Development of Metalloporphyrin for Diversified Applications: from Contrast Agent for Magnetic Resonance Imaging to Electrocatalyst for Carbon Dioxide Reduction

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Our program explores the structural and functional diversity of metalloporphyrin for the development of 1) next generation contrast agent (CA) for magnetic resonance imaging (MRI), and 2) novel electrocatalyst for CO2 reduction. Part 1 focuses on the design, synthesis and evaluation of new Mn3+-porphyrin (MnP) as Gd-Free MRI CA. MRI is based on spatially encoded NMR signals mainly from H2O protons. The image contrast of MRI can be enhanced by paramagnetic agent via shortening the NMR relaxation time of local 1H nuclei, thus enabling the detection of otherwise invisible disease. Gadolinium based CA (GBCA) has dominated clinic market for >30 years. Recently, however, GBCAs have been linked to severe side effects due to the low kinetic stability, causing the release and deposition of toxic Gd3+ ion in vivo. The low sensitivity, thus high dose of GBCA escalates the toxicity risk. To overcome these intrinsic limitations of GBCAs, we've been dedicated to developing Gd-free alternatives based on MnP. Through rational design, we've shown that new MnPs with higher sensitivity, stability and biocompatibility can be synthesized. This allowed us to further design different classes of MnPs specific for extracellular, liver-targeted, intravascular or intracellular applications, demonstrating the potential of MnP not only to replace the existing GBCAs, but also to enable new functions that classic GBCAs are unable to reach. This proposal explores the following directions: 1) study how metal-ligand interaction influences the MRI sensitivity and stability of MnPs; 2) optimize the key properties of MnPs by rational ligand modification; 3) design new strategy for MRI based reporter-gene system, allowing monitoring of protein-expression in live animals, 4) develop general approach for labeling antibody with MnPs-oligomer for targeted disease imaging; 5) explore new chemical reactions for MnP bioconjugation. Our long-term goal is to develop MRI probes for detecting diseases and visualizing biological activities in living objects with optimal safety, sensitivity, and specificity. Part 2 of the proposal will expand the functions of MP for electrochemical CO2 reduction. Based on the initial success, we will tackle the following key challenges in the field: 1) study mechanism of CO2 electrochemical reduction, focused on the order and energy barrier of electron and proton transfer; 2) design novel porphyrins with improved coupled efficiency between electron and proton transfer; 3) study the structure-activity relationship, in particular on how different metal ions and/or spin states influence the rate-determining step; and 4) develop new strategy for efficient immobilization of porphyrin catalyst on electrode surface. Rooted in the common ground of porphyrin chemistry, both parts of the program span the interface of organic, inorganic, biological, analytical, and physical chemistry, engaging and cultivating multidisciplinary collaborations, thus ideal for HQP training.