Photochemical pump and NMR probe: Chemically created NMR coherence on a microsecond time scale

Article abstract of DOI:10.1021/ja504732u

We report pump-probe experiments employing laser-synchronized reactions of para-hydrogen (para-H₂) with transition metal dihydride complexes in conjunction with nuclear magnetic resonance (NMR) detection. The pump-probe experiment consists of a single nanosecond laser pump pulse followed, after a precisely defined delay, by a single radio frequency (rf) probe pulse. Laser irradiation eliminates H₂ from either Ru(PPh₃) ₃(CO)(H)₂ 1 or cis-Ru(dppe)₂(H)₂ 2 in C₆D₆ solution. Reaction with para-H₂ then regenerates 1 and 2 in a well-defined nuclear spin state. The rf probe pulse produces a high-resolution, single-scan ¹H NMR spectrum that can be recorded after a pump-probe delay of just 10 μs. The evolution of the spectra can be followed as the pump-probe delay is increased by micro- or millisecond increments. Due to the sensitivity of this para-H₂ experiment, the resulting NMR spectra can have hydride signal-to-noise ratios exceeding 750:1. The spectra of 1 oscillate in amplitude with frequency 1101 ± 3 Hz, the chemical shift difference between the chemically inequivalent hydrides. The corresponding hydride signals of 2 oscillate with frequency 83 ± 5 Hz, which matches the difference between couplings of the hydrides to the equatorial ³¹P nuclei. We use the product operator formalism to show that this oscillatory behavior arises from a magnetic coherence in the plane orthogonal to the magnetic field that is generated by use of the laser pulse without rf initialization. In addition, we demonstrate how chemical shift imaging can differentiate the region of laser irradiation thereby distinguishing between thermal and photochemical reactivity within the NMR tube.

Full text of DOI:10.1021/ja504732u

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Article
Photochemical pump and NMR probe: chemically
created NMR coherence on a microsecond timescale
Olga Torres, Barbara Procacci, Meghan E. Halse, Ralph W. Adams, Damir Blazina, Simon
B Duckett, Beatriz Eguillor, Richard A Green, Robin N. Perutz, and David C. Williamson
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 19 Jun 2014
Downloaded from http://pubs.acs.org on June 25, 2014
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Photochemical pump and NMR probe: chemically created NMR
coherence on a microsecond timescale
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Olga Torres, Barbara Procacci, Meghan E. Halse, Ralph W. Adams, Damir Blazina,
Simon B. Duckett*, Beatriz Eguillor, Richard A. Green, Robin N. Perutz*, and David
C. Williamson
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Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
ABSTRACT. We report pump-probe experiments employing laser-synchronized reactions of
parahydrogen (para-H2) with transition metal dihydride complexes in conjunction with nuclear
magnetic resonance (NMR) detection. The pump-probe experiment consists of a single
nanosecond laser pump pulse followed, after a precisely defined delay, by a single rf probe
pulse. Laser irradiation eliminates H2 from either Ru(PPh3)3(CO)(H)2 1 or cis-Ru(dppe)2(H)2 2 in
C6D6 solution. Reaction with para-H2 then regenerates 1 and 2 in a well-defined nuclear spin
state. The rf probe pulse produces a high-resolution, single-scan 1H NMR spectrum that can be
recorded after a pump-probe delay of just 10 μs. The evolution of the spectra can be followed
as the pump-probe delay is increased by micro/millisecond increments. Due to the sensitivity
of this para-H2 experiment, the resulting NMR spectra can have hydride signal-to-noise ratios
exceeding 750:1. The spectra of 1 oscillate in amplitude with frequency 1101 ± 3 Hz, the
chemical shift difference between the chemically inequivalent hydrides. The corresponding
hydride signals of 2 oscillate with frequency 83 ± 5 Hz which matches the difference between
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couplings of the hydrides to the equatorial P nuclei. We use the product operator formalism
to show that this oscillatory behavior arises from a magnetic coherence in the plane orthogonal
to the magnetic field that is generated by use of the laser pulse without rf initialization. In
addition, we demonstrate how chemical shift imaging can differentiate the region of laser
irradiation thereby distinguishing between thermal and photochemical reactivity within the
NMR tube.
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INTRODUCTION
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Dynamic nuclear magnetic resonance (NMR) spectroscopy has numerous applications for
studying chemical exchange phenomena in the steady state.1 The exchange information is
present in the free induction decay (FID), which is recorded for several hundred milliseconds.
The exchange timescale accessible to line-shape analysis is typically determined by the
frequency difference between exchanging nuclei. Alternatively, exchange spectroscopy (EXSY)
experiments are used for probing slower dynamic exchange, where the accessible timescales
are determined by relaxation.2 In practice, the need for good signal-to-noise ratios for accurate
measurements plays a dominant role in determining the processes that can be followed. NMR
spectroscopy can also be used to follow much slower reactions as they evolve, through a series
of measurements at different times. Recently, flow methods, analogous to stopped-flow UV,
have been introduced which access faster timescales.3,4
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In contrast, numerous pump-probe methods have been employed to study kinetics on
much shorter timescales with the fast detection techniques of UV/vis absorption and
emission,5,6 IR,7 and Raman spectroscopy.8,9,10 In principle, NMR spectroscopy could be used in
time-resolved pump-probe measurements if its sensitivity can be enhanced; laser pump-probe
NMR spectroscopy might be expected to become a powerful tool given the complementary
structural information of an NMR spectrum. Inspired by research on in-situ laser photolysis and
our experiments with para-hydrogen (para-H2) hyperpolarization of NMR,11-13 we have
developed a time-resolved spectroscopy method using laser initiation and NMR detection and
illustrate it for pump-probe delays as short as 10 ꢀs.
In a standard NMR experiment, it is the Zeeman effect and the associated Boltzmann
statistics that generate a bulk magnetic order. The magnitude of this bulk magnetization
depends on a very small population difference and so gives rise to a weak NMR signal. This
signal is detected following a radio frequency (rf) excitation pulse, which interacts with the bulk
magnetization to produce a coherence in the plane orthogonal to the main magnetic field
which is then detected in the form of the FID. In the 14.1 T (600 MHz) magnetic field used here,
the Zeeman effect produces a difference in nuclear-spin-state populations that is 1 for every
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21,300 H nuclei present. Several hyperpolarization methods have been designed to improve
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the sensitivity of NMR by perturbing this population difference. Some notable examples include
optical pumping of noble gases,14,15,16 dynamic nuclear polarization,17,18 and photochemically-
induced dynamic nuclear polarization (photo-CIDNP).19,20,21 In the photo-CIDNP method, a spin-
correlated radical pair is used to generate NMR signal enhancements on the order of 102. The
photo-CIDNP approach has been used to observe short-lived radicals and to monitor reactivity
on millisecond to second timescales.22,23,24,25 In 1976, Ernst demonstrated that magnetic
oscillations due to a chemically-induced magnetic coherence can be observed if CIDNP is
initiated coherently on a very short timescale.26 A related chemically initiated magnetic
coherence is exploited here in our time-resolved NMR spectroscopy method to give rise to
NMR signal enhancements of several orders of magnitude that build up on microsecond
timescales. In our method, we use the long-lived and readily prepared para-H2 molecule, rather
than a radical, as the source of hyperpolarization, creating the potential for high-sensitivity
measurements.27,28
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Parahydrogen (para-H2) is a reactive molecule in which the nuclear spins are aligned
anti-parallel as the linear combination αβ−βα, and hence exist in a pure singlet state. Upon
reaction with para-H2, products with non-equilibrium states give rise to highly enhanced NMR
signals that have been used to probe chemical reactivity in many different ways. Bowers and
Weitekamp were the first to recognize the potential for NMR hyperpolarization using para-H2.
