Boron: Beyond the Reagent

硼在地球上储量丰富，以矿物质的形式存在于日常物品中，如玻璃、洗涤剂、阻燃剂、防腐剂和眼药水。硼在自然界中也以有机形式存在，包括植物酶，是包括我们自己在内的许多活着的物种饮食中的基本元素。在人造(合成的)有机化合物中加入硼，通常取代碳原子链中的一个碳原子，可以给分子的性质带来巨大的变化。当通过将硼与其他元素(如氮和氧)一起放在正确的位置来正确地“调整”这些“硼化”分子时，就可以利用它们的新特性来提供具有不同应用的化合物。这些材料的范围从“智能”材料(例如，在薄膜显示器中)，到在农用化学品和药品生产中的安全、“绿色”和经济有利的试剂，以及在另一个最近出现的应用中，药物分子本身。尽管毫无疑问，硼将继续是我们21世纪生存所必需的分子和材料中的关键元素，但将硼安装到这种“硼化”物种中以及从这些“硼化”物种中释放硼的工具已经落后于应用的增长。硼化分子中的碳-硼键可能是反复无常的：有时它是脆弱的，保持组装到位是一个挑战。在其他情况下，它太坚固，不能释放其有机分子货物，除非在恶劣的条件下，不可能控制结果。这项研究计划将驯服这些分子，以消除这些差距。我们组建了一支世界级的团队，将设计、制备和分析硼化分子的专家的深刻见解与最终用户专家结合在一起，他们将帮助指导我们的研究。我们将共同发现关键机遇，挖掘突破。到2025年，硼化分子的市场预计将达到17亿美元，这项工作将使化学、材料和生物科学的多尺度应用成为可能，并提供通往未来技术的门户。三个不同的、与专业知识相关的和交叉施肥的研究领域将被解决，直接为EPSRC的医疗保健技术、制造未来以及生产力和弹性国家1的主题做出贡献。在开发硼化药物的过程中，我们将发现如何调整碳-硼键的不稳定性，以开发新的含硼药物。它们将抵抗碳-硼键的裂解，直到它们将硼化的前药物传递到正确的位置，例如特定的器官，然后进行裂解，在正确的时间在正确的位置释放活性药物。这将确保目标药物的最佳浓度，避免不良副作用，并要求更低和更安全的剂量。在化学制造中，我们将设计具有可切换(武装/解除武装)反应能力的硼化试剂。如果需要，这些健壮的物种将很容易准备、储存和运输。然而，当准备好使用时，在添加少量的“释放”成分后，硼化试剂将迅速转换为其反应臂形式，提供有机分子有效载荷，为制造过程做好准备。这将减少浪费，提高安全性，并允许开发新的工艺。用于OLED等器件的智能含硼材料需要能够在长时间的器件寿命内提供高效的功能和稳定性。这就要求碳-硼键在这些应用中具有非常高的稳定性。我们将设计和测试新的硼化构建块，在广泛的操作条件下，这些构建块对有机碎片的“释放”具有免疫力。这将拓宽设备可以容忍的条件，并扩大其应用范围。

Boron is Earth-abundant, and present in its 'mineral form' in everyday objects, such as glass, detergents, flame-retardants, preservatives, and eye-drops. Boron is also found in 'organic form' in nature, including plant enzymes, and is an essential element in the diets of numerous living species, including ourselves. Inclusion of boron in man-made ('synthetic') organic compounds, often in place of one carbon atom in a chain of carbon atoms, can impart tremendous changes in the properties of a molecule. When these 'borylated' molecules are correctly 'tuned' by having the boron in the 'right place' together with other elements such as nitrogen and oxygen - their new properties can be harnessed to provide compounds with diverse applications. These range from 'smart' materials (e.g., in thin-film displays) through to safe, 'green' and economically advantageous reagents in the production of agrochemicals and pharmaceuticals, and, in another very recently emerging application, in the drug molecules themselves.Whilst there is no doubt that boron will continue to be a critical element in molecules and materials that are essential to our 21st century existence, the tools to install boron in, and to release boron from, such 'borylated' species have lagged behind the growth of the applications. The carbon-boron bond in borylated molecules can be fickle: on occasion it is fragile and keeping the assembly in place is the challenge. On other occasions it is too robust, resisting release of its organic molecule cargo, except under harsh conditions, where it is impossible to control the outcome. This research programme will tame these molecules to eliminate these gaps. We have assembled a world-class team that combines deep insight from experts in the design, preparation and analysis of borylated molecules, with end-user specialists who will help steer our investigations. Together, we will identify key opportunities and exploit the breakthroughs. With the market for borylated molecules expected to reach $1.7 Billion by 2025, this work will enable multi-scale applications across chemical, materials, and biological sciences, and provide a gateway to future technologies.Three divergent, expertise-related, and cross-fertilising research areas will be tackled, directly contributing to EPSRC themes of Healthcare Technologies, Manufacturing the Future, and the Productive and Resilient Nation.1. In developing borylated medicines, we will discover how to tune the instability of the carbon-boron bond to develop new boron-containing pharmaceuticals. These will resist carbon-boron bond cleavage until they have delivered the borylated pro-drug to the correct location, e.g., a specific organ, and then undergo cleavage to release the active drug in the right place at the right time. This will ensure the optimum concentration at the target, avoiding undesired side-effects, and requiring lower and safer doses.2. In chemical manufacturing, we will design borylated reagents with switchable (arm/disarm) reactivity. These robust species will be easily prepared, stored and transported, on large scales if required. Yet, when ready for use, on addition of small amount of a 'release' component, the borylated reagent will rapidly switch to its reactive armed form, delivering the organic molecule payload, primed for the manufacturing process. This will reduce waste, increase safety, and allow new processes to be developed.3. Smart boron-containing materials, used in devices such as OLEDs, need to be able to deliver efficient function and stability over long device lifetimes. This necessitates very high stability in the carbon-boron bond for these applications. We will design and test new borylated building blocks that are immune to 'release' of the organic fragment, under a wide range of operating conditions. This will broaden the conditions that the devices will tolerate and increase their application scope.