Antioxidants: The Chemical Complexity Behind a Simple Word

Area of Science:

• Computational chemistry and drug discovery.
• Biochemistry and molecular toxicology.

Background:

• Antioxidants counteract oxidative stress (OS) but require comprehensive evaluation beyond free radical scavenging.
• Molecules can exhibit pro-oxidant or toxic effects, necessitating a deep understanding of their chemistry.
• Existing methods often lack the scope to predict antioxidant activity (AOX) reliably.

Purpose of the Study:

• To highlight the utility of computational tools in evaluating antioxidant potential.
• To introduce novel protocols for a more holistic assessment of antioxidant activity.
• To guide the development of safer and more effective antioxidant drug candidates.

Main Methods:

• Focus on computational tools for assessing antioxidant activity (AOX).
• Consideration of ADME properties, solvent/pH effects, and toxicity.
• Development and application of QM-ORSA and CADMA-Chem protocols.

Main Results:

• Computational tools provide insights into chemoprotective effects and potential risks.
• Reactivity descriptors alone are insufficient; thermodynamics and kinetics are crucial.
• QM-ORSA and CADMA-Chem protocols integrate diverse reaction mechanisms and environmental factors.

Conclusions:

• Developed protocols offer a theoretical framework for investigating AOX and comparing with experimental data.
• These tools can elucidate the behavior of known antioxidants and aid in designing new ones.
• Comprehensive computational studies are essential for developing safe and efficacious antioxidants for OS-related diseases.