2E

1. Dr. Gerd Gemmecker
Room 5333a
Phone 2-8619
e-mail gemmecker@chem.wisc.edu
Gerd.Gemmecker@ch.tum.de
Chemistry 843 "Advanced NMR Spectroscopy" © Gerd Gemmecker, 1999
This course will cover the theory required to understand and successfully implement the methods of
state-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 spectra
and 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 one's own research, or a
research proposal.

2. 2
Some literature recommendations
Monographs
− 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
− 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
"First Exam"
1. What do the following acronyms stand for?
NMR
FT
COSY
NOE
2. Please make a sketch of the 1H 1D spectrum of diethyl ether:
3. What's 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
Applications of NMR
in synthesis
for checking the results in a fast and efficient way, concern. connectivity purity.
determination of solution structure
with similar accuracy as x-ray analysis, allowing to detect differences between crystall
and 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 interactions
mostly for biologically active compunds, e.g.,
enzyme - inhibitor
DNA - intercalator or repressor
receptor - hormon oder substrate
antibody - antigen
important, since all biological functions are based on intermolecular interactions, quite
often in a very complex way (complexes higher than binary)
molecular dynamics
from relaxation measurements, the dynamic behaviour of molecules can be derived on
various time scales – important for understanding chemical & biochemical reactivity,
protein folding etc.
General course of an NMR study
from simple to increasingly complex models, e.g.,
1 13
1. 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
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 equivalent
alchemy qualitative composition choice of nucleus / isotope
LIEBIG quantitative composition signal intensities / integrals
GERHARD & functional groups chemical shifts
LAURENT
KEKULÉ & connectivity J coupling
COUPER
VAN'T HOFF & spactial arrangement of atoms NOE ⇒ distances
BARTON
J couplings ⇒ dihedrals
KARPLUS dynamics relaxation & exchange rates