Ion-exclusion chromatography with mixed micellar mobile phases

Mixed ionic-nonionic surfactant mobile phases for ion-exclusion chromatography of carboxylic acids permitted the analysis time to be reduced by partitioning the analytes could be determined without interference even when they eluted near the void volume. These advantages result from the formation of mixed micelles of the two surfactants. The partition behaviour of both neutral and charged analytes to a nonionic micellar phase was evaluated on the basis of a retention model that included dissociation equilibria of analytes. In addition, the partition coefficients to mixed micellar phases were also determined by using this model.     

Partition equilibria of phenols between water and anionic micelles : Correlation with the Octanol/Water System

The partition equilibria of a series of thirty substituted phenols bearing different chemical groups between aqueous solutions and sodium dodecylsulfate micelles was investigated by using micellar high-performance liquid chromatography and by studying the variation of the acidity constant. The contribution of each substituent to the free energy of transfer from water to micelles was estimated. The group contribution approach is shown to be valid for polysubstituted compounds under well defined conditions. A comparison with partition coefficients obtained in classical two-phase system (1-octanol/water), frequently used as biochemical model systems, is discussed     

The use of a micellar mobile phase in the high-performance liquid chromatographic separation of hydroxybenzene derivatives

When aquenous micellar solutions are used as mobile phases in liquid chromatography, retention of solutes depends on the concentration of the micellar surfactant, and relevant information about the partition coefficient and related association constants between solutes and micelles can be calculated from the chromatographic results. The chromatographic parameters of a series of phenols and hydroxyphenols (1,2- and 1,4-diols) eluted with sodium dodecyl sulfate micelles were measured. The association constants evaluated were in good agreement with those obtained by other techniques.     

Joint solubilization of lipophilic drug amlodipine and glyceryl monolaurate in aqueous micellar solutions of Tween 80

The solubilization of lipophilic amlodipine (Am is a antihypertensive drug) and nonionic surfactant glyceryl monolaurate (GML is a skin permeation enhancer), as well as their joint solubilization (co-solubilization) have been measured by UV spectroscopy and refractometry in aqueous micellar solutions of Tween 80 (Tw). The properties of mixed micelles (Tw + GML, Tw + Am, Tw + GML + Am) have been studied, including the aggregation number of components, the localization of solubilizates, diffusion coefficients, the size and the degree of hydration. As a result of co-solubilization, (Tw + GML + Am) three-component micelles contain 4.2 times more molecules of the drug than (Tw + Am) two-component micelles. The experimental data on the kinetics of mass transfer of Am by micelles based on Tw are in good agreement with the calculations under diffusion theory; furthermore, three-component micelles carry Am more effectively than two-component micelles.     

Importance of micellar kinetics in relation to technological processes

The association of many classes of surface-active molecules into micellar aggregates is a well-known phenomenon. Micelles are in dynamic equilibrium, constantly disintegrating and reforming. This relaxation process is characterized by the slow micellar relaxation time constant, tau(2), which is directly related to the micellar stability. Theories of the kinetics of micelle formation and disintegration have been discussed to identify the gaps in our complete understanding of this kinetic process. The micellar stability of sodium dodecyl sulfate micelles has been shown to significantly influence technological processes involving a rapid increase in interfacial area, such as foaming, wetting, emulsification, solubilization, and detergency. First, the available monomers adsorb onto the freshly created interface. Then, additional monomers must be provided by the breakup of micelles. Especially when the free monomer concentration is low, which is the case for many nonionic surfactant solutions, the micellar breakup time is a rate-limiting step in the supply of monomers. The Center for Surface Science & Engineering at the University of Florida has developed methods using stopped flow and pressure jump with optical detection to determine the slow relaxation time of micelles of nonionic surfactants. The results showed that the ionic surfactants such as SDS exhibit slow relaxation times in the range from milliseconds to seconds, whereas nonionic surfactants exhibit slow relaxation times in the range from seconds (for Triton X-100) to minutes (for polyoxyethylene alkyl ethers). The slow relaxation times are much longer for nonionic surfactants than for ionic surfactants, because of the absence of ionic repulsion between the head groups. The observed relaxation times showed a direct correlation with dynamic surface tension and foaming experiments. In conclusion, relaxation time data of surfactant solutions correlate with the dynamic properties of the micellar solutions. Moreover, the results suggest that appropriate micelles with specific stability or tau(2) can be designed by controlling the surfactant structure, concentration, and physicochemical conditions (e.g., salt concentration, temperature, and pressure). One can also tailor micelles by mixing anionic/cationic or ionic/nonionic surfactants for a desired stability to control various technological processes.     

