Bimodal physiological effect of picolinic acid derivatives is determined by the zwitterion structure characteristics

: In order to define the mechanism of action and causes for the manifestation of the bimodal physiological effect of certain picolinic acid derivatives we carried out quantum chemical calculations (QCC MO, 3-21G/6-31G* basis) of picolinic acid (1), 3,6-dichloropicolinic acid (2), acepox (3), and tetrapin (4) zwitterions. The exocyclic bond C(pyr)-Cexo is enhanced in zwitterions 3 and 4 with the bimodal physiological effect and loosened in zwitterions 1 and 2 without the effect. Zwitterions of the molecules 1-4 also differ in the pattern of the boundary molecular orbitals and electric charge distribution. On the basis of the obtained data, we propose that the difference in the physiological effect of compounds 1-4 is due to the different behavior of their zwitterions in aqueous solution.