When,it the context of drg design,can a fluorine atom successfully substitute a hydroxyl group?

摘要

In this article,we deal with the question of whether a fluorine atom can substitute a hydorxyl groups in such a way that will lead to a compound showing a desired biologic activity,that,is,a potential new drug.It is obvious that a fluorine atom differs from a hydroxyl group,as it cannot donate hydrogen bonds.however,it can acdept them.Moreover,both fluorine and oxygen are of similar size and are the most electronegative elements.Therefore,a fluorine atom is thought to be a good substitute for a hydorxyl group.However,it was shown that for conformationally labile aliphatic compounds a replacement of a hydroxyl by a fluorine increases conformational diversity,so the fluorine-containing aliphatic molecules are present in equilibriumat room temperature as a mixture of several different conformers.Incontrast,for cyclic compounds the substitution of an OH grop by an F atom does not much change shape and electrostatic potential around corresponding conformers.Moreover,these compounds are present in equilibrium at room temperature in aqueous solutionas a mixture of thesamemost favored structures.