Efficient New Organic Reagents for Electron Transfer

该项目的首要目标是设计新的“绿色”化学，可以应用于制备药物化学中感兴趣的新型分子。总是需要新的方法来制备有趣的分子。我们的试剂的主要优势在于它们由简单而经济的地球丰富元素组成，硅，氧，氢，氮，并且它们避免了引起环境问题的元素。本项目将研究两类新型还原剂和氧化试剂的反应性：(i)自由基阴离子和（ii）自由基阳离子。《初步化学》由墨菲小组发表在领先期刊《Angew》上。化学。Int。编辑，2017,56,13747-13751。j。化学。Soc。浙江农业学报，2016,38,15482-15487。详细目标：(i)学生将研究最近在墨菲组中发现的在碱存在下使用硅烷试剂的反应范围；这些反应将应用于药物感兴趣的分子。这些将是杂环，如吡啶，嘧啶，恶唑和吡咯。到目前为止还没有进行这样的研究。（ii）学生将学习这些反应的机理。硅烷与碱混合形成的反应物质的性质，在文献中存在着激烈的争论。因此，学生将通过检查反应产物和副产物的化学结构，并在适当的情况下，通过使用物理有机化学方法（反应动力学，以及改性试剂对反应结果的影响）来验证建议，以探索有关反应性质的信息。（iii）根据从目标(i)和（ii）中收集的信息，学生将把我们的反应应用于新型底物。通过这种方式，我们将利用化学专业知识预测新的反应性，并预测如何将其应用于新候选药物的设计。（iv）我们将利用计算化学（DFT =密度泛函理论）方法从我们提出的关于反应机理的建议中进行选择。这个学生将能利用这一化学领域的训练。该计划将为参与该项目的学生提供广泛的化学前沿培训。我们的做法是在世界领先的期刊上发表文章，我们希望在这个项目中遵循这一做法。学生将有机会参加一个或多个国际研究会议并展示研究成果，并将利用大学为专业和个人发展提供的广泛模块计划。

The over-arching aim of the project will be to design new 'green' chemistry that can be applied to the preparation of new types of molecules that are of interest in pharmaceutical chemistry. New ways to prepare interesting molecules are always needed. The key advantage of our reagents is that they consist of simple and economical earth-abundant elements, silicon, oxygen, hydrogen, nitrogen, and they avoid elements that cause environmental concerns.This project will study the reactivity of new types of reductive and oxidative reagents that are of two classes: (i) radical anions and (ii) radical cations. Preliminary chemistry was published by the Murphy group in leading journals: Angew. Chem. Int. Ed. 2017, 56, 13747-13751. J. Am. Chem. Soc., 2016, 138, 15482-15487.Detailed aims:(i) The student will study the scope of reactions that have been recently discovered in the Murphy group, that use silane reagents in the presence of base; the reactions will be applied to molecules of pharmaceutical interest. These will be heterocycles such as pyridines, pyrimidines, oxazoles and pyrroles. No such studies have been conducted to date.(ii) The student will study the mechanisms of these reactions. There is hot debate in the literature on the nature of the reactive species formed on mixing silanes with base. Accordingly, the student will probe for information about the nature of the reactions, by examining the chemical structures of the products and the by-products of the reactions and, where appropriate, by using physical organic chemistry methods (reaction kinetics, and the effect of modified reagents on the outcomes of the reactions) to verify proposals. (iii) Based upon the information gleaned from aims (i) and (ii), the student will apply our reactions to new types of substrates. In this way, we will be predicting new reactivity using chemical expertise, and predicting how this can be applied to the design of new drug candidates.(iv) We will look to computational chemistry (DFT = density functional theory) methods to select from the proposals on reaction mechanism that we make. The student will be able to avail of training in this area of chemistry. The programme will provide broad training at the forefront of chemistry for the student engaged on the project. Our practice is to publish in world-leading journals, and we will wish to follow this practice in this project. The student will have the opportunity to attend and present research results at one or more international research meetings and will avail of a broad programme of modules provided by the University for professional and personal development.