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

CAS：可持续卡宾转移反应的血红素基催化剂的机理研究

• 批准号: 2054897
• 负责人: Yong Zhang
• 金额: $ 36万
• 依托单位: Stevens Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2054897&HistoricalAwards=false
• 关键词: CAS; Mechanistic; Investigation; Heme; based

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.

在化学催化计划的支持下，美国计算机研究以改善具有许多有吸引力的特性的可持续化学蛋白的催化剂设计，例如具有高产量的产品，立体选择性，在室温下，溶液的生物相容性和低毒剂。持续的是，Zhang博士的研究组涉及氮杂种和氮含量导致在某些过程中的某些过程中的某些过程，以教学，培训和学习为例。社区的结果。天然药物的合成和n-H插入的环境可用于合成氨基DS，生物碱，N-杂环化合物和发动机发动机都表现出许多出色的CATALLEC特性。环聚植物的VS。n-H插入化学选择性也未知，使某些血红素结构性因子催化性促进性态度的量子的量子量很严格。要帮助Desche d' -Zhang的研究与教学融为一体Broady传播了科学界和公众。该奖项反映了NSF'SF'Stutory Mission，并使用基金会的知识分子优点和更广泛的影响审查标准进行了评估。

项目成果

Computational Mechanistic Investigations of Biocatalytic Nitrenoid C−H Functionalizations via Engineered Heme Proteins

通过工程血红素蛋白生物催化类氮化合物 C–H 功能化的计算机制研究

• DOI: 10.1002/cbic.202300260
• 发表时间: 2023
• 期刊: ChemBioChem
• 影响因子: 3.2
• 作者: Zhang, Yong;Chu, Jia‐Min
• 通讯作者: Chu, Jia‐Min