Conjugation and encapsulation of photoactive metal complexes for medicinal applications

在过去的十年中，光催化已经复兴，最近的注意力转向了与医学相关的应用。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，但将光催化剂引入水和细胞环境的能力仍然是一个挑战，并且难以实现靶向特定细胞的能力。这限制了这些催化体系主要用于细胞表面应用。为了解决上述挑战，该项目寻求开发新的铱催化剂，其缀合到封装或靶向载体上。该项目将通过全氟芳族配体使用标记方法将活性光催化剂缀合到包含亲核残基的肽、类肽或聚合物支架上。这种方法比当前最先进的方法具有重大优势，因为与合成定制配体的严格且耗时的过程相比，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。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。将筛选库中的化合物以确定其抗微生物和抗癌特性。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.