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

Nuclear spin hyperpolarization techniques are revolutionizing the field of ¹³ C molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring ≈1 h) and costly (≈$USD10⁶ ). As a consequence of carbon's central place in biochemistry, tremendous progress using ¹³ C 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 ¹⁵ N, ³¹ P, and other heteronuclei using signal amplification by reversible exchange (SABRE) has been reported in 2015, but extension of this technique to ¹³ C has proven to be challenging. Here, we present efficient hyperpolarization of ¹³ C 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 ≈4.4 % using 50 % parahydrogen (P_13C >14 % would be feasible using more potent ≈100 % parahydrogen). Importantly, the ¹³ C polarization achieved via SABRE strongly depends not only upon spin-lattice relaxation, but also upon the presence of ¹⁵ N (I=1/2) versus quadrupolar ¹⁴ N (I=1) spins in the site binding the hexacoordinate Ir atom of the catalytic complex. We show that different ¹³ C nuclei in the test molecular frameworks-pyridine and acetonitrile-can be hyperpolarized, including ¹³ C 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.