Olive oil, partition coefficients

Abraham, M.H. and Ibrahim, A. (2006) Gas to olive oil partition coefficients a linear free energy analysis. Journal of Chemical Information and Modeling, 46, 1735-1741. 

Figure 6.7 Plot of the decadic logarithms of the air-olive oil partition coefficients versus the air-octanol partition constants for various sets of structurally related apolar, monopolar, and bipolar compounds. Note that olive oil is a mixture of compounds that may vary in composition. Therefore, we refer to A" a oUve oi] as the air-olive oil partition coefficient (and not constant, see Box 3.2). Adapted from Goss and Schwarzenbach (2001). The a and b values for the LFERs (Eq. 6-12) are alkanes (a - 1.15, b = 0.16), alkyl aromatic compounds (a = 1.08, b = 0.22), ethers (a = 0.97, 6 = 0.01), esters (a = 0.88, b = -0,14), ketones (a = 1.21, b = 1.06), alcohols (a = 0.98, b = 1.07).

Figure 6.8 Fitted (Eq. 6-13) versus experimental air-olive oil partition coefficients for a series of compounds including those in Fig. 6.7. Note that some of the relatively large scatter in the data may be due to the fact that olive oils from different origins may differ in composition.

For estimating the air-olive oil partition coefficient, calculate first the air-octanol partition constant from the air-water (Kisw) and octanol-water (Ki0Vi) partition constants given in Appendix C (Eq. 6-11) ... 

An alternative way of estimating the air-olive oil partition coefficient is to apply the LFER Eq. 6-13 using the constants given in Table 6.2 for the air-olive oil system ... 

An alternative approach to estimating the relative solubility of a compound in water versus nonpolar solvents is to determine the olive-oihwater partition coefficient. The olive-oihwater partition coefficient for the pesticide DDT is 1775. If the concentration of DDT is 3 mg/L in olive oil, what is... 

The lipophilicity of a solute affects its permeability in lipid bilayers. Lipophilicity is usually expressed in terms of its partitioning between water and an organic solvent, such as olive oil [95], oleyl alcohol [96], ether [97], or octanol [98]. Partition coefficient (PC) of a compound is expressed as its concentration ratio between organic medium and water at equilibrium ... 

Four neutral lipid models were explored at pH 7.4 (1) 2% wt/vol DOPC in dode-cane, (2) olive oil, (3) octanol, and (4) dodecane. Table 7.5 lists the effective permeabilities Pe, standard deviations (SDs), and membrane retentions of the 32 probe molecules (Table 7.4). The units of Pe and SD are 10 6 cm/s. Retentions are expressed as mole percentages. Figure 7.22a is a plot of log Pe versus log Kd (octanol-water apparent partition coefficients, pH 7.4) for filters loaded with 2% wt/vol DOPC in dodecane (model 1.0, hlled-circle symbols) and with phospholipid-free dodecane (model 4.0, open-circle symbols). The dashed line in the plot was calculated assuming a UWL permeability (see Section 7.7.6) Pu, 16 x 10-6 cm/s (a typical value in an unstirred 96-well microtiter plate assay), and Pe of 0.8 x 10-6 cm/s... 

Olive oil was the original model lipid for partition studies, and was used by Overton in his pioneering research [518,524], It fell out of favor since the 1960s, over concerns about standardizing olive oil from different sources. At that time, octanol replaced olive oil as the standard for partition coefficient measurements. However, from time to time, literature articles on the use of olive oil appear. For example, Poulin et al. [264] were able to demonstrate that partition coefficients based on olive oil-water better predict the in vivo adipose-tissue distribution of drugs, compared to those from octanol-water. The correlation between in vivo log Kp (adipose tissue-plasma) and log (olive oil-water) was 0.98 (r2), compared to 0.11 (r2) in the case of octanol. Adipose tissue is white fat, composed mostly of triglycerides. The improved predictive performance of olive oil may be due to its triglyceride content. 

Partition coefficients of a series of aliphatic hydrocarbons, including n-hexane, have been determined in human tissues (Perbellini et al. 1985). The following partition coefficients for n-hexane (olive oil/air, blood/air, tissue/air) were determined olive oil, 146 blood, 0.80 liver, 5.2 kidney, 3 brain, 5 fat, 104 muscle, 5 heart, 2.8 and lung, 1. Saline/air partition was not reported separately for n-hexane, but was very low for the range reported for the entire group of compounds (0.1-0.4). 

Gryns (1896), Hedin (1897), and especially Overton (1900) looked at the permeability of a wide range of different compounds, particularly non-electrolytes, and showed that rates of penetration of solutes into erythrocytes increased with their lipid solubility. Overton correlated the rate of penetration of the solute with its partition coefficient between water and olive oil, which he took as a model for membrane composition. Some water-soluble molecules, particularly urea, entered erythrocytes faster than could be attributed to their lipid solubility—observations leading to the concept of pores, or discontinuities in the membrane which allowed water-soluble molecules to penetrate. The need to postulate the existence of pores offered the first hint of a mosaic structure for the membrane. Jacobs (1932) and Huber and Orskov (1933) put results from the early permeability studies onto a quantitative basis and concluded molecular size was a factor in the rate of solute translocation. 

Assuming that for a solute the properties of the biological membrane resemble those of olive oil on an atomistic level, the membrane/donor partition coefficient K may be estimated from the olive oil-water partition coefficient tfoo/w according to the general relationship [16-18] ... 