Spectrophotometric study of anionic azo-dye light yellow (X6G) interaction with surfactants and its micellar solubilization in cationic surfactant micelles

Solubilization and interaction of azo-dye light yellow (X6G) at/with cationic surfactants cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC) was investigated spectrophotometricaly. The effect of cationic micelles on solubilization of anionic azo dye in aqueous micellar solutions of cationic surfactants was studied at pH 7 and 25 degrees C. The binding of dye to micelles implied a bathochromic shift in dye absorption spectra that indicates dye-surfactant interaction. The results showed that the solubility of dye increased with increasing surfactant concentration, as a consequence of the association between the dye and the micelles. The binding constants, K(b), were obtained from experimental absorption spectra. By using pseudo-phase model, the partition coefficients between the bulk water and surfactant micelles, K(x), were calculated. Gibbs energies of binding and distribution of dye between the bulk water and surfactant micelles were estimated. The results show favorable solubilization of dye in CTAB micelles.     

Scattering theory for threadlike micellar solutions

Association-dissociation equilibria and the static scattering function were formulated using precise thermodynamic functions for nonionic surfactant solutions including long, stiff, threadlike micelles. The present theory is applicable for micellar solutions with the surfactant concentration much higher than the critical micelle concentration and containing highly growing threadlike micelles. The scattering function formulated was compared with experimental light scattering data for aqueous solutions of a nonionic surfactant, penta(oxyethylene glycol) n-decyl ether (C12E5), at different surfactant concentrations and also temperatures.     

Contribution of molecular pathways in the micellar solubilization of monodisperse emulsion droplets

It is often proposed that oil solubilization in anionic and nonionic micelles proceeds by different mechanisms, with diffusion of the oil molecule thought to control the former, and the latter interfacially controlled. In order to investigate this hypothesis, the effect of aqueous phase viscosity, salt, and surfactant concentration during the solubilization process was studied. The progressive decrease in average droplet size of nearly monodisperse emulsions during solubilization in SDS or Tween 20 micellar solutions was monitored by light scattering, and the change in turbidity was measured by UV-vis spectrophotometer. The solubilization rates were analyzed using a population balance approach to calculate the mass transfer coefficients. Increasing the aqueous viscosity by adding sucrose reduced the mass transfer coefficients of n-tetradecane and n-dodecane but had a smaller effect on n-hexadecane. The strong dependence of the solubilization rate for the shorter chain length alkanes on aqueous viscosity supported a mechanism in which the oil undergoes molecular diffusion before being taken up by micelles. The dependence of the solubilization kinetics on surfactant concentration appeared consistent with this mechanism but yielded a slower micellar uptake rate than previously predicted theoretically. As the solute chain length increased in nonionic surfactant solutions, an interfacial mechanism mediated by micelles appeared to contribute substantially to the overall rate. Addition of salt only slightly increased the solubilization rate of n-hexadecane in SDS solutions and, thus, indicated a weak role of electrostatic interactions for ionic surfactants on the overall mechanism.     

Measurement of bilirubin partition coefficients in bile salt micelle/aqueous buffer solutions by micellar electrokinetic chromatography

The partition coefficients for the distribution of bilirubin between aqueous phosphateborate buffer and cholic, taurocholic, taurodeoxycholic, and taurochenodeoxycholic micelles have been measured by micellar electrokinetic chromatography at pH 8.5. Determination of the partition coefficients required that the critical micelle concentration and partial specific volumes be determined for each bile salt. Critical micelle concentrations were slightly higher for the trihydroxy bile salts. Partial specific volumes of the bile salt micelles differed very little from each other, and for each bile salt they were constant over the concentration range studied, which was typically from slightly above the critical micelle concentration to 35 mM. Capacity factors were corrected for the effects of applied voltage by extrapolation of the capacity factor to zero applied volts. The free solution mobility of bilirubin, determined in the absence of bile salt, was also corrected for the effects of applied voltage. Plots of extrapolated capacity factor versus phase ratio yield the partition coefficient as the slope of a linear fit to the data. Partition coefficients for bilirubin were significantly higher for dihydroxy bile salts than for trihydroxy bile salts.     

