Nuclear Magnetic Resonance 1

Lecture Date: February 11th, 2008

 Nuclear Magnetic Resonance

 Reading for NMR:

– Chapter 19 of Skoog, et al.
– Handout: “What SSNMR can offer to organic chemists”

 Nuclear Magnetic Resonance (NMR)

– Nuclear spin transitions, in the 5-900 MHz range
– Magnetic resonance imaging (MRI)
 The Electromagnetic Spectrum

 NMR, MRI
 EPR/ESR
 What is NMR?

 NMR is an experiment in which the resonance

frequencies of nuclear magnetic systems are
investigated.

 NMR always employs some form of magnetic field

(usually a strong externally applied field B0)

 NMR is a form of both absorption and emission

spectroscopy, in which resonant radiation is absorbed by
an ensemble of nuclei in a sample, a process causing
detectable emissions via a magnetically induced
electromotive force.
A. Abragam, The Principles of Nuclear Magnetism, 1961, Oxford: Clarendon Press.
 Things that can be learned from NMR data…

 Covalent chemical structure (“2D structure”)

– Which atoms/functional groups are present in a molecule
– How the atoms are connected (covalently bonded)
 3D Structure
– Conformation
– Stereochemistry
 Molecular motion
 Chemical dynamics and exchange
 Diffusion rate
 3D Distribution of NMR spins in a medium – an image!
– (Better known as MRI)
 Plus many more things of interest to chemists…
 History of NMR
 1920-1930: physics begins to grasp the
concepts of electron and nuclear spin
 1936: C. J. Gorter (Netherlands) attempts to
study 1H and 7Li NMR with a resonance
method, but fails because of relaxation
 1945-6: E. M. Purcell (Harvard) and F. Bloch
(Stanford) observe 1H NMR in 1 kg of parafin at
30 MHz and in water at 8 MHz, respectively P. C. Lauterbur F. Bloch
 1952: Nobel Prize in Physics to Purcell and
Bloch
 1957: P. C. Lauterbur and Holm independently
record 13C spectra
 1991: Nobel Prize in Chemistry to R. R. Ernst
(ETH) for FT and 2D NMR
 2002: Nobel Prize in Chemistry to K. Wuthrich
 2003: Nobel Prize in Medicine to P. C.
Lauterbur and P. Mansfield for MRI E. M. Purcell R. R. Ernst
Photographs from www.nobelprize.org
 Nuclear Magnetism

 A nuclear electromagnet is
created by the nucleons
(protons and neutrons) inside
the atomic nucleus.

 This little electromagnet has a

magnetic moment (J T-1)
– The magnetic moment is
proportional to the current flow
through the “nuclear loop” N

 The nucleus looks like a dipole From

http://education.jlab.org S
to a distant charge center
 Basic NMR Theory
 In a strong applied magnetic field
(B0), certain atomic nuclei will align
or oppose this field.

 This alignment is caused by the

magnetic moments of the nuclei,
which themselves are caused by
the internal structure of the
nucleus. Two nuclear properties
stand out:
– Spin (1/2 for 1H, 13C, etc…)
– Gyromagnetic ratio

 An excess of alignments is found

in the lower energy state
(determined by a Boltzmann
distribution).

 At room temperature, this excess is

very small, typically only 1 part per
trillion!
 Nuclear Spin

 In a classical sense the bulk nuclear

magnetization is observed to
“precess” at the Larmor frequency B0
(usually several hundred MHz):
 B0
 0   B0 0 
2
angular (rad/s) linear (Hz, cycles/s)

 The constant  is the magnetogyric

ratio.
Elements Accessible by NMR

White = only spin ½

Pink = spin 1 or greater (quadrupolar)
Yellow = spin ½ or greater Figure from UCSB MRL website
 Pulsed vs. Continuous-Wave NMR
 NMR effects are most commonly detected by resonant
radio-frequency experiments

 Continuous-wave NMR: frequency is swept over a range

(e.g. several kilohertz), absorption of RF by sample is
monitored
– Historically first method for NMR
– Poor sensitivity
– Still used in lock circuits

 Pulsed NMR – short pulses (at a specific frequency) are

applied to the sample, and the response is monitored.
– Much more flexible (pulse sequences followed from this…)
– Short pulses can excited a range of frequencies
 NMR Theory: The Rotating Frame
 The magnetization precesses at the Larmor frequency, the RF field(s)
oscillate at or near this same frequency
 The “rotating frame” rotates at this frequency, simplifies the picture for
analysis and understanding
z z

eye

Frame rotating at the Larmor frequency Frame is now still

(hundreds of MHz)
 Spin Systems
 The reason NMR is so applicable to structural problems is
that the governing interactions can be separated and
treated individually
– Experimentally, this results in spectral simplification (in that
transitions are not hopelessly entangled) and also allows for
detailed manipulations (pulse sequences) to extract information

