Today, the conventional NMR sample still consists of a cylindrical glass tube of 5-mm outer
diameter and ~20-cm length with a sample fill volume of 500-600 ?L. Ultra-high-field
NMR spectrometers up to 900 MHz and cryogenically cooled detector coils are available,
but, nevertheless, structural analysis of mass-limited samples in the microgram
range, e.g., natural product isolates, DNAs, proteins, drug metabolites, still remains
challenging. Recently 1- and 1.7-mm microprobes with 5- and 30-??L fill volume, respectively,
were developed. These new microliter probes allow the measurement of
one-dimensional 1H NMR and two-dimensional heteronuclear NMR spectra with a few
nanomoles (micrograms) of compound with high sensitivity, speed, and quality.1 The
introduction of these small volume probeheads has been a breakthrough for NMR
spectroscopy for structure elucidation of natural products and metabolic research.
These probeheads offer also advantages for linking chromatographic methods to NMR.
Another advantage of these microprobes is that with decreasing diameter of the NMR
detector coil, the NMR mass sensitivity (S/N per mole) increases approximately with
1/d. Thus, as compared to a standard 5 mm probehead, a 1.7 mm probehead has a
mass sensitivity of 2, i.e. the required sample amount can be divided by two for the
same results in term of signal-to-noise.2
Additional non-negligible advantages of these low-volume probes are that signals
from solvent impurities are much less prominent with decreasing sample volume.
For electrically conductive solvents such as salt-containing solutions there is also a
reduction of the “solvent noise” when going to smaller volumes. In addition, the
amount of expensive deuterated solvents can be dramatically reduced (often by 2 orders
of magnitude). In addition, signals from solvent impurities are much less prominent
with decreasing sample volume. For electrically conductive solvents such as saltcontaining
solutions there is also a reduction of the “solvent noise” when going to
smaller volumes.2
For the investigators of this proposal, the equipment will open
new fields to NMR spectroscopic research that are currently not feasible with the current
equipment available. Owing to the broad variety of samples falling into the application
field of a microprobe, e.g. proteins, DNAs, natural products, a diversified interdisciplinary
usership will be able to benefit from this microprobe. In view of the current
countrywide lack of accessibility to such a dedicated probehead within the Swiss
university institutions, the equipment will close this gap and will enable us to keep
up with modern state-of-the-art technologies, explore new applications fields and extend
our competences.
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