A slowly relaxing rigid biradical for efficient dynamic nuclear polarization surface-enhanced NMR spectroscopy: Expeditious characterization of functional group manipulation in hybrid materials

Article abstract of DOI:10.1021/ja210177v

A new nitroxide-based biradical having a long electron spin-lattice relaxation time (T_1e) has been developed as an exogenous polarization source for DNP solid-state NMR experiments. The performance of this new biradical is demonstrated on hybrid silica-based mesostructured materials impregnated with 1,1,2,2-tetrachloroethane radical containing solutions, as well as in frozen bulk solutions, yielding DNP enhancement factors (∈) of over 100 at a magnetic field of 9.4 T and sample temperatures of ～100 K. The effects of radical concentration on the DNP enhancement factors and on the overall sensitivity enhancements (σ^?) are reported. The relatively high DNP efficiency of the biradical is attributed to an increased T_1e, which enables more effective saturation of the electron resonance. This new biradical is shown to outperform the polarizing agents used so far in DNP surface-enhanced NMR spectroscopy of materials, yielding a 113-fold increase in overall sensitivity for silicon-29 CPMAS spectra as compared to conventional NMR experiments at room temperature. This results in a reduction in experimental times by a factor >12 700, making the acquisition of ¹³C and ¹⁵N one- and two-dimensional NMR spectra at natural isotopic abundance rapid (hours). It has been used here to monitor a series of chemical reactions carried out on the surface functionalities of a hybrid organic-silica material.

Full text of DOI:10.1021/ja210177v

Article
pubs.acs.org/JACS
A Slowly Relaxing Rigid Biradical for Efficient Dynamic Nuclear
Polarization Surface-Enhanced NMR Spectroscopy: Expeditious
Characterization of Functional Group Manipulation in Hybrid
Materials
Alexandre Zagdoun,† Gilles Casano,‡ Olivier Ouari,‡ Giuseppe Lapadula,§ Aaron J. Rossini,†
Moreno Lelli,† Mathieu Baffert,∥ David Gajan,§ Laurent Veyre,∥ Werner E. Maas,⊥ Melanie Rosay,⊥
Ralph T. Weber,⊥ Chloe Thieuleux,∥ Christophe Coperet,§ Anne Lesage,† Paul Tordo,*,‡
́
and Lyndon Emsley*,†
†Centre de RMN a
‡SREP LCP UMR 6264, Aix Marseille Universities, Faculte
§Department of Chemistry, Laboratory of Inorganic Chemistry, ETH Zurich, CH-8093, Zurich, Switzerland
̀
Tres
̀
Hauts Champs, Universite
́
de Lyon (CNRS/ENS Lyon/UCB Lyon 1), 69100 Villeurbanne, France
de Saint Jer me, 13013 Marseille, France
́
́ ̂
o
̈
̈
∥Institut de Chimie de Lyon, C2P2, CNRS/UCB Lyon 1/ESCPE Lyon, 69100 Villeurbanne, France
⊥Bruker BioSpin Corporation, Billerica, Massachusetts 01821, United States
S
* Supporting Information
ABSTRACT: A new nitroxide-based biradical having a long
electron spin−lattice relaxation time (T1e) has been developed
as an exogenous polarization source for DNP solid-state NMR
experiments. The performance of this new biradical is
demonstrated on hybrid silica-based mesostructured materials
impregnated with 1,1,2,2-tetrachloroethane radical containing
solutions, as well as in frozen bulk solutions, yielding DNP
enhancement factors (ε) of over 100 at a magnetic field of 9.4
T and sample temperatures of ∼100 K. The effects of radical
concentration on the DNP enhancement factors and on the
overall sensitivity enhancements (Σ†) are reported. The relatively high DNP efficiency of the biradical is attributed to an
increased T1e, which enables more effective saturation of the electron resonance. This new biradical is shown to outperform the
polarizing agents used so far in DNP surface-enhanced NMR spectroscopy of materials, yielding a 113-fold increase in overall
sensitivity for silicon-29 CPMAS spectra as compared to conventional NMR experiments at room temperature. This results in a
reduction in experimental times by a factor >12 700, making the acquisition of 13C and 15N one- and two-dimensional NMR
spectra at natural isotopic abundance rapid (hours). It has been used here to monitor a series of chemical reactions carried out on
the surface functionalities of a hybrid organic−silica material.
