Tuning Shortwave-Infrared J-aggregates of Aromatic Ring-Fused Aza-BODIPYs by Peripheral Substituents for Combined Photothermal and Photodynamic Therapies at Ultralow Laser Power.

Achieving photothermal therapy (PTT) at ultralow laser power density is crucial for minimizing photo-damage and allowing for higher maximum permissible skin exposure. However, this requires photothermal agents to possess not just superior photothermal conversion efficiency (PCE), but also exceptional near-infrared (NIR) absorptivity. J-aggregates, exhibit a significant redshift and narrower absorption peak with a higher extinction coefficient. Nevertheless, achieving predictable J-aggregates through molecular design remains a challenge. In this study, we successfully induced desirable J-aggregation (λabs max : 968 nm, ϵ: 2.96×105  M-1 cm-1 , λem max : 972 nm, ΦFL : 6.2 %) by tuning electrostatic interactions between π-conjugated molecular planes through manipulating molecular surface electrostatic potential of aromatic ring-fused aza-BODIPY dyes. Notably, by controlling the preparation method for encapsulating dyes into F-127 polymer, we were able to selectively generate H-/J-aggregates, respectively. Furthermore, the J-aggregates exhibited two controllable morphologies: nanospheres and nanowires. Importantly, the shortwave-infrared J-aggregated nanoparticles with impressive PCE of 72.9 % effectively destroyed cancer cells and mice-tumors at an ultralow power density of 0.27 W cm-2 (915 nm). This phototherapeutic nano-platform, which generates predictable J-aggregation behavior, and can controllably form J-/H-aggregates and selectable J-aggregate morphology, is a valuable paradigm for developing photothermal agents for tumor-treatment at ultralow laser power density.

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.

Near-IR absorbing J-aggregates of a phenanthrene-fused BODIPY as a highly efficient photothermal nanoagent.

A phenanthrene-[b]-fused BODIPY exhibited well-defined J-aggregation behavior in both pure hydrocarbon solution and aqueous solution. The highly stable J-aggregates showed narrowed and largely red-shifted absorption with λmax of 840 nm and enhanced molar absorption coefficients (271 000 M-1 cm-1). Encapsulation of J-aggregates within a micellar nanocapsule resulted in nanoparticles that demonstrated good biocompatibility, excellent photothermal stability, high photothermal conversion ability (η ∼ 46.9%) and an effective phototoxicity (IC50 ∼ 2 µg mL-1 in HeLa cells) under 808 nm laser irradiation.

Surfactant-stripped J-aggregates of azaBODIPY derivatives: All-in-one phototheranostics in the second near infrared window.

Development of multifacted phototheranostics with bright fluorescence and absorbance in the second near infrared (NIR-II) window is very appealing for precise cancer diagnosis and treatment, but still challenging nowadays. Herein, we synthesize a hydrophobic annularly fused azaBODIPY (termed as HBP) molecule with sharp NIR absorbance peaked at 878 nm and bright NIR-II fluorescence. With Pluronic F127 as the surfactant and hydrophobic paclitaxel (PTX) as the spacer, such HBP molecule would self-assemble to form surfactant-stripped HBP/PTX micelles with absorption peak red-shifted to 1012 nm and intrinsic NIR-II fluorescence negligibly disturbed. We found that such HBP/PTX micelles can be utilized as a bimodal NIR-II nano-probe to enable real-time tracking of lymph nodes and tumors under an NIR-II fluorescence imaging system, as well as clear visualization of tumor microvasculatures under an NIR-II photoacoustic imaging system. Furthermore, together with 1064 nm laser exposure, such HBP/PTX micelles would synergistically suppress the growth of tumors grown on the mice upon tumor accumulation. This work highlights the concise preparation of a type of all-in-one NIR-II phototheranostics from the newly synthesized HBP molecules, thereby enables NIR-II fluorescence/photoacoustic bimodal imaging guided synergistic cancer treatment via the NIR-II laser boosted photothermal therapy and chemotherapy.

Synthesis and Semiconducting Characteristics of the BF2 Complexes of Bisbenzothiophene-Fused Azadipyrromethenes.

