Geometrical isomerism and biological action MCQs With Answer

Geometrical isomerism and biological action MCQs With Answer is a focused review designed for B. Pharm students studying stereochemistry, pharmacology, and drug design. This concise guide explains how cis/trans (E/Z) arrangements around double bonds or in ring systems influence drug–receptor interactions, potency, selectivity, metabolism, toxicity, and physicochemical properties. Key concepts covered include Cahn–Ingold–Prelog (E/Z) rules, spectroscopic identification (NMR, IR), photochemical and catalytic isomerization, examples such as cisplatin and retinoids, and regulatory considerations for drug development. Practical implications for formulation, ADME, and therapeutic outcomes are emphasized. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What defines geometrical isomerism in organic molecules?

• Different molecular formulas with same connectivity
• Same connectivity but different spatial arrangement due to restricted rotation around a bond
• Mirror-image structures that are non-superimposable
• Isomers that differ only by protonation state

Correct Answer: Same connectivity but different spatial arrangement due to restricted rotation around a bond

Q2. Which nomenclature system is used to assign E/Z descriptors to double bonds?

• Cahn–Ingold–Prelog priority rules
• IUPAC cis/trans only
• NMR coupling constants
• Optical rotation

Correct Answer: Cahn–Ingold–Prelog priority rules

Q3. Which metal complex is a clinically active anticancer agent due to its specific geometric isomer?

• Transplatin
• Cisplatin
• Tetrachloroplatinate
• Platinum(IV) oxide

Correct Answer: Cisplatin

Q4. Which of the following pairs are geometric (cis/trans or E/Z) isomers?

• 1,2-Dichloroethene (cis) and 1,2-dichloroethene (trans)
• n-Butane and isobutane
• R- and S- lactic acid
• Ortho- and para-nitrotoluene

Correct Answer: 1,2-Dichloroethene (cis) and 1,2-dichloroethene (trans)

Q5. Which statement best describes the E isomer of a substituted alkene?

• Substituents of higher priority are on the same side of the double bond
• Substituents of higher priority are on opposite sides of the double bond
• The molecule is always more polar than the Z isomer
• E isomer indicates the molecule is chiral

Correct Answer: Substituents of higher priority are on opposite sides of the double bond

Q6. Which spectroscopic parameter is commonly used to distinguish cis and trans alkene protons?

• Carbon-13 chemical shift
• Vicinal 1H–1H coupling constant (J value)
• Mass spectral fragmentation pattern
• Infrared C=O stretching frequency

Correct Answer: Vicinal 1H–1H coupling constant (J value)

Q7. Which physical property commonly differs between geometric isomers and influences formulation?

• Molecular formula
• Number of rotatable bonds
• Dipole moment
• Isotopic composition

Correct Answer: Dipole moment

Q8. Which process can convert an E isomer to a Z isomer under laboratory conditions?

• Simple heating at room temperature without catalyst
• Photochemical (UV) isomerization
• Column chromatography on silica gel only
• Elemental analysis

Correct Answer: Photochemical (UV) isomerization

Q9. Why can geometrical isomers show different biological activity?

• They have different molecular formulas
• Spatial orientation of functional groups affects receptor binding and pharmacophore geometry
• Only one isomer can cross membranes by diffusion
• Isomers change the amino acid sequence of proteins

Correct Answer: Spatial orientation of functional groups affects receptor binding and pharmacophore geometry

Q10. Which analytical technique is most suitable to separate and quantify E/Z isomers of a drug during quality control?

• Polarimetry
• High-performance liquid chromatography (HPLC)
• Elemental analysis
• Simple melting point determination

Correct Answer: High-performance liquid chromatography (HPLC)

Q11. In cyclic compounds, what does the term “cis” indicate about substituent positions?

• Substituents are on opposite faces of the ring
• Substituents are on the same face of the ring
• The substituents are rotated 180 degrees around a single bond
• Substituents are attached to different carbon skeletons

Correct Answer: Substituents are on the same face of the ring

Q12. Which drug is an example of a clinically used geometric isomer: 13-cis-retinoic acid is known as which marketed drug?

• Tretinoin
• Isotretinoin
• All-trans-retinoic acid
• Retinol

Correct Answer: Isotretinoin

Q13. Which alkene is usually more thermodynamically stable?

