This journal is c the Owner Societies 2013 Phys. Chem. Chem. Phys.

, 2013, 15, 20717--20726 20717
Cite this: Phys. Chem. Chem. Phys., 2013,
15, 20717
A comparative study of
1
H and
19
F Overhauser DNP in
fluorinated benzenes
Oliver Neudert,
a
Carlos Mattea,
b
Hans Wolfgang Spiess,
a
Siegfried Stapf
b
and
Kerstin Mu¨nnemann*
a
Hyperpolarization techniques, such as Overhauser dynamic nuclear polarization (DNP), can provide a dramatic
increase in the signal obtained from nuclear magnetic resonance experiments and may therefore enable new
applications where sensitivity is a limiting factor. In this contribution, studies of the
1
H and
19
F Overhauser
dynamic nuclear polarization enhancements at 345 mT are presented for three different aromatic solvents
with the TEMPO radical for a range of radical concentrations. Furthermore, nuclear magnetic relaxation
dispersion measurements of the same solutions are analyzed, showing contributions from dipolar and scalar
coupling modulated by translational diffusion and different coupling efficiency for different solvents and
nuclei. Measurements of the electron paramagnetic resonance linewidth are included to support the analysis
of the DNP saturation factor for varying radical concentration. The results of our study give an insight
into the characteristics of nitroxide radicals as polarizing agents for
19
F Overhauser DNP of aromatic
fluorinated solvents. Furthermore, we compare our results with the findings of the extensive research
on Overhauser DNP that was conducted in the past for a large variety of other radicals.
1. Introduction
Hyperpolarization techniques like Dynamic Nuclear Polarization
(DNP) have the potential to overcome the sensitivity issue of
Nuclear Magnetic Resonance (NMR) thus enabling new applica-
tions of this important method in natural sciences and medicine.
These techniques allow for the creation of a non-equilibrium
population of nuclear spin states with greatly enhanced polariza-
tion, which provides significant enhancement of the NMR
signal compared to the thermal equilibrium polarization.
Therefore, hyperpolarization can help to overcome limitations
that result from the inherently low sensitivity of NMR com-
pared to other spectroscopic methods. For example, it can
facilitate the detection of nuclei with low natural abundance
and/or low magnetogyric ratios, in dilute solutions or for
very small sample amounts. Especially for clinical magnetic
resonance imaging, hyperpolarization can be used to track
contrast agents based on nuclear spins other than
1
H
1,2
or to
investigate metabolic processes.
3
For NMR spectroscopy, hyper-
polarization can dramatically reduce the measurement time,
for example, for multidimensional experiments on low natural
abundance nuclei,
4
for the study of proteins
5–7
or it can provide
surface enhanced detection.
8
Several chemical and physical methods have been developed
and refined to achieve such a state of hyperpolarization, for
instance, ParaHydrogen Induced Polarization (PHIP),
9,10
spin
exchange optical pumping
11,12
and dynamic nuclear polariza-
tion.
7,13–23
For nuclear spins in liquid solutions, Overhauser
DNP
15–20
is a versatile method for hyperpolarization, providing
signal enhancements of more than 2 orders of magnitude. It is
based on the transfer of thermal equilibrium polarization from
unpaired electron spins to nuclear spins, due to the much
larger magnetogyric ratio of electrons. The unpaired electrons
are provided by adding a radical to the liquid sample at a
concentration of a few mmol l
À1
and irradiating the sample
with microwave radiation at the frequency of the corresponding
electron spin transitions.
In the past there has been extensive research on Overhauser
DNP for several nuclei (
1
H,
19
F,
13
C,
31
P,
7
Li), a broad range of
magnetic fields from a few mT up to around 2 T and for a large
variety of solvents and radicals, e.g. TTBP
24–28
(2,4,6-tri-tert-
butylphenoxyl), GALV
24,29,30
(galvinoxyl), BDPA
30,31
(a,g-bisdi-
phenylene-b-phenylallyl) or DPPH
29,30
(2,2-diphenyl-1-picrylhy-
drazyl). The findings of the earlier work on Overhauser DNP
have been summarized in a number of expert reviews.
15–18
In
these studies, scalar couplings were found to affect
19
F DNP
enhancements of aromatic solvents, varying largely in intensity
and dynamics, depending for example on the fluorination of
the solvent and the chemical structure of the radicals. However,
during this period only little work was done on DNP using
a
Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz,
Germany. E-mail: muenne@mpip-mainz.mpg.de
b
Institute of Physics, Ilmenau University of Technology, D-98693 Ilmenau, Germany
Received 11th July 2013,
Accepted 16th October 2013
DOI: 10.1039/c3cp52912f
www.rsc.org/pccp
PCCP
PAPER
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20718 Phys. Chem. Chem. Phys., 2013, 15, 20717--20726 This journal is c the Owner Societies 2013
nitroxide radicals. The most extensive studies with this class of
radicals were done at magnetic fields below 10 mT by Bates
32
as
well as by Glazer and Poindexter.
33,34
In the last decade, DNP has experienced a revival inspired by
technical improvements in the field of high frequency micro-
wave resonant structures,
35
high power microwave sources
36
and the development of dissolution DNP.
21
Also liquid-state
DNP has seen renewed interest at both moderate and high
magnetic fields.
19,20
Different types of liquid-state DNP experi-
ments have been developed: experiments at magnetic fields
around 350 mT use permanent magnets or electromagnets and
employ microwave irradiation at frequencies around 10 GHz,
37–39
other experiments at high magnetic fields use superconducting
magnets with microwave irradiation at a few hundred GHz.
