Synthesis of Aza-BODIPYs, Their Differential Binding for Cu(II), and Results of Bioimaging as Fluorescent Dyes of Langerhans β-Cells

Abstract

Cellular labeling through the use of dyes is of great interest to the biomedical sciences for the characterization of the location and distribution of biomolecules and also for the tracking of the course of biological processes in both health and illness. This paper reports the synthesis, characterization, and subsequent evaluation as metal sensors and cell staining probes of four aza-BODIPY compounds [herein referred to as 7(a−d)]. Compounds 7(b−d) were found to display an outstanding selectivity for Cu(II) because their emission band at 720 nm was progressively quenched by this metal, presenting fluorescence quenching between 75 and 95%. On the other hand, cell imaging studies with pancreatic β-cells proved that aza-BODIPYs 7a and 7b showed selectivity for the cytoplasm, while 7c and 7d were selective for the cell membrane. Moreover, aza-BODIPY 7b allowed to characterize in a clear way a lipotoxic condition mediated by saturated fatty acids, a critical phenomenon on β-cell damage associated with diabetes mellitus type II. Taken together, the presented results highlight the obtained aza-BODIPY compounds as selective sensing/staining probes with the potential to be used in the biomedical field.

BODIPY-Based Molecules for Biomedical Applications

“…Miao et al developed various red to near-infrared emitting pyrrolyl BODIPY dyes and demonstrated good lipophilic character, excellent photostability, low cytotoxicity and intense NIR fluorescence of fluorophore pyrrolylBODIPY (Figure 2) in the mitochondrial of HeLa cells [45]. Rivero and co-workers synthesized, characterized, and evaluated different aza-BODIPY compounds as metal sensors and cell staining probes and they found aza-BODIPY (Figure 2) allowed them to characterize a lipotoxic condition mediated by saturated fatty acids, a critical phenomenon on β-cell damage associated with diabetes mellitus type II [46]. Wang et al synthesized and studied a series of mono-spiro-and di-amino acid−BODIPY derivatives, containing basic (histidine, lysine, and arginine), acidic (aspartic acid), polar (tyrosine, serine, and glutamine), and nonpolar (methionine) amino acid residues for potential therapeutic and/or imaging applications [47].…”

A NIR-Fluorochrome for Live Cell Dual Emission and Lifetime Tracking from the First Plasma Membrane Interaction to Subcellular and Extracellular Locales

“…toxicity, and excellent photo stability [20][21][22][23][24][25][26][27]. Previously, we reported a BF2-azadipyrromethene of general structure A as a lysosomal acidity off-to-on responsive probe with excellent photostabilities, good quantum yields, and no phototoxicity at concentrations used for imaging (Figure 1) [28].…”

“…Introduced in the early 2000s, the BF 2 -azadipyrromethenes are an exciting near-infrared (NIR) emissive platform from which application-specific imaging agents can be constructed [ 17 , 18 , 19 ]. They are ideally suited to both live cellular and in vivo imaging, with fluorescence wavelengths tunable within the low-level energy range of 650 to 850 nm, low toxicity, and excellent photo stability [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Previously, we reported a BF 2 -azadipyrromethene of general structure A as a lysosomal acidity off-to-on responsive probe with excellent photostabilities, good quantum yields, and no phototoxicity at concentrations used for imaging ( Figure 1 ) [ 28 ].…”