Nuclear magnetic double resonance MCQs With Answer

Nuclear magnetic double resonance MCQs With Answer

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Nuclear Magnetic Double Resonance (NMDR) MCQs With Answer for M.Pharm Students

Nuclear magnetic double resonance (NMDR) encompasses a family of NMR methods where two radiofrequency channels manipulate and observe nuclei simultaneously. For pharmaceutical analysis, these techniques are powerful for structural assignment, stereochemical elucidation, sensitivity enhancement, and reliable quantitation. Selective and broadband decoupling, NOE difference spectroscopy, INEPT/DEPT polarization transfer, STD-NMR for ligand–receptor screening, and solid-state SEDOR are among the most useful. This quiz targets practical and mechanistic understanding—how and why we apply double resonance, what parameters matter (power, selectivity, delays), and how data translate into chemical information. Mastery of these concepts helps M.Pharm students connect spectroscopic strategy to confident structure confirmation and interaction studies in modern pharmaceutical analytical techniques.

Q1. What best describes nuclear magnetic double resonance (NMDR) in solution NMR?

  • Application of two RF fields to manipulate one spin species while observing another, enabling decoupling and NOE-based experiments
  • Acquisition of 2D spectra via phase-encoding increments without additional irradiation
  • Purely computational deconvolution of overlapping multiplets
  • Gradient-based coherence selection technique

Correct Answer: Application of two RF fields to manipulate one spin species while observing another, enabling decoupling and NOE-based experiments

Q2. In 13C NMR, what is the key purpose of selective proton decoupling?

  • To collapse only the 13C multiplet associated with the irradiated 1H, aiding direct C–H assignment
  • To remove all 1H couplings from all carbons, maximizing sensitivity
  • To average chemical shift anisotropy in solids
  • To measure long-range heteronuclear coupling constants without ambiguity

Correct Answer: To collapse only the 13C multiplet associated with the irradiated 1H, aiding direct C–H assignment

Q3. What is the primary analytical advantage of off-resonance decoupling in 13C NMR?

  • Multiplets following the n+1 rule that reveal the number of directly attached hydrogens
  • Pure singlets for all carbons, maximizing resolution
  • Broad, noise-like baselines that suppress spinning sidebands
  • Selective enhancement of quaternary carbons only

Correct Answer: Multiplets following the n+1 rule that reveal the number of directly attached hydrogens

Q4. A 1D NOE difference experiment primarily reports on which interaction?

  • Through-space dipolar cross-relaxation with intensity varying approximately as r⁻⁶
  • Through-bond scalar J coupling with intensity varying as J²
  • Chemical exchange line broadening independent of distance
  • Quadrupolar relaxation dominated coupling

Correct Answer: Through-space dipolar cross-relaxation with intensity varying approximately as r⁻⁶

Q5. INEPT is a double-resonance polarization transfer method. Which timing is used to maximize transfer?

  • Delays matched to approximately 1/(4J) per J-evolution period
  • Delays set to the T1 of the observed nucleus
  • Delays equal to the chemical shift difference (Δν) periods
  • No delays; it is a continuous-wave saturation method

Correct Answer: Delays matched to approximately 1/(4J) per J-evolution period

Q6. DEPT is best described as which of the following?

  • A polarization-transfer experiment that differentiates CH, CH2, and CH3 by phase and intensity
  • A 2D exchange spectroscopy method for dynamic processes
  • A selective-decoupling method to measure long-range J couplings only
  • A solid-state technique for spinning sideband suppression

Correct Answer: A polarization-transfer experiment that differentiates CH, CH2, and CH3 by phase and intensity

Q7. For quantitative 13C NMR integrals, which decoupling strategy is most appropriate?

  • Inverse-gated 1H decoupling (decoupler off during relaxation, on only during acquisition)
  • Continuous broadband 1H decoupling throughout the entire experiment
  • No decoupling at any stage
  • Selective 1H decoupling at each individual proton frequency

Correct Answer: Inverse-gated 1H decoupling (decoupler off during relaxation, on only during acquisition)

Q8. In 13C{1H} NMR with steady-state proton decoupling, the heteronuclear NOE typically causes:

  • Positive intensity enhancement for protonated carbons and negligible enhancement for quaternary carbons
  • Negative intensity enhancement for all carbons
  • Equal enhancement for all carbons regardless of protonation
  • Exclusive enhancement of quaternary carbons only

Correct Answer: Positive intensity enhancement for protonated carbons and negligible enhancement for quaternary carbons

Q9. Saturation Transfer Difference (STD)-NMR is particularly useful in drug discovery because it:

  • Saturates receptor/protein resonances and reveals ligand binding epitopes in the difference spectrum
  • Measures scalar coupling constants in small molecules with high precision
  • Quantifies diffusion coefficients without gradients
  • Eliminates line broadening due to exchange by decoupling

Correct Answer: Saturates receptor/protein resonances and reveals ligand binding epitopes in the difference spectrum

