Octanol advantages

Leo AJ. Some advantages of calculating octanol-water partition coefficients. J Pharmaceut Sci 1987 76 166-8. 

Relationships between lipophilicity and retention parameters obtained by RPLC methods using isocratic or gradient condition are reviewed. Advantages and limitations of the two approaches are also pointed out, and general guidelines to determine partition coefficients in 1-octanol-water are proposed. Finally, more recent literature data on Hpophilicity determination by capillary electrophoresis of neutral compounds and neutral forms of ionizable compounds are compiled. Quotation is restricted to key references for every method presented - an exhaustive listing is only given for the last few years. 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

The special interaction terms are necessary to describe intramolecular interactions between different parts of the molecule that cannot be accounted for when considering the transfer of the isolated parts. Obviously, this type of approach has a big advantage in that it allows one to estimate a partition constant based solely on the compound s structure. Good results can be anticipated particularly in those cases where the partition constant of a structurally closely related compound is known, and thus only the contributions of the parts that are different between the two compounds have to be added and/or subtracted, respectively. The most advanced and most widely used method that is based on this concept is the structural group contribution method for estimating octanol-water partition constants. We will discuss this method in Chapter 7. 

Biffis et al. compared the catalytic performance of polymer gel immobilized Au NPs and Au/AC, with similar sized Au NPs, for alcohol oxidations in water [172]. Gold stabilized by polymer gel is advantageous over Au/AC for the use of hydrophobic substrates such as 1-octanol and 1-phenylethanol in aqueous media, although lower selectivity was obtained in some cases. For instance, polymer microgel supported Au NPs gave 1-octanoic acid by the oxidation of 1-octanol with a selectivity of 84% at 59% conversion, whereas Au/AC gave a selectivity of 93% at 65% conversion. 

Microemulsion electrokinetic chromatography, MEEKC (or MECC), is a relatively new technique which holds some promise of delivering octanol/water partition coefficients much more conveniently than the shake-flask method (Gluck, 1996 Ishihama, 1994). MEEKC is claimed to have all the advantages of an HPLC method but it is not suitable for solutes with pKas much below 7.0 (Adlard, 1995). It has been used over a log P range of -1.0 to +4.0. 

Particle-gas partitioning can be described by a variation of the Pankow absorption model, in which liquid-phase vapor pressure is replaced by the octanol-air partition coefficient as a fitting parameter (equations (22)-(25)). Section 10.3.4 states the advantages of doing so. Koa has been reported as a function of temperature for several PCB congeners, chlorobenzenes, PAHs, polychloronaphthalenes (PCNs), and p,p -DDT (Harner and Bidleman, 1996, 1998b Harner and Mackay, 1995 Komp and McLachlan, 1997). For others, Koa can be estimated from the ratio of the octanol-water partition coefficient to the Henry s law constant (H = Pa m3/ mol) (Finizio et al., 1997 Harner and Mackay, 1995 Simonich and Hites, 1995). 

Replacing P with the octanol-air partition coefficient (Koa) improves the absorption model. Advantages of the Koa - based model are twofold Koa is directly measureable as a function of temperature, and the model depends on the ratio of activity coefficients of the solute in octanol and the organic film on the particle (yoct/ yom). This ratio is more likely to be constant among classes of compounds than yom alone. 

An advantage of defining the problem in this manner is that the partition coefficient has become a central property in quantitative structure-activity relationships (QSAR) and a large data base of P values is available in the medicinal chemistry literature (22-24). In particular, if a correlation (Equation 15) between the polymer-water and octanol-water partition coefficients can be established for a series of solutes, it becomes possible to utilize log P (oc-tanol/water) value as a reference point from which to calculate the polymer-water value. 

The advantage of using fugacity to calculate the equilibrium distribution coefficients becomes apparent when one compares the fugacity capacities of a HOP for several different phases. For example, consider a region of the unsaturated zone just below the ground surface where naphthalene is distributed between air, water, pure phase octanol, and soil at equilibrium. The fugacity capacities for these phases are repeated below in Eqs. (46)-(49) ... 

The first exploitation of this relationship in a biological context was by Boyce and Milbarrow [28], who showed a relationship between the molluscicidal activity of some A -alkyltritylamines and their Rm values on TLC plates. Many publications have reported the application of TLC to determine the relative lipophilicity of compounds. The first chapter of the book Chromatographic Determination of Molecular Interactions Applications in Biochemistry, Chemistry, and Biology [29[ summarises the theory and presents the major application fields of the TLC method. The advantage of the method for the determination of lipophilicity is that the layers can be easily covered by octanol and by using an aqueous buffer the retention parameter would be directly proportional to the octanol-water partition coefficients. The drawbacks of this method are the limited reproducibility and precision. 

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