Transcript MSc: f-Elements, Prof. J.-C. Bünzli, 2008 Chapter 5 Chapter 5 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Selected applications Selected applications of 4f-elements Magnetocaloric effect and refrigeration Magnetic resonance medical imaging Catalysts for.

MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Chapter 5
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
Selected applications
Selected applications of 4f-elements
Magnetocaloric effect and refrigeration
Magnetic resonance medical imaging
Catalysts for DNA and RNA cutting
Lighting applications
Security ink
Luminescent chemical sensors
Luminescent biochemical sensors
Tracing biomolecular interactions
25 T
5
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
5.1 Magnetocaloric effect (MCE) and refrigeration
Definition
Magnetothermodynamic or magnetocaloric effect, or
adiabatic temperature change = heating or cooling of a
magnetic materials due to varying magnetic field.
Discovered for iron by Marburg in 1881.
The MCE is intrinsic to all magnetic materials and is due
to the coupling of the magnetic sublattice with the
magnetic field, which changes the magnetic part of the
entropy.
Analogy with gases:
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
• Isothermal magnetizing of a paramagnet reduces the
entropy, just as adiabatic compression of a gas does.
• The process is reversible and de-magnetizing restore
the initial entropy, similarly to expansion for a gas.
Thermodynamics of the MCE near the Curie temperature
(magnetic ordering temperature):
S (T,H ) = SM(T, H ) + Slat(T ) + Sel(T )
magnetic
lattice
electronic
large
variation with T
small, and small
variation with T
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
TCurie
S
Selected applications
H = 0
H > 0
DTad
D SM
Slat + Sel
T
DSM = isothermal magnetic entropy change = f(T0)
DTad = isentropic temperature change = = f(T0)
Maximum at TCurie
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Paramagnetic and ferromagnetic materials:
increasing H increases the magnetic order
and decreases S and
DTad (T, DH ) > 0 (the magnetic solid heats up)
DSM (T, DH ) < 0
decreasing H decreases the magnetic order
and increases S and
DTad (T, DH ) < 0 (the magnetic solid cools down)
DSM (T, DH ) > 0
Basic equations (Maxwell)
M = magnetization
C = heat capacity at constant pressure
H = magnetic field
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
 S (T ,H ) 
 M (T ,H ) 
 




H

T

T

H
For an isothermal and isobaric process:
DSM (T , DH ) =
H2
H
1
 M (T ,H ) 
dH


T

H
That is, the magnetic entropy change is proportional
to the derivative of magnetization with respect to T,
at constant field. The infinitesimal adiabatic T rise
(dT) for a reversible adiabatic-isobaric process is:


T
 M (T ,H ) 
dT   
dH
 

T
H
 C (T , H ) H 
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Integrating the latter equation yields:
DTad (T , DH ) = -
H2
H


T
 M (T ,H ) 
 dH

 

T
H
 C (T , H ) H 
• Paramagnets and ferromagnets heat up when H
increases.
• The largest effect occurs for T = TCurie.
• For a given DSM, DTad is larger at higher T, but also
when C is small. Therefore, paramagnets only display
sizeable MCE effect at T close to 0 K.
• Potential applications:
- liquefaction of helium and hydrogen
- reaching ultra low temperatures
- air conditioning and refrigeration
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Magnetic ordering upon lowering T is a cooperative
phenomenon generating large changes in bulk magnetization,
over a small T range around TCurie (or TNeel).
DSM / Jmol-1K-1
4f metals, alloys and compounds have a larger magnetic
entropy than 3d elements and are ideally suited for these
applications.
Gd (TCurie = 31 0C)
1.6
DH = 0-5 T
1.2
0.8
0.4
0.0
0
100
200
300 K
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Gd (TCurie = 31 0C)
12
DTad / K
Selected applications
DH = 0-5 T
9
6
6
0
0
100
200
300 K
• Field dependence is 3 K / T in low magnetic fields
and 2 K / T in higher magnetic fields
• All other compounds with TCurie > 290 K have lower
MCE effect
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Giant magnetocaloric effect (gMCE)
Looking for first-order transitions: they theoretically
occur at constant T and therefore (M/T )H can reach
large values (in theory, infinity)
Gd5(SixGe1-x)4
(0 < x < 0.5)
Pecharsky & Gschneidner, 1997
 DSM twice as large as for Gd
 Curie temperature can be tuned from 20 to 305 K
by varying x and by introducing small amounts of Ga
 the effect is reversible
Main application: continuous magnetic refrigeration
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Principle of the magnetic refrigerator
Apply H
Spins align
T increases
H = 0
Remove H
Spins randomize
T decreases
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
H > 0
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Chapter 5
Selected applications
Principle of the magnetic refrigerator
Gd nodules in
heat transfer fluid
Magnet (1-5 T)
Initial state
cold exchanger
5oC
25 T
5
Initial state
hot exchanger
25oC
Coupling to heat exchanger
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Step 1:
The magnetic field is
switched on, heating
the bed
25 T
5
Step 2: The flow of the cooling fluid is then switched on
25 T
5
heat is
extracted
The Gd bed is cooled by the cooling fluid
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Step 3
The flow of cooling fluid is stopped and the magnetic
field switched off
25 T
The bed
further cools
5
25 T
5
cold is transferred
Step 4
The fluid is forced
through the bed
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
© Astronautics Corporation
of America
Permanent
magnet
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
5.2 Magnetic resonance medical imaging (MRI)
Principle of the NMR experiment
A nucleus behaves like a small magnet
mM
nuclear spin
I= -1/2
I= +1/2
nucleus
1H, 13C, 19F,
nucleus
etc.
S
N
mM
N
S
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
S
H
S
Selected applications
Nuclear magnetic moments
align in a magnetic field
S
N
N
Transitions to the upper
level can be induced by
a radiofrequency field
N
h
E2
N
S
E1
H
S
N
If H  1,4 tesla,   60 MHz
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Upon excitation by a radiofrequency pulse, the nuclei
return to the ground state via two simultaneous and
exponential relaxation processes:
N  N0×et / T
T1 = longitudinal relaxation time
N  N0×et / T
T2 = transverse relaxation time
1
2
(transfer to surroundings)
(loss of phase)
The total rate of relaxation is proportional to:
krelax 
1
T1

