Hydrogen bonding and biological action MCQs With Answer

Hydrogen bonding and biological action MCQs With Answer

by

Hydrogen bonding and biological action MCQs With Answer

Understanding hydrogen bonding is central to B.Pharm students studying drug-receptor interactions, protein structure, solubility, bioavailability and drug design. These targeted MCQs cover hydrogen bond types, geometry, strength, intramolecular vs intermolecular effects, water-mediated interactions, effects on pKa and tautomerism, and their consequences for pharmacokinetics and pharmacodynamics. Emphasis is placed on real-world relevance: peptide backbone H-bonds, nucleic acid base pairing, desolvation penalties, Lipinski parameters and hydrogen bond networks in enzyme active sites. Clear explanations will help you connect molecular H-bonding principles to biological action and medicinal chemistry optimization. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary defining feature of a hydrogen bond?

  • An interaction involving covalent sharing of electrons between hydrogen and another atom
  • An electrostatic attraction between a hydrogen atom bonded to an electronegative atom and another electronegative atom
  • A van der Waals attraction between two hydrogen atoms
  • A ionic bond formed by proton transfer

Correct Answer: An electrostatic attraction between a hydrogen atom bonded to an electronegative atom and another electronegative atom

Q2. Which pair is a classic example of hydrogen bonding in nucleic acids?

  • Adenine–Guanine base pair
  • Adenine–Thymine base pair
  • Guanine–Guanine Hoogsteen pair
  • Cytosine–Cytosine mismatch

Correct Answer: Adenine–Thymine base pair

Q3. Which atom typically acts as a hydrogen bond donor in drug–protein interactions?

  • Carbonyl oxygen (C=O)
  • Amide nitrogen (N–H)
  • Aliphatic carbon (C–H)
  • Chlorine atom (Cl)

Correct Answer: Amide nitrogen (N–H)

Q4. How does hydrogen bonding generally affect aqueous solubility of small molecules?

  • Increases solubility by enabling interaction with water
  • Always decreases solubility by promoting crystal packing
  • Has no effect on solubility
  • Makes compounds volatile

Correct Answer: Increases solubility by enabling interaction with water

Q5. In an alpha-helix, hydrogen bonds form between which groups?

  • Side-chain hydroxyl groups of neighboring residues
  • Backbone C=O of residue i and N–H of residue i+4
  • Backbone N–H and side-chain carboxylate of residue i+2
  • Terminal amino group and C-terminal carboxyl

Correct Answer: Backbone C=O of residue i and N–H of residue i+4

Q6. Which statement about hydrogen bond strength is most accurate?

  • Hydrogen bonds are stronger than covalent bonds
  • Hydrogen bonds typically range from 1 to 40 kJ/mol depending on geometry and partners
  • All hydrogen bonds have identical strength regardless of atoms involved
  • Hydrogen bonds are purely repulsive interactions

Correct Answer: Hydrogen bonds typically range from 1 to 40 kJ/mol depending on geometry and partners

Q7. Which factor most weakens a hydrogen bond?

  • Short donor–acceptor distance
  • Optimal linear geometry (180°)
  • High dielectric constant solvent like water
  • Strong electronegativity difference between donor and acceptor

Correct Answer: High dielectric constant solvent like water

Q8. Intramolecular hydrogen bonding in a drug molecule typically:

  • Always increases water solubility
  • Reduces the effective polarity and may increase membrane permeability
  • Makes the molecule more flexible
  • Prevents any interaction with targets

Correct Answer: Reduces the effective polarity and may increase membrane permeability

Q9. Which descriptor is directly related to hydrogen bonding capacity in Lipinski’s rules?

  • Topological polar surface area (TPSA)
  • Number of rotatable bonds
  • Number of hydrogen bond donors and acceptors
  • Molar refractivity

Correct Answer: Number of hydrogen bond donors and acceptors

Q10. A water-mediated hydrogen bond in a protein–ligand complex is important because:

  • Water always disrupts binding and reduces affinity
  • Bridging water can enhance specificity and compensate for direct H-bond loss
  • It converts hydrogen bonds into covalent bonds
  • It prevents all entropic contributions to binding

Correct Answer: Bridging water can enhance specificity and compensate for direct H-bond loss

Q11. Which spectroscopic change indicates hydrogen bonding involving an O–H group?