Q10. Spin-Echo Double Resonance (SEDOR) is mainly associated with:

  • Solid-state NMR measurements of heteronuclear dipolar couplings via echo dephasing
  • Solution-state J-resolved spectroscopy for small molecules
  • Gradient selection in diffusion-ordered spectroscopy
  • Microwave–RF combined spectroscopy for radicals

Correct Answer: Solid-state NMR measurements of heteronuclear dipolar couplings via echo dephasing

Q11. ENDOR (Electron–Nuclear Double Resonance) is best classified as:

  • An EPR/ESR-based method that probes hyperfine couplings, not a conventional solution NMR experiment
  • A 13C quantitative NMR method for pharmaceutical impurities
  • A 2D NOESY variant for small molecules
  • A water suppression technique in protein NMR

Correct Answer: An EPR/ESR-based method that probes hyperfine couplings, not a conventional solution NMR experiment

Q12. A practical limitation of continuous-wave decoupling in solution NMR is:

  • RF heating and increased sample temperature, mitigated by power management and duty-cycle control
  • Permanent loss of magnetization even after relaxation
  • Inability to decouple heteronuclei at high fields
  • Incompatibility with any broadband pulses

Correct Answer: RF heating and increased sample temperature, mitigated by power management and duty-cycle control

Q13. Homonuclear selective decoupling in 1H NMR accomplishes which outcome?

  • Collapse of multiplets for spins coupled to the irradiated proton, simplifying patterns and aiding J assignment
  • Uniform enhancement of all proton peaks regardless of coupling
  • Reduction of chemical shift dispersion
  • Removal of dipolar couplings in solids

Correct Answer: Collapse of multiplets for spins coupled to the irradiated proton, simplifying patterns and aiding J assignment

Q14. Which statement correctly contrasts decoupling and NOE difference?

  • Decoupling removes scalar J splittings; NOE difference alters intensities via dipolar cross-relaxation without changing J
  • Both remove scalar couplings completely
  • Both rely exclusively on through-bond interactions
  • NOE difference removes scalar couplings; decoupling alters intensities only

Correct Answer: Decoupling removes scalar J splittings; NOE difference alters intensities via dipolar cross-relaxation without changing J

Q15. A standard 1D NOE difference experiment for small molecules is acquired by:

  • Alternating long, low-power on-resonance saturation of a chosen proton with an off-resonance control and subtracting the spectra
  • Applying a single hard 90° proton pulse and acquiring immediately
  • Recording a gradient echo with no selective irradiation
  • Using only broadband decoupling during acquisition

Correct Answer: Alternating long, low-power on-resonance saturation of a chosen proton with an off-resonance control and subtracting the spectra

Q16. How does molecular size affect the sign of 1H–1H NOE in solution?

  • Small molecules give positive NOE; large macromolecules often show negative NOE due to longer correlation times
  • Small molecules give negative NOE; large molecules give positive NOE
  • NOE sign is independent of molecular size
  • NOE is absent in all diamagnetic molecules

Correct Answer: Small molecules give positive NOE; large macromolecules often show negative NOE due to longer correlation times

Q17. Which of the following are established broadband 1H decoupling schemes used in heteronuclear NMR?

  • WALTZ-16, GARP, and MLEV-16 composite decoupling sequences
  • COSY, HSQC, and HMBC
  • NOESY, ROESY, and TOCSY
  • Echo-planar and RARE imaging sequences

Correct Answer: WALTZ-16, GARP, and MLEV-16 composite decoupling sequences

Q18. For selective irradiation (double resonance) that minimizes off-target effects, a best practice is to:

  • Use low-power, long-duration shaped pulses (e.g., Gaussian) centered on the target resonance
  • Use the highest possible RF power and shortest pulse
  • Irradiate at the center of the spectral window regardless of target
  • Use gradients instead of RF irradiation

Correct Answer: Use low-power, long-duration shaped pulses (e.g., Gaussian) centered on the target resonance

Q19. In steady-state 15N{1H} NMR with proton decoupling, the heteronuclear NOE is typically:

  • Negative for protonated nitrogens, often reducing signal intensity relative to quaternary nitrogens
  • Strongly positive for all nitrogens regardless of protonation
  • Zero for all nitrogens due to low gyromagnetic ratio
  • Positive for quaternary nitrogens only

Correct Answer: Negative for protonated nitrogens, often reducing signal intensity relative to quaternary nitrogens

Q20. How can double resonance help analyze a second-order ABX proton pattern in a small molecule?

  • By selectively irradiating one member (A or B), collapsing couplings to reveal simplified patterns and enabling extraction of specific J values
  • By increasing spectral complexity via added couplings
  • By converting the ABX system into a pure singlet
  • By suppressing chemical shift differences entirely

Correct Answer: By selectively irradiating one member (A or B), collapsing couplings to reveal simplified patterns and enabling extraction of specific J values

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