Ab Initio Study of Prednisolone, 6 -Fluoroprednisolone, 9 -Fluoroprednisolone, and 6 ,9 -Difluoroprednisolone

Abstract

A theoretical study of prednisolone, 6α-fluoroprednisolone, 9α-fluoroprednisolone, and 6α,9α-difluoroprednisolone has been performed at the ab initio HF/6-31G, MP2/6-31G, and B3LYP/6-31G levels. Structural information and the electronic features of prednisolone and its derivatives and the synergistic effect of 6α,9α-difluoroprednisolone was examined. Contrary to the AM1 and MNDO results, we found 9α-fluoroprednisolone is more stable than the 6α-fluoroprednisolone. The increased corticosteroid activity of the 6α,9α-difluoroprednisolone is most likely due to electronic effects, mainly related to the receptor binding.