Bio-Organic Chemistry, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Biomacromolecules. 2023 Sep 11;24(9):4148-4155. doi: 10.1021/acs.biomac.3c00487. Epub 2023 Aug 17.
The application of transition-metal catalysts in living cells presents a promising approach to facilitate reactions that otherwise would not occur in nature. However, the usage of metal complexes is often restricted by their limited biocompatibility, toxicity, and susceptibility to inactivation and loss of activity by the cell's defensive mechanisms. This is especially relevant for ruthenium-mediated reactions, such as ring-closing metathesis. In order to address these issues, we have incorporated the second-generation Hoveyda-Grubbs catalyst (HGII) into polymeric vesicles (polymersomes), which were composed of biodegradable poly(ethylene glycol)--poly(caprolactone--trimethylene carbonate) [PEG--P(CL--TMC)] block copolymers. The catalyst was either covalently or non-covalently introduced into the polymersome membrane. These polymersomes were able to act as artificial organelles that promote endosomal ring-closing metathesis for the intracellular generation of a fluorescent dye. This is the first example of the use of a polymersome-based artificial organelle with an active ruthenium catalyst for carbon-carbon bond formation.
过渡金属催化剂在活细胞中的应用为促进那些在自然界中不会发生的反应提供了一种很有前途的方法。然而，金属配合物的使用通常受到其有限的生物相容性、毒性以及对细胞防御机制的失活和活性丧失的敏感性的限制。这对于钌介导的反应（如闭环复分解反应）尤为重要。为了解决这些问题，我们将第二代 Hoveyda-Grubbs 催化剂 (HGII) 纳入聚合物囊泡（聚合物囊泡）中，这些聚合物囊泡由可生物降解的聚（乙二醇）-聚（己内酯-三亚甲基碳酸酯）[PEG-P(CL-TMC)]嵌段共聚物组成。催化剂要么通过共价键要么非共价键的方式引入聚合物囊泡膜中。这些聚合物囊泡可以作为人工细胞器，促进内体闭环复分解反应，从而在细胞内生成荧光染料。这是首次使用基于聚合物囊泡的人工细胞器和活性钌催化剂进行碳-碳键形成的例子。
