Hydrophobic parameters, calculation

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,... 

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],... 

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). 

Masuda, T., Jikihara, T., Nakamura, K., Kimura, A., Takagi, T., and Fujiwara, H. (1997) Introduction of solvent-accessible surface area in the calculation of the hydrophobicity parameter log P from an atomistic approach. J. Pharm. Sci. 86,57-63. 

Villar et al. developed an atomic hydrophobicity contribution that depends on the molecular conformation. The hydrophobicity parameters were calculated by including charge densities, atomic contributions to the total molecular surface area and the molecular dipole moment [47, 48]. This method is implemented in the SPARTAN software. 

A modification of the atomic approach was also proposed by Gaillard et al. using molecular lipophilicity potential (MLP) as a 3D source of two lipophilicity parameters calculated from the water-accessible surface, namely a hydrophobic parameter expressed as the sum ofthe positive lipophilicity potential (EM LP+) and a polar parameter expressed as the sum of the negative lipophilicity potential (EMLP—)... 

Lewis, D. F. V., The Calculation of Molar Polarizabilities by the CNDO/2 Method Correlation with the Hydrophobic Parameter, Log P. J. Comput. Chem, 1989 10, 145-151. 

Masuda, T., T. Jikhara, K. Nakamura, A. Kimura, T. Takagi, and H. Fujiwara. 1997. Introduction of Solvent-Accessible Surface Area in the Calculation of the Hydrophobicity Parameter log P from an Atomistic Approach. J. Pharm. Sci. 86, 57-63. 

Pussemier et al. (1989) found that log Koc for 12 aryl N-methylcarbamates correlated significantly to a linear combination of two parameters, % hydrophobic effect (calculated from RP-HPLC measurements) and 8 Hildebrand solubility parameter. The authors also used data for 16 phenylureas and 13 anilides from Briggs (1981) and obtained similar results. 

Fig. 2.13. The probability distributions of four structural parameters calculated for the structures of each cluster [25]. (a) The fraction of the native tertiary contacts Q. (b) The RMSD value of Ca atoms between a pair of structures that belong to the same cluster. The SASA for (c) hydrophobic and (d) hydrophilic side chains. Reproduced with permission from [25]...

As the equations show, linear correlations with the variables tr and a gave satisfactory results. This is certainly a simplification resulting from limited variance in the substituents. One would assume that square terms of the hydrophobic parameter are necessary in every correlation with biological activity not only to account for the random walk penetration process as in the original derivation of his equation by Hansch, but also, or even predominantly, as a description of the fact that numerous indifferent hydrophobic sites within the biological system compete with the site of action for the active molecule. In a first attempt we calculated regression equations for our hydrazones with the molecular parameter... 

To derive these equations, log P (hydrophobic parameter), MR (molar refrac-tivity index), and MV (molar volume) were calculated using software freely available on the internet (wwwlogP.com, www.daylight.com). The first-order valence molecular connectivity index of substituents was calculated as suggested by Kier and Hall [46,47]. In these equations, is cross-vahdated obtained by the leave-one-out jackknife procedure. Its value higher than 0.6 defines the good predictive ability of the equation. The different indicator variables in these equations were defined as follows. 

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). ... 

Hansch, C. Leo, A. The hydrophobic parameter measurement and calculation. In Exploring QSAR Fundamentals and Applications in Chemistry and Biology Heller, S.R., Ed. American Chemical Society Washington, 1995 97-122. 

Leo, A. (1991). Hydrophobic Parameter Measurement and Calculation. Methods Enzymol.,202, 544-591. 

AJ Leo. Hydrophobic parameter measurement and calculation. In JJ Langone, ed. Methods in Enzymology Molecular Design and Modeling Concepts and Applications, Part A, Proteins, Peptides and Enzymes. New York Academic Press, 1991, vol 202A, pp 544—591. 

In this equation, MR-4 is the calculated molar refractivity of the substituents at position 4 whereas jt-1 is the calculated hydrophobic parameter of the substituents at position 1. This equation contains a positive correlation with Clog P and a negative correlation with n-1, so one should preserve a hydrophihc group at N1 while boosting the molecule s overall hydrophobic-ity. The parabohc nature of this equation in terms of MR-4 suggests that the value of MR-4 shotdd be 1.82 for the maximum cytotoxicity against B16 melanoma cells. 

The best correlation for the mutagenicity of quinolines was obtained with the AMI-calculated net atomic charges on a carbon atom (q2) and the hydrophobic parameter (log P) [106],... 

Lewis DVF. The calculation of molar polarizabilities by the CNDO/2 method correlation with the hydrophobic parameter, logP. J Comput Chem 1989 10 145-151. 

Thermodynamic parameters and nature of the binding force. The interaction forces between a drug and a biomolecule may include hydrophobic forces, electrostatic interactions, van der Waals interactions, and hydrogen bonds. From the thermodynamic parameter calculation, the acting force can be identified.6 For the interaction of HSA and EHC, at 25 °C and 37 °C, A H=4.68 kJ/mol and A S=107 J/mol/K. While A G = -27.3 kJ/mol (25 °C), -28.6 kJ/mol (37 °C). It can be seen the positive value of AS indicate that the hydrophobic forces played a major role in the reaction. At the same time, hydroxyl and carbonyl groups in the EHC presumably interacted with polar groups of HSA, so the main sort of binding force between them probably includes both hydrophobic and dipole forces. 

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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