39–41
A third approach uses a two-center magnet and fast sample
shuttling,
42
taking advantage of both the larger DNP coupling
factor for microwave irradiation at around 350 mT and
the improved resolution and sensitivity of detection at high
magnetic fields. Together with the revival of research on DNP,
nitroxides have become an important class of radicals for
both liquid-state DNP
19,20
and solid-state DNP
7,8,22,23
due to
their stability, low toxicity, small size, solubility in different
solvents and possibility of covalent binding to proteins and
other molecules.
Recent Overhauser DNP experiments at X-band microwave
frequencies, i.e. at a magnetic field of around 350 mT, have
mainly been performed in aqueous solutions
38,43–46
because
biological applications were envisaged. In these experiments,
the most intensively studied examples involve
1
H DNP on water
protons with piperidine nitroxide radicals. There it was found
that the interaction between nuclear and electron spins is of
pure dipolar nature and that its dynamics mainly reflects
translational diffusion with a 10–25% contribution of rotational
diffusion.
47,48
In this contribution we attempt to expand the
scope of these recent experiments to include non-aqueous,
aromatic solvents and heteronuclei. We investigate Overhauser
DNP enhancements of
1
H and
19
F nuclear spins at 345 mT
using the stable aliphatic nitroxide radical TEMPO (2,2,6,6-
tetramethylpiperidine-1-oxyl) dissolved in three different non-
polar, aromatic solvents: benzene, 1,4-difluorobenzene (DFB)
and hexafluorobenzene (HFB). We report on enhancements
obtained for a wide range of radical concentrations between
5 mM and 320 mM. Furthermore we present Continuous Wave
Electron Paramagnetic Resonance (CW EPR) and Nuclear Magnetic
Relaxation Dispersion (NMRD) measurements, which are used to
support the interpretation of the DNP results by providing details
on the dynamics of molecular interactions and on the coupling
mechanisms between nuclear and electron spins. The scope of
this contribution is to investigate the properties and dynamic
interactions of TEMPO radical as a polarizing agent for aromatic
solvents, expanding the range of systems for which they can be
used and therefore to enable the study of chemical reactions
using Overhauser DNP.
19
F DNP could provide additional selectivity and sensitivity
for a range of NMR techniques that do not have chemical shift
resolution and are often performed at moderate or low magnetic
fields, such as time domain NMR,
49
field-cycling NMR relaxo-
metry
50
or single-sided NMR.
51
Moreover, due to the contribution of
scalar interactions,
19
F DNP enhancements reflect several physico-
chemical phenomena, such as complexation tendencies or transient
bonding and depend on the orbital disposition on both radical and
receptor molecules. Therefore,
19
F DNP may be helpful for the study
and monitoring of chemical reactions.
52
Finally, DNP coupling
factors in general reflect the dynamics and type of the molecular
interactions modulating the interaction between nuclear and
electron spins and may therefore be a measure of those.
53
2. Theory
2.1 DNP
The discussion of the theory of liquid-state Overhauser-DNP
will be restricted to a short summary of the necessary details;
an in-depth treatment can be found in several papers and
reviews.
15,54,55
The DNP signal enhancement E, which is the
ratio of the DNP-enhanced signal intensity and the signal that
is obtained from thermal equilibrium polarization, is given by:
E ¼ 1 Àx fs
o
e
o
n
(1)
where o
n
and o
e
are the Larmor frequencies of the measured
nuclear spin and the electron spin, respectively. The coupling
factor x is constant for a given system at a certain magnetic
field and temperature, and depends on the type and dynamics
of the interaction between electron and nuclear spins. The
leakage factor f is given by:
f ðcÞ ¼
R
rad
1;n
ðcÞ
R
1;n
ðcÞ
(2)
where R
1,n
is the total longitudinal relaxation rate and R
rad
1,n
(c) =
r
rad
1,n
c, with the radical concentration c and the relaxivity r
rad
1,n
, is
the relaxation rate contribution that results from the inter-
action between electron spin and nuclear spin. The saturation
factor s can be separated into two factors that depend on the
microwave power P and radical concentration c, respectively:
s(P,c) = s
rel
(P)s
max
(c) (3)
where s
max
(c) depends on the number of electron spin transitions
and on exchange effects mixing them, with 1/3 o s
max
o 1 for
14
N nitroxide radicals. The relative saturation factor s
rel
(P)
describes the level of saturation of the irradiated electron spin
transition and, for resonant excitation of a homogeneously
broadened transition, it is given by:
s
rel
ðPÞ ¼
o
1
2
T
1;e
T
2;e
1 þo
1
2
T
1;e
T
2;e
(4)
with o
1
= g
e
B
1
depending on the strength of the microwave
magnetic field B
1
¼ C
ffiffiffiffi
P
p
. T
1,e
and T
2,e
are, respectively,
the electron spin longitudinal and transversal relaxation
times. When inhomogeneous broadening is present, this
relation for s
rel
(P) does not apply strictly anymore. However,
it represents a reasonable approximation when inhomo-
geneous broadening is sufficiently small.
56
Thus, we introduce
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a parameter P
half
= (g
e
2
C
2
T
1,e
T
2,e
)
À1
for which s
rel
(P
half
) = 0.5.
s
rel
(P) can then be written as:
s
rel
ðPÞ ¼
P=P
half
1 þP=P
half
(5)
Hence, the extrapolated enhancement E
max
= lim
P-N
E(P) can
be obtained from measurements of the enhancement E(P) for
varying microwave power and subsequently fitting
EðPÞ ¼ 1 À 1 ÀE
max
ð Þ
P=P
half
1 þP=P
half
(6)
with E
max
and P
half
as the fitting parameters.
