MCQ Quiz: Relationships of Functional Groups to Pharmacological Activity

Understanding how chemical functional groups influence a drug’s pharmacological activity is foundational to medicinal chemistry and pharmacology. Functional groups affect solubility, absorption, metabolism, receptor binding, and toxicity. This MCQ quiz covers the physicochemical and biological impacts of common drug functional groups—essential knowledge for every Pharm.D. student.

1. Which of the following functional groups increases water solubility?

• A. Hydroxyl
• B. Methyl
• C. Phenyl
• D. Isopropyl
  Correct answer: A. Hydroxyl

2. A carboxylic acid group is generally:

• A. Basic
• B. Neutral
• C. Amphoteric
• D. Acidic
  Correct answer: D. Acidic

3. Which group enhances lipophilicity in a drug molecule?

• A. Amino
• B. Hydroxyl
• C. Alkyl
• D. Carboxyl
  Correct answer: C. Alkyl

4. Which of these groups is ionized at physiological pH (7.4)?

• A. Carboxylic acid (pKa ~4)
• B. Amide
• C. Ether
• D. Ketone
  Correct answer: A. Carboxylic acid (pKa ~4)

5. Which group can form hydrogen bonds with receptors?

• A. Hydroxyl
• B. Methyl
• C. Cyclopropyl
• D. Isobutyl
  Correct answer: A. Hydroxyl

6. An amino group generally acts as a:

• A. Neutral group
• B. Acidic group
• C. Basic group
• D. Hydrophobic group
  Correct answer: C. Basic group

7. Which group is commonly added to increase metabolic stability?

• A. Fluorine
• B. Hydroxyl
• C. Carboxyl
• D. Amide
  Correct answer: A. Fluorine

8. Aromatic rings contribute to:

• A. Increased water solubility
• B. Lipophilicity and π-π stacking
• C. Acidity
• D. Oxidation resistance
  Correct answer: B. Lipophilicity and π-π stacking

9. Ester groups are:

• A. More stable than amides
• B. Rapidly hydrolyzed in vivo
• C. Inactive in prodrugs
• D. Nonpolar and inert
  Correct answer: B. Rapidly hydrolyzed in vivo

10. The presence of multiple hydroxyl groups in a drug leads to:

• A. Increased lipophilicity
• B. Decreased hydrogen bonding
• C. Increased polarity
• D. Poor water solubility
  Correct answer: C. Increased polarity

11. The pKa of a functional group affects:

• A. Its molecular weight
• B. Its ionization and solubility at physiological pH
• C. Its taste
• D. Its melting point
  Correct answer: B. Its ionization and solubility at physiological pH

12. Ketones typically exhibit:

• A. High basicity
• B. Ability to form hydrogen bonds as acceptors
• C. Strong acidic behavior
• D. Instability in blood
  Correct answer: B. Ability to form hydrogen bonds as acceptors

13. Which group increases a drug’s binding to albumin?

• A. Carboxyl
• B. Sulfate
• C. Ether
• D. Aldehyde
  Correct answer: A. Carboxyl

14. Prodrugs are often created by modifying which group?

• A. Hydroxyl into ester
• B. Amide into ether
• C. Ether into aldehyde
• D. Sulfate into ketone
  Correct answer: A. Hydroxyl into ester

15. Which of the following functional groups is non-ionizable at physiological pH?

• A. Primary amine
• B. Carboxylic acid
• C. Amide
• D. Phenol
  Correct answer: C. Amide

16. A drug with many methyl groups is likely to be:

• A. Hydrophilic
• B. Ionized in plasma
• C. Lipophilic
• D. Unstable
  Correct answer: C. Lipophilic

17. Which group is a good hydrogen bond donor?

• A. Ether
• B. Ketone
• C. Alcohol
• D. Halide
  Correct answer: C. Alcohol

18. Which group is most commonly oxidized by liver enzymes?

• A. Carboxylic acid
• B. Hydroxyl
• C. Amide
• D. Methyl
  Correct answer: D. Methyl

19. Sulfonamides are used in drugs for their:

• A. Lipophilic properties
• B. Enzyme inhibition via acidic behavior
• C. Inert nature
• D. Antiseptic function
  Correct answer: B. Enzyme inhibition via acidic behavior

20. A tertiary amine in a drug usually provides:

• A. Lipid insolubility
• B. No interaction with receptors
• C. Basic character and ionic interaction capability
• D. Acidic stability
  Correct answer: C. Basic character and ionic interaction capability

21. The introduction of a chlorine atom can:

• A. Increase polarity
• B. Decrease metabolic stability
• C. Enhance lipophilicity and resist metabolism
• D. Make a drug unstable
  Correct answer: C. Enhance lipophilicity and resist metabolism

22. Which group improves oral bioavailability via membrane permeability?

• A. Hydroxyl
• B. Carboxyl
• C. Lipophilic alkyl chains
• D. Ionic phosphate
  Correct answer: C. Lipophilic alkyl chains

23. The bioisosteric replacement of a carboxyl group may reduce:

• A. Water solubility
• B. Receptor binding
• C. Ionization
• D. Metabolism
  Correct answer: C. Ionization

24. Which of the following can form a salt with hydrochloric acid?

• A. Ketone
• B. Amide
• C. Amine
• D. Alcohol
  Correct answer: C. Amine

25. Functional groups affect metabolism mainly through:

• A. Shape changes only
• B. Inducing enzymatic transformations (e.g., oxidation, hydrolysis)
• C. Heat activation
• D. UV light exposure
  Correct answer: B. Inducing enzymatic transformations (e.g., oxidation, hydrolysis)