In 1986, they predicted that if para-H2 were used in a hydrogenation reaction, reaction
products with a spin polarization on the order of unity could be created.29 They later confirmed,
experimentally, that under conditions where the symmetry of the molecular para-H2 was
broken through its transformation into chemically distinct proton environments in a product,
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signal enhancements in H NMR spectra did indeed result.30 Subsequently they refined their
approach to differentiate chemical transformations that proceed in a strong magnetic field
(Parahydrogen and Synthesis Allow Dramatically Enhanced Nuclear Alignment, PASADENA)30
from those proceeding in a low magnetic field prior to NMR detection in a strong magnetic field
(Adiabatic Longitudinal Transport after Dissociation Engenders Net Alignment, ALTADENA).31
The term PHIP (parahydrogen induced polarization) has also been used in the literature to
describe these effects more generally.32 Previous applications of PHIP have included detection
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of reaction products containing para-H2-derived protons in catalytic studies and in
vivo.27,33,34,35,36,37,38,39 Refinements of these methods called one-proton PHIP and Signal
Amplification By Reversible Exchange (SABRE) have also been described.33,35,40
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Parahydrogen hyperpolarization is most commonly described in the literature through
the use of energy level versus population diagrams41 with others favoring product operator
notation.42,43 It follows from the former description that when two new inequivalent proton
environments (I and S) are created from para-H2 in a product they yield enhanced anti-phase
NMR signals because the resulting energy level overpopulations reflect para-H2’s original
αβ spin orientation (Figure 1a). The product operator representation of the initial state in such
a product is the singlet: – ½(2IxSx + 2IySy + 2IzSz), which is made up of a zero quantum coherence
(ZQx = ½(2IxSx+2IySy)) and the longitudinal two-spin-order term: ½(2IzSz).43,44 It is interesting to
note that organic systems have been prepared in related states by Levitt, Bodenhausen and
Warren without laser synchronization and have potential applications because they can be
long-lived.45-48,49 Indeed, such long-lived states can also be generated by PHIP in symmetric
organic molecules as shown recently.50,51
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In a conventional high-field para-H2-enhanced experiment,30 the addition of para-H2
occurs asynchronously and the reaction time is long on the NMR timescale. Therefore the
amplitude of the ZQx coherence (and any associated terms) averages to zero (in the high field
limit) and so the only observed transitions arise as a result of the longitudinal two-spin order
term (Figure 1a). We seek here to probe the evolution of the para-H2-derived magnetization in
a new and efficient way, such that the enhanced signals can be monitored on microsecond
timescales. To achieve this goal, we first need to prepare a well-defined starting state. We do
this by using a laser pump pulse to initiate a reaction with para-H2 photochemically (Figure 2a).
Specifically, we use the light-induced electronic excitation of a transition metal complex to
achieve prompt ligand dissociation. In fact, loss of H2 occurs during the single 10-ns laser pulse
and para-H2 therefore reacts with the unsaturated reaction intermediate in a time-precise and
highly reproducible manner (Figure 3). We also need to consider carefully the behavior of the
ZQx coherence, which is now created synchronously and subsequently evolves into ZQy (Figure
1b) during the pump-probe delay according to the chemical shift and J-coupling differences
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between the I and S proton environments (as demonstrated in section 2). This method is so
reproducible that a series of measurements associated with a 2D-experiment can be collected.
We follow the evolution of these magnetic states, the zero-quantum coherences, through the
application of a probe NMR pulse. Thereby, we collect diagnostic information about the
product and, indirectly, learn about the reactivity of the intermediate from which the product is
formed (Figure 2b). This differs from previous work where continuous irradiation in an NMR
probe at low temperature has been used to build up the concentration of highly reactive
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species in order to enable their characterization; photoproducts such as alkane complexes
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reflect notable examples of this method.
The continuous irradiation approach has also
been used with para-H2 to observe new species. 54-56
In the studies reported here, only a short section of the sample tube within the NMR
detection coil is irradiated (Figure 2a),13 and a further, longer section of the active volume of
the coil is therefore unaffected by the laser beam. In a further technical development, we use
this selectivity to differentiate the region of the NMR tube where the photochemical reaction
occurs by making use of the NMR probe’s gradient coil to perform chemical-shift imaging. In
this case, we show that the enhanced signal is derived exclusively from the short irradiated
region of the tube and hence demonstrate thermal and photochemical activity can be
distinguished.
Figure 1. (a) Population-of-states model for a para-H2-derived reaction product containing nuclei I and S,
under PASADENA conditions with the resultant anti-phase NMR peaks illustrated. (b) Representation of
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the non-NMR-detectable zero-quantum coherences with associated product operators for two spins I
and S. 42
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Figure 2. (a) Schematic of the laser irradiation system: the unfocused laser beam is reflected off the
lower mirror into the probehead where a second mirror directs the beam onto the sample through a
hole in the housing; (b) NMR pump-probe sequence used in this PHIP study.
Two types of ruthenium dihydride complex are used in this study: Ru(PPh3)3(CO)(H)2 1
and cis-Ru(dppe)2(H)2 2 (Figure 3). They both undergo photochemical loss of H2 on a picosecond
timescale to generate Ru(CO)(PPh3)3 and Ru(dppe)2 (dppe = Ph2PCH2CH2PPh2), respectively,
before being reformed by reaction with hydrogen.57-60 The kinetics of reaction of these
intermediates with H2 have been determined previously by time-resolved absorption
spectroscopy; the time constants for recombination under 3 atm H2 (as used here) are 1.4 and
4.8 ꢀs respectively. Consequently, >99.99 % of the photo-products have reacted with para-H2
just 0.1 ms after the initial laser pulse, which makes them ideal candidates for this study.57,58
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Figure 3. Photochemical reactivity of compounds 1 and 2 towards para-H2 harnessed in this work. Blue
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denotes H nuclei not derived from para-H2, while green indicates hyperpolarized H nuclei originating
from para-H2 oxidative addition. The phosphorus nuclei in red are the dominant source of the magnetic
inequivalence of the hyperpolarized hydride nuclei in 2.
