Lecture on Electrophilicity, ATP, and Alcohol Metabolism

Jul 9, 2024

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Lecture on Electrophilicity, ATP, and Alcohol Metabolism

Electrophilicity of Carboxylic Acid Derivatives

  • Electrophilicity: Measure of how susceptible a carbon is to attack by a nucleophile.
  • Attack Mechanism: General process involves a base attacking, electrons kicking up, then electrons kicking back down and kicking off the leaving group.
  • Stability Factors: The stability of the leaving group greatly influences the forward nature of the reaction.
    • Conjugate Base Stability: More stable conjugate bases (lower pKa) make better leaving groups.
  • Order of Electrophilicity & Conjugate Acid pKa: (Increasing Electrophilicity)
    1. Acid Chloride (Cl-): pKa ~5
    2. Anhydride: Resonance stabilized, pKa ~4-5
    3. Ester: Resonance stabilized, pKa ~8
    4. Amide (R-NH2): pKa ~15.7
    5. Carboxylate Acid (R-COOH): pKa 16-18
    6. Impossible ones: e.g., hydride (H-), pKa 38

ATP and Energy Production

  • ATP Hydrolysis: ATP + H2O → ADP + Pi + Energy
  • Energy Release Mechanism:
    • Phosphor Anhydride Bond: Breaking the bond via hydrolysis releases energy.
    • Charge Separation: Repelling like charges is energetically favorable.
  • Biochemical Significance: Coupled reactions e.g., succinyl-CoA to succinate generating GTP.
  • Analogy to Orgo: ATP structure compared to phosphor anhydride bond breaking.

Alcohols

  • Primary Alcohol to Aldehyde: Reagent PCC (pyridinium chlorochromate).
  • Secondary Alcohol to Ketone: Reagent Jones (Na2Cr2O7 + H2SO4 or Cr03 + H2SO4 + Acetone).
  • Primary Alcohol to Carboxylic Acid: Jones reagent goes all the way to carboxylic acid.
  • Routes & Reactions: Key mentioned steps for transforming alcohols into other functional groups.
  • Phenols: Reaction with oxidants to form quinones.
  • Good Leaving Groups: Tosylates (OTS) formation and their mechanism.

Alcohol Metabolism

  • Two-step process: Alcohol to vinegar.
  • Ethanol (Alcohol) to Ethanal (Acetylaldehyde): Enzyme alcohol dehydrogenase.
  • Ethanal to Acetic Acid: Enzyme acetylaldehyde dehydrogenase.
  • Impact on NAD/NADH Ratio: Alcohol metabolism uses NAD, can lead to lactic acidosis.
  • Asian Glow: Deficiency in acetylaldehyde dehydrogenase causing flushing, nausea, and other symptoms.

Miscellaneous

  • Gasoline and LPG: Non-polar, lipophilic, can cross blood-brain barrier.

  • Runner's High: Results in a feeling of euphoria and lowered pain sensations.

  • PCC: Please Create Carbonyl, peridinium chlorochromate as a reagent for oxidation.

  • Clarification on structure and reactions of ATP analogs and coupling for energy cycles in biochemistry.

Additional Tips

  • Regular review of PKa values is crucial for understanding reaction mechanisms and stability.
  • Understanding the fundamentals of nucleophilicity and electrophilicity aids in mastering organic reactions.
  • Stay curious and question the mechanisms behind each step for deeper understanding in biochemistry and organic reactions.