A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

Abstract

Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C = 20 ± 2.5 % corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.

Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

“…Although SABRE hyperpolarization in aqueous media has been demonstrated, so far, the SABRE polarization levels in aqueous solutions are more than 10‐fold lower than those in alcoholic solutions, for example, in methanol here, largely due to significantly lower H 2 solubility in water . Two potential work‐arounds that can be envisioned in the context of biomedical applications are 1) the use of high‐pressure hyperpolarizers to increase the concentration of pH 2 in aqueous solutions or 2) the dilution of alcoholic solutions (e.g., based on ethanol) with a biocompatible buffer followed by in vivo injection, because the 15 N T 1 value is nearly 10 minutes in vitro and therefore the slow injection of larger volumes over several minutes may be feasible in the context of future in‐human applications.…”

Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation

“…For example, HP HEP has been extensively studied as a potential contrast agent in angiography studies . Because some of the PHIP techniques rely on the application of RF pulses, especially in the case of polarization transfer from protons to 13 C nuclei, the RF coils may interact with the highly proton‐hyperpolarized compounds, resulting in complicated non‐linear effects and depletion of hyperpolarization via RASER activity. Therefore, RASER effects may be considered as an obstacle in this context.…”

Hyperpolarized NMR Spectroscopy: d‐DNP, PHIP, and SABRE Techniques

“…[26] PHIP-SAHo ffers as ignificantly lower-cost (by approximatelyo ne ordero fm agnitude) and faster (by approximately one order of magnitude) [77,78] alternative to d-DNP. [1] An umber of automated devices for the PHIP hyperpolarization process have been developed, [60,61,[79][80][81][82][83][84][85][86][87] which have achieved 13 Cp olarizations of up to 25 %. Importantly,p arahydrogen-delivered polarization can be successfully transferred to other heteronuclei (such as 15 N [88] and 19 Fnuclei [89,90] ).…”