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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严格的计算研究，以改进可持续化学中选定的重要转变的催化剂设计。目标催化剂是经过改造的血红素蛋白，具有许多吸引人的特性，例如在室温下、在水溶液中以高产率提供产品，具有高化学、区域和立体选择性，具有生物相容性和低毒性。这些催化剂还包含最丰富且最便宜的过渡金属 Fe（铁）。也就是说，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挑战，特别是在环丙烷化和氮氢插入反应方面，特别是如果依赖铁催化的话。张博士的研究小组采用高精度计算技术来提供此类基于血红素的催化剂以前未知的机理信息。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活性和选择性。例如，这些见解可能会导致制药行业大规模实施的某些化学过程的改进。张博士的研究广泛地与教学、培训和学习相结合，来自不同群体、不同层次的学生，特别是来自弱势群体的学生广泛参与。他们利用多种渠道向社会广泛传播他们的研究成果。例如，参与这个由 NSF 支持的项目的学生在课堂上以及所在院系和/或大学内进行演示/报告。还有针对 K-12 机构、博物馆、新闻媒体（传统大众媒体和社交媒体）的外展计划，以增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-杂环化合物和生物共轭的合成。工程血红素蛋白在可持续的卡宾转移反应中表现出许多优异的催化特性。然而，某些催化环丙烷化和 N-H 插入仍然存在一些重大挑战，特别是对于缺电子底物。在一些实验系统中，各种环丙烷化与 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对一些血红素结构因子的先前未知的机制细节进行严格的量子化学计算研究，以增强具有挑战性的环丙烷化和N-H插入的催化反应性。深入了解不同催化剂组分的可变环丙烷化与 N-H 插入化学选择性，有助于设计用于选择性功能化的“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融入他们研究成果的课程和推广项目。张博士继续积极努力让来自不同层次不同群体的学生，特别是来自弱势群体的学生广泛参与。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 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，认为值得支持。