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; 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.

尽管有连续的进步，但候选药物的合成仍然是药物发现的限制因素。 商业现实意味着无法获得或测试花费太长时间的分子。 Photoredox 催化通过后期分子多样化迅速影响了这个问题，这是一个承诺的大道 以最少的努力来增加测试的化学空间。但是，可用反应受到 相关的少量鉴定催化剂。需要具有新属性的催化剂，以启用 新型的光电毒反应。半导体量子点（QD）代表催化剂的承诺类 与当前可用的任何不同。将异质催化剂的一些最佳特性与 均匀催化剂，QD具有令人印象深刻的，易于调整的光物理特性的便利性和 丰富的表面化学。光物理特性与支撑配体的相对独立性 为反应发展提供了引人入胜的新机会。但是，QD对药物的适应 材料科学与有机综合之间的重叠不佳的重叠使发现减慢了。这 计划的长期目标是QD表面化学实现的新型化学类型的发展。在 拟议的R21 Grant，材料科学家团队（罗切斯特大学的克劳斯集团）和 合成化学家（威斯康星大学麦迪逊分校的韦克斯组）将验证令人兴奋的潜力 QD Photoredox催化剂，为其使用制定协议，并与化学供应商合作制造这些新的 商业上可用的工具。我们的指导假设是，量子点的表面化学可以允许 通过加速电子传输和预先安排的催化剂或底物，新型的光氧反应。 该提案的具体目的是：（1）使用支撑和电活性配体微调属性 QD光电毒素催化剂的催化剂针对一系列已知反应； （2）确定连接的最佳方法 小分子催化剂至QD表面以增强多催化反应； （3）测试是否螺旋钻重组 可用于生成强烈降低的状态，潜在地在有机合成中有用。 （4）验证用途 QD表面化学与模板大环化反应。这种方法是创新的，因为QD是 与常用的光电毒素催化剂根本不同，将无法轻易反应性 带有小分子催化剂。拟议的研究很重要，因为新工具将被广泛制造 可用，可以轻松地将其纳入已建立的Photoredox研究计划中。