Ivan Lacko

Relationship between structure and solubilization properties of some bisquaternary ammonium amphiphiles

Abstract The effect of structure changes of two series of bis-quaternary ammonium salts, the so-called bola-amphiphiles, of N,N′-bis(alkyldimethyl)-α,ω-alkanediammonium dibromides type, where the alkyl chain had 8 to 16 carbon atoms and the connecting chain had 2 to 12 carbon atoms upon the solubilizing capacity and aggregation properties of their aqueous solutions was examined. From solubilization data the critical micelle concentration (CMC) was also determined. With N,N′-bis(alkyldimethyl)-1,6-hexanediammonium dibromides the solubilizing capacity as well as the CMC were linearly dependent upon structure changes. However, with N,N′-bis(decyldimethyl)-α,ω-alkanediammonium dibromides nonlinear relationships were observed with both characteristics related to structure changes. The maximum solubilizing capacity was observed with compound with n = 6 and 8 (m = constantly decyl) contrary to the CMC which was found to be maximal in the region of compounds with n = 4 to 6. The anomalous courses of these relationships were elucidated in terms of spatial arrangements of the micelles.

Quantitative relationships between structure and antimicrobial activity of new “Soft” bisquaternary ammonium salts

New surface-active bisquaternary ammonium salts derived from bis-(2-dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts. Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology. The nonlinear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration—CMC) was shown using Kubinyi’s bilinear model. The most effective compounds were those with the alkyl chain of 11–12 carbon atoms and with the CMC values around 0.7−1.0 mmol/L. These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria.

INTERACTION OF AMINE OXIDES AND QUATERNARY AMMONIUM SALTS WITH MEMBRANE AND MEMBRANE-ASSOCIATED PROCESSES IN E. COLI CELLS: MODE OF ACTION

The antimicrobials (1-methyldodecyl)dimethylamine oxide and (1-methyldodecyl)trimethylammonium bromide affect the cytoplasmic membrane of E. coli. The interaction results in release of intracellular material (K+, 260nm-absorbing material), an effect on dehydrogenase enzyme activity and inhibition of respiration. The final effect of both substances is the same; they differ only in their dynamics. The effect of the membrane was correlated with parameters characterizing these surfactants i.e. critical micelle concentration (c.m.c.) minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) over the concentration range of 10(-4) to 10(-1) mmol/dm3 of active substance. The three stage mode of action model can be summarized as follows: 1-polar (coulombic) interactions, 2-polar and hydrophobic interactions, 3-hydrophobic interactions (extraction and solubilization). The polar and hydrophobic interactions (1st and 2nd stage) are discussed also in relation to model membranes.

Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine.

We synthesized nine quaternary ammonium compounds (QUATs) starting from phenylalanine, N-alkyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromides, which were prepared as optically pure substances. Five compounds were prepared as S-enantiomers and four compounds as R-enantiomers. These compounds were evaluated by their activities against bacteria and fungi. Three microbial strains were used in the study: the gram-negative bacteria Escherichia coli, the gram-positive bacteria Staphylococcus aureus and the fungi Candida albicans. The activities were expressed as minimum bactericidal or fungicidal concentrations (MBC). The most active compounds were (2S)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide and (2R)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide, with MBC values exceeding those of commercial benzalkoniumbromide (BAB) used as standard. The relationships between structure and biological activity of the tested QUATs were quantified by the bilinear model (QSAR) and are discussed.

Biodegradable gemini surfactants. Correlation of area per surfactant molecule with surfactant structure

Values of the area per surfactant molecule of various single chain and gemini quaternary ammonium surfactants containing biodegradable amide and ester groups are obtained from the surface tension measurements and they are mutually compared. It was found that surfactant molecules with the ester group in their structure occupy smaller area at the air/water interface than the corresponding molecules with the amide group, mainly due to the higher conformational flexibility of ester groups. In decreasing the area per surfactant molecule value, hydrogen bonding (both inter- and intramolecular) plays a significant role when amide groups are present in the spacer of a gemini molecule. They must be separated by a polymethylene chain or a flexible group such as cyclohexane which is short enough to allow intramolecular hydrogen bonds. The flexible cyclohexane group with the amide group in single chain surfactants may lead to the formation of intermolecular hydrogen bonds among surfactant molecules which also results in the reduction of the area per surfactant molecule.

