深穴杯芳烃调控的碳(sp3)-氢键自由基官能化及其在生物共轭中的应用

近些年，超分子主体越来越多地被应用于有机反应中，这主要是因为其可以充当分子尺寸的反应器，从而大大提高反应的速率、调控反应的选择性以及开发新的反应历程等。然而这其中，超分子主体调控的自由基反应此前主要依赖于紫外光的激发而受到反应类型单一、适用范围狭窄等限制。因此，开发更为多样的超分子主体调控的自由基反应并实现催化，具有重要的研究价值与意义。本项目以水溶性深穴杯芳烃为基础，通过对其侧壁及边缘进行定向修饰与官能化，使得超分子主体具备分子反应器和自由基引发剂的双重功能，并结合分子间的氢原子转移过程对反应进行自由基引发与催化，从而在水中实现绿色的碳(sp3)-氢键自由基官能化，很好地解决以上的科学问题。另一方面，创新性地将该方法学应用于生物共轭研究中，实现对多种生物活性物质的端基修饰，这其中就包括鲜有研究的多肽/蛋白质中甲硫氨酸残基的端基修饰及其与色氨酸残基之间的架构性偶联。

Supramolecular hosts have been increasingly used in organic reactions in recent years, because they can act as molecular-sized reaction chamber, thereby greatly improving reaction rate, controlling reaction selectivity, and developing new reaction processes different from that of the bulk solutions, etc. However, among them, supramolecular hosts mediated radical reactions mostly depend on UV-activation and suffered from the limitations of reaction type and application scope. Therefore, it is of great research value and significance to achieve diverse radical reactions that mediated by supramolecular hosts and realize catalysis. This project is based on water-soluble deep cavitands, through directed modification and functionalization of their walls and edges, the supramolecular hosts function as molecular chambers and also serve as renewable and recyclable radical initiators. The cavitands catalyze the radical reaction through intermolecular hydrogen atom transfer (HAT) process, so as to realize selective radical functionalization of C(sp3)-H bond in water. On the other hand, this methodology could be innovatively applied to the bioconjugation of a variety of biologically active substances, including the rarely studied terminal modification of methionine residues in polypeptides/proteins and their constructive coupling with tryptophan residues.