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

Abstract

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 <b>2</b> 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 <b>3</b> and 4,4'-dimethoxy-BODIPY <b>5</b> are the least stable, toward addition of TFA, and the 4,4'-diphenyl and 4,4'-difluoro-BODIPYs <b>1</b> and <b>4</b> were found to have intermediate stability. The experimental analysis and comparison with theoretical calculations indicate that the 4,4'-dicyano-BODIPY <b>2</b> 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 <b>2</b>···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.