  • IR O–H stretching band shifts to higher frequency and narrows
  • IR O–H stretching band shifts to lower frequency and broadens
  • UV–Vis absorbance disappears
  • 1H NMR signal becomes upfield (shielded)

Correct Answer: IR O–H stretching band shifts to lower frequency and broadens

Q12. In protein beta-sheets, hydrogen bonds occur between:

  • Side-chain methyl groups
  • Backbone C=O and N–H of adjacent beta-strands
  • Terminal amino and terminal carboxyl only
  • Disulfide bridges

Correct Answer: Backbone C=O and N–H of adjacent beta-strands

Q13. How does hydrogen bonding influence pKa of a nearby acidic group?

  • Hydrogen bonding to the conjugate base can stabilize it and lower pKa
  • Hydrogen bonding has no effect on pKa
  • Hydrogen bonding always increases pKa by proton donation
  • Only ionic bonds affect pKa

Correct Answer: Hydrogen bonding to the conjugate base can stabilize it and lower pKa

Q14. Directionality of hydrogen bonds is important because:

  • They are strongest when donor–H–acceptor angle is near 180°
  • They function equally at any angle
  • They require donor–acceptor angle to be 90°
  • Hydrogen bonds are only distance dependent, not angular

Correct Answer: They are strongest when donor–H–acceptor angle is near 180°

Q15. Which pair is an example of an intramolecular hydrogen bond that can influence drug conformation?

  • Interstrand DNA base pair
  • Phenol OH hydrogen bonding to an adjacent carbonyl within the same molecule
  • Hydrophobic alkyl chain interactions
  • Metal coordination to nitrogen

Correct Answer: Phenol OH hydrogen bonding to an adjacent carbonyl within the same molecule

Q16. What is the role of hydrogen bonding in enzyme catalysis?

  • They never participate in catalysis
  • They stabilize transition states and orient substrates for reaction
  • They convert enzymes into rigid, inactive structures
  • They only assist in cofactor binding, not catalysis

Correct Answer: They stabilize transition states and orient substrates for reaction

Q17. Which of the following is considered a hydrogen bond acceptor?

  • Aliphatic hydrogen
  • Carbonyl oxygen
  • Tertiary carbon atom
  • Metal cation exclusively (never acceptor)

Correct Answer: Carbonyl oxygen

Q18. The replacement of a labile N–H donor by N–CH3 in a lead compound typically results in:

  • Increase in hydrogen bonding with the protein
  • Loss of a hydrogen bond donor potentially reducing binding affinity
  • Generation of a stronger hydrogen bond donor
  • No change in H-bonding properties

Correct Answer: Loss of a hydrogen bond donor potentially reducing binding affinity

Q19. How does deuterium substitution (H→D) affect hydrogen bonds?

  • Completely abolishes hydrogen bonding
  • Causes a small isotope effect often altering vibrational frequencies and reaction rates
  • Transforms hydrogen bonds into covalent bonds
  • Makes hydrogen bonds much stronger by an order of magnitude

Correct Answer: Causes a small isotope effect often altering vibrational frequencies and reaction rates

Q20. Cooperativity in hydrogen bonding networks means:

  • Each H-bond is independent of others
  • Formation of one H-bond can strengthen or weaken neighboring bonds
  • Only two H-bonds can exist in a molecule
  • Cooperativity applies only to covalent bonds

Correct Answer: Formation of one H-bond can strengthen or weaken neighboring bonds

Q21. Which metric in computational docking often accounts for hydrogen bonding?

  • Van der Waals radius exclusively
  • Hydrogen bond scoring functions and distance/angle penalties
  • Only lipophilicity scores
  • Rotatable bond count

Correct Answer: Hydrogen bond scoring functions and distance/angle penalties

Q22. A ligand that forms hydrogen bonds with backbone atoms rather than side chains is likely to be:

  • More sensitive to point mutations in the binding site
  • Less sensitive to mutations and more broadly conserved binding
  • Completely non-specific
  • Unable to bind in aqueous environments

Correct Answer: Less sensitive to mutations and more broadly conserved binding

Q23. Which statement correctly contrasts hydrogen bond donors and acceptors?

  • Donors provide lone pairs; acceptors provide protons
  • Donors provide a bonded hydrogen; acceptors provide lone pair electrons
  • Both donate protons
  • Only donors can be electronegative atoms

Correct Answer: Donors provide a bonded hydrogen; acceptors provide lone pair electrons

Q24. In solid-state drug formulations, hydrogen bonding influences:

  • Crystal packing, polymorphism and melting point
  • Only the drug’s color
  • Exclusively the vapor pressure
  • Hydrogen bonds are irrelevant in solids

Correct Answer: Crystal packing, polymorphism and melting point

Q25. Which of the following increases the likelihood of forming a strong hydrogen bond?