 This involves separation of electronic Hamiltonian from

the nuclear spin Hamiltonians

 NMR is thus “simplified” in that its data can be linked back

to “spin systems”. Examples of spin systems:
– Several 1H nuclei (i.e. hydrogen) within 2 or 3 covalent bonds of
each other
– A 1H nucleus attached to a 13C nucleus
 NMR Theory: RF Pulses
 RF pulses are used to drive the bulk magnetization to the desired
position
 The action of an RF pulse is determined by its frequency, amplitude,
length and phase
 For an on-resonant
z
pulse, the right hand rule predicts its action
z

y y

x x

Drawing depicts a 90o pulse Drawing depicts a 180o pulse

 NMR Theory: RF Pulses and Spin Echoes
An RF pulse:

Actually not “solid”,

contains RF
frequencies

Two pulses:

echo
(delays and extra
pulse)
 Selection Rules
 Single-quantum transitions (m =
+/- 1) are allowed by angular
momentum rules (which govern 
spins in NMR).
 Single-quantum states are SQ
X
directly detected in NMR
 X 
experiments
 However, it is possible to excite
double-quantum states (or zero-

quantum, triple-quantum, etc…),
let them evolve with time, then Energy levels for two coupled spins
convert them back to SQ states showing SQ (single quantum)
transitions in green and forbidden
for observation ZQ (zero quantum) and DQ (double
quantum) transitions in red
 NMR Theory: T1 Relaxation
 T1 relaxation: longitudinal
relaxation (re-establishment
of Boltzmann equilibrium)
by spins interacting with the z
“lattice”

 In practice, T1 controls how y

quickly FT experiments can x
be repeated for signal
averaging

 Measurements of T1 can
provide useful data on
molecular motions
 NMR Theory: T2 Relaxation
 T2 relaxation transverse
relaxation (dephasing of
coherence) by spins
interacting with each other z

 Controls how long

magnetization can be kept y
in the x-y plane x

 Controls the linewidth

(FWHH) of the NMR
signals:
1
 1/ 2 
 T2*
 NMR Theory: The Chemical Shift
 The electrons around a nucleus
shield are circulated by the big
magnetic field, inducing smaller
TPPO
fields. x
 Anisotropy:
y

 Units – ppm:    ref  PbSO4

 ( ppm)  10 6 x

 ref

 Shift-structure correlations – the

basis of NMR as an analytical
tool.
Above: the chemical shift in solids is not a single peak!
 Shift-structure correlations are
available for 1H, 13C, 15N, 29Si,
Typical 1H NMR Chemical Shielding
Typical 13C NMR Chemical Shielding
 Other Nuclei: 17
O NMR

Note – 17O NMR requires labeling or concentrated solutions,

and suffers from large solution-state linewidths (caused by
quadrupolar relaxation)
 NMR Theory: The Chemical Shift
 Contributions from electronegativity and ring current
effects:
1
Correlation of H Chemical Shift and Group
Electronegativity for CH 3X Compounds
4.5
4.0
Group Electronegativity

3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0.0 1.0 2.0 3.0 4.0 5.0
Relative Chemical Shift ()

Dailey et. al., J. Am. Chem. Soc., 77, 3977 (1955).

 NMR Theory: The Chemical Shift
 Contributions from ring current effects

 Above center of ring (z-axis): shielding

 In plane of ring ( axis): deshielding

Figure from http://www.chemlab.chem.usyd.edu.au/thirdyear/organic/field/nmr/ans02.htm

 NMR J-Coupling
 The J-coupling is an effect in which
nuclear magnetic dipoles couple to
each other via the surrounding
electrons.
 The effect is tiny but detectable!
 Typical J-values
– JHH can range from –15 to +15 Hz
2-4

and depends on the number of

bonds, bond angles, and torsion
angles

– 1JCH can range from 120 to 280 Hz,

but typically is ~150 Hz in most
organics

– 2-4JCH ranges from –15 to +15 Hz and

depends on effects similar to the 2-
4J
HH

 The narrow ranges that certain 1H and 13C J-

coupling values fall into make spectral
editing and heteronuclear correlation
experiments possible!!!
 J-Coupling: Effects on NMR Spectra
 Two basic types of coupling
– Homonuclear (e.g. 1H-1H)
– Heteronuclear (e.g. 1H-19F)
 Weak coupling
– Large difference in frequency
  >> J
 #Lines = 2 n I + 1
 All heteronuclear coupling is
“weak”
 More complex splitting patterns
can be visualized using
Pascal’s triangle (see text)
 Strong coupling
– Small difference in frequency
  ~ J
 Complex patterns
Figure simulated in Bruker Topspin 2.0 DAISY module
Inspired by S. W. Homans, A Dictionary of Concepts in NMR, Oxford 1989, p297.
 J-Coupling: Effects on NMR Spectra
ortho
 Example: meta para
monofluorobenzene
 Homonuclear coupling
between 1H:
– ortho-coupling
– meta-coupling
– para-coupling
 Heteronuclear coupling
between 1H and 19F:
– As above (ortho, meta,
and para).
– Observed from the 19F,
appears as a doublet of
triplets of triplets (ttd)
 Fluorine can be decoupled
from the 1H spectrum (not
shown)
 Structural and Conformational Analysis

