Chemistry
Partition Coefficient
The partition coefficient is a measure of the distribution of a solute between two immiscible phases, typically a hydrophobic organic solvent and water. It is defined as the ratio of the concentration of the solute in the two phases at equilibrium. The partition coefficient is an important concept in chemistry, particularly in the fields of analytical chemistry and drug development.
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eBook - ePubAir Pollution Calculations
Quantifying Pollutant Formation, Transport, Transformation, Fate and Risks
- Daniel A. Vallero(Author)
- 2019(Publication Date)
- Elsevier(Publisher)
P indicates decreasing water solubility and increasing lipophilicity.In biomedical and pharmacological parlance, P is often the ratio of a solvent in unionized water and in unionized n -octanol [9] , rendering it the same as the octanol-water coefficient (K ow ), discussed later in this chapter. In fact, the chemical authority, International Union of Pure and Applied Chemistry (IUPAC), considers the term, Partition Coefficient, to be obsolete, preferring “distribution constant” instead [10] . The distribution coefficient differs from the Partition Coefficient by including ionized solvents. Indeed, this book will follow the approach of air pollution and environmental venues, which considers the Partition Coefficient to an inclusive term for any type of partitioning at equilibrium, and K ow to be specific to octanol-water partitioning.4.2.3 Fugacity [11]
Recall for Chapter 3 that the chemical potential of a compound is a form of energy that can be absorbed or released during a reaction because of a change in the particle number of that compound. When temperature and pressure are held constant, chemical potential is the partial molar Gibbs free energy (see discussion in Chapter 3 ). At chemical equilibrium, the sum of the product of chemical potentials and stoichiometric coefficients is zero, since free energy is minimized. This is also true for equilibrium between physical phases, for example, environmental compartments.The fugacity of a substance is its potential to escape from one compartment to another. Fugacity is similar to chemical potential. However, fugacity is proportional to concentration, whereas chemical potential is not [12] . In the vapor or gas phase, substances vary in their tendency to escape from one compartment to another, for example, from the water to the air (see Fig. 4.2
eBook - PDFHazard Assessment of Chemicals
Current Departments
- Jitendra Saxena(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
Partition Coefficient and Water Solubility in Environmental Chemistry Cary T. Chiou Environmental Health Sciences Center Oregon State University Corvallis, Oregon I. Introduction 117 II. Partition Theory 118 A. Additivity of Partition Coefficient in Relation to Activity Coefficient 120 B. Effect of Solute Concentration 124 C. Effect of Temperature 125 D. Estimation of Partition Coefficient by HPLC Technique 127 III. Relationship between Partition Coefficients 128 A. Correlation between Partition Coefficient and Water Solubility . . . . 129 B. Correlation between Partition Coefficients of Two Solvent-Water Systems 139 IV. Bioconcentration from Water 141 V. Soil-Water Distribution 144 VI. Conclusion 150 References 150 I. INTRODUCTION Chemicals discharged into the environment may be found in various compart-ments: air, water, soil, and biota. Attempts to define environmental concen-trations must take into account the properties of the chemicals and the system variables. Considering this, it would be of value to characterize chemical trans-port and distribution in terms of system parameters. Physical and chemical prop-erties provide one criterion for determining the relative distribution of the chemi-117 HAZARD ASSESSMENT OF CHEMICALS: Copyright © 1981 by Academic Press, Inc. Current Developments, Vol. 1 All rights of reproduction in any form reserved. ISBN 0-12-312401-8 118 Cary T. Chiou cal between two phases at equilibrium and the transport rate from one phase to another. Both factors are important for assessing the impact of chemicals in physical and biological systems. The distribution of a compound between two immiscible (or partially miscible) phases in which it is soluble has been an important topic of study in chemistry since the earlier work of Berthelot and Jungfleisch (5) and Nernst (84).
