A straightforward approach to carborane-substituted BODIPY derivatives via nucleophilic aromatic substitution: Synthesis and photodynamic properties

Abstract

Neutral and water soluble anionic carborane derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) were efficiently synthesized via nucleophilic aromatic substitution of p-fluorine atom in meso-8-pentafluorophenyl-substituted BODIPYs with carborane S-nucleophiles. Using this synthetic approach a series of thiocarboranyl-BODIPYs was generated in good yields under mild reaction conditions such as room temperature and a short reaction time. Individual carborane-BODIPY conjugates formed stable complexes with serum albumin and generated singlet oxygen. In cell based experiments compounds 6 (8-[4-((m-carboran-9-yl)thio)-2,3,5,6-tetrafluorophenyl]-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) and 11 ({8-[4-((1-carba-closo-dodecaboran-1-yl)thio)-2,3,5,6-tetrafluorophenyl]-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene} caesium) were negligibly cytotoxic in the dark whereas the plasma membrane photodamage and cell death were registered rapidly after illumination. Thus, the new chemotype of boronated BODIPYs emerges as a biocompatible and efficient tool for binary therapeutic modalities.