The goal of this proposal is to address some of the fundamental reasons why parahydrogen induced polarization has not yet made its way into biomedical applications, which from a chemical perspective are as follows:

• the lack of available biocompatible parahydrogen catalysts (including those based on first-row metals).

• the lack of compatible substrates (biomolecules or drugs) suitable for hyperpolarization.

• effective ways to remove the catalysts remaining in the hyperpolarized product solutions.

Our studies in this arena have also determined that the following are requirements (research objectives) for biocompatible PHIP catalysts, thus providing an exclusive basis for our rapid developmen...

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The goal of this proposal is to address some of the fundamental reasons why parahydrogen induced polarization has not yet made its way into biomedical applications, which from a chemical perspective are as follows:

• the lack of available biocompatible parahydrogen catalysts (including those based on first-row metals).

• the lack of compatible substrates (biomolecules or drugs) suitable for hyperpolarization.

• effective ways to remove the catalysts remaining in the hyperpolarized product solutions.

Our studies in this arena have also determined that the following are requirements (research objectives) for biocompatible PHIP catalysts, thus providing an exclusive basis for our rapid development of these catalysts into the clinic, and a framework for our proposed studies. Objective 1. The late first-row transition metal catalyst must be low-spin. Thus, catalysts will be biased towards low-spin configurations by using electron-rich ligand frameworks. Objective 2. The catalyst needs to react with H2 (p-H2) in the presence of substrates. The rates of substrate exchange on the catalyst will be determined because of its importance for both hydrogenative and nonhydrogenative PHIP. Objective 3. The catalyst must exhibit pairwise addition of p-H2 and be benchmarked against other catalysts. Monitoring the hydrogenation of ethyl acrylate by 1H NMR will allow for the determination of pairwise addition of p-H2. Objective 4. The catalyst must tolerate substrates with key functional groups such as 13C=O or 15N. Critically, these functional groups exhibit long T1 relaxation times that prolong the observed hyperpolarized signal. Objective 5. The catalyst must facilitate substantial NMR signal enhancement of biorelevant molecules in a biorelevant system.

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