eBook - PDFPhysical Properties of the Steroid Hormones
International Series of Monographs on Pure and Applied Biology: Biochemistry, Vol. 3
- Lewis L. Engel(Author)
- 2013(Publication Date)
- Pergamon(Publisher)
The Partition Coefficient is then calculated using Equation (A). It is important that analyses be performed on both phases and the recovery calculated, since this provides the only means of knowing whether the solute has been completely dissolved. Analysis of both phases also increases the accuracy and precision in situations where the value of the Partition Coefficient differs greatly from unity. In such cases it is the ratio of a large to a small number (or the reciprocal) and a small error in the value of the small number produces a large effect upon the value of the ratio. If the Partition Coefficient in these situations is calculated from analysis of one phase only, a large error may be introduced. It is difficult to assign limits of errors to the measurement of this constant, since they depend upon both the analytical procedure employed and the numerical value of the Partition Coefficient. As pointed out above, values differing greatly from one may be subject to quite considerable error. The Partition Coefficient may also be estimated from countercurrent distribution curves. In this situation, both the precision and the accuracy of the value obtained 500h K 2.00J-100 0 50 % MeOH tn M e O H -H 2 0 60 70 © 3 0 % M e O H · 307oCHCI 3 Δ 5 0 % MeOH A 5 o % C H C I 3 D 70 %MeOH ■ 7 0 % CHCI 3 3*,17*<,2I - Trihy droxypregnane -II ,20-dtonel %MeOH in MeOH-Η,,Ο 20 30 40 50 60 70 30 40 50 60 70 % C H C I 3 in C H C I 3 -C C I 4 FIG. 7 Relation between phase composition and Partition Coefficient, K, for 3 a, 17,21-Trihydroxypregnane-ll,20-dione in the system Methanol : Water/Chloroform : Carbon tetrachloride. The ordinate is the Partition Coefficient (K) plotted on a logarithmic scale. The lower (solid) abscissa gives the composition of the lower phase and the upper (dashed) abscissa gives the composition of the upper phase. Variation in K with changing lower phase composition at three fixed upper phase compositions.
eBook - ePub- Des W. Connell(Author)
- 2018(Publication Date)
- CRC Press(Publisher)
A ) is given by=G ¯A+ RT ℓ n aG ¯A owhereis a standard reference free energy for the solute, R the universal gas constant, a the activity, and Τ the temperature (Kelvin). At equilibrium the partial molar free energies in each phase (A and B) are equal, hence∘G ¯Aℓ n(1)=a Aa BRT−G ¯B oG ¯A oFor a given temperature,and R are constants, and therefore∘ ,G ¯A∘G ¯B(2)= K = constanta Aa BEquation 2 is a mathematical statement of Nernst's distribution law. When the solutions are dilute, or when the solute is an ideal one, the activity is approximately equal to the concentration in each phase, and Equation 2 becomes= KC AC BThe dimensionless constant, K, is referred to as the Partition Coefficient of the solute between the two solvents A and B.11 From Equation 1 , it is apparent that the Partition Coefficient has a temperature dependence. Chiou et al.12 have suggested that the temperature effect on the Partition Coefficient is generally about 0.01 log units per degree around room temperature.An expression describing the Partition Coefficient may also be derived from the viewpoint of chemical potential. The chemical potential (μ) of a solute distributed between two phases A and B, is given byμ A=μ 0+ RT ℓn γ Aϕ Aμ B=μ 0+ RT ℓn γ Bϕ Bwhere μ° is the standard chemical potential of the solute and γ and ϕ the phase-specific solute volume fraction activity coefficient and volume fraction, respectively. Interphase solute transfer occurs spontaneously from the phase with the higher chemical potential, until μ is constant throughout the system,13
eBook - PDFMultimedia Environmental Models
The Fugacity Approach, Second Edition
- Donald Mackay(Author)
- 2001(Publication Date)
- CRC Press(Publisher)
PHASE EQUILIBRIUM 83 5.4 Partition CoefficientS 5.4.1 Fugacity and Solubility Relationships If we have two immiscible phases or media (e.g., air and water or octanol and water), we can conduct experiments by shaking volumes of both phases with a small amount of solute such as benzene to achieve equilibrium, then measure the concen-trations and plot the results as was shown in Figure 5.1. It is preferable to use identical concentration units in each phase of amount per unit volume but, when one phase is solid, it may be more convenient to express concentration in units such as amounts per unit mass (e.g., µ g/g) to avoid estimating phase densities. The plot of the concentration data is often linear at low concentrations; therefore, we can write C 2 /C 1 = K 21 and the slope of the line is K 21 . Some nonlinear systems are considered later. Now, since C 2 is Z 2 f 2 and C 1 is Z 1 f 1 , and at equilibrium f 1 equals f 2 , it follows that K 21 is Z 2 /Z 1 . A Z value can be regarded as “half” a Partition Coefficient. If we know Z for one phase (e.g., Z 1 as well as K 21 ), we can deduce the value of Z 2 as K 21 Z 1 . This proves to be a convenient method of estimating Z values. The line may extend until some solubility limit or “saturation” is reached. In water, this is the aqueous solubility, but, for some substances such as lower alcohols, there is no “solubility,” because the solute is miscible with water. In air, the “solu-bility” is related to the vapor pressure of the pure solute, which is the maximum partial pressure that the solute can achieve in the air phase. Partition Coefficients are widely available and used for systems of air-water, aerosol-air, octanol-water, lipid-water, fat-water, hexane-water, “organic carbon”-water, and various minerals with water.
