Two-stage ratiometric fluorescent responsive probe for rapid glutathione detection based on BODIPY thiol-halogen nucleophilic mono- or disubstitution

Abstract 3,5-dichloro-8-phenyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BOD-2Cl) (1) as a classical fluorescent dye was synthesized for the purpose of functionalization of BODIPY dye. Herein, it was applied for the purpose of achieving two-stage ratiometric fluorescent detection of glutathione based on the two-step thiol-halogen substitution reaction with the sulfhydryl group of glutathione at the 3 (mono-substitution) and 3,5-position (disubstitution) of 1 in CTAB micelles. The first stage induced fluorescent color change from green (λem = 530 nm) to yellow (λem = 562 nm) (I562nm/I530nm, mono-substitution), excess addition of glutathione caused the second stage fluorescent color change from yellow to red (λem = 597 nm) (I597nm/I562nm, disubstitution). It exhibits excellent properties with specific colorimetric and ratiometric fluorescent change to glutathione over cysteine and homocysteine. Further application to cellular ratiometric fluorescence imaging indicated that the probe was highly responsive to the glutathione in cells.

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