• Cis (Z) alkene due to higher dipole–dipole interactions
• Trans (E) alkene due to reduced steric hindrance
• Both are equally stable for all substituents
• Alkenes do not have thermodynamic stability differences

Correct Answer: Trans (E) alkene due to reduced steric hindrance

Q14. Geometrical isomers (E/Z) are classified as which type of stereoisomers relative to each other?

• Enantiomers
• Constitutional isomers
• Identical molecules
• Diastereomers

Correct Answer: Diastereomers

Q15. Which coordination geometries in metal complexes commonly exhibit geometric isomerism?

• Tetrahedral only
• Square planar and octahedral
• Linear only
• All coordination geometries equally

Correct Answer: Square planar and octahedral

Q16. Which experimental method gives direct, atomic-level confirmation of a compound’s geometry?

• Thin-layer chromatography
• X-ray crystallography
• UV–Vis absorbance maximum
• Boiling point measurement

Correct Answer: X-ray crystallography

Q17. For 1,2-disubstituted alkenes, which isomer typically has a higher dipole moment?

• Trans (E) isomer
• Cis (Z) isomer
• Both have identical dipole moments
• Dipole moment is undefined for alkenes

Correct Answer: Cis (Z) isomer

Q18. Under physiological conditions (37 °C, aqueous), geometric isomers of a stable alkene usually:

• Rapidly interconvert on the timescale of minutes without catalysis
• Do not interconvert significantly unless catalyzed or photoactivated
• Instantly racemize
• Convert into entirely different constitutional isomers

Correct Answer: Do not interconvert significantly unless catalyzed or photoactivated

Q19. Which of these factors most directly influences how geometric isomers differ in ADME properties?

• Their elemental composition
• Three-dimensional arrangement affecting lipophilicity and receptor interactions
• Total number of electrons
• Their color in solution

Correct Answer: Three-dimensional arrangement affecting lipophilicity and receptor interactions

Q20. Typical vicinal 1H–1H coupling constants (J) for alkene protons are approximately which values for trans and cis respectively?

• Trans ~5 Hz, Cis ~2 Hz
• Trans ~15 Hz, Cis ~10 Hz
• Trans ~0.5 Hz, Cis ~0.2 Hz
• Trans ~50 Hz, Cis ~40 Hz

Correct Answer: Trans ~15 Hz, Cis ~10 Hz

Q21. Which isomer is more likely to engage in intramolecular hydrogen bonding when two functional groups are on adjacent carbons?

• Trans isomer
• Cis isomer
• Neither is capable of hydrogen bonding
• Only racemic mixtures can hydrogen bond intramolecularly

Correct Answer: Cis isomer

Q22. Regulatory agencies require characterization of geometric isomers in drug candidates because:

• Isomers always have identical toxicology profiles
• Different isomers can have different potency, safety, and pharmacokinetics
• Geometrical isomerism changes elemental composition
• It determines the drug’s color

Correct Answer: Different isomers can have different potency, safety, and pharmacokinetics

Q23. Which outcome is NOT caused by geometric isomerism?

• Altered receptor binding and efficacy
• Changes in melting and boiling points
• Change in molecular formula
• Different metabolic pathways

Correct Answer: Change in molecular formula

Q24. Which hydrogenation method is commonly used to synthesize cis (Z) alkenes from alkynes selectively?

• Lindlar catalyst (poisoned Pd)
• Dissolving metal reduction (Na/NH3)
• Complete hydrogenation with Pd/C at high pressure
• Bromination followed by elimination

Correct Answer: Lindlar catalyst (poisoned Pd)

Q25. How can geometric isomerism alter membrane permeability of a drug molecule?

• By changing the elemental composition
• By altering molecular shape and lipophilicity, affecting passive diffusion
• By converting the compound into a polymer
• Membrane permeability is unaffected by geometry

Correct Answer: By altering molecular shape and lipophilicity, affecting passive diffusion

Q26. Which statement about cisplatin’s mechanism is correct and linked to its geometry?

• Cisplatin is inactive because it cannot bind DNA
• Cisplatin forms intra-strand DNA crosslinks due to its cis geometry, causing cytotoxicity
• Transplatin is the main clinical drug and is more active than cisplatin
• Cisplatin acts by inhibiting cell membrane synthesis only

Correct Answer: Cisplatin forms intra-strand DNA crosslinks due to its cis geometry, causing cytotoxicity

Q27. Which method is most appropriate to monitor the E/Z ratio in a reaction mixture in real time?

