Conspectus
Nuclear magnetic resonance (NMR) is a powerful technique for chemical
analysis. The use of NMR to investigate dilute analytes in complex
systems is, however, hampered by its relatively low sensitivity. An
additional obstacle is represented by the NMR signal overlap. Because
solutes in a complex mixture are usually not isotopically labeled,
NMR studies are often limited to
1
H measurements, which,
because of the modest dispersion of the
1
H resonances (typically
∼10 ppm), can result in challenging signal crowding. The low
NMR sensitivity issue can be alleviated by nuclear spin hyperpolarization
(i.e., transiently increasing the differences in nuclear spin populations),
which determines large NMR signal enhancements. This has been demonstrated
for hyperpolarization methods such as dynamic nuclear polarization,
spin-exchange optical pumping and
para
-hydrogen-induced
polarization (PHIP). In particular, PHIP has grown into a fast, efficient,
and versatile technique since the recent discovery of non-hydrogenative
routes to achieve nuclear spin hyperpolarization.
For instance,
signal amplification by reversible exchange (SABRE)
can generate proton as well as heteronuclear spin hyperpolarization
in a few seconds in compounds that are able to transiently bind to
an iridium catalyst in the presence of
para
-hydrogen
in solution. The hyperpolarization transfer catalyst acts as a chemosensor
in the sense that it is selective for analytes that can coordinate
to the metal center, such as nitrogen-containing aromatic heterocycles,
sulfur heteroaromatic compounds, nitriles, Schiff bases, diaziridines,
carboxylic acids, and amines. We have demonstrated that the signal
enhancement achieved by SABRE allows rapid NMR detection and quantification
of a mixture of substrates down to low-micromolar concentration. Furthermore,
in the transient complex, the spin configuration of
p
-H
2
can be easily converted to spin hyperpolarization
to produce up to 1000-fold enhanced NMR hydride signals. Because the
hydrides’ chemical shifts are highly sensitive to the structure
of the analyte associating with the iridium complex, they can be employed
as hyperpolarized “probes” to signal the presence of
specific compounds in the mixture. This indirect detection of the
analytes in solution provides important benefits in the case of complex
systems, as hydrides resonate in a region of the
1
H spectrum
(at ca. −20 ppm) that is generally signal-free. The enhanced
sensitivity provided by non-hydrogenative PHIP (nhPHIP), together
with the absence of interference from the complex matrix (usually
resonating between 0 and 10 ppm), set the detection limit for this
NMR chemosensor down to sub-μM concentrations, approximately
3 orders of magnitude lower than for conventional NMR. This nhPHIP
approach represents, therefore, a powerful tool for NMR analysis of
dilut...
