Toward basic understanding of the partition coefficient log P and its application in QSAR

2008 ◽  
Vol 19 (1-2) ◽  
pp. 71-79 ◽  
Author(s):  
H. Chuman
Keyword(s):  
Partition Coefficient ◽  
Log P ◽  
Basic Understanding

scholarly journals The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities

2015 ◽  
Author(s):  
Steve O'Hagan ◽  
Douglas B Kell
Keyword(s):  
Partition Coefficient ◽  
Molecular Similarity ◽  
Phospholipid Bilayer ◽  
Log P ◽  
Biophysical Properties ◽  
Apparent Permeability ◽  
Endogenous Metabolites

We bring together fifteen, nonredundant, tabulated collections (amounting to 696 separate measurements) of the apparent permeability (Papp) of Caco-2 cells to marketed drugs. While in some cases there are some significant interlaboratory disparities, most are quite minor. Most drugs are not especially permeable through Caco-2 cells, with the median Papp value being some 16.10-6 cm.s-1. This value is considerably lower than those (1310 and 230.10-6 cm.s-1) recently used in some recent simulations that purported to show that Papp values were too great to be transporter-mediated only. While these values are outliers, all values, and especially the comparatively low values normally observed, are entirely consistent with transporter-only mediated uptake, with no need to invoke phospholipid bilayer diffusion. The apparent permeability of Caco-2 cells to marketed drugs is poorly correlated with either simple biophysical properties, the extent of molecular similarity to endogenous metabolites (endogenites), or any specific substructural properties. In particular, the octanol:water partition coefficient, log P, shows negligible correlation with Caco-2 permeability. The data are best explained on the basis that most drugs enter (and exit) Caco-2 cells via a multiplicity of transporters of comparatively weak specificity.

Apparent octanol/water partition coefficients of pentachlorophenol as a function of pH

1982 ◽  
Vol 60 (16) ◽  
pp. 2104-2106 ◽  
Author(s):  
Klaus L. E. Kaiser ◽  
Ilze Valdmanis
Keyword(s):  
Aqueous Solution ◽  
Ionic Strength ◽  
Partition Coefficient ◽  
Linear Function ◽  
Partition Coefficients ◽  
Extreme Values ◽  
Log P ◽  
Water Partition Coefficient ◽  
Non Linear ◽  
Good Agreement

The apparent 1-octanol/water partition coefficient (log PApp) of pentachlorophenol (PCP) varies in non-linear function with pH of the aqueous solution. In the range of pH 1.2 to 13.5 extreme values of log PApp 4.84 at pH 1.2 and log PApp 1.3 at pH 10.5 were observed. In the alkaline regime, log PApp increases strongly with the ionic strength. The ion-corrected partition coefficient of PCP was found to be log P 5.05 in good agreement with literature values.

Determination of Ionization Constant (pKa) and Octanol–Water Partition Coefficient (Log P) of Cyclopiazonic Acid

2005 ◽  
Vol 88 (5) ◽  
pp. 1367-1370 ◽  
Author(s):  
Victor S Sobolev
Keyword(s):  
Partition Coefficient ◽  
Potentiometric Titration ◽  
Ionization Constant ◽  
Cyclopiazonic Acid ◽  
Log P ◽  
Experimental Conditions ◽  
Water Partition Coefficient

Abstract The ionization constant (pKa) and the octanol–water partition coefficient (log P) of the important mycotoxin cyclopiazonic acid (CPA) were determined by means of potentiometric titration, and the lipophilicity profile (log D) was calculated. Under the experimental conditions, pKa of CPA = 2.97 ± 0.09, log P = 3.83 ± 0.10, and log D at pH 7.4 = −0.58.

Diffusion of Drugs into Prostatic Fluid and Milk

1974 ◽  
Vol 8 (8) ◽  
pp. 470-475 ◽  
Author(s):  
Eric J. Lien ◽  
Jean Kuwahara ◽  
Robert T. Koda
Keyword(s):  
Protein Binding ◽  
Partition Coefficient ◽  
Blood Circulation ◽  
Antibacterial Agents ◽  
Log P ◽  
Clinical Implications ◽  
Degree Of Dissociation ◽  
Ph Values ◽  
Prostatic Fluid ◽  
Plasma Concentration Ratio

THE PROSTATIC FLUID/PLASMA CONCENTRATION RATIO of various sulfonamides, antibiotics and antibacterial agents, and the milk/plasma ratio of sulfonamides and basic drugs have been quantitatively correlated with the degree of dissociation, as represented by log U/D, and the partition coefficient (log P). Because of the lower pH values of the prostatic fluid (6.6) and milk (6.8) as compared with the plasma pH (7.4), the degree of dissociation appears to be the most important factor in determining the distribution of these weak acids or bases. Partition coefficient also plays a secondary role. The log Po for maximum diffusion into milk is lower than that for maximum gastrointestinal, buccal or percutaneous absorption. This may be attributed to plasma protein binding which prevents diffusion of the drug from the blood circulation into the milk since high lipophilicity favors protein binding. The clinical implications of the correlations obtained are discussed.