eBook - PDFUnderstanding Drug Release and Absorption Mechanisms
A Physical and Mathematical Approach
- Mario Grassi, Gabriele Grassi, Romano Lapasin, Italo Colombo(Authors)
- 2006(Publication Date)
- CRC Press(Publisher)
Drug Dissolution and Partitioning 305 5.3 PARTITIONING A detailed study of drug partitioning between a polar aqueous phase and an apolar one is very important since some drug physicochemical properties and in vivo behavior can be determined on the basis of this phenomenon. In particular, the drug Partition Coefficient P , strictly connected to drug lipophi-licity, has a paramount importance in predictive environmental studies [62] as it is used for the prediction of distribution among environmental compart-ments [63] in equations for the estimation of bioaccumulation in animals and plants [64] and in predicting the toxic effects of a substance [65]. Moreover, while lipophilicity encodes a wealth of structural information [66], especially in oral or parenteral administrations, drug bioavailability depends on P [67]. Additionally, the study of drug partitioning is also very important for what concerns drug release from disperse systems such as emulsions and micro-emulsions (see Chapter 8). Drug transfer between the two liquid phases (phase 1, polar; phase 2, apolar) can be better understood recalling the physics of the liquid–liquid interface in the light of the Gibbs theory [24]. According to this theory, phase 1 and 2 properties are constant all over the respective volume except for a thin region containing the interface, whose position is not exactly defined. For example, in the case of water (phase 1) and n -octanol (phase 2), while water and oil concentration is always constant in the respective bulk region, it decreases approaching the interface to get a minimum value in the opposite phase as evidenced in Figure 5.23. This gives origin to two stagnant layers, sandwiching the interface, whose properties differ from those of phase 1 and 2 bulks.
- M. O. Faruk Khan, v Philip, M. O. Faruk Khan, v Philip(Authors)
- 2018(Publication Date)
- Bentham Science Publishers(Publisher)
P value of -0.5 of less signifies water solubility; higher the negative value, more the water solubility.Partition Coefficient
In the field of organic and medicinal chemistry, a partition (P) is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium. Hence these coefficients are measures of differential solubility of the compound between these two solvents. The Partition Coefficient (Log P) is a measure of differential solubility of a compound in a hydrophobic solvent (n-octanol) and a hydrophilic solvent (water). The logarithm of these two values enables compounds to be ranked in terms of hydrophilicity (or lipophilicity). Lipophilic drugs with high Partition Coefficients are preferentially distributed to hydrophobic compartments such as lipid bilayers of cells while hydrophilic drugs (low Partition Coefficients) preferentially are found in hydrophilic compartments such as blood serum (Fig. 5 ). The propensity of partitioning of a compound from octanol to water is directly proportional to the number of hydrogen bonds it can form with water [8 ].Fig. (5)) Illustration of the Partition Coefficient of drug molecules.Lipid-Water Partition Coefficient
The octanol-water Partition Coefficient is the ratio of the concentration of a chemical in octanol and in water at equilibrium and at a specified temperature (Fig. 5 ). This is often termed as lipid-water Partition Coefficient (LWPC). Compounds with low log P values, that is high aqueous solubility, are good for dissolution but exhibit low permeability through lipid bilayer.In 1899, Charles E. Overton demonstrated that the greater the lipid solubility of a compound, the greater is its rate of penetration through a plasma membrane. This correlation, sometimes referred to as Overton's rule, provided one of the earliest indications that lipids are a major component of the plasma membrane [9 ]. A second breakthrough with regard to drug activity came in the early 1960s when Hansch and co-workers published the concept that a drug's activity was really a function of two processes [10 , 11 ]. The first being its transportation from point of entry to receptor site (pharmacokinetics) and the second being its interaction with the receptor (pharmacodynamics
- Cary T. Chiou(Author)
- 2003(Publication Date)
- Wiley-Interscience(Publisher)
