SectionC10a_BB - Tagged

Page 1: Introduction to Equilibrium Constants

  • Overview of CHEM10021 Chemistry for Bioscientists I.

  • Focus on equilibrium constant use in chemical reactions.

Page 2: Acid-Base Equilibria

  • Acid dissociation constant (K_a): a measure of the strength of an acid.

  • Stronger acids have larger K_a values while weaker acids have smaller K_a values.

  • pK_a conversion: pK_a = -log10(K_a).

Page 3: Types of Acids

  • Classification of acids:

    • Monoprotic (one proton), diprotic (two protons), triprotic (three protons).

  • Multiple pK_a values exist for polyprotic acids:

    • pK_a1, pK_a2, pK_a3 for diprotic and triprotic acids.

  • Mention of amino acids and their pK_a values.

Page 4: Dissociation of Polyprotic Acids

  • Example with triprotic acid: Phosphoric acid (H3PO4).

  • Dissociation steps:

    • H3PO4 ⇌ H+ + H2PO4−.

    • H2PO4− ⇌ H+ + HPO4^2−.

    • HPO4^2− ⇌ H+ + PO4^3−.

  • Concentrations and constants associated with each dissociation.

  • Citric acid as another example of a triprotic acid.

Page 5: Dissociation of Water

  • Water dissociation: H2O ⇌ H+ + OH−.

  • Activity of water is approximated as 1.

  • Concentration-based activity of ions.

  • Dissociation constant of water (K_w): K_w = [H+][OH−].

Page 6: Dissociation and Association Constants

  • Dissociation constant (K_d) measures propensity to dissociate reversibly.

  • Association constant (K_a) is the reciprocal of K_d.

Page 7: General Dissociation Reaction

  • Formula for dissociation: AxBy ⇌ xA + yB.

  • K_d defined: K_d = [A][B] / [AxBy].

  • Equilibrium concentrations of each species are emphasized.

Page 8: Protein-Ligand Interactions

  • K_d describes binding affinity of a ligand to a protein.

  • Influenced by non-covalent interactions.

  • Formation of ligand-protein complex (PL): PL ⇌ P + L.

  • Corresponding dissociation equation provided.

Page 9: Concentrations in Protein-Ligand Interactions

  • Definitions of [P], [L], and [PL]: concentrations of protein, ligand, and complex, respectively.

  • K_d corresponds to ligand concentration at which the binding site is half occupied.

  • Units of K_d (molar, M) and difference with pK_a units (M−1).

Page 10: Interpreting Kd Values

  • Smaller K_d indicates a more tightly bound ligand, denoting higher affinity.

  • Example: Ligand with nM K_d binds more tightly than ligand with uM K_d.

Page 11: Typical Kd Values in Drug Discovery

  • Initial screening K_d values: in the µM (10−6) range.

  • Hit to lead optimization K_d values: in nM (10−9) range.

  • Antibody K_d values: range from µM to nM (10−6 to 10−9).

  • High affinity: low nM to pM (10−9 to 10−12) range.

Page 12: Kinetics of Binding

  • Forward and backward rate constants: k_f (on), k_b (off).

  • Binding equilibrium: k_on[P][L] = k_off[PL].

Page 13: Relation of Kd to On and Off Rates

  • K_d relationship: K_d = k_off / k_on.

  • Derivation based on binding dynamics is discussed.

Page 14: Conclusion

  • Summary of equilibrium constants and their applications in bioscience.

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