RESULTS
1. Laser Pump - NMR Probe Experiments.
In our NMR pump-probe experiments, a single 10 ns laser pulse at 355 nm is followed by
a precisely defined pump-probe delay, τ, and a single rf pulse (Figure 2b). The resultant free
induction decay (FID) is collected over a period of 350 ms, in exactly the same way as for a
traditional NMR experiment. In this study, the reaction products were stable on this timescale.
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The result is a high-resolution H NMR spectrum that also encodes the evolution of any para-
H2-derived magnetic states during the pump-probe delay. In these studies, the sample consists
of either an optically dilute C6D6 solution of 1 or 2. In 1, the two protons originating from para-
H2 are placed in chemically distinct hydride environments while in 2 they are created chemically
equivalent, but magnetically inequivalent by virtue of phosphorus couplings. This is exemplified
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by the corresponding H {31P} pump-probe NMR spectra of 1 and 2 that are generated under
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para-H2 shown in Figure 4. The H NMR spectrum of 1 in Figure 4a was acquired with a 90˚ rf
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pulse (13.5 µs), τ = 0.05 ms and broadband P decoupling. It shows two anti-phase hydride
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signals at
δ
–6.47 and
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4b was acquired with a 90˚ rf pulse (13.5 µs), τ = 15 ms and selective 31P decoupling of the axial
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phosphorus environment. It shows two anti-phase hydride signals at δ –8.33 that are separated
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by a splitting equal to the difference in scalar coupling, |J(PH)trans – J(PH)cis| = 83 Hz. Both of
these spectra demonstrate enhanced signal intensity relative to the corresponding thermally
polarized 1H NMR spectra. The strength of this signal relative to the normal thermally polarized
hydride trace is quantified later in the manuscript.
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Figure 4. Single-laser shot, single 90o rf pulse, p-H2 enhanced 1H{31P} NMR spectra of the hydride region
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of (a) 1 with τ = 0.05 ms (broadband P decoupling), and (b) 2 with τ = 15 ms, (selective P decoupling
of axial phosphorus).
It is possible to use chemical-shift imaging to correlate the vertical position within the
sample tube to the chemical-shift encoded molecular response. This method uses an
incremented magnetic field gradient, applied along the z axis, to encode spatial position into
the NMR signal. When undertaken in conjunction with photolysis, we can map the PHIP-derived
signal enhancement onto this displacement axis. The spatially-resolved NMR spectrum
collected in this way is shown in Figure 5. It reveals that the hyperpolarized NMR signals for 2
are localized within a 3.2 mm region of the NMR tube. This measurement clearly highlights the
region where UV-excitation takes place and therefore allows for the spatial differentiation of
thermal and photochemical reactivity. In this case, 2 does not undergo thermal exchange with
parahydrogen at 298 K, and so there is no observed hyperpolarization of the hydride
resonances outside of the laser-irradiated region of the NMR tube. Consequently, we can
clearly state that the hydride signals we detect using the laser pump, NMR probe approach are
all the result of the photochemical step.
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Figure 5. (a) 3-D plot of signal intensity (vertical axis) vs chemical shift (ppm) and vertical displacement
(mm) relative to the base of the NMR coil for 2. (b) Projections of thermal signal intensity (0 – 9 ppm,
blue) and the enhanced hydride signal intensity (-7.3 to -9.3 ppm, red) onto the vertical axis of the NMR
tube.
The evolution of the photochemically-generated NMR signals for 1 and 2 was investigated
as a function of the pump-probe delay. A time sequence was recorded by measuring a series of
1H{31P} pump-probe NMR spectra for different values of τ, each employing one laser pulse and
one rf pulse as shown in Figure 2b. This series of spectra encodes the evolution of the magnetic
states that takes place during the pump-probe delay into the hydride signal intensity and can be
readily interpreted by either looking at each spectrum in turn or by following the change in
integrated signal intensity of the hydride resonances. Using the latter approach, we find that
the integrals of the hydride signals of 1 exhibit an increase in intensity out to 200 μs, with an
apparent rise time of ca. 70 μs (Figure 6a). Parallel kinetic measurements by UV spectroscopy
exhibit a much more rapid 1.4 μs rise time,58 thereby demonstrating that the reformation of 1 is
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much faster than this buildup of enhanced NMR signal. Further increase of τ as shown in Figure
6b reveals that this rise actually forms the initial part of a sinusoidal oscillation.
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This change in signal amplitude can be readily understood if we consider the effect of the
90˚ rf pulse, which rotates 2IzSz and ZQx into unobservable zero-quantum and double-quantum
terms while rotating ZQy (Figure 1b) into observable single-quantum terms (see section 2). The
observed oscillation in hydride signal amplitude as a function of τ is therefore due to the
periodic evolution that connects the initial ZQx state to the ZQy state, which proceeds under the
influence of the difference in chemical shifts between the two hydrides and/or the difference in
J coupling between the hydrides and a third nucleus (see section 2). We emphasize that even
though the initial x-y coherence is created chemically, rather than with a radio-frequency pulse,
it still leads to a diagnostic signal in this experiment. A fit of this NMR signal to an exponentially
decaying sine wave yields a frequency of 1101 ± 3 Hz (Figure 6b), in good agreement with the
chemical shift difference, 1098 Hz, observed in the thermally polarized NMR spectrum of 1.
In a classic 2D NMR experiment, a magnetic coherence is first created; next it is allowed
to evolve during a variable delay before it is ultimately recorded as a free induction decay (FID).
Fourier transformation then produces a 2D spectrum where the second dimension displays the
information encoded during the evolution period. Here we used the same procedure to obtain
2D pump-probe NMR spectra, where the photochemically created magnetic coherence is also
prepared with phase coherence. This is allowed to evolve during a variable pump-probe delay,
τ, and is then recorded as an FID following a 90˚ rf pulse. This 2D approach is made possible by
the reproducibility of the laser pump step and the synchronization with the NMR probe step.
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1
Figure 6c presents a 2D H pump-probe NMR spectrum of 1 acquired by varying τ from 0 to 14
ms in steps of 0.35 ms. In this spectrum, which was acquired without 31P decoupling, we
observe peaks at ±Δδ = 1103 ± 3 Hz due to the evolution between ZQx and ZQy under the
influence of the difference in hydride chemical shift, with an additional splitting due to
evolution under the influence of the difference in J coupling between the hydride ligands and
the equatorial phosphorus nucleus, |J(PH)trans − J(PH)cis| = 88 ± 5 Hz (89 Hz in the 1D spectrum).
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1
Figure 6. (a) Hydride signal integral versus τ for H{31P} NMR spectra of 1 (1 x 10-3 M, 3 atm para-H2).
