Hyperpolarization of common antifungal agents with SABRE
Keilian MacCulloch, Patrick TomHon, Austin Browning, Evan Akeroyd, Sören Lehmkuhl, Eduard Y. Chekmenev, Thomas Theis
Abstract
Abstract Signal amplification by reversible exchange (SABRE) is a robust and inexpensive hyperpolarization (HP) technique to enhance nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) signals using para hydrogen ( p H 2 ). The substrate scope of SABRE is continually expanding. Here, we present the polarization of three antifungal drugs (voriconazole, clotrimazole, and fluconazole) and elicit the detailed HP mechanisms for 1 H and 15 N nuclei. In this exploratory work, 15 N polarization values of ~1% were achieved using 50% p H 2 in solution of 3‐mM catalyst and 60‐mM substrate in perdeuterated methanol. All hyperpolarized 15 N sites exhibited long T 1 in excess of 1 min at a clinically relevant field of 1 T. Hyperpolarizing common drugs is of interest due to their potential biomedical applications as MRI contrast agents or to enable studies on protein dynamics at physiological concentrations. We optimize the polarization with respect to temperature and the polarization transfer field (PTF) for 1 H nuclei in the millitesla regime and for 15 N nuclei in the microtesla regime, which provides detailed insights into exchange kinetics and spin evolution. This work broadens the SABRE substrate scope and provides mechanistic and kinetic insights into the HP process.