BODIPY Dyes Research Articles

Photophysical properties of BODIPYs with sterically-hindered nitrophenyls in meso-position

During recent years, the BODIPY core became a popular scaffold for designing of dyes with desirable properties. In this paper, we extend the library of possible modification of BODIPYs, presenting experimental data for a new family meso-substituted with nitrophenyl groups. We also present quantum chemical calculations, which complement the experimental data and give additional insight in the underlying photochemical and photophysical processes. Optical properties of novel compounds are characterized. It is shown that the fluorescence quantum yield and the efficiency of singlet oxygen generation differs by two orders of magnitude across the family. In aqueous solution, red-shifted fluorescence emission band is detected, corresponding to aggregates. This band has shorter decay time and wide excitation spectrum. We show that photolysis is not accompanied by the release of nitric oxide (NO) which was observed earlier for some dyes with nitrophenyl substituents. The experimental data presented in this paper may be useful for further designing of BODIPY dyes and NO photodonors.

Anti-cooperative Self-Assembly with Maintained Emission Regulated by Conformational and Steric Effects.

Herein, we present a strategy to enable a maintained emissive behavior in the self‐assembled state by enforcing an anti‐cooperative self‐assembly involving weak intermolecular dye interactions. To achieve this goal, we designed a conformationally flexible monomer unit 1 with a central 1,3‐substituted (diphenyl)urea hydrogen bonding synthon that is tethered to two BODIPY dyes featuring sterically bulky trialkoxybenzene substituents at the meso‐position. The competition between attractive forces (H‐bonding and aromatic interactions) and destabilizing effects (steric and competing conformational effects) limits the assembly, halting the supramolecular growth at the stage of small oligomers. Given the presence of weak dye–dye interactions, the emission properties of molecularly dissolved 1 are negligibly affected upon aggregation. Our findings contribute to broadening the scope of emissive supramolecular assemblies and controlled supramolecular polymerization.

Development of environment-insensitive and highly emissive BODIPYs via installation of N,N'-dialkylsubstituted amide at meso position

Fluorescent dyes play a crucial role in fluorescence imaging and sensing technology. However, there is a dilemma that they are usually intrinsically hydrophobic which lacks of emission in water and modification with ionic groups to access water solubility may result in poor membrane permeability. Fluorescent dyes with strong fluorescence emission in both nonpolar and polar solvents are highly desirable. In this manuscript, we reported a strategy to develop fluorescent BODIPY dyes via installation of amide moiety at meso position of 1,3,5,7-tetramethyl-BODIPY and discovered that N,N'-dialkylsubstituted BODIPY amides possessed highly fluorescent emission with favorable environment-insensitive properties.

Achieving Photomultiplication in Dye‐Sensitized Narrowband Photodetectors by Electron Injection through a Thin Hole‐Transporting Layer

AbstractNarrowband photodetectors (NBPDs) that response to light with specific wavelength are attractive in imaging fields. Organic materials meet the demand of NBPDs well as active layer due to their tunable and the narrowband‐absorption properties. However, the responsivity is generally low caused by the hard exciton diffusion as well as severe recombination. Herein, a narrowband‐absorption BODIPY dye is synthetized and applied in vertical‐structural NBPDs as sensitizer bonding with the mesoporous titanium dioxide (mp‐TiO2). The close bonding between BODIPY dyes and mp‐TiO2 effectively enhances the dissociation of excitons. Importantly, the NBPDs present high photomultiplication, the first observation in such dye‐sensitized devices, which is due to the electron injection induced by a thin layer of Spiro‐OMeTAD covered on the hump parts of mp‐TiO2. The NBPDs exhibit high external quantum efficiency (EQE) of 534% at 510 nm with a full‐width at half‐maximum (FWHM) of 45 nm, a low dark current of 7.0 × 10‐5 mA cm‐2, and a high detectivity (D*) of 1.5 × 1013 cm Hz1/2 W‐1 (Jones) at −3 V. Besides, the devices own response speed within several milliseconds and excellent stability. The work proposes a strategy to fabricate photomultiplication‐type NBPDs by using intrinsic narrowband‐absorption dyes as active layer.

A Facile, Protein-Derived Supramolecular Theranostic Strategy for Multimodal-Imaging-Guided Photodynamic and Photothermal Immunotherapy In Vivo.