Abraham, M. H., P. L. Grellier, and R. A. McGill, Determination of olive oil-gas and hexadecane-gas partition coefficients, and calculation of the corresponding olive oil-water and hexadecane-water partition coefficients. J. Chem. Soc. Perkin Trans., 2, 797-803 (1987). 

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 ... 

The affinity of flavonoids for phospholipid membranes has been unequivocally demonstrated by many authors. Many biological functions of these compounds are also believed to be the result of flavonoid interactions with cell membranes. Partition coefficients for a large group of flavonoids between water and olive oil were determined, and it was shown that the hydrophobic-ity of the compounds is inversely proportional to the number of OH groups. 

Most log P values are determined with 1-octanol as the nonpolar solvent. Sometimes octanol-water partition coefficients are denoted Pow to make the nonpolar solvent more explicitly clear. Octanol effectively imitates many lipid membranes, especially those in the small intestine, where most drugs are absorbed. Other solvents are better suited to model other tissues in the body. Chloroform is more polar than octanol and simulates partitioning in oral tissues. Olive oil is less polar than octanol and models the blood-brain barrier. 

Macy, R. (1948) Partition coefficients of fifty compounds between olive oil and water at 20°C. J. Ind. Hyg. Toxicol. 30, 140. Mackay, D. (1982) Correlation of bioconcentration factors. Environ. Sci. Technol. 16, 274-278. 

The first chemical clue relating the structure of anesthetics to their potency was discovered in 1899 by a pharmacologist, Hans Horst Meyer, and an anesthetist, Charles Ernst Overton. Working independently, Meyer and Overton noted a strong correlation between the polarity of a compound and its potency as an anesthetic. They expressed polarity as the oil/gas partition coefficient, while anesthetic potency was expressed as the partial pressure in atmospheres. Figure 11.10 is a Meyer-Overton correlation for 18 anesthetics used on mice. Note that olive oil is used, and it has become the most commonly used reference solvent. 

The slope of the regression line implies that the MAC (minimal alveolar concentration effective in 50 percent of animals) is inversely proportional to partition coefficient or potency is directly proportional to partition coefficient. The Meyer-Overton correlation suggests that the site at which anesthetics bind is primarily a hydrophobic environment. Although a wide variety of compounds lie on the Meyer-Overton correlation line, there are many compounds that do not. This suggests that the chemical properties of the anesthetic site differ from those of olive oil. 

In the following Dp-values calculated with the refined Eq. (15-3) and partition coefficients KpF assumed to equal 1 are used for estimating worst case migration rates for additives from polyolefins with Eq. (7-51). These estimated values are compared with experimentally obtained migration values carried out under well defined conditions for several additives from HDPE and different PP-types (Table 15-3a) into olive oil (O Brian et al., 1999 and 2000). The results are summarized in Table 15-3b. 

Oil-water partition coefficient refers to the tendency of a chemical to distribute itself between lipid and aqueous phases when both are present. This can be measured for comparative purposes by adding the compound to a two-phase system such as olive oil-water or octanol-water, mixing the three components thoroughly, allowing the two phases to separate, and then determining the amount of the compound in each of the phases. Using the olive-water system, DDT has a partition coefficient of 316, indicating that the concentration of DDT in the olive oil is 316 times that in the water phase. 

Table 6.3 shows penetration rates of four insecticides dimethoate, paraoxon, dieldrin, and DDT, through cockroach cuticle. It is seen that the rates of penetration are inversely related to their partition coefficient in the olive oil-water system. In other words, the compound with the best solubility in water, as indicated by its partition coefficient, moved through the cuticle most rapidly. In this experiment, the insecticides were applied to the cuticle as acetone solutions, and it was suggested by the authors that this may have neutralized or canceled any barrier presented by the epicuticle. Thus, the data indicate the... 

Insecticide Half-time (min) Partition coefficient (olive oil-water)... 

Because of its apolar interior, the lipid bilayer is a barrier to diffusional equilibration of solutes between the two aqueous compartments that it separates. The ability of most small solute molecules (50 < molecular weight < 300) to cross the bilayer is directly proportional to their ability to partition into hexadecane or olive oil from an aqueous solution (58), which is an observation first made by Overton (59) and is often referred to as Overton s Law. Permeation of lipid bilayers by small polar molecules and ions seems to occur via one or a combination of both of two mechanisms depending on the nature of the permeants and the nature of the bilayers. First, a solubility-diffusion mechanism treats the bilayer as a slab of liquid hydrocarbon sandwiched between two bulk aqueous compartments. The permeant must partition into the bilayer slab from one of the aqueous compartments, diffuse across it, and leave by dissolving into the second aqueous compartment. In this case, the permeability coefficient, P, is given by ... 

In QSAR 54, LogP represents the olive oil/ water partition coefficient, MW is the molecular weight of the solute and defines its size, and Kfe is a crude approximation of the total number of hydrogen bonds for each molecule. The molecular weight descriptor has also been an omnipresent variable in QSAR studies pertaining to cross-resistance of various drugs in multidrug-resistant cell lines (169). was used because it most... 

Abraham, M.H., Grellier, RL. and McGill, R.A. (1987). Determination of Ohve Oil-Gas and Hexadecane-Gas Partition Coefficients, and Calculation of the Corresponding Olive Oil-Water and Hexadecane-Water Partition Coefficients. J.Chem.Soc.Perkin Trans.2,797-803. Abraham, M.H., Grellier, P.L., Hamerton, I., McGill, R.A., Prior, D.V. and Whiting, G.S. (1988). 

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