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Chem843 1

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Chem843 1

  1. 1. Dr. Gerd Gemmecker Room 5333a Phone 2-8619 e-mail gemmecker@chem.wisc.edu Gerd.Gemmecker@ch.tum.deChemistry 843 "Advanced NMR Spectroscopy" © Gerd Gemmecker, 1999This course will cover the theory required to understand and successfully implement the methods ofstate-of-the-art NMR spectroscopy, with the stress laid on structure elucidation by multidimensional(essentially 2D) NMR techniques.What will be covered? ⇒ Introduction to the principles of NMR (including build-up of an NMR spectrometer, general features of Fourier transform, relaxation, folding, sensitivity etc.) ⇒ theory required for the understanding of important experiments (Cartesian product operators) ⇒ a selection of the most widely-used 2D NMR techniques ⇒ interpretation of these spectraand what not? ⇒ quantum mechanical treatment of NMR (although some equations will occur!!!) ⇒ solid state NMR ⇒ working with NMR data bases ⇒ empirical correlations for chemical shifts (increment systems)What is required? ⇒ knowledge of 1D NMR, J coupling patterns, chemical shift etc., e.g., Chemistry 605 or 626 ⇒ regular (!) attention of the course, since most "individual sections" require an understanding of the previous ones. ⇒ "re-reading" (and "re-thinking"!) of the material on a regular basis, and working out your own solutions to the problems given in the course – to make sure that you have really grasped the concepts and developed a working knowledge!Credits / Grades:For credit, a report is required on an aspect of this course relevant to ones own research, or aresearch proposal.
  2. 2. 2Some literature recommendationsMonographs− A.Abragam "The principles of Nuclear Magnetism", Oxford University Press, 1978 (6. Auflage), ISBN 0-198-51236-9. (physics, very gut & very difficult to understand, the "old testament" of NMR)− R. R. Ernst, G. Bodenhausen, A. Wokaun "Principles of NMR in One and Two Dimensions", Oxford Science Publ. 1987, ISBN 0-198-55647-0. (physical chemistry, very exact & very difficult, the "new testament")− O. W. Sørensen, G. W. Eich, M. H. Levitt, G. Bodenhausen, R. R. Ernst, Progr. NMR Spectrosc. 16, 163-192 (1983). (the original article about product operators, but very readable! – if you skip some paragraphs)− R. K. Harris "Nuclear Magnetic Resonance Spectroscopy, A Physicochemical View", Longman Scientific & Technical 1986, ISBN 0-582-44653-8. (easily readable introduction to basic concepts, no modern techniques)− J. N. S. Evans "Biomolecular NMR Spectroscopy", Oxford University Press 1995, ISBN 0-198- 54766-8 (QP519.9.N83E94 1995). (stress on biomolecular NMR, incl. proteins & nucleic acids, but also including a compact, yet concise introduction, nice book, reasonably priced)− H. Kessler, M. Gehrke, C. Griesinger, Angew. Chem. Int. Edn. Engl. 1988, 27, 490-536. ( good review on all 2D techniques, incl. product operator explanation, still up to date)− W. R. Croasmun, W. M. K. Carlson, ed. "Two-Dimensional NMR Spectroscopy; Applications for Chemists and Biochemists", VCH 1994, ISBN 1-56081-664-3 (QD/96/N8/T87/1987). (mixture of introductory and application chapters, on heteronuclear spectroscopy etc., expensive)− D. Shaw, "Fourier Transform NMR Spectroscopy", Elsevier Scientific Publishing Co., New York, 1976 (Res. QC/762/S45/2/1984). (good on principle and features of FT, otherwise outdated)
  3. 3. 3− H. Friebolin, "Basic One- and Two-Dimensional NMR Spectroscopy", VCH, 2nd ed., 1993 (QP519.9/N83/F7513/1993). (introduction into principles and applications of 2D NMR, not much 2D theory)− J. K. M. Sanders, B. K. Hunter, "Modern NMR Spectroscopy, A Guide for Chemists", Oxford University Press, 2nd ed. 1993 (QD/96/N8/S25). (no product operator description, but very good description of applications for 2D techniques, incl. example spectra).− J. Cavanagh, W.J. Fairbrother, A. G> Palmer III, N. J. Skelton, "Protein NMR Spectroscopy, Principles and Practice", Academic Press, San Diego 1996, ISBN 0-12-164490-1 (QP551.P69726 1995) (Lots of theory, quantum-mechanics & product operators, FT, relaxation measurements, despite title large section on 2D methods)Journals J. Magn. Reson. Magn. Reson. Chem. J. Biomol. NMR (technical & theoretical (applications and data on (methods development &developments, also solid state compounds; review-like papers biomolecular applications) & imaging) on practical aspects of NMR techniques, processing etc.)
  4. 4. 4"First Exam"1. What do the following acronyms stand for? NMR FT COSY NOE2. Please make a sketch of the 1H 1D spectrum of diethyl ether:3. Whats the size of the H1-H2 and the H2-H3 3J couplings?4. What do you expect to learn in this course?5. Do you have any specific subjects that you would like to be treated here?
  5. 5. 5Applications of NMRin synthesisfor checking the results in a fast and efficient way, concern. connectivity purity.determination of solution structurewith similar accuracy as x-ray analysis, allowing to detect differences between crystalland solution structure, as well as influence of solvent.currently limited to ca. 10 kDa without isotopic labeling, ca. 30-40 kDa with isotope 13C,15 N (and 2H) labeling (proteins & nucleic acids).investigating intermolecular interactionsmostly for biologically active compunds, e.g., enzyme - inhibitor DNA - intercalator or repressor receptor - hormon oder substrate antibody - antigenimportant, since all biological functions are based on intermolecular interactions, quiteoften in a very complex way (complexes higher than binary)molecular dynamicsfrom relaxation measurements, the dynamic behaviour of molecules can be derived onvarious time scales – important for understanding chemical & biochemical reactivity,protein folding etc.General course of an NMR studyfrom simple to increasingly complex models, e.g., 1 131. selecting the nucleus to be studied (mostly H or C), often limited by the availability of larger amounts of the substanceand solubility (isotopic labeling).2. optimizing measurement conditions (temperature, solvent, etc. - often skipped in routine NMR for organic synthesis)3. assigning the resonances to the individual atom positions; for less complex molecules this can be done from 1D spectra considering the following parameters:
  6. 6. 6 a) "signal intensities" (integrals!) proportional to number of nuclei b) characteristic chemical shifts c) J coupling patterns (to find neighbouring positions connected by bonds) d) line widths (dependent on local flexibility, chemical exchange, proximity to quadrupolar nuclei or paramagnetic species) a complete assignment is a reliable proof for the postulated connectivity / formula;4. after that, conformationally sensitive parameters can be used to derive information about the 3D arrangement, mostly J couplings and NOE effects.5. additional experiments for measuring relaxation and exchange rates give additional information on dynamic aspects. Structural theory NMR equivalentalchemy qualitative composition choice of nucleus / isotopeLIEBIG quantitative composition signal intensities / integralsGERHARD & functional groups chemical shiftsLAURENTKEKULÉ & connectivity J couplingCOUPERVANT HOFF & spactial arrangement of atoms NOE ⇒ distancesBARTON J couplings ⇒ dihedralsKARPLUS dynamics relaxation & exchange rates

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