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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

基本信息

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

项目摘要

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.

在化学系化学催化项目的支持下，史蒂文斯理工学院的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。目标催化剂是工程化的血红素蛋白，具有许多吸引人的特性，如高产率、高化学选择性、区域选择性和立体选择性，在室温下，在水溶液中，具有生物相容性和低毒性。这些催化剂还加入了最丰富和最便宜的过渡金属铁(铁)。尽管如此，天然产物、药物和生物化合物合成中涉及的某些催化转化仍然存在巨大的挑战，特别是在环丙烷化和氮氢插入反应方面，特别是如果要依赖铁催化的话。张博士的研究小组使用高精度的计算技术来提供这种基于血红素的催化剂的以前未知的机理信息。特别是，张博士将致力于提高它们对这些具有挑战性的化学转化的催化反应性和选择性。例如，这种洞察力可能会导致在制药行业大规模进行的某些过程化学程序的改进。张博士的研究广泛地与教学、培训和学习相结合，来自不同群体、不同级别的学生广泛参与，特别是那些来自代表性不足的群体的学生。该署透过多个渠道，向社会广泛宣传其研究成果。例如，这个由NSF资助的项目的学生在他们的课堂上、在他们的系里和/或在大学里做演讲/报告。此外，还有针对K-12机构、博物馆、新闻媒体(包括传统大众媒体和社交媒体)的外展方案，增强了对该项目影响的科学认识。环丙烷化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-杂环化合物和生物偶联。工程化的血红素蛋白在可持续的卡宾转移反应中表现出了许多优良的催化性能。然而，某些催化环丙烷化和N-H插入仍然存在一些巨大的挑战，特别是对于缺乏电子的底物。在一些实验体系中，环丙烷化反应与N-H插入反应的不同化学选择性的来源也是未知的。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，研究以前未知的一些血红素结构因素的机制细节，以增强挑战环丙烷化和N-H插入的催化反应性。通过对不同催化剂组分的可变环丙烷化与N-H插入反应的化学选择性的研究，帮助设计用于选择性官能化的“匹配”催化剂。张博士的研究广泛地与教学、培训和学习相结合。他实验室的学生积极参与课堂和推广项目，将他们的研究成果纳入其中。张博士继续积极努力，让来自不同群体的学生在不同级别广泛参与，特别是来自代表人数不足的群体的学生。张博士的研究小组利用几个渠道向科学界和公众广泛传播他们的研究成果。这一奖项反映了NSF的法定使命，并通过使用基金会的学术价值和更广泛的影响审查标准进行评估，被认为值得支持。