Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion.

An efficient synthesis of 3-pyrrolylBODIPY dyes has been developed from a rational mixture of various aromatic aldehydes and pyrrole in a straightforward condensation reaction, followed by in situ successively oxidative nucleophilic substitution using a one-pot strategy. These resultant 3-pyrrolylBODIPYs without blocking substituents not only exhibit the finely tunable photophysical properties induced by the flexible meso-aryl substituents but also serve as a valuable synthetic framework for further selective functionalization. As a proof of such potential, one 3-pyrrolylBODIPY dye (581/603 nm) through the installation of the morpholine group is applicable for lysosome-targeting imaging. Furthermore, an ethene-bridged 3,3'-dipyrrolylBODIPY dimer was constructed, which displayed a near-infrared (NIR) emission extended to 1200 nm with a large fluorescence brightness (2840 M-1 cm-1). The corresponding dimer nanoparticles (NPs) afforded a high photothermal conversion efficiency (PCE) value of 72.5%, eventually resulting in favorable photocytotoxicity (IC50 = 9.4 µM) and efficient in vitro eradication of HeLa cells under 808 nm laser irradiation, highlighting their potential application for photothermal therapy in the NIR window.

Aromatic-Ring-Fused BOPPY Fluorophores: Synthesis, Spectral, Redox Properties, and Bioimaging Application.

Tetracoordinated organoboron dyes exhibiting strong fluorescence in either solution or the solid state are currently receiving much attraction in view of their photovoltaic, optoelectronic, and biological applications. Herein, a series of aromatic-ring-fused BOPPY dyes have been developed by one-pot condensation of formylated isoindoles or indoles and pyridinylhydrazine followed by subsequent borylation coordination. The facile synthesis provides excellent diversity of these unsymmetrical α-benzo- and ß-benzothiophene-fused BOPPY dyes with intriguing photophysical properties owing to their rigid and planar structure and extended π-conjugation while containing a reactive site. They display intense green to orange fluorescence in solution and red-to-near-infrared emission in the solid state, with high fluorescence quantum yields up to 92 and 21%, respectively, relatively large Stokes shifts, and excellent photostability. Furthermore, two representative benzo-fused BOPPY probes with morpholine or benzenesulfonamide groups were developed and used to selectively "light up" the subcellular organelles such as lysosomes and endoplasmic reticulum under ultralow concentration, respectively.

Unique Double Intramolecular and Intermolecular Exciton Coupling in Ethene-Bridged aza-BODIPY Dimers for High-Efficiency Near-Infrared Photothermal Conversion and Therapy.

Spatial electronic communications of chromophores are both theoretically and practically fascinating. Despite intramolecular or intermolecular exciton coupling was observed in multichromophoric oligomers and J-aggregates, respectively, it is unusual that they both occur in the same molecule. Herein, ethene-bridged aza-BODIPY dimers with intramolecular exciton splitting have been developed. By encapsulating the dimer into F-127 polymer, J-type aggregated nanoparticles were produced, which showed obvious intermolecular exciton coupling and dramatically redshifted absorption and emission peaks at 936 and 1003 nm, respectively. The fabricated nanoagents have high photothermal conversion ability (η=60.3 %) and are ultra-photostable, leading to complete tumor ablation with 915 nm laser irradiation. This phototherapeutic nanoplatform through modulating both intra- and intermolecular exciton couplings is a valuable paradigm for developing photothermal agents for tumor treatment.

Heavy-atom-free triplet benzothiophene-fused BODIPY derivatives for lipid droplet-specific biomaging and photodynamic therapy.

The twist fusion of a benzothiophene group and the introduction of a 4-methyloxystyryl donor group to the BODIPY core resulted in large spin-orbit coupling values and smaller singlet-triplet energy gaps for the novel infrared absorbed photosensitizers named BSBDP. They show a high reactive oxygen species efficiency exceeding 69% and a fluorescence quantum yield of 23% and are successfully applied in imaging-guided photodynamic therapy in vitro and in vivo.

Hybridization of triphenylamine to BODIPY dyes at the 3,5,8-positions: A facile strategy to construct near infra-red aggregation-induced emission luminogens with intramolecular charge transfer for cellular imaging.

A series of five BODIPY derivatives with triarylamine (TPA) moieties on their 3-, 5-, or 8-positions were reported, which showed wide-range fluorescence emissions across red and near infrared regions in their aggregation states. The influences of numbers and substituted positions of TPA groups on the optical and aggregation-induced emission (AIE) properties of these BODIPYs as well as organelle-specific imaging in live cells were investigated. The TPA groups installed at 3-/5-positions of BODIPY could effectively enlarge the conjugated system and red-shift the absorption and emission bands (λemmax up to 815 nm). In contrast, the TPA group linked to 8-position of BODIPY core has little contribution to decrease the HOMO-LUMO energy gap. Importantly, regardless the substitution positions of TPA groups, all these TPA-substituted BODIPYs (BTs) showed remarkable AIE performance and possessed high molar extinction absorption (up to âˆ¼ 63000 M-1 cm-1), two-photon absorption (up to 171 GM at 870 nm), and large Stokes shifts. The BODIPY with one TPA group (BT1 and FBT1) showed lipid droplets-specific localization while BODIPY with two and three TPA groups (BT2, BT3 and FBT2) preferred to enrich in lysosomes. These BODIPYs all have been successfully used in tracking the dynamic behaviors of lipid droplets or lysosomes in living cells. Furthermore, BT1 and FBT1 can quantitatively detect the overexpression of lipid droplets, and BT3 has been successfully used to observe lysosomes behaviors of lipophagy process in living cells. This work systematically studied the influence of the number and position of TPA units on the optical properties and AIE-activities of BODIPYs, which not only enriched the BODIPY-based AIE NIR probes for organelle-specific imaging in live cells, but also provided a practical strategy for the effective construction of organic dyes with NIR AIE activity.

Engineering BODIPY-based near-infrared nanoparticles with large Stokes shifts and aggregation-induced emission characteristics for organelle specific bioimaging.

Lipid droplets (LDs) and lysosomes, as two important subcellular organelles, play specific and indispensable roles in various cellular processes. The development of efficient LD- and lysosome-specific fluorescent bio-probes is of great importance. However, current commercial lipid droplet- (LD) and lysosome-specific fluorescent specific bio-probes often suffer from the aggregation-caused quenching (ACQ) effect, short absorption and emission wavelengths, poor photostability and low specificity. Herein, a typical ACQ luminogen BODIPY was directly conjugated to strong electron donating triarylamine units at its α-positions, giving near-infrared (NIR) fluorescent materials TPAB and 2TPAB with aggregation-induced emission (AIE). Both TPAB and 2TPAB nanoparticles were obtained by self-assembly, and showed NIR emissions, large Stokes shifts, good photostability and two-photon absorption. These nanoparticles presented remarkable bioimaging performances and were shown to specifically localize in LDs or lysosomes, respectively, depending on the number of triarylamine units attached. They have been successfully used to detect endogenous LD overproduction, and monitor abnormal activities of LDs/lysosomes, as well as real-time track the lipophagy process in cells. Their far NIR emission and two-photon excitation further supported their promising bioimaging application for lipid droplet tracking in liver tissue and live zebrafish larvae. Our work here enriches BODIPY based NIR AIE dyes and provides organelle specific bio-probes which are superior to currently used commercial ones.