Halogenated Bis(donor)‐aza‐BODIPY System for Inducing NIR Excitation: Effect of Thiophene and Aminophenyl Donors on Optical Properties and in vitro Tests for Breast Cancer

Abstract A series of near‐IR absorbing BF 2 ‐chelated aza‐boron‐dipyrromethene (AZBs) derivatives bearing aniline/thiophene electron donors were designed, synthesized, and characterized to study the effect of substitution on the photophysical properties. These molecules exhibit internal charge transfer (ICT) with a characteristic spectrum of dual absorption bands which allows electronic excitation in the wide spectral region of 500–820 nm. The ICT character was stablished by its inhibition upon protonation of the amino groups with trifluoroacetic acid (TFA) in CHCl 3 , observed as a visible colorimetric change from red to blue accompanied by an hypsofluoric shift of the emission band. Protonation of AZB‐4 in DMSO‐ d 6 upon the addition of TFA was monitored by 1 H, 11 B, and 19 F NMR. Thiophene Aza‐BODIPY p ‐(amino) phenyl derivatives also generated singlet oxygen ( 1 O 2 ) under the irradiation of laser light (532 and 800 nm). The 1 O 2 generation of these dyes was enhanced upon subsequent bromination of the molecule which favors intersystem crossing between singlet and triplet states. The aza‐BODIPY derivatives developed in this work have potential applicability as photosensitizers in photodynamic therapy, with sensibility in the window of biomedical interest (700 – 900 nm) and excellent photo and chemical stability even at high energy irradiation. Additionally, their dark and photoinduced cytotoxic activity was tested on a breast cancer cell line (MDA‐MB‐231 cells).