The saturation level s
2
for an EPR transition that is coupled
to another EPR transition by electron spin exchange was given
by Tu¨rke and Bennati,
57
assuming that the latter transition is
completely saturated by a pump pulse, i.e. s
1
= 1:
s
2
¼ 1 À2 2 þ
W
N
W
e
þ
o
EX
W
e

À1
(7)
where W
N
is the longitudinal relaxation rate of the nitrogen
nuclear spin and W
e
is the longitudinal electron spin lattice
relaxation rate. o
EX
is the Heisenberg spin exchange frequency,
which depends on the radical concentration.†
For TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and derivatives,
the termW
N
/W
e
is often found to be small or negligible compared to
unity.
43,57
Furthermore, DNP measurements carried out at 0.5 mM
radical concentration gave no indication of s
max
being larger
than 1/3. The maximum DNP saturation factor for a system
with three EPR transitions is then given by the average of the
saturation level of the pumped transition s
1
= 1 and the two
other transitions s
2
= s
3
, assuming W
N
/W
e
{1:
s
max
o
EX
ð Þ ¼
1
3
s
1
þs
2
þs
3
ð Þ ¼
1
3
3 À4 2 þ
o
EX
W
e

À1
" #
(8)
Therefore, the concentration-dependence of the extrapolated
enhancement is given by the expression
E
max
ðcÞ ¼ 1 Àx
r
rad
1;n
c
R
1;n
ð0Þ þr
rad
1;n
c
1
3
3 À4 2 þ
o
EX
W
e

À1
" #
o
e
o
n
(9)
2.2 EPR
Heisenberg Spin Exchange (HSE) between radicals can mix
different electron spin transitions when two radical molecules
interact with each other, leading to an increase in s
max
.
Furthermore, it leads to an increase in the peak-to-peak line-
width DB
pp
of the first derivative EPR spectrum, with a linear
dependence on the spin exchange frequency
58
o
EX
:
DB
pp
o
EX
ð Þ ÀDB
pp
ð0Þ ¼
4
3
o
EX
ffiffiffi
3
p
g
e
(10)
with o
EX
related to the radical concentration c by the exchange
rate k
exch
:
o
EX
= k
exch
c. (11)
Thus, k
exch
may be obtained by measuring the peak-to-peak
linewidth for several radical concentrations c. When strong
exchange is present, o
EX
is given by:
59
o
EX
= 16pDac. (12)
The translational diffusion coefficient D can be approximated
using the Stokes–Einstein relation
D = kT/6paZ (13)
where Z is the solvent viscosity, T is the absolute temperature,
a is the hydrodynamic radius of the radicals and k is Boltzmann’s
constant. Hence, k
exch
only depends on T and Z:
k
exch
= 8kT/3Z. (14)
2.3 NMRD
Three different sources of relaxation can be distinguished for the
nuclear spin relaxation rate R
1,n
= 1/T
1,n
: the relaxation rate of the
pure (degassed) solvent without dissolved molecular oxygen R
0
1,n
,
the radical-induced relaxation rate R
rad
1,n
(c) = r
rad
1,n
c and the relaxa-
tion rate induced by oxygen, R
oxygen
1,n
. The total relaxation rate can
be obtained by adding all relaxation mechanisms:
R
1,n
(c) = R
0
1,n
+ r
rad
1,n
c + R
oxygen
1,n
. (15)
Relaxations rates are, in general, dependent on the Larmor
frequency. For the analytic description of the relaxation disper-
sion r
rad
1,n
(o
n
), a model is used which combines dipolar and
scalar interactions modulated by translational diffusion.
60
The
correlation time t
t
for both interactions is given by:
t
t
¼
2d
2
D
n
þD
e
ð Þ
(16)
where D
n
and D
e
are self-diffusion constants of the molecules
carrying the nuclear and electron spin, respectively, and d is the
distance of closest approach between electron and nucleus. It is
assumed that t
t
À1
is much larger than the electron spin relaxation
and exchange rates and therefore translational diffusion is the
dominating mechanism of the modulation of electron spin–
nuclear spin interaction. Furthermore, this implies the assumption
that there is effectively no ‘‘sticking’’ phase of motion during
which rotational rather than translational diffusion would
cause modulation of the interaction.
The reduced spectral density for the translational diffusion
modulated dipolar interaction is given by:
60
j
d
ðuÞ¼
15
2
u
À5
u
2
À2þexpðÀuÞÁ u
2
À2
À Á
sinuþ u
2
þ4uþ2
À Á
cosu
Â Ã È É
(17)
where u ¼
ffiffiffiffiffiffiffiffiffiffiffiffi
ot
t
=2
p
. Assuming that scalar interactions are of
very short range with the magnitude decaying exponentially
† The spin exchange frequency o
EX
may as well include contributions from
chemical exchange which are not considered separately in this work.
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with the intermolecular distance, the reduced spectral density
for scalar interactions is given by:
60
j
s
ðuÞ ¼
1
2u
1 þexpðÀuÞ sin u Àcos u ð Þ ½ Š: (18)
The longitudinal relaxation rate, arising from dipolar interac-
tions between electron and nuclear spins, is given by:
61
1
T
1

dip
/ j
d
o
e
Ào
n
; t
t
ð Þ þ3j
d
o
n
; t
t
ð Þ þ6j
d
o
e
þo
n
; t
t
ð Þ ½ Š:
(19)
The contribution of scalar interaction is given by:
61
1
T
1

scal
/ j
s
o
e
Ào
n
; t
t
ð Þ ½ Š: (20)
By introducing a parameter 0 oM
d
o1 that describes the relative
contribution of the dipolar interaction to the total relaxation rate
in the limit o = 0 and making use of o
e
co
n
, the total radical-
induced relaxivity r
rad
1,n
can be obtained as follows:
r
rad
1,n
= r ˆ
rad
[M
d
(7j
d
(o
e
,t
t
) + 3j
d
(o
n
,t
t
)) + (1 À M
d
)10j
s
(o
e
,t
t
)]
(21)
with the amplitude r ˆ
rad
= lim
o
e,n
-0
r
rad
1,n
. The DNP coupling
factor x is then given by
15
x ¼
M
d
5j
d
o
e
; t
t
ð Þ À 1 ÀM
d
ð Þ10j
s
o
e
; t
t
ð Þ
M
d
7j
d
o
e
; t
t
ð Þ þ3j
d
o
n
; t
t
ð Þ ½ Š þ 1 ÀM
d
ð Þ10j
s
o
e
; t
t
ð Þ
(22)
where the mixing parameter M in eqn (43) in the work of
Hausser and Stehlik
15
was substituted by M = 2(1 À M
d
)/M
d
.
