CAS:Mechanistic Investigation of Heme-based Catalysts for Sustainable Carbene Transfer Reactions

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With support from the Chemical Catalysis program in the Division of Chemistry, Dr. Yong Zhang of Stevens Institute of Technology will conduct a rigorous computational study to improve catalyst design for selected important transformations in sustainable chemistry. The targeted catalysts are engineered heme proteins with numerous attractive properties, such as delivering products in high yield, with high chemo-, regio-, and stereoselectivity, at room temperature, in aqueous solution, with biocompatibility and low toxicity. These catalysts also incorporate the most abundant and least expensive transition metal, Fe (iron). That said, big challenges for certain catalytic transformations involved in synthesis of natural products, drugs, and biological compounds still persist, in particular regarding the reactions of cyclopropanation and nitrogen-hydrogen insertion, particularly if one is to rely upon Fe-catalysis. Dr. Zhang’s research group employs high accuracy computational techniques to provide the previously unknown mechanistic information of such heme-based catalysts. In particular, Dr. Zhang will work toward enhancing their catalytic reactivity and selectivity for these challenging chemical transformations. Such insights may lead to improvements in certain process chemistry procedures conducted on scale in the pharmaceutical industry, for example. Dr. Zhang’s research is broadly integrated with teaching, training, and learning, with broad participation of students from different groups at various levels, particularly those from underrepresented groups. Several channels are employed to broadly disseminate their research results to the community. For example, students in this NSF-supported project give presentations/reports in their classes, and within their department and/or university. There are also outreach programs for K-12 institutions, museums, news media (both traditional mass media and social media), enhancing the scientific understanding of the impacts of this project. Cyclopropanation is useful for synthesis of natural products and pharmaceutical compounds and N-H insertion is useful for synthesis of amino acids, alkaloids, N-heterocyclic compounds, and bioconjugation. Engineered heme proteins have exhibited numerous excellent catalytic properties for sustainable carbene transfer reactions. Yet there are still some big challenges for certain catalytic cyclopropanations and N-H insertions, particularly for electron-poor substrates. The origins of varied cyclopropanation vs. N-H insertion chemoselectivity in some experimental systems are also unknown. Dr. Yong Zhang’s research group is conducting a rigorous quantum chemical computational study of the previously unknown mechanistic details of some heme structural factors toward enhancing catalytic reactivities for challenging cyclopropanations and N-H insertions. Insights into variable cyclopropanation vs. N-H insertion chemoselectivity from different catalyst components are sought to help design 'matched ' catalysts for selective functionalization. Dr. Zhang’s research is broadly integrated with teaching, training, and learning. Students in his lab are actively involved in classes and outreach programs that incorporate their research results. Dr. Zhang continues his vigorous efforts to have broad participation of students from diverse groups at various levels, particularly including students from underrepresented groups. Several channels are employed by Dr. Zhang’s research group to broadly disseminate their research results to the scientific community and general public.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.