DOI: 10.1002/cphc.201600663
Communications
Limits in Proton Nuclear Singlet-State Lifetimes Measured
with para-Hydrogen-Induced Polarization
+
[a]
+ [a]
[a]
[b, c]
Yuning Zhang , Xueyou Duan , Pei Che Soon, Vladimꢀr Sychrovsk y´ ,
[a]
[a]
James W. Canary,* and Alexej Jerschow*
The synthesis of a hyperpolarized molecule was developed,
where the polarization and the singlet state were preserved
over two controlled chemical steps. Nuclear singlet-state life-
times close to 6 min for protons are reported in dimethyl fu-
marate. Owing to the high symmetry (AA’X X ’ and A sys-
tant when applications of hyperpolarization are considered for
contrast agents, for example, or in cases where long-term stor-
age of magnetization would be desired. It is also of interest
whether weaker relaxation mechanisms can be measured and
exploited for structural or dynamical characterization.
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3
2
tems), the singlet-state readout requires either a chemical de-
symmetrization or a long and repeated spin lock. Using DFT
calculations and relaxation models, we further determine nu-
clear spin singlet lifetime limiting factors, which include the in-
tramolecular dipolar coupling mechanism (proton–proton and
proton–deuterium), the chemical shift anisotropy mechanism
para-Hydrogen-induced polarization enhancement (PHIP)
can provide polarization enhancements of up to several thou-
sand times through the hydrogenation of a molecule with
[3]
a para-H -enriched gas, or through the transfer of magnetiza-
2
tion in an intermediate complex, without the addition of H to
2
[4]
the molecule. The enhanced polarization could, in principle,
be stored in a nuclear singlet state for later readout. Although
transfer of the polarization to low-g nuclei is of interest, owing
(symmetric and antisymmetric), and the intermolecular dipolar
coupling mechanism (to oxygen and deuterium). If the limit of
paramagnetic relaxation caused by residual oxygen could be
lifted, the intramolecular dipolar coupling to deuterium would
become the limiting relaxation mechanism and proton life-
times upwards of 26 min could become available in the mole-
cules considered here (dimethyl maleate and dimethyl fuma-
rate).
to the longer T times, storage directly in the proton spins is
1
[6]
desirable as well, especially for certain imaging applications.
Inherent symmetry in the molecules of study can reduce the
[7]
action of major relaxation mechanisms (such as certain dipo-
[8]
lar coupling interactions, the chemical shift anisotropy, and
singlet–triplet leakage), but symmetry alone does not guaran-
[8]
tee long lifetimes.
In this work, our goal was to study the proton singlet life-
times of organic molecules in solution with increased degrees
of magnetic equivalence, including a molecule with an inver-
sion center. The increased symmetry requires the use of special
Over the last several years, it has been established that nuclear
spin singlet states can have lifetimes of up to several orders of
[1]
magnitude longer than the longitudinal relaxation time T1.
The most impressive results to date have been achieved for
[9]
readout techniques, which include field cycling, pulse se-
1
5
13
[3c,7a,b,10]
[7d,11]
N and C spin singlets, where lifetimes of 23–26 min and
quences,
and chemical reactions.
We have previ-
[
1c,e,2]
more than 1 h were reported,
respectively. Owing to the
ously demonstrated a chemical readout method based on
a bio-inspired thiol-addition reaction, which can desymmetrize
high gyromagnetic ratio g, proton spins are inherently more
prone to singlet-breaking mechanisms, and we thus investigat-
ed what the limiting lifetimes might be for proton spins in or-
ganic molecules of high symmetry. Such questions are impor-
[
11b]
the molecule and can, thus, reveal the singlet signals.
An-
[
7b,c,10a,b]
other approach is based on a weak spin lock (SLIC),
which we have adapted to the readout of singlet states under
[12]
weak chemical inequivalence with a multiple readout meth-
[3c]
od. Both of these techniques, as well as the PHIP enhance-
ment, are essential for accessing the singlet states in the mole-
cules of study, which would otherwise remain invisible. Multi-
configuration ab initio calculations provide a means for calcu-
lating dipolar coupling and chemical-shift relaxation contribu-
tions to the singlet lifetime limits.
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[
a] Y. Zhang, X. Duan, Dr. P. C. Soon, Prof. J. W. Canary, Prof. A. Jerschow
Department of Chemistry
New York University
00 Washington Sq. East, New York, NY 10003 (USA)
E-mail: james.canary@nyu.edu
[
b] Dr. V. Sychrovsky´
We present here results on the vinylene proton singlets of
the dimethyl maleate (DMM) and dimethyl fumarate (DMF)
molecules. DMF is currently an important, commercially avail-
Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic, v.v.i.
Flemingovo nꢀm eˇ stꢁ 2, 166 10, Praha 6 (Czech Republic)
[13]
[
c] Dr. V. Sychrovsky´
Department of Electrotechnology, Electrical Engineering
Czech Technical University
able pharmaceutical. We obtained its hyperpolarized version
from PHIP-prepared DMM through isomerization with a secon-
[14]
dary amine. The singlet state of the DMM was preserved in
DMF despite the low symmetry of the intermediate.
Technickꢀ 2, 166 27, Prague 6 (Czech Republic)
+
[
] These authors contributed equally to this work
Both DMM and DMF form nearly equivalent AA’X X’ systems
(with A denoting the vinylene protons and X the methyl pro-
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ChemPhysChem 2016, 17, 1 – 6
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ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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