Overview of CHEM10021 Chemistry for Bioscientists I.
Focus on equilibrium constant use in chemical reactions.
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).
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.
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.
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−].
Dissociation constant (K_d) measures propensity to dissociate reversibly.
Association constant (K_a) is the reciprocal of K_d.
Formula for dissociation: AxBy ⇌ xA + yB.
K_d defined: K_d = [A][B] / [AxBy].
Equilibrium concentrations of each species are emphasized.
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.
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).
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.
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.
Forward and backward rate constants: k_f (on), k_b (off).
Binding equilibrium: k_on[P][L] = k_off[PL].
K_d relationship: K_d = k_off / k_on.
Derivation based on binding dynamics is discussed.
Summary of equilibrium constants and their applications in bioscience.