The Concept of free energy MCQs With Answer is a focused resource for B. Pharm students studying thermodynamics in pharmaceutical sciences. This introduction covers Gibbs free energy, Helmholtz free energy, chemical potential, ΔG = ΔH − TΔS, and links to drug stability, solubility, dissolution, and binding equilibria. Questions emphasize standard free energy (ΔG°), temperature dependence, the ΔG–K relationship, Nernst equation applications, activity coefficients, and free energy of mixing—key for formulation and biopharmaceutics. Practical problem-solving and conceptual depth make these MCQs ideal for exam prep and laboratory interpretation. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which expression correctly defines Gibbs free energy change for a process at constant pressure and temperature?
- ΔG = ΔH + TΔS
- ΔG = ΔH − TΔS
- ΔG = ΔU − TΔS
- ΔG = ΔS − TΔH
Correct Answer: ΔG = ΔH − TΔS
Q2. For a chemical reaction at equilibrium under standard conditions, what is the value of ΔG?
- ΔG < 0
- ΔG > 0
- ΔG = 0
- ΔG = ΔH
Correct Answer: ΔG = 0
Q3. The standard free energy change ΔG° is related to the equilibrium constant K by which equation?
- ΔG° = RT ln K
- ΔG° = −RT ln K
- ΔG° = −R/T ln K
- ΔG° = R/T ln K
Correct Answer: ΔG° = −RT ln K
Q4. Which free energy is most appropriate when studying processes at constant volume and temperature?
- Gibbs free energy (G)
- Enthalpy (H)
- Helmholtz free energy (A or F)
- Entropy (S)
Correct Answer: Helmholtz free energy (A or F)
Q5. A negative ΔG for a reaction indicates what about the process under the given conditions?
- The process is non-spontaneous
- The process is spontaneous
- The process is at equilibrium
- The process is endothermic
Correct Answer: The process is spontaneous
Q6. How does ΔG depend on reaction quotient Q and standard free energy ΔG°?
- ΔG = ΔG° − RT ln Q
- ΔG = ΔG° + RT ln Q
- ΔG = −ΔG° + RT ln Q
- ΔG = RT ln(Q/ΔG°)
Correct Answer: ΔG = ΔG° + RT ln Q
Q7. Which statement correctly contrasts Gibbs and Helmholtz free energies?
- Gibbs is for constant V, Helmholtz for constant P
- Gibbs = U − TS, Helmholtz = H − TS
- Gibbs applies to constant P; Helmholtz applies to constant V
- Helmholtz determines spontaneity at constant pressure
Correct Answer: Gibbs applies to constant P; Helmholtz applies to constant V
Q8. The chemical potential µ of a component is defined as which thermodynamic derivative?
- µ = (∂H/∂n)T,P
- µ = (∂G/∂n)T,P
- µ = (∂S/∂n)T,P
- µ = (∂A/∂T)n,V
Correct Answer: µ = (∂G/∂n)T,P
Q9. What is the effect on ΔG° when the equilibrium constant K for a reaction increases at constant temperature?
- ΔG° becomes more positive
- ΔG° becomes more negative
- ΔG° remains unchanged
- ΔG° equals zero
Correct Answer: ΔG° becomes more negative
Q10. For a redox reaction, the relationship between ΔG and cell potential E is given by which equation?
- ΔG = +nFE
- ΔG = −nFE
- ΔG = −F/n E
- ΔG = nF/E
Correct Answer: ΔG = −nFE
Q11. Which relation links the standard free energy change and standard electrode potential E°?
- ΔG° = +nFE°
- ΔG° = −nFE°
- ΔG° = −F/n E°
- ΔG° = RT ln E°
Correct Answer: ΔG° = −nFE°
Q12. For an ideal solution, the free energy of mixing (ΔGmix) is expressed as:
- ΔGmix = nRT Σ xi
- ΔGmix = nRT Σ xi ln xi
- ΔGmix = −nRT Σ xi ln xi
- ΔGmix = nΣ xi ln xi
Correct Answer: ΔGmix = nRT Σ xi ln xi
Q13. Which change in sign of ΔH and ΔS leads to a reaction that is spontaneous only at low temperatures?
- ΔH > 0, ΔS > 0
- ΔH < 0, ΔS < 0
- ΔH > 0, ΔS < 0
- ΔH < 0, ΔS > 0
Correct Answer: ΔH < 0, ΔS < 0
Q14. Which statement about activities and concentrations in non-ideal solutions is correct?
