Chloroform/water partitioning system

Cieplak, P., Caldwell, J. W., Kollman, P. A., Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation aqueous solution free energies of methanol and IV-methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases, J. Comput. Chem. 2001, 22, 1048-1057... 

Mechanical Models for Organic and Biological Systems Going Beyond the Atom Centered Two Body Additive Approximation Aqueous Solution Free Energies of Methanol and N-Methyl Acetamide, Nucleic Acid Base, and Amide Hydrogen Hydrogen Bonding and Chloroform/Water Partition Coefficients of the Nucleic Acid Bases. 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

DNPH-steroids can be separated by HPLC with several partition systems [31,32] including 1 % /3,/3 -oxydipropionitrile (BOP) on Zipax with eluting solvents containing 0-20% tetrahydrofuran in heptane or 2-methylheptane, or 1% ethylene glycol on Zipax with 3% chloroform in heptane as the mobile phase. Reversed-phase chromatography with 1.0% hydrocarbon polymer (HCP) or 1% cyanoethyl silicone (ANH) on Zipax and methanol-water as the mobile phase can be useful for the separation of several polar steroids. Gradient elution (water to methanol) on octadecylsilane (ODS), Permaphase (chemically bonded on Zipax), also provides a separation of polar DNPH-steroids. The separation of five DNPH-steroids on 1.5% BOP coated on Zipax is shown in Fig.4.13. 

A second physicochemical parameter influencing chemical penetration through membranes is the relative lipid solubility of the potential toxicant that can be ascertained from its known partition coefficient. The partition coefficient is a measure of the ability of a chemical to separate between two immiscible phases. The phases consist of an organic phase (e.g., octanol or heptane) and an aqueous phase (e.g., water). The lipid solvent used for measurement is usually octanol because it best mimics the carbon chain of phospholipids, but many other systems have been reported (chloroform/water, ether/water, olive oil/water). The lipid solubility and the water solubility characteristics of the chemical will allow it to proportionately partition between the organic and water phase. The partition coefficients can be calculated using the following equation ... 

Moreover, A log P was proposed as a molecular descriptor for modeling hydrogen bonding capacity it corresponds to the difference between the partition coefficient experimentally determined in octanol/water (log Pow) and partition coefficients determined in other systems, such as octanol/water-heptane/water (logPaijj) systems and octanol/water-chloroform/water (log PCH3C1) systems [El Tayar, Tsai et al, 1991b Winiwarter, Ax et al., 2003]. 

Selection of the octanol-water system is often justified in part beeause, like biological membrane components, oetanol is flexible and contains a polar head and a nonpolar tail. Hence, the tendency of a drug molecule to leave the aqueous phase and partition into oc-tanol is viewed as a measure of how efficiently a drug will partition into and diffuse across biological barriers such as the intestinal membrane. Although the octanol-water partition coefficient is, by far, most commonly used, other solvent systems such as cyclohexane-water and chloroform-water systems offer additional insight into partitioning phenomena. 

Principles of Use. Solvent/water partition coefficients (Ksw) have been measured for numerous solutes in a targe variety of solvent systems. These K w values, like Kow, have found wide use in structure-activity correlations, especially for pharmaceuticals. Some of the more frequently used organic solvents are ethyl ether, n-butanol, chloroform, cyclohexane, benzene, and vegetable oils. In analogy with Eq. 1-1, KsW is defined as the ratio of the solute s concentration in the organic phase to that in the aqueous phase of the two-phase system at equilibrium. Low solute concentrations are employed in the measurement. 

Since vitamin D and its metabolites are fat-soluble sterols, partition into organic solvents provides significant purification by removal of water-soluble contaminants. Solvent systems for extraction fall into two basic categories (see Table 4) [1] total lipid extraction, for example, methanol-chloroform-water (2 1 0 8) (83) or ethanol-water (9 1) (84), and [2] selective lipid extraction, for example, ether, ethylacet-ate-cyclohexane (1 1), hexane, dichloromethane, or hexane-isopropanol (1 2). 

The data are qualitatively parallel with those reported in the case of polystyrene derivatives, however, they differ in that the methacrylamide derivatives extract much more effectively than the polystyrene derivatives. One of the reasons for the high extracta-bility of the methacrylamide derivatives s ascribed to their higher partition coefficients in agugous phase. The e tgactions by the derivatives of polyacrylate and polyacrylamide showed the same tendencies, although the extractions were carried out in a chloroform-water system. 

Sorenson and Arlt Liquid-Liquid Equilihiium Data Collection, DECHEMA, Frankfurt, Germany, 1979) report several sets of liquid-liquid equilibrium data for the system acetone-water-chloroform, but the lowest solute concentrations reported at 25 C were. 3 weight percent acetone in the water layer in equilibrium with 9 weight percent acetone in the chloroform layer. This gives a partition ratio K of, 3.0. 

SAQ 5.5 An aqueous solution of sucrose is prepared. It is shaken with an equal volume of pure chloroform. The two solutions do not mix. The sucrose partitions between the two solutions, and is more soluble in the water. The value of /((partition) for this water-chloroform system is 5.3. What percentage of the sucrose resides in the chloroform ... 

The octanol-water (Po/ ) partition coefficient was found to be 1.96 for the /7-octanol/pH 7.4 Mcllvaine buffer system, and 0.48 for the chloroform/pH 7.4 Mcllvaine buffer system. These determinations were conducted at 33"C to mimic the temperature of the cornea. 

Safari et al. (1993) examined the interesterification of milk fat by the lipase from Rhizomucor miehei in various organic solvents (hexane, hexane-choloroform (70 30, v/v), and hexane-ethylacetate (70 30, v/v)). The addition of chloroform or ethyl acetate to hexane increased lipase activity. It was suggested that the polarity of the solvent influences the partitioning of water in the system with consequent effects on enzymic activity. Bornaz et al. 

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