Hydrophobic parameters

Figure C2.5.2. Scaling of the number of MBS C(MES) (squares) is shown for the hydrophobic parameter = -0.1 and A = 0.6. Data were obtained for the cubic lattice. The pairs of squares for each represent the quenched averages for different samples of 30 sequences. The number of compact stmctures C(CS) and self-avoiding confonnations C(SAW) are also displayed to underscore the dramatic difference of scaling behaviour of C(MES) and C(CS) (or C(SAW)). It is clear that C(MES) remains practically flat, i.e. it grows no faster than In N.

Leo AJ. Hydrophobic parameter measurement and calculation. Methods Enzymol 1991 202 544-91. 

This is an inverted parabolic relation in terms of ttx (calculated hydrophobic parameter of the substituents), which suggests that activity of these compounds first decreases as the hydrophobicity of substituents increases and after a certain point (inversion point ttx = 0.67), activity begins to increase. This may correspond to an allosteric reaction [54]. The indicator variable I is assigned the value of 1 and 0 for the presence and absence of N(CH3)2 substituent at the X position. Its positive coefficient suggests that the presence of a N(CH3)2 substituent at X position, increases the activity. REC is the relative effective concentration i.e., concentration relative to topotecan, whose value is arbitrarily assumed as 1, that is able to produce the same cleavage on the plasmid DNA in the presence of human topo I. 

The indicator variable I is assigned the value of 1 for the presence of amide derivatives and 0 for the esters. Its negative coefficient suggests that esters would be preferred over amides for this data set. nx is the calculated hydrophobic parameter of the X-substituents. Its positive coefficient suggests that the highly hydrophobic X-substituents would be preferred. 

This is an inverted bilinear relation in terms of ClogP (calculated hydrophobic parameter of the whole molecule), which suggests that activity of... 

Kim, K. H. Calculation of hydrophobic parameters directly from three-dimensional structures using comparative molecular field analysis. J. Comput.-Aided Mol. Des. 1995, 9,... 

Dubin, P. L. and Principi, J. M., Hydrophobic parameter for aqueous size exclusion chromatography gels, Anal. Chem., 61, 780, 1989. 

PL Dubin, JM Principi. Hydrophobicity parameter of aqueous size exclusion chromatography gels. Anal Chem 61 780-781, 1989. 

Nakagawa, Y., Izumi, K., Oikawa, N., Sotomatsu, T., Shigemura, M., Fujita, T., Analysis and prediction of hydrophobicity parameters of substituted acetanilides, benzamides and related aromatic-compounds, Environ. Toxicol. Chem. 1992, 3 3, 901-916. 

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. 

The lipophilicity and specific surface area of a similar set of synthetic dyes was also determined on an alumina-based RP-TLC stationary phase and the linear relationship between the two hydrophobicity parameters was calculated. The result of the calculation is depicted in Fig. 3.6. The good correlation between these physicochemical parameters indicated that from the chromatographic point of view these compounds behave as a homologous series of analytes, however, their chemical structures are markedly different [87],... 

If the coefficient of the hydrophobic parameter is approximately equal to one, then expect complete desolvation about substituent X of the ligand. 

Braumann, T. Determination of hydrophobic parameters by reversed-phase liquid chromatography theory, experimental techniques, and application in studies on quantitative structure-activity relationships, J. Chromatogr., 373 191-225, 1986. 

Tomlinson, E. Chromatographic hydrophobic parameters in correlation analysis of structure-activity relationships, J. Chromatogr. A, 113(l) l-45, 1975. 

Yamagami, C., Takao, N., and Fujita, T. Hydrophobicity parameter of diazines. 1. Analysis and prediction of partition coefficients of monosubstituted diazines, Quant Struct.-Act Relat, 9(4) 313-320, 1990. 

Yamagami, C. and Takao, N. Hydrophobicity parameters determined by reversed-phase liquid chromatography. VII. Hydrogen-bond effects in prediction of the Log P values for benzyl 7V,7V-dimethylcarbamate, Chem. Pharm. Bull., 41 (4) 694-698,1993. 

Five new pyridazinones were synthesized with substitutions in the two-position of the phenyl ring as given in Table II. Using the Hansch approach, correlations were made between the experimentally determined 18 2/18 3 ratios and the values and a,a values taken out of the data collection of Hansch and Leo (15) (Table II and Equations 1-3). The hydrophobic parameter is derived from the 1-octanol/water partition coefficient and o is the Hammett electronic parameter. 

The close agreement between the experimental and calculated (Equation 9) ratios of 18 2/18 3 support exclusion of the 4-hydroxylphenyl analogue from the calculations. Examination of Equation 9 shows an interdependence between the biological activity and the hydrophobic properties of the chemical used, commonly found with many QSAR equations. This interdependent relationship is determined by the and terms, respectively. These terms control phenomena of hydrophobic interactions with receptors and phenomena of transport and distribution within the total biological systems. The occurrence of squared terms of the hydrophobic parameter in structure-activity correlations has been explained on the assumption that the compound has to penetrate several lipophilic-hydrophilic barriers or compartments on its way to the site of action (16, 17). This is consistent with the uptake of pyridazinones by roots and sbsequent translocation to the shoots (chloroplast) as the site of action (13). 

Equations 18-20 give about the same results and the standard obtained in the procedure that led to Equation 20 is shown in Figure 7. Since these equations contain only steric parameters, the picture obtained from the MTD method can directly be used to compare the biological activity of the compounds. MTD and MTD are in principle the same in this example because no electronic and hydrophobic parameters are involved. However, extrapolation outside the hypermolecule is not permissible. 

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... 

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