Conjugation and encapsulation of photoactive metal complexes for medicinal applications

在过去的十年里，光催化已经看到了复兴，最近的注意力转向了光催化的医学相关应用。许多研究人员已经证明了光氧化还原和金属光氧化还原反应在细胞环境中的应用价值，如蛋白质标记，抗癌治疗和抗菌开发。尽管报道了各种各样的医学应用，但将光催化剂进入水环境和细胞环境的能力仍然是一个挑战，并且能够靶向特定细胞很难实现。这限制了这些催化系统主要应用于细胞表面。为了解决上述挑战，该项目希望开发新的铱催化剂，将其结合到封装或靶向载体上。该项目将使用标记方法，通过全氟芳香配体将活性光催化剂偶联到包含亲核残基的肽、类肽或聚合物支架上。与目前最先进的技术相比，这种方法具有主要优势，因为与合成定制配体的刚性和耗时的过程相比，它提供了一种高度灵活的方式，可以将化学实体附着在肽/类肽/聚合物骨架上。我们将优化一系列附加光催化剂的支架，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，以确定其抗菌和抗癌特性。细胞渗透和定位将通过应用高分辨率显微镜技术进行探测。

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.