Theranostic systems that permit both diagnosis and treatment in vivo are highly appealing means by which to meet the demands of precision medicine. However, most such systems remain subject to issues related to complex molecular design and synthesis, potential toxicity, and possible photoactivity changes. Herein, a novel supramolecular theranostic strategy involving biomarker protein activation (BPA) and a host-guest strategy is proposed. To exemplify BPA, a facile "one-for-all" nanotheranostic agent for both albumin detection and cancer treatment is demonstrated, which utilizes a nanoparticulate heavy-atom-free BODIPY dye derivative (B4NPs). The fluorescence and photoactivity of BODIPY dyes are completely suppressed by aggregation-induced self-quenching in the nanoparticulate state. However, a Balb/c nude mouse model is used to confirm that following the disassembly of injected B4NPs, BODIPY specifically binds albumin in vivo, accompanied by significantly enhanced biocompatibility and photothermal conversion efficiency. More importantly, this supramolecular host-guest BPA strategy enables the resultant nanoplatform to act as a facile and efficient strategy for photodynamic and photothermal immunotherapy.

Fluorophore-mediated Photooxidation of the Guanine Heterocycle.

Fluorescent dyes are routinely used to visualize DNA or RNA in various experiments, and some dyes also act as photosensitizers capable of catalyzing oxidation reactions. The present studies explored whether the common labeling dyes fluorescein, rhodamine, BODIPY, or cyanine3 (Cy3) can function as photosensitizers to oxidize nucleic acid polymers. Photoirradiation of each dye in the presence of the guanine (G) heterocycle, which is the most sensitive toward oxidation, identified slow rates of nucleobase oxidation in the nucleoside and DNA contexts. For all four fluorophores studied, the only product detected was spiroiminodihydantoin (Sp) suggesting the dyes functioned as Type II photosensitizers and generate singlet oxygen (1O2). The nucleoside reactions were then conducted in D2O solutions, known to increase the lifetime of 1O2, which resulted in a ~6-fold increase in the Sp yield, further supporting the classification of these dyes as Type II photosensitizers. Lastly, we inspected the pattern of G reactivity with the dyes upon photoirradiation in the context of a parallel-stranded G-quadruplex. The G nucleotides in the two exterior G-tetrads were found to be oxidation prone, providing the third line of evidence that the dyes are Type II photooxidants. The present work found that the common dyes fluorescein, rhodamine, BODIPY, or Cy3 can drive G oxidation but with a slow rate and low overall yield. This will likely not impact many experiments using dyes to study nucleic acids except for those that have long exposures with high-intensity lights, such as sequencing-by-synthesis experiments using fluorescence as the readout.

Fluorescence Anisotropy Studies on Bodipy (Pyrromethene 546) Dye as a Novel Thermal Probe.

In the present work, fluorescence anisotropy studies of BODIPY (pyrromethene 546 or C14H17BF2N2) dye have been performed and found that it has a potential to be used as a thermal probe to measure the temperature of microfluid. It is well-known that a dye rotates in its excited state, so to control the molecular rotation of the dye in the excited state, sorbitol is used in the solution. It has been found that adding sorbitol, fluorescence anisotropy increases, fluorescence lifetime decreases. It has been found that adding sorbitol, temperature sensitivity increases. To study the effect of -CH2 groups on fluorescence properties, another BODIPY (pyrromethene 597 or C22H33BF2N2) dye is also used, as C14H17BF2N2 and C22H33BF2N2 have similar structures with a difference of only -8CH2 groups. It has been found that C22H33BF2N2 has superior properties over C14H17BF2N2, i.e., pyrromethene 597 shows larger temperature sensitivity as compared to pyrromethene 546, even without the addition of sorbitol.

New BODIPY Dyes Based on Benzoxazole as Photosensitizers in Radical Polymerization of Acrylate Monomers.

A series of 2-phenacylbenzoxazole difluoroboranes named BODIPY dyes (1–8) was designed and applied as photosensitizers (PS) for radical photopolymerization of acrylate monomer. The light absorption within the ultraviolet-visible (UV–Vis) range (λmax = 350–410 nm; εmax = 23,000–42,500 M−1cm−1), that is strongly influenced by the substituents on the C3 and C4 atoms of phenyl ring, matched the emission of the Omnicure S2000 light within 320–500 nm. The photosensitizer possess fluorescence quantum yield from about 0.005 to 0.99. The 2-phenacylbenzoxazole difluoroboranes, together with borate salt (Bor), iodonium salt (Iod) or pyridinium salt (Pyr) acting as co-initiators, can generate active radicals upon the irradiation with a High Pressure Mercury Lamp which initiates a high-performance UV–Vis light-induced radical polymerization at 320–500 nm. The polymers obtained are characterized by strong photoluminescence. It was found that the type of radical generator (co-initiator) has a significant effect on the kinetic of radical polymerization of acrylate monomer. Moreover, the chemical structure of the BODIPY dyes does not influence the photoinitiating ability of the photoinitiator. The concentration of the photoinitiating system affects the photoinitiating performance. These 2-phenacylbenzoxazole difluoroborane-based photoinitiating systems have promising applications in UV–Vis-light induced polymerization.