Blue: experimental points, Red line: exponentially decaying sine wave of 1101 ± 3 Hz generated using
the fit parameters from (b) (inset trace illustrates the spectrum at τ = 0.05 ms). (b) Analogous H{31P}
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hydride signal integrals out to 5 ms. Red line: fit to exponentially decaying sine wave of 1101 ± 3 Hz. (c)
2D 1H pump-probe NMR spectrum of 1 where the vertical dimension corresponds to evolution during τ.
Inset: 2x zoomed view.
The related complex cis-Ru(dppe)2(H)2 (2) (Figure 3) is more complicated than 1 having
chemically equivalent but magnetically inequivalent hydride ligands (AA′) that form an AA’XX’Y2
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spin system; X and Y are equatorial and axial P nuclei, respectively. Normally, the hydride
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ligands of 2 yield a complex 36-component multiplet (Figure 7a) at
δ −8.33 that simplifies to a
pseudo doublet separated by |J(PH)trans + J(PH)cis| = 53 Hz upon decoupling Y (Figure 7b).61
When this complex is monitored by pump-probe NMR spectroscopy with para-H2, both its
hydride and equatorial 31P signals (X) are observed to be hyperpolarized. Strikingly, the hydride
signal now appears as a deceptively simple anti-phase doublet of triplets due to the enhanced
intensity of a sub-set of the 36 expected transitions (Figure 7c). The enhanced transitions reflect
those nuclear spin states that are overpopulated by the evolution of the initial singlet state of
the para-H2-derived 1H nuclei. The resulting dramatically simplified doublet feature is separated
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by |J(PH)trans − J(PH)cis| = 83 Hz, and a splitting of 23 Hz due to axial P interactions is visible.
These measurements therefore reveal that J(PH)trans is ±68 Hz with J(PH)cis restricted to ∓15 Hz;
31
decoupling of the axial P-nuclei (Y) yields J(HH) = 6 Hz as the anti-phase splitting (Figure 7d).
The NMR spectra in Figure 7 demonstrate that the hyperpolarized signals derived from a single
FID can be detected with 1H NMR signal-to-noise ratios of ca. 750:1, which compare to those of
45:1 for 32 scans under thermal conditions. This equates to the ready detection of ca. 10
nanomoles of material in a single transient.
Density matrix simulations of the hyperpolarized 1H NMR spectra of 1 and 2 are presented
in the Supporting Information (Figure S5) to support these deductions. The couplings and
chemical shifts obtained from these simulations were in agreement with those obtained using
standard NMR characterization methods (Figure S1 and Figure S2).
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Figure 7. Thermal H NMR spectra of 2. (a) fully coupled. (b) with selective axial P decoupling. Pump-
probe H NMR spectra (90˚ rf pulse, τ = 15 ms) of 2. (c) fully coupled. (d) with selective axial 31P
1
decoupling. The signal-to-noise ratios (SNR) are also shown.
The hydride signals of 2 also oscillate in amplitude as the pump-probe delay τ is varied
1
(Figure S4). The resulting 2D H pump-probe NMR spectrum of 2 (Figure 8a) reveals that this
oscillation now has frequency ± 83 ± 5 Hz and matches the difference between the cis and trans
J couplings of the hydrides to the equatorial 31P nuclei (|J(PH)trans − J(PH)cis|). Hence the
hydride-phosphorus couplings of 2 play an analogous role to the hydride chemical shift
difference in 1 in causing evolution of the ZQx term. In addition to this 1H hyperpolarization, the
equatorial 31P nuclei (δ 65.7) of 2 become hyperpolarized, as shown by the 2D P pump-probe
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spectrum in Figure 8b, which was acquired with 90° rf excitation and subsequent detection on
the phosphorus channel. The axial phosphorus nuclei (δ 79.6) are, however, not hyperpolarized
under these conditions because the difference in their couplings to the hydrides (J(PaxHA) -
J(PaxHB)) is effectively zero.
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Figure 8. 2D pump-probe NMR spectra of 2 where the vertical dimension corresponds to evolution
during τ and (a) 1H is recorded and (b) 31P is monitored.
2. Analysis of evolution of magnetization. In these NMR pump-probe experiments, the
photodissociation of the two hydride ligands occurs within the laser pulse.57 Hydrogen re-
addition from the para-H2 reservoir (3 atm) then occurs following the laser pulse, on a
1
timescale of a few microseconds.57,58 Therefore, the para-H2-derived H nuclei initially retain
their relative spin orientations and can be described by the singlet state: ꢀꢁꢃ2ꢄꢅꢆꢅ ꢇ 2ꢄꢈꢆꢈ ꢇ
ꢂ
2ꢄꢉꢆꢉꢊ.11 It is noteworthy that, unlike more conventional PASADENA para-H2 experiments
where only the longitudinal two-spin order term, 2ꢄꢅꢆꢅ, is preserved, here we benefit from the
ꢁ
ꢂ
survival of the zero-quantum term, ꢋꢌꢈ ꢍ ꢃ2ꢄꢈꢆꢈ ꢇ 2ꢄꢉꢆꢉꢊ. This is a consequence both of the
coherent way in which we initiate the re-addition step and the reaction rate, which is fast
relative to the evolution of the ꢋꢌꢈ coherence. If the hydrides are chemically inequivalent (δν ≠
0), this ꢋꢌꢈ term evolves during the pump-probe delay (τ) into a ꢋꢌꢉ coherence: ꢋꢌꢉ ꢍ
ꢁ
ꢃ
ꢊꢁꢃ
ꢊ
ꢂꢃ2ꢄꢉꢆꢈ ꢀ 2ꢄꢈꢆꢉꢊ, under the application of the operator 2ꢎꢏꢐꢑ ꢄꢅ ꢀ ꢆꢅ , as demonstrated
ꢂ
by Equation 1.43 Similarly, a difference between the J couplings of the two hydrides (I and S) to
a third nucleus, T, (JIT
- JST ≠ 0) will result in the evolution of ꢋꢌꢈ into 2ꢋꢌꢉꢒꢅ under the
ꢔꢃ
ꢊ
ꢃ
ꢊ
influence of the operator: ꢓ ꢕꢖꢗ ꢀ ꢕꢘꢗ ꢙꢚ 2 ꢄꢅ ꢀ ꢆꢅ ꢒ , as shown by Equation 2. These
ꢅ
ꢂ
evolutions serve two important functions in the pump-probe experiment. First, the evolution
of ꢋꢌꢈ into ꢋꢌꢉ produces a detectable magnetic state from the intial NMR-silent singlet state.
Second, the evolution frequencies encode important diagnositc information into the NMR
response.
