Ionized solutes, distribution coefficient

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 papers in the second section deal primarily with the liquid phase itself rather than with its equilibrium vapor. They cover effects of electrolytes on mixed solvents with respect to solubilities, solvation and liquid structure, distribution coefficients, chemical potentials, activity coefficients, work functions, heat capacities, heats of solution, volumes of transfer, free energies of transfer, electrical potentials, conductances, ionization constants, electrostatic theory, osmotic coefficients, acidity functions, viscosities, and related properties and behavior. 

Often the measure of hydrophobicity desired is an apparent log P of an ionizable solute at a pH where it is partly ionized and thus more hydrophilic. This is most often termed a distribution coefficient and reported as Tog D. These can be calculated from a measured pKa and the neutral log P, if it assumed that the octanol phase contains a negligible portion of the ionic species. This is a good assumption if the pKa of the solute is no more than 3.0 log units on the ionized side of the pH of measurement. 

If the solute were a salt, having the formula Mv+Av and was nonionized in one phase and completely ionized in the other phase, the distribution coefficient would be expressed as... 

The partition coefScient is defined as the ratio of the concentration of a solute in the organic phase to its concentration in the water phase. This definition applies to the same neutral microspecies. However, many small molecules of pharmaceutical, agricultural and environmental interest may assume different protomeric and tautomeric forms, which increases the complexity of the above (simple) definition. Indeed, many small molecules contain moieties that ionize in water, thus contributing to a decrease in lipophilicity. The distribution coefficient, log D y, measures the pH-dependent distribution of drug in octa-nol-water phases at pH xy. 

Because the degree of ionization is a function of the pH of the aqueous phase and the pKa of the solute, the apparent partition coefficient P fluctuates as the pH of the aqueous phase (usually a buffer solution) is changed, whereas the true (or corrected) partition coefficient (P) should remain constant. However, in reality the different buffer species may not only affect P but also P because of different degrees of ion-pair formation and the different polar nature of the counterions used. Among the different buffer species, 1-octanol-phosphate buffer appears to give the most consistent results compared with 1-octanol-water. In some publications, the apparent partition coefficient P is also described as the distribution coefficient D. 

Solvent extraction of the slightly ionized mercury (II) azide complex, HgNs, or neutral Hg(N3)2 in the pH range 4-6 has been investigated. With n-butanol the distribution coefficient is 10.6 at 25°C. The complex obeys Beer s law at 248 nm in both aqueous and butanol solution [23]. 

Haddad et al. measured retention volumes for a variety of bases on a quaternary ammonium functionalized PS-DVB stationary phase using dilute aqueous sodium hydroxide as the eluent [11]. Values for the retention volumes and distribution coefficients of selected bases are given in Table 8.3. Strong bases, which are fully ionized a the eluent pH, elute at the column void volume and have a value of 1.0. Solutes intermediate between these two extremes are partly ionized and generally can be separated by an ion-exclusion mechanism. 

Acetic acid often is found in dilute solution from processes that use it as a raw material or solvenL. Fermentation processes also produce acetic acid in dilute solution. In many of these cases the solution pH is high enongh so ther the BCelic acid is iouized partially or completely. The present discussion is restricted to the recovery of un-ionized acetic acid. At a pH below the pA , all the acetic acid can be removed in ihe un-ionized lone. At a higher pH the acetate ion does not distribute into the second phase, and a large distribution coefficient is required for the un-ionized form to shift the equilibrium and obtain an attractive removal capacity. 

Many substances are partially ionized in the aqueous layer as weak acids. This introduces a pH effect on the extraction. Consider, for example, the extraction of benzoic acid from an aqueous solution. Benzoic acid (HBz) is a weak acid in water with a particular ionization constant Ka (given by Equation 18.4). The distribution coefficient is given by... 

A partition coefficient measurement involves the equilibration of a solute between an aqueous and an organic phase. A compound that is ionizable will be present a combination of ionic and neutral species, determined by its pifa values(s) and the pH of the aqueous phase. Hence, the equilibrium of a solute between the aqueous and organic phases will depend on pH in a manner that is dependent on the structure (and hence properties) of the solute. The measurement of such an equilibrium results in a distribution coefficient, which is defined as the ratio of the total concentrations of all species of the compound in the non-polar to the polar phase. The log of this is the logZ) value. Because it is usually assumed that charged species do not partition to the non-aqueous phase, logZ) values are lower than logP values for the same compound. This is depicted in Figure 3.6. 

