π-Spacer Effects in 2,6-Disubstituted BODIPY Fluorophores for Mitochondrial Imaging

Abstract

Mitochondria are highly dynamic subcellular organelles that serve as central hubs of energy metabolism, signaling, and stress regulation, and their dysfunction is closely linked with a wide range of diseases. Herein, we report the rational design, synthesis, photophysical properties and bioimaging applicability of a new class of BODIPY-based fluorophores with tunable optical properties upon altering the π-spacer units. Notably, the incorporation of phenyl and triphenylamine (TPA) π-spacers at the 2,6-positions of the BODIPY core induced a pronounced bathochromic shift, affording far-red to near-infrared (NIR) emission (600-850 nm), particularly for TPA-substituted derivatives. Further, the introduction of cationic (quaternary ammonium) groups significantly improved mitochondrial localization in Ph-BDP-NMe 3 , effectively overcoming aggregation and poor cellular uptake associated with lipophilic analogues. Overall, this work demonstrates a robust molecular engineering strategy to synthesize mitochondria-targeted BODIPY fluorophores with enhanced photophysical performance. probes, Ph-BDP-NMe 3 and TPA-BDP-NMe 3 . All the precursors and target molecules were well characterized by 1 H NMR, 13 C NMR, 11 B NMR, and 19 F NMR spectroscopy, as well as high-resolution mass spectrometry (HRMS) analytical techniques. Details of the synthesis and characterization data are shown in the Supporting Information.