1
T2
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Unpaired electrons generate strong fluctuating magnetic
fields and if there are located nearby a nucleus, they
will stimulate nuclear relaxation.
Potential relaxation agents:
High spin FeII
4 unpaired eMnII, FeIII
5
EuII, GdIII
7
DyIII
5
meff = 5.5
5.9
8.6
10.6
small iron particles (super-paramagnetism)
large iron particles (ferromagnetism)
organic radicals (1 unpaired e-)
Gadolinium is usually the best and principally reduces T1
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Measurement of transient signal:
antenna
N
S
S
signal
relaxation
N
N
N
N
N
S
N
S
N
S
S
nuclei aligned in
magnetic field
S
radiofrequency
coil
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
S
radiofrequency
pulse
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Chapter 5
Selected applications
Principle of MRI
Various tissues have different relaxation times
Tissue
Fat
Liver
Muscle
White matter
Grey matter
Spleen
Pancreas
T1/ms
150
250
450
300
475
400
275
T2/ms
150
44
64
133
118
107
43
Therefore, differentiation can be made
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Principle of MRI with contrast agent
• Proton relaxation from water molecules is measured
• Water molecules outside the cells are put into contact
with the (Gd-containing) contrast agent, so that their
relaxation is faster (106-fold!) and discrimination can
be made with respect to water molecules inside the cell
• The effect of the contrast agent, called relaxivity is
defined as follows:
1
ri 
DTi  [CA]
i  1, 2
mmol-1s-1
DTi = difference in Ti without and with CA
[CA] = concentration of contrast agent
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Principle of MRI
The image is measured “slice by slice
and reconstructed
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
©
Guerbet
SA, Paris
T1-weighted images
T2-weighted images
tumor
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
First generation contrast agents
Gd3+
-OOC
N
N
-OOC
N
COO-
Gd3+
-OOC
COO-
CH3HN
COO-
O
N
N
N
[Gd(dtpa-bma)]
LogK = 22.1
LogK = 16.9
O
-
O
O
O
N
-
O
N
O
O
N
CH3
OH
N
Gd3+
-
O
O
O
[Gd(dota)]- Dotarem®
LogK = 25.8
r1 = 4.6 mM-1s-1
-
N
N
-O
Omniscan®
O
Gd3+
-
O
COO-
[Gd(dtpa)]2- Magnevist®
r1 = 3.7 mM-1s-1
COONHCH3
r1 = 3.4 mM-1s-1
N
N
-O
O
[Gd(HP-DO3A)] ProHance®
LogK = 23.8
r1 = 3.7 mM-1s-1
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
The search for high relaxivity
Important parameters are:
- water exchange rate (both inner and outer sphere)
- rotational correlation time of the molecule tR
- electron spin relaxation time tS
tR
tS
[Gd(dota)]-:
tM = 1/kM = 244 ns
ts = is the longitudinal electron
spin relaxation time = 1 ns
tR = 80 ps
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
tM
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Chapter 5
Selected applications
Theoretical relaxivity
for an slowly rotating
molecule (tR > 30 ns)
One solution for increasing
tR is to couple the contrast
agent with proteins (BSA)
or to insert it into highmolecular weight compounds
(such as dendrimers).
logt1s
logtM
[Gd(dota)]S. Aime et al. Chem. Soc. Rev. 1998, 27, 19
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Present state: relaxivities up to 90 mMs-1
HO2C
CO2H
CO2H
N
N
R
H4AAZT
[Gd(AAZT)]-
r = 7.1 mMs-1
N
CO2H
But:
the conjugate with BSA
{[Gd(AAZT)]-(BSA)}
has r = 90 mMs-1
logtM
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
logt1s
29
Chapter 5
Selected applications
Specific contrast agents
Contrast enhancement agent for blood vessels targeted