A dye-andrographolide assembly as a turn-on sensor for detection of phthalate in both cells and fish

Phthalates can penetrate the environment and enrich various aquatic organisms through the food chain, which is involved in promoting the growth of breast cancer. It is of current interest to develop new sensors for phthalates. We herein reported a hydrogen-bond competing fluorescent sensor, BANP, for the detection of dibutyl phthalate (DBP). The BANP compound was synthesized by assembling andrographolide (Andro), nitro- and cyano-substituted BODIPY dye (BCN), and polyethylene glycol derivatives (DSPE-mPEG5000). BANP was found to be a turn-on fluorescent probe for DBP in water with a detection limit of 0.13 μg/g; the DBP-water system acts as a hydrogen bond switch to turn on the fluorescence. And BANP fluorescently detected DBP in contaminated fish meat. Moreover, BANP sensed the DBP-induced growth of human breast cancer MCF-7 cells, and the release of Andro in the DBP-cultivated cancer cells inhibited the proliferation of the MCF-7 cells. Taken together, BANP is a DBP-responsive probe for sensitive DBP detection in water, cells, and fish meats. The BANP sensor may be used in both in vitro fluorescence and cellular imaging analyses. Our results show that guest-induced reassembly brings forth significant fluorescence change, which is a promising way of designing new fluorescent probes for the analysis of phthalates in the environment and food.

Robust Chemical Strategy for Stably Labeling Polyester-Based Nanoparticles with BODIPY Fluorophores.

Aliphatic polyesters are among materials most extensively used for producing biodegradable polymeric nanoparticles currently in development as delivery carriers and imaging agents for a range of biomedical applications. Their clinical translation requires robust particle labeling methodologies that allow reliably monitoring the fate of these formulations in complex biological environments. In the present study, a practical and versatile synthetic strategy providing conjugates of poly(D,L-lactide) representative of this class of polymers with BODIPY fluorophores varying in functional groups and excitation/emission maxima was investigated as a tool for making traceable nanoparticles. Polymer-probe conjugation was accomplished by carbodiimide-induced and 4-(dimethylamino)pyridinium 4-toluenesulfonate-catalyzed esterification of the polymer's terminal hydroxyl group, either directly with a carboxy-functionalized fluorophore or with amine-protected amino acids (Boc-glycine or Boc-6-aminohexanoic acid). In the latter case, the amino acid-derivatized polymeric precursors were reacted with amine-reactive BODIPY dyes after the removal of the protective group. Unlike nanoparticles encapsulating a strongly hydrophobic BODIPY505/515 (logPo/w = 4.3), nanoparticles labeled covalently with its carboxy-functionalized analogue (BODIPY FL) demonstrated stable particle-tracer association under perfect sink conditions. Furthermore, in contrast to the encapsulated dye rapidly partitioning from particles onto cell membranes but not stably retained by cultured cells, the internalization of the covalently attached probe was an irreversible process requiring the presence of serum, consistent with active nanoparticle uptake by endocytosis. In conclusion, the conjugation of particle-forming polymers with BODIPY fluorophores offers an effective and accessible labeling strategy for making traceable polyester-based biodegradable nanoparticles and is expected to facilitate their development and optimization as therapeutic carriers and diagnostic agents.

Dramatically Enhanced X-ray Scintillation of BODIPY via Sensitization by an Organic Metal Halide

X-ray scintillators based on organic chromophores have the potential to deliver low-cost radiation detection products with fast response signals. However, their relatively low performance compared with that of widely used inorganic scintillators in terms of X-ray attenuation and light output has limited their applications. Here we report a dramatically improved scintillation performance for a BODIPY dye, difluoro(4-(1,1-dimethylethyl)-2-{1-[4-1,1-dimethylethyl)-3,5-dimethyl-2H-pyrrol-2-ylidene-N] ethyl-3,5-dimethyl-1H-pyrrol-2-ylidene-N] ethyl}-3,5-dimethyl-1H-pyrrolato-N) boron (PM 570), via sensitization by a 0D organic metal halide, tetraphenylphosphonium manganese bromide ((C24H20P)2MnBr4). By blending PM 570 and (C24H20P)2MnBr4 in an appropriate ratio together in a polydimethylsiloxane matrix, we prepare plastic scintillators to exhibit a more than 15-fold increment of radioluminescence from PM 570. Such an enhancement is attributed to the excellent X-ray scintillation property of (C24H20P)2MnBr4 and the efficient energy transfer from (C24H20P)2MnBr4 to PM 570. These multicomponent plastic scintillators also exhibit an excellent linear response to the X-ray dose rate and a low detection limit of 22.5 nGy s–1.

Photoactivatable Fluorescent Tags for Dual-Modality Positron Emission Tomography Optical Imaging.

