Lipid solubility, octanol-water partition coefficients

In order for a substance to be absorbed, it must cross biological membranes. Most substances cross by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the octanol/water partition coefficient (Log P) value and the water solubility. The Log value provides information on the relative solubility of the substance in water and the hydrophobic solvent octanol (used as a surrogate for lipid) and is a measure of lipophilicity. Log P values above zero indicate that the substance is more soluble in octanol than water, i.e., is lipophilic, and values below zero (negative values) indicate that the substance is more soluble in water than octanol, i.e., is hydrophilic. In general, moderate Log P values (between 0 and 4) are favorable for absorption. However, a substance with a Log P value around 0 and low water solubility (around 1 mg/1) will also be poorly soluble in lipids and hence not readily absorbed. It is therefore important to consider both the water solubility of a substance and its Log P value when assessing the potential of that substance to be absorbed. 

There are two methods for crossing the BBB passive diffusion or active transport. Passive diffusion is the route preferred by most neuroactive drugs. Lipid solubility is a desired chemical property for a molecule to diffuse across the BBB. For a molecule to cross the BBB by passive diffusion it should have a molecular weight less than 650 g/mol and should have a logP (logarithm of the octanol-water partition coefficient) value... 

The partition coefficient Kq of an organic compound in the 1-octanol/water system is used to assess the bioaccumulation potential and the distribution pattern of drugs and pollutants. The partition coefficient of imidazole and ILs strongly depends on the hydrogen bond formed by these molecules and is less than one due to the high solubility in water. The low value of the 1-octanol/water partition coefficient is required for new substances, solvents, insecticides to avoid bioaccumulation. Kqw is an extremely important quantity because it is the basis of correlations to calculate bioaccumulation, toxicity, and sorption to soils and sediments. Computing the activity of a chemical in human, fish, or animal lipid, which is where pollutants that are hydrophobic will appear, is a difficult task. Thus, it is simpler to measure the 1-octanol/water partition coefficient. This parameter is used as the primary parameter characterizing hydrophobisity. 

There have been a number of solvent systems utilized in the measurement of the partition coefficient (Livingstone 2003). By far the most commonly used in the last few decades has been the octanol-water solvent pair. The octanol-water partition coefficient is the most commonly measured and applied in QSAR analysis, and it will be the subject of this discussion. By convention the logarithm to the base 10 of the partition coefficient is taken, and known as log or log P. In a series of compounds, a higher log Kow represents more hydrophobic compounds (i.e., more soluble in lipid), and a lower log Kow represents more hydrophilic compounds (i.e., more water soluble). 

Cornea The cornea is an important mechanical barrier protecting the intraocular tissues. It is considered to be the main pathway for ocular penetration of topically apphed drugs. However, due to its unique structure, with the hydrophilic stroma sandwiched between the highly lipophilic epithelium and the less lipophilic endothelium, the penetration of compounds through the cornea depends on their n-octanol-water partition coefficient. Only drugs with a partition coefficient between 10 and 100 that show both lipid- and water-soluble properties can readily pass through the cornea. 

As judged from octanol/water partitioning experiments in the presence and absence of Tween 80, the principal effect of adding surfactant to the TFMS herbicides at the 0.1% (w/v) level was to alter their relative solubilities in the aqueous and lipid phases. Since the trifluoro-methanesulfonanilides are all quite hydrophobic, the addition of Tween 80 in every case increased the water solubility of the compound in question and hence decreased its octanol/water partition coefficient (6). 

Recently van Haelst et al. [241, 242] have determined the bioconcentration factors of single TCBT isomers in zebra mussels Dreissena polymorpha ) and in adult female guppies (Poecilia reticulata). The bioconcentration factors on a wet weight basis (BCF ) and on a lipid basis (BCFl) of eight tetrachlorobenzyltoluenes (TCBTs) isomers in mussels are compiled in Table 14. The melting points, water solubilities, and the n-octanol/water partition coefficients (log... 

