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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 79 (1975), S. 2340-2344 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 82 (1978), S. 2240-2245 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 101 (1979), S. 5194-5197 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 616 (1990), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 103 (1995), S. 8666-8678 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Various mean-field potentials in a model lipid bilayer are calculated by means of molecular dynamics (MD) simulation. The bilayer assembly consists of 200 chain molecules. The anisotropic united atom model is employed for nonbonded interactions and is extended to allow bond length to vary with time. The interfacial translational order is systematically varied and found to correlate strongly with the chain orientational order. A new torsional potential is developed and shown to give order parameters in better agreement with experiment than the Padilla–Toxvaerd potential. Nonbonded interaction reduces the trans–gauche and gauche–gauche transition barriers by 0.9—1.5 kcal/mole. The mean trans–gauche energy difference near the chain tail is close to that in liquid hydrocarbons but 0.34 kcal/mol lower than that in the highly ordered chain region. In contrast to the Marcelja model, both mean intermolecular dispersive and repulsive energies depend exponentially on the chain orientational parameter and the repulsive component has a poor and inverse correlation with the reciprocal of the chain end-to-end displacement along the bilayer normal. Inclusion of spatial heterogeneity effects of the interaction energy, a treatment similar to the Gruen model [Biochim. Biophys Acta 367, 165 (1980)], does not give a better description of the mean intermolecular interaction. A new and unified model for the mean intermolecular interaction energy is developed based on our present MD simulation data. Various possible chain configurations which are responsible for these results are discussed. Finally, our MD results suggest that, consistent with the "wobble in a cone'' model, a chain molecule can rotate freely within an angular range without being subjected to a strong potential force. © 1995 American Institute of Physics.
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  • 6
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 110 (1999), S. 1807-1818 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: A thorough understanding of the effects of chain ordering on solute partitioning and transport across biomembranes requires a detailed account of various dissolution processes in lipid bilayers. In this study, the dissolution properties and related molecular processes for noble gases in the alkyl chain region of lipid bilayers were obtained by means of molecular dynamics simulation. The excess chemical potential exhibits a plateau value in the ordered peripheral region followed by a steep decline near the center of the bilayer. The strong entropic effects as manifested by the larger Barclay–Butler constants than commonly encountered in hydrocarbon solvents indicate that solute partitioning into membranes is driven primarily by changes of lipid chain conformation or/and an extra confinement of solute in the bilayer interior. Solute partitioning into lipid bilayers is analyzed in terms of two contributions: (1) the free energy for cavity creation to accommodate a solute, which is analyzed by scaled particle theory; and (2) the interaction energy between the inserted solute and surrounding molecules in the bilayer. The unfavorable free energy for cavity creation is found to be primarily responsible for the substantial decrease of solubility into the membranes from that into a hydrocarbon solvent (dodecane) when the solute size is increased. The observed linear decrease of the excess chemical potential with solute surface area arises from linear but opposite dependencies of the reversible work for cavity creation and the intermolecular interaction energy on solute surface area and may be described by an anisotropic surface-tension model. © 1999 American Institute of Physics.
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  • 7
    ISSN: 1573-904X
    Keywords: lipid bilayer membranes ; bilayer permeability ; unstirred boundary layers ; pH effects ; buffer effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The diffusion of weak acids or bases across planar lipid bilayer membranes results in aqueous boundary layer pH gradients. If not properly taken into account, such pH gradients will lead to errors in estimated membrane permeability coefficients, P m. The role of the permeant concentration, the buffer capacity, and the physicochemical properties of both permeant and buffer on the magnitude and impact of such pH gradients have been explored. A theoretical model has been developed to describe the diffusion of both permeant and buffer species. Significant pH gradients develop depending on solution pH and the pK a's, concentrations, and P m values of both permeant and buffer. The relative error in experimentally determined P m values was calculated as the ratio, r, between apparent P m values (obtained from flux measurements using an equation which neglected boundary layer pH gradients) and its true value. Simulated r values ranged from 1 (0% error) to 〈0.01 (〉100% error) for weak acids, decreasing with decreasing buffer capacity and increasing solute flux. The buffer capacity required for an r 〉 0.95 was calculated versus pH for permeants varying in pK a and P m. Membrane-permeable buffers significantly reduce boundary layer pH gradients through a feedback effect due to buffer cotransport. Apparent P m values of p-hydroxymethyl benzoic acid across lecithin bilayer membranes at 25°C were obtained as a function of permeant concentration in various buffers [glycolic, 2-(N-morpholino)ethane-sulfonic, and formic acids]. Predictions agreed closely with experimental fluxes.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-904X
