Hammett linear free energy

Modification of Chemical Structure of Drug The use of a Hammett linear free-energy relationship to investigate the effects of substituents on the rates of aromatic side-chain reactions such as hydrolysis of esters has been alluded to earlier vis-a-vis attainment of optimum stability [9,10]. Degradation of erythromycin under acidic pH conditions is inhibited by substituting a methoxy group for the C-6 hydroxyl as found for the acid stability of clathromycin, which is 340 times greater than that of erythromycin [70]. 

The control of drug stability by modifying chemical structure using appropriate substituents has been suggested for dmgs for which such a modification does not reduce therapeutic efficacy. The Hammett linear free energy relationship for the effect of substituents on the rates of aromatic side-chain reactions, such as the hydrolysis of esters, is given by... 

The Hammett linear free-energy relationship is expressed in the following equations for equilibria and rate data, respectively ... 

The Hammett linear free energy relationship is a widely used extrathermody-namic relationship for organic reactions. Although developed specifically for dissociation constants, in principle the method is applicable to any organic reaction. 

L.P. Hammett, Linear free energy relationships in rate and equilibrium phenomena, Trans. Faraday Soc. (1938), 156-165. 

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