Partition coefficients Solvents, choice

Initially the process utilized butyl acetate as a solvent, but more recently isopropyl ether has been used, although the latter has a much lower partition coefficient for phenol. The reason for this choice of solvent is that the separation of solvent and phenol by distillation is easier and less costly. 

The isolation method of solvent extraction has been suggested as a potentially feasible process to concentrate trace organic compounds from finished drinking water (4). One positive attribute of the solvent extraction method is that its performance for any given compound is theoretically predictable from a partition coefficient of a compound between the water sample and an organic solvent. The partition coefficient can be experimentally determined for any solute in any two-phase solvent system (7, 8). Variables of the extraction procedure such as solvent-to-water ratio and the choice of solvents can be adjusted to achieve optimum recovery. 

Centrifugal partition chromatography (CPC) relies on centrifugal force rather than gravitation for the retention of the stationary phase and solvents can be pumped at higher speeds through the instruments. In addition, no need for droplets formation is required. This allows shorter separation times, without loss of resolution, and an infinite choice of solvents with the only requirement of forming two immiscible phases, stable with the time. Chloroform-based systems have been mostly used for the separation of saponins due to their favourable partition coefficient towards such solvents. [116, 119, 120]. 

The Partition Coefficient itself is a constant. It is defined as the ratio of concentration of compound in aqueous phase to the concentration in an immiscible solvent, as the neutral molecule. The partition coefficient (P) therefore is the quotient of two concentrations and is usually given in the form of its logarithm to base 10 (log P). The Log P will vary according to the conditions under which it is measured and the choice of partitioning solvent. 

Owing to the impossibility of compiling partition coefficients for a substance into every possible set of solvents/phases, a reference that is commonly accepted is the octanol/water partition coefficient, Kj0tW. This solvent (i.e., the 1-octanol) is a good reference choice as it mimics (to a reasonable extent) the solvent behavior of lipids in biota as well as that of humic substances in soils. Extensive tables of Kio w values are readily available (see for example, the CRC Handbook for Chemistry and Physics). Such data help predict the environmental fate of many substances (see Casey and Pittman, 2005). 

Reversed-phase high-performance liquid chromatography (RP-HPLC) is the usual method of choice for the separation of anthocyanins combined with an ultraviolet-visible (UV-Vis) or diode-array detector (DAD)(Hebrero et al., 1988 Hong et ah, 1990). With reversed-phase columns the elution pattern of anthocyanins is mainly dependent on the partition coefficients between the mobile phase and the Cjg stationary phase, and on the polarity of the analytes. The mobile phase consists normally of an aqueous solvent (water/carboxylic acid) and an organic solvent (methanol or acetonitrile/carboxylic acid). Typically the amount of carboxylic acid has been up to 10%, but with the addition of a mass spectrometer as a detector, the amount of acid has been decreased to as low as 1 % with a shift from trifluoroacetic acid to formic acid to prevent quenching of the ionization process that may occur with trifluoroacetic acid. The acidic media allows for the complete displacement of the equilibrium to the fiavylium cation, resulting in better resolution and a characteristic absorbance between 515 and 540 nm. HPLC separation methods, combined with electrochemical or DAD, are effective tools for anthocyanin analysis. The weakness of these detection methods is a lack of structural information and some nonspecificity leading to misattribution of peaks, particularly with electrochemical... 

The correct choice of a solvent system is of paramount importance for a successful CPC separation. Selection of a two-phase (biphasic) solvent system for CPC is similar to choosing the solvents for other chromatographic methods such as for a normal column or HPLC (50). Important criteria are the polarity of the sample components and their solubility, charge state, and their ability to form complexes, etc. The most critical points in selecting solvent systems for CPC are two-fold one is solubility of the sample and the second is the difference in partition coefficients of the molecular species that are to be separated. 

The choice of the solvent system is the key parameter to a good separation. On one hand, its physical properties define Sp, N, and R on the other hand, the relative polarities of its two phases define the partition coefficients of the solutes and, as a result, the selectivi-ties and the retention factors. Usually, solvent systems are biphasic and made of three solvents, two of which are immiscible. 

We only give basic directions for the choice of a solvent system. If the polarities of the solutes are known, the classification established by Ito [1] can be taken as a first approach. He classified the solvent systems into three groups, according to their suitability for apolar molecules ( apolar systems), for intermediary polarity molecules ( intermediary system), and for polar molecules ( polar system). The molecule must have a high solubility in one of the two immiscible solvents. The addition of a third solvent enables a better adjustment of the partition coefficients. When the polarities of the solutes are not known. Oka s [8] approach uses mixtures of n-hexane (HEX), ethyl acetate (EtOAc), n-butanol (n-ButOH), methanol (MeOH), and water (W) ranging from the HEX-MeOH-W, 2 1 1 (v/v/v) to the n-BuOH-W, 1 1 (v/v) systems and mixtures of chloroform, methanol, and water. These solvent series cover a wide range of hydrophobicities from the nonpolar n-hexane-methanol-water system to the polar n-butanol-water system. Moreover, all these solvent systems are volatile and yield a desirable two-phase volume ratio of about 1. The solvent system leading to partition coefficients close to the unit value will be selected. 

Oka et al. [5] proposed a choice of various solvent systems to purify antibiotics. They have to fulfill various criteria. The settling time of the solvent system should be shorter than 30 s to ensure the satisfactory retention of the stationary phase. The partition coefficient of the target compounds should be close to 1, and the separation factor (a) between the compounds must be larger than 1.5. Two series of solvent systems can provide an ideal range of the K values for a variety of samples n-hexane-ethyl acetate-n-bu-tanol-methanol-water and chloroform-methanol-water. These solvent series cover a wide range of hy-drophobicity, continuously, from the nonpolar n-hexane-methanol-water system to a more polar n-butanol-water system. 

