Other hydrophobic parameters

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 

Good correlations are also obtained between log P and log R. The log values for the hydrolysis of Af-acetyl-L-amino acid methyl esters catalysed by a-chymotrypsin show a good correlation with the effluent volumes (log o) of amino acids from cation exchange resins (Fig. 19). 

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As noted by the original authors (Dorovska et al., 1972), and cited by Fersht (1985), there is an excellent linear correlation between log/ccat/KM and the Hansch hydrophobicity parameters (v) of the side chains (Fig. 9, A), except for the two branched side chains (valine and isoleucine residues). However, since the ku values for the esters do vary somewhat (Table A6.8), the values of pKrs do not correlate as strongly with ir (Fig. 9, B). Moreover, the plot shows distinct curvature which probably indicates the onset of a saturation effect due to the physical limits of the Sj binding pocket, adjacent to the enzyme s active site. Still, the points for valine and isoleucine deviate below the others, suggesting that the pocket has a relatively narrow opening. 

These results give some insight in the scope and limitations of the MTD, MTD and STERIMOL parameters. Let us first compare the MTD and MTD methods. In the example of the benzyl chrysanthemates the regression equations have only steric terms, sothat there is no difference between the two methods in principle. In the case of the benzoylphenyl ureas the intercorrelation between the MTD values and the other parameters is very low, so it is understandable that there is hardly any difference. But in the four other studies there was much more intercorrelation between the MTD values on the one hand and the electronic and/or hydrophobic parameters on the other hand, and in these cases the MTD method gives slightly better results. Our preliminary conclusion from the examples discussed, is that the MTD is the preferable one, both from fundamental and... 

In some instances, chlorine is successfully replaced with a difluoromethoxy group while retaining desirable properties. Flucythrinate was introduced after fenvalerate by two different companies the only difference was the replacement of the 4-chloro group of fenvalerate with a difluoromethoxy group in flucythrinate. These two molecules have similar insecticidal properties, and though the chemical groups chlorine and difluoromethoxy are chemically different, their Hammet electronic values a and their hydrophobic parameters n lie relatively close to each other in parameter space (Fig. 29) [118]. 

Based on the earlier work of Meyer and Overton, who showed that the narcotic effect of anesthetics was related to their oil/water partition coefficients, Hansch and his co-workers have demonstrated unequivocally the importance of hydrophobic parameters such as log P (where P is, usually, the octanol/water partition coefficient) in QSAR analysis.28 The so-called classical QSAR approach, pioneered by Hansch, involves stepwise multiple regression analysis (MRA) in the generation of activity correlations with structural descriptors, such as physicochemical parameters (log P, molar refractivity, etc.) or substituent constants such as ir, a, and Es (where these represent hydrophobic, electronic, and steric effects, respectively). The Hansch approach has been very successful in accurately predicting effects in many biological systems, some of which have been subsequently rationalized by inspection of the three-dimensional structures of receptor proteins.28 The use of log P (and its associated substituent parameter, tr) is very important in toxicity,29-32 as well as in other forms of bioactivity, because of the role of hydrophobicity in molecular transport across cell membranes and other biological barriers. 

Sometimes the use of quantum chemically determined indices (1, 24, 57) or oxidation-reduction potentials (58) instead of the Hammett-Taft constants, the use of chromatographically obtained hydrophobicity parameter, ARm, (5, 59) instead of w or log P, or the addition of other variables such as those for hydrogen bonding (60), dipole moments (61),... 

The lipophilicity of PSA polymers, which is markedly affected by chemical composition, may influence drug solubility (Table 5). In general, acrylic copolymers have medium lipophilicity compared with other PSA polymers, and have the most excellent drug solubility. A suitable lipophilicity of copolymers can be obtained by changing the compositional content of comonomers. The lipophilicity of acrylic copolymers can be roughly estimated by the theoretical calculation of the hydrophobic parameters of copolymers according to the hydrophobic fragments of each comonomer, or the calculation of the octanol-water partition coefficients (log PC). ... 

Figure 3.29 shows density distributions for a number of lipid monolayers on water, as obtained by MD simulation ). We see that DPPC and GLCB have a broader interface, which is a result of their bigger head groups. The thickness of the interface is less for hydrophobic surfaces. It cannot be seen from these pictures that water molecules occasionally penetrate the hydrophobic core, but video animations showed this clearly. Various other dynamic parameters (rates of various internal motions) could be established. The water dipole contribution to the Volta potential V was also assessed. 

Elevated pressures can induce functional and structural alterations of proteins. The effects of pressure are governed by Le Chatelier s principle. According to this principle, an increase in pressure favours processes which reduce the overall volume of the system, and conversely increases in pressure inhibit processes which increase the volume. The effects of pressure on proteins depend on the relative contribution of the intramolecular forces which determine their stability and functions. Ionic interactions and hydrophobic interactions are disrupted by pressure. On the other hand, stacking interactions between aromatic rings and charge-transfer interactions are reinforced by pressure. Hydrogen bonds are almost insensitive to pressure. Thus, pressure acts on the secondary, tertiary, and quaternary structure of proteins. The extent and the reversibility, or irreversibility, of pressure effects depend on the pressure range, the rate of compression, and the duration of exposure to increased pressures. These effects are also influenced by other environmental parameters, such as the temperature, the pH, the solvent, and the composition of the medium. 

By these methods, the protein is partitioned in a system containing two phases, each phase having a different polarity. From the concentrations of protein in each phase, the energy needed to transfer a protein molecule from one phase to the other can be calculated and used as a hydrophobic parameter value. Such systems are based on special combinations of polymers, such as dextran and polyethylene... 

Among the two hydrophobic supports, octadecyl-sepabeads presented the best result concerning YLL immobilized activity (15.5 U/g), as its activity was over twice higher than YLL immobilized onto octyl-agarose (7.0 U/g). The other immobilization parameters calculated (immobilization yield and activity retention) were also better for octadecyl sepabeads (Table 1). These results were probably related with the chemical nature of hydrophobic supports. When a very hydrophobic support like octadecyl-sepabeads is used, there might be an increment of the affinity between the support and the substrate that... 

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