A Survey of Hammett Substituent Constants and Resonance and Field Parameters

TLDR: The Hammett equation has been widely used for the study and interpretation of organic reactions and their mechanisms as discussed by the authors, and it is astonishing that u constants, obtained simply from the ionization of organic acids in solution, can frequently predict successfully equilibrium and rate constants for a variety of families of reactions in solution.

Abstract: The Hammett equation (and its extended forms) has been one of the most widely used means for the study and interpretation of organic reactions and their mechanisms. Although the Hammett methodology has been criticized by theoreticians because of its empirical foundation, it is astonishing that u constants, obtained simply from the ionization of organic acids in solution, can frequently predict successfully equilibrium and rate constants for a variety of families of reactions in solution. Almost every kind of organic reaction has been treated via the Hammett equation, or its extended form. The literature is so voluminous and extensive that there is no complete review of all that has been accomplished. Hammett's success in treating the electronic effect of substituents on the rates and equilibria of organic reactions1P2 led Taft to apply the same principles to steric and inductive and resonance effects? Then, more recently, octanol/ water partition coefficients (P) have been used for rationalizing the hydrophobic effects of organic compounds interacting with biological systems? The use of log P (for whole molecules) or n (for substituents), when combined with electronic and steric parameters, has opened up whole new regions of biochemical and pharmacological reactions to study by the techniques of physical organic chemistry.sf3 The combination of electronic, steric, hydrophobic, hydrophilic, and hydrogen-bonding7 parameters has been used to derive quantitative structure-activity relationships (QSAR) for a host of interactions of organic compounds with living systems or parts thereof. The binding of organic compounds to proteins,8 their interaction with enzymess and with cellsloJ1 and tiasues,12 their inhibition of organelles,l' and as antimalarial^'^