Partition coefficient optimum

Partitioning into the CNS will be important for hallucinogens, as for any drug that acts centrally. Correlation between 1-octanol/water partition coefficients and human activity has been reported (13). Regression analysis of log human activity on log P yielded a parabolic fit with an optimum at log P 3.14. The derived equation accounted for only 62% of the variance but included compounds with a variety of substitution patterns and, presumably, qualitative differences in activity. 

Although it is generally considered that response to a toxicant is determined by the availance J Cdt, it must clearly also be expected that there is some threshold of concentration below which the toxicant can be tolerated indefinitely the toxicant arrives so slowly that replacement and repair reactions can compensate for any damage. At the other extreme if the pulse is too rapid the temporary disruption of the vital process may be too short to produce irreversible effects. There is thus likely to be only a defined range of pulse forms producing the specified biological response for any applied dose and since pulse form depends so strongly on P. an optimum value for the partition coefficient within a series of related compounds. 

It may be concluded from these various arguments that the random walk concept will not in itself give rise to an optimum partition coefficient for biological effect, except in the early stages of the build up to the steady state. A maximal internal availance at an optimal value of P only arises when uptake competes with chemical decay or an excretion process with a different permeability relationship. The explanation of an optimum P value is more likely to involve effects on the form of the pulse of toxicant reaching the site of action, which result in the effect of the chemical transferred, rather than the availance, being greatest at a particular polarity. 

Taking as a reference the EON = 5 oligomer, which is close to optimum formulation in a system with n-heptane and water at ambient temperature, and has a partition coefficient of 0.02, it means that the EON = 3 oligomer is 6 times less hydrophilic, and the EON = 7 oligomer 8 times more hydrophilic. 

Similar to the criterion of the minimal partition coefficient, one can also use the criterion of the minimal selectivity. This criterion (a , ) is defined as follows an extraction liquid composition is optimal if there is no other composition that gives a higher value for the minimal selectivity (maximise In other words the optimum composition is that... 

In the right part of Figure 7.1, the maximal minimal partition coefficient is found in O,. Here, the composition where the ratio of the partition coefficients of compounds i and j reaches its optimum, Oo, is also the composition that gives a robust selectivity. Optima with respect to maximal partition coefficients of both compounds are obtained with different compositions. The response surfaces are not completely parallel. Little variation in the composition of the extraction liquid does influence... 

The isolation method of solvent extraction has been suggested as a potentially feasible process to concentrate trace organic compounds from finished drinking water (4). One positive attribute of the solvent extraction method is that its performance for any given compound is theoretically predictable from a partition coefficient of a compound between the water sample and an organic solvent. The partition coefficient can be experimentally determined for any solute in any two-phase solvent system (7, 8). Variables of the extraction procedure such as solvent-to-water ratio and the choice of solvents can be adjusted to achieve optimum recovery. 

The lipophilicity of the drug, as reflected by its w-octanol/buffer partition coefficient (PC), with the optimum PC being in the range 10-100. 

Window Method of Purnell. In 1975 Laub and Purnell44 suggested a largely empirical method for finding the optimum mixture of liquids that would give the best separation for a given sample containing at least three analytes. Their only assumption was a common one—that GC retentions as measured by partition coefficients are additive in proportion to the volume fractions of the liquids used to make the mixed stationary phase that is,... 

According to Kaur and Smitha [36], the optimum lipophilicity for corneal absorption is found in drugs with an n-octanol-water partition coefficient between 10 and 100. For drugs with smaller partition coefficients (highly hydrophilic drugs), the lipophilic epithelium forms the rate-limiting barrier, whereas the hydrophilic stroma... 

The hydrophile-lipophile balance is related to the solubility of a surfactant. At high HLB the surfactant is very water soluble while at low HLB the surfactant is very lipid soluble. Because HLB is solubility related, it is in turn related to the partition coefficient (or ratio of the solubility of the surfactant in a lipid phase to its solubility in an aqueous phase). A high HLB value suggests a low oil/water partition coefficient, and conversely a low HLB shows a high partition coefficient. Hence, an optimum surfactant HLB for enhancing biological activity also implies an optimum partition coefficient for activity enhancement. 

Because partition coefficients are temperature-dependent, there is usually an optimum temperature for headspace SPME. As the temperature rises, more analytes are released from the matrix to the headspace, a process that results in high analyte concentrations in the headspace and favours extraction. At high temperatures, however, coating/headspace partition coefficients decrease and the matrix-dependent optimum extraction temperature... 

These possible steric effects have been evaluated by an approach involving partition coefficients. In this way, an estimate of comparative lipophilicity can be made since this property is felt to influence the ease of membrane transport and thus eventual availability to the site of action. A number of psychotomimetic phenylisopropylamines have been studied in an octanol-water partition system, and the correlation of the resulting values, with central activity has provided a relationship that suggests an optimum lipophilicity for maximum biological activity (Barfknecht et al. 1975). These partition values have been correlated to serotonin receptor stimulation capability (Nichols and Dyer 1977) and have recently been extended to a number of phenethylamine compounds (Nichols et al. 1977). 

The in vitro antibacterial activity of members of leucomycin complex increased with increasing partition coefficient and removal of testification of the three hydroxyl of the macrolide ring. The in vitro activity of the NH lincomycin was positively correlated with log partition coefficeint (Optimum > 2.7). Electronic and steric factors also influenced the activity of leucomycin and lincomycin antibiotics (78). 

QSAR studies were carried out to determine what the optimum angle should be for activity. This resulted in an ideal angle for 4> of 30°. A correlation was worked out between the dipole moment orientation, partition coefficient, and activity as follows ... 

The optimum pH for the purification of YADH, with 1% of the PEG substituted with PEG-FGF, was found to be approximately 5.0. Of course this does not take into account any synergistic effects that might exist between the system parameters. The partition coefficient could be increased by lowering the pH further. Little could actually be gained in reality by doing this however, as the overall purification factor decreased due to a rapid increase in the total protein partition coefficient and the fact that the enzyme became increasingly labile below pH 5. Above pH 5, the partition coefficient decreased rapidly even with the ligand present. 

When an alcohol is added, because alcohol has different partition coefficients in oil and water phases, generally optimum salinity will be affected by WOR. For example. Table 7.6 shows the WOR effect on optimum salinity (Baviere et al., 1981). Three systems were used ... 

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