  • Less electronegative acceptor atom
  • Long donor–acceptor distance (>4 Å)
  • High polarity and optimal linear geometry
  • Presence of bulky groups preventing approach

Correct Answer: High polarity and optimal linear geometry

Q26. Water molecules in binding sites often act as:

  • Irreversible covalent inhibitors
  • Hydrogen bond bridges between ligand and protein
  • Strong acids that denature proteins
  • Electron donors for redox reactions only

Correct Answer: Hydrogen bond bridges between ligand and protein

Q27. Which functional group is both a good hydrogen bond donor and acceptor?

  • Alcohol (–OH)
  • Tertiary amine (–NMe2)
  • Alkane (–CH3)
  • Halogen (–Cl)

Correct Answer: Alcohol (–OH)

Q28. Hydrogen bonding can affect a drug’s permeability across lipid membranes by:

  • Enhancing membrane solubility regardless of intramolecular H-bonds
  • Reducing apparent polarity when intramolecular H-bonds form, improving permeability
  • Always blocking membrane passage
  • Transforming into ionic bonds within the membrane

Correct Answer: Reducing apparent polarity when intramolecular H-bonds form, improving permeability

Q29. Which experimental technique can provide direct evidence of hydrogen bonding geometry in crystals?

  • Mass spectrometry
  • X-ray crystallography or neutron diffraction
  • TLC (thin-layer chromatography)
  • UV–visible spectrophotometry only

Correct Answer: X-ray crystallography or neutron diffraction

Q30. Hydrogen bonding contributes to the specificity of drug binding primarily because:

  • It is highly directional and depends on precise atom placement
  • Hydrogen bonds form anywhere without spatial requirements
  • They are non-directional and very weak
  • They always create covalent attachments

Correct Answer: It is highly directional and depends on precise atom placement

Q31. In designing hydrogen bond interactions, replacing an H-bond donor with a bioisostere that preserves H-bonding is useful because:

  • It always reduces activity
  • It can retain binding while improving metabolic stability
  • It converts the drug into a protein
  • It eliminates all polar contacts

Correct Answer: It can retain binding while improving metabolic stability

Q32. Which of the following is true about water displacement from a binding site upon ligand binding?

  • Displacing tightly bound water can be entropically favorable and increase affinity
  • Water displacement is always unfavorable
  • Water cannot be displaced in biological systems
  • Displacement always reduces ligand solubility making binding impossible

Correct Answer: Displacing tightly bound water can be entropically favorable and increase affinity

Q33. A strong hydrogen bond donor in an aromatic heterocycle is typically:

  • Protonated tertiary amine
  • Pyrrole-type NH (e.g., indole NH)
  • Quaternary ammonium salt
  • Perfluorinated alkane chain

Correct Answer: Pyrrole-type NH (e.g., indole NH)

Q34. Which hydrogen bonding pattern stabilizes the alpha-helix?

  • Circular hydrogen bonds between side chains only
  • i → i+4 backbone hydrogen bonds forming a regular helix
  • Random hydrogen bonds between solvent molecules
  • Disulfide bridges locking the helix

Correct Answer: i → i+4 backbone hydrogen bonds forming a regular helix

Q35. What effect does methylation of a hydrogen bond acceptor oxygen typically have?

  • Increases its ability to accept hydrogen bonds
  • Removes or weakens its hydrogen bond acceptor capacity
  • Converts it into a hydrogen bond donor
  • Turns it into a metal-binding site exclusively

Correct Answer: Removes or weakens its hydrogen bond acceptor capacity

Q36. Which of the following best describes a bifurcated hydrogen bond?

  • A single donor forms H-bonds with two acceptors or vice versa
  • A hydrogen bond that is also ionic
  • A bond that only exists at high pressure
  • A bond between three hydrogen atoms

Correct Answer: A single donor forms H-bonds with two acceptors or vice versa

Q37. Why are hydrogen bonds important in determining drug polymorphism?

  • They influence intermolecular recognition and packing arrangements in the crystal lattice
  • Polymorphism is only governed by covalent bonds
  • Hydrogen bonds prevent any crystal formation
  • They only affect solution properties, not solids

Correct Answer: They influence intermolecular recognition and packing arrangements in the crystal lattice

Q38. Which chemical modification can reduce a drug’s hydrogen bond donor count without dramatically changing shape?