biological solids6−13 as well as for hybrid or inorganic
INTRODUCTION
Nuclear magnetic resonance (NMR) is one of the richest
■
materials.14−17 The dramatic sensitivity gain provided by the
DNP approach has thus enabled the determination of the
interstrand architecture of amyloid fibrils11−13 and the
elucidation of the bonding topologies at the surface of
functionalized mesostructured materials.15 In this approach,
samples are dissolved or impregnated with a solution
containing stable exogenous paramagnetic centers such as
nitroxides or trityls,18 which act as polarizing agents. Most high-
field solid-state DNP NMR experiments are carried out in the
presence of biradical polarizing agents19 as they can transfer
polarization through the cross-effect (CE) mechanism, which is
sources of structural and dynamic information for molecular
and materials sciences. However, it is traditionally limited by its
intrinsic poor sensitivity. Dynamic nuclear polarization (DNP)
has in principle the potential to increase NMR sensitivity by
orders of magnitude by transferring polarization from unpaired
electrons to nuclei. First discovered in the 1950s with low
magnetic fields,1−3 high-field DNP NMR experiments are now
possible with gyrotron sources, which are capable of delivering
high-power high-frequency microwaves (MW).4,5 In this
respect, in the past few years, DNP-enhanced solid-state
NMR spectroscopy under magic angle spinning (MAS)
conditions has made great progress, and DNP signal enhance-
ment factors (ε) of up to ∼250 have been reported at high
fields (up to 9.4 T) and low temperatures (<100 K) for
Received: October 25, 2011
Published: December 19, 2011
© 2011 American Chemical Society
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currently the most efficient mechanism for DNP at high
fields.20
The CE relies upon having a three-spin system consisting of
two dipolar coupled electrons and a nucleus. For polarization
transfer to occur from the electrons to the nucleus upon
saturation of one of the EPR frequencies, the two unpaired
electrons should have a significant dipolar coupling, and their
EPR frequencies must differ by the nuclear Larmor frequency
(here proton).18
Initial CE high-field DNP experiments were performed with
solutions doped with high concentrations of monoradical
species, such as TEMPO.21 Much effort has been recently
devoted to the design and synthesis of more efficient radicals
for DNP.21−24 Griffin and co-workers demonstrated that
biradical polarizing agents yielded significant improvements in
the DNP process, and therefore in the sensitivity enhancement
factors.19 The success of biradicals is primarily attributed to the
uniformly short distance between the two unpaired electrons in
a biradical, which guarantees that all unpaired electrons are
dipolar coupled to at least one other electron. With nitroxide-
based biradicals, the EPR frequency difference is provided by g-
anisotropy, and the difference in EPR frequencies can match
1
the H Larmor frequency when the gxx (or gyy) component of
the g tensor of one of the unpaired electrons is parallel to the
gyy (gzz) component of the other.25,26 Recently, triradical,23
heterogeneous biradical species or mixtures of radical
species,27,28 and metal ions29 have been proposed as
alternatives to dinitroxide polarizing agents.
The water-soluble biradical TOTAPOL22 (Figure 1d) is
today the most commonly employed exogenous polarizing
agent in DNP solid-state NMR, in particular for biological
applications.30 TOTAPOL was shown, however, to have a
relatively flexible structure,25 and as a result the frequency
matching condition for the CE mechanism is only properly
fulfilled for the fraction of the biradicals that adopts the correct
conformation. Another step forward was achieved by Griffin,
Tordo, and co-workers who introduced bTbK26 (Figure 1e), a
binitroxide radical in which the two TEMPO molecules are
linked by a rigid tether. The rigid tether constrains the
orientation of the TEMPO moieties, such that the gzz
components of the two g-tensors are roughly orthogonal. It
was demonstrated that bTbK provides DNP enhancement
factors, which are 1.4 times larger than TOTAPOL under
similar conditions.26 We have more recently shown that this
biradical may be readily combined with organic solvents for the
investigation of water incompatible materials.31
The electron spin−lattice relaxation time T1e is another
factor that impacts the DNP process. It is known that a longer
T1e facilitates saturation of the EPR transition.21,32 This effect
partially accounts for the improved DNP at lower sample
temperature,5,33 because electron relaxation rates slow sig-
nificantly with temperature.34,35 However, this factor has not
been so far considered directly in the design of biradicals for
DNP.
Figure 1. (a) Transmission electron microscopy image of the hybrid
mesostructured silica material studied here. (b) Schematic representa-
tion of the pores. The blue circle represents the organic moieties
present on the mesoporous surface. The shaded gray area represents
the bulk silica. (c) Structure of Mat-PhOH.36 Different types of silicon
atoms present at the surface are labeled here. (d−f) Structures of
TOTAPOL, bTbK, and bCTbK.
show that this biradical yields proton and silicon-29 cross-
polarization (CP) DNP enhancement factors that are between
2.5 and 4 times larger than bTbK. The reduction in
experimental times provided by DNP experiments with
bCTbK further pushes back the limits of solid-state NMR
spectroscopy in terms of sensitivity, notably for the structural
investigation of dilute surface species. This polarizing mixture is
directly applicable to study a wide range of problems. We show
here that with the high sensitivity provided by DNP with
bCTbK, it becomes possible to expediently monitor the
stepwise functionalization at the surface of hybrid materials
by 1H, 13C, 29Si, as well as 15N solid-state NMR spectroscopy at
natural isotopic abundance. Notably, high-quality one-dimen-
sional 15N solid-state NMR spectra can be acquired with
experiment times on the order of 1 h, and two-dimensional
1H−15N HETCOR spectra can be acquired in less than 12 h.