Determination of solute partition behavior with room-temperature ionic liquid based micellar gas-liquid chromatography stationary phases using the pseudophase model

The use of micelles in ionic liquid based gas-chromatography stationary phases was evaluated using equations derived for a "three-phase" model. This model allows the determination of all three partition coefficients involved in the system, and elucidates the micellar contribution to retention and selectivity. Four types of micellar-ionic liquid columns were examined in this study: 1-butyl-3-methylimidazolium chloride with sodium dodecylsulfate or dioctyl sulfosuccinate, and 1-butyl-3-methylimidazolium hexafluorophosphate with polyoxyethylene-100-stearyl ether or polyoxyethylene-23-lauryl ether. The partition coefficients were measured for a wide range of probe molecules capable of a variety of types and magnitudes of interactions. In general, most probe molecules preferentially partitioned to the micellar pseudophase over the bulk ionic liquid component of the stationary phase. Therefore, addition of surfactant to the stationary phase usually resulted in greater solute retention. It is also shown that the selectivity of the stationary phase is significantly altered by the presence of micelles, either by enhancing or lessening the separation. The effects of surfactant on the interaction parameters of the stationary phase are determined using the Abraham solvation parameter model. The addition of sodium dodecylsulfate and dioctyl sulfosuccinate to 1-butyl-3-methylimidazolium chloride stationary phases generally increased the phase's hydrogen bond basicity and increased the level of dispersion interaction. Polyoxyethylene-100-stearyl ether and polyoxyethylene-23-lauryl ether surfactants, however, enhanced the pi-pi/n-pi, polarizability/dipolarity, and hydrogen bond basicity interactions of 1-butyl-3-methylimidazolium hexafluorophosphate to a greater degree than the ionic surfactants with 1-butyl-3-methylimidazolium chloride. However, these nonionic surfactants appeared to hinder the ability of the stationary phase to interact with solutes via dispersion forces. Therefore, it is possible to effectively predict which analytes will be most highly retained by these micellar-ionic liquid stationary phases.     

Study of protein binding and micellar partition of highly hydrophobic molecules in a single system using capillary electrophoresis

The measurement of protein binding of highly hydrophobic molecules is challenging due to poor solubility and strong adsorption, and further complicated by the competition of lipophilic partition in biological systems. Here, an attempt is presented to simultaneously simulate protein binding and lipophilic partition of hydrophobic molecules in a single system using CE. In this system, the incorporated biocompatible micelles also facilitate the protein binding study of hydrophobic molecules by enhancing their solubility (27 to 10(4) times) and eliminating the problematic adsorption. An equation is derived to describe the competition of protein binding and lipophilic partition and to estimate the protein binding constants in nonmicellar aqueous solution. Five polycyclic aromatic hydrocarbons (PAHs) and HSA were used as model hydrophobic compounds and protein, respectively. The study of the competition between lipophilic partition and protein binding reveals that the binding of the PAHs to HSA is governed by hydrophobic interactions and such binding (except naphthalene) can be eliminated by the lipophilic partition in the nonionic surfactant Tween-20. The developed method may be extended to evaluate the interactions of various macromolecules (receptors, enzymes, proteins, and DNA/RNA) and hydrophobic molecules.     

Spin probes in micellar and polymer self-associating systems

The results of studies of micellar and self-associating polymer systems by spin probe ESR spectroscopy are summarized. The local dynamics and structures of low-molecular-weight micelles built of cationic surfactants bearing long alkyl chains (from C₁₆ to C₂₂), gels of hydrophobically modified polymers, polymer micelles, micellar complexes of nonionic surfactant (Brij58) with hydrogels based on polyacrylic acid, and associates formed in aqueous solutions of poly(diphenylenesulfophthalide) are discussed. Interest in these systems is caused by prospects of their practical use as carriers in drug delivery, in biotechnology, for the enhancement of oil production, and in other purposes.     

Intermolecular interactions governing solubilization in micelles of poly(alkylene oxide) surfactants

Partition coefficients for 39 low-molecular-mass compounds between water and micelles of an ethylene oxide-propylene oxide block copolymer (Pluronic P85) and the monolauryl ether of poly(ethylene oxide) (Brij 35) have been measured by the methods of fluorescence spectroscopy, fluorescence anisotropy, and dialysis kinetics. The tested compounds include aromatic hydrocarbons, phenols, naphthols, xanthene dyes, anthracycline antibiotics, and porphyrins. The multifactor analysis of the partition coefficients in terms of the linear free-energy relationships has been performed. It has been shown that the H-donating ability of compounds facilitates their solubilization in Pluronic micelles and has no effect on solubilization in micelles of monolauryl ether of poly(ethylene oxide). This difference indicates that, when solubilization occurs in Pluronic micelles, the compounds under study appear in a hydrophobic core composed of poly(propylene oxide) blocks.     

