Partition coefficients INDEX

In the equation, a is the proportion of the active substance dissolved and suspended in the gel phase, P is the proportion between the quantities of the active substance found in the droplets and dissolved in the polymer membrane, K is the partition coefficient. Index I shows the partitioning between the liquid and the matrix, index m is the partitioning between the membrane bordering the liquid droplets and the matrix, and index p is the partitioning between the membrane and the acceptor medium. (The same applies to indexes I, m, and p of diffusion constant D.)... 

Chemioai and physical properties appearance, coiour, odour, moleouiar weight, melting point, refractive index, ionisation constants, partition coefficients, solubility under different conditions of pH or solvent... 

Kier and coworkers found that the molecular connectivity-index and such molecular properties as polarizability, molecular volume," and partition coefficients between water and octanol"" show very good correlation. Because all of these properties could be correlated with biological activity. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Barbato, F. La Rotonda, M. I. Quaglia, E, Interactions of nonsteroidal antiinflammatory drugs with phospholipids comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes, J. Pharm. Sci. 86, 225-229 (1997). 

The studies with barbiturates revealed that the logarithm of the retention time is linearly related to the octanol/water partition coefficients [66,67]. It has been observed that the retention index of the drug is linearly related to the octanol/water partition coefficient (logP), and that results are very close to that of the 2-keto alkane standard (solid line in Fig. 15.9). 

As the logarithm of 1-octanol-water partition coefficient (log P) describes the hydrophobicity of molecules and the retention of solutes in RP-HPLC depends on the hydrophobicity, a strong correlation can be expected between the log V value and the retention of solutes in RP-HPLC. Besides log P, a considerable number of physicochemical parameters have been tested for their capacity to predict retention in RP-HPLC. Thus, Snyder s polarity index, fraction of positively and negatively charged surface area, molecular bulkiness, nonpolar surface area, electron donor and acceptor capacity, various ster-ical parameters, and the energy of highest occupied molecular orbit have all been included in QSRR calculations. 

Many bixxer compounds contain both hydrophobic and hydrophilic sites which can alter cell membranes through penetration. There is a correlation between bitter intensity and hydrophobicity-solubility indexes such as fee octanol/water partition coefficient, lo (7). Penetration may directly affect cAMP phosphodiesterase as part of fee transduction process (see below). A bitter receptor protein may be involved wife certain bitters, such as specific structural requirements wife fee bitter tasting dipeptides and denatonium salts (27). The latter is used in some consumer products to avoid accidental ingestion. A receptor mechanism is also supported by fee existence of a genetic "taste blindness" for some bitter materials (see below). 

Octanol/Water Partition Coefficient (Kow) — the equilibrium ratio of the concentrations of material partitioned between octanol and water. This coefficient is considered to be an index of the potential of a chemical to be bioaccumulated. Higher values of K, are associated with greater bioaccumulative potential. 

One of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood is its solubility characteristics (Table 25-2). The blood gas partition coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood compared with that of inspired gas. The partition coefficients for desflurane and nitrous oxide, which are relatively insoluble in blood, are extremely low. When an anesthetic with low blood solubility... 

Selected compound-specific functions, property-temperature-property relationships, or structure-temperature-property relationships are supplied and discussed in this book for density (Section 3.5), refractive index (Section 4.5), surface tension (Section 5.4), viscosity (Section 6.4), vapor pressure (Section 7.4), enthalpy of vaporization (Section 8.5), aqueous solubility (Section 11.8), and air-water partition coefficients (Section 12.5). 

Sasan, M. T., and Y. Inel, Application of the Characteristic Root Index Model to the Estimation of /V-Octanol / Water Partition Coefficients Polychlorinated Biphenyls. Chemosphere, 1995 30, 39-50. 

Wang, Y.H., Wong, P.K. (2002) Mathematical relationships between vapor pressure, water solubility, Henry s law constant, n-octanol/water partition coefficient and gas chromatographic retention index of polychlorinated-dibenzo-dioxins. Water Res. 36, 350-355. 

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