¹⁵N hyperpolarisation of the antiprotozoal drug ornidazole by Signal Amplification By Reversible Exchange in aqueous medium

Abstract

Signal amplification by reversible exchange (SABRE) offers a cost-effective route to boost nuclear magnetic resonance (NMR) signal by several orders of magnitude by employing readily available para-hydrogen as a source of hyperpolarisation. Although 1 H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of 1 H makes it harder to employ them in a range of timedependent NMR experiments. Heteronuclear spins, for example, 13 C and 15 N, in general have much longer T 1 lifetimes and thereby are found to be more suitable for hyperpolarised biological applications as demonstrated previously by para-hydrogen induced polarisation (PHIP) and dynamic nuclear

Spin Hyperpolarization in Modern Magnetic Resonance

“…Hyperpolarized 15 N-labeled nitroimidazoles can potentially address this shortcoming, because, during metabolism, the 15 N NMR signals of the labeled sites experience substantial changes in chemical shifts 872 (up to a few hundred ppm, Figure 104b). 842 Several representative examples from this class of compounds have been hyperpolarized via SABRE-SHEATH with 15 N polarization exceeding 50%: metronidazole (including [ 15 N 3 ]metronidazole, Figure 102), ornidazole, 873 and nimorazole. 842 Given that these compounds are already approved for medical use for treatment of anaerobic infections, rapid clinical translation may be envisioned.…”

Real-Time Reaction Monitoring of Azide–Alkyne Cycloadditions Using Benchtop NMR-Based Signal Amplification by Reversible Exchange (SABRE)

“…Owing to the associated interest and importance, SABRE-based experiments on SPAAC using 15 N-containing synthons were recently performed, focusing on 15 N nuclei within the structure . However, hyperpolarization can also be delivered to various structural components combined with 1 H, − 13 C, ,, and 15 N , NMR signals; therefore, there is the possibility of observing a wider range of hyperpolarization by also focusing on other NMR-active nuclei.…”

Parahydrogen in Reversible Exchange Induces Long-Lived 15N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole

“…A number of FDA-approved drugs have been HP via SABRE, to date, including metronidazole 34−36 ornidazole, 37 nimorazole, 38 pyrazinamide, isoniazid, 39 clotrimazole, fluconazole, voriconazole, 40 and dalfampridine. 41,42 These drugs target hypoxia, tuberculosis, fungal and bacterial infections, and multiple sclerosis.…”

“…A number of FDA-approved drugs have been HP via SABRE, to date, including metronidazole − ornidazole, nimorazole, pyrazinamide, isoniazid, clotrimazole, fluconazole, voriconazole, and dalfampridine. , These drugs target hypoxia, tuberculosis, fungal and bacterial infections, and multiple sclerosis. Moreover, they are HP via SABRE using five- or six-membered N-heterocyles rather than the nitrile moiety studied in this work.…”