Tafts steric parameter s

The fundamental assumption of SAR and QSAR (Structure-Activity Relationships and Quantitative Structure-Activity Relationships) is that the activity of a compound is related to its structural and/or physicochemical properties. In a classic article Corwin Hansch formulated Eq. (15) as a linear frcc-cncrgy related model for the biological activity (e.g.. toxicity) of a group of congeneric chemicals [37, in which the inverse of C, the concentration effect of the toxicant, is related to a hy-drophobidty term, FI, an electronic term, a (the Hammett substituent constant). Stcric terms can be added to this equation (typically Taft s steric parameter, E,). 

To verify such a steric effect a quantitative structure-property relationship study (QSPR) on a series of distinct solute-selector pairs, namely various DNB-amino acid/quinine carbamate CSPpairs with different carbamate residues (Rso) and distinct amino acid residues (Rsa), has been set up [59], To provide a quantitative measure of the effect of the steric bulkiness on the separation factors within this solute-selector series, a-values were correlated by multiple linear and nonlinear regression analysis with the Taft s steric parameter Es that represents a quantitative estimation of the steric bulkiness of a substituent (Note s,sa indicates the independent variable describing the bulkiness of the amino acid residue and i s.so that of the carbamate residue). For example, the steric bulkiness increases in the order methyl < ethyl < n-propyl < n-butyl < i-propyl < cyclohexyl < -butyl < iec.-butyl < t-butyl < 1-adamantyl < phenyl < trityl and simultaneously, the s drops from -1.24 to -6.03. In other words, the smaller the Es, the more bulky is the substituent. The obtained QSPR equation reads as follows ... 

FIGURE 1.11 Systematic optimization of structural binding and stereorecognition increments of amino acid side chain (Rsa) carbamate residue (Rso)- Dependency of separation factors on the steric bulkiness of amino acid and carbamate residues as quantified by their corresponding Taft s steric parameters Es sa Eg so- (1) ionic interaction (2) jr-jr-interaction (3) hydrogen bonding (4) steric interaction. (Reproduced from M. Lammerhofer et al., J. Sep. ScL, 29 1486 (2006). With permission.)... 

Figure 8. Experimental data on the effect of (a) Taft s steric parameter for ethers and (b) modified Small s number for hydrocarbons on their reverse osmosis separations in systems involving dilute aqueous solutions and cellulose acetate membranes...

Px is the partition coefficient of a derivative and PH is that for the parent compound.) Also used were Hammett s o- constant, Taft s polar constant, steric parameter, Es. In a few examples (Equations 17, 21, 24, and 30), P values from oleyl alcohol/water have been used. In one instance (Equation 69) the chemical shift of a phenolic proton has been used for comparison with the a constant. Where possible, the experimentally measured partition coefficients for all members of the series have been used. In other instances only one member of a set has been measured. Values for the other members were obtained by taking advantage of the additivity principles of log P and tr. Details are given elsewhere (4, 7, and 8). For the new work of Table II, log P values for the parent compounds are given in the footnotes. 

Figure 10 Theoretical (a) and practical (b) representation of QSARs. Panel b describes a QSAR for the methanotrophic oxidation (activity of methane monooxygenase) of 6>r /i6>(Ci2)-substituted biphenyls. The structural backbone was biphenyl, and the substituents considered included all halogens, methyl-, methoxy-, hydroxyl-, nitro-, and amino-moieties (Lindner et al, 2003). The molecular descriptors used in (b) are (charge on the ortho-csubon), (Taft s steric parameter), and log ow...

In a detailed structure-activity study Gil and Wilkinson (1977) found that of 47 substituted 1,2,3-benzothiodiazoles the 6-butyI derivative 19 is the most active inhibitor of microsomal oxidation. Regression analyses have shown that the activity of the S-, 6- and 3,6-substituted compounds can be satisfactorily described in terms of the hydrophobic bonding constant n and the Hammett constant r whereas that of the 4-substituted derivatives depend on n and the Taft s steric parameter ,. 

The ketene s less bulky substituent (S), as expressed by a less negative value of Taft s steric parameter [59], [60, Chap. 4], faces its reaction... 

Taft s steric parameter for the substituent group in the organic molecule, — solute separation, —... 

Electronic and Steric Constants - In addition to hydrophobic parameters, homolytic and steric constants were successfully used in the structure-activity studies of 1,3-benzodioxole synergists of carbaryl in flies. Although the hydrophobic character of the synergists is quite important (log P = 4), electronic substituent effects paralleled those for homolytic arylation and improved the correlation. Use of Hammett s electronic constant (o) and Taft s steric parameter (E ) gave a better correlation when used with the hydrophobic substituent constant. Observations in this study have suggested a possible mechanism of action of the synergists on the molecular level. 

In SAR work, the biological activity of compounds is usually expressed by the values of IC50 or ED50. Physico-chemical properties used in SAR can be broadly classified into three general tjq)es electronic parameters, steric parameters and hydrophobic parameters. Electronic parameters include Hammett constants o ,(7, <7 ), Swain and Lupton field parameter (F), Swain and Lupton resonance parameter (R), etc. Steric parameters include Taft s steric parameter (Eg), molecular volume (Vm), molecular surface area (Area), molecular weight (MW), van der Waals radius (r), molar refractivity (MR), parachor (Pr), etc. Hydrophobic parameters include partition coefficient (LogP), distribution coefficient (LogD), substituent constant ( ), solubility... 

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