Chemically sulfa drugs are amphoteric. They act as the weak organic acid with pKa (4.79- 8.56). However they are weakly soluble in water, their solubility is increased at alkaline pH. Sodium salts are however easily soluble in water.
The basic sulfonamides structure comprises the sulfonamide group and the amino group in the para position of the benzene ring. The nitrogen of amino group at para position is nominated as N4 while nitrogen of SO2 NH2 is nominated as N1. A large number of sulfonamide derivatives were attained by substitution of the hydrogen atom on the nitrogen of sulfonamide group (N1), while a small number of active sulfonamide drugs were attained by substitution of the hydrogen atom on the nitrogen of aromatic amino group (N4). By substitution at N1 and N4 po¬sitions about 5000 compounds are produced. Among them, 30 are of clinical importance. Sulfanilamide and its derivatives are prevalently known as sulfonamide or sulfa drug. The introduction of numerous substituents ensued in the products with different pharmacodynamics, pharmacokinetic (a degree of protein binding, excretion, metabolism) and physicochemical properties. The structure of some important sulfonamide antimicrobial drugs are shown below (Anand, 1975).