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ꢣ
ꢞ
ꢃ
ꢊ ꢃ ꢊ
ꢞꢟꢠꢡꢢ ꢤ ꢦꢧ
ꢥ
ꢥ
ꢃ
ꢊ
ꢃ
ꢊ
ꢛꢜꢝ ꢨꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢪ ꢛꢜꢝ ꢫꢬꢭ ꢞꢟꢠꢡꢢ ꢇꢛꢜꢮ ꢭꢯꢰ ꢞꢟꢠꢡꢢ
(1)
(2)
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ꢔ
ꢂ
ꢃ
ꢱ
ꢊ
ꢃ
ꢊ
ꢵꢚ ꢶ ꢖ ꢦꢘ ꢗ
ꢷ ꢷ
ꢓ
ꢦꢱ
ꢲꢳ
ꢴꢳ
ꢷ
ꢃ ꢃ ꢊ ꢊ
ꢋꢌꢈ ꢨꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢪ ꢋꢌꢈ cos ꢎ ꢕꢖꢗ ꢀ ꢕꢘꢗ ꢙ ꢇ 2ꢋꢌꢉꢒꢅ sin ꢎ ꢕꢖꢗ ꢀ ꢕꢘꢗ ꢙ
ꢊ ꢊ
ꢃ ꢃ
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At the end of the τ evolution period, prior to the application of the rf pulse, the state of
the system will contain contributions from the longitudinal two-spin-order term as well as the
zero-quantum coherence terms: ꢋꢌꢈ and ꢋꢌꢉ. Upon application of a broadband (i.e. non-
1
selective) pulse, which rotates both of the H nuclei by an angle, θ, all of these terms will give
rise to NMR-observable magnetic states according to Eq. 3 (single-quantum states only).
ꢺ
ꢺ
ꢸ ꢃ
ꢊ ꢹ ꢓꢖ ꢻꢘ ꢚ ꢸ ꢃ
ꢊ ꢸ
2ꢄꢅꢆꢅ ꢨꢩꢩꢩꢩꢩꢪ ꢶ 2ꢄꢈꢆꢅ ꢇ 2ꢄꢅꢆꢈ ꢶ sin 2ꢼ
ꢶ
ꢹ ꢓꢖ ꢻꢘ ꢚ
ꢺ
ꢺ
ꢸ ꢃ
ꢊ ꢸ
ꢋꢌꢈ ꢨꢩꢩꢩꢩꢩꢪ ꢀ ꢶ 2ꢄꢈꢆꢅ ꢇ 2ꢄꢅꢆꢈ ꢶ sin 2ꢼ
ꢹ ꢓꢖ ꢻꢘ ꢚ
ꢺ
ꢺ
ꢋꢌꢉ ꢨꢩꢩꢩꢩꢩꢪ ꢀ ꢸꢶ ꢓ2ꢄꢉꢆꢅ ꢀ 2ꢄꢅꢆꢉꢚ sin ꢼ
(3)
First, we note that the ZQx and longitudinal two-spin order terms give rise to the same
single-quantum states but with opposite signs. This means that observable NMR signal can only
be obtained from these terms if their amplitudes differ and ꢼ ≠ 90˚. Second, inspection of Eq.
3 shows that a 90˚ pulse will in fact generate observable signal exclusively from the ꢋꢌꢉ
coherence, while other pulse rotation angles, such as 45˚, can be used to detect contributions
from the other states, particularly the longitudinal two-spin-order term (2ꢄꢅꢆꢅ). All of the
spectra reported here were measured with a 90˚ pulse and so show exclusively the evolution of
ꢋꢌꢉ during τ. This contrasts with a traditional PHIP experiment, where a 45˚ pulse is used
because only the longitudinal two-spin-order term, 2ꢄꢅꢆꢅ, is present, and it produces the
maximum detectable response. 30
1
The oscillation observed in the H{31P} spectra of 1 (Figure 6b) is completely described by
1
Equation 1. The 2D H pump-probe spectrum of 1 in Figure 6c can be understood through the
application of both Equations 1 and 2 to the initial ꢋꢌꢈ state. As the longitudinal two-spin-order
term does not evolve during the pump-probe delay and is not observed with a 90˚ rf pulse, it is
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not considered further in this discussion. For the case of chemically inequivalent hydrides, the
evolution due to the chemical shift and J coupling terms can be considered sequentially. As the
pump-probe delay is changed, Equation 1 shows that there will be a sinusoidal oscillation in the
amplitude of the probed ꢋꢌꢉ state, where the oscillation frequency is equal to the chemical-
shift difference (δν = 1098 Hz in 1). In a 2D spectrum this will correspond to peaks at ±δν in the
indirect (τ) evolution dimension. According to Equation 2, there will be an additional oscillation
due to the difference in the trans and cis J couplings between the hydrides and the in-plane
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phosphorus nucleus, Δ
splitting in the indirect (τ) evolution dimension of the 2D spectrum with peaks at at δν ꢇ ½Δ
and δν – ½Δ
. This is precisely what is observed in Figure 6c.62 In addition, the form of the
J ꢍ |JꢃPHꢊtrans − JꢃPHꢊcis| = 89 Hz. This oscillation will produce a further
J
J
1
hyperpolarized H NMR spectrum in the direct dimension can be interpreted in a
straightforward way. Each hydride gives rise to an anti-phase doublet of triplets, where the
anti-phase splitting is equal to the homonuclear hydride-hydride coupling, the doublet splitting
31
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1
is equal to the equatorial P – 1H coupling and the triplet splitting is equal to the axial P – H
coupling.
In complex 2, the hydrides are chemically equivalent but magnetically inequivalent and so
there is no evolution due to the chemical shift terms, as shown by Equation 1. Equation 2
describes the evolution of ꢋꢌꢈ when two magnetically inequivalent nuclei are coupled to a
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single third nucleus. The presence of two equatorial P nuclei (T and R) in 2 can therefore be
analyzed by the application of Equation 2 twice in succession (once for the coupling to T and
once for the coupling to R, where R replaces T in Equation 2) leading to an effective oscillation
1
frequency of ΔJ and peaks in the 2D H pump-probe spectrum at +ΔJ and -ΔJ (Figure 7a).