In this Article, we introduce a new biradical, bis-cyclohexyl-
TEMPO-bisketal (bCTbK, Figure 1f), a bulky derivative of
bTbK, in which the geminal dimethyl groups have been
replaced by spirocyclohexyl moieties. In agreement with
previous relaxation rate measurements on spirocyclohexyl
functionalized nitroxide radicals,35 we show that, in 1,1,2,2-
tetrachloroethane (“tetrachloroethane”) at 100 K, bCTbK has a
T1e value that is almost twice as long as that for bTbK. On a
model hybrid mesostructured silica-based material,14,36 we
EXPERIMENTAL SECTION
■
Synthesis and characterization of the hybrid mesostructured silica
materials are described in the Supporting Information. The biradical
TOTAPOL was purchased in crystalline form from DyNuPol Inc.,
MA, and used without further purification. The solvents were
purchased from Sigma-Aldrich and used without further purification.
Synthesis of bCTbK. bCTbK was prepared in a four-step
sequence starting from 2,2,6,6-tetramethylpiperidin-4-one. The 2,6-
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Figure 2. (a) Proton DNP (εH) and silicon DNP enhancement (εSi,CP). (b) The 29Si quenching factor (θSi) shown as a function of bCTbK
†
concentration in 1,1,2,2-tetrachloroethane. (c) Overall (ΣSi,CP and Σ Si,CP) sensitivity enhancements. Note that εH quantifies the enhancement of the
solvent and εSi,CP quantifies that of the surface. Experimental details and definition of the enhancement factors are given in the Supporting
Information.
Table 1. DNP Efficiency Comparison and Electron Spin−Lattice Relaxation Times for the TOTAPOL, bTbK, and bCTbK
Biradicals under Optimal Conditions
ab
,
ac
,
ac
,
bd
,
e
e
biradical
solvent
water
εH
εSi,CP
ΣSi,CP
IIm(13C)
T1e (μs)
T2e (μs)
f
TOTAPOL
bTbK
−
26(3)
31(3)
21(3)
52(3)
15(4)
12(5)
0.75(3)
0.51(2)
1.00(4)
554(4)
453(4)
762(4)
1.6(1)
1.5(1)
2.8(1)
tetrachloroethane
tetrachloroethane
bCTbK
105(3)
38 (7)
a
b
Measured on Mat-PhOH impregnated with a 16 mM biradical solution. Estimated errors are given in parentheses. Recorded on a triple resonance
CPMAS probe at 99 K. The difference of DNP efficiency between the two probes can be attributed to differences of the hardware (e.g., waveguide
efficiency and alignment) and the lower temperature that could be reached with the triple resonance probe. See the Supporting Information for a
more detailed characterization of the DNP efficiency dependence on the biradical concentration on this probe. This explains the discrepancy
c
d
between εH and εSi for bCTbK in tetrachloroethane. Recorded on a double resonance CPMAS probe at 102 K. In this case, it is not possible to
quantify the overall sensitivity enhancement for carbon due to the fact that it is impossible to obtain a MW off carbon spectrum with high enough
S/N ratio to calculate reliable integrals in a reasonable experimental time. However, it is possible to compare the relative efficiency of the different
biradicals for enhancing the carbon resonances by comparing the integrated intensities per unit of mass (IIm). Here, the IIm values of the aromatic
resonances of Mat-PhOH impregnated with the various biradical containing solutions are displayed. The concentration of the bTbK and TOTAPOL
solutions was 12 mM, and the bCTbK one was a 16 mM solution (concentration giving optimal sensitivity for each biradical). The IIm of Mat-PhOH
e
impregnated with a 16 mM solution of bCTbK in tetrachloroethane was taken as a reference. Electron spin−lattice (T1e) and spin−spin (T2e)
relaxation times were measured on the edge of the EPR line in a frozen bulk solution at 90 K with 8 mM biradical concentration at an EPR resonance
f
1
frequency of 94 GHz. For TOTAPOL, glycerol was added to water to form a glass (60%/40% glycerol/H2O by volume). The H resonance of
water is too broad to calculate a reliable proton DNP enhancement.
cyclohexyl-substituted piperidin-4-one 2 (see the Supporting In-
formation) was prepared according to the method described by
Yamada and Utsumi37 and was then reacted with pentaerythritol to
afford the spirodiamino precursor of bCTbK. Subsequent oxidation of
the spirodiamino precursor by hydrogen peroxide in the presence of
sodium tungstate provided the dinitroxide bCTbK (see the Supporting
Information for further experimental details).