Experimental methods and prediction with COSMO-RS to determine partition coefficients in complex surfactant systems

Surfactant-based separation processes are a promising alternative to conventional organic solvent processes. A crucial parameter to describe the efficiency of such processes is the partition coefficient between the surfactant aggregates (micelles) and the aqueous bulk phase. In this work, several experimental methods to determine these partition coefficients (micellar liquid chromatography, micellar enhanced ultrafiltration, and cloud point extraction) are evaluated and compared. In addition, these results are compared to predictions with the thermodynamic model COSMO-RS. In particular, systems with the nonionic surfactant TritonX-100 are studied. The partition equilibria of various solutes (pyrene, naphthalene, phenanthrene, phenol, 3-methoxyphenol, and vanillin) and the influence of different additives (alcohols) are investigated. All experimental methods show very good reproducibility. Moreover, the results from different methods are in good agreement, supplementing one another concerning the temperature ranges. Notably, the COSMO-RS model is capable of predicting partition coefficients between micelles and water in the investigated temperature range and at different alcohol concentrations. The results demonstrate the potential of the model COSMO-RS to facilitate the selection of optimized process parameters for a given separation problem. By predicting partition equilibria in multicomponent systems, the selection of surfactant, temperature, and appropriate additives can be facilitated.     

The chromatographic quantification of hydrophobicity using micellar mobile phases

Summary In micellar liquid chromatography (MLC), the hydrophobicity of a compound is the predominant factor in its retention and interaction with micelles. A non-linear empirical model can describe the dependence between the retention factor (logk) in MLC and the logarithm of partition coefficients octanol-water (logP). An algorithm based on such a model has been used to makelogP predictions. Retention data for series of neutral compounds eluted with different mobile phases and alkyl-bonded stationary phases have been used to test the predictive ability of the algorithm. The results of this approach are compared with those obtained from automatic computational software packages.     

On the calculation of diffusion coefficients and aggregation numbers of nonionic surfactants in micellar solutions

The calculation of the diffusion coefficients of nonionic surfactants as functions of their concentrations in micellar solutions has been analyzed within the framework of the quasi-chemical version of the law of mass action. The methods of the introduction of initial calculation parameters, calculation scheme for an ideal mixture of monomeric molecules and micelles, and corrections for varying solution viscosity have been considered. Numerical estimations have been performed using aqueous tetraoxyethylene octyl ether, pentaoxyethylene hexyl ether, and octyl-β-D-glucopyranoside solutions as examples.     

Abnormal micellar growth in sugar-based and ethoxylated nonionic surfactants and their mixtures in dilute regimes using analytical ultracentrifugation

To develop structure-property relationships for surfactants that control their adsorption, solubilization, and micellization behavior in mixed systems and to develop predictive models based on such relationships, it is necessary to acquire quantitative information on various species present in these complex systems. The analytical ultracentrifugation technique is selected for the first time to characterize the species present in mixed micellar solutions due to its powerful ability to separate particles on the basis of their size and shape. Two nonionic surfactants, n-dodecyl-beta-D-maltoside (DM) and nonyl phenol ethoxylated decyl ether (NP-10), and their 1:1 molar ratio mixture were investigated in this study. Micelles of the nonionic surfactants and their mixture are asymmetrical in shape at the critical micelle concentration (cmc). Interestingly, unlike ionic surfactants, the micellar growths of the nonionic surfactants were found to occur at concentrations immediately above the cmc. The results from both sedimentation velocity and sedimentation equilibrium experiments suggest coexistence of two types of micelles in nonyl phenol ethoxylated decyl ether solutions and in its mixture with n-dodecyl-beta-D-maltoside, while only one micellar species is present in n-dodecyl-beta-D-maltoside solutions. Type 1 micelles were primary micelles at the cmc, while type 2 micelles were elongated micelles. The differences in the micellar shapes of n-dodecyl-beta-D-maltoside and nonyl phenol ethoxylated decyl ether are attributed to packing parameters detected by their molecular structures.     

Counter ion condensation on mixed cationic/nonionic micellar systems: Bjerrum's electrostatic condition

The association of counter-ions with mixed ionic/nonionic micelles has been investigated in the case of dodecyl/tetradecyl/ and hexadecyl-trimethylammonium bromide with two nonionic surfactants: dodecylpolyoxyethylene 23 and Triton X-100. The degree of association has been measured by potentiometry using a Bromide ion-selective electrode. Previous results with sodium and copper dodecylsulfate suggesting that in the nonionic-rich composition domain, bare mixed micelles are formed without associated counter-ions have been confirmed. These results are in agreement with the prediction of Bjerrum's condition for ion association. The effect of copper dodecylsulfate on the cloud point of Triton X-100 has also been determined as a means of investigating mixed micelles with multivalent counter-ions. The dramatic cloud point increase observed, even larger than with sodium dodecylsulfate, has been discussed as evidence of the solvation of divalent ions by ether groups, a factor which complicates the analysis of multivalent counterion condensation on mixed micelles.