Mechanistic Investigation into Modern Catalytic Reactions

现代催化反应的机理研究

基本信息

批准号：
10685545
负责人：
Jennifer Hirschi
金额：
$ 29.65万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2027-08-31
项目状态：
未结题

项目摘要

Project Summary: Mechanistic understanding of emerging catalytic methodologies is an important factor in the successful application of novel transformations to the synthesis of pharmaceuticals and other high- value chemicals. Despite this, there is a significant lag between new reaction discovery and its mechanistic description. This research program addresses this challenge in two important areas of contemporary catalysis – photoredox catalysis and biocatalysis by engineered enzymes. Photocatalysts harness the power of visible light to generate highly reactive radical intermediates that can be strategically channeled to participate in a variety of valuable bond-formations. There are a variety of photophysical approaches for the detection and characterization of these open-shell intermediates. However, experimental probes of the transition state geometry, of key bond-forming and bond-breaking events in photoredox catalysis, are virtually non-existent. In this context, this research program establishes 13C kinetic isotope effects as the elusive experimental probe of the transition state geometry of photoredox reactions. In addition to shedding light on these complex reaction mechanisms, this measurement serves as an important experimental benchmark to calibrate theoretical methods to accurately evaluate the rate- and selectivity-determining steps in these reactions. Directed evolution of cytochromes P450 has led to the discovery of carbene- and nitrene-transfer activity of these heme-containing enzymes. Mechanistic investigations of these systems have largely been limited to theoretical studies due to the inherent challenges associated with conducting standard physical organic experiments in enzymatic systems. This program utilizes a newly developed intramolecular 13C kinetic isotope effect technique along with classical kH/kD experiments to gain insight into the transition state geometry of C–C and C–N bond-forming steps in these reactions. High-level QM/MM calculations and MD simulations are also utilized to interpret experimental findings and understand the origin of selectivity in these biocatalytic reactions.

项目摘要：对新兴催化方法的机理理解是一个重要因素成功地将新颖的转化应用于药物和其他高科技的合成尽管如此，新反应的发现与其实际应用之间仍存在显着的滞后。该研究计划在两个重要领域解决了这一挑战。现代催化——光氧化还原催化和工程酶生物催化。光催化剂利用可见光的力量产生高活性自由基中间体可以战略性地引导其参与各种有价值的债券形成。用于检测和表征这些开壳的各种光物理方法然而，过渡态几何、关键键形成和的实验探针。光氧化还原催化中的键断裂事件实际上不存在。计划将 13C 动力学同位素效应建立为过渡态的难以捉摸的实验探针光氧化还原反应的几何结构除了揭示这些复杂的反应机制之外，该测量可作为校准理论方法的重要实验基准准确评估这些反应中的速率和选择性决定步骤。细胞色素 P450 的定向进化导致卡宾和氮宾转移的发现这些含血红素酶的活性已在很大程度上进行了机理研究。由于与执行标准相关的固有挑战，仅限于理论研究酶系统中的物理有机实验该程序利用了新开发的技术。分子内 13C 动力学同位素效应技术以及经典的 kH/kD 实验以获得洞察深入了解这些反应中 C-C 和 C-N 键形成步骤的过渡态几何结构。 QM/MM 计算和 MD 模拟也用于解释实验结果和了解这些生物催化反应选择性的起源。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Altering the Localization of an Unpaired Spin in a Formal Ni(V) Species.

改变形式 Ni(V) 物质中不成对自旋的定位。

DOI：
10.1002/chem.202302824
发表时间：
2024
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
0
作者：
Awasthi,Ayushi;Mallojjala,SharathChandra;Kumar,Rakesh;Eerlapally,Raju;Hirschi,JenniferS;Draksharapu,Apparao
通讯作者：
Draksharapu,Apparao

Copper-Phosphido Catalysis: Enantioselective Addition of Phosphines to Cyclopropenes.

铜-磷基催化：膦对环丙烯的对映选择性加成。

DOI：
10.1002/anie.202306511
发表时间：
2023
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
0
作者：
Daniels,BrianS;Hou,Xintong;Corio,StephanieA;Weissman,LindseyM;Dong,VyM;Hirschi,JenniferS;Nie,Shaozhen
通讯作者：
Nie,Shaozhen