(De)coding SABRE of [1-¹³C]pyruvate

Area of Science:

• Magnetic Resonance Imaging
• Hyperpolarized Contrast Agents
• Catalysis

Background:

• Hyperpolarized pyruvate is crucial for biomedical imaging, but efficient Signal Amplification by Reversible Exchange (SABRE) enhancement is challenging.
• Existing methods struggle to maximize ¹³C polarization for pyruvate, limiting its diagnostic potential.

Purpose of the Study:

• To comprehensively investigate and optimize SABRE hyperpolarization of pyruvate.
• To explore novel iridium-NHC catalysts and understand the factors governing polarization efficiency.
• To develop a predictive model for rational SABRE protocol design.

Main Methods:

• Synthesis and testing of seven distinct iridium-NHC catalysts for pyruvate SABRE.
• Density Functional Theory (DFT) calculations to analyze coupling strengths and binding geometries.
• Variable-temperature experiments on free and catalyst-bound pyruvate.
• Development of a detailed mechanistic model incorporating kinetics, concentrations, and relaxation.

Main Results:

• IMes catalyst achieved ~3% ¹³C polarization (extrapolated to ~10% at 100% parahydrogen).
• Alternative catalysts (IPr, SIPr) showed ~20% lower performance but enabled natural abundance ¹³C detection.
• DFT and experimental data indicated exchange dynamics, not coupling strength, are key to polarization efficiency.
• A novel temperature-jump protocol increased free pyruvate polarization by ~30%.

Conclusions:

• Catalyst design and understanding exchange dynamics are critical for optimizing pyruvate SABRE.
• The developed mechanistic model provides a predictive framework for SABRE systems.
• The temperature-jump protocol offers a new strategy for enhancing free pyruvate signals in biomedical imaging.