Cholesterol–diaryl ketone stereoisomeric dyads as models for “clean” type I and type II photooxygenation mechanisms

Abstract

Cholesterol (Ch) is a major target for oxidative degradation in cell membranes, a process which can occur by two mechanisms: Type I (via free radicals) and Type II (mediated by ¹O₂). In the present work, several dyads have been synthesized from β- and α-Ch and ketoprofen (KP) or tiaprofenic acid (TPA). Upon irradiation under anaerobic conditions, KP–α-Ch dyads were efficiently photolyzed, via intramolecular hydrogen abstraction from C-7. By contrast, KP–β-Ch, TPA–α-Ch, and TPA–β-Ch remained unchanged after prolonged irradiation. The transient absorption spectra of KP–α-Ch were assigned to the short-lived biradicals resulting from intramolecular hydrogen abstraction. Interestingly, the spectra and lifetimes obtained for the TPA-derived dyads were very similar to those of the TPA triplet excited state. For the KP–α-Ch dyads, generation of singlet oxygen was expectedly negligible. Conversely, for TPA–α-Ch a Φ_Δ value as high as 0.5 was determined. Thus, KP-based dyads are appropriate models for clean type I Ch oxidation, whereas the TPA derivatives are suitable systems for investigation of the purely type II process.