Taft steric constant

Regression analysis is currently the most widely used correlative method in drug design. This is because it simplifies problems within a set of compounds by using a limited number of descriptors, notably the Hansch hydrophobic constant n, Hammet constants, or other electronic characteristics of substituents, and the Taft steric constant Eg. 

Dubois steric constant - steric descriptors (O Taft steric constant) dummy variables indicator variabies... 

A linear combination of - Kier shape descriptors obtained from an empirical relationship between Taft steric constant Eg and group k indices [Kier, 1986b] and defined by the following [Kier, 1987d] ... 

Both the b and k values were estimated by regression analysis from the Taft steric constant Es and the Charton steric constant in an iterative procedure using 96 substituents. The k values are equal to 1.0 for the second period elements, except for the fluorine atom (k = 0.8) k = 1.2,1.3, and 1.7 for the third, fourth, and fifth period elements, respectively. 

The Taft steric constant Es was proposed as a measure of steric effects that a substituent X exerts on the acid-catalyzed hydrolytic rate of esters of substituted acetic acids XCH2COOR [Taft, 1952], The basic assumption is that the effect of X on acid hydrolysis is purely steric, as the reaction constant q for acid hydrolysis of substituted esters is close to zero. 

Therefore, the Taft steric constant is calculated as the average value from four series of kinetic data (hydrolysis of ethyl esters in 79 % aqueous acetone by volume at 25°C, esterification of carboxylic acids in methanol at 25°C, esterification of carboxylic acids in ethanol at 25°C, hydrolysis of ethyl esters in 69 % aqueous acetone by volume at 25°C) ... 

A rescaled set of the Taft steric constant was defined for the series of esters of substituted formic acids XCOOR as ... 

To correct the hyperconjugation effect due to the a-hydrogens, a corrected Taft steric constant (Hancock steric constant) was proposed ... 

In order to account for both C-C and C-H hyperconjugation effects a different correction for Taft steric constant was proposed [Palm, 1972], obtaining the Palm steric constant ... 

The Dubois steric constant E is a revised Taft steric constant defined using the acid-catalyzed esterification of carboxylic acids (at 40°C) as reference reaction [Mac-Phee et al., 1978a MacPhee et al, 1978b]. 

The Taft-Kutter-Hansch steric constants (TKH Es) constitute a combined set of parameters of the original Taft steric constants and those extended by Kutter and Hansch [Kutter and Hansch, 1969 Hansch, 1970 Sotomatsu and Fujita, 1989] by using a correlation with the average of the minimum and maximum van der Waals radii as defined by the equation ... 

Values of the Taft steric constants are collected in Table S-2 for some substituents. A Model of the Frontier Steric Effect is a theoretical approach recently proposed to estimate the Taft steric constant of substituents on the basis of the fundamental characteristics of the constituent atoms [Cherkasov and Jonsson, 1998b] ... 

The average of the minimum and maximum van der Waals radii as defined by Charton was correlated to the Taft steric constant (see above). 

Distinguishing the contributions of carbon and hydrogen atoms, the Bowden-Wooldridge steric constant Ef" is defined by a correlation equation with the Taft steric constant ... 

The most popular substituent constants are electronic substituent constants, - Hansch-Fujita hydrophobic substituent constants and -> steric substituent constants such as - Taft steric constant, - Charton steric constant, -> substituent front strain, and - steric density parameter. 

Dubois steric constant —> steric descriptors (0 Taft steric constant)... 

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