by Keyword: Pyruvic acid
Eills, James, Picazo-Frutos, Roman, Bondar, Oksana, Cavallari, Eleonora, Carrera, Carla, Barker, Sylwia J, Utz, Marcel, Herrero-Gomez, Alba, Marco-Rius, Irene, Tayler, Michael C D, Aime, Silvio, Reineri, Francesca, Budker, Dmitry, Blanchard, John W, (2023). Enzymatic Reactions Observed with Zero- and Low-Field Nuclear Magnetic Resonance Analytical Chemistry 95, 17997-18005
We demonstrate that enzyme-catalyzed reactions can be observed in zero- and low-field NMR experiments by combining recent advances in parahydrogen-based hyperpolarization methods with state-of-the-art magnetometry. Specifically, we investigated two model biological processes: the conversion of fumarate into malate, which is used in vivo as a marker of cell necrosis, and the conversion of pyruvate into lactate, which is the most widely studied metabolic process in hyperpolarization-enhanced imaging. In addition to this, we constructed a microfluidic zero-field NMR setup to perform experiments on microliter-scale samples of [1-C-13]-fumarate in a lab-on-a-chip device. Zero- to ultralow-field (ZULF) NMR has two key advantages over high-field NMR: the signals can pass through conductive materials (e.g., metals), and line broadening from sample heterogeneity is negligible. To date, the use of ZULF NMR for process monitoring has been limited to studying hydrogenation reactions. In this work, we demonstrate this emerging analytical technique for more general reaction monitoring and compare zero- vs low-field detection.
JTD Keywords: Fumarates, Hydrogenation, Magnetic resonance imaging, Magnetic resonance spectroscopy, Nmr j-spectroscopy, Pyruvic acid
Schmidt, AB, Eills, J, Dagys, L, Gierse, M, Bock, M, Lucas, S, Bock, M, Schwartz, I, Zaitsev, M, Chekmenev, EY, Knecht, S, (2023). Over 20% Carbon-13 Polarization of Perdeuterated Pyruvate Using Reversible Exchange with Parahydrogen and Spin-Lock Induced Crossing at 50 μT Journal Of Physical Chemistry Letters 14, 5305-5309
Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13C polarization (T1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.
JTD Keywords: hydrogen, nmr, Carbon isotopes, Carbon-13, Magnetic resonance imaging, Magnetic resonance spectroscopy, Pyruvic acid, Sabre