Complexation – introduction MCQs With Answer

Complexation – introduction MCQs With Answer

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Complexation – introduction MCQs With Answer

Complexation is a pivotal concept in pharmaceutics involving reversible association between drug molecules and ligands or host molecules to form defined complexes. For B.Pharm students, mastering types of complexation—coordination complexes, chelates, and inclusion complexes like cyclodextrins—along with stoichiometry, formation (stability) constants, kinetics, and thermodynamics is essential for enhancing solubility, stability, bioavailability, and targeted delivery. This introduction highlights core principles, analytical techniques (Job’s method, phase-solubility studies, spectrophotometry, potentiometry, NMR), and formulation applications to help interpret experimental data and optimize drug design. Focused understanding of complexation strengthens formulation strategy and exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is complexation in pharmaceutics?

  • An irreversible chemical reaction forming a new covalent drug
  • A reversible association between a drug and a ligand or host
  • A process that always decreases drug solubility
  • A method to esterify drugs for prodrug formation

Correct Answer: A reversible association between a drug and a ligand or host

Q2. Which of the following best describes a chelate?

  • A monodentate ligand bound to a metal ion
  • A ligand that forms multiple bonds to a single metal ion creating a ring
  • An inclusion complex formed by cyclodextrin encapsulation
  • A covalently bonded metal-organic framework

Correct Answer: A ligand that forms multiple bonds to a single metal ion creating a ring

Q3. Which parameter quantifies the stability of a complex?

  • Partition coefficient (log P)
  • Stability or formation constant (Kf)
  • Minimum inhibitory concentration (MIC)
  • Retention factor (Rf)

Correct Answer: Stability or formation constant (Kf)

Q4. The general expression for a 1:1 complex formation constant Kf is:

  • Kf = [M][L] / [ML]
  • Kf = [ML] / ([M][L])
  • Kf = [M] + [L] / [ML]
  • Kf = [ML] × [M][L]

Correct Answer: Kf = [ML] / ([M][L])

Q5. Inclusion complexes in pharmaceutics commonly involve which host molecule?

  • Sodium chloride
  • Cyclodextrins
  • Polyvinyl alcohol
  • EDTA

Correct Answer: Cyclodextrins

Q6. Job’s method (method of continuous variations) is used to determine:

  • The pH of maximum solubility
  • The stoichiometry of a complex
  • The rate constant of complex formation
  • The melting point of a complex

Correct Answer: The stoichiometry of a complex

Q7. Phase-solubility analysis primarily assesses:

  • Thermal stability of a drug
  • Variation of drug solubility with ligand concentration
  • Permeability across biological membranes
  • Color change during complexation

Correct Answer: Variation of drug solubility with ligand concentration

Q8. A higher magnitude of Kf indicates:

  • Less stable complex
  • More stable complex
  • No complex formation
  • Faster complex decomposition

Correct Answer: More stable complex

Q9. Which analytical technique can directly assess metal–ligand binding stoichiometry and environment?

  • Mass spectrometry only
  • Nuclear magnetic resonance (NMR)
  • Flame photometry only
  • Thin layer chromatography

Correct Answer: Nuclear magnetic resonance (NMR)

Q10. EDTA is commonly used in formulations as a:

  • Surfactant
  • Chelating agent to sequester metal ions
  • Primary solvent
  • Flavoring agent

Correct Answer: Chelating agent to sequester metal ions

Q11. In a 1:2 metal:ligand complex (M:L2), the overall formation constant β2 relates to:

  • β2 = [M][L]^2 / [ML2]
  • β2 = [ML2] / ([M][L]^2)
  • β2 = [ML] / ([M][L])
  • β2 = [ML2]^2 / ([M][L])

Correct Answer: β2 = [ML2] / ([M][L]^2)

Q12. Which factor commonly decreases complex formation between a drug and metal ion?

  • Appropriate ligand denticity
  • High competing ion concentration
  • Optimal pH for complexation
  • Presence of a strong chelator

Correct Answer: High competing ion concentration

Q13. Cyclodextrin complexation usually enhances drug properties by:

  • Degrading the drug molecule
  • Increasing aqueous solubility and stability
  • Generating covalent drug–carrier bonds
  • Reducing molecular weight

Correct Answer: Increasing aqueous solubility and stability

Q14. In drug–cyclodextrin inclusion complexes, the drug typically locates:

  • On the exterior hydrophilic surface
  • Inside the hydrophobic cavity of cyclodextrin
  • Covalently attached to cyclodextrin rim
  • Between two stacked cyclodextrins only

Correct Answer: Inside the hydrophobic cavity of cyclodextrin

Q15. Which statement differentiates chelation from simple complexation?

  • Chelation involves monodentate ligands only
  • Chelation forms ring structures with multidentate ligands increasing complex stability
  • Simple complexation always forms covalent bonds
  • Chelation decreases affinity for metal ions compared to monodentate binding

Correct Answer: Chelation forms ring structures with multidentate ligands increasing complex stability

Q16. Spectrophotometric titration to study complexation relies mainly on:

  • Electrical conductivity changes
  • Absorbance changes due to complex formation
  • Changes in melting point
  • Mass change upon evaporation

Correct Answer: Absorbance changes due to complex formation

Q17. Which pH-related effect commonly influences metal–ligand complex stability?

