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The interaction with a model membrane, the formation of DNA nanoparticles, and the transfection ability of a homologous series of bispyridinium dihexadecyl cationic gemini surfactants, differing in the length of the alkyl spacer bridging the two pyridinium polar heads in the 1 and 1' positions (P16-n with n = 3, 4, 8, 12), have been studied by means of differential scanning calorimetry (DSC), atomic force microscopy, electrophoresis mobility shift assay, and transient transfection assay measurements. The results presented here show that their performance in gene delivery is strictly related to their structure in solution. For the first time the different transfection activities of the compounds can be explained by referring to their thermodynamic properties in solution, previously studied. The compound with a spacer formed by four carbon atoms, showing unexpected enthalpic properties vs concentration in solution, is the only one giving rise to a transfection activity comparable to that of the commercial reagent, when formulated with L-α-dioleoylphosphatidylethanolamine. We suggest that P16-4 behaves like molecular tongs able to grip basic groups near each other, allowing the formation of compact and nearly spherical DNA particles. The compound with the longest spacer gives rise to loosely condensed structures by forming a sort of bow, not able to give rise to transfection notwithstanding the double positive charge of the molecule. On the other hand, DSC measurements on synthetic membranes show that the compounds with the shortest spacers (three and four methylene groups) practically do not interact with the 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine membrane, while compounds P16-8 and, particularly, P16-12 induce the formation of surfactant-rich and surfactant-poor domains in the membrane, without showing any peculiarity for compound P16-4. This could suggest that the mechanisms involved in the interaction with the model membrane and in gene delivery are substantially different and could strike a blow for an endocytosis mechanism for the internalization in the cell of the DNA nanoparticles.

A series of pyridinium-based cationic surfactants has been synthesised and their amphiphilic properties have been studied by conductivity and surface tension measurements. The modification of the substitution pattern on the pyridinium ring by hydrophobic moieties (methyl vs. hydrogen and presence or not of condensed benzene ring) gave the opportunity to investigate structure-activity relationships. Characterization by conductivity and surface tension measurements shed light on the behaviour at the air/water interface and in the micellar environment. In particular, the tendency to form ion pairs at very low concentration was evidenced for all the surfactants substituted on the ring, but not for the simple pyridinium ones. The formation of ion pairs affects both the conductivity and the surface tension plots, showing that a series of steps is involved during the adsorption to the air/water surface. An attempt was made to qualify the single steps in the adsorption at the surface layer. Those steps were attributed to different chemical species (free surfactant ions or ion pairs) and to different arrangements of the surfactant. This work also represents a contribution of investigation at very low surfactant concentrations and high surface tension values.

Apparent and partial molar enthalpies at 298 K of the aqueous solutions of cationic gemini surfactants 1,1'-didodecyl-2,2'-dimethylenebispyridinium dimethanesulfonate (12-Py(2)-2-(2)Py-12 MS); 1,1'-didodecyl-2,2'-trimethylenebispyridinium dimethanesulfonate (12-Py(2)-3-(2)Py-12 MS); 1,1'-didodecyl-2,2'-tetramethylenebispyridinium dimethanesulfonate (12-Py(2)-4-(2)Py-12 MS); 1,1'-didodecyl-2,2'-octamethylenebispyridinium dimethanesulfonate (12-Py(2)-8-(2)Py-12 MS); 1,1'-didodecyl-2,2'-dodecamethylenebispyridinium dimethanesulfonate (12-Py(2)-12-(2)Py-12 MS) were measured as a function of concentration and are here reported for the first time. They show a very peculiar behavior as a function of the spacer length, not allowing for the determination of a -CH 2- group contribution when this group is added to the spacer. The curve of the compound with a four-carbon-atom-long spacer lies between those of the compound with a spacer of 2 and 3 carbon atoms, instead of that below the latter, as expected. This surprising behavior, never found before in the literature and different from that found for the more popular m- s- m-type bisquaternary ammonium gemini surfactants, could be explained by a conformation change of the molecule, caused by stacking interactions between the two pyridinium rings, mediated by the counterion and appearing at an optimum length of the spacer. The hypothesis is also supported by the data obtained from the surface tension vs log c curves, showing that A min, the minimum area taken at the air-water interface by the molecule, is significantly lower for 12-Py(2)-4-(2)Py-12 MS than that of the other compounds of the same homologous series, and that the same compound has a greater tendency to form micelles instead of adsorbing at the air/water interface. The evaluation of the micellization enthalpies, by means of a pseudophase transition model, agrees with the exposed trends. These results confirm the great crop of information that can be derived from the study of the solution thermodynamics of aggregate systems and in particular from the curves of apparent and molar enthalpies vs concentration.