 J-coupling is widely used (in conjunction with 2D NMR) to

assemble portions of a molecule
– In this case, the J-coupling is simply detected in a certain range
and its magnitude is not examined closely

 J-coupling is also used to study conformation and

stereochemistry of organic/organometallic/biochemical
systems in solution
– In this case, the J-coupling is measured e.g. to the nearest 0.1 Hz
and analyzed more closely

W. A. Thomas, Prog. NMR Spectros., 30 (1997) 183-207.

 J-Coupling: Angle Effects
 Karplus relationships – the
effects of bond and torsion
angles on J-coupling
 Bond angles, dihedral
(torsion) angles, 4 and 5-
bond angles
In[1]:=

In[3]:=


 

 

J _ : 4.22 Cos  2  0.5 Cos   4.5

Plot J  , , 0, 

9
Coupling constant (Hz)

0.5 1 1.5 2 2.5 3

Graphics
Out[3]=  Dihedral angle (radians)
 Dipolar Coupling

 The magnetic dipolar interaction

between the moments of two spin-1/2
nuclei
– One spin senses the other’s orientation directly
through space

 The dipolar coupling is simply related to

the internuclear distance between the
spins:  
D  0  I S
8 2 r 3

 The truncated (secular) dipolar Hamiltonians (relevant to

NMR) have the form:
 
H DHomonuclear  D 1  3 cos 2   I z S z  14  I  S   I  S   
 
H DHeteronuclear  D 1  3 cos 2   I z S z 
 Dipolar Coupling
 Example – what’s the dipolar coupling between a 13C and a 15N
nucleus 1.32 angstroms apart?
The permeability constant (in kg m sec2 A2 ) and Planck's constant (in Joule sec):

0  4   107;
  6.62608 1034 
 2 ;

The gyromagnetic ratios for 13C and 15N, in units of radians Tesla1 sec1 :

I  6.728  107;




S  2.712  107;


I
S  0
R r_ :  
r3 2 4
N R 1.32  1010

1331.53

The dipolar coupling is therefore 1.332 kHz.

 The Nuclear Overhauser Effect

 The idea: detect the “cross-relaxation” caused by

instantaneous dipolar coupling in an NMR or EPR
experiment.

 This was conceived by A. W. Overhauser, while a

graduate student at UC Berkeley in 1953

 Overhauser predicted that saturation of the conduction

electron spin resonance in a metal, the nuclear spins
would be polarized 1000 times more than normal!!!
 The Nuclear Overhauser Effect
 Dipolar coupling is a direct magnetic interaction
between the moments of two spin-1/2 nuclei.
 The coherent effects of dipolar coupling are
averaged away in solution-state NMR by rapid
molecular tumbling.

 However, the dipolar

interaction can still
play a role via in
solution-state NMR
via dipolar cross-
relaxation
mechanisms, better
known as the
nuclear Overhauser
effect (NOE).
 NMR Spectrometer Design

 The basic idea:

 NMR Magnets
 Superconducting magnets:
 Resonance

 The natural frequency of a inductive-capacitive circuit:

1
r 
LC

 The NMR system requires a resonant circuit to detect

nuclear spin transitions – this circuit is part of the probe
 Resonant Circuits in Probes

 Figure from Bruker Instruments

 NMR Probe Design

 The NMR probe –

designed to efficiently
produce an
inductance (~W) and
detect the result (<
mW)
 NMR Electronics
 NMR transmitter and receiver designs
 Further Reading

 A. E. Derome, “Modern NMR Techniques for Chemistry

Research”, Pergamon 1987.
 P. W. Atkins and R. S. Friedman, “Molecular Quantum
Mechanics, 3rd Ed.”, Oxford 1997.
 A. Abragam, “Principles of Nuclear Magnetism”, Oxford,
1961.
 R. R. Ernst, G. Bodenhausen, and A. Wokaun,
“Principles of Nuclear Magnetic Resonance in One and
Two Dimensions”, Oxford, 1987.
 C. P. Slichter, “Principles of Nuclear Magnetic
Resonance”, Springer-Verlag, 1996.