  • pH does not affect complexes
  • Protonation of ligand donor atoms reduces binding
  • Lower pH always increases binding constant
  • Only temperature affects stability

Correct Answer: Protonation of ligand donor atoms reduces binding

Q18. A 1:1 complex shows which phase-solubility profile according to Higuchi and Connors?

  • AL-type linear increase indicating 1:1 complex
  • AP-type precipitation
  • BS-type complex with slope >1
  • Undefined profile unrelated to stoichiometry

Correct Answer: AL-type linear increase indicating 1:1 complex

Q19. In potentiometric titration for complex formation, the electrode monitors:

  • Light scattering from complexation
  • pH or potential changes related to free metal or ligand
  • Viscosity changes
  • Chromatographic retention time

Correct Answer: pH or potential changes related to free metal or ligand

Q20. Which is true about kinetics versus thermodynamics in complexation?

  • Thermodynamics predicts speed of complex formation
  • Kinetics determines whether a complex is ultimately favored at equilibrium
  • Thermodynamics indicates stability at equilibrium; kinetics indicates rate of formation
  • Kinetics and thermodynamics are identical concepts

Correct Answer: Thermodynamics indicates stability at equilibrium; kinetics indicates rate of formation

Q21. Which ligand is bidentate?

  • Water
  • Ethylenediamine (en)
  • Chloride ion
  • Sodium ion

Correct Answer: Ethylenediamine (en)

Q22. The primary pharmaceutical benefit of forming a metal–drug chelate may be:

  • Increasing drug molecular weight drastically
  • Reducing metal-catalyzed degradation of the drug
  • Converting drug into a prodrug always
  • Making the drug non-bioavailable

Correct Answer: Reducing metal-catalyzed degradation of the drug

Q23. Which statement is correct about host–guest complexation?

  • Host–guest complexes always involve covalent bonding
  • They involve non-covalent interactions like hydrogen bonding, Van der Waals forces, and hydrophobic effects
  • They only occur in gaseous phase
  • Guest molecules are chemically transformed by the host

Correct Answer: They involve non-covalent interactions like hydrogen bonding, Van der Waals forces, and hydrophobic effects

Q24. In titration to determine Kf, a departure from linearity in Job’s plot indicates:

  • Instrumental failure only
  • The stoichiometry of the complex corresponds to the maximum point
  • No complexation occurs at any ratio
  • That phase-solubility cannot be performed

Correct Answer: The stoichiometry of the complex corresponds to the maximum point

Q25. Which method can provide direct thermodynamic parameters (ΔH, ΔS) for complexation?

  • Isothermal titration calorimetry (ITC)
  • Thin layer chromatography
  • Optical microscopy
  • Ultracentrifugation

Correct Answer: Isothermal titration calorimetry (ITC)

Q26. A ligand that donates two pairs of electrons to a metal is called:

  • Monodentate
  • Bidentate
  • Tridentate
  • Ambidentate

Correct Answer: Bidentate

Q27. Which property of cyclodextrins is most important for inclusion complex formation?

  • Hydrophobic interior and hydrophilic exterior
  • High acidity
  • Covalent reactivity
  • High crystallinity only

Correct Answer: Hydrophobic interior and hydrophilic exterior

Q28. Masking agents are used to:

  • Enhance the flavor of drugs
  • Sequester interfering metal ions in analytical assays
  • Decrease drug solubility intentionally
  • Convert drugs into ionic forms

Correct Answer: Sequester interfering metal ions in analytical assays

Q29. Which is a common effect of complexation on drug absorption?

  • Always decreases absorption
  • May increase absorption by enhancing solubility or decrease it by preventing permeation
  • Eliminates first-pass metabolism entirely
  • Has no effect on permeability or solubility

Correct Answer: May increase absorption by enhancing solubility or decrease it by preventing permeation

Q30. Which factor favors formation of a metal–ligand complex?

  • High protonation of ligand donor atoms
  • Presence of competing strong acids
  • Appropriate donor atom type and geometry complementarity
  • Very low ligand concentration always

Correct Answer: Appropriate donor atom type and geometry complementarity

Q31. In a competitive complexation assay, a decrease in signal indicates:

  • Formation of free ligand only
  • Displacement of reporter by the analyte forming a new complex
  • Destruction of the instrument
  • No binding interactions at all

Correct Answer: Displacement of reporter by the analyte forming a new complex

Q32. Which of the following is NOT typically a ligand donor atom?

  • Nitrogen
  • Oxygen
  • Carbon of an aromatic ring without activation
  • Sulfur

Correct Answer: Carbon of an aromatic ring without activation

Q33. The Henderson-Hasselbalch equation is useful in complexation studies to:

  • Calculate partition coefficients directly
  • Estimate the degree of ionization of ligands affecting binding
  • Measure the kinetic rate constant
  • Determine molecular weight of complexes

Correct Answer: Estimate the degree of ionization of ligands affecting binding

Q34. Which analytical technique is most useful for determining molecular mass of noncovalent complexes?