These two parameters are intimately involved with each other particularly in the charged state. Hydrophobicity, as measured by log P, refers to the partitioning of a solute that remains neutral over the pH range in question, while log D (distribution coefficient or apparent log P) constitutes a measure of the partitioning of both the neutral and charged species of a compound at a particular pH. Thus log D is related to log P via the ionization constant, pKa. 

Kii = ionization constant for mercaptan in aqueous solution. mr distribution coefficient for total mercaptan content between alkaline solutions and naphtha. 

The partition coefficient technically refers to the quotient of the solute concentration in the organic phase divided by the concentration of un-ionized solute in the aqueous phase, whereas the distribution ratio counts both ionized and un-ionized solute in the aqueous phase. This distinction is important in systems where the extracted species is present as a neutral and an ionized species in the aqueous phase and only the neutral species can be extracted into the organic phase. In carrier-facilitated extraction, the distinction is less important as solutes must be complexed by the extractant or form an ion-pair with it prior to extraction into the organic phase the solute is often in its ionized form prior to complexation. 

As discussed later, the values and physicochemical meaning of this parameter change from one organic solvent to another. By definition, partition coefficients apply to solutes in a single, well-defined electrical state. Most published partition coefficients are those of neutral species, whereas the accurate measurement of the log F values of ions and zwitterions remains a current challenge. As such, partition coefficients must be carefully discriminated from distribution coefficients (log D), which apply to ionizable solutes at a given pH and are thus the combined expression of the lipophilicity of at least two ionic species in a pH-dependent proportion. ... 

Lipophilicity of a molecule is measured by its distribution behavior in a biphasic system either liquid-liquid (partition coefficient in 1-octanol-water) or solid-liquid (retention in RP-TLC or RP-HPLC) systems. According to definition suggested by lUPAC lipophilicity expresses the affinity of a molecule for a lipophilic environment. A reference scale representing lipophilicity appears to be the solute distribution between octanol and water. Berthod Carda-Broch (Berthod Carda-Broch) proposed another lipophilicity scale measuring ionic liquid BMIM PFg-water distribution constants. Relationship between the obtained values and respective octanol-water coefficients for a series of aromatic compounds differing in acid-base properties revealed that only the neutral compounds or ionizable ones with zwitterionic properties showed similar distribution behavior in the... 

FIG. 4 Thermodynamic equilibria for the interfacial distribution of a solute X which can be ionized n times, and X being its most acidic (or deprotonated) and its most basic (or protonated) forms, respectively. X and are the dissociation constants in the aqueous and organic phase, respectively, and P is the partition coefficient of the various species between the two phases. 

Sorption coefficients generally are determined from an isotherm, a diagram that depicts the distribution of the test chemical between a solid sorbent and the solution in equilibrium with it over a range of concentrations at constant temperature. These isotherms can be linear or nonlinear, depending on the properties of the test chemical and solid and on the aqueous phase concentration of the chemical. In many cases, sorption isotherms are linear at low concentration but tend to become nonlinear (sorption tends to decrease) as the concentration of chemical in the aqueous phase increases, especially for polar or ionizable... 

Commonly this equation and Eq. (35) are used to determine the normalized isotropic distribution. Consideration of Eq. (36) shows that various quantities of the collision processes and a few plasma parameters are involved in its coefficients and naturally have an immediate impact on its solution. With respect to the atomic data of the various collision processes, these are the momentum-transfer cross section Q (U), the total cross sections Qj U), the corresponding excitation or dissociation energies of the ground-state atoms or molecules, and the mass ratio m jM. With regard to the plasma parameters, the electric field strength E and the density N of the atoms or molecules occur, but only in the form of the reduced field strength E/N. All these quantities have to be known for a specific weakly ionized plasma in order to determine the isotropic distribution MU) by solving Eq. (36). 

Octanol is quite insoluble in water and vice versa hence the partition coefficients are not strongly temperature dependent, being mostly in the order of 0.001 to 0.01 log units per K (Lyman, 1990b). Even the low mutual solubility - at equilibrium the aqueous phase contains 4.5 x 10" mol/11-octanol and the organic phase contains 2.3 mol/1 water (Lyman, 1990b) - reveals so that the 1-octanol/water partition coefficient does not equal the ratio of the compounds solubilities in the individual solvents. This miscibility of the solvent phases, as well as ionization and association phenomena, limits the stringent validity of the presumed Nemst distribution, which, moreover, requires infinite dilution. Hence, at concentrations > 0.01 mol/1, is frequently observed to be dependent on the solute concentration. 

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