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© 2012, K.S. Suslick
Paramagnetic NMR
I. Overview of Paramagnetic NMR: Origins
II. Components of Paramagnetic Shifts
Scalar / Contact
Dipolar / Pseudocontact
III. Applications
A. Electronic Structure & Spin Distribution
B. Stereochem and Structure
C. Equilibrium Dynamics & Solvation
D. Lanthanide Shift Reagents
E. Bioinorganic Applications
F. Contrast agents for MRI
© 2012, K.S. Suslick
Paramagnetic 1H NMR
Was initially ignored because people thought
the signals would be so broad as to be useless.
“They” were wrong, sometimes.
Do see Broader lines. But the range of  increases hugely.
Broadening from fast Spin-Lattice Relaxation (T1N).
If lines are too broad, will often give useful EPR.
If e- relaxation times are fast enough, T1N is unaffected.
Many paramag. cmpds have paramag 1H NMR & EPR.
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© 2012, K.S. Suslick
Paramagnetic 1H NMR
The presence of a paramagnetic metal ion causes line
broadening of all NMR signals from nuclei close to the
metal ion: too close, too broad to be seen!
The radius of the "blind" sphere
depends on the metal ion.
The size of the blind sphere changes
with the nuclear type, being smaller
for 13C than for 1H.
The effect decreases rapidly with
increasing distances from metal ion,
so that it is negligible outside of an
outer "paramagnetic effects" sphere.
"Blind Sphere"
© 2012, K.S. Suslick
Paramagnetic 1H NMR
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© 2012, K.S. Suslick
Paramagnetic 1H NMR
© 2012, K.S. Suslick
Paramagnetic 1H NMR: Relaxation Time
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© 2012, K.S. Suslick
When Do We See Paramagnetic NMR?
© 2012, K.S. Suslick
When Do We See Paramagnetic NMR?
?
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© 2012, K.S. Suslick
When Do We See Paramagnetic NMR?
Octahedral Tetrahedral
CoII, NiII
CrII, FeIII
© 2012, K.S. Suslick
Paramagnetic NMR Chemical Shifts
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© 2012, K.S. Suslick
Paramagnetic NMR Hamiltonian
These determine the energies of the different nuclear
(and electronic) spin states (i.e., the Zeeman splitting
for the nuclear spin states).
i.e., The Paramagnetic Chemical Shift.
© 2012, K.S. Suslick
Components of Paramagnetic Shifts
The components of Paramagnetic Shifts are separated into
Scalar or Contact Shift
vs.
Dipolar or Pseudo-Contact Shift
This division is really an artifact of viewing molecules
through LCAO-MOT:
Both Shifts are due to the same coupling phenomenon
of electron mag moment coupling to nuclear mag moment.
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© 2012, K.S. Suslick
Components of Paramagnetic Shifts
Contact Shift – Consider the Electron and Nucleus
as simply a coupled doublet,
But with a J ~ 1 x106 Hz !
Not an equal coupling, so intensities are not equal,
and the weighted mean position is not at midpoint.
Under fast relaxation, doublet collapses into a singlet
far away from the original nuclear chemical shift.
Dipolar Shift – through space interaction between
electron & nucleus, also called pseudo-contact shift,
often small in magnitude.
© 2012, K.S. Suslick
Scalar or Contact Coupling
Due to direct overlap of unpaired e- spin density
at the nucleus: “Fermi” contact.
If we assume isotropic unpaired e- density:
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© 2012, K.S. Suslick
Scalar or Contact Coupling
avg. spin polarization
Define an Heff that converts the energy splitting into an effective mag field change:
For an S = ½ system,
© 2012, K.S. Suslick
Scalar or Contact Coupling
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© 2012, K.S. Suslick
Temperature Dependence of Scalar Coupling
For comparison,
H2TPP has δ = 9 ppm
© 2012, K.S. Suslick
Through-Bond Propagation of Fermi Contact
(i.e., Scalar Coupling) via Spin-Transfer
3 classes:
e.g., L→M:
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© 2012, K.S. Suslick
Dipolar or Pseudo-Contact Coupling
If unpaired e- spin density is NOT isotropic, then dipoledipole
interactions “through space” can occur between the
e- spin density and the nucleus.
For an axial system, ICBST:
Hpc / H = pc / 
© 2012, K.S. Suslick
Two Contributors to Paramagnetic Shifts
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© 2012, K.S. Suslick
Where is Paramagnetic NMR Useful?
• Applications
A. Electronic Structure & Spin Distribution
B. Stereochem and Structure
C. Equilibrium Dynamics & Solvation
D. Lanthanide Shift Reagents
E. Bioinorganic Applications
F. Contrast agents for MRI
• Inorganic – any metal that has unpaired e- will
cause chemical shift range to be extremely large.
• Proteins – many proteins contain paramagnetic
ions (often Fe+3) in their active site. But one can
also substitute paramagnetics (e.g., Co+2 for Zn+2)
into the protein to spread out the chemical shifts
near the active site.
© 2012, K.S. Suslick
Size of Paramagnetic Chemical Shifts
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© 2012, K.S. Suslick
Classic Early Paramagnetic NMR:
Bob Connick, 1960’s
Water exchange rates coordinated to metal ions
increasingTemp→
© 2012, K.S. Suslick
Chemical Shift Range for Paramagnetic NMR
Particularly useful when studying Fe Porphyrins
Fe+3 = d5, Fe+2 = d6 (may be diamagnetic)
Ex.: Inorg. Chem. 1992, 31, 2248-2255
Study undertaken to connect oxidized heme, called an
oxophlorin to verdoheme, a known heme breakdown
product.