Sample Preparation for NMR Experiments. Samples were
prepared by impregnating 8.9−9.8 mg of dry powder with ca. 17 μL of
a radical containing solution. The total mass of impregnated material
was determined, and the sample was mixed using a glass-stirring rod to
obtain a homogeneous distribution of the radical containing solution
in the powder. The impregnated powder was then packed into a 3.2
mm sapphire NMR rotor to maximize MW penetration into the
sample. The mass of impregnated material inside the rotor was
determined, and a tight polyfluoroethylene plug was inserted to
prevent any leakage of the solvent during spinning. The rotor was
capped with a zirconia drive tip and quickly inserted into the DNP
spectrometer. See http://pubs.acs.org/JACSbeta/scivee/index.
html#video2 for a video demonstration of the sample preparation
procedure.
DNP enhancement maximum of TOTAPOL (263.334 GHz), with an
estimated 4 W power of the MW beam at the output of the probe
1
waveguide. 29Si spectra and H spectra of Mat-PhOH impregnated
with radical containing solutions were recorded using a double
resonance low-temperature CPMAS probe with a sample spinning
1
frequency of 8 kHz and a sample temperature of 102 K. H, 13C, and
15N spectra were recorded using a triple resonance low-temperature
CPMAS probe with a sample temperature of 99 K and sample
spinning frequencies of 12 kHz for the 13C spectra and 8 kHz for the
15N spectra. SPINAL-6438 heteronuclear decoupling was applied
during acquisition (ω1H/2π = 89 kHz). Additional experimental details
are provided in the Supporting Information. Pulse programs are
available on request. Processing of the spectra was done using the
Topspin software package, and fitting of NMR relaxation measure-
ments was done using Kaleidagraph.
EPR Spectroscopy. All measurements were conducted at W band
(94 GHz EPR frequency) on a Bruker Elexsys E680 EPR
spectrometer, with sample temperatures of 90 K. T1e was measured
using inversion−recovery sequences, and the curves were fitted with
biexponential functions to obtain T1e. The slow component of the fit is
identified as T1e, while the fast component (<90 μs) is attributed to
spectral diffusion and is not reported here.
Solid-State NMR Spectroscopy. All spectra were acquired on a
Bruker Avance III 400 MHz DNP NMR spectrometer equipped with a
263 GHz gyrotron microwave system5 (B0 = 9.4 T, ωH/2π = 400
MHz, ωC/2π = 100 MHz, ωSi/2π = 79.5 MHz). The field sweep coil
of the NMR magnet was set so that MW irradiation occurred at the
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(the calculation of these factors here is detailed in Table S3).17
Σ† is an estimation of the overall gain in sensitivity obtained by
carrying out low-temperature DNP solid-state NMR experi-
ments instead of conventional room-temperature experi-
ments.17
RESULTS AND DISCUSSION
■
bCTbK DNP Efficiency. The DNP efficiency of bCTbK
was evaluated by impregnating a model mesoporous silica-
based material Mat-PhOH36 containing phenolic ligands
incorporated at the surface of the pores ((Figure 1a−c). The
material was impregnated with bCTbK containing tetrachloro-
ethane solutions of various concentrations. Tetracholorethane
was used because we have previously shown that this solvent
provides optimal DNP enhancements (ε) for bTbK.31 Figure
2a displays the dependence of the proton (εH) and silicon
(εSi,CP) DNP enhancement on the radical concentration (where
ε is defined as the ratio of the integrated intensities of the
spectra acquired with and without microwave irradiation under
otherwise identical conditions). εH is found to peak at 65 for a
radical concentration of 15.8 mM (similar to optimum
concentrations previously observed for other biradicals).17,31
εSi,CP peaks at 52 for a concentration of 19.8 mM. The
difference between the silicon enhancement at 15.8 and 19.8
mM is small, so the offset between the optimal concentration
for proton and silicon is within experimental error. Note these
curves were obtained with a double-resonance probe at 102 K.
Higher enhancements for proton were obtained with a triple
resonance probe at 99 K (see Table 1, footnote b, Figure 3, and
As expected, and as previously observed on other systems, θ
diminishes as the radical concentration increases (Figure
2b).17,31 Here, however, quenching appears to be less than
for water/TOTAPOL with θ = 0.39 for Mat-PhOH
impregnated with a 12 mM solution of TOTAPOL in water
and 0.54 for a 12 mM solution of bCTbK in tetrachloroethane.
Figure 2c displays the overall sensitivity enhancements for
silicon with (Σ†Si,CP) and without (ΣSi,CP) the Boltzmann factor
as a function of the radical concentration.
