Global chemical reactivity parameters for several chiral beta-blockers from the Density Functional Theory viewpoint.

Background And Aim: Beta-adrenergic antagonists have been established as first line treatment in the medical management of hypertension, acute coronary syndrome and other cardiovascular diseases, as well as for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices, glaucoma, and have recently become the main form of treatment of infantile hemangiomas. The aim of the present study is to calculate for 14 beta-blockers several quantum chemical descriptors in order to interpret various molecular properties such as electronic structure, conformation, reactivity, in the interest of determining how such descriptors could have an impact on our understanding of the experimental observations and describing various aspects of chemical binding of beta-blockers in terms of these descriptors.

Methods: The 2D chemical structures of the beta-blockers (14 molecules with one stereogenic center) were cleaned in 3D, their geometry was preoptimized using the software MOPAC2012, by PM6 method, and then further refined using standard settings in MOE; HOMO and LUMO descriptors were calculated using semi-empirical molecular orbital methods AM1, MNDO and PM3, for the lowest energy conformers and the quantum chemical descriptors (HLG, electronegativity, chemical potential, hardness and softness, electrophilicity) were then calculated.