W3.1_Equilibria

Question 1

Name the six common generalised equilibria equations in pharmacology.

Answer 1

• Reactivity (stability, prodrugs): CH3COOCH3 + H2O ⇌ CH3COOH + CH3OH
• Ionisation (pH, pKa): HA ⇌ H+ + A-
• Lipophilicity (logP/D): Drug(aq) ⇌ Drug (org)
• Solubility and permeability: Drug(s) ⇌ Drug(aq)
• Crystallisation/state changes: Drug in GI ⇌ Drug in blood
• Protein-ligand interactions: Protein + Ligand ⇌ Protein-ligand complex

Question 2

In an A ⇌ B equilibrium, how are the rates of forward and backward reaction determined? What are the properties of equilibrium and how is equilibrium constant calculated?

Answer 2

• Rate of reaction: determined by concentration of reactants and rate constants
• Forward rate = k(1)/[A]
• Backward rate = k(2)/[B]
• Equilibrium: forward and reverse rates at equal rates, no observable change, X complete conversion
• Equilibrium constant: Kc=[B]/[A] OR Kc’= [A]/[B] (we choose the way we look)

Question 3

Describe a profile of percentage distribution. What does the value of Kc indicate? How can the Kc value be calculated from rates and how would rate change impact Kc?

Answer 3

• Kc < 1: eqm favours L.H.S.
• Kc = 1: eqm equal on both sides
• Kc > 1: eqm favours R.H.S.
• Rate-related: Kc≡k(1)/k(2)
• Same Kc can be achieved at different rates

Question 4

Explain the Le Chatelier’s principle. What are the three common changes and how can they impact the equilibrium? Will they impact the Kc value?

Answer 4

• Le Chatelier’s principle: change in variable -> shift in eqm position (≠ Kc) that counteracts the change
• Change in pressure of system (ex. increased pressure -> shift to the side with less moles of gas reduced pressure -> shift to the side with more moles of gas)
• Change of concentration of components (addition -> shift position to less concentrated side), vice versa
• Change of temperature (heated -> favours endothermic reaction cooled -> favours exothermic reaction), will change Kc
• Unless temperature is changed, eqm will reestablish without changing Kc

Question 5

In an A + B ⇌ C equilibrium, describe how its forward, backward rates, and Kc value are found.

Answer 5

• Forward rate = k(1)[A][B]
• Backward rate = k(2)[C]
• Kc=[C]/([A]*[B])mol^-1dm^3=k1/k2
• If swapped (C ⇌ A + B) ->Kc=[A]*[B]/[C]moldm^3

Question 6

If a graph of [B] and [C] is drawn, what can it be used for and what would the function be called?

Answer 6

• Figure out ratio of [B]:[C] (useful in pH) <- Kc[A]=[B][C]
• sigmoid function

Question 7

In an aA + bB ⇌ cC + dD equilibrium, how can its Kc value be calculated? Describe a situation where two equilibria would share common states.

Answer 7

• Kc=[C]^c[D]^d/([A]^a[B]^b)
• more common in synthetic chemistry instead
• competitive binding between enzyme-inhibitor and enzyme-substrate complexes