Inorganic click reactions in the inner metal coordination sphere as a quick access to combinatorial metal complex synthesis and luminescent probes (iClick^2)

内部金属配位球中的无机点击反应可快速合成组合金属配合物和发光探针 (iClick^2)

• 批准号: 524338748
• 负责人: Professor Dr. Patrick Nürnberger
• 金额: --
• 依托单位: Institut für Anorganische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/524338748?language=en
• 关键词: Inorganic; click; reactions; inner; metal

Inspired by the great success of click reactions in organic chemistry, as highlighted by the 2022 Nobel Prize in Chemistry to Bertozzi, Meldal, and Sharpless, and the significant structure-reactivity relationships we have gathered in the last years on the scope of iClick (inorganic click) reactions for metal complex modification directly in the inner coordination sphere of a metal center, this project aims to push the boundaries of the iClick reaction towards applications in biology along three lines: In a first work package, new alkynes and metal azido complexes as reactive luminescent probes in living cells with facile options for bioconjugation will be prepared to specifically address cellular target structures. In particular, by proper molecular design, the alkyne reactivity will be tuned to ensure fast iClick reactions go along with low cytotoxicity. In the second part of the project, new methods for combinatorial iClick reactions to quickly access a large chemical space will be developed. This will allow to screen for suitable dipolarophiles that give rise to iClick triazolato products with favorable photophysical properties and provide access to a broad panel of bioconjugates that are able to address different cellular targets. Automated protocols for quick "activity-based" screening will be developed in which only those complexes are synthesized on a preparative scale for further investigations that show promising properties in simple read-outs. Finally, the systems identified in the previous work packages will be comprehensively characterized for their photophysical properties and then passed on to microscopy studies in living cells for compounds that show low activity in cytotoxicity screening.

受点击反应在有机化学领域的巨大成功的启发，正如Bertozzi， Meldal和Sharpless获得2022年诺贝尔化学奖所强调的那样，以及我们在过去几年中在iClick（无机点击）反应范围内直接在金属中心的内配位球中修饰金属络合物的重要结构-反应性关系，该项目旨在推动iClick反应在生物学中的应用：在第一个工作包中，新的炔和金属叠氮配合物作为活细胞中的反应性发光探针，具有简单的生物偶联选择，将专门用于细胞目标结构。特别是，通过适当的分子设计，炔的反应性将被调整，以确保快速的iClick反应伴随着低细胞毒性。在该项目的第二部分，将开发用于组合iClick反应的新方法，以快速访问大的化学空间。这将允许筛选合适的亲偶极试剂，产生具有良好光物理性质的iClick三唑啉产品，并提供能够解决不同细胞目标的广泛生物偶联物。快速“基于活性”筛选的自动化方案将被开发出来，其中只有那些复合物在准备规模上被合成，以进行进一步的研究，在简单的读出中显示出有希望的特性。最后，在之前的工作包中确定的系统将全面表征其光物理特性，然后将其传递到活细胞的显微镜研究中，用于细胞毒性筛选中显示低活性的化合物。