The choice of a solvent model for the hydrophobic interaction. Obviously the selectivity of the biological system cannot be modeled by a solvent. However, solvents can be chosen to model the partial desolvation observed in protein-protein interactions (see above) because there is a qualitative analogy between water and non-polar solvents and the interaction of small molecules with biological systems. This can be expressed as a quantitative relation between partition coefficients and the binding to biological systems (receptors, proteins, membranes, etc.) It... 

The demonstration of metabolism in compressed biphasic systems allowed us to explore the effect of solvent choice and pressure on biocompatibility. Biocompatibility of liquid solvents is frequently correlated with the -octanol water partition coefficient (log F) of the solvent (46). The log P of a substance is defined as the ratio of the molarity of the substance at infinite... 

In principle the diffusant-solvent or the diffusant-poly-mer interaction parameter can be empirically determined from a single solution datum such as a heat of mixing, a critical temperature, a solution density, etc. However, in some systems intelligent choices of A and Ap can made from limited data. An example of this kind is the partitioning of the n-alkanes between linear polyethylene (PE) and n-heptane. In Table I, the partition coefficients Kp and K are calculated from Eqs. (29) and (22) for selected n-alkanes at 25°C. Equation of state parameters required in the calculations were obtained from references 8 and 9. For PE, the equilibrium amount of n-heptane absorbed is 4>s -26 (16). Entries enclosed within parentheses are K values and those without are Kg values. Entries that are crossed out with solid lines are considered unlikely values of the partition coefficient those with broken lines are considered more probable than those crossed-out with solid lines, but less probable than the clear entries. 

In contrast, some parameters are properties of individual solvent molecules. Examples are dipole moment and log P (the octanol-water partition coefficient). These parameters are appropriate where individual solvent molecules are engaged in interactions away from the bulk phase. Thus, log P is used sensibly to describe the tendency of solvents to interact with (and affect the functioning of) the enzyme molecules. However, these parameters are not good choices when bulk solvent behavior is important, such as its ability to solvate water or reactants (and hence affect their availability to the enzyme). Even when such mechanisms are important, it is quite common to see correlations presented against log P. However, any relationship probably reflects the correlation of log P with appropriate scales of bulk solvent behaviour. 

A partition coefficient is defined by the ratio of the concentrations of a compound in two immiscible phases that are at equilibrium. It is common, though not necessary, for one phase to be water and the second an organic solvent, such as hexane, benzene, ether, and so on. It is important to emphasize that Aqw is not the ratio of the solubilities of the compound in octanol and water, because, since the two liquids are at equilibrium, the octanol phase will be saturated with water and the water with octanol. The use of n-octanol dates from the late nineteenth century when water-octanol was chosen as a surrogate to reflect uptake of pharmaceuticals into organisms. In retrospect, this turned out to be a wise choice and over the past 30 years there has been a continuing interest in the study of initially stimulated... 

While partition coefficients from many different organic solvent/water systems have been used in early structure-activity relationships, n-octanol became the organic solvent of choice after the pioneering work of Hansch on n-octanol/water partition coefficients of substituted phenoxyacetic acids and the lipophilicity parameter 7t derived from these partition coefficients [14, 15, 17, 18, 173, 180]. 

Several hundreds of linear relationships between various kinds of (mostly nonspecific) biological data and n-octanol/water partition coefficients have been published e.g. [18, 182]). However, the choice of n-octanol/water as the standard system for drug partitioning must be reconsidered in the light of some recent results. Principal component analysis of partition coefficients from different solvent systems [188 —190] shows that lipophilicity depends on solute bulk, polar, and hydrogen-bonding effects [189] isotropic surface areas, i.e. areas where no water molecules bind and hydrated surface areas, were correlated with the first and the second principal components of such an analysis [190]. 

Nowadays high-performance liquid chromatography (HPLC) [230-235] is the method of choice in many (especially industrial) laboratories. Log k values, which are calculated from t the retention time of the compound, and tg, the retention time of the solvent front (eq. 27), are closely correlated with n-octanol/water partition coefficients, e.g. by eq. 28 [231]. 

The equation in this form cannot be used directly since we do not have experimental values for the partition coefficient of the permeability barrier within the membrane. What we do have for each permeant are values of partition coefficients for various model organic solvents which we want to test as descriptors of the cell membrane barrier, and hence as possible estimates of the K values. In order to test the reasonableness of a particular choice of organic solvent we transform Eqn. 8 into the generalised form... 

The type of microbial strain is decisive for the choice of contact between cell and separative force. Pseudomonas species for instance, support direct contact with more polar solvents than Saccharomyces cerevisiae [40], A correlation between the solvent toxicity and its hydrophobicity was obtained by plotting the cellular activity retention against the Hansch parameter logwhich gives the logarithm of the partition coefficient of the solvent in the octanol-water two-phase system [30,76]. 

The range of most convenient hydrophobicity of organic compounds for reversed-phase (RP) HPLC separation may be estimated approximately as —1 < log P < + 5 (log P is the logarithm of the partition coefficient of the compound being characterized in the standard solvent system 1-octanol/water). Highly hydrophUic substances with log P < —1 need a special choice of analysis conditions, e.g., introduction of ion-pair additives into the eluents. Another approach is their conversion to more hydrophobic derivatives by the modification of functional groups with active hydrogen atoms. 

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