Topological control in radical reactions of cholesterol in model dyads

Abstract

Cholesterol is one of the most important building blocks of cell membranes. It is also one of the main targets for oxidation via Type I hydrogen abstraction (HA), which leads to a variety of physiological consequences in the human body. To provide a deeper understanding of the oxidation mechanism, steady-state ¹H CIDNP, steady-state and laser-flash photolysis in combination with quantum mechanical calculations were applied to study HA in three model systems. The experiments involved photoinduced reactions in a cholesterol–benzophenone mixture and two derivatives, in which aminocholestene and benzophenone are covalently coupled yielding a dyad. It has been found, that a specific orientation of the benzophenone moiety toward the allylic hydrogens of cholesterol/aminocholestene is crucial for the efficient HA. Such a confined topology may play an important role for the particular oxidation of cholesterol in cell membranes.