Novel Platinum(II) Tetrazine Complex Capable of Live-Cell IEDDA Reaction.

The development of the first Pt(II) tetrazine complex, trans-[Pt(II)Cl(dmso)(CH-Tz-Bz-NH)] (1), is reported, which exhibits good in vitro cytotoxicity against MDA-MB-231 cells and succesfully undergoes inverse electron demand Diels-Alder (IEDDA) reactions with trans-cyclooctene (TCO) and bicyclononyne (BCN) derivates in solution. We demonstrate a live-cell IEDDA reaction of 1 with a BF-azadipyrromethene fluorophore (NIR-AZA) posessing a BCN handle. A live-cell bioorthogonal reaction is established using fluorescence lifetime imaging microscopy (FLIM), through a fluorescence lifetime change of 0.3 ns from BF-azadipyrromethene fluorophore starting material to IEDDA Pt fluorophore reaction product. As there is a distinct difference in fluorescence lifetimes between starting material and product, this approach removes the necessity for designing challenging off to on fluorogenic Pt probes and washing steps when developing bioorthogonal cell-imaging strategies for Pt complexes.