Technology Development: Tailored Nano-Molecular Systems for New Modes of Reactivity

技术开发：用于新反应模式的定制纳米分子系统

• 批准号: 10401246
• 负责人: TODD D KRAUSS
• 金额: $ 18.71万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401246
• 关键词: Area; Binding; Biological; Birth; Catalysis; Characteristics; Charge; Chemicals; Chemistry; Complex; Development; Diffuse; Dyes; Electron Transport; Electrons; Energy Transfer; Foundations; Genetic Recombination; Goals; Grant; Image; Kinetics; Ligands; Molecular; Molecular Target; Organic Synthesis; Outcome; Oxidation-Reduction; Pharmaceutical Preparations; Photons; Process; Property; Protocols documentation; Quantum Dots; Reaction; Reducing Agents; Research; Scientist; Semiconductors; Series; Solar Energy; Space Explorations; Surface; System; Testing; Translating; Universities; Vision; Wisconsin; Work; base; catalyst; computerized tools; drug candidate; drug development; drug discovery; drug synthesis; innovation; materials science; nano; new technology; new therapeutic target; prevent; programs; quantum chemistry; side effect; small molecule; technology development; tool; two-photon

Despite continual advancements, the synthesis of drug candidates remains a limiting factor in drug discovery. Commercial realities mean that molecules that take too long to access are not made or tested. Photoredox catalysis has quickly made an impact on this problem via late-stage molecule diversification, a promising avenue to increase the chemical space tested with minimal effort. However, the available reactions are limited by the relatively small number of identified catalysts. There is a need for catalysts with new properties that will enable new types of photoredox reactions. Semiconductor quantum dots (QDs) represent a promising class of catalysts that are unlike any currently available. Combining some of the best properties of heterogeneous catalysts with the convenience of homogeneous catalysts, QDs have impressive, easily tuned photophysical properties and a rich surface chemistry. The relative independence of the photophysical properties from the supporting ligands provides a compelling, new opportunities for reaction development. However, the adaptation of QDs to drug discovery has been slowed by the poor overlap between the materials science and organic synthesis. This program’s long-term goals are the development of new types of chemistry enabled by QD surface chemistry. In the proposed R21 grant, a team of materials scientists (Krauss group at the University of Rochester) and synthetic chemists (Weix group at the University of Wisconsin-Madison) will validate the exciting potential of QD photoredox catalysts, develop protocols for their use, and work with chemical suppliers to make these new tools commercially available. Our guiding hypothesis is that the surface chemistry of quantum dots can allow new types of photoredox reactions by accelerating electron transfer and pre-arranging catalysts or substrates. The specific aims of this proposal are to: (1) use supporting and electroactive ligands to fine-tune the properties of QD photoredox catalysts against a suite of known reactions; (2) determine the best approach to attaching small molecule catalysts to the QD surface to enhance multicatalytic reactions; (3) test if Auger recombination can be used to generate strongly reducing states potentially useful in organic synthesis; and (4) validate the use of QD surface chemistry to template macrocyclization reactions. The approach is innovative because QDs are fundamentally different from commonly used photoredox catalysts and will enable reactivity not easily possible with small molecule catalysts. The proposed research is significant because the new tools will be made widely available and can be easily incorporated into established photoredox research programs.

尽管不断取得进步，候选药物的合成仍然是药物发现的限制因素。 商业现实意味着需要很长时间才能获得的分子无法制造或测试。 催化通过后期分子多样化迅速对这个问题产生了影响，这是一个有前途的途径 以最小的努力增加测试的化学空间然而，可用的反应受到限制。 已鉴定的催化剂数量相对较少，因此需要具有新性能的催化剂。 新型光氧化还原反应半导体量子点（QD）代表了一类有前途的催化剂。 与现有的任何催化剂不同，它结合了非均相催化剂的一些最佳性能。 由于均相催化剂的便利性，量子点具有令人印象深刻、易于调节的光物理性质和 丰富的表面化学性质。光物理性质与支持配体的相对独立性。 然而，量子点对药物的适应为反应的发展提供了引人注目的新机会。 由于材料科学和有机合成之间的重叠程度较低，发现速度已经放缓。 该计划的长期目标是开发由量子点表面化学实现的新型化学。 拟议的 R21 拨款、材料科学家团队（罗切斯特大学克劳斯小组）和 合成化学家（威斯康星大学麦迪逊分校的 Weix 小组）将验证 QD 光氧化还原催化剂，开发其使用方案，并与化学品供应商合作制造这些新的 我们的指导性假设是量子点的表面化学可以允许。 通过加速电子转移和预先安排催化剂或底物来实现新型光氧化还原反应。 该提案的具体目标是：（1）使用支持和电活性配体来微调性能 QD 光氧化还原催化剂对一系列已知反应的影响 (2) 确定最佳的附着方法； 将小分子催化剂添加到量子点表面以增强多催化反应（3）测试是否发生俄歇复合； 可用于产生在有机合成中可能有用的强还原态；以及（4）验证其用途； 量子点表面化学来模板大环化反应该方法是创新的，因为量子点是 与常用的光氧化还原催化剂根本不同，并且将实现不易发生的反应 所提出的研究意义重大，因为新工具将被广泛制造。 可用并且可以轻松地纳入已建立的光氧化还原研究计划中。

项目成果

CdS Quantum Dots for Metallaphotoredox-Enabled Cross-Electrophile Coupling of Aryl Halides with Alkyl Halides.

• DOI: 10.1021/acscatal.3c01984
• 发表时间: 2023-06
• 期刊: ACS catalysis
• 影响因子: 12.9
• 作者: Julianna M. Mouat;Jonas K. Widness;Daniel G. Enny;Mahilet T. Meidenbauer;Farwa Awan;Todd D. Krauss;D. Weix