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

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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.