Computer simulation study on the concentration distribution of spherical colloids within confined spaces of well‐defined pores

Aside from the virial expansion and density functional methods, theoretical results on the concentration partitioning behavior for charged colloids within cylindrical pores have not been presented so far. With the increase of relative solute size as well as solute concentration, however, the approximate analytic methods have proven to be unreliable. A suitable Monte Carlo simulation, which is proved as a rigorous technique for concentrated colloids, has been applied in the present study. The concentration profiles within the pore representing the effects of solute concentration as well as solution ionic strength are obtained via a stochastic process, from which the partition coefficient is estimated. Previously developed analyses on the linearized Poisson‐Boltzmann (P‐B) equation are employed for the estimation of long‐range electrostatic interaction. Both the singularity method and the analytical solution with series representation properly determine respective interaction energies between pairs of solute particles and between the solute particle and the pore wall. The effect of solute‐solute and solute‐wall interactions associated with repulsive energy is presented on the partitioning of colloids. Simulation results show that the partition coefficient is evidently enhanced when no particle‐wall interaction exists. Hindered diffusion can be predicted by the simplifying assumption of the centerline approximation analogy, where a dependence on the solute concentration becomes greater as the solution ionic strength decreases.     

Thermodynamic aspects of the partitioning of a solute in a gel–solvent system

An expression is derived for the partitioning of a solute molecule in a two-phase system: swollen gel and free solvent. The approach is thermodynamic, and no specific mechanism for the accessibility of the solute to the gel is assumed. Instead, general interaction terms between the components, i.e., polymer–solvent–solute, are introduced.     

Characterization of solvation properties of lipid bilayer membranes in liposome electrokinetic chromatography

The nature of solute interactions with biomembrane-like liposomes, made of naturally occurring phospholipids and cholesterol, was characterized using electrokinetic chromatography (EKC). Liposomes were used as a pseudo-stationary phase in EKC that provided sites of interactions for uncharged solutes. The retention factors of uncharged solutes in liposome EKC are directly proportional to their liposome-water partition coefficients. Linear solvation energy relationship (LSER) models were developed to unravel the contributions from various types of interactions for solute partitioning into liposomes. Size and hydrogen bond acceptor strength of solutes are the main factors that determine partitioning into lipid bilayers. This falls within the general behavior of solute partitioning from an aqueous into organic phases such as octanol and micelles. However, there exist subtle differences in the solvation properties of liposomes as compared to those of octanol and various micellar pseudo-phases such as aggregates of sodium dodecyl sulfate (SDS), sodium cholate (SC), and tetradecylammonium bromide (TTAB). Among these phases, the SDS micelles are the least similar to the liposomes, while octanol, SC, and TTAB micelles exhibit closer solvation properties. Subsequently, higher correlations are observed between partitioning into liposomes and the latter three phases than that into SDS.     

Self-aggregation of cationic surfactants onto oxidized cellulose fibers and coadsorption of organic compounds

In this work, the adsorption of cationic surfactant and organic solutes on oxidized cellulose fibers bearing different amounts of carboxylic moieties was investigated. The increase in the amount of -COOH groups on cellulose fibers by TEMPO oxidation induced a general rise in surfactant adsorption. For all tested conditions, that is, cellulose oxidation level and surfactant alkyl chain length (C12 and C16), adsorption isotherms displayed a typical three-region shape with inversion of the substrate zeta-potential which was interpreted as reflecting surfactant adsorption and aggregation (admicelles and hemimicelles) on cellulose fibers. The addition of organic solutes in surfactant/cellulose systems induced a decrease in surfactant cac on the cellulose surface thus favoring surfactant aggregation and the formation of mixed surfactant/solute assemblies. Adsorption isotherms of organic solutes on cellulose in surfactant/cellulose/solute systems showed that solute adsorption is strictly correlated to (i) the surfactant concentration, solute adsorption increases up to the surfactant cmc, where solute partitioning between the cellulose surface and free micelles causes a drop in adsorption, and to (ii) solute solubility and functional groups. The specific shape of solutes adsorption isotherms at a fixed surfactant concentration was interpreted using a Frumkin adsorption isotherm, thus suggesting that solute uptake on cellulose fibers is a coadsorption and not a partitioning process. Results presented in this study were compared with those obtained in a previous work investigating solute adsorption in anionic surfactant/cationized cellulose systems to better understand the role of surfactant/solute interactions in the coadsorption process.     