Thermodynamic properties of aqueous solutions of newly synthesized compounds, namely, N-[2-(beta-D-glucopyranosyl)ethyl]-N,N-dimethyl-N-alkylammonium bromides with hydrophobic tails of 12 (C12DGCB) and 16 (C16DGCB) carbon atoms, determined as a function of concentration by means of direct methods, are reported here. Dilution enthalpies, densities, and sound velocities were measured at 298 K, allowing for the determination of apparent and partial molar enthalpies, volumes, and compressibilities. Changes in thermodynamic quantities upon micellization were derived using a pseudophase-transition approach. From a comparison with the corresponding acetylated compounds N-[2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)ethyl]-N,N-dimethyl-N-dodecylammonium bromide (C12AGCB) and N-[2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyanosyl)ethyl]-N,N-dimethyl-N-hexadecylammonium bromide (C16AGCB), the role played in the micellization process by the acetylated glycosyl moiety was inferred: it enhances the hydrophobic character of the molecule and lowers the change in enthalpy of micelle formation by about 1.5 kJ mol(-1). By comparing the volume of C12DGCB with those of DEDAB and DTAB, the volumes taken up by the (beta- d-glucopyranosyl)ethyl and beta- d-glucopyranosyl groups were found to be 133 and 99 cm3 mol(-1), respectively. Regarding the interaction with DPPC membranes, it seems that the sugar moiety of the hexadecyl deacetylated compound gives rise to hydrogen bonds with the oxygen atoms of the lipid phosphates, shifting the phase transition of DPPC from a bilayer gel to a bilayer liquid crystal to lower temperatures. C16AGCB induces significantly greater changes than C16DGCB in the structure of liposomes, suggesting the formation of domains. The interaction is strongly enhanced by the presence of water. Neither compound interacts strongly with DNA or compacts it, as shown by EMSA assays and AFM images. Only C16AGCB is able to deliver little DNA inside cells when coformulated with DOPE, as shown by the transient transfection assay. This might be related to the ability of C16AGCB to form surfactant-rich domains in the lipid structure.

Compost humic acid-like (cHAL) polymeric matter (MW = 15610), isolated in 12% yield from food and green waste compost, exhibits very good surfactant properties in aqueous solution: i.e., critical micelle concentration (cmc) = 403 mg/L and surface tension at cmc = 36.1 mN/m. Values of cmc are confirmed also by conductivity and phenanthrene solubility measurements. These results, compared with those for other major commercial and research surfactants, propose cHAL as a competitive low-cost biosurfactant.

[reaction: see text] In this work, we report the synthesis of a new series of glucocationic surfactants, a class of surfactants we introduced very recently. The preparation of the surfactants is based on the synthesis of the 2-bromoethyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside, whose preparation was studied in order to improve yields and stereoselectivity of this key intermediate. These glucocationic amphiphiles were prepared and studied as a model of cationic surfactants marked with a carbohydrate moiety. The use of carbohydrates as markers on cationic lipids was recently introduced to induce recognition by specific receptors, present on the surface of cell membranes. The chemicophysical characterization of these model structures can give more insight on the aggregation behavior. Conductivity and surface tension measurements were performed in order to characterize the compounds from the amphiphilic point of view. The results showed a different effect of the glucosidic moiety on the cmc value with respect to the glucopyridinium cationic surfactants. The surfactants also showed the tendency to form premicellar aggregates in solution when the hydrophobicity is raised.

The apparent and partial molar enthalpies, apparent molar volumes, and adiabatic compressibilities at 298 K of the aqueous solutions of the cationic gemini surfactants propanediyl-alpha,omega-bis(octyldimethylammonium bromide) (8-3-8) and propanediyl-alpha,omega-bis(dodecyldimethylammonium bromide) (12-3-12) have been measured as a function of concentration. The trends of the partial molar enthalpies versus concentration are the first well documented thermodynamic evidence of sphere to rod transition in the micellar phase, involving a detectable quantity of heat, and allow the determination of the change in enthalpy associated with this transition. The changes in enthalpies upon micellization and for the sphere to elongated micelles transition, DeltaH(s)(-->)(r), have been obtained from the experimental data by using a pseudo-phase transition approach: -1.5 kJ mol(-1) for 8-3-8 and -3.9 kJ mol(-1) for 12-3-12. No evidence of the above transition is found in the trends of volumetric properties versus m. The apparent adiabatic molar compressibilities for the compounds under investigation are also reported here for the first time: a negative group contribution for the methylene group is evaluated, when the surfactants are present in solution as a single molecule, reflecting its solvation structure. In the micellar phase, the -CH(2)- group contribution becomes positive. A value of 1.17 x 10(-3) cm(3) bar(-1) mol(-1) for the change in adiabatic molar compressibility upon micellization is obtained. The lower values of the methylene group contributions to the volumetric properties for the monomers support the hypothesis of partial association of the chains before the cmc.

A new series of pyridinium cationic gemini surfactants was prepared by quaternization of the 2,2'-(alpha,omega-alkanediyl)bispyridines with N-alkylating agents, whose reactivity is briefly discussed. Particularly useful was the use of long-chain alkyl triflates (trifluoromethanesulfonates) for both overcoming the sterical hindrance in the pyridines and obtaining higher synthetic yields. Well-known 4,4'-(alpha,omega-alkanediyl)bis(1-alkylpyridinium) structures showed narrow temperature ranges for practical applications, due to their high Krafft points, while the new 2,2'-(alpha,omega-alkanediyl)bis(1-alkylpyridinium) series, accounted for good surface active properties. Due to the Krafft points below 0 degrees C, they could be exploited as solutions in water at any temperature. The characterization of the behavior of the series was performed by conductivity measurements. Some of the proposed structures exhibited unusual surface active behavior, which was interpreted in terms of particular conformational arrangements.