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.