3. Materials and methods
3.1 Samples
TEMPO(2,2,6,6-tetramethylpiperidine-1-oxyl) was dissolved in three
different solvents: benzene, 1,4-difluorobenzene (DFB) and hexa-
fluorobenzene (HFB) to give radical concentrations in the range
between 5 mM and 320 mM. Approximately 13 ml of each sample
was filled into a glass tube (outer diameter: 3 mm, inner diameter:
2 mm), resulting in a filling height of about 4 mm. Degassed
samples were prepared by at least three successive freeze–pump–
thaw cycles with the solutions contained inside the glass tubes and
filled with argon gas after the last cycle. Degassing led to a small
loss of solvent and, hence, to a slightly increased radical concen-
tration. The resulting concentrations were accessed by measure-
ments of the nuclear spin-lattice relaxation time T
1,n
, which will be
discussed in the later parts of the manuscript. All samples were
closed using tube-sealing compound (Critoseal, Leica BioSystems,
Nussloch, Germany) and, on top of it, epoxy glue, in order to
improve gas impermeability.
3.2 Setup and measurements
All DNP and EPR experiments were performed at the Max Planck
Institute for Polymer Research using a mobile DNP setup which
is based on a home-built permanent magnet array.
62
The magnet
consists of two coaxially nested discrete Halbach dipoles, which
can be rotated relative to each other. For NMR/EPR detection
and microwave irradiation an ENDOR (electron nuclear double
resonance) probe head (EN4118K-MD4, Bruker BioSpin GmbH,
Rheinstetten, Germany) was used. The microwave resonator
was critically coupled and the built-in radio-frequency (RF) coils
were matched to a home-built tunable RF circuit.
EPR detection in the setup is based on a home-built EPR
detection unit
56
and a stepper motor (PD 57, TRINAMIC Motion
Control GmbH & Co. KG), which controls the rotation of the two
Halbach dipoles and allows for field swept CW EPR experi-
ments. All EPR experiments were performed at 9.69 GHz
microwave frequency and with 10 mW microwave power. Due
to the magnetic field inhomogeneity of the permanent magnet
array, noticeable inhomogeneous broadening of the EPR spec-
tra may be present. However, comparison with line width
measured with the same samples using a commercial benchtop
EPR spectrometer (Miniscope MS200, Magnettech GmbH, Ber-
lin, Germany) gave no evidence of additional broadening. This
may be due to the relatively large inherent line widths of our
samples (see Section 4.1).
For NMR detection a Kea2 NMR spectrometer (Magritek Ltd,
Wellington, New Zealand) was used, operating at 14.7 MHz and
13.8 MHz for
1
H and
19
F NMR experiments, respectively. The
microwave signal for DNP experiments was generated using a
Hewlett Packard HP 8350 B microwave source and amplified
using a Varian (Varian Associates, California, USA) traveling
wave tube amplifier, providing CW irradiation with a power of
up to 15 W. The microwave signal was switched using a TTL
channel of the NMR spectrometer, which was connected to the
‘‘pulse in’’ input of the microwave source. DNP experiments
were carried out by applying CW microwave irradiation for a
period of 5 Â T
1,n
prior to the NMR experiment with the
magnetic field set to the central resonance field measured by
CW EPR. The NMR signal was obtained by adding several
echoes of a Carr–Purcell–Meiboom–Gill (CPMG) sequence.
The number of echoes was chosen such that the duration of
the NMR experiment was about two times the transversal
relaxation time. Reference signals were obtained from the same
experiment with the microwave switched off and several repeti-
tions were averaged in order to improve the signal-to-noise
ratio. The ratio o
e
/o
n
was obtained from the ratio of the
microwave frequency and the NMR frequency and the average
value of all experiments was used (Table 2).
A flow of dry nitrogen gas through the cavity and around the
sample was applied at all times in order to achieve stable
coupling conditions and to control the sample temperature. A
Pt100 sensor was used to measure the temperature of the gas
flow directly before it entered the cavity. An electric heater
controlled by a LakeShore 325 Temperature Controller was
used to ensure a constant flow temperature of 21.5 1C.
Due to the vanishing electric dipole moment of the solvents,
no direct sample heating from the microwave electric field was
expected. However, at high microwave power and long irradia-
tion times, heating of the microwave resonator itself was
observed, which led to a shift in the resonance frequency.
The cooling of the microwave resonator and return to critical
coupling conditions after long, high power microwave pulses
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were studied by observing the reflected microwave power.
Waiting times for successive DNP experiments were chosen
accordingly in order to ensure constant coupling conditions for
all experiments. Furthermore, resonator heating may result in a
comparatively small indirect sample heating effect.
3.3 NMRD measurements
NMRD measurements were performed at the Ilmenau University
of Technology on a Fast Field Cycling (FFC) relaxometer (Spin-
master FFC2000, Stelar s.r.l., Pavia, Italy) for magnetic field
strengths in the range of 0.23 mT to 0.54 T. Additional measure-
ments between 4.7 T and 11.7 T were done on high field magnets
at the Max Planck Institute for Polymer Research. NMRD mea-
surements for
1
H and
19
F nuclear spins were carried out at room
temperature for three different air-saturated solvents, benzene,
DFB and HFB, with at least 29 field steps for a 5 mM radical
concentration in the different solvents and with 9 field steps for
the pure solvents.
