Organic photoredox catalysts as sustainable and cost-effective replacement forprecious metal complexes in light-driven drug synthesis

有机光氧化还原催化剂作为光驱动药物合成中贵金属配合物的可持续且经济有效的替代品

• 批准号: 10011197
• 负责人: Chern-Hooi Lim
• 金额: $ 76.64万
• 依托单位: NEW IRIDIUM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011197
• 关键词: Age; Amines; Architecture; Area; Benchmarking; Catalysis; Chemistry; Coupling; Development; Electrons; Elements; Generations; Health; Human; Hydrophobicity; Industrialization; Iridium; Life; Light; Measures; Metals; Methods; Nobel Prize; Oxidants; Palladium; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Photochemistry; Process; Production; Property; Public Health; Reaction; Reducing Agents; Research; Route; Ruthenium; Safety; Savings; Scheme; Scientist; Small Business Innovation Research Grant; Solubility; Solvents; Structure; System; Technology; Therapeutic; Time; United States National Institutes of Health; absorption; aqueous; base; catalyst; chemical reaction; commercialization; cost; cost effective; design; drug candidate; drug development; drug discovery; drug synthesis; empowered; hydrophilicity; improved; interest; metal complex; novel; novel therapeutics; phenoxazine; quantum; research and development; simulation

PROJECT SUMMARY The underlying technology developed in this project is photoredox catalysis, an active research area with growing academic and industrial interest. The impact of photoredox catalysis is expected to exceed palladium catalysis, the Nobel-prize-winning chemistry that fueled the golden age of drug discovery. Photoredox catalysis uses light to activate chemical reactions, as opposed to heat in conventional processes. Unique single-electron radical chemistry is accessed through light absorption enabling new reactivities and unprecedented process efficiencies e.g. synthesis of drug candidates in fewer steps. Of additional industrial interest, it also permits the use of low-cost and structurally diverse raw materials in drug development and manufacturing that are otherwise unreactive in conventional processes. From a public health perspective, photoredox catalysis has the potential to substantially lower the cost of therapeutics and improve overall human health by enabling accelerated drug development and reduced drug manufacturing costs. Completing this NIH SBIR Phase II project will result in the commercialization of high performance organic photoredox catalyst (PC) products. PCs are the key enabler of photoredox catalysis. However, PCs predominantly used today are based on iridium and ruthenium, two rare and expensive precious metals that do not scale beyond R&D usage, posing serious cost and supply issues for industrial use. Organic PCs provide the solution. Made from abundant elements, they are sustainable and can easily scale to meet industrial demand. Notably, the organic PCs of interest here were designed by quantum simulations to possess critical properties resolving many limitations of earlier generations. In many applications, they were shown to match and in some cases exceed the performance of precious metal PCs. The organic PCs developed here provide the scalable solution for photoredox catalysis required for drug development and manufacturing. Specifically, this project integrates three main components pivotal to enabling industrial application of photoredox catalysis, namely i) organic PCs, ii) photochemical reactions, and iii) photoreactor technology. For organic PCs (Aims 1 and 2), a number of PC candidates will be synthesized with expanded ranges of reactivities capable of accommodating many industrial reaction conditions. For photochemical reactions (Aims 3 and 4), novel and medicinally important reactions (with extended substrate scope) with stated customer interest will be developed using various classes of organic PCs. Finally, for photoreactor integration (Aim 5), commercially available photoreactor designs and associated reaction conditions will be identified that maximize the performance of organic PCs.

项目总结 该项目开发的基础技术是光氧化还原催化，这是一个活跃的研究领域， 学术界和工业界的兴趣与日俱增。预计光氧化还原催化的影响将超过钯 催化，诺贝尔奖获得者化学，推动了药物发现的黄金时代。光氧化还原催化 使用光来激活化学反应，而不是传统工艺中的热。独特的单电子 通过光吸收获得自由基化学，从而实现新的反应和前所未有的过程 效率，例如在更少的步骤中合成候选药物。具有额外的工业利益，它还允许 在药品开发和制造中使用低成本和结构多样化的原材料 在传统工艺中不起反应。从公共健康的角度来看，光氧化还原催化具有潜在的 通过加速药物治疗大幅降低治疗成本并改善整体人类健康 开发和降低药品制造成本。 完成NIH SBIR第二阶段项目将导致高性能有机化合物的商业化 光氧化还原催化剂(PC)产品。PC是光催化氧化还原的关键使能器。然而，个人电脑 今天主要使用的是基于Ir和Ru的，这两种稀有而昂贵的贵金属 规模不能超出研发用途，对工业用途造成严重的成本和供应问题。有机PC提供了 解决方案。它们由丰富的元素制成，是可持续的，可以很容易地扩大规模，以满足工业需求。 值得注意的是，这里感兴趣的有机PC是通过量子模拟设计的，具有关键性质 解决了前几代人的许多限制。在许多应用中，它们被证明是匹配的，在一些应用中 机壳的性能超过了贵金属电脑。这里开发的有机PC提供了可扩展的 药物开发和制造所需的光氧化还原催化溶液。 具体地说，该项目集成了三个主要组件，这些组件对实现 光氧化还原催化，即：1)有机PC，2)光化学反应，3)光反应技术。为 有机PC(目标1和目标2)，将合成一些具有更大反应范围的PC候选化合物 能够适应多种工业反应条件。对于光化学反应(目标3和4)， 新的和医学上重要的反应(具有扩展的底物范围)将是明确的客户兴趣 使用各种类型的有机PC开发。最后，用于光反应堆集成(目标5)，商业化 将确定可用的光反应器设计和相关反应条件，以最大限度地提高 有机PC的性能。