Water-saturated octanol

The solubility of chemicals, drugs or pollutants in water (S ), in octanol (S ), their saturation concentration in air Qii), as well as their partitioning in the corresponding two-phase systems [octanol-water (P /w = Q/Cw), air-water (Pair/w = C IC ) and air-octanol (Paij/ = C /Co)] are important physicochemical parameters in medicinal chemistry and in environmental research. The following correlahons of those properties with HYBOT descriptors have been published recently [54—58] ... 

It has been shown for many RPLC methods that correlations between log Pod and retention parameters were improved by separating compounds in two classes, i.e. H-bond acceptor and donor compounds. Minick et al. [23] propose to add 0.25% (v/v) of 1-octanol in the organic porhon of the mobile phase (methanol was preferred in this study) and to prepare the aqueous portion with 1-octanol-saturated water to minimize this discriminahon regarding H-bond properties. For a set of heterogenous neutral compounds, the addition of 0.25% (v/v) of 1-octanol in methanol and the use of water-saturated 1-octanol to prepare mobile phase improve the correlahon between log few obtained on the LC-ABZ column and log Poc, [13]. 

In almost all theoretical studies of AGf , it is postulated or tacitly understood that when an ion is transferred across the 0/W interface, it strips off solvated molecules completely, and hence the crystal ionic radius is usually employed for the calculation of AGfr°. Although Abraham and Liszi [17], in considering the transfer between mutually saturated solvents, were aware of the effects of hydration of ions in organic solvents in which water is quite soluble (e.g., 1-octanol, 1-pentanol, and methylisobutyl ketone), they concluded that in solvents such as NB andl,2-DCE, the solubility of water is rather small and most ions in the water-saturated solvent exist as unhydrated entities. However, even a water-immiscible organic solvent such as NB dissolves a considerable amount of water (e.g., ca. 170mM H2O in NB). In such a medium, hydrophilic ions such as Li, Na, Ca, Ba, CH, and Br are selectively solvated by water. This phenomenon has become apparent since at least 1968 by solvent extraction studies with the Karl-Fischer method [35 5]. Rais et al. [35] and Iwachido and coworkers [36-39] determined hydration numbers, i.e., the number of coextracted water molecules, for alkali and alkaline earth metal... 

Scherrer, R. A. Crooks, S. L., Titrations in water-saturated octanol A guide to partition coefficients of ion pairs and receptor-site interactions, Quant. Struct.-Act. Relat. 8,59-62 (1989). 

A direct in vivo assessment was carried out with the single-pass perfusion approach in the human jejunum by using the Loc-I-Gut technique with R/S-verapamil (log D6 5 2.7, octanol/water pH 7.4 MW 455 Da) as the model compound for CYP 3A4 and P-gp-mediated local intestinal kinetics [2, 34, 35, 122] (see Figs. 7.7 and 7.9). The Peff for both enantiomers at each of the concentrations (4.0, 40, 120, and 400 mg L-1) was 2.5 x 10 4, 4.7 x 105.5 x 104 and 6.7 x 104 cm s-1, respectively (Fig. 7.15) [34, 35], A luminal concentration of 400 mg L 1 is expected to be achieved in the upper part of the small intestine after oral administration of a 100-mg dose of verapamil in an immediate-release dosage form [1, 34, 35], The three other perfusate concentrations represent fractions of the dose when 30%, 10%, and 1%, respectively are left to be absorbed [34, 35], The increased in vivo jejunal Peff of R/S-vcrapamil, along with its increased luminal perfusate concentration, is in accordance with a saturable efflux mechanism mediated by... 

The experimental approaches are similar to those for solubility, i.e., employing shake flask or generator-column techniques. Concentrations in both the water and octanol phases may be determined after equilibration. Both phases can then be analyzed by the instrumental methods discussed above and the partition coefficient is calculated from the concentration ratio Q/Cw. This is actually the ratio of solute concentration in octanol saturated with water to that in water saturated with octanol. 

The octanol-water partition coefficient, Kow, is the most widely used descriptor of hydrophobicity in quantitative structure activity relationships (QSAR), which are used to describe sorption to organic matter, soil, and sediments [15], bioaccumulation [104], and toxicity [105 107J. Octanol is an amphiphilic bulk solvent with a molar volume of 0.12 dm3 mol when saturated with water. In the octanol-water system, octanol contains 2.3 mol dm 3 of water (one molecule of water per four molecules of octanol) and water is saturated with 4.5 x 10-3 mol dm 3 octanol. Octanol is more suitable than any other solvent system (for) mimicking biological membranes and organic matter properties, because it contains an aliphatic alkyl chain for pure van der Waals interactions plus the alcohol group, which can act as a hydrogen donor and acceptor. 

