Ferdinand Devínsky

Cut-off effects in biological activities of surfactants

In the homologous series of long hydrocarbon chain surface active compounds, their various biological activities increase progressively with increasing chain length up to a critical point, beyond which the compounds cease to be active. The paper reviews several hypotheses of this cut-off effect in biological activities and experimental evidences supporting them. It is suggested that the lateral expansion of the phospholipid bilayer of biological membranes caused by the intercalation of long-chain amphiphile molecules between the phospholipid molecules and the mismatch between their hydrocarbon chain lengths results in the creation of free volume in the bilayer hydrophobic region. The elimination of the free volume via the hydrocarbon chain trans-gauche isomerisation or interdigitation results in the bilayer thickness change or in its destabilisation and formation of non-bilayer phase(s). In combination with the partition and ionisation equilibria of amphiphiles in the lipid/aqueous phase systems, the free volume predicts similar chain length and pH dependencies as observed in biological experiments. It is suggested that the free volume mechanism, in combination with other mechanisms, could be responsible for the cut-off effects in biological activities of amphiphiles.

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.

Cut-off Effect in Antimicrobial Activity and in Membrane Perturbation Efficiency of the Homologous Series of N,N-Dimethylalkylamine Oxides†

Abstract— The antimicrobial activity of the homologous series of N,N‐dimethylalkylamine oxides (DMAO) was found to be quasi parabolically dependent on alkyl chain length with a maximum at n ∼ 15 and n ∼ 12 for Staphylococcus aureus and Escherichia coli, respectively. The physicochemical properties of DMAOs as characterized by critical micelle concentrations, retention times of 1‐alkenes generated from DMAOs by gas‐liquid chromatography, Rm values in reversed phase chromatography, and bacterial lipid/aqueous phase partition coefficients were found to correlate with the alkyl chain length. The effect of DMAOs on the structure of the model membrane prepared from isolated lipids from Escherichia coli as detected by a spin probe method was maximal for the alkyl chain length n ∼ 10–12 coinciding with the maximum in the antimicrobial activity observed with Escherichia coli. It is suggested that the cut‐off in the DMAO antimicrobial activity is caused by the cut‐off in the DMAO perturbing effect on the membrane structure.

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.

Interaction of surfactants with model and biological membranes.: II. Effect of N-alkyl-N,N,N-trimethylammonium ions on phosphatidylcholine bilayers as studied by spin probe ESR

The interaction of N-alkyl-N,N,N-trimethylammonium (CnTMA, n = 6-18) salts (iodides and/or bromides) with model membranes prepared by hydration of egg yolk phosphatidylcholine (EYPC) over aqueous salt solutions has been studied by m-doxyl stearic acid (m-DSA, m = 12 and 16) spin probe method. In disoriented EYPC bilayers the CnTMA salts decrease the orientational order parameter S33 of m-DSA evaluated from the powder pattern ESR spectra. This effect is maximal for C6TMA. In oriented EYPC bilayers prepared by the parallel-beam sputtering method and hydrated over saturated NaCl solution the order parameter S33 calculated from the angular dependence of the nitrogen hyperfine splitting is decreased in the presence of C6TMA. The order parameter S11 obtained from the angular dependence of line positions indicates deviation of m-DSA motion from axial symmetry. C6TMA increases the probability of gauche conformations of the lipid chains by about 13-14%, and decreases the effective energy difference between the trans and gauche conformations by about 420-480 J/mol, at molar ratio of EYPC/C6TMA = 2:1. The angular dependence of linewidths is analysed by employing a theory of spin relaxation based on the strong collision model for molecular reorientations. The correlation time tau 0 of the reorientation of an axis orthogonal to the doxyl ring of 16-DSA is decreased in the presence of C6TMA, while that of 12-DSA is not influenced by it. The ratio of tau 2/tau 0 is increased in the presence of C6TMA for the both spin probes. The results are explained using the free-volume model of the CnTMA-EYPC membrane interaction.

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.

Spherical dodecyltrimethylammonium bromide micelles in the limit region of transition to rod-like micelles. A light scattering study

Abstract Dynamic and static light scattering measurements were performed on dodecyltrimethylammonium bromide aqueous solutions in the presence of sodium bromide at different concentrations. The power law dependence was applied to the diffusion coefficient D vs. c b ( c , surfactant concentration) and the decrease of the parameter b with increasing salt concentration was observed. The dependencies of D and b on the salt concentration are decreasing and show a plateau at intermediate salt concentrations. The Debye plot from the static light scattering measurements shows the presence of stable spherical micelles in the solution at low salt concentration with molecular weight about 23 000 and aggregation number 65–80. The logarithmic plot of the molecular weight vs. the ionic strength shows two linear regions with an intercept at the salt concentration 1.9 M. However, the values of the molecular weight and the aggregation number are too small to allow the assumption of a rod structure.