CHEM 781: Tentative Course outline :

Week 1:

9/3 What is NMR, NMR in the spectrum of spectroscopic methods, description of one nuclear spin

Lab: Basic training on the DPX300 spectrometer.

Week 2:

9/8 Energy levels, Macroscopic magnetization, effect of a radio frequency pulse, rotating frame

9/10 Effect of pulse in rotating frame, concept of coherence, free precession after pulse, creation of oscillating x- and y- magnetization.

Lab1: Introduction to the NMR spectrometer I: optimizing field homogeneity

Week 3:

9/15 spectrometer components (magnet, probe, transmitter, receiver), lock, digitization of signal (Dwell time and dynamic range), quadrature detection, fourier transform, effect of window functions, filters

9/17 Phase errors: zero and first order. Basic relaxation: exponential decay of signal, T₁ vs. T₂, T₂^*. Bloch equations, Ernst angle. Artefact suppression with phase cycling: Signal accumulation vs. artefact subtraction

Lab2: Introduction to the NMR spectrometer II: acquire one pulse experiment, optimize parameters, shimming, understand window functions

Week 4:

9/22 origin of chemical shift: diamagnetic shielding, chemical shift scale, integral and number of protons, structure and electron density effects on shift

9/24 Chemical shift II: ring currents and anisotropy effects of functional groups: aromatics vs. anti aromatics, cyclopropane, olefins, acetylenes, hydrogen bonds. Empirical increment systems

Lab 2 continued

Week 5:

9/29 two spin system: mechanisms of dipolar and indirect spin spin coupling, first order spectra, connectivity and multiplicity

10/1 coupling constants and structure: ¹J_CH, ²J_HH, ³J_HH: cis/trans isomers, Karplus equation. NMR and symmetry: enantiomers, prochiral centers.

Lab3: Acquire 1D ¹H and ¹³C spectra of simple unknown: Strategy of structure elucidation, double bond equivalents. Relaxation delay and integrals. Determine structure using chemical shift and multiplet information, increment calculation

Week 6:

10/6 In class presentations: 1H NMR without deuterated solvent (Eric Bloch) / Analyzing multiplet patterns (Tang Xiong)

10/8 Decoupling in carbon spectra: Use of 180 pulses for decoupling. Decoupling schemes (WALTZ, GARP, MLEV) . Decoupling and NOE: Cross relaxation and signal enhancement, gated decoupling, inverse gated decoupling schemes

Week 7:

10/13 Spectral editing using spin echo techniques, building blocks for pulse sequences. Magnetization transfer and signal enhancement: SPT, INEPT experiments. Refocused INEPT and editing

10/15 In Class Presentation: Use of Deuterium Isotope shifts (Nathalia Stein) Lecture: Concept of product operators related to vector picture, basic rotations summary, DEPT experiment.

Lab 4: Heteronuclear double resonance experiments (one pulse, decoupled, gated decoupled, APT, DEPT)

Week 8:

10/20 In Class Presentations: Binding Constants by NMR using chemical shift change (Robert Hoppe) / Sensitivity enhancement of low- nuclei (Adam Nothnagel)

10/20 The second dimension: Components excitation, evolution, mixing, detection. Quadrature detection in the indirect dimension. Example exchange, application to C-H correlation using INEPT mixing.

10/22 Sensitivity of Inverse vs. direct detection. HSQC and HMQC. Editing in HSQC. Suppression of ¹H-¹²C signal.

Lab 5: Structure determination/assignment of a compound of medium complexity

A: 1D methods + CH correlation

Week 9:

10/27 In class presentations: Application of ¹⁵N correlation spectroscopy (Cory Hawkins)/ Measuring Dipolar Coupling constants in Solution (Alan Pawlak)

10/29 Connectivity: Proton-proton COSY. Long range correlations through CH couplings: HMBC.

Lab5: Structure determination/assignment of a compound of medium complexity

B: connecting groups with COSY and HMBC

Week 10:

11/3 Splitting patterns in 2D spectra. Passive coupling in HMQC spectra. Measuring coupling constants fro DQF-COSY or PE. COSY.

11/5 NOE and distance. 1D NOE experiment, 2D NOESY and EXSY. Large vs. small molecules. ROESY

Lab 5: continued

Week 11:

11/10 Additional experiments: TOCSY for total correlation of spin system. INADEQUATE, ADEQUATE for C-C connectivity.

11/12 NMR and dynamics: fast vs. slow exchange saturation transfer, EXSY. Chemical exchange and lineshape

Lab 6: Conformational analysis using PE COSY and NOESY / 1D NOE (continued)

Week 12:

11/17 Relaxation and dynamics. Measurement of relaxation times: direct or indirect. Application to molecular dynamics.

11/19 field gradients vs. phase cycling: solvent suppression and filter. Composite pulses, selective excitation

Lab 6: Conformational analysis using PE COSY and NOESY / 1D NOE (continued)

Week 13

11/24 Student Presentations: Automated Structure elucucation (Uddin Nazim)/ Parahydrogen Induced polarization (Richard Sniatynsky)

11/26 No Class

Week 14:

12/1 Combining sequences: HSQC-TOCSY, 3D NMR. Labeled molecules, protein techniques.

12/3: other nuclei: quadrupolar nuclei, NMR of metals and coupling to metals. Periodic table of NMR

Lab 7: Water suppression and selective pulses.

Week 15:

12/8 State of the art of solution NMR and exotica: Problems at highest field, TROSY, coupling through hydrogen bonds, para hydrogen.

12/10 NMR in paramagnetic compounds: paramagnetic shift, complementary ESR-NMR