Nonbenzenoid BODIPY Analogues: Synthesis, Structural Organization, Photophysical Studies, and Cell Internalization of Biocompatible N-Alkyl-Aminotroponyl Difluoroboron (Alkyl-ATB) Complexes.

ABSTRACT

The alkyl-BODIPY derivatives are lipid types of fluorescent molecules that exhibit a unique structure and functions including sensing of hydrophobic microenvironments in living cells. Their synthesis involves multisteps from the core structure dipyrromethene scaffold. The alkyl-BODIPY analogues are sought to derivatize with minimal synthetic steps even by altering the core structures derived from benzenoid aromatic moiety. Recently, the nonbenzenoid scaffold (aminotropone) has been explored to synthesize troponyl-BODIPY analogues, which are fluorescent. In the repertoire of nonbenzenoid analogue, N-alkyl-aminotroponyl difluoroboron (alkyl-ATB) is rationally designed comprising long-chain hydrocarbons to explore the lipid type of fluorescent molecules. This report describes the synthesis, photophysical studies, structural organization, and biocompatibilities of ATB derivatives containing different lengths of alkyl chain at 2-aminotropone scaffold. The photophysical studies of ATB derivatives reveal their fluorescence behaviors in organic solvents (CH3OH/CH3CN) with a quantum yield of ∼10 to 15%. These ATB derivatives also exhibit fluorescence characters in the solid state though their quantum yield is relatively low. Cell permeability and cytotoxicity studies reveal that alkyl-ATB derivatives are permeable to HeLa/HEK293T cell lines and show negligible cytotoxicity. The biocompatibility of alkyl-ATB derivatives is studied and confirmed by cell viability (MTT) assay to the HeLa/HEK293T cell lines. Importantly, the cell internalization studies of the representative alkyl-ATB molecule by fluorescence microscopy show that octyl-ATB is efficiently detectable at the cytoplasmic membrane and cellular nucleus in HeLa cells. Hence, alkyl-ATB derivatives are potential fluorescent molecules for developing probes to visualize cellular components under a fluorescence microscope.