- Activities equal concentrations always
- Activity = concentration × activity coefficient
- Activity coefficient is always 1 for ionic solutions
- Activities are irrelevant to free energy
Correct Answer: Activity = concentration × activity coefficient
Q15. The free energy change for transferring a drug from aqueous phase to octanol (partition) is related to the partition coefficient Kp by:
- ΔG° = −RT ln Kp
- ΔG° = +RT ln Kp
- ΔG° = −R ln Kp
- ΔG° = RT Kp
Correct Answer: ΔG° = −RT ln Kp
Q16. Which condition is true when ΔG for a reaction mixture is negative but ΔG° is positive?
- The reaction cannot proceed
- The reaction is spontaneous under the current non-standard conditions
- The reaction is at standard conditions
- The equilibrium constant must be >1
Correct Answer: The reaction is spontaneous under the current non-standard conditions
Q17. Van’t Hoff equation relates the temperature dependence of equilibrium constant K to which thermodynamic quantity?
- ΔS°
- ΔG°
- ΔH°
- ΔU
Correct Answer: ΔH°
Q18. Which of the following correctly expresses the temperature dependence of spontaneity when ΔH > 0 and ΔS > 0?
- Spontaneous at low T only
- Spontaneous at high T only
- Never spontaneous
- Always spontaneous
Correct Answer: Spontaneous at high T only
Q19. In biochemical binding, ΔG° for ligand-receptor binding is related to the dissociation constant Kd by:
- ΔG° = −RT ln(1/Kd)
- ΔG° = −RT ln Kd
- ΔG° = RT ln(1/Kd)
- ΔG° = RT ln Kd
Correct Answer: ΔG° = −RT ln(1/Kd)
Q20. Which is true about a reaction with ΔG = 0 and ΔG° < 0?
- System is at equilibrium under standard conditions
- System is at equilibrium under current conditions
- Standard state and current state are identical
- The reaction must be non-spontaneous
Correct Answer: System is at equilibrium under current conditions
Q21. For an ideal gas reaction, how does increasing total pressure at constant temperature generally affect ΔG?
- ΔG becomes more positive for gas-producing reactions
- ΔG becomes more negative for gas-producing reactions
- ΔG is independent of pressure for gases
- ΔG equals ΔH at higher pressure
Correct Answer: ΔG becomes more positive for gas-producing reactions
Q22. Which thermodynamic potential is minimized at constant temperature and volume for spontaneous processes?
- Gibbs free energy (G)
- Helmholtz free energy (A)
- Enthalpy (H)
- Internal energy (U)
Correct Answer: Helmholtz free energy (A)
Q23. The effect of ionic strength on activity coefficients primarily influences which pharmaceutical property?
- Viscosity only
- Solubility and equilibrium positions of ionizable drugs
- Color of the solution
- Melting point only
Correct Answer: Solubility and equilibrium positions of ionizable drugs
Q24. If a reaction has ΔH < 0 and ΔS > 0, what can be said about spontaneity?
- Spontaneous at all temperatures
- Spontaneous only at low T
- Spontaneous only at high T
- Never spontaneous
Correct Answer: Spontaneous at all temperatures
Q25. The reaction quotient Q equals the equilibrium constant K when:
- The system is at the start of reaction
- The system is at equilibrium
- ΔG is maximum
- ΔH is zero
Correct Answer: The system is at equilibrium
Q26. Which expression gives the standard free energy change for ionization related to pKa?
- ΔG° = 2.303 RT pKa
- ΔG° = −2.303 RT pKa
- ΔG° = RT ln pKa
- ΔG° = −RT ln pKa
Correct Answer: ΔG° = 2.303 RT pKa
Q27. In a coupled biochemical reaction, a non-spontaneous step can proceed if coupled to a spontaneous one such that:
- Sum of ΔG values is positive
- Sum of ΔG° values equals zero
- Sum of ΔG values is negative
- Individual ΔG values must both be negative
Correct Answer: Sum of ΔG values is negative
Q28. Which is true for ΔG° of dissolution of a poorly soluble drug when solubility increases?
- ΔG° becomes more positive
- ΔG° becomes more negative
- ΔG° remains constant
- ΔG° equals ΔH°
Correct Answer: ΔG° becomes more negative
Q29. The relationship between free energy change and maximum useful work wmax at constant T and P is:
- wmax = ΔH
- wmax = −ΔG
- wmax = ΔG
- wmax = −ΔH
Correct Answer: wmax = −ΔG
Q30. For ionization equilibria, increasing pH generally favors which form of a weak acid?
- Protonated (HA)
- Neutral non-ionized form
- Deprotonated (A−)
- The solid crystalline form
Correct Answer: Deprotonated (A−)
Q31. Which is a correct interpretation of a large negative ΔG° for receptor-ligand binding?