Equation 11 implies that under these idealized conditions a log-log plot of S versus K will hage a slope ojj -1 and an intercept of -log V (19). The factors Yw/yw and 1/yq can be viewed as corrections for the activity change in the aqueous phase caused by the octanol dissolved in the water, and for nonideality in the octanol caused by the incompatibility of the solute with water-saturated octanol, respectively. 

Nonidealities in Water-Saturated Octanol. Chiou et al. (19), Tewari et al. (25) and Banerjee et al. (26) presented solubility data and octanol/water partition coefficients for 125 organic solutes. 

The most important factor in determining KQW is the aqueous-phase activity coefficient (aqueous solubility) of the organic solute. The observed partition coefficients are less than the ideal partition coefficients (K w) as result from 1) the incompatibility of the solute in water-saturated octanol and, to a lesser degree,... 

The use of distribution coefficients for the QSAR treatment of ionizable compounds has been extended to consideration of ion-pair partitioning into biolipid phases. Two experimental methods for determining ion-pair partition coefficients are described. One is a single-phase titration in water-saturated octanol, in which case (for acids) log Pj = log P + pKa - pKa. The other is a two-phase titration (octanol/water) from which the ratio (P + 1)/(Pj + 1) can be calculated. An example outcome is that the uncoupling activity of phenols can be represented by an equation in log instead of log D and pKa. 

We decided to try a direct titration in water-saturated octanol. What we hoped to achieve, if not duplicating literature values, was to obtain partition coefficients proportional to "true" values so that regression analyses could be run and would be meaningful. Secondly, this should be a rapid method to assess structural features in a series for their effect on ion-pair partitioning. 

Table I. HaIf-Neutralization pH for Benzoic Acids and Phenols in Water-Saturated Octanol.

Figure 6, HaIf-neutralization potentials of benzoic acids in water-saturated octanol vs their corresponding aqueous pKa values.

Molecular Size of the Compounds The size and molecular length of the PPCP compound can also influence the efficacy of the membrane. Molecular length is, in this instance, defined as the maximum length of the molecule, whereas molecular width refers to its cross-sectional diameter. Kimura et al. (2003) tested 11 neutral pharmaceutically active compounds that greatly vary in molecular weight, octanol-water partition coefficients (Xqw), and dipole moments for regeneration by two distinctly different RO membranes. AU of the assays were conducted at 20°C (pH 7 + 0.1) and filtration was done over a 24-h period. A key assumption from that experiment was that by the end of that duration, the membrane was saturated. The percent regeneration K) of the compound by the membrane was calculated from... 

Calculate the activity coefficients of (a) n-octane, and (b) aniline in water-saturated (see Table 5.1) u-hexane (%,), toluene (yt), diethylether (yiA), chloroform (y c), n-octanol (y0), and in water from the Kuw values given in Table 7.1. The aqueous solubilities of the two compounds are given in Appendix C. Compare and discuss the results. 

S. E. Debolt and P. A. Kollman. Investigation of structure, dynamics, and solvation in 1-octanol and its water-saturated solution - molecular-dynamics and free-energy perturbation studies. J. Am. Chem. Soc., 117(19) 5316—5340, 1995. 

The octanol-air partition coefficient was calculated initially as the quotient of the octanol-water coefficient (Kow) and air-water partition coefficient (KAW) (Paterson et al., 1991a). Recently, direct measurements obtained by passing purified air over an octanol solution of the chemical have become available (Harner and Mackay, 1995 Harner and Bidleman, 1996 Harner and Bidleman, 1997 Komp and McLachlan, 1997a), and an interpolation method based on GC retention times has been proposed (Zhang et al., 1999). The measurements indicate that the calculated values may underestimate the true KqA values. It has been postulated that this is because the octanol-water partition coefficient does not represent partitioning between pure octanol and pure water, but rather between octanol saturated with water and water saturated with octanol (Hamer and Mackay, 1995). 

Immobilized HRP with chitosan in 2-oxindole (regioselectivity 99%) in water-saturated isooctane or 1-octanol The enzymatic activity of the immobilized [37]... 

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