The part of the NMRD profiles of the pure solvents that was
measured on the FFC relaxometer was fitted using the model of
Bloembergen, Purcell and Pound.
63
The fitted curves were used
to calculate the pure solvent relaxation rates at those magnetic
fields at which the relaxation of the radical solutions was
measured. At high fields, direct measurements of the pure
solvent relaxation rates at the respective fields were used. The
difference between the relaxation rates of the radical solution
and the pure solvent, divided by the radical concentration, was
calculated to obtain the radical-induced relaxivity r
rad
1,n
(o
n
).
3.4 Concentration of degassed samples
R
1,n
(c) was measured using the mobile DNP setup for all non-
degassed samples with well-defined radical concentrations.
A linear fit of the radical concentration dependence led to
r
rad
1,n
(o = 2p14.7 MHz) and (R
0
1,n
+ R
oxygen
1,n
). R
0
1,n
was obtained
from a sample of degassed pure solvent. The results are given in
Table 1. The radical concentration c of the degassed samples
was obtained from the measured relaxation rate R
deg
1,n
(c) = R
0
1,n
+
r
rad
1,n
c using a rearranged form of eqn (15):
c ¼
R
deg
1;n
ðcÞ ÀR
0
1;n
r
rad
1;n
: (23)
4. Results and discussion
4.1 Electron spin exchange frequencies
In order to determine the electron spin exchange rate k
exch
normalized to the radical concentration, the peak-to-peak
linewidths DB
pp
of degassed and non-degassed samples were
determined from the CW EPR spectra for radical concentra-
tions between 0.5 mM and 20 mM. DB
pp
represents the average
peak-to-peak linewidth of all three EPR transitions; uncertainty
intervals were estimated from the deviation of these three
linewidths from the average value and from the uncertainty
of the visual determination of the exact peak position. For the
non-degassed samples, the dependence of DB
pp
on the radical
concentration was fitted by a linear function from which k
exch
was obtained.
An example for the CW EPR spectra that were obtained for
different radical concentrations in HFB is given in Fig. 1. The
line width is increasing up to about c = 40 mM as a result of
electron spin exchange among the radicals. For radical con-
centrations above 40 mM, all three hyperfine lines coincide and
the line width decreases for increasing radical concentrations.
In general, relatively large linewidths are observed for all solvents,
compared to aqueous solutions of the similar nitroxide radical
TEMPOL (4-hydroxy-TEMPO). For example, a degassed sample
of 4.9 mM TEMPO in HFB gave a peak-to-peak linewidth of
(2.9 Æ 0.1)G whereas for a solution of 5 mM TEMPOL (4-hydroxy-
TEMPO) in water‡ we measured a peak-to-peak linewidth of
(1.72 Æ 0.02)G using the previously mentioned benchtop EPR
spectrometer. The presence of dissolved molecular oxygen in
non-degassed samples results in additional line broadening.
For example, a non-degassed solution of 5 mM TEMPO in HFB
gave a peak-to-peak linewidth of (4.8 Æ 0.4)G. Hence, relatively
short electron spin relaxation times are expected and the
Table 1 Nuclear spin relaxation at 345 mT: relaxation rate of the pure, degassed solvents (R
0
1,n
), radical-induced relaxivity (r
rad
1,n
) and relaxation rate of the pure, air-
saturated solvents (R
0
1,n
+ R
oxygen
1,n
)
Benzene (
1
H) DFB (
1
H) DFB (
19
F) HFB (
19
F)
R
0
1,n
[s
À1
] 0.110 Æ 0.001 0.15 Æ 0.01 0.18 Æ 0.02 0.228 Æ 9,995
r
rad
1,n
[s
À1
mM
À1
] 0.121 Æ 0.004 0.173 Æ 0.003 0.097 Æ 0.001 0.133 Æ 0.002
(R
0
1,n
+ R
oxygen
1,n
) [s
À1
] 0.31 Æ 0.01 0.63 Æ 0.05 0.596 Æ 0.077 0.81 Æ 0.03
Fig. 1 CW EPR spectra measured for air-saturated solutions of TEMPO in HFB.
‡ The solubility of oxygen in water at room temperature is about 100 times
smaller than for HFB. Therefore no degassing was needed for the water solutions.
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maximum achievable relative saturation factor s
rel
(P) is limited
by the maximum available microwave power P.
The results of the line width analysis are given in Table 2:
the lowest exchange rate (k
exch
)
EPR
and the largest linewidth at
0.5 mM concentration were observed for HFB, for which the
solubility of oxygen is about three times as large as for benzene.
64
The exchange rate for HFB was 32% smaller than for benzene,
which is in good agreement with the ratio of viscosities. Conse-
quently, similar values for (k
exch
)
EPR
would be expected for benzene
and DFB. However, noticeably larger exchange rates (k
exch
)
EPR
were
observed for DFB. The same observation was made for the
exchange parameters (k
exch
/W
e
)
DNP
and (k
exch
/W
e
)
DNP,degassed
, which
were obtained from DNP experiments with air-saturated and
degassed samples, respectively. This may indicate that the electron
spin exchange for TEMPO in DFB solutions not only depends
on the macroscopic viscosity but is also affected by further
molecular interactions.
Considering the uncertainty interval and the viscosity of
water at room temperature, which is 1 mPa s, our result for the
exchange rate of benzene is close to the value of 2.0 Â 10
9
s
À1
M
À1
given by Tu¨rke and Bennati
57
for the exchange rate of
TEMPONE-D,
15
N (4-oxo-TEMPO) in water at room temperature.
Using eqn (14), this would correspond to an exchange rate of
3.1 Â 10
6
s
À1
mM
À1
for benzene at the same temperature.
