BODIPY-carbazole multichromophoric systems for green LED-assisted photodynamic therapy of breast cancer: synthesis, optoelectronic properties, DFT and antitumor studies

Abstract

A series of five BODIPY dyes substituted with carbazole (Cz) units at different positions and one derivative containing an iodine atom in Cz were synthesized via the Suzuki–Miyaura cross-coupling reaction. Their photophysical and electrochemical properties were studied in order to correlate chemical modifications with intersystem crossing (ISC) from singlet to triplet states, which is a key aspect for their potential use as photosensitizers in antitumor photodynamic therapy (PDT). From the combined experimental analysis and DFT and STEOM-DLPNO-CCSD, electron transfer, which is a pathway for ISC, was observed to occur from Cz to the BODIPY core only when Cz was introduced at either the 2- or 2,6-positions. In contrast, substitution at the meso-phenyl position resulted in electronic isolation of the two chromophores because of their orthogonality. The iodine-substituted molecule can yield the triplet state through spin–orbit coupling (SOC), facilitated by the heavy-atom effect of iodine. Given its higher singlet oxygen yield, as determined by UV-Vis spectroscopy, this derivative was further evaluated for its PDT performance in vitro against breast and lung cancer cells as well as healthy human cells and murine fibroblasts. Upon green light irradiation, a significant therapeutic effect was observed, with MDA-MB-231 breast cancer cells showing the highest sensitivity to the photosensitizer.