  • Electrospray ionization mass spectrometry (ESI-MS)
  • Infrared spectroscopy only
  • Ultraviolet light microscopy
  • Paper chromatography

Correct Answer: Electrospray ionization mass spectrometry (ESI-MS)

Q35. Which description fits an AL-type phase-solubility diagram?

  • Linear increase in drug solubility with added complexing agent
  • Initial rise then plateau due to precipitation
  • No change in solubility
  • Negative slope indicating decreased solubility

Correct Answer: Linear increase in drug solubility with added complexing agent

Q36. Which term describes host–guest complexes stabilized primarily by hydrophobic interactions?

  • Coordination complexes
  • Inclusion complexes
  • Ionic salts
  • Covalent adducts

Correct Answer: Inclusion complexes

Q37. In chelation therapy, chelators remove toxic metals by:

  • Converting metals into gaseous form
  • Forming soluble chelate complexes that are excreted
  • Biotransforming metals into nutrients
  • Adsorbing metals onto skin

Correct Answer: Forming soluble chelate complexes that are excreted

Q38. Which is an example of a pharmaceutical application of complexation?

  • Using EDTA to stabilize formulations against metal-catalyzed oxidation
  • Using complexation to increase drug melting point only
  • Using complexation to eliminate solubility entirely
  • Avoiding any cyclodextrin in oral products

Correct Answer: Using EDTA to stabilize formulations against metal-catalyzed oxidation

Q39. A ligand with multiple binding sites that can wrap around a metal is called:

  • Monodentate ligand
  • Polydentate or multidentate ligand
  • Counter ion
  • Hydrogen bond donor only

Correct Answer: Polydentate or multidentate ligand

Q40. Which effect is most likely when a drug forms a strong complex with plasma proteins or metals?

  • Increased free drug concentration
  • Decreased free (pharmacologically active) drug concentration
  • Instantaneous elimination of drug
  • Complete chemical degradation

Correct Answer: Decreased free (pharmacologically active) drug concentration

Q41. Which technique can provide information about complex geometry and electronic environment?

  • UV-Vis spectroscopy only
  • X-ray crystallography
  • Paper chromatography
  • Simple pH measurement

Correct Answer: X-ray crystallography

Q42. For a drug that is weakly basic, complexation with cyclodextrin will most likely:

  • Decrease its aqueous solubility at all pH
  • Increase apparent solubility by including the neutral or charged form
  • Convert it into a strong acid
  • Prevent absorption due to covalent binding

Correct Answer: Increase apparent solubility by including the neutral or charged form

Q43. Which statement about formation constant (Kf) and biological relevance is correct?

  • Very high Kf always guarantees better therapeutic effect
  • Appropriate Kf is required: too low gives dissociation, too high may prevent release
  • Kf has no effect on drug release or bioavailability
  • Lower Kf values always improve drug targeting

Correct Answer: Appropriate Kf is required: too low gives dissociation, too high may prevent release

Q44. A drug that complexes strongly with metal ions in the gastrointestinal tract may show:

  • Increased oral bioavailability due to enhanced permeation
  • Reduced absorption due to insoluble complexes
  • No change in pharmacokinetics
  • Immediate enzymatic activation

Correct Answer: Reduced absorption due to insoluble complexes

Q45. Which descriptor refers to ligand ability to form stable complexes by chelate effect?

  • Monodenticity
  • Multidenticity
  • Hydrophobicity only
  • Acidity only

Correct Answer: Multidenticity

Q46. Which analysis helps determine binding constants from UV-Vis data?

  • Benesi–Hildebrand method
  • Gel permeation chromatography
  • Thermogravimetric analysis
  • Kjeldahl method

Correct Answer: Benesi–Hildebrand method

Q47. Which of the following is an advantage of forming drug–cyclodextrin complexes for topical formulations?

  • Increased local irritation always
  • Improved drug solubility and reduced local irritation
  • Complete prevention of skin permeation
  • Formation of irreversible covalent adducts with skin proteins

Correct Answer: Improved drug solubility and reduced local irritation

Q48. In metal analysis, masking agents are used to:

  • Enhance colorimetric response of all metals
  • Temporarily complex specific interfering metal ions
  • Precipitate metals for gravimetric analysis only
  • Convert metals into gaseous species

Correct Answer: Temporarily complex specific interfering metal ions

Q49. Which factor is least likely to be changed by complexation?

  • Drug intrinsic chemical structure (covalent backbone)
  • Aqueous solubility
  • Permeability
  • Stability against degradation

Correct Answer: Drug intrinsic chemical structure (covalent backbone)

Q50. Which concept explains why multidentate ligands form more stable complexes than equivalent monodentate ligands?

  • Increased entropic favorability and chelate effect
  • Lower coordination number only
  • They form covalent bonds instead of coordinate bonds
  • They change the metal to nonmetal

Correct Answer: Increased entropic favorability and chelate effect

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