Water system, octanol

Based on Hquid—Hquid equiHbrium principles, a general model of octanol—water partitioning is possible if accurate activity coefficients can be determined. First, phase equiHbrium relationships based on activity coefficients permit Hquid—Hquid equiHbrium calculations for the biaary octanol—water system. Because the two components are almost immiscible ia each other, two phases form an octanol-rich phase containing dissolved water, and a water-rich phase containing dissolved octanol. 

Distribution of benzodiazepines in I-octanol - water system was investigated by a direct shake flask method at the presence of the compounds used in HPLC mobile phases the phosphate buffer with pH 6,87 (substances (I) - (II)), acetic and phosphate buffer, perchloric acid at pH 3 (substances (III) - (VI)). Concentrations of substances in an aqueous phase after distribution controlled by HPLC (chromatograph Hewlett Packard, column Nucleosil 100-5 C, mobile phase acetonitrile - phosphate buffer solution with pH 2,5, 30 70 (v/v)). 

With only few exceptions, most log P programs refer to the octanol-water system. Based on Rekker s fragmental constant approach, a log P calculation for aliphatic hydrocarbon-water partitioning has been reported [96]. Another more recent approach to alkane-water log P and log D is based on the program VolSurf [97]. It is believed that these values may offer a better predictor for uptake in the brain. 

For multi-pH liposome-water distribution measurements in 0.15 M NaCl or KCl solutions, the difference between the true pKj and pK (and between logPMBM and logPMBM) is about 1 log unit for bases and 2 log units for acids. Liposomes formed from phosphatidylcholine have a tendency to stabilize the charged drug more effectively than that in the octanol-water system [71]. Table 3.1 shows liposome-water examples of the relative pKj shifts. The average values cited in the examples are close the diff 1-2 approximation noted above. 

In the BBB-PAMPA lipid formulation illustrated in Fig. 3.4, the diff values, defined as the difference log Pq-log Pi, range from 2.9 (morphine) to 4.2 (warfarin), somewhat similar to the values observed in the octanol-water system. However, it is premature to propose a pdiffi-A approximation, given the limited amount of data reported. With other lipid formulations, larger differences are usually observed. In Double-Sink PAM PA, and especially in hexadecane-PAMPA, transport of ionized drugs has not been reported [84]. 

Parhtioning in the octanol-water system was characterized by the solvahon equahon [59] ... 

Seiler, P. Interconversion of lipophilicities from hydrocarbon/water into the octanol/water system. Eur. J. Med. Chem. 1974, 9, 473 79. 

H-bonding occurs intramolecularly between ortho-substituted donors and acceptors like in o-nitrophenol. In terms of H-bonding between aromatic ortho substituents, the octanol-water system seems to be sensihve to a very restricted class. The only clear-cut cases result from a carbonyl group directly attached to the ring acting... 

The difficulties and low-throughput nature of the experimental dual determination, especially in alkane-water systems, the development of other techniques more amenable to automation, as well as more refined computational approaches for octanol-water systems, aU have contributed to Umit the use of the alkane-water system as a second bulk-phase system. However, efforts have been devoted to the development of log (alkane) computational prediction methods by Rekker et al. [13] as well as Caron and Ermondi [14]. 

We have tried to cover some of the important aspects of the determination and use oflog P and log D parameters. Far from being exhaushve, this chapter attempted to offer some considerations and perspective in a field where, after 40 years from its beginning at the hand of Corwin Hansch et al, there does not seem to be much alternative to the balance of forces encoded by the octanol-water system to model lipophilicity. 

Bouchard, G., Galland, A., Garrupt, P. A., Gulaboski, R., Mirceski, V., Scholz, F., Girault, H. H. Standard partition coefficients of anionic drugs in the n-octanol/water system determined by voltammetry at three-phase electrodes. Phys. Chem. Chem. Phys. 2003, 5, 3748-3751. 

To clarify the relation between potential oscillation and features of interface o/wl, potential oscillation at the interface was measured in the presence of inorganic and organic electrolytes in phase wl, and potential oscillations in the octanol membrane system were compared with interfacial potential between octanol and aqueous solutions of a two-phase octanol-water system with and without surfactant [27]. Figure 8 shows potential oscilla-... 

FIG. 9 Upper potential values, a.sds lower potential values, b.sds of the first oscillation at the interface between phases o and wl of the octanol membrane (A), interfacial potential of a two-phase octanol-water system in the absence of SDS, c.sds (B) and those in the presence of 10 mM SDS (in the case of inorganic electrolyte, 1 mM), d.sds (C)- TMACI tetramethylammonium chloride TEACI tetraethylammonium chloride TPACI tetrapropylammonium chloride TBACI tetra-butylammonium chloride AcNa sodium acetate PrNa sodium propionate, BuNa sodium n-butyrate VaNa sodium w-valerate. (Ref 27.)... 

FIG. 10 Effects of concentrations of SDS (A) and CTAB (B) on interfacial potential of a two-phase octanol-water system. (Ref. 27.)... 

Seiler [250] proposed a way of estimating the extent of hydrogen bonding in solute partitioning between water and a lipid phase by measuring the so-called A log P parameter. The latter parameter is usually defined as the difference between the partition coefficient of a solute measured in the octanol-water system and that measured in an inert alkane-water suspension AlogP = log Kp oet — log Kp aik. 

Chmelfk, J. Hudecek, J. Putyera, K. Makovicka, J. Kalous, V. Chmelikova, J., Characterization of the hydrophobic properties of amino acids on the basis of their partition and distribution coefficients in the 1-octanol-water system, Collect. Czech. Chem. Commum. 56, 2030-2040 (1991). 

Escher, B. I. Schwarzenbach, R. P., Partitioning of substituted phenols in liposome-water, biomembrane-water, and octanol-water systems, Environ. Sci. Tech. 30,260-270(1996). 

Seiler P. (1974). Interconversions of lipophilicites from hydrocarbon/water systems in the octanol/water systems. Eur J Med Chem 9 473-479. 

Chiou, C. T., Schmedding, D. W., Manes, M. (1982) Partitioning of organic compounds in octanol-water system. Environ. Sci. Technol. 16, 4-10. 

Hammers, W.E., Meurs, G.J., De Ligny, C.L. (1982) Correlations between liquid chromatographic capacity ratio data on Lichrosorb RP-18 and partition coefficients in the octanol-water system. J. Chromatogr. 247, 1-13. 

Watarai, H., Tanaka, M., Suzaki, N. (1982) Determination of partition coefficient of halobenzenes in heptane/water and 1-octanol/water systems and comparison with the scaled particle calculation. Anal. Chem. 54, 702-705. 

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. 

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