Applications of NMR spectroscopy MCQs With Answer

Applications of NMR spectroscopy MCQs With Answer

Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy is a cornerstone technique in pharmaceutical analysis, offering detailed information about molecular structure, dynamics, purity and interactions. For M.Pharm students, mastering NMR applications is essential for drug characterization, impurity profiling, polymorph analysis, ligand-binding studies and quantitative determinations. This quiz set focuses on advanced, application-oriented concepts such as 2D and solid‑state NMR, quantitative NMR (qNMR), relaxation phenomena, diffusion‑based methods, and specialized experiments used in medicinal chemistry and formulation science. The questions are designed to reinforce practical understanding and prepare students for real‑world instrumental analysis in pharmaceutical research and quality control.

Q1. Which of the following is the primary application of high-resolution NMR spectroscopy in small-molecule pharmaceuticals?

• Molecular structure elucidation and stereochemical assignment
• Elemental composition analysis by mass-to-charge ratios
• Quantification of trace metals in formulations
• Determination of particle size distribution

Correct Answer: Molecular structure elucidation and stereochemical assignment

Q2. Which two-dimensional NMR experiment is best for observing direct one‑bond 1H–13C correlations?

• HSQC (Heteronuclear Single Quantum Coherence)
• HMBC (Heteronuclear Multiple Bond Correlation)
• COSY (Correlation Spectroscopy)
• NOESY (Nuclear Overhauser Effect Spectroscopy)

Correct Answer: HSQC (Heteronuclear Single Quantum Coherence)

Q3. HMBC is particularly useful in structure elucidation because it provides which type of correlation?

• Long‑range (2–3 bond) heteronuclear 1H–13C correlations
• Direct one‑bond 1H–13C correlations only
• Through‑space dipolar correlations
• Coupling constant measurements between protons

Correct Answer: Long‑range (2–3 bond) heteronuclear 1H–13C correlations

Q4. What is the primary application of DOSY (Diffusion-Ordered Spectroscopy) in pharmaceutical mixtures?

• Measurement of diffusion coefficients to distinguish components in mixtures
• Direct measurement of coupling constants for conformational analysis
• Enhancement of sensitivity for low‑abundance nuclei
• Determination of absolute stereochemistry

Correct Answer: Measurement of diffusion coefficients to distinguish components in mixtures

Q5. Magic Angle Spinning (MAS) reduces anisotropic broadening in solid‑state NMR by spinning the sample at which angle relative to B0?

• 54.74°
• 45°
• 90°
• 30°

Correct Answer: 54.74°

Q6. For accurate quantitative NMR (qNMR), which acquisition parameter is most critical to ensure integrals reflect molar amounts?

• Relaxation delay at least 5 × longest T1 of nuclei
• Use of proton decoupling during acquisition
• Maximum number of scans irrespective of relaxation
• Always using a 30° pulse to save time

Correct Answer: Relaxation delay at least 5 × longest T1 of nuclei

Q7. Which solid‑state NMR technique is commonly used to improve sensitivity and resolution for pharmaceutical solids (polymorphs, formulations)?

• CP/MAS (Cross Polarization with Magic Angle Spinning)
• HSQC
• COSY
• NOESY

Correct Answer: CP/MAS (Cross Polarization with Magic Angle Spinning)

Q8. Nuclear Overhauser Effect (NOE) measurements are used in structure determination primarily to provide what information?

• Through‑space distance constraints (typically up to ~5 Å)
• Scalar coupling constants between bonded atoms
• Absolute atomic masses
• Diffusion coefficients of molecules

Correct Answer: Through‑space distance constraints (typically up to ~5 Å)

Q9. Which NMR technique is widely used in fragment‑based drug discovery to identify weak-binding ligands to a target protein?

• STD NMR (Saturation Transfer Difference)
• DEPT
• HMBC
• DOSY

Correct Answer: STD NMR (Saturation Transfer Difference)

Q10. Which instrumental change most directly improves intrinsic NMR sensitivity for detecting low‑abundance nuclei?

