cu2+, Ni2+, and Co2+) have been synthesized and characterized. Absorption spectrophotometry in the UV, visible, and IR regions, as well as 1Н NMR spectroscopy, have been employed to study their spectral properties in water and organic media. Adsorption properties and micelleforming and solubilizing abilities of the amphiphilic complexes have been investigated in aqueous solutions by the methods of tensiometry and conductometry, as well as by solubilization of a water-insoluble dye (Orange OT). The values of the critical micelle concentration, adsorption parameters at a water/air interface, and solubilization capacity S of complex micelles have been determined. It has been shown that the most pronounced decrease in the critical micelle concentration (as large as two to three times) and differences in the adsorption characteristics and the S values as compared with those of ligand D-16 are observed for complexes of copper and lanthanum. The S values for these complexes are 1.3−2.5 and 3−6.5 times higher than those for D-16 and cetyltrimethylammonium bromide, respectively.

Supramolecular catalytic systems based on 1, 4-diazabicyclo[2.2.2]octane, its alkylated quaternary derivatives, and lanthanum nitrate

Spectrophotometry was used to study the catalytic effects of the systems composed of N-monoand N, N-dialkylated 1, 4-diazabicyclo[2.2.2]octanes and lanthanum nitrate on the hydrolysis rate of O-alkyl O-4-nitrophenyl chloromethylphosphonates (Alk = Et, Bun, and n-hexyl). The mechanism of action and efficiency of the catalytic system depend on the structure of the heterocycle, its propensity to aggregation and complexation with the lanthanum cation, and the relative content of the components in solution. The maximum catalytic effect (a ∼115-fold increase in the hydrolysis rate constant) was achieved in micellar solutions of the cationic monoalkylated derivative of 1, 4-diazabicyclo[2.2.2]octane and lanthanum nitrate.

Aminolysis ofO-alkylO-4-nitropyenyl chloromethylphosphonates in reverse micellar solutions of the nonionic surfactant

The reaction ofn-hexylamine withO-alkylO-4-nitrophenyl chloromethylphosphonates in toluene solutions of poly(ethylene glycol)-600 monolaurate (PM) has been studied by spectrophotometry. The reverse micelles of the nonionic surfactant increase more than tenfold the observed rate constant of aminolysis. The catalytic activity of the surfactant is practically independent of the alkyl radical length of phosphonate. An increase in the concentration of amine results in a decrease in the catalytic efficiency. The character of the dependence of the rate constant on the concentration of PM is affected by the alkyl chain length of the substrate.

Kinetics of alkaline hydrolysis of ethylp-nitrophenyl ethylphosphonate in the reverse micellar system: sodium dodecyl sulfate-hexanol-water

The kinetics of alkaline hydrolysis of ethylp-nitrophenyl ethylphosphonate in the reverse micellar system sodium dodecyl sulfate—hexanol—water was studied. At high pH and low water content, the process occurs at the surface layer and can satisfactorily be described by the pseudo-phase model equation.