• FT-IR spectroscopy without any reference
• Gas chromatography (GC) or HPLC with appropriate standards
• Optical rotation for achiral alkenes
• Melting point analysis

Correct Answer: Gas chromatography (GC) or HPLC with appropriate standards

Q28. Which general effect do trans (E) isomers often have compared to cis (Z) isomers regarding packing and melting point?

• Trans isomers pack less efficiently and have lower melting points
• Trans isomers pack more efficiently and often have higher melting points
• Both have identical packing and melting points
• Cis isomers are always solids while trans are liquids

Correct Answer: Trans isomers pack more efficiently and often have higher melting points

Q29. Photostability concerns for drug products relate to geometric isomerism because:

• Light can induce E/Z isomerization, altering potency or safety
• Light always destroys both isomers equally
• Photochemical reactions only affect metals
• Isomerization by light is irrelevant to pharmaceuticals

Correct Answer: Light can induce E/Z isomerization, altering potency or safety

Q30. Which analytical technique would best confirm intramolecular hydrogen bonding differences between cis and trans isomers?

• 1H NMR chemical shift changes with solvent and temperature studies
• Elemental analysis
• Simple thin-layer chromatography without standards
• Refractometry only

Correct Answer: 1H NMR chemical shift changes with solvent and temperature studies

Q31. Trans fatty acids differ from cis fatty acids in that trans fats:

• Introduce kinks into the fatty acid chain increasing fluidity
• Are straighter, resembling saturated fats, and are associated with higher cardiovascular risk
• Are always healthier than cis fats
• Have a different elemental composition than cis fats

Correct Answer: Are straighter, resembling saturated fats, and are associated with higher cardiovascular risk

Q32. Which synthetic method generally yields the thermodynamically favored alkene isomer?

• Kinetic control at low temperature yields thermodynamic product
• Thermal or equilibrium-controlled reactions favor the more stable (usually trans) isomer
• Photochemical reactions always give thermodynamic products
• Any method yields only cis isomer inherently

Correct Answer: Thermal or equilibrium-controlled reactions favor the more stable (usually trans) isomer

Q33. Which statement about geometric isomer characterization in drug dossiers is true?

• Only elemental composition data is required
• Both identity and proportion of geometric isomers must be characterized and controlled
• Manufacturers can ignore minor isomers entirely
• Isomer ratios are irrelevant to bioequivalence

Correct Answer: Both identity and proportion of geometric isomers must be characterized and controlled

Q34. The process of interconverting E and Z isomers typically requires:

• Simple rotation around a single bond without energy input
• Breaking or weakening of the π bond, often via light or catalysis
• Only changing pH in neutral molecules
• Addition of an enantiomeric catalyst

Correct Answer: Breaking or weakening of the π bond, often via light or catalysis

Q35. Which of the following cannot distinguish geometric isomers?

• 1H NMR coupling constants and chemical shifts
• X-ray crystallography
• Elemental analysis (CHNS)
• Chromatographic separation with standards

Correct Answer: Elemental analysis (CHNS)

Q36. Which practical implication of geometric isomerism is most relevant during formulation development?

• Isomeric form can change color but not solubility
• Isomerism affects solubility, stability, and excipient compatibility
• Only the racemate matters for formulation
• Geometrical isomerism is irrelevant for solid dosage forms

Correct Answer: Isomerism affects solubility, stability, and excipient compatibility

Q37. Which isomer of 1,2-dichloroethene has a net dipole moment approaching zero?

• Cis-1,2-dichloroethene
• Trans-1,2-dichloroethene
• Both have identical non-zero dipole moments
• Neither has a dipole moment

Correct Answer: Trans-1,2-dichloroethene

Q38. In drug metabolism, geometric isomerism can affect which of the following?

• Only the elemental composition of metabolites
• Rate of enzymatic oxidation and site-specific metabolism
• Whether the drug becomes a polymer in vivo
• Only the color of urine after administration

Correct Answer: Rate of enzymatic oxidation and site-specific metabolism

Q39. Which reagent/system is known to produce predominantly trans (E) alkenes from alkynes?

• Lindlar catalyst hydrogenation
• Dissolving metal reduction (sodium in liquid ammonia)
• Pd/C full hydrogenation
• Radical bromination only

Correct Answer: Dissolving metal reduction (sodium in liquid ammonia)

Q40. Which pair illustrates that geometric isomers can have different therapeutic uses?

