Jan B. F. N. Engberts

Toward a better understanding of the driving force for micelle formation and micellar growth

Abstract The thermodynamic data for micelle formation of four selected 1-methyl-4-(C12-alkyl)pyridinium iodides in H2O at 25 and 95°C are described. The enthalpy of micellization (ΔHmic) remains invariant within experimental error upon alkyl chain branching. The free energy of micellization (ΔHmic) is only slightly affected by the large increase in temperature, although both the enthalpy and the entropy are dramatically influenced. These results can be rationalized when it is assumed that London-dispersion interactions represent the main attractive force for micelle formation. Enthalpies for the sphere-to-rod transition (ΔHsr) were calculated from the temperature dependence of the critical rod concentration using the ladder model. These enthalpies are in good accord with measured ones. ΔHsr values reflect the reduction of the apolar part of the surfactant molecule exposed to water at the sphere-to-rod transition. For surfactants having a high packing parameter, ΔHsr becomes more exothermic and more of this exposed area will be reduced compared with those having a low packing parameter. The former surfactants pack better into a rod-like micelle, resulting in less water penetration, than the latter surfactants.

Polymer–micelle interactions: physical organic aspects

This review presents a summary of attempts to characterize the morphology of the complexes formed between ionic and non-ionic surfactants and water-soluble polymers. It is now generally accepted that complex formation involves the binding of micelles to the macromolecule. This binding process modifies the size and properties of the micelles and affects the Gibbs energy of the polymer. A complex combination of interaction forces provides the driving force for complexation. Criteria for polymer-micelle interaction are discussed. Particular emphasis is placed on the role of charge and structure of the surfactant headgroup and on the effect of polymers on the micellar structure and properties of cetyltrimethylammonium salts.

Phase behavior of cationic amphiphiles and their mixtures with helper lipid influences lipoplex shape, DNA translocation, and transfection efficiency.

Cationic lipids are widely used for gene transfection, but their mechanism of action is still poorly understood. To improve this knowledge, a structure-function study was carried out with two pyridinium-based lipid analogs with identical headgroups but differing in alkyl chain (un)saturation, i.e., SAINT-2 (diC18:1) and SAINT-5 (diC18:0). Although both amphiphiles display transfection activity per se, DOPE strongly promotes SAINT-2-mediated transfection, but not that of SAINT-5, despite the fact that DOPE effectively facilitates plasmid dissociation from either lipoplex. This difference appears to correlate with membrane stiffness, dictated by the cationic lipid packing in the donor liposomes, which governs the kinetics of lipid recruitment by the plasmid upon lipoplex assembly. Because of its interaction with the relatively rigid SAINT-5 membranes, the plasmid becomes inappropriately condensed, which results in formation of structurally deformed lipoplexes. This structural deformation does not affect its cellular uptake but, rather, hampers plasmid translocation across endosomal and/or nuclear membranes. This is inferred from the observation that both lipoplexes effectively translocate much smaller oligonucleotides into cells. In fact, SAINT-5/DOPE-mediated transfection is greatly improved when, before lipoplex assembly, the plasmid is stabilized by condensation with polylysine. The results emphasize a role of the structural shape of the plasmid in gaining cytosolic/nuclear access. Moreover, it has been proposed that such a translocation is promoted when the lipoplex adopts the hexagonal phase, and data are presented that demonstrate that the lamellar SAINT-5/DOPE lipoplex adopts such a phase after its interaction with acidic phospholipid-containing membranes.

ZWITTERIONIC POLYMERS .1. SYNTHESIS OF A NOVEL SERIES OF POLY(VINYLSULFOBETAINES) - EFFECT OF STRUCTURE OF POLYMER ON SOLUBILITY IN WATER

Abstract Six novel poly(vinylsulphobetaines) have been prepared by polymerization of the corresponding monomers. The monomers were obtained by addition of tertiary amines to alkenylsulphonylchlorides. The zwitterionic polymer derived from vinylsulphonylchloride exhibited the usual water solubility characteristics, i.e. insoluble in water, soluble in dilute sodium chloride solutions. By contrast, the polymer derived from 1-propenesulphonylchloride was found to be soluble both in water and in 0–2 M sodium chloride solutions. Furthermore, the intrinsic viscosity of the latter polymer undergoes only a very small change upon addition of salt. These results are rationalized by assuming the operation of steric effects on intrasalt interactions in the macromolecules.

Thermodynamics of Micellar Systems: Comparison of Mass Action and Phase Equilibrium Models for the Calculation of Standard Gibbs Energies of Micelle Formation

Micellar colloids are distinguished from other colloids by their association-dissociation equilibrium in solution between monomers, counter-ions and micelles. According to classical thermodynamics, the standard Gibbs energy of formation of micelles at fixed temperature and pressure can be related to the critical micelle concentration. This relation is different for two models which are widely used to describe micelle formation, namely the Phase Separation and the Mass Action Models. These approaches and the assumptions upon which they are based are analysed in this paper. We show that the two models can be generalised to include surfactant salts having different stoichiometries.

