RESUMEN
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.
Asunto(s)
Calcitriol/análogos & derivados , ADN/química , Liposomas/química , Fosfatidilcolinas/química , Tensoactivos/química , Animales , Calcitriol/química , Bovinos , Concentración OsmolarRESUMEN
Synthesis of five alkylphosphocholines with branched alkyl chains (Isophol-PCs) with different length of alkyl chains was described. Isophol(8)-PC and Isophol(12)-PC represent new compounds. The physico-chemical properties of Isophol-PCs were determined, critical micelle concentration and types of formed aggregates in aqueous solutions were investigated. The biological activities of Isophol-PCs have been studied for the first time in the present study. Antimicrobial activities of alkylphosphocholines were studied against bacteria (Staphylococcus aureus, Escherichia coli), yeast (Candida albicans) and pathogenic free-living amoebae (Acanthamoeba lugdunensis and Acanthamoeba quina). A. lugdunensis and A. quina are relatively insusceptible to action of miltefosine (standard compound of alkylphosphocholines) and therefore they are good models for studies of amoebicidal action of the investigated compounds. Relationship between structure, physico-chemical and biological activities of Isophol-PCs was discussed. S. aureus and C. albicans were sensitive to action of Isophol(16)-PC, Isophol(20)-PC. E. coli was not sensitive to action of all studied alkylphosphocholines in the concentrations equal to, or less than 10mM. Among all the synthesized compounds, Isophol(16)-PC had the highest level of activity against both strains of Acanthamoeba. The minimum trophocidal concentrations of Isophol(16)-PC against A. lugdunensis and A. quina are about four times lower than the minimum trophocidal concentrations of miltefosine against both strains.
Asunto(s)
Antiinfecciosos/farmacología , Fosforilcolina/farmacología , Acanthamoeba/efectos de los fármacos , Acanthamoeba/crecimiento & desarrollo , Antiinfecciosos/síntesis química , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Micelas , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fosforilcolina/análogos & derivados , Fosforilcolina/síntesis química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Relación Estructura-Actividad , Factores de TiempoRESUMEN
The solubilisation of two natural compounds, griseofulvin and rutin, in micellar solutions of mixtures of gemini (N,N'-didecyl-N,N,N',N'-tetramethylethane-1,2-diyldiammonium dibromide) and heterogemini (decyl 2-[decyl(dimethyl)ammonio]ethylphosphate) surfactants has been studied. The highest solubilisation capacities were found for mixtures with a molar fraction of heterogemini surfactant equal or greater than the molar fraction of gemini surfactant. The relationship between synergism in surface properties of mixtures of surfactants and their solubilisation properties was also investigated.
Asunto(s)
Griseofulvina/química , Compuestos de Amonio Cuaternario/química , Rutina/química , Tensoactivos/química , Espectroscopía de Resonancia Magnética , Micelas , Estructura Molecular , Solubilidad , Soluciones , Propiedades de SuperficieRESUMEN
The physico-chemical properties of dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine (HPC) and cetyltrimethylammonium bromide (CTAB) were investigated. The surface properties, such as the critical micelle concentration (cmc), the surface tension value at the cmc (gamma(cmc)), and the surface area at the surface saturation per head group (A(cmc)) were determined by means of surface tension measurements. Micelle size was determined using the dynamic light scattering method. The influence of dialkylamino groups and heterocyclic ring size on surface-active properties was investigated. Surface activity and micellar size of prepared analogues of HPC and CTAB were mutually compared.
Asunto(s)
Compuestos de Cetrimonio/química , Nitrógeno/química , Fosforilcolina/análogos & derivados , Tensoactivos/química , Aminas , Compuestos Heterocíclicos , Micelas , Fosforilcolina/química , Tensión SuperficialRESUMEN
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.
Asunto(s)
Antifúngicos/síntesis química , Antineoplásicos/farmacología , Pruebas de Sensibilidad Microbiana , Acanthamoeba , Antibacterianos/farmacología , Antifúngicos/farmacología , Antiprotozoarios , Candida albicans/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Concentración 50 Inhibidora , Estructura Molecular , Fosforilcolina/análogos & derivados , Extractos Vegetales , Relación Estructura-ActividadRESUMEN
A series of dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimethylammonium bromide have been synthesized. The prepared compounds exhibit significant cytotoxic, antifungal and antiprotozoal activities. Alkylphosphocholines possess higher antifungal activity against Candida albicans in comparison with quaternary ammonium compounds. However, quaternary ammonium compounds exhibit significant higher activity against human tumor cells and Acanthamoeba lugdunensis compared to alkylphosphocholines. In addition, their haemolytic toxicity has been investigated. The relationship between structure and biological activity of the tested compounds is discussed.
