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.

在化学催化计划中的化学分部的支持下，史蒂文斯理工学院的杨张博士将进行一项严格的计算研究，以改善可持续化学中精选重要转变的催化剂设计。靶向催化剂是具有许多吸引人的特性的工程性血红素蛋白，例如在室温下，具有高化学，区域和立体选择性的高产物，具有高化的化学，区域性和立体选择性，在水溶液中，具有生物相容性和低毒性。这些催化剂还结合了最丰富，最便宜的过渡金属Fe（铁）。也就是说，对于合成天然产物，药物和生物学化合物的合成的某些催化转化的巨大挑战仍然存在，特别是关于环丙烷化和氮 - 氢插入的反应，尤其是在依靠FE催化的情况下。张博士的研究小组采用了高精度计算技术，以提供此类基于血红素的催化剂的先前未知的机械信息。特别是，张博士将致力于增强其对这些挑战化学转化的催化反应性和选择性。例如，这种见解可能会改善制药行业规模进行的某些过程化学程序。张博士的研究与教学，培训和学习广泛融合在一起，来自不同级别的不同级别的学生，尤其是来自代表性不足的群体的学生的广泛参与。几个渠道被用来将其研究结果广泛传播给社区。例如，这个由NSF支持的项目中的学生在其课程以及他们的系和/或大学中提供演讲/报告。还针对K-12机构，博物馆，新闻媒体（传统的大众媒体和社交媒体）提供外展计划，从而增强了对该项目影响的科学理解。环丙谁可用于合成天然产物和药物化合物，N-H插入可用于合成氨基酸，生物碱，N-杂环化合物和生物结合。设计的血红素蛋白具有许多出色的催化特性，可用于可持续的卡宾转移反应。然而，对于某些催化环丙者和N-H插入仍然存在一些巨大的挑战，特别是对于电子贫困的底物。在某些实验系统中，各种环丙烷与N-H插入化学选择性的起源也未知。 Yong Zhang博士的研究小组正在进行一项严格的量子化学计算研究，对一些血红素结构因素的先前未知的机理细节，以增强挑战环植物和N-H插入的催化反应性。感测到来自不同催化剂成分的N-H插入化学选择性与N-H插入化学选择性的见解，以帮助设计“匹配”催化剂以进行选择性功能化。张博士的研究与教学，培训和学习广泛融合。他的实验室的学生积极参与纳入研究结果的课程和外展计划。张博士继续努力在不同级别的潜水员团体的学生中广泛参与，尤其是包括代表性不足的学生。张博士的研究小组采用了几个渠道，将其研究结果广泛传播给科学界和公众。该奖项反映了NSF的法定使命，并使用基金会的知识分子优点和更广泛的影响评估审查标准，认为通过评估被认为是宝贵的支持。

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