Pharmacophoric features of biguanide derivatives: an electronic and structural analysis.

The structure and electronic structure of drugs determine their mechanism of action. Correct structural representation of drugs helps in the proper identification of pharmacophoric features. Biguanide derivatives are a very important class of drugs, but their electronic structure was not clearly understood. Ab initio MO and density functional studies revealed the structure of the most stable tautomer of biguanide. (i) Electron delocalization, (ii) 1,3-H shift, (iii) 1,5-H shift, (iv) protonation, and (v) deprotonation processes, etc., have been investigated for biguanide. The molecular electrostatic potential (MESP) surfaces of neutral, protonated, and deprotonated biguanide have been shown to be similar in their most stable arrangements. The electrostatic potential of the complementary surface where these systems may bind also could be identified. Finally, the most stable structure of the important biguanide derivatives has been given after performing a conformational search.