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| CHEMISTRY 781: Nuclear Magnetic Resonance Spectroscopy: Theory and Practice (Semester 1, Fall 2004) |
CHEM 781: Tentative Course outlineWeek 1: 9/2 What is NMR, NMR in the spectrum of spectroscopic methods, description of one nuclear spin 9/7 Energy levels, Macroscopic magnetization, effect of a radio frequency pulse, rotating frame
Lab: Basic training on the DPX300 spectrometer.
Week 2: 9/9 Effect of pulse in rotating frame, concept of coherence, free precession after pulse, creation of oscillating x- and y- magnetization. 9/14 spectrometer components (magnet, probe, transmitter, receiver), lock, digitization of signal (Dwell time and dynamic range), quadrature detection, fourier transform, effect of window functions, filters Lab1: Introduction to the NMR spectrometer: acquire one pulse experiment, optimize parameters, shimming, understand window functions Week 3: 9/16 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 9/21 origin of chemical shift: diamagnetic shielding, chemical shift scale, integral and number of protons, structure and electron density effects on shift Lab1: Continue Week 4: 9/23 Chemical shift II: ring currents and anisotropy effects of functional groups: aromatics vs. anti aromatics, cyclopropane, olefins, acetylenes, hydrogen bonds. Empirical increment systems 9/28 two spin system: mechanisms of dipolar and indirect spin spin coupling, first order spectra, connectivity and multiplicity Lab2: Acquire 1D 1H and 13C spectra of simple unknown: Strategy of structure elucidation, double bond equivalents. Determine structure using chemical shift and multiplet information, increment calculation Week 5: 9/30 coupling constants and structure: 1JCH, 2JHH, 3JHH: cis/trans isomers, Karplus equation. coupling through hydrogen bonds NMR and symmetry: enantiomers, prochiral centers. 10/5 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 6: 10/7 Spectral editing using spin echo techniques, building blocks for pulse sequences. Magnetization transfer and signal enhancement: SPT, INEPT experiments. Refocused INEPT and editing 10/12 Concept of product operators related to vector picture, basic rotations summary, DEPT experiment. Lab 3: Heteronuclear double resonance experiments (one pulse, decoupled, gated decoupled, APT, DEPT) Week 7: 10/14 In class presentation: 1H NMR without deuterated solvent / Analyzing multiplet patterns 10/19 In class presentation: Sensitivity enhancement of low-γ nuclei:(10/19) ; The second dimension: Components excitation, evolution, mixing, detection. Week 8: 10/21 Quadrature detection in the indirect dimension. Example exchange, application to C-H correlation using INEPT mixing. 10/26 Sensitivity of Inverse vs. direct detection. HSQC and HMQC. Editing in HSQC. Suppression of 1H-12C signal. Lab 4: Structure determination/assignment of a compound of medium complexity A: 1D methods + CH correlation
Week 9: 10/28 Connectivity: Proton-proton COSY. Long range correlations through CH couplings: HMBC. Examples Menthol and Camphour 11/2 In class presentation: Application of 15
N correlation spectroscopy (Two presentations) Lab 4: Structure determination/assignment of a compound of medium complexity B: connecting groups with COSY and HMBC Week 10: 11/4 In class presentation: Automated structure elucidation, 2D NMR of W-183 and V-51. 11/9 Additional experiments: TOCSY for total correlation of spin system. INADEQUATE, ADEQUATE for C-C connectivity. More detailed look at 2D NMR: Splitting patterns in 2D spectra. Lab 4 finish Week 11: 11/11 E-COSY: Passive coupling in HMQC spectra. Measuring coupling constants from DQF-COSY or PE. COSY. Long range 1H/13C couplings from HSQMBC spectra 11/16 Cross relaxation and NOE: measure of distance. 1D
NOE experiment Lab 5: Conformational analysis using PE COSY and NOESY / 1D NOE Week 12 11/18 2D NOESY and EXSY. Large vs. small molecules and ROESY. Example camphour finish Lab 5 11/23: >NMR and dynamics: fast vs. slow ^M exchange saturation transfer, EXSY. Chemical exchange and lineshape Week 13: 11/25 Thanksgiving 11/30 Relaxation and dynamics. Measurement of relaxation times: direct or indirect. Application to molecular dynamics Week 14: 12/2 Artefact and solvent suppression: Presaturation, Field gradients12/7 Combining sequences: HSQC-TOCSY, 3D NMR. Labeled molecules, protein techniques. Three dimensional structure determination of macromolecules Lab: Demonstation: 3D structure calculation of a small protein>Week 15: 12/9 other nuclei: quadrupolar nuclei, NMR of metals and coupling to metals. Periodic table of NMR 12/14 NMR in paramagnetic compounds: paramagnetic shift, complementary ESR-NMR |
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