SABRE-SHEATH\nHyperpolarization of [1,5-<sup>13</sup>C<sub>2</sub>]Z-OMPD for Noninvasive\npH Sensing

Hyperpolarized (HP) <sup>13</sup>C-labeled probes are\nemerging\nas promising agents to noninvasively image pH in vivo. HP [1,5-<sup>13</sup>C<sub>2</sub>]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid)\nin particular has recently been used to simultaneously report on kidney\nperfusion, filtration, and pH homeostasis, in addition to the ability\nto detect local tumor acidification. In previous studies, dissolution\ndynamic nuclear polarization was used to hyperpolarize Z-OMPD. Here,\nwe pioneered the hyperpolarization of [1,5-<sup>13</sup>C<sub>2</sub>]Z-OMPD via SABRE-SHEATH (signal amplification by reversible exchange\nin shield enabling alignment transfer to heteronuclei), which is relatively\nsimple and fast and promises to be highly scalable. With SABRE-SHEATH,\nwe achieve enhancement values of ∼3950 and ∼2400 at\n1.1 T (<i>P</i><sub>13C</sub> = 0.4 and 0.25%) on the labeled\nC-1 and C-5 positions of Z-OMPD. Density functional theory calculations\nat the B3LYP level of theory were used to investigate possible binding\nmodes of Z-OMPD on the iridium-based polarization transfer catalyst.\nThe experimental and theoretical results suggest that the equatorial\nbinding mode to the catalyst, where Z-OMPD binds to the catalyst at\nboth C-1 and C-5 carboxylate positions, is the most stable complex.\nThe HP signals were used to measure the Z-OMPD chemical shift as a\nfunction of pH showing an ∼3 ppm shift across pH 4–11.\nThis work lays a foundation for the development of a simple, low-cost\nhyperpolarization technique to image pH.