Collaborative Research: Enantioselectivity in Heterogeneous Catalysts via the Addition of Chiral Modifiers

合作研究：通过添加手性修饰剂实现多相催化剂的对映选择性

• 批准号: 1854439
• 负责人: Francisco Zaera
• 金额: $ 26.13万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1854439&HistoricalAwards=false
• 关键词: Collaborative; Research; Enantioselectivity; Heterogeneous; Catalysts

Biomolecular building blocks can exhibit either right- or left-handed symmetries; such building blocks are known as enantiomers. All biomolecules found in living organisms have only one "handedness', that is, the molecules exist only in one enantiomeric form. Moreover, different enantiomers of the same molecule can interact with living organisms in completely different ways, sometimes beneficially and sometimes with catastrophic effects. As the wrong handedness can cause harm, pharmaceuticals and agrochemicals must be synthesized in enantiopure forms. This synthesis may be accomplished by purification after the drug has been synthesized, but that approach is often difficult and cumbersome. It is preferable to develop processes in which only one enantiomer of the drug is made. Enantiopure syntheses can be accomplished by using solid-phase catalysts with surfaces that are specifically modified to preferentially produce molecules with only one handedness. There have been a number of trial-and-error efforts to discover such heterogeneous catalysts, but success has so far been limited. Drs. Tysoe (University of Wisconsin-Milwaukee) and Zaera (University of California-Riverside) have considerable experience in studying the surface chemistry of catalytic systems under ideal conditions. Their research project focuses on understanding the molecular interactions that control enantio-selectivity in more complex and realistic systems for the advanced manufacturing of pharmaceuticals. Drs. Tysoe and Zaera are strongly committed to educating women and minorities, in particular, Hispanic students both in the laboratory and through formal courses. They participate in outreach programs at Milwaukee and Riverside, and are incorporating the research associated with this project into those activities. With funding from the Chemical Catalysis Program of the Chemistry Division, Drs. Tysoe and Zaera are studying the surface chemistry of model palladium(111) and platinum(111) chiral catalysts modified by a cinchonidine analog, 1-(1-naphthyl) ethylamine (NEA), using scanning tunneling microscopy (STM), infrared absorption spectroscopy, reactivity measurements, and first-principles density functional theory (DFT) calculations. This research provides a molecular-level understanding of the diastereomeric interactions between a number of prochiral reactants and NEA, and the forces that control them. They are investigating whether the detailed molecular understanding of the chiral surface chemistry from single-crystal studies in ultrahigh vacuum is relevant to the reaction pathways occurring under realistic conditions, that is, under atmospheric pressures and in the presence of a liquid phase. The resulting understanding may provide insights into how to improve catalytic selectivity. The research may facilitate the targeted design of supported heterogeneous enantioselective catalysts. Such an ability is expected to have a significant economic impact in the pharmaceutical and agrochemical industries. Drs. Tysoe and Zaera focus on educating women and minorities through their research and outreach programs as part of the broader impacts of the project.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.

生物分子构建块可以表现出右手或左手对称性；这种构建块被称为对映体。在生物体中发现的所有生物分子只有一种“利手”，即分子只以一种对映体形式存在。此外，同一分子的不同对映体可以以完全不同的方式与生物相互作用，有时是有益的，有时是灾难性的。由于用手不当会造成伤害，药物和农用化学品必须以对映体的形式合成。这种合成可以在药物合成后通过纯化来完成，但这种方法通常是困难和繁琐的。最好是开发只制造一种药物对映体的方法。对映体的合成可以通过使用固相催化剂来完成，固相催化剂的表面经过专门的修饰，可以优先生成只用一只手的分子。已经有一些反复尝试的努力来发现这种多相催化剂，但到目前为止，成功是有限的。Tysoe博士(威斯康星大学密尔沃基分校)和Zaera博士(加州大学河滨分校)在理想条件下研究催化体系的表面化学方面拥有丰富的经验。他们的研究项目侧重于了解在更复杂和现实的系统中控制对映体选择性的分子相互作用，以用于先进的制药制造。Tysoe博士和Zaera博士坚定地致力于在实验室和通过正规课程教育妇女和少数民族，特别是西班牙裔学生。他们参加了密尔沃基和河滨的外展项目，并将与该项目相关的研究纳入这些活动。在化学部化学催化计划的资助下，Tysoe博士和Zaera博士正在使用扫描隧道显微镜(STM)、红外吸收光谱、反应性测量和第一性原理密度泛函理论(DFT)计算，研究由辛可尼定类似物1-(1-萘基)乙胺(NEA)修饰的模型钯(111)和铂(111)手性催化剂的表面化学。这项研究从分子水平上了解了一些前手性反应物和NEA之间的非对映异构体相互作用，以及控制它们的作用力。他们正在调查在超高真空下单晶研究对手性表面化学的详细分子理解是否与现实条件下发生的反应路径有关，即在大气压和液体存在的情况下。由此产生的理解可能会为如何提高催化选择性提供见解。该研究有助于负载型多相对映选择性催化剂的靶向性设计。这种能力预计将对制药和农用化学品行业产生重大的经济影响。作为该项目更广泛影响的一部分，Tysoe博士和Zaera博士专注于通过他们的研究和推广计划来教育妇女和少数族裔。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

In-situ and operando spectroscopies for the characterization of catalysts and of mechanisms of catalytic reactions

• DOI: 10.1016/j.jcat.2021.08.013
• 发表时间: 2021-08
• 期刊: Journal of Catalysis
• 影响因子: 7.3
• 作者: F. Zaera

Molecular approaches to heterogeneous catalysis

• DOI: 10.1016/j.ccr.2021.214179
• 发表时间: 2021-12
• 期刊: Coordination Chemistry Reviews
• 影响因子: 20.6
• 作者: F. Zaera

Adsorption and Reactivity of Chiral Modifiers in Heterogeneous Catalysis: 1-(1-Naphthyl)ethylamine on Pt Surfaces

多相催化中手性修饰剂的吸附和反应活性：1-(1-萘基)乙胺在 Pt 表面上

• DOI: 10.1021/acscatal.2c01627
• 发表时间: 2022
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Wang, Zihao;Fernández-Escamilla, Héctor Noé;Guerrero-Sánchez, Jonathan;Takeuchi, Noboru;Zaera, Francisco
• 通讯作者: Zaera, Francisco

Adsorption of Chiral Modifiers from Solution onto Supported Platinum Catalysts: The Effect of the Solvent, Other Coadsorbates, and the Support

• DOI: 10.1021/acs.jpcc.0c01309
• 发表时间: 2020-03
• 期刊: Journal of Physical Chemistry C
• 影响因子: 3.7
• 作者: Yufei Ni;Zihao Wang;Ilkeun Lee;F. Zaera