Asunto(s)
Antifúngicos , Antineoplásicos , Compuestos de Cetrimonio/química , Compuestos Heterocíclicos/química , Nitrógeno , Fosforilcolina/análogos & derivados , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Candida albicans/efectos de los fármacos , Cationes , Línea Celular Tumoral , Cetrimonio , Compuestos de Cetrimonio/farmacología , Humanos , Estructura Molecular , Nitrógeno/química , Fosfatos/química , Fosforilcolina/química , Fosforilcolina/farmacología , Compuestos de Amonio Cuaternario/químicaRESUMEN
The present study deals with the determination of hydrodynamic size of DNA/cationic gemini surfactant complex in sodium bromide solution using the dynamic light scattering method. Cationic gemini surfactants with polymethylene spacer of variable length were used for the interaction with DNA. The scattering experiments were performed at constant DNA and sodium bromide concentrations and variable surfactant concentration in the premicellar and micellar regions as a function of surfactant spacer length. It was found that the DNA conformation strongly depends on the polymethylene spacer length as well as on the surfactant concentration relative to the surfactant critical micelle concentration. Gemini surfactant molecules with 4 methylene groups in the spacer were found to be the least efficient DNA compacting agent in the region above the surfactant cmc. Gemini molecules with the shortest spacer length (2 methylene groups) and the longest spacer length (8 methylene groups) investigated showed the most efficient DNA compaction ability.
Asunto(s)
Compuestos de Benzalconio/química , ADN/química , Tensoactivos/química , Animales , Bromuros/química , Fluoresceínas , Yodoacetamida/análogos & derivados , Luz , Micelas , Conformación de Ácido Nucleico , Tamaño de la Partícula , Salmón , Dispersión de Radiación , Compuestos de Sodio/químicaRESUMEN
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.
Asunto(s)
Compuestos de Amonio Cuaternario/química , Tensoactivos/química , Aire , Amidas/química , Ciclohexanos/química , Enlace de Hidrógeno , Luz , Modelos Moleculares , Estructura Molecular , Tensión Superficial , Agua/químicaRESUMEN
Aggregation properties of biodegradable ammonium surfactants containing amide and ester groups in the bulk and at the air-water interface were investigated as a function of surfactant tail length m using dynamic light scattering and surface tension experimental methods. The results indicate that surfactants containing an ester group in the structure display higher aggregation ability in the volume and form more densely packed layer of molecules at the air-water interface than those with an amide group. The results of physical measurements were correlated with 3D models of respective surfactant molecules. As the results indicate, a surfactant molecule headgroup containing an ester group shows higher flexibility than that with an amide group in its structure, which is documented by somewhat smaller headgroup size and denser packing at the air-water interface.
Asunto(s)
Luz , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/metabolismo , Tensoactivos/química , Tensoactivos/metabolismo , Alquilación , Modelos Moleculares , Conformación Molecular , Tamaño de la Partícula , Soluciones , Propiedades de SuperficieRESUMEN
Areas per surfactant molecule at the liquid/hydrophobic solid (A(LS)) and the liquid/air (A(LA)) interface as a function of the spacer length are reported for cationic gemini surfactants having (CH2)n spacer s. A(LA) increases with increasing spacer length up to 6-8 CH2 groups in the spacer and then levels off. A(LS) values indicate a more closely packed arrangement of the surfactant molecules than that at the liquid/air interface. Comparison of A(LA) and A(LS) values indicates that the surfactant molecules at the liquid/hydrophobic solid interface are almost three times as closely packed as those at the liquid/air interface. A comparison of the experimental values of the area per surfactant molecule at both interfaces was made with those calculated from dimensions of the surfactant molecule in vacuo.