Although this approach does not take into account the effect of the strong coupling of the
1
AA’XX’ system, it is sufficient to provide an intuitive understanding of the peaks in the 2D H
pump-probe spectrum. In contrast, inclusion of strong coupling is required to explain the
31
1
observed hyperpolarization of the equatorial P nuclei in Figure 7b. The H-31P coupled state
generated by Equation 2, 2ꢋꢌꢉꢒꢅ, does not yield any observable single-quantum states
following the application of an rf pulse on the phosphorus channel. Therefore magnetic states
31
31
of this type cannot account for the observed P hyperpolarization in the 2D P pump-probe
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spectrum in Figure 7b. However, in the strong coupling regime the coupled state, 2ꢋꢌꢉꢒꢅ, will
1
1
5
6
ꢃ
ꢊ
evolve into 2 ꢄꢅ ꢀ ꢆꢅ ꢒ under the influence of the non-secular part of the H- H J-coupling
ꢅ
interaction, ꢎꢕꢖꢘꢓ2ꢄꢈꢆꢈ ꢇ 2ꢄꢉꢆꢉꢚ, as demonstrated by Equation 4.43
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ꢽꢱ ꢓꢶꢖ ꢘ ꢻꢶꢖ ꢘ ꢚꢵ
ꢲꢴ
ꢾ
ꢾ
ꢺ ꢺ
ꢸ
ꢃ
ꢊ
ꢃ
ꢊ
2ꢋꢌꢉꢒꢅ ꢨꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢩꢪ 2ꢋꢌꢉꢒꢅ cos 2ꢎꢕꢖꢘꢙ ꢇ 2ꢃꢄꢅ ꢀ ꢆꢅꢊꢒ sin 2ꢎꢕꢖꢘꢙ
(4)
ꢅ
ꢶ
It is this 2 ꢄꢅ ꢀ ꢆꢅ ꢒ state that gives rise to the 31P NMR signals observed following the
ꢃ
ꢊ
ꢅ
31
application of an rf pulse to the phosphorus channel in the 2D P pump-probe spectrum in
Figure 7b. While transfer from para-H2-derived 1H nuclei to a heteronucleus has been achieved
previously in combination with rf irradiation63 or in the low-field regime,64,65 this is an example
of spontaneous transfer of para-H2 hyperpolarization to a heteronucleus in the high field
regime.
CONCLUSION
In this paper, we have demonstrated that NMR spectroscopy can be used in a laser pump-NMR
probe mode to access microsecond-millisecond timescale events in an approach analogous to
other laser based time-resolved spectroscopies. Our measurements were made possible by
combining laser-synchronized chemical initiation with para-H2 hyperpolarization. Crucially, in
the pumping stage of the experiment, x-y coherence is created through a chemical reaction
which proceeds on a microsecond timescale. This x-y coherence responds to the molecular
environment as manifest in both the 1D spectra and the oscillatory evolution of the spectra as a
function of the pump-probe delay. This chemically generated coherence contrasts with the
normal situation for NMR spectroscopy where x-y coherences are the direct result of a radio
frequency pulse. Furthermore, this method differs significantly from traditional para-H2
methods of PASADENA and ALTADENA, which lack a synchronous initiation step and hence only
yield time-averaged magnetic states prior to rf excitation.44 For example, when transition metal
complexes are examined, the oscillations of the zero quantum coherence are obscured because
of the asynchronous H2 cycling (multiple H2 addition and elimination). Similarly, multiple
asynchronous catalytic steps normally cause time-averaging in instances where hydrogenation
products are formed irreversibly.
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In the two cases illustrated here, Ru(PPh3)3(CO)(H)2 1 and cis-Ru(dppe)2(H)2 2, the signals
oscillate for different reasons. In the case of 1, it is the creation of two chemically inequivalent
hydrides that leads to an oscillation of frequency 1101 ± 3 Hz corresponding to their chemical
shift difference. For 2, however, it is magnetic inequivalence that results in a smaller oscillation
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frequency of 83 ± 5 Hz corresponding to a difference in spin-spin coupling |JꢃPHꢊtrans − JꢃPHꢊcis|.
This approach therefore readily differentiates the spin topology of the product and is applicable
to compounds with either chemical inequivalence or magnetic inequivalence via differences in
J-coupling. We have also demonstrated that we can monitor changes in the spectra observed
with successive pump-probe delays differing from one another by 10 μs. The rise time of the
oscillations sets an upper limit for the formation of the product that is measured as 70 μs in the
case of 1. The timescale of our experiments is defined by the frequency difference between the
two hydride resonances in the case of 1 and by the difference in spin-spin coupling in the case
of 2.
The sensitivity of the method is illustrated by single scans with signal-to-noise ratios as
high as 750:1 that detect nanomole amounts of product. The potential of this method as a
diagnostic probe for photo-induced reactions is further demonstrated by chemical-shift imaging
combined with laser irradiation that can differentiate thermal and photochemical reactivity in
situ within the timeframe of the experiment.
We are currently working to develop a full theoretical framework and optimize the
experimental parameters so as to extend the method to other types of reaction product that
have been observed with para-H2 hyperpolarization.28 In the future, we seek to exploit its
remarkable potential to quantify chemical kinetics on a microsecond timescale while
simultaneously benefiting from the structural information provided by NMR detection. In
principle, any system that can be initiated synchronously and sensitized with para-H2 could be
followed using our method. Another potential application of this technique is as a test-bed for
NMR pulse sequences designed to manipulate long-lived singlet states.
EXPERIMENTAL
All NMR spectra were recorded on a Bruker Avance widebore 600 MHz spectrometer
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fitted with a BBO probe. Laser photolysis was carried out with a pulsed Nd:YAG laser
(Continuum Surelite II) fitted with a frequency tripling crystal (output 355 nm). Operating
conditions were typically: 10 Hz repetition rate, flash lamp voltage 1.49 kV, and Q-switch delay
increased from the standard to 320 ms yielding a laser power of 85 mW. The unfocused laser
beam is directed at the base of the spectrometer and reflected up into the probe via a mirror
(Figure 2a). Adjustment screws control the vertical and horizontal position of the mirror which
is on a kinematic mount. The system is fully shielded from the operator and the screws of the
kinematic mount can be adjusted from outside the shield. The laser radiation is incident on a
fixed mirror that is level with the sample and passes through a hole in the probe onto the NMR
tube. Standard NMR tubes fitted with Young’s taps were used. The samples contained 1–2 mg
of compound and approximately 0.4 mL of solvent. A sample of 2 in C6D6 was used for laser
alignment with para-H2 amplification in real time.
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Standard NMR pulse sequences were modified for use with para-H2 by including a
synchronized laser initiation sequence prior to NMR excitation (Figure 2b). A purpose-written
program was used to control the laser firing from the NMR console with the laser set on
external triggering. The fire signals are sent to the laser via a BNC cable. The program sets the
laser to fire three warm-up shots before opening the shutter for the fire signal. The NMR pulse
is initiated at a set delay time (τ) following the fire signal. The intrinsic time delay between
sending the fire signal from the spectrometer and the actual firing of the laser pulse was
measured with a photodiode and an oscilloscope to be 140 μs. This signal delay was
incorporated into the pulse sequence such that synchronized measurements with a time delay,
τ
, were achieved by setting the spectrometer delay to: τ + 140 μs. The precision of this delay
between the laser and rf pulses is controlled by the 200 ns clock of the spectrometer.
2D pump-probe NMR experiments were carried out by acquiring a series of 1D spectra in
which the delay between the laser pulse and the rf excitation, τ, was incremented in the usual
way to assemble a 2D data-set. This 2D data-set was subsequently Fourier transformed under
magnitude mode to generate 2D spectra such as those presented in Figures 6c and 8.
