Measurement of hydrophobicity

Valko et al. [37] developed a fast-gradient RP-HPLC method for the determination of a chromatographic hydrophobicity index (CHI). An octadecylsilane (ODS) column and 50 mM aqueous ammonium acetate (pH 7.4) mobile phase with acetonitrile as an organic modifier (0-100%) were used. The system calibration and quality control were performed periodically by measuring retention for 10 standards unionized at pH 7.4. The CHI could then be used as an independent measure of hydrophobicity. In addition, its correlation with linear free-energy parameters explained some molecular descriptors, including H-bond basicity/ acidity and dipolarity/polarizability. It is noted [27] that there are significant differences between CHI values and octanol-water log D values. 

Ghose, A. K. and Crippen, G. M. (1986) Atomic physiochemical parameters for three-dimensional structure-directed quantitative structure-activity relationships I. Partition coefficients as a measure of hydrophobicity. J. Comput. Chem. 4, 565-577. 

Figure 3.11 Comparison of the retention of toluene to decylbenzene as a measure of hydrophobicity of different octadecyl-bonded silica gels with different carbon loadings. Columns , LOC-ODS-E O, LOC-ODS-NE O, HIC-ODS-E A, HIC-ODS-NE eluent, 80% aqueous acetonitrile at 30 °C. Compounds. 1, toluene 2, nonylbenzene.

W.A. Ducker, Z. Xu, and J.N. Israelachvili Measurements of Hydrophobic and DLVO Forces in Bubble-Surface Interactions in Aqueous Solutions. Langmuir 10, 3279 (1994). 

Electronic descriptors were calculated for the ab initio optimized (RHG/STO-3G) structures. In addition, logP as a measure of hydrophobicity and different topological indices were also calculated as additional descriptors. A nonlinear model was constructed using ANN with back propagation. Genetic algorithm (GA) was used as a feature selection method. The best ANN model was utilized to predict the log BB of 23 external molecules. The RMSE of the test set was only... 

Ray C, Brown JR, Akhremitchev BB. Single-molecule force spectroscopy measurements of hydrophobic bond between tethered hexadecane molecules. J Phys Chem B 2006 10 17578-17583. 

Drug binding is enhanced by hydrophobicity in that portion of the drug that binds to the pocket toe. Quantitative structure-activity relationship (QSAR) analysis of these compounds have consistently shown that the most predictive parameter of antiviral activity is a measure of hydrophobicity, the octanol water partition coefficient (logP) [80,82,85]. These studies have also consistently shown that there is no apparent correlation between electrostatic potential or dipole moment and potency. 

Note that a useful operational measure of hydrophobicity is the octanol/water log P parameter (Hansch and Leo, 1979). This is a free energy-related parameter and is frequently thought of as synonymous with hydrophobicity, but it undoubtedly incorporates both AGh and AGy w components so is not pure hydrophobicity in the sense above. Lipophilicity is a more appropriate name. Contrary to common belief, log P is mostly enthalpic (Taylor, 1990 Da et al., 1992). 

Calculate the surface tension (ysv) of the protein (solid/air), which is a measure of hydrophobicity (Keshavarz and Nakai, 1979) based on Young s relationship ... 

Selective extractions can be carried out by careful selection of pH. When extracting organic species it must be remembered that compounds may exist as different species, depending on the pH. Pnw, the partition coefficient of a solute between octanol and water, is a common measure of hydrophobicity. High values of log Pow are favorable for extraction. Reversed-phase HPLC has also been extensively used. 

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. 

Solubility in water is one of the most important physical chemical properties of a substance, having numerous applications to the prediction of its fate and its effects in the environment. It is a direct measurement of hydrophobicity, i.e., the tendency of water to "exclude" the substance from solution. It can be viewed as the maximum concentration which an aqueous solution will tolerate before the onset of phase separation. 

Recently, Huibers et al. (1996) presented a predictive model using topological predictors, which is capable of predicting CMC values for a wide variety of nonionic surfactants. Zoeller and Blankschtein (1995) attempted to predict CMC based on molecular-thermodynamic theory. Others have tried to predict the influence of temperature (Muller, 1993 Di Toro et al., 1990), of ionic strength (Carale et al., 1994 Di Toro et al., 1990), and of mixing (Zoeller et al., 1995) on the CMC. Combinations of these techniques could make it possible to predict CMCs as a measure of hydrophobicity of surfactants under given environmental conditions. 