• Isotretinoin (13-cis-retinoic acid) vs tretinoin (all-trans-retinoic acid)
• R-ibuprofen vs S-ibuprofen
• D- and L-glucose
• Sodium chloride vs potassium chloride

Correct Answer: Isotretinoin (13-cis-retinoic acid) vs tretinoin (all-trans-retinoic acid)

Q41. Which property change often explains why cis and trans isomers smell different?

• Different elemental composition causing a new functional group
• Different spatial shape leading to altered interaction with olfactory receptors
• Isomerization always produces toxic smells
• Only chiral centers affect smell

Correct Answer: Different spatial shape leading to altered interaction with olfactory receptors

Q42. During stability testing, observation of a new E/Z ratio suggests what risk for a drug product?

• Potential loss of efficacy or formation of a toxic isomer
• Only cosmetic changes with no clinical implications
• Guaranteed increase in potency
• Elemental composition has changed

Correct Answer: Potential loss of efficacy or formation of a toxic isomer

Q43. Which statement correctly contrasts enantiomers and geometric isomers?

• Enantiomers differ by E/Z descriptors; geometric isomers are mirror images
• Enantiomers are non-superimposable mirror images; geometric isomers are diastereomers differing by restricted rotation
• Both terms mean the exact same thing
• Only enantiomers can affect biological activity

Correct Answer: Enantiomers are non-superimposable mirror images; geometric isomers are diastereomers differing by restricted rotation

Q44. What role do priority rules play in distinguishing cis/trans from E/Z?

• Priority rules are irrelevant for geometric nomenclature
• Cis/trans is simple when identical substituents are present; E/Z uses priority rules for non-identical substituents
• E/Z can be assigned without considering substituent atoms
• Cis/trans and E/Z are always interchangeable

Correct Answer: Cis/trans is simple when identical substituents are present; E/Z uses priority rules for non-identical substituents

Q45. Which practical separation technique exploits small polarity differences between geometric isomers?

• Distillation with no column
• Preparative HPLC or column chromatography with suitable stationary phase
• Simple filtration through cotton wool
• Recrystallization without solvent screening

Correct Answer: Preparative HPLC or column chromatography with suitable stationary phase

Q46. Which statement is correct regarding the thermodynamic vs kinetic control of alkene formation?

• Kinetic control usually yields the most stable (thermodynamic) alkene
• Thermodynamic control favors the more stable (often trans) product, while kinetic control favors the faster-forming product which may be cis
• Kinetic and thermodynamic control refer only to temperature measurement techniques
• Only photochemical reactions show kinetic control

Correct Answer: Thermodynamic control favors the more stable (often trans) product, while kinetic control favors the faster-forming product which may be cis

Q47. Which experimental observation would most directly indicate E/Z isomerization occurred during a photostability test?

• Change in elemental composition by CHN analysis
• Appearance of a new peak and change in peak ratios in HPLC with known standards
• Unchanged HPLC profile
• Only a minor temperature rise in the sample

Correct Answer: Appearance of a new peak and change in peak ratios in HPLC with known standards

Q48. Which of the following is NOT a consequence of geometric isomerism relevant to pharmaceutics?

• Altered pharmacodynamics and receptor selectivity
• Different pharmacokinetics and metabolism
• Change in atomic number of constituent atoms
• Variations in formulation stability and solubility

Correct Answer: Change in atomic number of constituent atoms

Q49. For a drug candidate with an alkene prone to isomerization, which control strategy is most appropriate during formulation?

• Ignore isomerization because it never affects drugs
• Use photostable packaging, antioxidants, and proper pH to minimize isomerization
• Only measure flash point
• Store drug under high-intensity UV light to maintain stability

Correct Answer: Use photostable packaging, antioxidants, and proper pH to minimize isomerization

Q50. In regulatory submissions, should both geometric isomers of a drug be evaluated for safety and efficacy?

• No, only the major isomer needs evaluation
• Yes, both the identity and biological effects of each isomer or isomeric ratio should be evaluated
• Only physical properties are required, not biological effects
• Regulators only require evaluation of racemic mixtures

Correct Answer: Yes, both the identity and biological effects of each isomer or isomeric ratio should be evaluated

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