4.2 DNP experiments
An example of the DNP enhancements that were obtained for
the different radical concentrations with varying microwave
power in HFB is given in Fig. 2 (symbols). Furthermore, the
plot shows fits of the microwave power dependence according
to eqn (6) (lines). Relative saturation factors s
rel
(P) between 0.54
and 0.68 were achieved for 14 W microwave power. Despite the
limitation in the achievable saturation, which is a result of the
large EPR line width, an accurate extrapolation to infinite micro-
wave power was still possible due to the very good agreement
between the fit model and the enhancement data.
Extrapolated enhancements E
max
(c) for air-saturated and
degassed samples are shown in Fig. 3. Air-saturated samples
show increasing extrapolated enhancements up to a radical
Table 2 Results from DNP, NMRD and CW EPR measurements. The correlation times of translational diffusion t
t
and the contribution of dipolar interaction M
d
to the
relaxivity were obtained from fitting eqn (21) to the NMRD data. The coupling factor x
NMRD
was calculated using eqn (22) and the NMRD fitting parameters. The
exchange parameters (k
exch
/W
e
)
DNP
, x
DNP
and (k
exch
/W
e
)
DNP,degassed
were obtained from fitting extrapolated DNP enhancements E
max
(c) using eqn (9). (k
exch
)
EPR
was obtained from CW EPR by fitting peak-to-peak linewidths DB
pp
(c) using eqn (10) and (11). The EPR peak-to-peak linewidths at 0.5 mM radical concentration
DB
pp
(0.5 mM) serve as a qualitative measure for the electron spin relaxation time
Benzene (
1
H) DFB (
1
H) DFB (
19
F) HFB (
19
F)
x
DNP
0.33 Æ 0.01 0.38 Æ 0.01 0.143 Æ 0.005 0.094 Æ 0.003
x
NMRD
0.32 Æ 0.02
b
0.35 Æ 0.04 0.14 Æ 0.12 0.10 Æ 0.02
a
(k
exch
/W
e
)
DNP
[mM
À1
] 0.30 Æ 0.06 0.82 Æ 0.20 2.2 Æ 1.4 0.32 Æ 0.08
(k
exch
/W
e
)
DNP,degassed
[mM
À1
] 0.40 Æ 0.08 1.6 Æ 0.6 1.0 Æ 0.4 0.24 Æ 0.12
(k
exch
)
EPR
[s
À1
mM
À1
] 3.7 Æ 0.5 4.6 Æ 0.5 2.5 Æ 0.2
DB
pp
(0.5 mM) [G] 3.2 Æ 0.3 3.2 Æ 0.2 4.3 Æ 0.2
M
d
1.0
b
1.00 Æ 0.08 0.78 Æ 0.18 0.75 Æ 0.03
a
t
t
[10
À11
s] 3.4 Æ 0.5
b
2.3 Æ 0.5 3.1 Æ 1.0 4.2 Æ 0.1
a
Z [mPa s] 0.6502 (20 1C)
67
0.6390 (20 1C)
67
0.944 (20 1C)
c
o
e
/o
n
659.50 Æ 0.03 700.97 Æ 0.02
a
The amplitude was fixed to the value of the low-field plateau and values below 10
7
rad s
À1
were excluded from the fit.
b
The parameter M
d
= 1 was
fixed.
c
The value was obtained by fitting an Arrhenius model to the literature data
68
and extrapolating to 20 1C.
Fig. 2
19
F Overhauser DNP enhancements obtained for air-saturated solutions
of TEMPO in HFB together with fits according to eqn (6). The resulting extra-
polated enhancements E
max
are given in Fig. 3.
Fig. 3
1
H and
19
F Overhauser DNP extrapolated enhancements E
max
obtained
for air-saturated (filled symbols) and degassed (open symbols) solutions of
TEMPO in benzene (
1
H: squares), DFB (
1
H: circles,
19
F: up-pointing triangles)
and HFB (
19
F: down-pointing triangles) together with fits for air-saturated
samples according to eqn (9). The fit parameters are given in Table 2.
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concentration of about 80 mM. Extrapolated enhancements at
very high radical concentrations, i.e. larger than 160 mM, which are
expected to depend only on the coupling factor, show significant
differences for the different nuclei on the one hand, and for the
same nuclei but different solvents on the other hand. For both
nuclei, DFB provides the largest enhancements at all radical
concentrations. Results for E
max
(c) from degassed samples are
roughly in agreement with those from air-saturated samples.
Removing dissolved oxygen from the samples results in
smaller EPR line widths and lower longitudinal relaxation rates for
both nuclear and electron spins. As a result, relative saturation
factors (eqn (4)), maximum saturation factors (eqn (8)) and leakage
factors (eqn (2)) should be larger. Therefore, under the same
experimental conditions, both measured and extrapolated enhance-
ments should be larger for the degassed samples compared
to air-saturated samples. While relative saturation factors for
degassed samples were indeed larger, this behavior was not
consistently reproduced in the extrapolated enhancements.
Fits of E
max
(c) from air-saturated samples according to eqn (9),
with the fit parameters x
DNP
and (k
exch
/W
e
)
DNP
(see Table 2), are given
as dashed lines in Fig. 3. Relatively good agreement with the data is
obtained for benzene and HFB samples, whereas the results for DFB
show larger scattering and some deviations from the respective fits.
The results are given in Table 2: considerably lower coupling factors
are observed for DNP experiments on
19
F nuclei compared to
1
H nuclei, indicating that there is significant contribution of scalar
interaction between electron and
19
F nuclear spins. Regardless
of the scatter observed in some fits, uncertainties for the
coupling factors are below 3.5%. Furthermore, the values for
x
DNP
show a good agreement with those obtained independently
from NMRD measurements (x
NMRD
, see Section 4.3).
