Stability of a Series of BODIPYs in Acidic Conditions: An Experimental and Computational Study into the Role of the Substituents at Boron

[Image: see text] Boron-dipyrromethene (BODIPY) dyes have been extensively investigated in recent years for a variety of bioanalytical and bioimaging applications. The success of these applications relies on the stability of BODIPYs, particularly under acidic conditions. In this work, the stability of a series of 4,4′-disubstituted BODIPYs (−F, −CN, −Ph, −Me, −OMe) toward addition of excess trifluoroacetic acid (TFA) was studied systematically and comprehensively through (11)B and (1)H NMR, UV–vis, fluorescence, thin layer chromatography, mass spectrometry, and infrared. The results indicate that 4,4′-dicyano-BODIPY 2 is the most stable among this series and remains unchanged even 3 days after addition of excess TFA. On the other hand, 4,4′-dimethyl-BODIPY 3 and 4,4′-dimethoxy-BODIPY 5 are the least stable, toward addition of TFA, and the 4,4′-diphenyl and 4,4′-difluoro-BODIPYs 1 and 4 were found to have intermediate stability. The experimental analysis and comparison with theoretical calculations indicate that the 4,4′-dicyano-BODIPY 2 has the greater aromaticity of the series, as evaluated by the BLA parameter, decreased charge on boron, and upon TFA addition it forms an unusually stable BODIPY 2···TFA complex. On the other hand, all other BODIPYs decompose within hours after TFA addition. Computational modeling demonstrates that 4,4′-dicyano substitution increases aromaticity and stabilizes the B–N bond, resulting in the most stable compound from the series studied.