Asunto(s)
Tensoactivos/química , Aire , Cationes/química , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Solventes/química , Propiedades de SuperficieRESUMEN
The structure of aggregates formed by interaction of DNA with unilamellar dilauroylphosphatidylcholine (DLPC) vesicles (DNA:DLPC=1:1 base/mol) in the presence of gemini surfactant butane-1,4-diyl-bis(dodecyldimethylammonium bromide) (C12GS) was investigated using synchrotron small angle X-ray diffraction. In the concentration range C12GS+:DLPC< or =1 mol/mol, a condensed lamellar Lalphac phase was found with a repeat period of lipid bilayer stacking in the range d approximately 5.70-6.53 nm and the DNA interhelical distance d(DNA) approximately 3.52-3.99 nm, depending on the concentration of C12GS. At molar ratio C12GS+:DLPC> or =0.35:1, the diffractograms have shown the presence of a second lamellar phase with the repeat period d approximately 5.31 nm which slightly decreases with increasing concentration of C12GS+. The increasing fraction of this phase in the aggregates with increasing concentration of C12GS supports the association of this phase with microscopic domains enriched by surfactant molecules. The temperature behaviour of aggregates was investigated in the range 25-60 degrees C and the transversal thermal expansivities of the observed phases were determined.
Asunto(s)
Butilaminas/química , ADN/química , Fosfatidilcolinas/química , Compuestos de Amonio Cuaternario/química , Tensoactivos/química , Membrana Dobles de Lípidos/química , Modelos Químicos , Modelos Estadísticos , Sincrotrones , Temperatura , Termodinámica , Difracción de Rayos XRESUMEN
The influence of 1,4-butanediamonium-N,N'-dialkyl-N,N,N',N'-tetramethyl dibromides (CmA, m = 7-16 is the number of alkyl carbons) on the egg yolk phosphatidylcholine (EYPC) bilayer thickness and lipid surface area at the bilayer-aqueous phase interface is studied using X-ray diffraction on fluid lamellar CmA + EYPC + H2O phases as a function of CmA:EYPC and H2O:EYPC molar ratios and the alkyl chain length m. At the constant CmA:EYPC = 0.4 and H2O:EYPC = 18 molar ratios, the CmA induced bilayer thickness decrease shows a minimum and the lipid surface area increase a maximum at the alkyl chain length m = 9. The obtained results are discussed in the context of a structural perturbation model of the cut-off effect in biological potencies of surfactants which occurs when increasing the alkyl substituent chain length above the critical value.
Asunto(s)
Yema de Huevo/metabolismo , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Lípidos/química , Liposomas/química , Modelos Químicos , Modelos Estadísticos , Dispersión de Radiación , Difracción de Rayos XRESUMEN
Effects of non-ionic surfactants N-alkyl-N,N-dimethylamine-N-oxides (C(n)NO, n is the number of alkyl carbons) on the structure of egg yolk phosphatidylcholine (EYPC) bilayers in the lamellar fluid phase was studied by small-angle X-ray diffraction as a function of H(2)O:EYPC and C(n)NO:EYPC molar ratios. The bilayer thickness d(L) and the lipid surface area at the bilayer-aqueous interface S(L) were calculated from the repeat period, d of the lamellar phase, based on the model that water and EYPC + CnNO molecules form separated layers and that their molecular volumes are additive. In the studied range of m=CnNO:EYPC molar ratios up to 1:1, d(L) and S(L) change linearly. The slopes Delta L = delta dL/ delta m and Delta S= delta S L / delta m are equal to -0.876 +/- 0.027 nm and 0.347 +/- 0.006 nm2 for C(6)NO, -1.025+/-0.060 nm and 0.433+/-0.025 nm(2) for C(8)NO, -0.836+/-0.046 nm and 0.405+/-0.018 nm(2) for C(10)NO, -0.604+/-0.015 nm and 0.375+/-0.007 nm(2) for C(12)NO, -0.279+/-0.031 nm and 0.318+/-0.005 nm(2) for C(14)NO, -0.0865+/-0.070 nm and 0.2963 +/-0.014 nm(2) for C(16)NO, and -0.040+/-0.022 nm and 0.297+/- 0.002 nm(2) for C(18)NO, respectively, at full bilayer hydration. The peak-peak distance in the bilayer electron density profile, which relates to the P-P distance d(PP), obtained from the first four diffraction peaks by the Fourier transform also depends linearly on m, and the slope Delta PP = delta dPP/delta m is -0.528+/-0.065 nm for C(6)NO, -0.680+/-0.018 nm for C(8)NO, -0.573+/-0.021 nm for C(10)NO, -0.369+/-0.075 nm for C(12)NO, -0.190+/-0.015 for C(14)NO, -0.088+/-0.016 nm for C(16)NO and -0.094+/-0.016 nm for C(18)NO. The effects of C(n)NO on Delta(L), Delta(S) and Delta(PP) are the results of C(n)NO insertion into EYPC bilayers and depend on the hydrophobic mismatch between C(n)NO and EYPC hydrocarbon chains and on the lateral interactions of C(n)NO and EYPC in the bilayer.