Regarding the parameters (k
exch
/W
e
)
DNP
as well as (k
exch
/
W
e
)
DNP,degassed
, electron spin exchange between the radicals
appears to be significantly more effective for radical solutions
in DFB compared to benzene and HFB. However, the observed
difference for DFB between
1
H and
19
F is not reasonable and is
probably a result of the scattered data, especially for
19
F on DFB
(Fig. 3). As a result of the shorter electron spin relaxation times in
our experiments (see Section 4.1), most values for (k
exch
/W
e
)
DNP
are
lower than the value 1.2 mM
À1
which can be calculated from the
work of Tu¨rke and Bennati
57
using the given result T
1e
= (2W
e
)
À1
=
298 ns and the previously mentioned value k
exch
= 2.0 Â10
9
s
À1
M
À1
.
4.3 NMRD measurements
The NMRD profiles of
1
H and
19
F nuclear spins are shown in Fig. 4
(symbols). For all measurements, the profiles show a plateau of
constant relaxivity for nuclear Larmor frequencies below o
n
=
10
6
rad s
À1
. At larger magnetic fields, between 10
6
rad s
À1
and
10
9
rad s
À1
Larmor frequency, a decay is observed which results
from the contribution of the dipolar and scalar spectral density
functions at the electron spin Larmor frequency.
Fits of the NMRD profiles according to eqn (21) with the fit
parameters r ˆ
rad
, M
d
and t
t
are shown in Fig. 4 as dashed lines,
the corresponding parameters are given in Table 2. Furthermore,
DNP coupling factors x
NMRD
are given in the table, which were
calculated using the fit parameters and eqn (22).
A good agreement between the measured NMRD profile and
the fit model is obtained for measurements on benzene and
DFB. For the relaxation of
1
H, only dipolar coupling to the
electron spin is expected.
17,18,65
Hence, M
d
= 1 was fixed for the
fit of the benzene data in order to minimize the effect of scatter
in the high field regime. For
19
F the fit parameter M
d
is mainly
determined by the few high field relaxation data points, which is
a consequence of the fact that the spectral density function for
scalar interaction j
s
(o
e
,t
t
) is close to zero in these fields and only
contributions from dipolar interaction remain for the relaxation.
Comparing benzene and HFB, approximately the same
relaxivities for
1
H and
19
F are observed in the high field limit,
where spectral densities at the electron spin Larmor frequency
and hence, the scalar relaxation rates, are almost zero. This
indicates that for both solvents benzene and HFB, the dipolar
interactions with the electron spin are of similar strength. In
the low field limit a value about 33% larger is observed for HFB,
representing the additional relaxivity originating from scalar
interactions. For DFB, in contrast, the observed
19
F relaxivities
are significantly smaller than the
1
H relaxivities. Hence, the
electron spin, which is located on the partially negatively charged
oxygen and on the nitrogen atom,
66
interacts much more strongly
with
1
H on DFB than with the much more electronegative
19
F
on DFB. Furthermore, comparing the same nuclei on different
solvents, the interaction with the electron spin is stronger for
1
H on DFB than for
1
H on benzene but is weaker for
19
F on DFB
than for
19
F on HFB.
The fit for the
19
F relaxation dispersion of HFB shows
some deviations from the measured data in the range o
n
=
10
5
. . .10
7
rad s
À1
. For this fit, the amplitude r ˆ was fixed to the
value of the relaxivity at the low field plateau and data for which
o
n
o 10
7
rad s
À1
were neglected for the fitting procedure. Never-
theless, a good agreement between the data and the fit model at
9 Â 10
7
rad s
À1
, the Larmor frequency relevant for X-band DNP
experiments, was achieved. Although this behavior indicates
that, in contrast to the other solvents, the radical–solvent
Fig. 4 Dispersion of the
1
H and
19
F radical-induced relaxivity for air-saturated
solutions of TEMPO in benzene (
1
H: squares), DFB (
1
H: circles,
19
F: up-pointing
triangles) and HFB (
19
F: down-pointing triangles) together with the best fits
according to eqn (21). The fit parameters are given in Table 2.
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interaction for HFB may not sufficiently be described by the
applied model involving only translational diffusion.
While for
1
H NMRD measurements on DFB the parameter
M
d
indicates no scalar coupling, the results for
19
F measure-
ments clearly show a contribution of scalar coupling. Within
the uncertainty of the fitted value for M
d
from the DFB data, no
definite conclusion can be drawn from the NMRD profile on
whether the scalar coupling contribution for this solvent is
different from that for HFB. However, regarding the coupling
factors for
19
F that were obtained from DNP experiments, a
rather small difference between DFB and HFB is observed,
which cannot be explained only by variations in t
t
, even if the
large uncertainty interval for t
t
is taken into account. This is in
qualitative agreement with observations from
19
F DNP experi-
ments using the radicals BDPA
31
or DPPH,
29
where increasing
scalar coupling strength was observed for an increasing number
of fluorine atoms per molecule. However, the small extent of this
effect that was observed for our system rather suggests a
similarity to the behaviour of the GALV radical, which showed
no significant dependence on the fluorination of the solvent.
29
Furthermore, our findings are in agreement with the work of
Bates as well as Glazer and Poindexter, who showed that
19
F DNP
on HFB exhibits a significant but not dominating contribution of
scalar coupling with aliphatic nitroxide radicals,
32,34
in contrast
to aromatic nitroxide radicals.
34
The calculated coupling factors x
NMRD
are, within the error,
in agreement with the coupling factors obtained from DNP. The
relatively large uncertainties for x
NMRD
are a result of their
sensitivity to variations in the parameter M
d
, which is mainly
defined by the few high field points in the NMRD profiles.
