A novel terpene-BODIPY conjugates based fluorescent probes: Synthesis, spectral properties, stability, penetration efficiency into bacterial, fungal and mammalian cells

Abstract

The design of fluorescent probes based on biocompatible luminophores for medical diagnostics is one of the rapidly developing areas worldwide. Here, we report the synthesis of a novel BODIPYs containing a propanoic acid residue at the α-position of one of the pyrrole rings conjugated to (+)-myrtenol or thiotherpenoid. Both conjugates are quite photostable (t_1/2 ∼ 40 h) and exhibit high fluorescence efficiency (φ^fl ∼ 77–90 %). The advantage of the newly synthesized terpene-BODIPY conjugates lies in their stability and absence of fluorescence quenching over a wide pH range (1.65–9.18). Moreover, the affinity of the conjugates for lipid biostructures was significantly improved compared to the original α-BODIPY carboxylic acid. As opposed to unconjugated BODIPY, which shows negligible activity against any cell type used in the study, the luminophores with either (+)-myrtenol or thioterpenoid effectively stained the membranes of Gram-positive bacteria, while Gram-negative bacteria were not stained. In eukaryotic cells, both conjugates readily stained organelles, but not the cell and nuclear membranes, suggesting these compounds as tools for differential staining of microbes or cell structures. Taken together, our data demonstrates that conjugation of BODIPY to terpenoids significantly improves the fluorescence abilities and modulates the selectivity of the conjugates against various cells.