Σ
Si,CP and Σ†Si.CP peak at 15.8 mM with a value of 38 and 113,
respectively. As expected, ΣSi,CP is always lower than εSi,CP as it
accounts for the decrease in θ and T1(1H) with increasing
radical concentration (Figure S3), the latter meaning that more
scans can be acquired in the same amount of time. A value of Σ†
= 113 translates into a reduction in experimental time by a
factor of 12 700 as compared to ordinary room-temperature
experiments.
Performance in Frozen Bulk Solutions and Other
Solvents. bCTbK also provides high enhancements in frozen
bulk solution (εH = 63, εC,CP) = 67, Figure S4), as compared to
εH = 22 for bTbK.31The high enhancements provided by
bCTbK also mean that reasonable ε of ∼30 can be obtained for
nonoptimal solvents (e.g., εH = 23 and εSi,CP = 26 for a 12 mM
solution of bCTbK in mesitylene as opposed to εH = 6 for a 10
mM solution of bTbK in mesitylene,31 both impregnated in
Mat-PhOH, Figure S5). This therefore extends the number of
solvents that can be used for DNP experiments, which is a
necessity if chemically reactive systems are to be studied by
DNP SENS in the future.
Comparison with Previously Used Biradicals. Under
the same experimental conditions, both TOTAPOL and bTbK
are found to be typically less efficient than bCTbK (εSi,CP = 31
for TOTAPOL/water and εSi,CP = 21 for bTbK/tetrachloro-
ethane, both impregnated within Mat-PhOH, Table 1). With
εSi,CP = 52, Mat-PhOH impregnated with bCTbK solutions
provides the best enhancement obtained so far under any
conditions for this model material. This corresponds to an
improvement in the DNP efficiency by a factor of about 2.5
with respect to bTbK in tetrachloroethane.
We attribute the improved performance of the bCTbK
biradical mainly to more favorable electron relaxation times.
The DNP efficiency of biradicals has been shown to be
significantly dependent on T1e, as a longer T1e allows for a
better saturation of the EPR line, therefore increasing the DNP
effect.21,23,32 The effect of higher electron saturation on the
DNP enhancement has previously been demonstrated by
Thurber et al. by using field-modulation during the polarization
buildup.23 To the best of our knowledge, biradicals have not
been previously developed for use as DNP polarizing agents to
specifically have long relaxation times. We designed the bCTbK
biradical to benefit from the optimal geometry of bTbK, while
also having longer relaxation times. The methyl groups around
each nitroxide center in bTbK were replaced with spirocyclo-
hexyl groups in bCTbK, increasing the size and rigidity of the
radical. Both the low-temperature and the room-temperature
EPR spectra of bTbK and bCTbK dissolved in tetrachloro-
ethane are similar, which suggests that the g and A tensors of
both biradicals are similar.
Figure 3. Comparison between the X-ray structure of bTbK and the
DFT optimized geometry of bCTbK (optimized at the B3LYP/6-
31G(d,p) level).
Figure S2), with εH peaking at 105 for Mat-PhOH impregnated
with a 16 mM bCTbK solution in tetrachloroethane (note that
an enhancement of 105 corresponds to a 1% proton
polarization at 400 MHz and 99 K, as compared to 0.0097%
for the thermal equilibrium polarization, without DNP). The
increased ε observed with a different probe was attributed to
the slightly lower sample temperatures as well as to slightly
higher MW power at the sample.
Note that ε quantifies the observed DNP efficiency, but it
does not take into account factors such as the reduction in
NMR signal intensity or changes in longitudinal relaxation
times caused by the introduction of a paramagnetic radical in
the sample.17,23 We have recently shown how the equivalent
fraction of NMR active nuclei that contributes to the NMR
signal (the quenching factor θ) can be experimentally
measured, and we introduced overall sensitivity enhancement
factors Σ and Σ†, which take into account these parameters.17
The factor Σ† also takes into account the additional sensitivity
enhancement (Boltzmann) factor of ∼3 obtained by carrying
out the experiments at 100 K rather than at room temperature
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Because bCTbK has not yet yielded crystals suitable for
diffraction, to confirm that the structures of these two spiro
radicals are similar, the geometry of both radicals was optimized
with DFT calculations (Figure 3, Table 2). The accuracy of the
add another parameter to consider for further rational design of
polarization agents for DNP experiments.
