Quantitative Structure-Activity Relationships (QSAR) PDF

Quantitative Structure-Activity Relationships (QSAR) Patrick Chapter 18 4. Steric Factors Taft’s Steric Factor (Es) Measured by comparing the rates of hydrolysis of substituted aliphatic esters against a standard ester under acidic conditions Es = log kx - log ko kx represents the rate of hydrolysis...

Quantitative Structure-Activity Relationships (QSAR) Patrick Chapter 18 4. Steric Factors Taft’s Steric Factor (Es) Measured by comparing the rates of hydrolysis of substituted aliphatic esters against a standard ester under acidic conditions Es = log kx - log ko kx represents the rate of hydrolysis of a substituted ester ko represents the rate of hydrolysis of the parent ester Limited to substituents which interact sterically with the tetrahedral transition state for the reaction Cannot be used for substituents which interact with the transition state by resonance or hydrogen bonding May undervalue the steric effect of groups in an intermolecular process (i.e. a drug binding to a receptor) Molar Refractivity (MR) - a measure of a substituent’s volume MR = (n 2 - 1) (n 2 - 2) x mol. wt. density Correction factor Defines volume for polarisation (n=index of refraction) Verloop Steric Parameter - calculated by software (STERIMOL) - gives dimensions of a substituent - can be used for any substituent Example - Carboxylic acid B4 B B3 3 B2 B1 B L 4