Mathematical model for the prediction of the overall profile of in vitro solute release from polymer networks

The loading of solutes onto and their release from hydrogel-based devices can be better understood when they are treated as a partition phenomenon. Partition activity (alpha) is a parameter that determines the existence of partition phenomena. It expresses the physical chemical affinities of the solute between the solvent and hydrogel phases. When alpha=0, there is no release of the solute from the hydrogel; however, if alpha>0, there is partitioning of the solute between the solvent and the hydrogel phases, and release of the solute from the hydrogel can be observed. The mathematic model proposed here predicts the overall release profile of vitamin B(12), methylene blue (MB), and acid orange 7 (AO) from semi-interpenetrating network (semi-IPN) hydrogels composed of PNIPAAm and PAAm. Experimental release tests demonstrated that alterations on variables of the system change both the released fraction and the release rate of such solutes, confirmed by the changes on values of alpha (an equilibrium parameter) and k(R) (an kinetic parameter). The modeling of solute release describes the alpha effects on release of the solute from polymer networks. The solute release mechanism is viewed here as a diffusional transport process and as a partition phenomenon. The partitioning of the solutes occurs between the solvent phase and the hydrogel phase, and the possible physical chemical affinities of the solute between hydrogel and solvent are considered.     

Development of predictive retention-activity relationship models of antipsychotic drugs by micellar liquid chromatography.

The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaocumulation. The use of micellar solutions of Brij35 as mobile phases in reversed liquid chromatography has proven to be valid in predicting some biological activities of different kinds of drugs. In this paper, the correlations between the logarithm of capacity factors and pharmacokinetic, preclinical pharmacology and therapeutic efficacy parameters of phenothiazines are studied. Parabolic quantitative retention-activity relationship models with predictive and interpretative ability have been obtained.     

The Effect of Solute Concentration on Equilibrium Partitioning in Polymeric Gels

The effect of solute concentration on the equilibrium partitioning of sphere-like, colloidal solutes in stiff polymer hydrogels is examined theoretically and experimentally. The theoretical development is a statistical mechanics approach, and allows quantitative calculations to be performed to determine the concentration-dependent partition coefficient correct to first order in solute concentration at specific surface charge densities. The theory predicts that repulsive steric and/or electrostatic solute-fiber interactions exclude solute from the gel phase, but that repulsive solute-solute interactions cause partitioning into the gel to increase with increasing solute concentration. These trends are enhanced for larger solutes, increased fiber volume fractions, or stronger electrostatic repulsion. Partition coefficients have also been measured for two proteins, bovine serum albumin (BSA) and alpha-lactalbumin (ALA), in a system consisting of a salt solution and cubes of agarose hydrogel. To investigate the effect of electrostatic interactions, the experiments were performed at 0.15 M KCl and 0.01 M KCl. The theory underpredicts the strong electrostatic repulsion between BSA macromolecules at the lower ionic strength. The experimental results for ALA show the influence of an attractive interaction between the protein macromolecules, in addition to hard-sphere repulsive and electrostatic interactions. Copyright 2001 Academic Press.     

Effects of concentration on the partitioning of macromolecule mixtures in agarose gels

To test the effects of solute concentration on the equilibrium partitioning of single macromolecules and macromolecule mixtures between bulk solutions and gels, the partition coefficient in agarose was measured for BSA and for four narrow fractions of Ficoll with Stokes radii of 30-59 A. Solutions of each test macromolecule were equilibrated with a known volume of gel, final liquid concentrations measured, and partition coefficients (gel concentration divided by bulk concentration) calculated by applying a material balance. The partition coefficient of each macromolecule was measured in 4 and 6% gels under dilute conditions and with BSA present at initial concentrations up to 13.5 g/dl. As expected, the partition coefficients decreased with increasing agarose concentration and with increasing macromolecular size. Moreover, increasing the BSA concentration increased the partition coefficient of BSA itself and that of all four Ficolls. This effect was most pronounced for the largest test solutes. Measurements at two ionic strengths confirmed that electrostatic interactions were negligible under the conditions used. The experimental results were compared with predictions from a previously developed excluded volume theory for the partitioning of mixtures of rigid, spheroidal macromolecules in fibrous media. Agarose was represented as a randomly oriented array of cylindrical fibers, BSA as a prolate spheroid, and Ficoll as a sphere. The quantitative agreement between the model predictions and the data was generally quite good, indicating that steric interactions among solute molecules and between solute molecules and gel fibers could explain the partitioning results. The theory is simple enough computationally to be applied to a variety of processes that are influenced by the equilibrium partitioning of macromolecules.     