The effect of stereochemistry upon carbohydrate hydration. A molecular dynamics simulation of β-d-galactopyranose and (α,β)-d-talopyranose

Abstract This paper reports a molecular dynamics simulation study of β- d -galactopyranose and (α,β)- d -talopyranose in aqueous solution. Special emphasis was placed on the intramolecular next-nearest neighbour oxygen distances in the carbohydrate molecule and the hydrogen bonding of the hydroxy functionalities of the carbohydrates with water. The average number of hydrogen bonds of the hydroxy groups of the carbohydrates depends on the stereochemistry of the molecule. In contrast to the HO-2 and HO-4 of d - galactopyranose, those of d -talopyranose are shielded. This is a consequence of an intramolecular hydrogen bond between the HO-2 and HO-4 in d -talopyranose, which also explains why the apparent hydrophobicity of d -talose is found to be greater than that of d -galactose.

Synthesis and characteristics of biodegradable pyridinium amphiphiles used for in vitro DNA delivery

Pyridinium amphiphiles have found practical application for the delivery of DNA into eukaryotic cells. A general synthetic method starting from (iso)nicotinoyl chloride has been devised for the preparation of pyridinium amphiphiles based on (bio)degradable esters, allowing structural variation both in the hydrophobic part and in the headgroup area. By means of differential scanning calorimetry, transmission electron microscopy and UV measurements, some characteristics, including hydrolytic behaviour, have been determined. In vitro transfection ability and toxicity have been determined using the eukaryotic COS-7 cell line.

Micelle—polymer complexes: Aggregation numbers, micellar rate effects and factors determining the complexation process

This paper describes a study of the interaction of anionic sodium dodecyl sulfate (SDS) and cationic cetyltrimethylammonium bromide (CTAB) micelles with two structurally related, neutral polymers, poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO) of different hydrophobicity. Mean aggregation numbers (n) were measured for PEO- and PPO-complexed SDS micelles both in water and in aqueous solutions containing 0.4 M NaBr. Interaction of the SDS micelles with the polymers results in decreased n values, the effect being more pronounced for PPO than for PEO. The n values were employed in a detailed kinetic analysis of the effects of PEO and PPO on the SDS-induced inhibition of the neutral hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole (1) in water and aqueous 0.4 M NaBr solutions. Particular emphasis is placed on the binding of 1 to the micellar aggregates. It was found that 1 binds less effectively to the polymer-complexed micelles than to unperturbed SDS micelles, most likely as a result of decreased surfactant headgroup packing in the SDS-polymer complexes. The effect of PPO on the reaction of alkyl- and arylsulfonylmethyl sulfonates with hydroxide ions catalyzed by CTAB micelles was also studied. PPO greatly decreases the micellar catalysis, most likely by reducing the effective substrate binding to the surfactant assemblies. The present and previous results suggest that the hydrophobicity of the polymer is a major factor determining micelle-polymer interaction. The general finding, that anionic micelles bind more strongly to uncharged water-soluble polymers than cationic micelles, is rationalized in terms of hydration shell overlap effects of polymer and surfactant headgroup in the micelle-polymer complex.

Catalysis by surfactant aggregates in aqueous solutions

Catalysis of organic reactions by unfunctionalized surfactant aggregates (micelles, vesicles) in aqueous solution is largely determined by medium effects induced at the micellar binding sites and by entropy effects due to compartimentalization, The efficiency of these catalytic effects responds to changes in size and shape of the surfactant assemblies. These effects are discussed for a series of 1-alkyl-4-alkylpyridinium halide surfactants using the highly medium dependent decarboxylation of 6-nitrobenzisoxazole-3-carboxylate (6-NBIC) as a model reaction. The decarboxylation of 6-NBIC is also strongly catalyzed in the presence of hydrophobically modified poly(alkylmethyldiallylammonium bromides), provided that the flexibility of the polymer main chain allows the formation of hydrophobic microdomains. A test for possible substrate orientation effects on the efficiency of micellar catalysis was performed for the reaction of the sulfonates R,S02CH20S02R2 with OH- ions in the presence of CTAB micelles. Large variations in the hydrophobicities of R1 and R, led to only small changes in the second-order rate constant for reaction in the micellar pseudophase. These results are in accord with recent insights into the structure of micellar aggregates.

Calcium-induced fusion of didodecylphosphate vesicles: the lamellar to hexagonal II (HII) phase transition.

SummaryElectron microscopic techniques have been employed to investigate the ability of didodecylphosphate vesicles (diameter approx. 900 Å) to fuse in the presence of Ca2+. As revealed by negative staining, Ca2+ induces extensive fusion and large vesicles with diameters up to 7000 Å are formed. In a processsecondary to fusion, the fused vesicles display a tendency to flatten and are subsequently transformed into extended tubular structures. Freeze-fracture electron microscopy, in conjunction with31P NMR and selected area electron diffraction measurements indicate that the tubes are packed in a hexagonal (HII) array and that the amphiphiles are converted from the lamellar to the hexagonal HII phase.The relationship between membrane fusion and the lamellar-to-hexagonal phase transition is discussed in terms of formation and abundance of transiently stable inverted micellar intermediates at contact regions between two interacting membranes. A model for the conversion of the (vesicular) lamellar into the (tubular) hexagonal HII phase is presented, taking into account the molecular shape of the amphiphile. The relevance of using simple synthetic amphiphiles as models for phospholipid bilayers and complex biomembrane behavior is briefly discussed.