Design and implementation of a J-coupled spectrometer for multidimensional structure and relaxation detection at low magnetic fields

Abstract

In recent years, it has been realized that low and ultra-low field (mT–nT magnetic field range) nuclear magnetic resonance spectroscopy can be used for molecular structural analysis. However, spectra are often hindered by lengthy acquisition times or require large sample volumes and high concentrations. Here, we report a low field (50 μT) instrument that employs a linear actuator to shuttle samples between a 1 T prepolarization field and a solenoid detector in a laboratory setting. The current experimental setup is benchmarked using water and 13C-methanol with a single scan detection limit of 2 × 1020 spins (3 µl, 55M H2O) and detection limit of 2.9 × 1019 (200 µl, 617 mM 13C-methanol) spins with signal averaging. The system has a dynamic range of >3 orders of magnitude. Investigations of room-temperature relaxation dynamics of 13C-methanol show that sample dilution can be used in lieu of sample heating to acquire spectra with linewidths comparable to high-temperature spectra. These results indicate that the T1 and T2 mechanisms are governed by both the proton exchange rate and the dissolved oxygen in the sample. Finally, a 2D correlation spectroscopy experiment is reported, performed in the strong coupling regime that resolves the multiple resonances associated with the heteronuclear J-coupling. The spectrum was collected using 10 times less sample and in less than half the time from previous reports in the strong coupling limit.

Quantitation of Nuclear Magnetic Resonance Spectra at Earth’s Magnetic Field

“…The JCS were collected using a previously described, homebuilt spectrometer. 24 The samples were first prepolarized in a 0.84 T Halbach magnet to increase SNRs for detection at Earth's field. Next, the samples were shuttled with a linear actuator into Earth's magnetic field, where a pulse-acquire NMR experiment was performed.…”

“…Previously, this was observed in Earth's field NMR for neat 13 C-methanol samples and appeared to be a concentration effect. 22,24 In these studies, the correct intensities were only obtained after significant dilution in a deuterated solvent. As the MF sample studied here was neat, the intensity mismatch may be expected but warrants further investigation into the origin of this phenomenon.…”

“…27 Recent studies have demonstrated unique JCS between small molecules with similar chemical structures in the absence of discernible chemical shifts. [22][23][24]28,29 Quantitation of the JCS can only proceed by understanding the spin systems in the molecule and their corresponding resonances.…”

“…On the other hand, as the applied magnetic field is decreased, a concomitant decrease in the chemical shift dispersion and NMR signal occurs, resulting in peak overlap and poor SNRs. At Earth’s magnetic field (∼50 μT), the chemical shift dispersion (∼10 ppm) of the 1 H signal is reduced to ∼20 mHz, which is typically smaller than the peak widths observed at these μT fields. − While chemical shifts for other nuclei such as 19 F and 129 Xe have been observed, it is unlikely that quantitation at Earth’s magnetic field via chemical shift differences will be ubiquitous for all nuclei and closely related molecules. ,, Instead of chemical shifts, heteronuclear J -couplings break the magnetic equivalence of the nuclear spins at these μT magnetic fields and result in a unique spectral signature: the J -coupled spectrum (JCS) . Recent studies have demonstrated unique JCS between small molecules with similar chemical structures in the absence of discernible chemical shifts. − ,, Quantitation of the JCS can only proceed by understanding the spin systems in the molecule and their corresponding resonances.…”

Fast-field-cycling, ultralow-field nuclear magnetic relaxation dispersion

“…The main existing NMRD technique uses fast-field-cycling (FFC) electromagnets [9][10][11][12] of around 1 T for efficient inductive NMR signal detection, but these must be used unshielded with active cancelation of ambient fields to access below the geomagnetic field range 13,14 . Alternatively, NMRD is performed by transporting samples between persistent high-and ultralow-field locations [15][16][17][18][19] , but relatively slow transport times limit the observable τ c at the high end. The limits of these existing techniques are illustrated by the magenta-and blue-shaded regions, respectively, of Figure 1.…”