for E-selectin, which is secreted upon inflammation
(e.g. in subjects with hepatitis)
Gd3+
CO2H
-OOC
HN
O
N
N
N
CO2H
COONH
COO-
O
O
O
HO
OH
O
OH
OH
HO
[Gd(dtpa)B(sLe*)A]
12-step synthesis with overall yield of 5 % …
HO
O
OH
OH
D-mannopyranosyl
derivative
S. Boutry et al. Magn. Res. Med. 2005, 53, 800
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Prolonged vascular
residence: 50 min in
hepatitis vs 30 min in
[Gd(dtpa)B(sLe*)A]
healthy subject
E-selectin
healthy
hepatitis
S. Boutry et al. Magn. Res. Med. 2005, 53, 800
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Supramolecular chemosensors based on relaxivity
(OMe)7
(OMe)6
O
H
O
OH2
N
N
O
O
P
(OMe)7 O
N
O
O
N
O
O
O
OH2
N
N
O
O
N
N
logK = 4.9
O
N
O
Gd
O
Gd
O
O
Enhancement of
relaxivity by a
factor 1.3
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
O
O
MS-325
AngioMARK®
32
Chapter 5
Selected applications
Calcium sensor
O
O
-O
-O
ON
Gd3+ H2O
N
O
Ca2+
O
N
O
Gd3+
O
-O
N
H2O
-OOC
COOCOO- -OOC
N
N
N
-O
-O
O
O
O
OO
NN
OOC
+Ca2+
O
N
N
N
O
-O
O
-
N
N
COONCOON
N
O
O
O
O-
N OOCN
O
Gd3+
O
-Ca2+
N
O-
O-
Gd3+
O
O-
O
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
Calcium sensor based on a contrast agent
Relaxivity/s-1mM-1
6.0
5.5
5.0
4.5
4.0
3.5
3.0
-9
-8
-7
-6
-5
Log[Ca2+]
-4
-3
W.H. Li, S.E. Fraser, T.J. Meade, J.Am. Chem. Soc., 1999, 121, 1413
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
5.3 Catalysts for DNA and RNA cutting
5' CH2
Base
O
5' CH2
H
H
H
O 3'
H
HO P O
H3C
H
H
O 3'
H
OH
H
H
Base
O
H
H
O 3'
H
H
5' CH2
HO P O
Base
O
H
H
O 3'
H
OH
H
H
N H
C
N
Base
O
H
H
O 3'
H
H
H
5' CH2
O
H
Thymine
H
N H
H
Base
H
H
O 3'
H
OH
H
deoxy
ribose
N
O
C
N
H N
N
O
1'
H
N
N
Cytosine
DNA
1'
deoxy
ribose
Adénine
H
O
C
N
O
5' CH2
H
N
N
1'
HO P O
O
H N
N
deoxy
ribose
O
5' CH2
O
H
HO P O
O
H
Base
O
C
1'
deoxy
ribose
H N
H
Guanine
RNA
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
DNA/RNA cleavage:
- biotechnology
- therapy
- artificial enzymes
Cleavage at phosphodiester
bridges
Lifetimes:
- DNA alone
- catalyst
- RNA alone
- catalyst
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
2´108 years
few hours
103 years
few minutes
36
Chapter 5
Selected applications
1992
Komiyama et al. demonstrate that LnIII
chlorides are active catalysts, especially
CeCl3
1994
Komiyama demonstrates that CeIV is better
J. Morrow proves the same effect with
a cyclen derivative, [La(trif)(tcmc)]2+
H2N
O
H2N
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
O
NH2
N
N
N
N
O
O
NH2
37
Chapter 5
Selected applications
Present status
CeIV is the best catalyst for DNA cutting
TmIII, YbIII, LuIII are best catalysts for RNA cleavage
Proposed mechanism for DNA cleavage
In fact, the active species seems to be an hydrolyzed
species containing CeIV. At pH 7.4, the following species
are present in solution:
[Ce(OH)]3+, [Ce(OH)2]2+, [Ce2(OH)2]6+, [Ce2(OH)3]5+,
[Ce2(OH)4]4+
3.8 Å
4+
H
OH
Ce
O
O
Ce
OH
H
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
OH
O
R O
P
R
O
O
R O
Ce
P
O HO H
O Ce
O
HO
H O
oligonucleotide
O
O
CeIV
CeIV
+
R
O
H
P O
O
substrate DNA
O
O
P O
O
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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Chapter 5
Selected applications
RNA splitting
HO
N X
N
0.1
Dy
N
N
X
N
0.0
HO
kobs / min-1
0.2
Sc Y La Ce Pr Nd Eu Sm Gd Tb Ho Tm Yb Lu CeIV
N
N
N
Tb
M. Komiyama in Handbook on the Physics and
Chemistry of Rare Earths, Vol. 34, Ch. 222, 2005.
N
N
N
MSc: f-Elements, Prof. J.-C. Bünzli, 2008
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