Monitoring Chemical Reactions on a Surface. Devel-
oping functional materials has become a major field of research
in recent years due to their application in various areas such as
catalysis, drug delivery, or gas purification. Understanding the
structures and the chemical transformation of their surface
functionalities at a molecular level is essential to provide reliable
structure−property relationships, which are essential to the
design and the controlled synthesis of the targeted functional
materials. In this respect, solid-state NMR would be a method
of choice, as it allows one to access structures, conformations,
and dynamics of molecules, including surface species. However,
the applicability of NMR is typically limited by its inherent low
sensitivity, with the low concentration of the surface
functionalities (typically <10 mmol/g), and the low natural
abundance of most of the relevant NMR active nuclei (1% for
carbon-13 and 0.3% for nitrogen-15).39
Table 2. Distances, Angle, and Dipolar Coupling for bTbK
and bCTbK
b
c
e
dN−O
a
dO−O
(Å)
dN−N
(Å)
D
d
compound
(Å)
ψ
(MHz)
bTbK (X-ray)
1.283
1.289
1.285
1.286
1.285
1.286
13.030
13.342
13.249
10.777
11.034
79.57
80.36
77.56
30.9
f
bTbK (DFT )
28.8
f
bCTbK (DFT )
10.990
29.3
a
b
c
N−O bond length of the two nitroxides. O1−O5 distance. N2−N6
d
distance. Angle between the mean C3N1O2C4 and C7N5O6C8 planes.
e
From the dipole point approximation (D = 52 160/dee, where dee is
f
the mean electron−electron distance). Optimized at the B3LYP/6-
31G(d,p) level.
calculations was confirmed by noting that the calculated
geometry of bTbK closely matches that obtained from its
single-crystal X-ray diffraction structure (Table 2). DFT
calculations show that bTbK and bCTbK share analogous
structures: (i) the calculated angles ψ between the mean planes
C3N1O2C4 and C7N5O6C8 (Figure 3) differ by less than 3°, and
(ii) the intramolecular nitrogen−nitrogen (N1−N7) distances
in bTbK and bCTbK are predicted to differ by only 0.044 Å.
This suggests that the electron−electron dipolar couplings are
on the order of 29 MHz and are nearly identical for both
radicals.
Having confirmed that the major structural features and EPR
tensor parameters for both bTbK and bCTbK are essentially
the same, it is then clear that the improved DNP enhancements
obtained with bCTbK can be mainly attributed to its slower
electron relaxation. T1e is found to be 1.7 times higher for
bCTbK (762 μs) than for bTbK (453 μs) (Table 1) under
otherwise identical conditions. It is known that for radicals in
glassy organic solvents around 100 K, Raman processes are the
dominant relaxation mechanism, suggesting that T1e is likely to
increase as the rigid size/molecular mass of the radical is
increased.34 It has also been observed that methyl groups lead
to shorter transverse relaxation times.35 We also note that the
T1e of bCTbK in tetrachloroethane is longer than that of
TOTAPOL in water (554 μs), despite the fact that electron
relaxation times of nitroxides in frozen solutions are known to
increase with the polarity of the solvent.34 A water-soluble
version of bCTbK is expected to have an even longer T1e,
possibly leading to higher enhancements. The high DNP
efficiency of bCTbK can thus be partially attributed to both its
favorable orientation of the TEMPO moieties and its long T1e.
Note that T1e is known to be anisotropic along the EPR line,
and it has been measured in this study at the high-field edge of
the spectrum, corresponding to the zone irradiated during DNP
experiments.
1
1
Figure 4. (a) Structure, (b) H−13C CP spectra, and (c) H−15N
spectra of compounds Mat-PrN3, Mat-PrNH2, and Mat-PrIm. The
most probable assignments based on the observed chemical shift
resulting from this spectrum are shown. The asterisks indicate spinning
sidebands, and the open circles note the presence of byproducts or
incomplete conversion from the previous synthetic steps. The proton
enhancements with a sample spinning frequency of 12 kHz are also
reported. Experimental details are described in the text and in the
Supporting Information.
We recently demonstrated that DNP SENS makes it possible
to probe in acceptable experimental times (hours) the surfaces
of various materials such as pure as oxides (silica,16 alumina40),
functionalized hybrid organic−inorganic silica materials,14
functionalized silica nanoparticles,15 and metal organic frame-
works (MOFs)41 at natural isotopic abundance. However, DNP
enhancement factors rarely exceeded 40 in our hands. To
demonstrate the potential of the large enhancements provided
by the bCTbK polarizing mixture, we investigate the stepwise
chemical transformation and the formation of imidazolium-
containing materials (Mat-PrIm), which can be used as
permanently immobilized “ionic liquids”42−46 or as precursors
to N-heterocyclic carbenes,47,48 an important class of ligands for
stable single-site catalysts (Figure 4a).
