Cholesterol-diaryl ketone stereoisomeric dyads as models for "clean" type I and type II photooxygenation mechanisms

Org Biomol Chem. 2008 Mar 7;6(5):860-7. doi: 10.1039/b718068c. Epub 2008 Jan 31.

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 beta- and alpha-Ch and ketoprofen (KP) or tiaprofenic acid (TPA). Upon irradiation under anaerobic conditions, KP-alpha-Ch dyads were efficiently photolyzed, via intramolecular hydrogen abstraction from C-7. By contrast, KP-beta-Ch, TPA-alpha-Ch, and TPA-beta-Ch remained unchanged after prolonged irradiation. The transient absorption spectra of KP-alpha-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-alpha-Ch dyads, generation of singlet oxygen was expectedly negligible. Conversely, for TPA-alpha-Ch a Phi delta) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol / chemistry*
  • Ketones / chemical synthesis
  • Ketones / chemistry*
  • Models, Chemical*
  • Molecular Structure
  • Oxygen / chemistry*
  • Photochemistry
  • Quantum Theory
  • Stereoisomerism
  • Time Factors

Substances

  • Ketones
  • Cholesterol
  • Oxygen