Hydrolysis MCQs With Answer

Hydrolysis MCQs With Answer
Hydrolysis is a central concept for B. Pharm students, covering mechanisms, kinetics, and pharmaceutical implications such as drug stability, ester hydrolysis, amide hydrolysis, acid-base catalysis, and enzymatic hydrolysis. This introduction highlights key terms like pH-rate profile, pseudo-first-order kinetics, buffer catalysis, prodrug activation, and aqueous degradation pathways. Understanding factors that influence hydrolytic rates — including temperature, ionic strength, neighboring group participation, and leaving-group ability — is essential for formulation, stability testing, and rational prodrug design. These MCQs deepen conceptual and problem-solving skills relevant to pharmaceutical chemistry and drug development. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is hydrolysis in the context of pharmaceutical chemistry?

• Oxidation of drug molecules by oxygen
• Cleavage of a bond by reaction with water, including ester and amide hydrolysis
• Conversion of a drug into an insoluble salt
• Formation of a complex with metal ions

Correct Answer: Cleavage of a bond by reaction with water, including ester and amide hydrolysis

Q2. Under conditions where water concentration is effectively constant, hydrolytic reactions typically follow which kinetics?

• Second-order kinetics with respect to water
• Pseudo-first-order kinetics with respect to substrate
• Zero-order kinetics in all reactants
• Mixed-order kinetics that cannot be simplified

Correct Answer: Pseudo-first-order kinetics with respect to substrate

Q3. Which functional group generally hydrolyzes faster under comparable conditions?

• Amides
• Esters
• Ketones
• Alcohols

Correct Answer: Esters

Q4. How does acid catalysis accelerate carbonyl hydrolysis?

• By deprotonating water to form a stronger nucleophile
• By protonating the carbonyl oxygen, increasing electrophilicity of the carbonyl carbon
• By forming a covalent bond between buffer and substrate
• By irreversibly converting substrate into an inactive complex

Correct Answer: By protonating the carbonyl oxygen, increasing electrophilicity of the carbonyl carbon

Q5. In a log k versus pH profile, a slope of +1 generally indicates which catalytic mode?

• Specific acid catalysis
• Specific base catalysis
• General acid catalysis
• No catalytic involvement

Correct Answer: Specific base catalysis

Q6. The mechanism of base-catalyzed ester hydrolysis proceeds by which pathway?

• Radical chain reaction
• Bimolecular nucleophilic acyl substitution via a tetrahedral intermediate
• SN1-like carbocation formation at the alkyl side
• Concerted pericyclic rearrangement

Correct Answer: Bimolecular nucleophilic acyl substitution via a tetrahedral intermediate

Q7. Why are amides generally more resistant to hydrolysis than esters?

• Amides form stronger hydrogen bonds with water
• Resonance delocalization between the nitrogen lone pair and the carbonyl reduces carbonyl electrophilicity
• Amides have larger steric bulk around the carbonyl
• Amides cannot form tetrahedral intermediates

Correct Answer: Resonance delocalization between the nitrogen lone pair and the carbonyl reduces carbonyl electrophilicity

Q8. Under pseudo-first-order conditions, the half-life (t1/2) of hydrolysis is:

• Directly proportional to initial substrate concentration
• Independent of initial substrate concentration and equal to ln2/kobs
• Dependent on water concentration only
• Equal to the activation energy divided by temperature

Correct Answer: Independent of initial substrate concentration and equal to ln2/kobs

Q9. Which experimental observation indicates general acid-base catalysis rather than specific catalysis?

• Rate is independent of buffer concentration at constant pH
• Rate varies with buffer concentration at constant pH
• Rate changes only with ionic strength
• Rate depends solely on temperature

Correct Answer: Rate varies with buffer concentration at constant pH

Q10. What is neighboring group participation in hydrolysis?

• Solvent molecules forming micelles around the substrate
• An intramolecular nucleophile assisting formation of cyclic intermediates that accelerate hydrolysis
• Buffer ions neutralizing the substrate surface charge
• Hydrophobic interactions that slow water access

Correct Answer: An intramolecular nucleophile assisting formation of cyclic intermediates that accelerate hydrolysis

Q11. Which statement best describes ester prodrugs used in pharmaceutics?

• They are designed to resist enzymatic hydrolysis indefinitely
• They are hydrolyzed by esterases in vivo to release the active parent drug
• They always convert to toxic metabolites on hydrolysis
• They only undergo acid-catalyzed hydrolysis in the stomach

Correct Answer: They are hydrolyzed by esterases in vivo to release the active parent drug

Q12. According to the Arrhenius equation, how does hydrolysis rate change with temperature?

• Rate decreases linearly with temperature
• Rate increases exponentially with temperature; activation energy can be obtained from ln k versus 1/T
• Rate is independent of temperature if pH is constant
• Rate is inversely proportional to activation energy

Correct Answer: Rate increases exponentially with temperature; activation energy can be obtained from ln k versus 1/T

Q13. How does ionic strength commonly influence hydrolysis rates?

• Ionic strength never affects hydrolysis reactions
• Ionic strength affects rates when charged reactants or transition states are involved by screening electrostatic interactions
• Ionic strength only affects reactions in non-aqueous solvents
• Ionic strength increases solvent viscosity, which always stops hydrolysis

Correct Answer: Ionic strength affects rates when charged reactants or transition states are involved by screening electrostatic interactions

Q14. How can you experimentally demonstrate buffer catalysis of an ester hydrolysis?