Chemical-shift imaging (CSI) was used to correlate the vertical position within the sample
tube to chemical shift (Figure 5). The CSI method used here employs an incremented magnetic
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field gradient along the z-axis to encode spatial information into the phase of the detected
signals. Subsequent Fourier transformation of the 2D data-set gives a chemical shift spectrum in
the directly observed dimension (F2) and position in the indirect evolution dimension (F1). The
pulse sequence used for chemical-shift imaging is shown in the Supporting Information (Figure
S3). The maximum gradient strength used is dependent on the number of increments and the
length and shape of the gradient pulse. For the 1H experiments, we used 1 ms half-sine gradient
pulses, with maximum strength of 5.99 G/cm, and 64 data points in the second dimension. This
corresponds to a field of view of 2 cm (Figure S6). A two-step phase cycle of the 180˚ pulse was
used to remove artifacts in the image.
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ASSOCIATED CONTENT
Supporting Information
NMR characterization data, additional spectra with simulations and further technical
descriptions. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding authors: simon.duckett@york.ac.uk; robin.perutz@york.ac.uk
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
We are grateful for support to EPSRC (grant EP/K022792/1), the Ministerio de Ciencia e
Innovación and the Fundación Española para la Ciencia y la Tecnología (OT), and the Spanish
MEC Consolider Ingenio 2010-ORFEO-CSD2007-00006 research programme (BE). Catherine
Sexton, Sarah Henshaw and Pedro Aguiar provided experimental help.
REFERENCES
(1)
Mann, B. E. In Encyclopedia of Nuclear Magnetic Resonance; Grant, D. M., Harris, R. K.,
Eds.; Wiley: Chichester, UK, 1996, p 3400.
(2)
(3)
Perrin, C. L.; Dwyer, T. J. Chem. Rev. 1990, 90, 935.
Bart, J.; Kolkman, A. J.; Oosthoek-de Vries, A. J.; Koch, K.; Nieuwland, P. J.; Janssen, H.;
van Bentum, P. J. M.; Ampt, K. A. M.; Rutjes, F. P. J. T.; Wijmenga, S. S.; Gardeniers, H.; Kentgens, A. P.
M. J. Am. Chem. Soc. 2009, 131, 5014.
20
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Page 21 of 24
Journal of the American Chemical Society
1
2
3
4
5
6
(4)
(5)
(6)
(7)
Wagner, G. E.; Sakhaii, P.; Bermel, W.; Zangger, K. Chem. Commun. 2013, 49, 3155.
Zewail, A. H. Angew. Chem., Int. Ed. 2000, 39, 2587.
Zhang, R.; Newcomb, M. Acc. Chem. Res. 2008, 41, 468.
Butler, J. M.; George, M. W.; Schoonover, J. R.; Dattelbaum, D. M.; Meyer, T. J. Coord.
7
8
Chem. Rev. 2007, 251, 492.
9
(8)
Kukura, P.; McCamant, D. W.; Mathies, R. A. Annu. Rev. Phys. Chem. 2007, 58, 461.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(9)
(10)
(11)
Nibbering, E. T. J.; Fidder, H.; Pines, E. Annu. Rev. Phys. Chem. 2005, 56, 337.
Browne, W. R.; McGarvey, J. J. Coord. Chem. Rev. 2007, 251, 454.
Anwar, M. S.; Blazina, D.; Carteret, H. A.; Duckett, S. B.; Halstead, T. K.; Jones, J. A.;
Kozak, C. M.; Taylor, R. J. K. Phys. Rev. Lett. 2004, 93.
(12)
Calladine, J. A.; Torres, O.; Anstey, M.; Ball, G. E.; Bergman, R. G.; Curley, J.; Duckett, S.
B.; George, M. W.; Gilson, A. I.; Lawes, D. J.; Perutz, R. N.; Sun, X.-Z.; Vollhardt, K. P. C. Chem. Sci. 2010,
1, 622.
(13)
(14)
(15)
(16)
Ampt, K. A. M.; Duckett, S. B.; Perutz, R. N. Dalton Trans. 2007, 2993.
Schroder, L.; Lowery, T. J.; Hilty, C.; Wemmer, D. E.; Pines, A. Science 2006, 314, 446.
Happer, W. Rev. Mod. Phys. 1972, 44, 169.
Garimella, P. D.; Meldrum, T.; Witus, L. S.; Smith, M.; Bajaj, V. S.; Wemmer, D. E.;
Francis, M. B.; Pines, A. J. Am. Chem. Soc. 2014, 136, 164.
(17)
Ardenkjaer-Larsen, J. H.; Fridlund, B.; Gram, A.; Hansson, G.; Hansson, L.; Lerche, M. H.;
Servin, R.; Thaning, M.; Golman, K. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 10158.
(18)
(19)
(20)
(21)
(22)
Müller-Warmuth, W.; Meise-Gresch, K. Adv. Magn. Reson. 1983, 11, 1.
Schäublin, S.; Wokaun, A.; Ernst, R. R. J. Magn. Reson. 1977, 27, 273.
Trease, D.; Bajaj, V. S.; Paulsen, J.; Pines, A. Chem. Phys. Lett. 2011, 503, 187.
Goez, M.; Kuprov, I.; Mok, K. H.; Hore, P. J. Mol. Phys. 2006, 104, 1675.
Harper, S. M.; Neil, L. C.; Day, I. J.; Hore, P. J.; Gardner, K. H. J. Am. Chem. Soc. 2004, 126,
3390.
(23)
Kiryutin, A. S.; Morozova, O. B.; Kuhn, L. T.; Yurkovskaya, A. V.; Hore, P. J. J. Phys. Chem.
B 2007, 111, 11221.
(24)
Mok, K. H.; Nagashima, T.; Day, I. J.; Jones, J. A.; Jones, C. J. V.; Dobson, C. M.; Hore, P. J.
J. Am. Chem. Soc. 2003, 125, 12484.
(25)
Perrier, S.; Mugeniwabagara, E.; Kirsch-De Mesmaeker, A.; Hore, P. J.; Luhmer, M. J. Am.
Chem. Soc. 2009, 131, 12458.
(26)
(27)
(28)
Schaublin, S.; Wokaun, A.; Ernst, R. R. Chem. Phys. 1976, 14, 285.
Duckett, S. B.; Mewis, R. E. Acc. Chem. Res. 2012, 45, 1247.
Green, R. A.; Adams, R. W.; Duckett, S. B.; Mewis, R. E.; Williamson, D. C.; Green, G. G. R.
Prog. Nucl. Magn. Reson. Spectrosc. 2012, 67, 1.
(29)
(30)
(31)
(32)
Bowers, C. R.; Weitekamp, D. P. Phys. Rev. Lett. 1986, 57, 2645.