scholarly journals Actual solubility (S|real.|), level of hydrophilic-lipophilic balance (HLBRequ., HLBD, HLBG) and partition coefficient (log P) of phytochemicals contained in Ext. Camellia sinensis L. aqu. siccum in the light of general Hildebrand-Scatchard-Fedors theory of solubility

2018 ◽  
Vol 64 (2) ◽  
pp. 46-59 ◽  
Author(s):  
Zbigniew Marczyński ◽  
Beata Skibska ◽  
Sławomira Nowak ◽  
Jerzy Jambor ◽  
Marian Mikołaj Zgoda
Keyword(s):  
Partition Coefficient ◽  
Phase Boundary ◽  
Green Tea ◽  
Camellia Sinensis ◽  
Mass Exchange ◽  
Selective Extraction ◽  
Optimal Choice ◽  
Log P ◽  
Correlation Equations ◽  
Hydrophilic Lipophilic Balance

Summary Introduction: Using the general Hildebrand-Scatchard-Fedors theory of solubility, the mole fraction (x2) of solubility of phytochemicals contained in the dry green tea leaves was calculated which determines the profile of pharmacological activity. Objective: The applicative purpose of the study was to estimate the actual solubility of phytochemicals – S|real.| [mol/dm3] in water and in water-ethanol solutions of diversified polarity (εM) for their selective extraction and optimal formulation of oral solid dosage form. Methods: The basic physico-chemical and structural quantities of phytochemicals and corresponding mathematical equations of general Hildebrand-Scatchard-Fedors theory of solubility were used to calculate the actual solubility – S|real.| and the level of hydrophilic-lipophilic balance (HLB). Results: The calculated actual solubility values – S|real.| [mol/dm3] collated with correlation equations enabled the assessment of phytochemical capability for the process of mass exchange on phase boundary. Correlation equations for the dependence log P = f (– log S|real.|) point to the structural preferences of phytochemicals in the kinetics of the mass exchange (diffusion) through the natural phase boundary. Conclusions: Calculations and correlations between the values characterizing the actual solubility – S|real.|, media polarity (water, ethanol and their solutions) and the partition coefficient (log P) including the level of hydrophilic-lipophilic balance (HLB) show that basing on thermodynamic components of the general Hildebrand-Scatchard-Fedors theory of solubility, the diffusion profile of phytochemicals contained in the green tea extract (Ext. Camellia sinensis L. aqu. siccum) through the biological phase boundary as well as optimal choice of the extraction medium for selective extraction of the class of phytochemicals can be estimated.

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. Relationship of the lipophilicity of the apochelator to its ability to mobilise iron from reticulocytes in vitro

1994 ◽  
Vol 72 (6) ◽  
pp. 659-666 ◽  
Author(s):  
P. Ponka ◽  
D. R. Richardson ◽  
J. T. Edward ◽  
F. L. Chubb
Keyword(s):  
Iron Overload ◽  
Partition Coefficient ◽  
Iron Chelation ◽  
Maximum Activity ◽  
Log P ◽  
Design And Synthesis ◽  
Pyridoxal Isonicotinoyl Hydrazone ◽  
Relationship Of ◽  
Orally Active

Analogues of the iron (III) chelator, pyridoxal isonicotinoyl hydrazone (PIH) show high potential as orally active agents for the treatment of iron-overload diseases, such as thalassemia. In the present study, the n-octanol–water partition coefficients of 30 analogues of PIH were measured by thin-layer chromatography and also calculated using the additive schemes of Rekker. The purpose was to examine the relationship between lipophilicity of the apochelator and its ability to promote the release of 59Fe from reticulocytes loaded with nonheme 59Fe. Interestingly, maximum activity occurred when the partition coefficient of the apochelator was approximately 1 (log P = 0). Considering the results in the context of the design and synthesis of more active analogues of PIH, it can be suggested that before initiating synthesis, a useful indication of biological activity can be determined by examining the lipophilicity of the molecule, using the schemes of Rekker to calculate the partition coefficient. By using this strategy, analogues of PIH with inappropriate lipophilicity can be excluded before initiating the expensive process of screening in biological models.Key words: iron chelation, iron mobilisation, iron overload, pyridoxal isonicotinoyl hydrazone.

scholarly journals Quantitative Structure-Activity Study against Plasmodium falciparum of a Series of Derivatives of Azetidine-2-Carbonitriles by the Method of Density Functional Theory

2021 ◽  
Vol 11 (2) ◽  
pp. 162
Author(s):  
Mamadou Guy-Richard Koné ◽  
Jean Stéphane N’dri ◽  
Georges Stéphane Dembélé
Keyword(s):  
Plasmodium Falciparum ◽  
Standard Deviation ◽  
Partition Coefficient ◽  
Correlation Coefficient ◽  
Cross Validation ◽  
Molecular Descriptors ◽  
Regression Coefficient ◽  
Log P ◽  
Quantitative Structure ◽  
Structure Activity