Passive diffusion of sulfonamides into human red cells is determined by plasma dmg binding and lipid solubility. Apparent partition coefficients between chloroform and water at pH 7.4 show an almost linear relation with penetration constant for sulfonamides and a number of other acids. Penetration rates of sulfonamides into the aqueous humour and cerebrospinal fluid also correlate with partition coefficients (Fig. 5.11) moreover, as can be seen from the data in Fig. 5.12, the antibacterial effects of fatty acids and esters towards B. subtilis correlate with octanol/water partition coefficients. 

Root uptake has been proven to be an important pathway for contaminants with intermediate octanol-water partitioning coefficients (Aiow)- Variable uptake of an organic compound by different plants has been observed. Plant species such as Daucus carota (carrot) and Pastinaca sativa (parsnip) with swollen storage roots did not translocate chemicals as well as expected from barley experiments. While the lipid content was considered a factor, plant structure, root types, and other properties may all play a role. The effect of the chemical itself was best illustrated by the increasing root concentration factor (RCF) and the bell-shaped transpiration stream concentration factors (TSCF) relative to logAiow- The physiochemical properties of compounds, including the Ko, solubility, and... 

Chemical modification can be used to manipulate lipid solubility and permeation through membranes. Leu -enkephalin is a pentapeptide Tyr-Gly-Gly-Phe-Leu-OH of M 627 Met -enkephalin is identical except for the replacement of methionine for leucine. Leu-enkephalin (Figure 8.12b) has an octanol/ water partition coefficient of 0.6 addition of an 1-adamantane moiety (Figure 8.12c) increases the partition coefficient to 132 and enhances permeation into the brain [50]. 

In Equation 10.11, C (t) is the concentration of the compound in the SC lipid phase at time t, 5 is its solubility in these lipids (taken to be the product of water solubility and octanol-water partition coefficient K a)> id b is a positive exponent with a value of about 2.7 (Kasting and Saiyasombati, 2001). The value of b was estimated based on an analysis of the Flynn skin permeability database (Johnson et al., 1997), which represents steady-state permeabilities obtained with hydrated human skin in vitro. It is possible that a somewhat higher value of b may apply for volatile disposition on air-dried skin if it is more size selective than hydrated skin. Such a refinement has not been attempted here. 

The uptake of organic contaminants by plants from biosolids-amended soil depends on the physicochemical properties of organic compoimds and the physiology of plants [92-95]. Plant uptake of organic chemicals and their distribution within plants have been shown to be affected by (1) the organic chemicals physicochemical properties, including solubility, vapor pressure, octanol-water partition coefficient Kow)> and Henry s law constants (iC ), (2) environmental conditions such as temperature, air disturbance and soil organic matter content, and (3) plant characteristics, for example the shape of the leaves, type of root system, and lipid and cuticle characteristics and contents [94]. 

When the organic phase is /r-octanol, the partition coefficient is represented by the or the octanol-water partition coefficient. The relationship is parabolic when the log of the inverse of the concentration is plotted against the log of the partition coefficient and reflects the influence that the degree of lipophilicity has on the movement of compounds across biological membranes. At low lipid solubilities, compounds do not pass as readily through membranes as do compounds that are more lipid soluble. 

Correlations between the bioaccumulation tendency of organic chemicals in aquatic organisms and 1-octanol/water partition coefficients show a loss of linearity for very hydrophobic compounds. In order to establish the possible cause(s) of this phenomenon, the roles of metabolism, exposure time, membrane permeation, lipid solubility, and bioavailability on the bioconcentration potential of chemicals, are discussed. Data are presented showing their relative importance. It is concluded that, although insufficient experimental data presently exist which can conclusively establish the cause(s), reduced lipid solubility and reduced bioavailability are the most likely factors contributing to the loss of linear correlation for non-metabolizing chemicals. 

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