- Weak binding with high Kd
- Strong binding with low Kd
- The binding is non-specific
- Binding is entropically unfavorable
Correct Answer: Strong binding with low Kd
Q32. The standard free energy change for a reaction at 25°C is −5.7 kJ mol−1. What is the equilibrium constant K approximately? (R = 8.314 J mol−1 K−1)
- K ≈ 0.01
- K ≈ 1
- K ≈ 10
- K ≈ 100
Correct Answer: K ≈ 10
Q33. Which factor does not directly affect the Gibbs free energy of a single-component pure solid?
- Temperature
- Pressure
- Amount of substance (extensive nature aside)
- Chemical potential of a different species
Correct Answer: Chemical potential of a different species
Q34. In pharmaceutical formulation, lowering ΔG of mixing improves which property?
- Thermal decomposition
- Phase separation tendency
- Drug-excipient miscibility
- Viscosity only
Correct Answer: Drug-excipient miscibility
Q35. The sign of ΔG for the hydrolysis of ATP under cellular conditions is typically:
- Positive
- Zero
- Negative
- Undefined
Correct Answer: Negative
Q36. For an isothermal process, which of these changes corresponds to maximum non-expansion work available?
- ΔH
- −ΔG
- ΔS
- −ΔA
Correct Answer: −ΔG
Q37. Which equation expresses activity a in terms of concentration c and activity coefficient γ?
- a = γ + c
- a = γ / c
- a = γ × c
- a = c / γ
Correct Answer: a = γ × c
Q38. A reaction with positive ΔG° can be made spontaneous by:
- Decreasing concentration of reactants
- Using non-standard conditions that make ΔG negative
- Keeping system at standard state only
- Raising temperature always
Correct Answer: Using non-standard conditions that make ΔG negative
Q39. Which thermodynamic parameter is directly accessible from a van’t Hoff plot (ln K vs 1/T)?
- ΔG°
- ΔS°
- ΔH°
- ΔU
Correct Answer: ΔH°
Q40. In the Nernst equation, increasing the concentration of oxidized species relative to reduced species will do what to the cell potential?
- Decrease the potential
- Increase the potential
- Leave potential unchanged
- Make potential purely imaginary
Correct Answer: Decrease the potential
Q41. Which of these is the correct expression for the Helmholtz free energy A?
- A = H − TS
- A = U − TS
- A = G − PV
- A = U + TS
Correct Answer: A = U − TS
Q42. For a solvation process, a more negative ΔG° indicates:
- Lower solubility
- Higher solubility
- No change in solubility
- Less favorable dissolution
Correct Answer: Higher solubility
Q43. Which of the following best describes the relation between ΔG and spontaneity for coupled enzymatic steps?
- Only the individual ΔG values matter
- Coupling cannot affect spontaneity
- Net ΔG of coupled steps determines overall spontaneity
- Equilibrium constants add directly to give net spontaneity
Correct Answer: Net ΔG of coupled steps determines overall spontaneity
Q44. Increasing temperature will always favor the side of a reaction with greater entropy when:
- ΔS < 0
- ΔH < 0
- ΔS > 0
- ΔH > 0
Correct Answer: ΔS > 0
Q45. Which experimental measurement can be used to estimate ΔG° of a binding interaction?
- UV-visible spectrum only
- Binding affinity (Kd or Ka)
- Molar mass alone
- Viscosity of the solution
Correct Answer: Binding affinity (Kd or Ka)
Q46. The free energy change for mixing two ideal liquids is negative because:
- Enthalpy change is highly positive
- Entropy of mixing is positive
- Entropy of mixing is negative
- Interactions are always unfavorable
Correct Answer: Entropy of mixing is positive
Q47. For a reaction with ΔH = 0 and ΔS > 0, the temperature dependence of ΔG indicates:
- Reaction is non-spontaneous at all T
- Reaction becomes spontaneous as T increases
- Reaction becomes non-spontaneous as T increases
- Reaction is spontaneous only at T = 0 K
Correct Answer: Reaction becomes spontaneous as T increases
Q48. Which quantity must be known to convert ΔG° at one temperature to another using Kirchhoff relations?
- ΔCp (heat capacity change)
- Activity coefficients only
- Number of moles only
- Color change of reactants
Correct Answer: ΔCp (heat capacity change)
Q49. The driving force for spontaneous diffusion of a drug down its chemical potential gradient is:
- Increase in Gibbs free energy
- Decrease in Gibbs free energy
- Increase in enthalpy only
- None of the thermodynamic potentials
Correct Answer: Decrease in Gibbs free energy
Q50. Which statement best links free energy changes to pharmaceutical stability?
- A more negative ΔG for degradation means better stability
- Positive ΔG for degradation indicates spontaneous degradation
- Positive ΔG for degradation indicates non-spontaneous degradation under those conditions
- ΔG has no relevance to degradation pathways
Correct Answer: Positive ΔG for degradation indicates non-spontaneous degradation under those conditions

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