Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

Background: Since their first synthesis, silicon xanthenes and the subsequently developed silicon rhodamines (SiR) gained a lot of attention as attractive fluorescence dyes offering a broad field of application. We aimed for the synthesis of a fluorinable pyridinyl silicon rhodamine for the use in multimodal (PET/OI) medical imaging of mitochondria in cancerous cells. Results: A dihalogenated fluorinatable pyridinyl rhodamine could be successfully synthesized with the high yield of 85% by application of a halogen dance (HD) rearrangement. The near-infrared dye shows a quantum yield of 0.34, comparable to other organelle targeting SiR derivatives and absorbs at 665 nm (ε(max) = 34 000 M(−1)cm(−1)) and emits at 681 nm (τ = 1.9 ns). Using colocalization experiments with MitoTracker(®) Green FM, we could prove the intrinsic targeting ability to mitochondria in two human cell lines (Pearson coefficient >0.8). The dye is suitable for live cell STED nanoscopy imaging and shows a nontoxic profile which makes it an appropriate candidate for medical imaging. Conclusions: We present a biocompatible, nontoxic, small molecule near-infrared dye with the option of subsequent radiolabelling and excellent optical properties for medical and bioimaging. As a compound with intrinsic mitochondria targeting ability, the radiolabelled analogue can be applied in multimodal (PET/OI) imaging of mitochondria for diagnostic and therapeutic use in, e.g., cancer patients.