A Three‐Component Assembly Promoted by Boronic Acids Delivers a Modular Fluorophore Platform (BASHY Dyes)

Abstract

The modular assembly of boronic acids with Schiff‐base ligands enabled the construction of innovative fluorescent dyes [boronic acid salicylidenehydrazone (BASHY)] with suitable structural and photophysical properties for live cell bioimaging applications. This reaction enabled the straightforward synthesis (yields up to 99 %) of structurally diverse and photostable dyes that exhibit a polarity‐sensitive green‐to‐yellow emission with high quantum yields of up to 0.6 in nonpolar environments. These dyes displayed a high brightness (up to 54 000 m −1 cm−1). The promising structural and fluorescence properties of BASHY dyes fostered the preparation of non‐cytotoxic, stable, and highly fluorescent poly(lactide‐co‐glycolide) nanoparticles that were effectively internalized by dendritic cells. The dyes were also shown to selectively stain lipid droplets in HeLa cells, without inducing any appreciable cytotoxicity or competing plasma membrane labeling; this confirmed their potential as fluorescent stains.

Theoretical spectroscopy of BASHY dyes

“…τ 1 does only marginally evolve when going from the GS to the ES. τ 2 quantifies the overall planarity of the compound and is much larger in 1 than in 2, as foreseen by the experimental group [11]. This, however, did not lead to the hoped increase in fluorescence quantum yield (φ f ) that is very small in 2.…”

“…[11] that concluded to a significant charge transfer for 9. More in details, these calculations were performed using the LR-PCM/CAM-B3LYP/6-31G(d,p) level on four ground-state structures, which led to a strong overestimation (ca.…”

“…They next synthesized 3-9 and obtained a promising emission quantum yield of 62 % for 5 in chloroform. This dye is photostable: a prolonged irradiation under an intense xenon lamp only led to a decrease in the fluorescence intensity by 10 % [11]. Clearly, more is welcome to understand the nature of these dyes and the present work is a theoretical effort in that direction.…”

“…Very recently, Gois and coworkers proposed yet another family of boron(III) derivatives with improved properties: Boronic Acid SalicylideneHYdrazone (BASHY) dyes (see 1-9 in Fig. 1) [11]. These chromogens can be easily substituted, are photostable and present emission quantum yield that can reach up to 60 % in a nonpolar environment.…”

Modern Synthetic Avenues for the Preparation of Functional Fluorophores

“…The group of Pischel and Gois developed a three‐component sequential condensation reaction of a boronic acid, a salicylaldehyde, and an amino substrate to obtain fluorescent boron‐containing heterocycles with polarity‐dependent fluorescence emission (Figure 2 A) 5. These structures were suitable for the imaging of dendritic cells as well as cancer cells.…”