Colors of bruise are due to breakdown of heme to
bilirubin (yellow).
Endogenous production of CO!
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© 2012, K.S. Suslick
Heme Degradation
© 2012, K.S. Suslick
Heme Degradation: Oxophlorin
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© 2012, K.S. Suslick
Heme Degradation: Oxophlorin
b,b’ etc. mean methylene H are diastereotopic:
dimerization makes opposite sides
of ring inequivalent.
© 2012, K.S. Suslick
N
N
N
N
Iron (III)Octaethylporphyrin chloride, ClFeOEP
Fe
Cl
H
H
H
H meso's
Shifts of Fe(OEP)Cl
S=5/2, 5 coordinate
CH3’s show up at 6.7ppm
CH2’s show up at 44.5 & 40.5ppm
meso H’s show up at –56.1ppm
Methylenes are diastereotopic:
top and bottom of molecule are
not equivalent.
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© 2012, K.S. Suslick
Shifts of Fe(OEP)Cl
S=5/2, 5 coordinate
CH3’s show up at 6.7ppm
CH2’s show up at 44.5 & 40.5ppm
meso H’s show up at –56.1ppm
Methylenes are diastereotopic:
top and bottom of molecule are
not equivalent.
N
N
N
N
Iron (III)Octaethylporphyrin chloride, ClFeOEP
Fe
Cl
H
H
H
H meso's
© 2012, K.S. Suslick
N
N
N
N
Fe
S
[Fe(TPA)SPh]+
o
m
p



Isotropic shifts resulting from
dipolar and contact mechanisms
in FeII TPA complexes
Paramagnetic NMR of a FeII Tripyridyl Amine
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© 2012, K.S. Suslick
Paramagnetic NMR of Ferrodoxin
solvent
&buffer
diamag
protein
© 2012, K.S. Suslick
Active Site of ß-Lactamase
• ß-lactamase enzyme cleaves the lactam ring,
preventing the drugs from killing bacteria. It is a
protective enzyme in bacteria that imparts antibiotic
resistance.
• Active site is ??
• Enzyme is a metalloenzyme but with Zn+2, d10 and
diamagnetic.
• Replace Zn+2 with Co+2 (just by ion exchange), and
enzyme still retains activity.
• Co+2 is paramagnetic. Parts of the protein close to
the Co+2 will show paramagnetic shifts.
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© 2012, K.S. Suslick
Paramagnetic 1H NMR of
Co(II) substituted ß-lactamase
• See three strong signals in 45-55ppm range.
• When D2O is added these peaks disappear.
• Suggests three different amino acids bind the
metal contain exchangeable protons. The
imidazole residue of Histidine binds metals, and
have exchangeable protons.
© 2012, K.S. Suslick
Active Site of metallo-ß-Lactamase
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© 2012, K.S. Suslick
Structural Uses of Paramagnetic NMR
Paramagnetic NMR Constraints
Nuclear relaxation provides metal-nucleus distances.
Pseudocontact shifts provide the angular coordinates of
the metal ion and new structural constraints.
Contact shifts may provide dihedral angle constraints.
© 2012, K.S. Suslick
Structural Uses of Paramagnetic NMR
Paramagnetic effects are measured as differences in
NMR spectra recorded from the target molecule in
the paramagnetic and diamagnetic states.
Data measured with a paramagnetic ion must be
compared with corresponding data obtained with
a chemically similar but diamagnetic metal ion.
Diamagnetic Reference
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© 2012, K.S. Suslick
Type II Cu2+ – Cu,Zn SOD
© 2012, K.S. Suslick
The final solution structure of
monomeric Cu,Zn SOD
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© 2012, K.S. Suslick
Lanthanide Shift Reagents (S.R.)
• S.R.s are paramagnetic Lewis Acids that bind to
functional groups of organics w/ complex NMR.
• Subsequent paramag shift reduces complexity and
increases ease of assignments.
• Amount of shift can be used (under certain conditions)
to calculate structures of the organic as bound
to the S.R.
• Less useful these days with large field NMRs and
multi-dimensional NMR.
• But S.R. became reborn as MRI contrast agents due
to increased relaxation rates of interacting waters!
© 2012, K.S. Suslick
Lanthanide Shift Reagents (S.R.)
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© 2012, K.S. Suslick
Lanthanide Shift Reagents (S.R.)
NMR of di-n-butyl ether
O[CH2CH2CH2CH3]2
SR are idiosyncratic:
rely on strength of
Lewis acid-base
interactions.
© 2012, K.S. Suslick
MRI Contrast Agents
 Chemical agents influencing the contrast behavior of
magnetic resonance images and spectra. Commonly
used agents include paramagnetic and
superparamagnetic media.
 Contrary to x-ray contrast agents which are directly
visible, magnetic resonance imaging contrast agents
influence the behavior of the surrounding tissue; thus
they are indirect contrast agents
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© 2012, K.S. Suslick
MRI Contrast Agents
Traditional shift and contrast agents are largely based
on high relaxivity Gd(III) complexes.
(1) Fe(III) is substantially less toxic than Gd(III) and
therefore holds promise for eventual in vivo
applications.
(2) The high relaxivity of Gd(III) complexes arises
fundamentally from fast ligand exchange rates but
comparatively weak f orbital based binding.