biostudies-literatureO'Dowd PDScience Foundation Ireland under Grant numberse202500376https://www.ebi.ac.uk/biostudies/studies/S-EPMC12447375biostudies-literatureUnknown26(18)The development of the first Pt(II) tetrazine complex, trans-[Pt(II)Cl<sub>2</sub>(dmso)(CH<sub>3</sub>-Tz-Bz-NH<sub>2</sub>)] (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<sub>2</sub>-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<sub>2</sub>-azadipyrromethene fluorophore starting material to IEDDA Pt fluorophore reaction product. As there is a distinct difference iChembiochem : a European journal of chemical biologyNovel Platinum(II) Tetrazine Complex Capable of Live-Cell IEDDA Reaction.PMC1244737512/RC/2275_P221/FFP-P/10216Benny AHarford APiskareva OKing EWu DO'Dowd PDO'Shea DFGriffith DMTwamley BfalseNovel Platinum(II) Tetrazine Complex Capable of Live-Cell IEDDA Reaction.The development of the first Pt(II) tetrazine complex, trans-[Pt(II)Cl<sub>2</sub>(dmso)(CH<sub>3</sub>-Tz-Bz-NH<sub>2</sub>)] (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<sub>2</sub>-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<sub>2</sub>-azadipyrromethene fluorophore starting material to IEDDA Pt fluorophore reaction product. As there is a distinct difference i2025-01-01T00:00:00Z2025 Sep2026-06-03T14:59:08.873Z2026-04-28T03:11:13.307ZS-EPMC124473754088007410.1002/cbic.202500376