Application of ¹⁵N₂-Diazirines as a Versatile Platform for Hyperpolarization of Biological Molecules by d-DNP

¹⁵N₂-Diazirines represent an attractive class of imaging tags for hyperpolarized magnetic resonance imaging (HP-MRI), offering desirable biocompatibility, ease of incorporation into a variety of molecules, and ability to deliver long-lasting polarization. We have recently established hyperpolarization of ¹⁵N₂-diazirines in organic solvents using SABRE-Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH). Yet, the current challenge of SABRE-SHEATH in water, specifically poor polarization efficiency, presents a barrier in examining the practical use of ¹⁵N₂-diazirines for HP-MRI. Herein, we show that efficient polarization of diverse ¹⁵N₂-diazirine-labeled molecules in water can be readily achieved by dissolution dynamic nuclear polarization (d-DNP), a hyperpolarization technique used in clinical practice. Hyperpolarization by d-DNP also demonstrates greater enhancement for long-lasting ¹⁵N signals, in comparison with SABRE-SHEATH. Various biologically important molecules are studied in this work, including amino acid, sugar, and drug compounds, demonstrating the great potential of ¹⁵N₂-diazirines as molecular tags in broad biomedical and clinical applications.