Lifetime of Parahydrogen in Aqueous Solutions and Human Blood

Abstract

Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2), was instrumental in the early days of quantum mechanics and allows to boost the NMR signal by several orders of magnitude. pH2‐induced polarization (PHIP) is based on the survival of pH2 spin order in solution, yet its lifetime has not been investigated in aqueous or biological media required for in vivo applications. Herein, we report longitudinal relaxation times (T1) and lifetimes of pH2 (τnormalPnormalOnormalC ) in methanol and water, with or without O2, NaCl, rhodium‐catalyst or human blood. Furthermore, we present a relaxation model that uses T1 and τnormalPnormalOnormalC for more precise theoretical predictions of the H2 spin state in PHIP experiments. All measured T1 values were in the range of 1.4–2 s and τnormalPnormalOnormalC values were of the order of 10–300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP.

In-Cell Structural Biology by NMR: The Benefits of the Atomic Scale

“…Sensitivity is the eternal Achille’s heal of NMR spectroscopy. Magnetic hyperpolarization methods (DNP, para-hydrogen) have been cheered in the last years for their theoretical game-changing signal enhancement of several ordered of magnitudes. − Their applications on live cells are however limited by the short lifetime of hyperpolarization at physiological temperature, i.e., about 1 min or less. − DNP-ssNMR has been used to characterize proteins in cellular samples . However, the current DNP-agent molecules are effective at ∼100 K or less, which provokes low spectral resolution, high costs and technicity and limits the applications.…”

Instrumentation for Hydrogenative Parahydrogen-Based Hyperpolarization Techniques

“…Before the addition, the lifetime of gaseous − or dissolved − pH 2 is typically long (days or many minutes, respectively). However, once bound to the catalyst or the precursor, ,− the lifetime of the spin order is drastically reduced because the added protons, referred to as I 1 and I 2 , interact with the environment and the rest of the (now larger) spin system.…”

Synthesis of13C and2H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate

“…pH 2 can be produced in bulk and stored for days, making it a convenient and readily available source of nuclear spin order. [15][16][17] The spin order of pH 2 can be used to enhance the 13 C [18][19][20][21] or 15 N [22][23][24] magnetization of a contrast agent either by temporary contact (signal amplification by reversible exchange, SABRE) [25] or by pairwise addition of pH 2 to an unsaturated precursor (catalytic hydrogenation). [26] The fact that many biologically interesting compounds do not have an unsaturated precursor has long hindered the development of PHIP.…”

“…At 77 K (liquid nitrogen), the pH 2 fraction is about 50 %, and at 21 K (boiling point of H 2 ), it is >99 %. pH 2 can be produced in bulk and stored for days, making it a convenient and readily available source of nuclear spin order [15–17] …”