Improved DNP efficiency may also arise from longer spin−
spin relaxation times (T2e), as T2e has also been hypothesized to
help maintain the frequency match condition for the CE.21
In summary, these results show the influence of electron
relaxation times on the efficiency of polarizing agents and thus
Here, the imidazolium unit was introduced by a stepwise
postfunctionalization of Mat-PrN3 prepared by a direct
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1
1
Figure 5. (a) Pulse sequence for the 2D SENS H-X HETCOR experiments. (b−d) Contour plots of a 2D SENS H−13C HETCOR spectra of
compounds Mat-PrN3, Mat-PrNH2, and Mat-PrIm, respectively. (e) Contour plot of a 2D DNP SENS H−15N HETCOR of Mat-PrIm. (f)
1
Contour plot of a 2D DNP SENS H−29Si HETCOR of Mat-PrIm. All compounds were impregnated with a 16 mM solution of bCTbK in
1
tetrachloroethane. The contact time was 100 μs for the H−13C experiments, 1 ms for the H−15N correlation experiments, and 250 μs for the
1
1
51
1H−29Si. During t1, eDUMBO-122 homonuclear decoupling was applied.
synthesis approach.49 This included a Staudinger reduction
providing an aminopropyl unit in Mat-PrNH2 followed by its
conversion into Mat-PrIm via reaction with formaldehyde,
glyoxal, and benzylamine (Figure 4, see the Supporting
Informatino for additional experimental details). Note that
Mat-PrN3 was prepared by a direct synthesis approach, that is,
by a cohydrolysis co-condensation of (EtO)3SiPrN3 and
(EtO)4Si in the presence of a structure-directing agent, here
Pluronic-P123. This allows the formation of high-surface area
mesostructured materials as evidenced by TEM and N2
adsorption experiments (see the Supporting Information) as
well as the controlled site distribution of surface functionalities.
Moreover, the nonpolar nature of azido group enables one to
access a broad range of concentrations, including high
concentrations, and makes it possible to prepare a variety of
materials via postfunctionalization or click chemistry.50 To
monitor these synthetic steps at the surface of materials with
conventional room-temperature solid-state NMR would be
prohibitively time-consuming (experiments typically take
between 12 and 24 h for a one-dimensional carbon-13
CPMAS spectra; see the Supporting Information). In particular,
acquisition of 2D correlation spectra or nitrogen-15 spectra at
natural isotopic abundance is not conceivable even when they
would be necessary for unambiguous assignment.
polarizing agent, high-quality 1D H−13C CPMAS spectra (10
1
min, Figure 4b) and a 2D H−13C correlation spectra (3.5 h,
1
Figure 5a−d) may be acquired and allow for the complete
characterization of the carbon skeletons. The nitrogen-
containing functionalities were identified with 1H−15N
CPMAS spectra (14 h each, Figure 4c). These high-quality
15N CPMAS spectra even allow for minor reaction byproducts
to be observed. Note that spectra with a signal-to-noise ratio of
20, high enough for routine characterization, can be acquired in
40 min (see Figure S6). A 2D 1H−15N correlation spectrum of
Mat-PrIm was also acquired overnight (14 h, Figure 5e, vide
infra). None of these would have been possible without the
gain in sensitivity provided by DNP SENS. These results are all
the more impressive considering that 15N is an extremely
unreceptive NMR nucleus due to its low magnetogyric ratio
and low natural abundance. Note that with bTbK, experimental
lengths 6 times longer would have been necessary to get the
same sensitivity.
The interpretation and assignment of the DNP enhanced
solid-state NMR spectra are now discussed in detail. The 13C
CPMAS spectra of Mat-PrN3 display three carbon resonances
with chemical shifts of 8.1, 21.1, and 53.0 ppm, as expected
from its proposed structure. They correlate with protons whose
chemical shifts are 1.1, 2.15, and 3.2 ppm, respectively (Figure
5b), which is coherent with a propylazide moiety. The 15N
spectra of Mat-PrN3 display three resonances at 73.7, 219.5,
and 248.5 ppm, confirming the presence of the azide group
(Figure 4c). Upon conversion to Mat-PrNH2 with the
Here, DNP SENS provides a means of routine character-
ization, by enabling the expedient acquisition of carbon-13,
nitrogen-15 and silicon-29 1D and 2D solid-state NMR spectra
at natural isotopic abundances. For example, using bCTbK as a
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Staudinger reaction, the 13C resonance of C3 is shifted from
53.0 to 41.5 ppm, consistent with conversion of the azide group
into an amine.
CONCLUSION
■
Here, we introduced a new biradical, bCTbK, as a polarization
source for DNP NMR experiments. This derivative of the well-
known bTbK provides high DNP and sensitivity enhancements
due to its rigid structure and absence of methyl groups, leading
to slow electron relaxation and enhanced saturation of the EPR
line. We expect that the very high enhancements will make this
radical the polarization source of choice for the characterization
of materials. As bCTbK is also a very efficient polarization
source for bulk frozen solution, its applications are not limited
to the study of surfaces, and it could be used for the study of
proteins in lipid environments, polymers, or in dissolution
DNP experiments, for instance. Design and testing of water-
soluble versions of bCTbK for biological applications are
currently underway.
