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

IF 2.8 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

ChemBioChem Pub Date : 2025-08-29 DOI:10.1002/cbic.202500376

Paul D. O’Dowd, Dan Wu, Alby Benny, Ellen King, Alice Harford, Brendan Twamley, Olga Piskareva, Donal F. O’Shea, Darren M. Griffith

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Abstract

The development of the first Pt(II) tetrazine complex, trans-[Pt(II)Cl₂(dmso)(CH₃-Tz-Bz-NH₂)] (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 BF₂-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 BF₂-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.

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新型铂（II）四氮配合物可用于活细胞IEDDA反应

报道了首个Pt（II）四嗪配合物trans-[Pt(II)Cl2(dmso)(CH3-Tz-Bz-NH2)](1)的开发，该配合物对MDA-MB-231细胞具有良好的体外细胞毒性，并在溶液中成功地与反式环烯（TCO）和双克隆炔（BCN）衍生物进行了反电子需求Diels-Alder （IEDDA）反应。我们证明了1与具有BCN手柄的bf2 -氮杂基吡咯甲烷荧光团（NIR-AZA）的活细胞IEDDA反应。利用荧光寿命成像显微镜（FLIM）建立了一个活细胞生物正交反应，从bf2 -氮杂二吡罗甲烷荧光团起始物质到IEDDA Pt荧光团反应产物的荧光寿命变化为0.3 ns。由于起始材料和产物之间的荧光寿命存在明显差异，因此在开发Pt复合物的生物正交细胞成像策略时，该方法消除了设计具有挑战性的荧光Pt探针和洗涤步骤的必要性。

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来源期刊

ChemBioChem 生物-生化与分子生物学

CiteScore

6.10

自引率

3.10%

发文量

407

审稿时长

1 months

期刊介绍： ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).