    Keywords: emulsions ; stability ; field-flow fractionation ; size distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The combination of sedimentation field-flow fractionation (SedFFF) and photon correlation spectroscopy (PCS) is shown to provide a detailed record of the droplet sizes present in fat emulsions commonly used in parenteral nutrition. The technique presented has been used to record size distribution data for a particular emulsion (Liposyn-II), demonstrating its high stability and lot-to-lot uniformity. The technique is also able to demonstrate how additions of small amounts of electrolytes [0.45% (w/v) NaCl, 0.05% (w/v) CaCl2] tend to destabilize the emulsion, suggesting some caution in the use of total parenteral nutrition (TPN) mixtures. In contrast, a 1:1 mixture with human serum caused no sign of instability in the Liposyn-II. Using the emulsion as a carrier for lipophilic drugs necessitates adding solutions of the drug in nonaqueous solvents, such as DMSO (dimethyl sulfoxide). This solvent's destabilizing effect results in a droplet coalescence that becomes severe after 3–5 days following a 10% (v/v) addition, while a 5% (v/v) addition reaches the same level of coalescence in 10 days.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-904X
    Keywords: cosalane ; solubility ; facilitated dissolution ; partition coefficient ; group contribution approach ; pH-solubility behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The selection of cosalane (NSC 658586) by the National Cancer Institute for further development as a potential drug candidate for the treatment of AIDS led to the exploration of the solubility behavior of this extremely hydrophobic drug, which has an intrinsic solubility (S0) approaching 1 ng/ml. This study describes attempts to reliably measure the intrinsic solubility of cosalane and examine its pH-solubility behavior. Methods. S0 was estimated by 5 different strategies: (a) direct determination in an aqueous suspension; (b) facilitated dissolution; (c) estimation from the octanol/water partition coefficient and octanol solubility; (d) application of an empirical equation based on melting point and partition coefficient; and (e) estimation from the hydrocarbon solubility and functional group contributions for transfer from hydrocarbon to water. Results. S0 estimates using these five methods varied over a 5 × 109-fold range. Method (a) yielded the highest values, two-orders of magnitude greater than those obtained by method (b) (facilitated dissolution, 1.4 ± 0.5 ng/ml). Method (c) gave a value 20-fold higher while that from method (d) was in fair agreement with that from facilitated dissolution. Method (e) yielded a value several orders-of-magnitude lower than other methods. A molecular dynamics simulation suggests that folded conformations not accounted for by group contributions may reduce cosalane's effective hydrophobicity. Ionic equilibria calculations for this weak diprotic acid suggested a 100-fold increase in solubility per pH unit increase. The pH-solubility profile of cosalane at 25°C agreed closely with theory. Conclusions. These studies highlight the difficulty in determining solubility of very poorly soluble compounds and the possible advantage of the facilitated dissolution method. The diprotic nature of cosalane enabled a solubility enhancement of 〉107-fold by simple pH adjustment.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 10 (1993), S. 1533-1543 
    ISSN: 1573-904X
    Keywords: lauric acid ; fatty acids ; self-association ; mesophase ; solubility ; lipid bilayers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The solubility and solution behavior of lauric acid (LA) and its 1:1 acid soap (potassium hydrogen dilaurate) were investigated at 32°C over a pH range of 2.5–8.5 and at varying KC1 concentrations to examine the self-association of this long-chain carboxylic acid under these conditions. LA's solubility in water exhibited the classical pH dependence of a monocarboxylic acid with no evidence of self-association. In 0.1 M KC1 between pH 6.3 and pH 7.3, filtered samples were turbid, suggesting the presence of high molecular weight aggregates (mesophase), which could be removed by ultrafiltration. The apparent LA solubility vs pH profile in ultrafiltered samples was consistent with a solid phase consisting of either the free acid (pH 〈 6.5) or potassium hydrogen dilaurate (pH 〉 6.5), again with no evidence of self-association to form low molecular weight species (dimers, etc.). Quasi-elastic light scattering (QLS) studies and mannitol trapping experiments indicated that vesicles were present in samples containing mesophase. The mesophase composition was characterized and a mass-action law for mesophase formation was developed to describe the apparent LA solubility versus pH in the mesophase region in terms of three parameters. The index of cooperativity, θ, indicated that the mesophase consists of approximately 25 molecules of LA with an acid:anion ratio, ρ, of 1.7. The standard free energy of mesophase formation per mole of monomer was determined to be −6.3 kcal/mol. The aggregate size determined thermodynamically is several orders of magnitude less than that of the mesophase particle size determined by QLS measurements, suggesting that the LA monomer concentration in equilibrium with mesophase may be governed by a small unit domain of the vesicle. These observations may have a bearing on the thermodynamics of self-assembly of lipid bilayer membranes.
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