Constants, Hansch

Hansch constant contribution of a substituent to log P Negative logarithm of the ionization constant... 

DOUBLE-RECIPROCAL PLOT HANSCH CONSTANT HANSCH EQUATION HANSCH S CORRELATION ANALYSIS Hapten,... 

Hansch constant A Hansch constant describes the lipophi-licity of a substituent on a parent molecule. Hansch constants, denoted with the symbol tt, are often used in Hansch analyses to link lipophilicity changes to biological activity. 

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. 

Hydrophilicity — The tendency of a molecule to be hydrated by water. The logarithm of the partition coefficient log(P) in the biphasic system octan-l-ol/water can be explored as a measure of the hydrophilicity of the molecules or a moiety [i]. The more negative value of log(P) means a higher hydrophilicity of the investigated compound. See also -> Hansch constant. 

Normally one expects that methyl groups increase the lipophilicity. Indeed, the logP (logarithm of the partition coefficient P between n-octanol and water) is 2.69 for toluene, compared to logP = 2.13 for benzene. More generally, the passage of (M)-H to (M)-CH3 gives place to a positive increment of 0.52 in Hansch constants calculations (see Chapter 23). 

On the other hand, fluorination can exert an influence on the lipophilicity of organic molecules, particularly at positions adjacent to atoms or groups having n electrons. Hansch constants derived from octanol/water partition coefficients of substituted benzenes (ref. 4) are summarized in Table 1. 

Hansch constants derived from octanol/ water partition coefficients of subtituted benzenes (ref. 4). 

Fig. 22.4 Molecular properties can be divided into experimental (subdivided into biological and physicochemical) and in silico (subdivided into structural and substructural) properties, physicochemical and biological properties. Examples of experimental data are IC50 (binding affinity), MIC (antibacterial minimum inhibition concentration), LD50 (lethal dose), Vd (volume of distribution), F% (bioavailability), pKg (ionization constant), log P (partition coefficient from shake flask determination), log kn,(lipophilicity from HPLC measurement), A (hydrogen bond capability), solubility. Examples of calculated properties, either for whole molecule or for substituents or buildings blocks, are MW (molecular weight), MR (molar refractivity), molecular volume, PSA (polar surface area), HA (number of H-bond acceptors), HD (number of H-bond donors), CLOGP (calculated log P values), L (substituent length), B5 (substituent width), cr (Hammett constant), F, R (field and resonance parameters), TT (Hansch constant), f (hydrophobic fragmental constant).

Several authors have attempted to interpret the differences in adsorption behavior of different compounds within the same group of pesticides. Briggs (23) has studied the effect of changes in substituent groups in substituted phenylurea compounds and alkyl-N-phenyl carbamates on the partition of these compounds between solutions and soils in contact with solutions. He found a linear relationship between the logarithms of the partition coeflBcients and the Hammett constants and the Taft constants of the substituted phenylurea compounds. However, in alkyl-N-phenylcarbamates, linear relationships between the logarithms of the partition coefficients and the Hansch constants of the compounds are obtained. The Hansch constant (tt) is defined in the following way by Fujita et al. (24) ... 

NTD s are calculated for the R2 side chains. Some of the molecules of Table 29 extend beyond the hypermolecule of Figure 10, especially the D-aminoacid derivatives, in which R2 sticks out from vertex j = 14 towards j = 9,8, etc. All new vertices are assigned Sy +1, i.e., they are considered as part of cavity walls. Electronic and hydrophobic effects are taken into account by introducing a-Hammett and 7r-Hansch constants in a(i.e., a=a + a a + 012 in Eq.2 for A ). 

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