Lipophilicity substituent constant

Two parameters are commonly used to represent lipophilicity, namely the partition coefficient (P) and the lipophilicity substituent constant (it). The former parameter refers to the whole molecule whilst the latter is related to substituent groups. 

Lipophilic substituent constants are also known as hydrophobic substituent constants. They represent the contribution that a group makes to the partition coefficient and were defined by Hansch and co-workers by the equation ... 

Fan, W.-Q. and Jiang, X. K., Effect of hydrophobic-lipophilic interactions on chemical reactivity. 6. The first example of correlation of hydrophobic-lipophilic substituent constants with chemical reactivity for a simple substrate-solvent system, /. Am. Chem. Soc., 1985,107, 7680-7684. 

Table 2. Linear interdependences between lipophilic and steric substituent constants (17 hydrocarbon substituents)... 

The effects of fluonnauon on lipophilicity and acidity are discussed in this section Several useful substituent constants are compiled m Table 9... 

Hansch constant — A measure of the capability of a solute for hydrophobic (lipophilic) interaction (see - hydrophobic effect) based on the partition coefficient, P, for distribution of the solute between octan-l-ol and water. The most general way of applying P in correlation analysis, etc. is as logP, but the behavior of substituted benzene derivatives maybe quantified by a substituent constant scale, n, which is defined in a way analogous to the Hammett a scale. There are various n scales, depending on the substrate series used as reference. See also - hy-drophilicity. 

The bacteriostatic activity of a series of substituted trans-3-benzoylacrylic acids has been successfully correlated by Hansch linear free energy relations involving polar and partition substituent constants. The activity-lipophilicity relations for this series closely parallel those found previously for other antibacterial agents, with an ideal lipophilic character for gram-positive cells of 6.1 and, for linear dependence, a slope of 0.7. A polar reaction constant, p, of about —0.6 to —0.7 is given. A possible mode of action for these acids and their related substituted cis- and trans-3-benzoyl acrylic acids and esters is discussed as an enzyme-inhibitor interaction. 

Hansch-Fujita hydrophobic substituent constants - lipophilicity descriptors... 

These hydrophobic substituent constants are commonly used in - Hansch analysis to encode the lipophilic behavior of the substituents the hpophiUcity of the whole molecule is obtained by adding to the lipophilicity of the unsubstituted parent compound (logPn) the lipophilic contributions of the substituents ... 

Well-known substituent descriptors are the substituent constants which are experimentally determined descriptors among them, - electronic substituent constants, steric substituent descriptors, and lipophilicity substituent descriptors such as - Hansch-Fujita hydrophobic constants are the most commonly used in QSAR/QSPR modelling. 

R. Rekker and R. Mannhold, Calculations of Drug Lipophilicity, VCH, Weinheim, 1992 H. Kubinyi, Prog. Drug Res., 1979, 23, 97 C. Hansch and A.J, Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology, Wiley-Interscience, New York, 1979, pp. 18-43. 

Early QSAR studies were mainly focused on analyzing the effect of aromatic substituents on activity in congeneric compound series using substituent constants to describe the steric, electronic and lipophilic characteristics of the substituents. Hansch and Fujita proposed a method to describe quantitatively relationships between biological activity and chemical descriptors. This can be expressed as follows ... 

Hansch-Fujita hydrophobic substituent constants (= hydrophobic substituent constants, n) The lipophilicity is calculated by analogy with the —> Hammett equation as... 

Since the lipophilic character was found important for physiological dispositions of barbiturates, several workers investigated the relationship between partition coefficient and structural parameters (Taft s polar and steric substituents constants, number of C-atoms) of these compounds.548,549 Partitioning of barbiturates was also proved to be a significant factor for their... 

There is no excuse for not making an effort to choose the appropriate compounds to form the basis of the intended QSAR. Even if little information is available on the relevant descriptors, there is at least always the possibility of using a 7r/cr-substituent constants diagram of the candidate chemicals to assess the intercorrelations between lipophilic and electronic properties. 

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