by Keyword: fumarate
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
Eills, J, Picazo-Frutos, R, Burueva, DB, Kovtunova, LM, Azagra, M, Marco-Rius, I, Budker, D, Koptyug, IV, (2023). Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-13C]succinate Chemical Communications 59, 9509-9512
We show that catalyst-free aqueous solutions of hyperpolarized [1-13C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-13C]fumarate via PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/Al2O3 catalyst. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-13C]succinate as a hyperpolarized contrast agent.
JTD Keywords: acid, c-13, conversion, fumarate, in-vivo, metabolism, order, Induced polarization
