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

在化学系化学催化项目的支持下，史蒂文斯理工学院张勇博士将进行一项严格的计算研究，以改进可持续化学中选定的重要转化的催化剂设计。目标催化剂是具有许多吸引人的特性的工程血红素蛋白，例如在室温、水溶液中以高产量、高化学、区域和立体选择性递送产物，具有生物相容性和低毒性。这些催化剂还含有最丰富和最便宜的过渡金属铁（铁）。也就是说，在天然产物、药物和生物化合物的合成中，某些催化转化的巨大挑战仍然存在，特别是在环丙烷化和氮-氢插入反应方面，特别是在依赖铁催化的情况下。张博士的研究小组采用高精度的计算技术，提供了这种血红素基催化剂以前未知的机制信息。特别是，张博士将致力于提高这些具有挑战性的化学转化的催化反应性和选择性。例如，这种见解可能导致在制药工业中大规模进行的某些过程化学过程的改进。张博士的研究广泛地与教学、培训和学习相结合，来自不同层次的不同群体的学生广泛参与，特别是那些来自代表性不足群体的学生。他们利用多个渠道向社会广泛传播研究成果。例如，在这个nsf支持的项目中，学生们在他们的课堂上、在他们的部门和/或大学里做演讲/报告。此外，还有面向K-12机构、博物馆、新闻媒体（包括传统大众媒体和社交媒体）的外展计划，以加强对该项目影响的科学理解。环丙烷化可用于天然产物和药物化合物的合成，N-H插入可用于氨基酸、生物碱、n -杂环化合物和生物偶联的合成。工程血红素蛋白在可持续的碳转移反应中表现出许多优异的催化性能。然而，对于某些催化环丙烷化和N-H插入，特别是对于电子贫乏的底物，仍然存在一些巨大的挑战。在一些实验系统中，不同环丙烷化与N-H插入化学选择性的起源也是未知的。张勇博士的研究小组正在进行一项严格的量子化学计算研究，研究一些血红素结构因素的先前未知的机制细节，以增强具有挑战性的环丙烷化和N-H插入的催化反应性。对不同催化剂组分的环丙烷化与N-H插入化学选择性的深入研究有助于设计“匹配”的选择性功能化催化剂。张博士的研究广泛地与教学、培训和学习相结合。在他的实验室里，学生们积极地参与到将他们的研究成果结合在一起的课堂和拓展项目中。张博士继续他的积极努力，让来自不同群体的学生广泛参与各个层面，特别是包括来自代表性不足的群体的学生。张博士的研究小组通过多种渠道向科学界和公众广泛传播他们的研究成果。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.