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 11B and 1H 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.
