Electronic properties, drugs

The next step in the development of the extrathermodynamic approach was to find a suitable expression for the equilibrium constant in terms of physicochemical and conformational (steric) properties of the drug. Use was made of a physicochemical interpretation of the dissociation constants of substituted aromatic acids in terms of the electronic properties of the substituents. This approach had already been introduced by Hammett in 1940 [14]. The Hammett equation relates the dissociation constant of a substituted benzoic acid (e.g. meta-chlorobenzoic acid) to the so-called Hammett electronic parameter a ... 

Electronic. Electronic properties also affect the pharmacodynamic phase of drug action. The electronic properties of a molecule are governed by the... 

One of the major advantages of NMR over other structural techniques such as x-ray crystallography is that it has the potential to provide information not only on structure but also on the electronic properties of molecules. Many potential drug leads contain ionizable groups and a determination of their charge state in solution and/or at the bound site or, if relevant, their tautomeric form, can be important in the design of analogues. 

Hamor and Lien have analyzed anticonvulsant activities of sulfamoyl-benzoates. For the test of antistrychnine activity, compounds having the same aromatic substituents are used so that no 2o-(X,Y) term appears in Equation 22. They have suggested that the similarity of equations in terms of steric, hydrophobic, and electronic properties of substituents indicates a common anticonvulsant mechanism for the two biological effects of this set of compounds. They have also suggested that the mechanism of action of these drugs was quite different from those of barbiturates and other hypnotics where quite different structure-activity correlations of physicochemical significance have been obtained. 

The model that emerges from this study consists of a receptor site which has the ability to accept electrons from an electron-donating drug. The association is similar to a Michaelis-Menten type hence, the biological reaction would have a relatively short half-life. In addition to these electronic considerations, a proper balance of hydrophobic and hydrophilic properties must be maintained. 

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