This behavior is analogous to the trend observed for the inverse of CMC. Since the inverse of the CMC can be viewed as a measure of hydrophobicity, the relationship between substitution position of the p-sulfophenyl-moiety and the sorption coefficients is indicative of the influence of hydrophobicity on sorption. 

Many modelers believe that, as far as possible, it is desirable, if not essential, that predictive techniques should based on fundamental physicochemical properties such as the partition coefficient (Cronin and Schultz, 2003 Schultz and Cronin, 2003). The use of physicochemical properties is described in more detail in Chapter 4. Physicochemical properties tend to describe fundamental molecular effects, such as the partition coefficient being a measure of hydrophobicity. There is a belief that such properties may be related to the mechanism of action of a molecule and are thus less susceptible to spurious correlation. 

The primary supposition of any toxicological QSAR is that the potency of a compound is dependent upon its molecular structure, which is typically quantified by chemical properties (Schultz et al., 2002). Chemical descriptors include a variety of types, including atom, substituent, and molecular parameters. The most transparent of these are the molecular-based empirical and quantum chemical descriptors. Empirical descriptors are measured descriptors and include physicochemical properties such as hydrophobicity (Dearden, 1990). Quantum chemical properties are theoretical descriptors and include charge and energy values (Karelson et al., 1996). Physicochemical and quantum chemical descriptors are for the most part easily interpretable with regard to how that property may be related to toxicity. The classic example of this, the partitioning of a toxicant between aqueous and lipid phases, has been used as a measure of hydrophobicity for over a century (Livingstone, 2000). 

Busscher HJ, Sjollema J, Van der Mei HC (1990) Relative importance of surface free energy as a measure of hydrophobicity in bacterial adhesion to solid surfaces. In Doyle RJ, Rosenberg M (eds) Microbial Cell Surface Hydrophobicity. American Society for Microbiology,... 

Hydrophobicity, from the greek hydro water and phobia aversion, is a term referring to the way a molecule likes or does not like water. A compound with a high hydrophobicity will not be water soluble. It is ap-olar. Conversely, a compound with a low hydrophobicity is said to be hydrophilic or polar. It is likely to be water soluble. In between the two extremes, the hydrophobicity varies. A scale is needed. The problem is that the hydrophobicity, or the polarity of a compound, depends on several parameters such as the dipole moment, the dielectric constant, the polarizability, the proton donor or acceptor character, or even the boiling point to molecular mass ratio. Since the end of the nineteenth century, the octanol-water partition coefficient, P i, was used with success as a measure of hydrophobicity. The log is the convenient scale. Compounds with a positive log Po/w value are more and more hydrophobic or apolar as the value increases. Compounds with a negative log value are hydrophilic or polar [1]. 

Ghose, A.K. and Crippen, G.M. (1986). Atomic Physicochemical Parameters for Three-Dimensional-Structure-Directed Quantitative Structure-Activity Relationships. I. Partition Coefficients as a Measure of Hydrophobicity. J.ComputChem., 7, 565-577. 

Kaliszan, R., Nasal, A. and Bucinski, A. (1994). Chromatographic Hydrophobicity Parameter Determined on an Immobilized Artificial Membrane Column Relationships to Standard Measures of Hydrophobicity and Bioactivity. Eur.J.Med.Chem.,29,163-170. 

Index scale can be used as a measure of hydrophobicity of compounds for QSAR/QSPR modeling studies [Ishihama, Oda et al., 1996 Fatemi, 2003],... 

Hydrophobicity The preference of a solute to dissolve in apolar solvents or molecules over polar solvents. A common measure of hydrophobicity is the partition or distribution coefficient in the -octanol/water system, often used to predict pharmacokinetics and pharmacodynamics in QSAR and Hansch analysis. 

Solubility in water has been proposed as a measure of hydrophobicity and has been shown to be related to the free energy of transfer from water to ethanol [72]. Fig. 17 illustrates a plot of log versus log = mole fraction of the substance at... 

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