Theoretical study on some non-selective beta-adrenergic antagonists and correlation to their biologically active configurations

The non-selective classification refers to those beta-blockers capable of blocking both beta 1 and beta 2 receptors with equivalent efficacy. All of these beta-blockers consist of an aryloxypropanolamine side chain linked to an aromatic or heteroaromatic ring. Each of these drugs possesses at least one chiral center, and high degree of enantioselectivity in binding to beta-adrenergic receptor. In this research, ab initio method with 6-31G* basis set was employed for investigation of correlation between optimized geometry and biologically active configuration on both enantiomers of Timolol, Nadolol, Bunolol, and Propranolol. These calculations show higher stabilities for (S)-enantiomer compared with (R)-antipode, for each stereoisomer. Also, torsion angles around the N2C3C4O5 bond confirm that (S)- and (R)-Propranolol have the lowest and highest dihedral angles related to other non-selective beta-blockers, respectively. Furthermore, the (S)-enantiomers of beta-blockers reveal the more negative natural charges for oxygen atom in hydroxyl as well as nitrogen atom in aryloxypropanolamine group than related (R)-enantiomer.