A theoretical study for the structure of propranolol and some fluorinated derivatives

This paper reports on studies of the theoretical geometrical structure of propranolol and three of its fluorinated derivatives: 1-(2,2,2-trifluoroethylamino)-3-(1-naphthyloxy)-2-propanol [trifluoroethyl-propranolol], 1-(2,2,3,3.3-pentafluoropropylamino)-3-(1-naphthyloxy)-2-propanol [pentafluoropropyl-propranolol], and 1-(2,2,3,3,4,4,4-heptafluorobutylamino)-3-(1-naphthyloxy)-2-propanol [heptafluorobutyl-propranolol]. The semiempirical method AM1 was used to optimize the structures. In the minimum energy state the geometries of the naphthyl moiety and the non-fluorinated portions of the analogs are quite similar to that of the parent. Dipole moments, charge density distributions, and electrostatic potential distributions all point to the significance of the ether oxygen in all four compounds and the increasing contribution of the side-chain terminal to the activity of the molecule with increasing number of fluorines.