A novel type of dibenzothiophene [b]-fused core-expanded azaBODIPYs were obtained through an efficient post-functionalization of tetrabrominated azadipyrromethenes, using CuI-catalyzed cyclization, followed by BF2 complexation. These dyes show nearly planar skeletons, strong NIR absorption with maximum peaks up to 733 nm, and remarkable low-lying LUMO level of -4.15 eV. The field-effect transistor based on 1b exhibits bipolar transport properties, with the highest electron and hole mobilities up to 0.012 and 0.046 cm2 V-1 s-1, respectively.

Phenanthro[b]-Fused BODIPYs through Tandem Suzuki and Oxidative Aromatic Couplings: Synthesis and Photophysical Properties.

A new synthetic method to build phenanthrene-fused boron dipyrromethenes (BODIPYs) through tandem Suzuki couplings on readily available 2,3,5,6-tetrabromoBODIPYs, followed by an intramolecular oxidative aromatic coupling mediated by iron(III) chloride is reported. This efficient synthesis allows a very straightforward approach for tuning the absorption and emission of BODIPYs in the red/near-infrared (NIR) range. These resulting phenanthrene-fused BODIPYs exhibit strong absorption (extinction coefficients up to 2.2 × 105 M-1 cm-1) and emission in the near-infrared (NIR) range (688-754 nm). Substituents on the resulting phenanthrene rings have a significant impact on the photophysical properties of these phenanthrene-fused BODIPYs.

Synthesis, Crystal Structure, and the Deep Near-Infrared Absorption/Emission of Bright AzaBODIPY-Based Organic Fluorophores.

Annularly fused azaBODIPY-based organic fluorophores (HBPs 2) containing up to 13 aromatic ring fusions were synthesized by a Suzuki coupling reaction with bromoazadipyrromethenes and a subsequent regioselective oxidative ring-fusion reaction. X-ray analysis indicates almost planar dipyrrin cores for all crystals but overall curved or "wave" conformations for those HBP dyes. These molecules exhibit unique structural and physical properties including excellent spectral selectivity (negligible absorption between 300 and 700 nm), sharp near-infrared (NIR) absorption (up to 878 nm) and emission (up to 907 nm), large extinction coefficient (up to 4.5 × 105 M-1 cm-1), and excellent photostabilities.

Direct Synthesis of Dipyrrolyldipyrrins from SNAr Reaction on 1,9-Dihalodipyrrins with Pyrroles and Their NIR Fluorescence "Turn-On" Response to Zn2.

A set of dipyrrolyldipyrrins have been efficiently synthesized from a direct SNAr reaction on 1,9-dihalodipyrrins with pyrroles and show intense absorption in the NIR region (650-800 nm, as HCl salts). Substituents on both 1,9-dihalodipyrrins and pyrroles greatly affected the reactivity of this SNAr reaction and the absorption properties of the resultant dipyrrolyldipyrrins. These dipyrrolyldipyrrins show sensitive and selective "turn-on" fluorescence response toward Zn2+.

[a]-Phenanthrene-Fused BF2 Azadipyrromethene (AzaBODIPY) Dyes as Bright Near-Infrared Fluorophores.

A new substitution pattern of BF2 azadipyrromethene (azaBODIPY) dyes was obtained by phenanthrene fusion through a key palladium-catalyzed intramolecular C-H activation reaction. These [a]-phenanthrene-fused azaBODIPYs have a near planar structure of the phenanthrene-fused azadipyrromethene core in the crystalline state. The chromophore absorbs (log ε > 5) and fluoresces (ϕ = 0.32-0.38) strongly above 700 nm with excellent photostability and may be used as an attractive bright NIR bioimaging agent.

Synthesis, Structure, and Properties of Near-Infrared [b]Phenanthrene-Fused BF2 Azadipyrromethenes.

A new class of phenanthrene-fused BF2 azadipyrromethene (azaBODIPY) dyes have been synthesized through a tandem Suzuki reaction and oxidative ring-fusion reaction, or a palladium-catalyzed intramolecular C-H activation reaction. These phenanthrene-fused azaBODIPY dyes are highly photostable and display markedly redshifted absorption (up to λ=771 nm) and emission bands (λ≈800 nm) in the near-infrared region. DFT calculations and cyclic voltammetry studies indicate that, upon annulation, more pronounced stabilization of the LUMO is the origin of the bathochromic shift of the absorption and high photostability.