  • Conversion of NH to N–Me (methylation)
  • Adding an extra hydroxyl group
  • Introducing a charged carboxylate
  • Incorporating a bulky phenyl ring

Correct Answer: Conversion of NH to N–Me (methylation)

Q39. In protein–ligand binding energetics, hydrogen bonds often contribute mainly to:

  • Only entropic gain
  • Both enthalpic stabilization and entropic penalties due to desolvation
  • Only increasing molecular weight
  • Making binding irreversible

Correct Answer: Both enthalpic stabilization and entropic penalties due to desolvation

Q40. Which is a common geometric criterion used to define a hydrogen bond in structural biology?

  • Donor–acceptor distance less than 3.5 Å and donor–H–acceptor angle >120°
  • Distance greater than 6 Å
  • Any two atoms in a molecule are considered H-bonded
  • Only covalent bond lengths are considered

Correct Answer: Donor–acceptor distance less than 3.5 Å and donor–H–acceptor angle >120°

Q41. Which interaction can sometimes mimic hydrogen bonding in drug design (an H-bond isostere)?

  • Hydrophobic alkyl–alkyl contact
  • Halogen bonding or directed polar interactions like C–H···O
  • Ionic bonding that replaces hydrogen bonds completely
  • Purely steric clash

Correct Answer: Halogen bonding or directed polar interactions like C–H···O

Q42. A ligand that forms multiple strong hydrogen bonds with buried polar residues may suffer from which penalty?

  • High desolvation penalty reducing net binding free energy
  • No change in binding energetics
  • Instant covalent bond formation
  • Improved oral bioavailability by default

Correct Answer: High desolvation penalty reducing net binding free energy

Q43. Which base pairing interaction includes three hydrogen bonds?

  • Adenine–Thymine (A–T)
  • Guanine–Cytosine (G–C)
  • Adenine–Uracil (A–U)
  • Any mismatched pair

Correct Answer: Guanine–Cytosine (G–C)

Q44. In NMR spectroscopy, hydrogen-bonded protons typically appear:

  • More upfield (shielded) than free protons
  • More downfield (deshielded) producing a shifted, often broadened signal
  • As a sharp singlet always at 0 ppm
  • Invisible in all NMR solvents

Correct Answer: More downfield (deshielded) producing a shifted, often broadened signal

Q45. Hydrogen bonding between drug molecules in solution can lead to:

  • Self-association, aggregation or reduced free concentration
  • Complete prevention of absorption always
  • Instant chemical decomposition
  • Guaranteed improved permeability

Correct Answer: Self-association, aggregation or reduced free concentration

Q46. Which of the following is a consequence of strengthening a hydrogen bond by improving geometry in a ligand?

  • Always decreased selectivity
  • Potential increase in binding affinity and specificity
  • Conversion of the ligand into an enzyme
  • Loss of all entropic contributions

Correct Answer: Potential increase in binding affinity and specificity

Q47. Which property of hydrogen bonds makes them reversible and suitable for dynamic biological interactions?

  • Extremely high covalent bond strength
  • Moderate strength and non-covalent, allowing formation and breakage under physiological conditions
  • They are permanent once formed
  • They only occur at absolute zero temperature

Correct Answer: Moderate strength and non-covalent, allowing formation and breakage under physiological conditions

Q48. Which drug design strategy uses hydrogen bonding to improve selectivity among similar targets?

  • Designing ligands to make conserved hydrophobic contacts only
  • Exploiting unique hydrogen bond donors/acceptors in the target’s binding pocket
  • Eliminating all polar groups from the ligand
  • Relying solely on increasing molecular weight

Correct Answer: Exploiting unique hydrogen bond donors/acceptors in the target’s binding pocket

Q49. What is the effect of solvent competition on ligand–protein hydrogen bonds?

  • No effect; solvent cannot compete with protein–ligand H-bonds
  • Solvent (water) can outcompete weak ligand H-bonds, reducing effective binding
  • Solvent converts H-bonds into covalent bonds instantly
  • Solvent only stabilizes ligand in gas phase

Correct Answer: Solvent (water) can outcompete weak ligand H-bonds, reducing effective binding

Q50. Which property is used to estimate the overall hydrogen bonding potential of a drug molecule for permeability predictions?

  • Number of chiral centers only
  • Topological polar surface area (TPSA) and counts of H-bond donors/acceptors
  • Molar mass exclusively
  • Color and odor

Correct Answer: Topological polar surface area (TPSA) and counts of H-bond donors/acceptors

Leave a Comment