Relative Stability of Clonidine Isomers

Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics.However, due to its capacity in lowering blood pressure, CND has been successfully employedin the treatment of hypertension for over 25 years [1]. On based the position of Cl substituents,CND has several isomers with different chemical and biological activities (CND2-CND2-3, see Fig. 1). The relative stability of CND isomers in the gas phase and aqueous solutionhas been investigated using DFT calculations. The geometry optimizations have beenperformed at the B3LYP/6-31G(d,p) level of theory using the Gaussian09 program package[1,2]. The trend in the stabilities of isomers estimated in the gas phase and aqueous solution isCND2-3 > CND2-2> CND2> CND2-1. The ortho/para isomer (CND2-1/CND2-3) is theleast/most stable isomer because of the electronic and steric effects.