Detailed Notes on Free Radicals

FREE RADICALS

Definition

  • Free radicals are chemical species with one or more unpaired electrons in the outermost shell.
  • They can be atoms, molecules, or ions.
  • Defined as a reactive intermediate formed through the homolytic cleavage of a covalent bond.

Characteristics of Free Radicals

  • Electrically neutral but electron deficient (lacking electrons to complete octet).
  • High reactivity; seek out electrons from other species to stabilize themselves.
  • Paramagnetic due to unpaired electrons.
Types of Free Radicals
  • Reactive Oxygen Species (ROS) include:
  • Superoxide
  • Peroxide
  • Hydroxyl radical

Formation and Structure

  • Formed by homolytic cleavage of covalent bonds, whereby each atom retains one electron from the bond.
  • Conditions for Homolytic Cleavage:
  • Occurs under high-energy conditions, such as:
    • Thermal cleavage (heat exposure)
    • Photolysis (UV exposure)
    • Presence of radical initiators (e.g., peroxides)

Example of Hemolytic Cleavage

  • Formation of Chlorine Radicals:
  • Reaction: [\text{Cl}_2 \xrightarrow{hv} 2 \text{Cl}^\bullet ]
  • Chlorine radicals are crucial in radical chain reactions, e.g., halogenation.

Sources of Free Radicals

  1. Endogenous Sources: Produced naturally during metabolic processes (e.g., mitochondrial electron transport chain).
  2. Exogenous Sources: Result from external factors such as:
  • Pollution
  • Radiation
  • Cigarette smoke
  • Certain chemicals

Stability of Free Radicals

  • Three primary types:
  • Benzylic
  • Allylic
  • Alkyl (1°, 2°, and 3°)
  • Stability Ranking: Tertiary > Secondary > Primary > Methyl
  • Benzylic radicals are more stable than allylic radicals due to resonance stabilization.

Free Radical Reactions

Types of Reactions
  1. Combination of Two Radicals: Two radicals react to form a stable product.
  2. Radical Reaction with a Molecule: A radical reacts with a stable molecule to propagate the reaction.
Reaction Steps
  1. Initiation:
  • Requires energy for the cleaving of covalent bonds to generate free radicals.
  • Example: Formation of chlorine radicals from Cl₂ using UV light.
  1. Propagation:
  • Radicals react with stable molecules, creating new radicals and continuing the chain reaction.
  • Example: Free radical halogenation with methane.
  1. Termination:
  • Two radicals combine to form a stable product, ceasing the chain reaction.
  • Examples of reactions leading to stable products include:
    • CH₃* + Cl* → CH₃Cl + Energy
    • CH₄ + Cl₂ → CH₃Cl + HCl

Inhibition of Free Radical Reactions

  • Chain Inhibitors:
  • Can inhibit propagation of chain reactions (e.g., O₂ can act as a radical inhibitor).

Antioxidants

  • Role: Molecules that prevent free radicals from causing oxidative damage.
  • Sources:
  • Vitamin C, Vitamin E, some B vitamins,
  • Alpha-lipoic acid, selenium, zinc, and through dietary sources, primarily fruits and vegetables.
Effects of Antioxidants
  • They stabilize free radicals by donating electrons without destabilizing themselves, thus terminating chain reactions.

Oxidative Stress

  • Definition: An imbalance between free radicals and antioxidants, leading to cellular damage.
  • Associated with chronic diseases such as:
  • Cancer
  • Diabetes
  • Cardiovascular diseases
  • Neurodegenerative conditions

Conclusion

  • Free radicals are essential in numerous biological processes but excessive levels can lead to oxidative stress and related diseases.
  • Antioxidants play a vital role in maintaining balance and protecting against oxidative damage.