Analysis of solute diffusion in poly(vinyl alcohol) hydrogel membrane

Measurement of diffusion and partitioning of solutes having molecular weights ranging 180–66000 in PVA gel membranes with various crosslinking degree were carried out. With increasing solute size or decreasing number of average molecular weight between crosslinks of the membranes, both the solute permeability and partition coefficient decreased. In spite of similar solute sizes, the more hydrophilic solute ribonuclease showed higher permeability and partition coefficient than the less hydrophilic α-lactalbumin, probably due to interaction with the hydrophilic PVA. The solute diffusion through swollen gel membrane was analyzed by the equation based on free volume theory. In this analysis equation, the partition coefficient, which is defined as the ratio of solute concentration in gel membrane standardized by water volume in the membrane to that in bulk solution, was introduced as the probability of a diffusing species finding a mesh with a volume of at least the solute size. The efficiency of the proposed analysis equation was confirmed by the experimental results of the effects of solute size and water volume fraction in the membrane.     

Large influence of cholesterol on solute partitioning into lipid membranes

Cholesterol plays an important role in maintaining the correct fluidity and rigidity of the plasma membrane of all animal cells, and hence, it is present in concentrations ranging from 20 to 50 mol %. Whereas the effect of cholesterol on such mechanical properties has been studied exhaustively over the last decades, the structural basis for cholesterol effects on membrane permeability is still unclear. Here we apply systematic molecular dynamics simulations to study the partitioning of solutes between water and membranes. We derive potentials of mean force for six different solutes permeating across 20 different lipid membranes containing one out of four types of phospholipids plus a cholesterol content varying from 0 to 50 mol %. Surprisingly, cholesterol decreases solute partitioning into the lipid tail region of the membranes much more strongly than expected from experiments on macroscopic membranes, suggesting that a laterally inhomogeneous cholesterol concentration and permeability may be required to explain experimental findings. The simulations indicate that the cost of breaking van der Waals interactions between the lipid tails of cholesterol-containing membranes account for the reduced partitioning rather than the surface area per phospholipid, which has been frequently suggested as a determinant for solute partitioning. The simulations further show that the partitioning is more sensitive to cholesterol (i) for larger solutes, (ii) in membranes with saturated as compared to membranes with unsaturated lipid tails, and (iii) in membranes with smaller lipid head groups.     

Influence of Solute Charge and Hydrophobicity on Partitioning and Diffusion in a Genetically Engineered Silk‐Elastin‐Like Protein Polymer Hydrogel

The influence of solute hydrophobicity and charge on partitioning and diffusion in physically crosslinked networks of a genetically engineered SELP polymer was investigated. A series of fluorescent dyes were used to assess the impact of solute charge and hydrophobicity on release behavior. The mechanism of solute release from the SELP hydrogel appeared to vary as a function of dye hydrophobicity. The extent of FITC attachment to amine‐terminated G4 dendrimers influenced SELP hydrogel partitioning more than dendrimer diffusion properties. Results suggest the possibility of controlling solute release from SELP hydrogels by modifying the hydrophobicity and surface charge of drugs and drug/polymer conjugates as well as the possibility of “designing‐in” solute‐specific interactions.

     

An Extension and New Interpretation of Ościk's Equation for Describing Liquid Chromatography with Mixed Mobile Phases. II. Partition and Adsorption Effects

Abstract

Previously [J. Liquid Chromatogr. 8 (1985) 1363] it was shown that an equation having a form similar to O?cik's classical equation was derivable from a model involving solute partitioning (with no solute and solvent displacement) between a bulk-liquid mobile phase and a surface-influenced stationary liquid layer. Based on a recent general theory, we now propose a solute retention model which reveals an alternative molecular basis of O?cik's equation, which has been successfully applied to a range of liquid adsorption chromatographic systems. According to this model, solute is distributed between the     

Basic polymers for the cleavage of fluorenylmethoxycarbonyl amino-protecting groups in peptide synthesis

Increased efficiency in the cleavage of $\text{N}$-fluorenylmethoxycarbonyl derivatives by basic resins is obtained using polymer systems designed to take account of solvation and solute partitioning effects.     