26. A thiol group is:

• A. Strongly basic
• B. Hydrophilic
• C. Nucleophilic and prone to oxidation
• D. Always neutral
  Correct answer: C. Nucleophilic and prone to oxidation

27. Which group is crucial in forming covalent bonds with enzyme active sites?

• A. Methyl
• B. Aldehyde
• C. Sulfhydryl
• D. Ether
  Correct answer: C. Sulfhydryl

28. The presence of a nitro group may:

• A. Decrease lipophilicity
• B. Reduce polarity
• C. Increase toxicity risk
• D. Promote ionization
  Correct answer: C. Increase toxicity risk

29. Ether groups contribute to:

• A. High solubility
• B. Poor metabolic stability
• C. Chemical inertness and moderate polarity
• D. Rapid metabolism
  Correct answer: C. Chemical inertness and moderate polarity

30. The addition of a phosphate group to a drug molecule generally:

• A. Enhances CNS penetration
• B. Reduces water solubility
• C. Improves aqueous solubility and prodrug utility
• D. Prevents oral absorption
  Correct answer: C. Improves aqueous solubility and prodrug utility

31. Which type of bond do functional groups form in enzyme active sites?

• A. Peptide
• B. Hydrogen, ionic, or covalent
• C. Metallic
• D. Salt bridge only
  Correct answer: B. Hydrogen, ionic, or covalent

32. Ionization state affects:

• A. Color only
• B. Taste
• C. Absorption and distribution
• D. Melting point
  Correct answer: C. Absorption and distribution

33. Functional groups affect drug-receptor binding by:

• A. Only changing size
• B. Interacting via non-covalent forces
• C. Inducing pain
• D. Stimulating heat generation
  Correct answer: B. Interacting via non-covalent forces

34. A phenol group is:

• A. Non-polar
• B. Basic
• C. Weakly acidic and aromatic
• D. Always ionized
  Correct answer: C. Weakly acidic and aromatic

35. Alkyl chains increase:

• A. Solubility in water
• B. Ionization
• C. Lipophilicity
• D. UV absorbance
  Correct answer: C. Lipophilicity

36. Functional groups may be metabolically transformed in the liver by:

• A. Lipase only
• B. Cytochrome P450 enzymes
• C. Salivary enzymes
• D. Renal excretion
  Correct answer: B. Cytochrome P450 enzymes

37. An alcohol group is prone to which metabolic reaction?

• A. Sulfation or glucuronidation
• B. Oxidative deamination
• C. Nitration
• D. Decarboxylation
  Correct answer: A. Sulfation or glucuronidation

38. A basic drug is most likely to be absorbed in the:

• A. Stomach
• B. Colon
• C. Mouth
• D. Small intestine
  Correct answer: D. Small intestine

39. The term “bioisostere” refers to:

• A. A toxic group
• B. A chemically identical group
• C. A group that mimics biological properties of another
• D. A group that increases weight
  Correct answer: C. A group that mimics biological properties of another

40. Ultimately, functional group design in drugs aims to:

• A. Increase taste appeal
• B. Decrease manufacturing costs
• C. Optimize pharmacokinetics and pharmacodynamics
• D. Avoid prodrug development
  Correct answer: C. Optimize pharmacokinetics and pharmacodynamics

41. Which functional group is most susceptible to hydrolysis in the body?

• A. Alkene
• B. Amide
• C. Ester
• D. Ether
  Correct answer: C. Ester

42. Carboxylic acids can interact with receptor sites through:

• A. Covalent bonds only
• B. Hydrogen bonding and ionic interactions
• C. Metallic bonding
• D. Halogen bonding
  Correct answer: B. Hydrogen bonding and ionic interactions

43. What is the primary effect of introducing a methyl group near a basic amine?

• A. Enhance solubility
• B. Increase polarity
• C. Reduce basicity through electron donation
• D. Increase basicity through electron donation
  Correct answer: D. Increase basicity through electron donation

44. Which of the following functional groups is often used to modify a drug into a prodrug?

• A. Ether
• B. Ester
• C. Amide
• D. Hydroxyl
  Correct answer: B. Ester

45. A drug containing a nitro group may undergo which metabolic reaction?

• A. Oxidation
• B. Nitration
• C. Reduction
• D. Methylation
  Correct answer: C. Reduction

46. Introduction of a sulfonic acid group generally makes the compound:

• A. More basic
• B. Less water-soluble
• C. Highly acidic and hydrophilic
• D. Lipophilic
  Correct answer: C. Highly acidic and hydrophilic

47. Which functional group acts as an electron-withdrawing group in aromatic rings?

• A. Nitro
• B. Methyl
• C. Hydroxyl
• D. Amine
  Correct answer: A. Nitro

48. A tertiary alcohol is less reactive than a primary alcohol because of:

• A. Strong acidity
• B. Hydrogen bonding
• C. Steric hindrance
• D. Electrophilicity
  Correct answer: C. Steric hindrance

49. The term “soft drug” refers to:

• A. A drug that acts slowly
• B. A drug metabolized predictably into inactive products
• C. A drug with high solubility
• D. A drug with a flexible structure
  Correct answer: B. A drug metabolized predictably into inactive products

50. Functional group modifications are primarily aimed at:

• A. Altering color
• B. Improving taste
• C. Enhancing drug stability, selectivity, or bioavailability
• D. Decreasing cost
  Correct answer: C. Enhancing drug stability, selectivity, or bioavailability