Let us designate the two separate phases of interest as A and B. By Eq. (1.41), the equality in chemical potential of the solute in phases A and B requires that the solute activities in the two phases be identical at equilibrium (i.e., a i,A = a i,B ), or (3.1) where x i and g i are as defined earlier. Thus, the Partition Coefficient of solute i on the basis of its mole fractions in phases A and B is then (3.2) To the extent that g i,A and g i,B may vary with x i,A and x i,B , respectively, K * i,AB may then vary with x i,A and x i,B . If the solute is present at low concentrations in both phases A and B, as is commonly the case, K * i,AB will be practically invari- ant because g i,B and g i,A should be essentially constant. The Partition Coefficient of a solute is expressed more frequently as the ratio of the solute molar concentrations rather than the respective mole frac- tions in the two phases involved, because the former can be measured more readily and finds more practical utility. If the solute of interest is dilute, the solute mole fraction and the solute molar concentration are linearly related to each other such that x i,A = C i,A A and x i,B = C i,B B (3.3) where C i,A is the molar concentration of solute i in phase A (mol/L), C i,B the molar concentration of solute i in phase B, A the molar volume of the phase A solvent (L/mol), and B the molar volume of the phase B solvent. Substi- tuting Eq. (3.3) into (3.2) gives V V V V K x x i i i i i , , , , , AB A B B A * = = g g x x i i i i g g ( ) = ( ) A B 3 Interphase Partition Equations 30 PARTITION BETWEEN AN ORGANIC SOLVENT AND WATER 31 (3.4) In natural aquatic systems, contaminants are usually present at subsaturated levels in water, and thus one is largely interested in the Partition Coefficients of contaminants at low concentrations between an organic phase and water.
eBook - PDFPartitioning In Aqueous Two – Phase System
Theory, Methods, Uses, and Applications To Biotechnology
- Harry Walter(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
Interactions between the sol-vent and either polymer play essentially no role in determining com-patibility. When conditions are such that two phases are present at equilibrium, the process by which a mixed phase system physically separates under the influence of gravity is extremely complex. The rate of separation depends on the density difference between the phases, their viscosities, and the interfacial tension of the phase boundary. A variety of stream-ing phenomena as well as drop and globule coalescence and settling are observed. The detailed mechanisms by which the two phases are deliv-ered to their equilibrium locations vary depending on how far the phase system is from the critical point on the phase diagram. 28 Donald E. Brooks ef al. III. THEORY OF PARTITIONING A. Molecular Partitioning 1. Partition of a Polymer Utilizing Flory-Huggins theory, it is straightforward to derive an approximate expression for the Partition Coefficient of a third polymer added at low concentration to a two-polymer phase system. The proce-dure is to write down the expression for AG m for a four-component system containing the solvent (component 1) and three polymers, one (component 4, the material being partitioned) in very low concentra-tion relative to the other two (components 2 and 3, the phase poly-mers). For simplicity we assume that all components are equally solu-ble in the solvent, i.e., that 12 = 3 = 4 . The chemical potential , 4 is then calculated, using Eq. (9), to be: .o kT (13) + 3 X34 -p-j + 2( --) - X233j The standard state chemical potential refers to the chemical poten-tial of the pure component 4 before it is mixed with components 1, 2, and 3 (vide infra). When expressions like Eq. (13) are written for each phase, they can be equated at equilibrium since the chemical potentials must be equal under these conditions.
eBook - ePubHandbook of Preformulation
Chemical, Biological, and Botanical Drugs, Second Edition
- Sarfaraz K. Niazi(Author)
- 2019(Publication Date)
- CRC Press(Publisher)
P value of a drug, and in certain cases, predictions can be made; these are important in assessing the endogenous toxicity of compounds and their activity.Partition Coefficient (P) is a ratio of the concentration in two immiscible solvents:
where the values in brackets describe measured concentrations.P = [ organic ] / [ aqueous ](4.53) log P =log 10( partition coefficient )(4.54) In practical terms, the uncharged or neutral molecule exists for bases >2 pKa units above the pKa and for acids >2 pKa units below the pKa . In practice, the log P will vary according to the conditions under which it is measured and the choice of the partitioning solvent.It is worth noting that this is a logarithmic scale; therefore, log P = 0 means that the compound is equally soluble in water and in the partitioning solvent. If the compound has a log P = 5, then the compound is 100,000 times more soluble in the partitioning solvent. A log P = –2 means that the compound is 100 times more soluble in water; that is, it is quite hydrophilic.Log P values have been studied in approximately 100 organic liquid–water systems. As it is virtually impossible to determine lop P
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