Partitioning of organic compounds in phases imitating the headgroup and core regions of phospholipid bilayers

Solvation free energies of drugs, peptides, and other small molecules in the core and headgroup regions of phospholipid bilayers determine their conformations, accumulation, and transport properties. The transfer free energy includes the energy terms for the formation of a cavity for the solute, the interactions of the solute with phospholipids, electrostatic interactions of the solute with the membrane, and dipole potentials and entropy terms. The interaction energies with phospholipids can be estimated by correlating the partitioning in surrogate solvent systems and in the bilayer. As the headgroup surrogate, we use diacetylphosphatidylcholine (DAcPC), the acetylated headgroup of the most abundant mammalian phospholipid, phosphatidylcholine, which forms a homogeneous solution with acceptable viscosity when mixed with water in ratios similar to those in the fully hydrated bilayer. The two-phase system of n-hexadecane (C16) as the core surrogate and hydrated DAcPC was used to monitor partitioning of 16 nonionizable compounds. On the bilogarithmic scale, the C16/DAcPC partition coefficients correlate neither with those in the C16/water and 1-octanol/water systems nor with their difference, which is frequently used as a parameter of hydrogen bonding for prediction of the bilayer location of the solutes. The C16/DAcPC system provides a satisfactory emulation of the solvation properties of the bilayer regions, as reflected in correct predictions of the bilayer location for those of the studied chemicals, for which this information is available.     

Solute-Solvent Interactions in the Nematic and Smectic A Phases of 4 4-di-n-Heptylazoxybenzene Studied by Deuteron NMR

The orientational order parameters have been measured by deuteron N.M.R. of both solute (at low dilution) and solvent in various binary mixtures involving the liquid crystal 4,4'-di-n-heptylazoxybenzene (HAB). The solutes studied were azoxybenzene-d₁₀ and n-heptylbenzene-d₇ which are fragments of HAB, azobenzene-d₁₀ because of its similarity to azoxybenzene, and anthracene-d₁₀ because of its known structure and symmetric shape. The major and biaxial order parameters of the solutes are analysed in terms of a molecular field model for the potential of mean torque for biaxial particles. The behaviour of the solute order parameters on approaching and entering the smectic A phase is interpreted in terms of a temperature and phase dependent partitioning of the solute between aromatic and aliphatic regions of the solvent.     

Spectral curve deconvolution in micellar systems with H-point curve isolation and H-point standard addition methods

A method for spectral curve deconvolution is described, evaluated and applied to micellar systems. The technique is based on combination of H-point curve isolation method (HPCIM) and H-point standard addition method (HPSAM). HPCIM is used for extracting the spectrum of solute in micellar pseudophase and HPSAM is used for calculation of equilibrium concentrations of solute in aqueous phase for each sample. The outputs of procedure are spectrum of dye molecules in micellar pseudophase free from contribution of the dye in the aqueous phase, and partition coefficients of considered solutes between micelle and water phase. The effects of noise and extent of solute partitioning on the reliability of the method are evaluated using model data. The applications of the method to the study of interaction of two different solutes, m-cresol purple (m-CP) and Azure C with Brij-35 and 2-amino-cyclopentene-1-dithiocarboxylic acid (ACDA) with cetyltrimethylamonium bromide (CTAB) micellar systems are presented.     

Rapid estimation of octanol-water partition coefficients using synthesized vesicles in electrokinetic chromatography

Vesicle electrokinetic chromatography (VEKC) using vesicles synthesized from the oppositely charged surfactants cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) and from the double-chained anionic surfactant bis(2-ethylhexyl)sodium sulfosuccinate (AOT) was applied to the indirect measurement of octanol-water partition coefficients (log Po/w). A variety of small organic molecules with varying functional groups, pesticides, and organic acids were evaluated by correlating log Po/w and the logarithm of the retention factor (log k') and comparing the calibrations. A linear solvation energy relationship (LSER) analysis was conducted to describe the retention behavior of the vesicle systems and compared to that of octanol-water partitioning. The solute hydrogen bond donating behavior is slightly different with the vesicle interactions using CTAB-SOS vesicles as compared to the octanol-water partitioning model. The AOT vesicle and octanol-water partitioning systems showed similar partitioning characteristics. VEKC provides rapid separations for determinations of log Po/w in the range of 0.5 to 5 using CTAB-SOS vesicles and 0 to 5.5 using AOT vesicles.