Conjugation and encapsulation of photoactive metal complexes for medicinal applications

在过去的十年里，光催化已经复兴，最近人们的注意力转向了光催化在医学上的相关应用。许多研究人员已经展示了光氧化还原和金属光氧化还原反应在细胞环境中的价值，应用于蛋白质标记、抗癌治疗和抗菌开发等。尽管已报道了多种医学应用，但将光催化剂带入水和细胞环境的能力仍然是一个挑战，并且能够针对特定的细胞一直很难实现。这限制了这些催化系统的使用，主要是细胞表面的应用。为了解决上述挑战，本项目寻求开发连接到胶囊或靶向载体上的新的Ir催化剂。这个项目将使用一种通过全氟芳香族配体的标记方法，将活性光催化剂连接到含有亲核残基的多肽、类肽或聚合物支架上。与目前最先进的方法相比，这种方法有一个重大优势，因为它提供了一种高度灵活的方式，将化学实体连接到肽/类肽/聚合物骨架上，而不是合成定制配体的僵硬和耗时的过程。我们将优化一系列添加了光催化剂的支架，产生一个用于评估的化合物库。将对文库中的化合物进行筛选，以确定它们的抗菌和抗癌性能。将通过应用高分辨率显微镜技术来探索细胞的穿透和定位。

Photocatalysis has seen a renaissance over the past decade, with attention recently turning to medicinally relevant applications of photocatalysis. Many researchers have shown the value of photoredox and metallophotoredox reactions in cellular environments with applications such as protein tagging, anticancer therapies and anti-bacterial development. Despite the variety of medicinal applications reported, the ability to get photocatalysts into aqueous and cellular environments remains a challenge and being able to target specific cells has been difficult to achieve. This has limited the use of these catalytic systems to mainly cell surface applications. To address the aforementioned challenges this project looks to develop new iridium catalysts which are conjugated onto a encapsulation or targeting vector. This project will use a tagging approach through perfluoroaromatic ligands to conjugate the active photocatalyst onto a peptide, peptoid or polymer scaffold which incorporates a nucleophilic residue. This approach has a major advantage over the current state-of-the-art, as it offers a highly flexible way to attach chemical entities onto peptide/peptoid/polymer backbones compared to the rigid and time-consuming process of synthesising bespoke ligands. We will optimise a range of scaffolds to which photocatalysts are appended, producing a library of compounds for evaluation. Compounds within the library will be screened to determine their antimicrobial and anticancer properties. Cell penetration and localisation will be probed through the application of high resolution microscopy techniques.