<p>This work deals with a Quantitative Structure-Activity study against <em>Plasmodium</em> <em>falciparum</em> of a series of Azetidine-2-carbonitrile derivatives. Using the MLR and MNLR methods from excel and xlstat software, we have been able to develop two QSAR models based on molecular descriptors and plasmodial activity. Calculation level B3LYP/6-311 G (d, p) was used to determine molecular descriptors. The statistical indicators of the first model obtained by the MLR method are: the regression coefficient found was <strong>R<sup>2</sup></strong> = 0.939 with a standard deviation S =0.266, Fischer's coefficient F =82.064, and a cross-validation correlation coefficient  =0.935. The parameters of the second model developed by the MNLR method are: the regression coefficient <strong>R<sup>2</sup></strong>: de 0.953, a standard deviation S of 0.258, the Fischer's test F of 108.957, and the correlation coefficient of the cross-validation  =0.951. Moreover, these models have shown some interesting statistical performance. The energy of the highest occupied molecular orbital (E<sub>HOMO</sub>), the dipole moment (µD), and the partition coefficient (log P) are the molecular descriptors responsible for the <em>Plasmodium falciparum</em> activity of Azetidine-derivatives 2-carbonitriles. Furthermore, the partition coefficient is the primary descriptor for predicting the biological activity of the studied compounds. From the findings, Eriksson <em>et al.</em> and the external validation criteria of Tropsha used to implement the test are verified and accurate.</p>

scholarly journals Influence of aminoacid anions on the absorption process of Mg2+ ions in vitro

2002 ◽  
Vol 70 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Marcoin W. ◽  
Szulc B.
Keyword(s):  
Small Intestine ◽  
Partition Coefficient ◽  
Absorption Rate ◽  
Positive Influence ◽  
Log P ◽  
Rate Measurement ◽  
Absorption Process ◽  
Flow Through ◽  
Magnesium Salts

Influence of aminoacid anions on the absorption process of Mg2+ ions in vitro - The results of the research on influence of modification in the structure of magnesium salts with glycine on the process of Mg (11) ions absorption were presented in this paper. A flow-through apparatus containing a piece of small intestine of a rat was used for the absorption rate measurement of selected organic magnesium salts. The results of the investigations showed the positive influence of modification of the structure on the absorption process. A correlation was established between quantity of absorbed magnesium and the partition coefficient values (log P).

scholarly journals Development and Validation of Liquid Chromatography-Based Methods to Assess the Lipophilicity of Cytotoxic Platinum(IV) Complexes

Inorganics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 130 ◽  
Author(s):  
Matthias Klose ◽  
Sarah Theiner ◽  
Hristo Varbanov ◽  
Doris Hoefer ◽  
Verena Pichler ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Partition Coefficient ◽  
High Performance ◽  
Dynamic Range ◽  
Detection Methods ◽  
Log P ◽  
Drug Candidates ◽  
Development And Validation ◽  
Lipophilicity Parameters ◽  
Crucial Parameter

Lipophilicity is a crucial parameter for drug discovery, usually determined by the logarithmic partition coefficient (Log P) between octanol and water. However, the available detection methods have restricted the widespread use of the partition coefficient in inorganic medicinal chemistry, and recent investigations have shifted towards chromatographic lipophilicity parameters, frequently without a conversion to derive Log P. As high-performance liquid chromatography (HPLC) instruments are readily available to research groups, a HPLC-based method is presented and validated to derive the partition coefficient of a set of 19 structurally diverse and cytotoxic platinum(IV) complexes exhibiting a dynamic range of at least four orders of magnitude. The chromatographic lipophilicity parameters φ0 and Log kw were experimentally determined for the same set of compounds, and a correlation was obtained that allows interconversion between the two lipophilicity scales, which was applied to an additional set of 34 platinum(IV) drug candidates. Thereby, a φ0 = 58 corresponds to Log P = 0. The same approaches were successfully evaluated to determine the distribution coefficient (Log D) of five ionisable platinum(IV) compounds to sample pH-dependent effects on the lipophilicity. This study provides straight-forward HPLC-based methods to determine the lipophilicity of cytotoxic platinum(IV) complexes in the form of Log P and φ0 that can be interconverted and easily expanded to other metal-based compound classes.

scholarly journals 1-Octanol-water partition coefficient of some cyanopyridine and chalcone compounds

2017 ◽  
Vol 46 (3) ◽  
pp. 342-356
Author(s):  
Shipra Baluja ◽  
Anchal Kulshrestha ◽  
Jagdish Movalia
Keyword(s):  
Partition Coefficient ◽  
Log P ◽  
Water Partition Coefficient ◽  
El Sistema

Los coeficientes de reparto (P) de algunos compuestos sintetizados derivados de cianopiridina y chalcona se estudiaron en el sistema 1-octanol-agua a diferentes valores de pH. Se observa que log P depende del pH y de la naturaleza del gruposustituyente presente en los compuestos. El grupo central también desempeña un papel importante en la naturaleza hidrofílica/hidrofóbica de los compuestos. No hayuna tendencia regular para la variación de log P con el pH.

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