Standard partition coefficient

Bouchard, G., Galland, A., Garrupt, P. A., Gulaboski, R., Mirceski, V., Scholz, F., Girault, H. H. Standard partition coefficients of anionic drugs in the n-octanol/water system determined by voltammetry at three-phase electrodes. Phys. Chem. Chem. Phys. 2003, 5, 3748-3751. 

The standard Gibbs energy of the ion transfer is a direct measurement of lipophilicity, and is related to the standard partition coefficient of the ion in the biphasic system through the following equation ... 

Thus, the presence of the axial OH substituent on C14 appears to enhance both agonist and antagonist potencies. However, for neither pair of agonists has activity or binding been studied in model or in vitro systems, nor have intraventricular whole animal potencies or standardized partition coefficients been obtained for either pair. 

Partition coefficients are thought to reflect the probability that a compound can diffuse, from the site of administration to a site of biological action, within a standard time interval (21). The electronic and steric factors, o and E, are assumed to reflect the reactivity of a crucial reaction site on the molecule, e.g., in the case of the nltrosamines, the ease of enzymatic oxidation of an a C-H bond (8, 24). 

Gel Filtration. The lyophilized protein was redissolved in 50 mM phosphate buffer, pH 7.4 0.15 m NaCl 0.013 % sodium azide and loaded on a Superdex 75HR1030 column equilibrated with the same buffer. Elution was downward flow (0.15 ml/min) and 0.25 ml fi actions were collected. Fractions with pectin lyase activity were combined, dialyzed against distilled water and used in the next step. To estimate the molecular mass of PNL, the column was calibrated with standard proteins (Sigma MW-GF-70 Albumin, 66,000 Da Carbonic Anhidrase, 29,00 Cytochrome, 12,400 and Aprotinin, 6,500). The proteins were eluted in the conditions described above and their volumes (F ) were calculated fi om the peak maximum of the absorbance at 280 nm. The partition coefficient was obtained fi om the relationship where F, represents the bed volmne of column and F the void volume (which was calculated using blue dextran. Sigma). The molecular mass was determined using a standard curve of vs the logarithm of the molecular masses of the standards [28, 29]... 

A relative scale of the standard Gibbs energies of ion transfer or the standard ion transfer potentials can be established based on partition and solubility measurements. The partition eqnilibrium of the electrolyte can be characterized by a measnrable parameter, the partition coefficient P x-... 

To further analyze the relationships within descriptor space we performed a principle component analysis of the whole data matrix. Descriptors have been normalized before the analysis to have a mean of 0 and standard deviation of 1. The first two principal components explain 78% of variance within the data. The resultant loadings, which characterize contributions of the original descriptors to these principal components, are shown on Fig. 5.8. On the plot we can see that PSA, Hhed and Uhba are indeed closely grouped together. Calculated octanol-water partition coefficient CLOGP is located in the opposite corner of the property space. This analysis also demonstrates that CLOGP and PSA are the two parameters with... 

Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic (= fat-loving) environment and is commonly measured by the partition coefficient, (where aaa represent a generic biphasic system, e.g. oct indicates the standard octanol-water). P is valid for a single electrical species, to be specified (P for neutral forms and P for ionized species). The distribution coefficient, expressed as is a pH-dependent descriptor (Eq. 3) for ionizable solutes and results from the weighted contributions of all electrical forms present at this pH ... 

The quantitative descriptor of lipophilicity, the partition coefficient P, is defined as the ratio of the concentrations of a neutral compound in organic and aqueous phases of a two-compartment system under equilibrium conditions. It is commonly used in its logarithmic form, logP. Whereas 1-octanol serves as the standard organic phase for experimental determination, other solvents are applied to better mimic special permeation conditions such as the cyclohexane-water system for BBB permeation. Measurement of log P is described in Chapters 12 and 13 as well as in Ref [22]. 

However, as stated above, the partition coefficients measured by the shake-flask method or by potenhometric titration can be influenced by the potenhal difference between the two phases, and are therefore apparent values which depend on the experimental condihons (phase volume ratio, nature and concentrahons of all ions in the solutions). In particular, it has been shown that the difference between the apparent and the standard log Pi depends on the phase volume raho and that this relationship itself depends on the lipophilicity of the ion [80]. In theory, the most relevant case for in vivo extrapolation is when V /V 1 as it corresponds to the phase ratio encountered by a drug as it distributes within the body. The measurement of apparent log Pi values does not allow to differentiate between ion-pairing effect and partihoning of the ions due to the Galvani potential difference, and it has been shown that the apparent lipophilicity of a number of quaternary ion drugs is not due to ion-pair partitioning as inihally thought [80]. 

Pauletti, G. M., Wunderli-Allenspach, H. Partition coefficients in vitro Artificial membranes as a standardized distribution model. Bur. J. Pharm. Sci. 1994, 1, 273-282. 

For symmetrical electrolytes, of, e.g., type 1 1, such a liquid-liquid interface, in equilibrium, is described by the standard Galvani potential, usually called the distribution potential. This very important quantity can be expressed in the three equivalent forms, i.e., using the ionic standard potentials, or standard Gibbs energies of transfer, and employing the limiting ionic partition coefficients [3] ... 

The partition coefficient of a substance between several Immiscible solvent pairs can be combined with retention time data to confirm the identity of a substance when a pure standard is available [706]. Devised by Bowman and Beroza, the substance specific partition coefficient ("p-value") was defined as the fractional amount of substance partitioning into the less polar phase of an equal-volume, two-phase system. Only nanogram quantities of sample are required for the measurement and p-values are often sufficiently characteristic to distinguish between closely related substances. 

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. 

Leahy, D. E. Taylor, P. J. Wait, A. R., Model solvent systems for QSAR. 1. Propylene glycol dipelargonate (PGDP). A new standard for use in partition coefficient determination, Quant. Struct. Act. Relat. 8, 17-31 (1989). 

Wasik, S.P., Tewari, Y.B., Miller, M.M., Martire, D.E. (1981) Octcmol/Water Partition Coefficients and Aqueous Solubilities of Organic Compounds. NBSIR 81-2406., U.S. Department of Commerce, National Bureau of Standards, Washington, D.C. 

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). 

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