RESEARCH

1)          Nuclear Spin Hyperpolarization

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are extremely powerful analytical tools used to study structure and dynamics of materials and living species. However, due to the weak interaction of nuclei with the applied magnetic fields (less than 0.2 J/mol), measured NMR signals are extremely low even at the fields of modern NMR spectrometers. For example, at 3 Tesla, a magnetic field that is thousands of times larger than the Earth’s field, there is only a net polarization of approximately 1 out of 100,000 nuclear spins. This means that typical polarization (%P) in conventional high-field NMR experiments is only 0.001% out of the theoretically possible 100%. We use hyperpolarization with the goal of polarizing allnuclear spins in chemicals under study. In the Lab, instead of 0.001% we readily achieve 10-30% polarization.

Hyperpolarization Toolkit:

-Parahydrogen-Induced Polarization (PASADENA/ALTADENA, SABRE)

-Chemically-Induced Dynamic Nuclear Polarization (CIDNP)

-Dynamic Nuclear Polarization (DNP)

-Spin-Exchange Optical Pumping (SEOP)

Relevant Publications:

• D. A. Barskiy, S. Knecht, A. V. Yurkovskaya, K. L. Ivanov. SABRE: Chemical Kinetics and Spin Dynamics of the Formation of Hyperpolarization. Prog. Nucl. Magn. Reson. Spectrosc., 2019, 114, 33-70.
• K. Kovtunov, E. Pokochueva, O. Salnikov, S. Cousin, D. Kurzbach, B. Vuichoud, S. Jannin, E. Chekmenev, B. Goodson, D. Barskiy, I. Koptyug. Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques. Chem. Asian J., 2018, 13 (15), 1857-1871.
• D. A. Barskiy, A. M. Coffey, P. Nikolaou, D. M. Mikhaylov, B. M. Goodson, R. T. Branca, G. J. Lu, M. G. Shapiro, V.-V. Telkki, V. V. Zhivonitko, et al. NMR Hyperpolarization Techniques of Gases. Chem. Eur. J., 2017, 23 (4), 725–751.

2)          Nuclear Spin Engineering

Precise coherent control of the nuclear spin dynamics made NMR spectroscopy a unique tool that allows scientists testing quantum mechanics and the basic laws of nature. However, due to the limitations imposed by molecular symmetry, some transformations between nuclear spin states are not possible. In the Lab, we combine coherent control over spins (RF pulses, magnetic fields, etc.) with the ability of governing chemical transformations (using light, adding catalysts/inhibitors to facilitate/suppress reactions) to prepare spin states which are not accessible otherwise. Nuclear spin systems engineered in such a way find applications in quantum computing, non-equilibrium quantum dynamics, and storage of the quantum memory on the timescale of hours in solution.

Nuclear Spin Engineering Toolkit:

-Long-lived Spin States

-SABRE/SABRE-relay

-Chemically-Induced Dynamic Nuclear Polarization (CIDNP)

Relevant Publications:

• S. Knecht, J. W. Blanchard, D. Barskiy, et al. Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution. Proc. Nat. Acad. Sci., 2021, 118 (13), e2025383118.
• K. Sheberstov, L. Chuchkova, Y. Hu, I. Zhukov, A. Kiryutin, A. Eshtukov, D. Cheshkov, D. Barskiy, J. Blanchard, D. Budker, K. Ivanov, A. Yurkovskaya. Photochemically induced dynamic nuclear polarization of heteronuclear singlet order. J. Phys. Che. Lett., 2021, 12, 19, 4686-4691.
• D. A. Barskiy*, L. A. Ke, X. Li, V. Stevenson, N. Widarman, H. Zhang, A. Truxal, A. Pines. Rapid Catalyst Capture Enables Metal-Free para-Hydrogen-Based Hyperpolarized Contrast Agents. J. Phys. Chem. Lett., 2018, 9, 2721–2724.

3)          Novel NMR methodology

Zero- to Ultralow-field NMR

Despite the tremendous utility, conventional NMR has severe limitations associated with the use of large magnetic fields. First, magnetic fields of several Tesla are often achieved by using superconducting magnets which are costly and hard to transport. Second, cryogens needed for operation of such magnets necessitate advanced research infrastructure and are available only in the well-equipped scientific center. While NMR can also be performed in transportable “bench-top” permanent magnet systems (1–2 T) with reduced sensitivity and resolution, it is possible to study the behavior of nuclear spins in the complete absence of an applied field. This form of NMR, also known as zero- to ultralow-field (ZULF) NMR, can provide chemical resolution in mixtures with a high sensitivity (10 fT/Hz^0.5) without a need for strong, persistent magnetic fields. Direct detection of spin−spin coupling spectra (also called J-spectra) at zero field provides molecular “fingerprints” suitable for chemical analysis. Relying on recent advances in atomic magnetometry, we are developing methodology of portable and inexpensive ZULF NMR for applications beyond chemical laboratory.

NMR-based search for dark matter and molecular parity violations

The weak interaction has been shown experimentally to violate parity in both nuclear and atomic scale experiments. We seek to use the exquisite precision of NMR spectroscopy to observe parity violation in static systems on the molecular scale. Employing the techniques of diastereomeric splitting and co-magnetometry, we attempt to resolve residual chemical shift differences in enantiomers of chiral compounds caused by nuclear-spin-dependent contributions of the weak interaction. We are currently working on identifying main sources of experimental error such analyses and looking for suitable chemistries that amplify the sought-for effects.

Relevant Publications:

• P. Put, S. Pustelny, D. Budker, E. Druga, T. Sjolander, A. Pines, D. Barskiy. Zero- to Ultralow-Field NMR Spectroscopy of Small Biomolecules. Anal. Chem, 2021, 93, 6, 3226–3232, https://doi.org/10.1021/acs.analchem.0c04738; (FRONT COVER, ACS Editor’s Choice).
• D. A. Barskiy, M. C. D. Tayler, I. Marco-Rius, J. Kurhanewicz, D. B. Vigneron, S. Cikrikci, A. Aydogdu, M. Reh, A. N. Pravdivtsev, J.-B. Hövener, J. W. Blanchard, T. Wu, D. Budker, A. Pines. Zero-field Nuclear Magnetic Resonance of Chemically Exchanging Systems. Nat. Commun., 2019, 10 (1), 3002.
• D. Barskiy, J. W. Blanchard, M. Reh, T. Sjolander, A. Pines, D. Budker. Zero-field J-spectroscopy of Quadrupolar Nuclei. ArXiv, 2021, https://arxiv.org/abs/2011.05618.

J. W. Blanchard, B. Ripka, B. A. Suslick, D. Gelevski, T. Wu, K. Munnemann, D. A. Barskiy, D. Budker. Towards Large-Scale Steady-State Enhanced Nuclear Magnetization with In Situ Detection. Mag. Res. Chem.,. https://doi.org/10.26434/chemrxiv.13567481.v1