Synthesis, Properties, and Semiconducting Characteristics of BF2 Complexes of ß,ß-Bisphenanthrene-Fused Azadipyrromethenes.

Three novel π-extended BF2 complexes of ß,ß-bisphenanthrene-fused azadipyrromethenes containing nine fused rings have been synthesized on the basis of a tandem Suzuki coupling reaction on readily available 2,6-dibromoazaBODIPYs followed by an intramolecular oxidative aromatic coupling mediated by iron(III) chloride. These resultant BF2 complexes exhibit strong absorption (extinction coefficients up to 2.4 × 105 M-1 cm-1) and emission in the near-infrared (NIR) range (790-816 nm) with excellent photo and thermal stabilities. The hole mobility of the thin-film field-effect transistors of these dyes fabricated by a solution process reaches up to 0.018 cm2 V-1 s-1.

One-pot synthesis and properties of well-defined butadiynylene-BODIPY oligomers.

A homogeneous series of well-defined butadiynylene-BODIPY oligomers containing up to four BODIPY moieties have been synthesized from a "one-pot" oxidative homocoupling reaction of 2,6-di((trimethylsilyl)ethynyl)BODIPY. Further derivation of the resultant BODIPY dimer generates a water-soluble, red-emitting butadiyne-linked BODIPY dimer with pyridinium ions, which can ratiometrically detect viscosity, based on the two fluorescent conformers with the two BODIPY cores twisted and planar to each other depending on the viscosity of the environment.

Synthesis, Structure, and Properties of ß-Vinyl Ketone/Ester Functionalized AzaBODIPYs from FormylazaBODIPYs.

Postfunctionalization of azaBODIPY (the BF2 complex of azadipyrromethene) is highly desirable due to the strong tunable absorption bands at wavelengths above 650 nm and the wide-ranging applications of this class of dyes in biomedicine and materials science. Currently available postfunctionalization methods for this class of dyes have been limited to the Pd-catalyzed coupling reactions on ß-halogenated (brominated or iodinated) azaBODIPY platforms. In this work, we report a new strategy for the facile postfunctionalization of the azaBODIPY chromophore with various vinyl ketone and vinyl esters based on a Wittig reaction on our previously developed ß-formylazaBODIPYs and our recently developed ß-bromo-ß'-formylazaBODIPYs. Our strategy uses easily accessible starting materials and mild reaction conditions. It is highly compatible with various common phosphonium ylides (aliphatic, aromatic, and ester substituted ones). These resultant bromo-containing ß-vinyl ketone/ester functionalized azaBODIPYs are potential photosensitizers and can be further functionalized via coupling reactions. The ester groups on some of these resultant azaBODIPYs can be further hydrolyzed to achieve the desired water solubility and conjugate with the biomolecule and solid surface.

Dipyrrolylquinoxaline difluoroborates with intense red solid-state fluorescence.

A set of organic fluorescent dyes of dipyrrolylquinoxalines (PQs ) and their BF2 complexes (BPQs ) were synthesized from commercial reagents, and were characterized by their X-ray structural analysis, and optical and electrochemical properties. BPQs showed intense broad absorption in the visible region in the solution-state. In comparison with that of PQs , there is an over 110 nm red-shift of the absorption maximum in the BPQs (up to 583 nm). Interestingly, dyes all exhibit red solid-state fluorescence with moderate to high fluorescence quantum yields except for PQ which showed bright yellow solid-state fluorescence. X-ray structures of BPQs showed the planar structure of quinoxaline with one pyrrole unit via the BF2 chelation and the almost perpendicular orientation of the uncoordinated pyrrole to the NBN core plane (the dihedral angle of 70-73°). The extended π-conjugation was in good agreement with the observed red-shift of the spectra. These dyes formed well-ordered intermolecular packing structures via the intermolecular hydrogen bonding between the N atoms of quinoxaline moieties and the NH units of adjacent pyrroles. The lack of π-π stacking in their crystal packing structures may explain the interestingly intense solid-state fluorescence of these dyes.