Extraordinary radical scavengers: 4-mercaptostilbenes

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Biochemistry

Background:

• Resveratrol, a natural stilbene, has garnered interest for its antioxidant and chemopreventive properties.
• There is a continuous search for more potent antioxidants and cancer chemoprevention agents.
• Thiophenol derivatives are hypothesized to possess superior radical-scavenging capabilities compared to phenol analogs.

Purpose of the Study:

• To synthesize and evaluate novel resveratrol-directed 4-mercaptostilbenes as potential antioxidants and chemopreventive agents.
• To compare the radical-scavenging activity of these new compounds with resveratrol and other known antioxidants.
• To elucidate the reaction mechanisms underlying their radical-scavenging activity in different solvent environments.

Main Methods:

• Synthesis of eight resveratrol-directed 4-mercaptostilbene derivatives.
• Kinetic measurements of reaction rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.)) radicals using stopped-flow UV/Vis spectroscopy at 25°C in methanol and ethyl acetate.
• Acidified-kinetic analysis to investigate reaction mechanisms.

Main Results:

• 4-mercaptostilbenes demonstrated extraordinary radical-scavenging activity, significantly exceeding that of resveratrol.
• In methanol, some derivatives were up to 10,000 times more active than resveratrol and hundreds of times more effective than established antioxidants like α-tocopherol and ascorbic acid.
• Reaction mechanisms varied with solvent polarity and acidity, proceeding via sequential proton loss electron transfer in methanol and potentially electron transfer or direct hydrogen atom transfer in ethyl acetate.

Conclusions:

• Substitution of the 4-OH group with a 4-SH group in the stilbene scaffold is a highly effective strategy for enhancing radical-scavenging activity.
• The synthesized 4-mercaptostilbenes represent a promising class of compounds for developing superior antioxidants and cancer chemoprevention agents.
• Radical-scavenging efficacy and mechanisms are significantly influenced by molecular structure, acidity, radical type, and solvent properties.