Pyridinium- and bromine-substituted distyryl-BODIPY dyes for mitochondria-targeted photodynamic therapy

Abstract

Abstract A series of 1-methylpyridinium-substituted brominated distyryl-BODIPY dyes, PyB X I ( X = H, M, or Br), was synthesized to achieve cooperative singlet oxygen ( 1 O 2 ) production through qualitatively different dual intersystem crossing (ISC) pathways: spin–orbit charge-transfer ISC (SOCT-ISC) and heavy-atom-induced ISC. Upon photoexcitation of the PyB X I dyes, charge-transfer states were preferentially formed through photoinduced electron transfer from the distyryl-BODIPY core to the 1-methylpyridinium moiety, however, followed by nonradiative charge recombination rather than the desired SOCT-ISC. This resulted in negligible fluorescence and 1 O 2 quantum yields in the non-brominated dye PyBHI. The introduction of bromine atoms improved 1 O 2 quantum yield from 0.0034 for the mono-brominated dye PyBMI to 0.0061 for the di-brominated dye PyBBrI, attributable to the heavy atom effect. Nonetheless, the 1 O 2 production efficiency of these dyes remained limited, as photoinduced electron transfer was considered to occur nearly two orders of magnitude faster than singlet-to-triplet ISC. In vitro assays using MCF-7 and HeLa cells demonstrated that PyBBrI induced significant cell death, with IC 50 values of ca. 95 and 220 nM, respectively, confirming its potential for use in cancer therapy.