The nitrogen spectrum now displays one main resonance at
34.3 ppm, characteristic of the NH2 group (Figure 4c). The
byproducts observed on the 15N spectrum at 89 ppm are
attributed to a small amount of unconverted starting azide units
(ca. 10%). One interpretation for the incomplete conversion is
the inaccessibility of some of these organic fragments on the
surface. The carbon-13 spectrum of Mat-PrIm, obtained
subsequently upon reaction with formaldehyde, glyoxal, and
benzylamine, displays resonances with chemical shifts charac-
1
teristic of aromatic groups (129.2 ppm 13C/6.8 ppm H) and
1
(122.1 ppm 13C/6.8 ppm H), as well as the three expected
aliphatic resonances (Figures 4b and 5d). The 15N spectrum
confirms the presence of imidazolium nitrogen atoms with the
most intense resonance centered at 185 ppm (the two nitrogen
resonances being not resolved, Figure 4c).
The high efficiency of this radical was demonstrated for DNP
SENS by following a series of chemical reactions on the surface
of materials, monitoring the 13C, 29Si, H, and 15N chemical
1
shifts at natural isotopic abundance using multidimensional
correlation experiments. The reduction in experiment time by
DNP SENS experiments with bCTbK is estimated to be on the
order of 12 700 as compared to room-temperature experiments.
These experiments would have previously been impossible to
undertake at natural isotopic abundance in reasonable time.
This study demonstrates that DNP SENS can be used routinely
to characterize materials and surface compounds, as solution-
state NMR is used today in molecular chemistry.
This work also illustrates that there is still much room for
improvement of the polarization sources in DNP experiments
and adds a new parameter to consider in the rational design of
biradicals for DNP. Rigid radicals with bulkier functionalities
are known; such radicals could have even longer electron
relaxation times, which could lead to higher DNP enhance-
ments.
The complete and detailed characterization of Mat-PrIm was
further obtained by the acquisition of a 2D 1H−15N correlation
spectrum (Figure 5e), which shows three resolved cross peaks,
all consistent with the structure of Mat-PrIm. The cross peak at
1
(185.6 ppm 15N/8.9 ppm H) corresponds to a correlation
between the nitrogens and aromatic protons, notably the C6−H
1
proton. A shoulder at (131.1 ppm 13C/8.9 ppm H) can be
discerned in the 1H−13C HETCOR spectra corresponding to a
correlation between C6 and this proton. The cross peak at
1
(185.3 ppm 15N/5.4 ppm H) corresponds to the correlations
between Na′′ and Nb′′ and the CH2 protons of C3′′ and C7. The
peak at (187.2 ppm 15N/1.9 ppm 1H) indicates the correlation
between the protons of C2′′ and Na′′, which is the only nitrogen
close enough for magnetization transfer with this CP contact
time (1 ms). The 15N chemical shift for this cross peak is
slightly different from those of the previous two, confirming the
presence of two distinct imidazolium nitrogens in the molecule.
This analysis is confirmed by the lower intensity of this peak as
compared to the other two, indicating a longer distance from
the protons correlating with the other nitrogen, once again
compatible with the molecular structure of Mat-PrIm.
ASSOCIATED CONTENT
■
S
* Supporting Information
Additional experimental details of preparation of materials and
radicals, measurement of quenching and enhancement factors,
comparison of radical efficiency, and 15N NMR spectra of Mat-
PrN3, Mat-PrNH2, and Mat-PrIm. This material is available
free of charge via the Internet at http://pubs.acs.org.
The conformation of the organic moieties with respect to the
surface is also important to help understand the folding of
functionalities and the derived properties. A 2D 1H−29Si
correlation spectrum of Mat-PrIm could be acquired in 10 min.
AUTHOR INFORMATION
■
1
The cross peak at (−64.7 ppm 29Si/1.2 ppm H) shows the
Corresponding Author
paul.tordo@univ-provence.fr; lyndon.emsley@ens-lyon.fr
expected correlations between the T site silicon atoms (silicon
bonded to the carbon of the organic moiety) and the aliphatic
protons of carbon C1′′ and C2′′. The cross peak at (−99.8 ppm
ACKNOWLEDGMENTS
■
1
29Si/7.6 ppm H) shows a correlation between the Q sites
A.J.R. acknowledges support from a EU Marie-Curie IIF
Fellowship (PIIF-GA-2010-274574). Financial support is
acknowledged from EQUIPEX contract ANR-10-EQPX-47-
silicon atoms and the aromatic protons. This correlation
indicates that the imidazolium ring is in close proximity to the
surface of the material and that the tether folds to maximize the
interaction between the aromatic groups and the surface
functionalities.15
In summary, the combination of the multidimensional
proton, carbon, nitrogen, and silicon spectra clearly provides
the mean to unambiguously and rapidly characterize these
surface compounds at a molecular level. This demonstrates
how, due to the large enhancements provided by the bCTbK
biradical, DNP SENS can now be routinely applied to
characterize materials and surface compounds.
01, and the ETH Zurich. We acknowledge A. Roussey for the
̈
preparation of Mat-PhOH.36
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