In the work of Glazer and Poindexter
34
the scalar coupling of
the electron spin of 4-oxo-TEMPO with HFB was explained by a
collision of the radical oxygen with the center of the HFB ring
(center collision). Due to the positive electrostatic potential of
HFB above the center of the ring,
69
this contact presumably leads
to a comparatively close approach of the partially negatively
charged oxygen and nitrogen atoms on the radical, which carry
the major part of the electron spin density. In contrast, the direct
collision of the radical oxygen with the fluorine atoms on HFB
(edge collision) should exhibit a much larger distance of closest
approach, due to the negative electrostatic potential around them.
Therefore, center collisions should have a major contribution to
both dipolar and scalar
19
F spin lattice relaxation rates. Further-
more, these center collisions may explain our observation that
the dipolar hyperfine interaction for
19
F on HFB is of compar-
able strength as for
1
H on benzene, even though, regarding the
different electrostatic potentials,
69
the edge collisions should
not be as effective for the
19
F relaxation of HFB as they are for
the
1
H relaxation of benzene.
Regarding the deviations from the diffusion model that are
observed for the
19
F NMRD profile of HFB, one may assume that
during a center collision a labile solvate complex is formed, which
has a characteristic lifetime longer than the translational correla-
tion time. Hence, a rotational diffusion component may contribute
to the
19
F relaxation dispersion. This observation might indicate a
similar dynamic behaviour of TEMPO as compared to the radicals
GALV (galvinoxyl) and TTBP (2,4,6-tri-tert-butylphenoxyl): for
the latter two radicals Mu¨ller-Warmuth et al.
24
found that the
magnetic field dependence of the
19
F DNP coupling factor in
HFB can be explained by using two different correlation times
for the scalar interaction. In contrast, the benzene molecule has
a negative electrostatic potential above the center of the ring.
69
Hence, central collisions should only have a weak contribution
to the
1
H relaxation and should not lead to the formation of a
solvate complex. Consequently, the relaxation dispersion of
benzene can be described assuming only translational diffusion.
Due to the large electronegativity of the fluorine atoms, DFB
has a more positive electrostatic potential near the hydrogen
atoms than benzene.
69
Hence, edge collisions with
1
H should
have a smaller distance of closest approach d. This is reflected
in the larger
1
H relaxivity compared to benzene and in the
1
H translational correlation time t
t
, which is smaller than for
benzene despite similar viscosities and, hence, comparable
diffusion coefficients D. Furthermore, center collisions might
have a stronger contribution than for benzene, due to the less
negative electrostatic potential above the center of the DFB
ring. However, they should not be as strong as for HFB, which
explains the smaller
19
F relaxivities at high field and the smaller
contribution of scalar coupling for
19
F on DFB compared to HFB.
Again, edge collisions are expected to have a comparatively small
effect for the relaxation of
19
F on DFB.
However, further experiments are necessary to test this
interpretation, such as temperature dependent NMRD measure-
ments, molecular dynamics simulations and magnetic field-
dependent measurements of the DNP coupling factor. Moreover,
DNP and NMRD studies using other fluorinated aromatic solvents,
for example 1,2-difluorobenzene, 1,3-difluorobenzene, trifluoro-
benzene, tetrafluorobenzene and pentafluorobenzene, should
reveal further insight into the interactions between TEMPO
and the solvent and should help to clarify the remaining issues.
5. Conclusion
We have obtained the DNP coupling factor and a description of
the concentration-dependent maximum saturation factor from
analyzing DNP enhancements for
1
H and
19
F for a range of radical
concentrations in three different solvents. For
1
H we have obtained
enhancements comparable to those obtained for aqueous solutions
of 4-oxo-TEMPO.
57
Due to the contribution of scalar coupling to the
electron spins, enhancements were significantly smaller for
19
F. For
both nuclei solutions of DFB provided the largest enhancements.
Analysis of NMRD profiles for every solvent and nucleus allowed
distinguishing between the influence of molecular dynamics
and the contribution of different coupling mechanisms on the
DNP enhancements.
1
H and
19
F NMRD profiles of benzene and
DFB samples were successfully described by fitting a diffusion
model that included both dipolar and scalar interactions. For
HFB, the fit revealed deviations from the diffusion model,
indicating the presence of another type of dynamics, such as
for example rotational diffusion. Coupling factors were derived
from the fit parameters and were found to be in good agree-
ment with the DNP results for all solvents. For DFB,
1
H dipolar
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relaxivities were found to be larger than for benzene, while
19
F
dipolar relaxivities were found to be smaller for DFB compared
to HFB. Furthermore, a larger scalar contribution was found for
19
F on HFB compared to
19
F on DFB. The characteristics of the
NMRD profiles were interpreted in terms of the different
electrostatic potentials of the solvents interacting with the
partially negatively charged oxygen and nitrogen atoms on the
radical, which have the largest electron spin density. Remark-
ably, both DNP and NMRD experiments gave indications that
the properties of aliphatic nitroxide radicals for DNP on aro-
matic solvents may to some extent be comparable to the
aromatic radical GALV.
Both DNP and CW EPR experiments revealed an increased
EPR line mixing efficiency for TEMPO in DFB, which cannot be
explained only by differences in the solvent viscosity. Measure-
ments of the saturation transfer between the different electron
spin transitions using Pulsed ELDOR
57
could help to understand
these differences in the efficacy of electron spin exchange.
Finally, the results of our detailed study may already add to a
comprehensive understanding of
1
H and
19
F DNP on aromatic
solvents for a broad range of different radicals and may thus
provide useful information for applications of
19
F DNP.
Acknowledgements
This work was supported by the Max Planck Graduate Center with
the Johannes Gutenberg-Universita ¨t Mainz (MPGC). Helpful discus-
sions with Dariush Hinderberger are gratefully acknowledged.
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