Bowers, C. R.; Weitekamp, D. P. J. Am. Chem. Soc. 1987, 109, 5541.
Pravica, M. G.; Weitekamp, D. P. Chem. Phys. Lett. 1988, 145, 255.
Eisenschmid, T. C.; Kirss, R. U.; Deutsch, P. P.; Hommeltoft, S. I.; Eisenberg, R.; Bargon, J.;
Lawler, R. G.; Balch, A. L. J. Am. Chem. Soc. 1987, 109, 8089.
(33)
Lopez-Serrano, J.; Duckett, S. B.; Aiken, S.; Lenero, K. Q. A.; Drent, E.; Dunne, J. P.;
Konya, D.; Whitwood, A. C. J. Am. Chem. Soc. 2007, 129, 6513.
(34)
Godard, C.; Duckett, S. B.; Henry, C.; Polas, S.; Toose, R.; Whitwood, A. C. Chem.
Commun. 2004, 1826.
(35)
(36)
Permin, A. B.; Eisenberg, R. J. Am. Chem. Soc. 2002, 124, 12406.
Giernoth, R.; Huebler, P.; Bargon, J. Angew. Chem., Int. Ed. 1998, 37, 2473.
21
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Page 22 of 24
1
2
3
4
5
6
(37)
Viale, A.; Santelia, D.; Napolitano, R.; Gobetto, R.; Dastru, W.; Aime, S. Eur. J. Inorg.
Chem. 2008, 4348.
(38)
Bhattacharya, P.; Harris, K.; Lin, A. P.; Mansson, M.; Norton, V. A.; Perman, W. H.;
Weitekamp, D. P.; Ross, B. D. Magn. Reson. Mat. Phys. Biol. Med. 2005, 18, 245.
7
8
9
(39)
2008, 319, 442.
(40)
Bouchard, L.-S.; Burt, S. R.; Anwar, M. S.; Kovtunov, K. V.; Koptyug, I. V.; Pines, A. Science
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Adams, R. W.; Aguilar, J. A.; Atkinson, K. D.; Cowley, M. J.; Elliott, P. I. P.; Duckett, S. B.;
Green, G. G. R.; Khazal, I. G.; Lopez-Serrano, J.; Williamson, D. C. Science 2009, 323, 1708.
(41)
(42)
Duckett, S. B.; Sleigh, C. J. Prog. Nucl. Magn. Reson. Spectrosc. 1999, 34, 71.
Sorensen, O. W.; Eich, G. W.; Levitt, M. H.; Bodenhausen, G.; Ernst, R. R. Prog. Nucl.
Magn. Reson. Spectrosc. 1983, 16, 163.
(43)
(44)
Natterer, J.; Bargon, J. Prog. Nucl. Magn. Reson. Spectrosc. 1997, 31, 293.
Natterer, J.; Schedletzky, O.; Barkemeyer, J.; Bargon, J.; Glaser, S. J. J. Magn. Reson.
1998, 133, 92.
(45)
Levitt, M. H. Annu. Rev. Phys. Chem. 2012, 63, 89.
(46)
Pileio, G.; Bowen, S.; Laustsen, C.; Tayler, M. C. D.; Hill-Cousins, J. T.; Brown, L. J.; Brown,
R. C. D.; Ardenkjaer-Larsen, J. H.; Levitt, M. H. J. Am. Chem. Soc. 2013, 135, 5084.
(47)
(48)
Feng, Y.; Davis, R. M.; Warren, W. S. Nat. Phys. 2012, 8, 831.
Ahuja, P.; Sarkar, R.; Jannin, S.; Vasos, P. R.; Bodenhausen, G. Chem. Commun. 2010, 46,
8192.
(49)
(50)
Carravetta, M.; Levitt, M. H. J. Am. Chem. Soc. 2004, 126, 6228.
Franzoni, M. B.; Buljubasich, L.; Spiess, H. W.; Muennemann, K. J. Am. Chem. Soc. 2012,
134, 10393.
(51)
Zhang, Y.; Soon, P. C.; Jerschow, A.; Canary, J. W. Angew. Chem., Int. Ed. 2014, 53, 3396.
(52)
Calladine, J. A.; Duckett, S. B.; George, M. W.; Matthews, S. L.; Perutz, R. N.; Torres, O.;
Khuong, Q. V. J. Am. Chem. Soc. 2011, 133, 2303.
(53)
Ball, G. E.; Brookes, C. M.; Cowan, A. J.; Darwish, T. A.; George, M. W.; Kawanami, H. K.;
Portius, P.; Rourke, J. P. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 6927.
(54)
(55)
(56)
Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C. Chem. Commun. 2002, 2704.
Clark, J. L.; Duckett, S. B. Dalton Trans. 2014, 43, 1162.
Eguillor, B.; Caldwell, P. J.; Cockett, M. C. R.; Duckett, S. B.; John, R. O.; Lynam, J. M.;
Sleigh, C. J.; Wilson, I. J. Am. Chem. Soc. 2012, 134, 18257.
(57)
Colombo, M.; George, M. W.; Moore, J. N.; Pattison, D. I.; Perutz, R. N.; Virrels, I. G.; Ye,
T. Q. J. Chem. Soc., Dalton Trans. 1997, 2857.
(58)
Cronin, L.; Nicasio, M. C.; Perutz, R. N.; Peters, R. G.; Roddick, D. M.; Whittlesey, M. K. J.
Am. Chem. Soc. 1995, 117, 10047.
(59)
Campian, M. V.; Perutz, R. N.; Procacci, B.; Thatcher, R. J.; Torres, O.; Whitwood, A. C. J.
Am. Chem. Soc. 2012, 134, 3480.
(60)
Schott, D.; Callaghan, P.; Dunne, J.; Duckett, S. B.; Godard, C.; Goicoechea, J. M.; Harvey,
J. N.; Lowe, J. P.; Mawby, R. J.; Muller, G.; Perutz, R. N.; Poli, R.; Whittlesey, M. K. Dalton Trans. 2004,
3218.
(61)
(62)
Gunther, H. Angew. Chem., Int. Ed. 1972, 11, 861.
The difference in couplings between the hydrides and the axial phosphorus
nuclei is very small (< 5 Hz). While we would expect an additional splitting in the 2D spectrum
due to this difference, it is not resolved in Figure 6c.
(63)
Roth, M.; Koch, A.; Kindervater, P.; Bargon, J.; Spiess, H. W.; Munnemann, K. J. Magn.
Reson. 2010, 204, 50.
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(64)
(65)
Goldman, M.; Johannesson, H. C. R. Phys. 2005, 6, 575.
Hövener, J-B.; Chekmenev, E. Y.; Harris, K. C.; Perman, W. H.; Robertson, L. W.; Ross, B.
D.; Bhattacharya, P. Magn. Reson. Mat. Phys. Biol. Med. 2009, 22, 111.
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