The ionic strength effect on the DNA complexation by DOPC — gemini surfactants liposomes

Liposome dispersions obtained from the mixture of gemini surfactants of the type alkane-α,ω-diyl-bis(alkyldimethylammonium bromide) and helper lipid DOPC create complexes with DNA showing a regular inner microstructure, identified by small angle X-ray diffraction as condensed lamellar phase (L(α)(c)). In addition to the L(α)(c) phase, a coexisting lamellar phase L(B) was also identified in the complexes formed, with periodicities in the range ~8.8-5.7nm, at ionic strengths corresponding to 50-200mM NaCl. The periodicities of L(B) phase did not correspond to those identified in liposome dispersion without DNA using small angle neutron scattering. The observed phase separation is shown to depend on the interplay between the surface charge density of cationic liposomes, ionic strength and method of complex preparation. The effect of ionic strength on complex formation was studied by isothermal titration calorimetry and zeta potential measurements. High ionic strength reduces the fraction of bound DNA in the complexes, and the isoelectric point is attained at a ratio of DNA/gemini surfactant which is lower than the one that can be estimated by calculation based on nominal charges of CLs and DNA.

Dynamic light scattering and electrokinetic potential of bis(quarternary ammonium bromide) surfactant micelles as the function of the alkyl chain length

Abstract The micellar properties of bis(quarternary ammonium bromide) surfactants were studied by means of dynamic light scattering and electrokinetic measurements. The coexistence of small spherical micelles and large aggregates for surfactants with eight to 12 carbon atoms in the alkyl chain is observed. Below this region, only spherical micelles appear and above 12 carbon atoms, large aggregates are present. The electrokinetic measurements of zeta potential correspond with the light scattering results. Bimodality in the peaks was observed in the region of nine to 12 carbon atoms in the alkyl chain. As follows from the light scattering results, solubilization with a monomeric surfactant showed that, in the case of dodecyltrimethylammonium bromide (DTAB) and 12-4-12 surfactant, the presence of large aggregates decreases strongly with increasing DTAB concentration in the system. No such observation was made when hexadecyltrimethylammonium bromide (CTAB) was present in the system with 16-4-16 surfactant, where only unimodal size spectra were registered.

Photosynthesis-inhibiting Effects of Cationic Biodegradable Gemini Surfactants

Abstract Cationic biodegradable gemini surfactants 3,8-diaza-4,7-dioxodecane-1,10-diylbis(alkyldimethylammonium bromide) (I) with R = C9H19–C18H37 inhibited photosynthetic electron transport (PET) in spinach chloroplasts and reduced chlorophyll (Chl) content in Chlorella vulgaris. The inhibitory effects of I intensively depended on the length of alkyl chain showing quasi-parabolic (Chlorella vulgaris) or bilinear (PET) course. IC50 value related to reduction of Chl content in C. vulgaris for dodecyl derivative was 0.6 × 10−6 mol dm−3 indicating its strong anti-algal effect. Using EPR spectroscopy as the site of inhibitory action of I in the photosynthetic apparatus the intermediates Z∗ and D∗ or their close surroundings were determined. As a further target of I inhibitory action the manganese cluster occurring on the donor side of photosystem II was estimated.

Aggregates of sodium hyaluronate with cationic and aminoxide surfactants in aqueous solution — light scattering study

Aggregation properties of sodium hyaluronate (NaHA) with different types of surfactants in aqueous sodium chloride solution have been studied by using static and dynamic light scattering method. Molecular weight, second virial coefficient, radius of gyration, and hydrodynamic radius have been calculated. The polymer — surfactant aggregate growth was found in complexes of NaHA with an ionic surfactant (dodecyltrimethylammonium bromide) and ionic, dimeric surfactants (dodecanediyl-α,ω-bis(dimethyloctylammonium bromide) and N,N′-bis(dodecyldimethyl)-4,13-dioxo-3,14-dioxahexadecane-1,16-diyldiammonium dibromide). In case of dodecyldimethylamine oxide (DDAO), the decreasing molecular weight and aggregate size of the NaHA — DDAO complex with increasing DDAO concentration were found above the surfactant critical micelle concentration, indicating the absence of electrostatic interactions between NaHA and DDAO that would lead to the increase in aggregate size. This behaviour may be ascribed to the non-ionic character of DDAO.

Synthesis and biological activity of dialkylphosphocholines

A series of dialkylphosphocholines were prepared and evaluated for their biological activity. The antiprotozoal activity was determined against Acanthamoeba lugdunensis. Compound 15 exhibited excellent trophocidal activity. None of the tested dialkylphosphocholines exhibited better fungicidal activity against Candida albicans than miltefosine. The antineoplastic activity was determined against HeLa. The most cytotoxic was compound 10, which was more active against tumor cells as against normal cells.