CHEM 781: Tentative Course outline

Week 1:

  • 9/4 What is NMR, introduction to nuclear spin and spin of complex nuclei, Spin magnetic moment, Energy levels
  • 9/6 Macroscopic magnetization, effect of a radio frequency pulse, rotating frame, Effect of pulse in rotating frame, Concept of coherence, free precession after pulse, relaxation of magnetization Basic relaxation: exponential decay of signal, T1 vs. T2, T2*. Bloch equations

Week 2:

  • 9/11 Spectrometer components (magnet, probe, transmitter, receiver). Digitization of signal (Dwell time and dynamic range), quadrature detection, fourier transform, effect of window functions, filtersPhase errors: zero and first order. Artefact suppression with phase cycling: Signal accumulation vs. artefact subtraction
  • 9/13 Lab1: Introduction to the NMR spectrometer part1 I: optimizing field homogeneity and pulse length

Week 3:

  • 9/18     Field Gradients: Introduction and use for artefact removal, outline of other uses. Chemical shift: macroscopic vs. microscopic shielding, chemical shift scale, integral and number of protons, structure and electron density effects on shift, ring currents and anisotropy effects of functional groups: aromatics vs. anti aromatics, cyclopropane, olefins, acetylenes. systems
  • 9/20 Lab1 : Introduction to the NMR spectrometer part II: Effect of receiver gain, digital resolution and truncation, understand window functions

Week 4:

  • 9/25 Chemical shift (cont.):Effect of hydrogen bonds on chemical shift, Empirical methods of estimating chemical shift NMR and symmetry: Enantiomers vs diastereomers, diastereotopic atoms.
    Spin-Spin coupling:Two spin system: mechanisms of dipolar and indirect spin spin coupling
  • 9/27 Lab 2: Quantitative NMR: Determine alcohol concentration in a sample of wine: Run spectrum on sample without deuterated solvent, obtain accurate integrations.

Week 5:

  • 10/2 first order spectra, connectivity and multiplicity coupling constants and structure: 1JCH, 2JHH,3JHH. 3JHH: cis/trans isomers, Karplus equation. Vector picture of coupled spins. Decoupling in carbon spectra: Use of 180 pulses for decoupling. Decoupling schemes (WALTZ, GARP, MLEV) .
  • 10/4 Lab 3: Small molecule Structure: Manual, database based and automated analysis

Week 6:

  • 10/9 Decoupling and Intensity: Cross relaxation and signal enhancement by NOE, gated decoupling, inverse gated decoupling schemes. Spectral editing using spin echo techniques, building blocks for pulse sequences. Magnetization transfer and signal enhancement: SPT, INEPT experiments. Refocused INEPT and editing. DEPT experiment.
  • 10/11 Student Presentations:
    1. 1H-NMR without deuterated solvents: Reaction monitoring and reagent analysis
    2. Analyzing multiplet patterns
    3. Use of Deuterium Isotope shifts
    4. Quantitative C-13 NMR: Compound Ratios and Polymer endgroups.

Week 7:

  • 10/16 The second dimension: Components excitation, evolution, mixing, detection. Example INEPT mixing, application to C-H correlation. Sensitivity of Inverse vs. direct detection. HSQC and HMQC. Editing in HSQC.
  • 10/18 Lab 4: Heteronuclear double resonance experiments (one pulse, decoupled, gated decoupled, APT, DEPT)

Week 8:

  • 10/23 Suppression of 1H-12C signal and use of gradients. Quadrature detection in the indirect dimension. Connectivity: Proton-proton COSY. Example Menthol
  • 10/25 Student presentations:
    1. Determination of Enantiomeric excess by 13C NMR
    2. Application of 15 N correlation spectroscopy I
    3. Application of 15 N correlation spectroscopy II
    4. Measuring Binding Constants by NMR using chemical shift change

Week 9:

  • 10/30 Long range correlations through CH couplings by HMBC. TOCSY and INADEQUATE/ADEQUATE experiments. Composite sequences: HSQC TOCSY and 3D NMR.
  • 11/1 Lab 4: Structure of a compound of medium complexity: 1D methods + CH correlation.

Week 10:

  • 11/6 Operators for two spin systerm. Splitting patterns in 2D spectra. Passive coupling in HMQC spectra. Measuring coupling constants fro DQF-COSY or PE. COSY.
  • 11/8 Lab 5: Structure of a compound of medium complexity: Assignment using COSY and HMBC spectra. Use of CMC-se for automated assignment.

Week 11:

  • 11/13 NOE and distance. 1D NOE experiment, 2D NOESY. Example Camphour. Large vs. small molecules. ROESY for intermediate molecular sizes.
  • 11/15 Student Presentations:
    1. Automated structure elucidation
    2. Dipolar Coupling constants in Solution
    3. Diffusion Coefficient and Molecular weight by 31P-NMR

    Lab 5: (continued)

Week 12:

  • 11/20 Structure determination of biopolymers. Introduction to relaxation. Dipolar relaxation and distance. T1 vs. T2. Relaxation mechanisms and Cross correlated relaxation. Application TROSY.
  • 11/22 No class

Week 13

  • 11/27 NMR and dynamics: Relaxation and dynamics. Lineshape and Chemical exchange. Exchange and Magnetization Transfer.
  • 11/29 Lab 6: Conformational analysis using PE COSY and NOESY / 1D NOE

Week 14:

  • 12/4 Enhancing Sensitivity: Non Boltzmann populations: DNP, CIDNP and PHINP.
  • 12/6: Lab 6 continued.

Week 15:

  • 12/11 ESR and NMR of paramagnetic molecules.