Structure-activity relationships. The nature of chemical bonds. Adsorption. The influence of seemingly inert groups on biological action

Abstract

Most categories of physiological action are highly dependent on details of chemical structure: if these are varied, even slightly, the degree of action is usually radically changed. For example, the vitamin activity of thiamine (7.1) (tested on pigeons) drops to 5 per cent if the methyl-group is removed from the pyrimidine ring, and to < 1 per cent if the methyl-group is removed from the thiazole ring (Schultz, 1940). Finally, if an extra methyl-group is inserted into the thiazole ring (between nitrogen and sulphur), the vitamin activity completely disappears (Bergel and Todd, 1937). This rule of the essential nature of every part of a molecule usually does not apply to a side-chain. For example, the long aliphatic side-chain in the 3-position of vitamin K₁ (7.2) can be pruned without affecting the principal actions of this vitamin. In such a case, it is evident that the side-chain lacks all of those atoms responsible for adsorption of this vitamin on the receptors.