The Absence of Quadrupolar Nuclei Facilitates Efficient 13C Hyperpolarization via Reversible Exchange with Parahydrogen

Nuclear spin hyperpolarization techniques are revolutionizing the field of C-13 molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring approximate to 1 h) and costly (approximate to $USD10(6)). As a consequence of carbon's central place in biochemistry, tremendous progress using C-13 d-DNP bioimaging has been demonstrated to date including a number of clinical trials. Despite numerous attempts to develop alternatives to d-DNP, the competing methods have faced significant translational challenges. Efficient hyperpolarization of N-15, P-31, and other heteronuclei using signal amplification by reversible exchange (SABRE) has been reported in 2015, but extension of this technique to C-13 has proven to be challenging. Here, we present efficient hyperpolarization of C-13 nuclei using micro-Tesla SABRE. Up to ca. 6700-fold enhancement of nuclear spin polarization at 8.45 T is achieved within seconds, corresponding to P-13C approximate to 4.4% using 50% parahydrogen (P-13C > 14% would be feasible using more potent approximate to 100% parahydrogen). Importantly, the C-13 polarization achieved via SABRE strongly depends not only upon spin-lattice relaxation, but also upon the presence of N-15 (I = 1/2) versus quadrupolar N-14 (I = 1) spins in the site binding the hexacoordinate Ir atom of the catalytic complex. We show that different C-13 nuclei in the test molecular frameworks-pyridine and acetonitrile-can be hyperpolarized, including C-13 sites up to five chemical bonds away from the exchangeable hydrides. The presented approach is highly scalable and can be applied to a rapidly growing number of biomolecules amendable to micro-Tesla SABRE.