• Using a higher static magnetic field strength
• Increasing the number of scans only
• Shortening the relaxation delay arbitrarily
• Decreasing sample temperature without probe modification

Correct Answer: Using a higher static magnetic field strength

Q11. DEPT (Distortionless Enhancement by Polarization Transfer) experiments in 13C NMR are used to:

• Differentiate carbon types: CH, CH2, and CH3
• Measure diffusion coefficients for carbon atoms
• Provide long‑range 13C–1H correlations
• Directly observe quaternary carbons with highest sensitivity

Correct Answer: Differentiate carbon types: CH, CH2, and CH3

Q12. In qNMR an internal standard should ideally have which properties?

• Chemically inert, stable, non‑overlapping signal and known purity
• Strong paramagnetism to shorten relaxation times
• High molecular weight polymer to minimize volatility
• Multiple overlapping resonances with analyte peaks

Correct Answer: Chemically inert, stable, non‑overlapping signal and known purity

Q13. Which pulse sequence is routinely used to measure longitudinal relaxation time T1?

• Inversion‑recovery experiment
• Spin‑echo (Hahn) experiment
• DEPT‑135
• Gradient‑selected COSY

Correct Answer: Inversion‑recovery experiment

Q14. What is the primary cause of increased line broadening in NMR spectra of viscous formulations or large biomolecules?

• Short transverse relaxation time T2 (fast spin‑spin relaxation)
• Long longitudinal relaxation time T1
• Increased scalar J-coupling values
• Excessive decoupling power applied during acquisition

Correct Answer: Short transverse relaxation time T2 (fast spin‑spin relaxation)

Q15. HSQC commonly correlates which pair of nuclei for structural assignment?

• One‑bond 1H–13C correlations (heteronuclear single quantum coherence)
• Long‑range 1H–13C correlations across 3 bonds
• Through‑space 1H–1H correlations
• 13C–13C one‑bond correlations only

Correct Answer: One‑bond 1H–13C correlations (heteronuclear single quantum coherence)

Q16. Variable‑temperature NMR experiments are most useful in pharmaceuticals for studying which phenomenon?

• Conformational exchange rates and activation barriers (kinetics)
• Elemental impurities such as heavy metals
• Absolute molecular weight determination by integration
• Routine quantification of excipient content at room temperature

Correct Answer: Conformational exchange rates and activation barriers (kinetics)

Q17. Lanthanide shift reagents and chiral solvating agents in NMR are primarily applied to:

• Induce chemical shift differences between enantiomers for chiral discrimination
• Increase signal intensity of quaternary carbons by decoupling
• Measure diffusion coefficients more accurately
• Stabilize proteins against thermal denaturation during NMR

Correct Answer: Induce chemical shift differences between enantiomers for chiral discrimination

Q18. Which analytical technique is complementary to powder X‑ray diffraction for identifying pharmaceutical polymorphs and assessing local chemical environments?

• Solid‑state NMR (ssNMR)
• HPLC with UV detection
• Liquid‑state 1H NMR in CDCl3 only
• Infrared spectroscopy without solid sampling accessories

Correct Answer: Solid‑state NMR (ssNMR)

Q19. INEPT (Insensitive Nuclei Enhanced by Polarization Transfer) is used in heteronuclear experiments to:

• Enhance sensitivity by polarization transfer from 1H to low‑γ nuclei (e.g., 13C, 15N)
• Measure through‑space NOE contacts exclusively
• Suppress solvent signals without gradients
• Provide long‑range 1H–1H coupling constants

Correct Answer: Enhance sensitivity by polarization transfer from 1H to low‑γ nuclei (e.g., 13C, 15N)

Q20. For obtaining medium‑range (≤5 Å) interproton distances to build 3D structures of small molecules or peptides in solution, which NMR experiment is most appropriate?

• NOESY (Nuclear Overhauser Effect Spectroscopy)
• COSY
• HSQC
• HMBC

Correct Answer: NOESY (Nuclear Overhauser Effect Spectroscopy)

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