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

尽管不断取得进展，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，需要太长时间才能获得的分子不会被制造或测试。光氧化还原 催化通过后期分子多样化迅速对这个问题产生了影响，这是一个很有希望的途径。 以最小的努力增加测试的化学空间。然而，可用的反应受到以下因素的限制 已确定的催化剂数量相对较少。需要具有新性质的催化剂，以使 新型光氧化还原反应。半导体量子点是一类很有前途的催化剂。 这不同于目前可用的任何一种。将多相催化剂的一些最佳性能与 由于均相催化剂的便利性，量子点具有令人印象深刻的、易于调整的光物理性质和 丰富的表面化学成分。光物理性质与支持配体的相对独立性 为反应发展提供了令人信服的新机遇。然而，量子点对药物的适应性 材料科学和有机合成之间的重叠很少，这减缓了发现的速度。这 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。在……里面 提议的R21拨款，一个材料科学家团队(罗切斯特大学的克劳斯小组)和 合成化学家(威斯康星大学麦迪逊分校的韦克斯小组)将验证 QD光氧化还原催化剂，开发它们的使用协议，并与化学品供应商合作制造这些新的 商业上可以买到的工具。我们的指导性假设是量子点的表面化学可以 通过加速电子转移和预先安排催化剂或底物的新型光氧化还原反应。 这项提议的具体目的是：(1)使用支撑性和电活性配体来微调性质 QD光氧化还原催化剂与一系列已知反应的对比；(2)确定连接的最佳方法 QD表面的小分子催化剂促进多催化反应；(3)测试俄歇复合 可用于产生可能在有机合成中有用的强还原状态；以及(4)验证其用途 从量子点表面化学到模板大环化反应。这种方法是创新的，因为量子点是 从根本上不同于常用的光氧化还原催化剂，并将使反应活性不容易实现 使用小分子催化剂。拟议的研究具有重要意义，因为新工具将被广泛使用 可供选择，并可轻松整合到现有的光氧化还原研究计划中。

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.