• Measure rate at different pH values but constant buffer concentration
• Change buffer concentration at constant pH; a change in rate indicates buffer catalysis
• Keep all conditions constant and vary light exposure
• Only measure the reaction at extremely high temperature

Correct Answer: Change buffer concentration at constant pH; a change in rate indicates buffer catalysis

Q15. Which analytical technique is most commonly used to quantify hydrolysis and its products in drug stability studies?

• Polarimetry
• High-performance liquid chromatography (HPLC)
• Flame photometry
• Viscometry

Correct Answer: High-performance liquid chromatography (HPLC)

Q16. For formulation to enhance hydrolytic stability, which approach is commonly used?

• Store at pH near the substrate’s maximum hydrolysis rate
• Adjust and maintain pH to a region of minimal hydrolysis and control temperature
• Increase water content to saturate hydrolysis
• Expose formulation to sunlight to deactivate water

Correct Answer: Adjust and maintain pH to a region of minimal hydrolysis and control temperature

Q17. Which acyl functional group is most susceptible to hydrolysis under aqueous conditions?

• Amide
• Acid chloride
• Phenol
• Ether

Correct Answer: Acid chloride

Q18. Aspirin (acetylsalicylic acid) mainly undergoes hydrolysis in plasma by which enzyme class?

• Proteases
• Esterases
• Kinases
• Lipoxygenases

Correct Answer: Esterases

Q19. In a pH-rate profile, a slope of −1 in log k versus pH indicates which condition?

• Specific base catalysis
• Specific acid catalysis where rate ∝ [H+]⁻¹
• No pH dependence
• Buffer catalysis only

Correct Answer: Specific acid catalysis where rate ∝ [H+]⁻¹

Q20. When designing an ester prodrug for predictable hydrolysis in blood, which property is most important?

• Complete insolubility in aqueous media
• Known rate of esterase-catalyzed hydrolysis and appropriate lipophilicity for absorption
• High chemical reactivity toward air oxidation
• Ability to form strong chelates with metal ions

Correct Answer: Known rate of esterase-catalyzed hydrolysis and appropriate lipophilicity for absorption

Q21. A pronounced solvent isotope effect (rate in H2O vs D2O) suggests what about the rate-determining step?

• It does not involve proton transfer
• It involves proton transfer or hydrogen-bonding changes in the transition state
• It is diffusion-controlled only
• It is purely entropic with no bond changes

Correct Answer: It involves proton transfer or hydrogen-bonding changes in the transition state

Q22. For a simple first-order hydrolysis with rate constant k = 0.023 min⁻¹, what is the half-life?

• Approximately 0.03 minutes
• Approximately 30 minutes
• Approximately 3 minutes
• Approximately 23 minutes

Correct Answer: Approximately 30 minutes

Q23. How can metal ions act to catalyze hydrolysis of carbonyl compounds?

• By increasing solvent polarity dramatically
• By acting as Lewis acids to activate water or polarize the carbonyl for nucleophilic attack
• By reducing the substrate’s molecular weight
• By absorbing the product and preventing reaction

Correct Answer: By acting as Lewis acids to activate water or polarize the carbonyl for nucleophilic attack

Q24. Which lactone ring sizes typically hydrolyze faster due to ring strain?

• Five- and six-membered lactones
• Three- and four-membered lactones
• Large 12-membered lactones only
• Lactones do not hydrolyze in water

Correct Answer: Three- and four-membered lactones

Q25. How do electron-withdrawing substituents adjacent to a carbonyl affect hydrolysis?

• They decrease the rate by destabilizing the transition state
• They increase the rate by stabilizing positive charge in the transition state and enhancing electrophilicity
• They have no effect on hydrolysis
• They convert hydrolysis into a radical pathway

Correct Answer: They increase the rate by stabilizing positive charge in the transition state and enhancing electrophilicity

Q26. Which buffer anion can act as a nucleophilic catalyst for ester hydrolysis?

• Perchlorate
• Acetate
• Nitrate
• Helium

Correct Answer: Acetate

Q27. If a hydrolysis rate is first order in substrate and first order in hydroxide, the overall rate law is:

• Rate = k[substrate]
• Rate = k[OH-]
• Rate = k[substrate][OH-] (second-order overall)
• Rate = k[substrate]^2

Correct Answer: Rate = k[substrate][OH-] (second-order overall)

Q28. Which gastrointestinal condition favors acid-catalyzed hydrolysis of an oral drug?

• Neutral pH in the small intestine
• Highly basic pancreatic fluid
• Low pH in the stomach
• Presence of bile salts only

Correct Answer: Low pH in the stomach

Q29. How does the pKa of the leaving group affect hydrolysis rate?

• Lower pKa (better leaving group) increases hydrolysis rate
• Higher pKa always increases hydrolysis rate
• pKa of leaving group has no effect on hydrolysis
• Only steric factors matter, not pKa

Correct Answer: Lower pKa (better leaving group) increases hydrolysis rate

Q30. What is a standard approach in accelerated stability testing for hydrolytically labile drugs?

• Store at extremely low temperatures and dry conditions only
• Subject samples to elevated temperature and controlled humidity to predict long-term stability
• Expose samples to pure oxygen while keeping temperature constant
• Mix the drug with reactive metals to speed degradation

Correct Answer: Subject samples to elevated temperature and controlled humidity to predict long-term stability

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com