Fluorescent protein conjugates are vital tools in a wide range of scientific disciplines from basic biochemical research to applications in clinical pathology and intraoperative surgery. We report the synthesis and characterization of photoactivatable fluorophores (PhotoTags) based on the functionalization of coumarin, fluorescein, BODIPY, rhodamine B, and cyanine dyes with a photochemically active aryl azide group. Photochemical labeling experiments using human serum albumin produced fluorescent proteins in high yields under irradiation with ultraviolet light for <15 min. We also synthesized DFO-RhodB-PEG3-ArN3─a photoactivatable compound that can be radiolabeled with 89Zr for applications in optical imaging and positron emission tomography. One-pot 89Zr-radiolabeling and light-induced protein conjugation produced [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab. Proof-of-concept studies in vitro and in vivo confirmed that [89Zr]ZrDFO-RhodB-PEG3-azepin-trastuzumab is a potential dual-modality agent for detecting human epidermal growth factor receptor 2 (HER2/neu) expression. Overall, the PhotoTag technology represents a rapid, synthetically versatile, and user-friendly approach for generating novel protein conjugates.

Mitochondrion-targeting PEGylated BODIPY dyes for near-infrared cell imaging and photodynamic therapy.

A series of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-based photosensitizers (AmBXI, X = H, M, Br) featuring a cationic mitochondrion-targeting group and near-infrared (NIR) absorption was synthesized. After extending the photosensitizers' π conjugation via Knoevenagel reaction, both the absorbance and emission maxima of AmBXI shifted to the phototherapeutic wavelength range (650-900 nm). Theoretical computations indicate that the introduction of bromine atoms promotes spin-orbit coupling, so that for each additional bromine atom in AmBXI an increase in singlet oxygen quantum yield would be expected (0.3%, 2.2%, and 4.1%, for AmBHI, AmBMI, and AmBBrI, respectively). Moreover, AmBXI photosensitizers exhibited low cytotoxicity in the dark and high phototoxicity, with the half maximal inhibitory concentrations of AmBBrI found to be 46.93 nM and 22.84 nM, while those of AmBMI were 129.7 nM and 58.34 nM in HeLa and MCF-7 cancer cells, respectively. Notably, introduction of a single bromine atom was enough to produce a cytotoxic effect. Furthermore, the presence of a quaternary ammonium group in AmBXI enabled the dyes to localize and stain the negatively charged mitochondria. The results presented herein indicate the straightforward and facile synthesis of NIR-light triggered mitochondrion-targeting photosensitizers.

BINOL blocks as accessible triplet state modulators in BODIPY dyes

BINOL moieties of different electronic demand are useful blocks for enabling the photo-production and modulation of triplet excited states in readily-accesible BINOL-based O-BODIPY dyes from standard F-BODIPY precursors. The rapid and rational development of smarter triplet-enabling BODIPY dyes on the basis of this strategy (e.g., TADF biomarker 4a or room temperature phosphor 4g) paves the way for advancing photonic applications based on organic triplet photosensitizers.

Novel A-π-D-π-A-type BODIPY dyads as small-molecule donors for solution-processed organic solar cells

Two novel narrow-bandgap A-π-D-π-A-type BODIPY dyes were synthesizedviaa one-step Stille reaction with “D-π” segment at the β-site of BODIPY unit, where CTBDP-based device gave an impressive PCE of 5.85% with an excellentJscof 17.70 mA cm−2.

Microwave-assisted direct synthesis of BODIPY dyes and derivatives.

A microwave-assisted one-pot synthesis of BODIPY dyes from pyrroles and acyl chlorides is reported. This protocol features short reaction times, low temperatures, minimum amount of solvent, scalability, versatility, and good yields of the products. These simple, efficient and sustainable conditions can be also applied to the synthesis of derivatives such as BOPHY, BOAHY and BOPAHY.

In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics.

Through the activation of packing arrangements of dyes to modulate their photophysical and/or photochemical properties, not only new NIR-II dyes but tumor-specific NIR-II imaging and therapy can also be achieved. Herein, we designed an acid-responsive polypeptide nanoparticle (P-ipr@Gal) encapsulated with a pH-sensitive amphiphilic polypeptide (P-ipr) as a carrier for the galactose-conjugated BODIPY (Gal-BDP) dye. When P-ipr@Gal NPs are enriched in tumor regions by the EPR effect, the acidic microenvironment (pH 6.4-6.8) promotes the disintegration of P-ipr@Gal nanomicelles and the release of sufficient Gal-BDP. The protonation of the julolidine nitrogen of the Gal-BDP dye switched on the molecular stacking transformation from the H-aggregate to J-aggregate. The J-aggregate significantly enhanced the redshift absorption and emission intensity, which enhanced the fluorescence brightness and photothermal therapeutic effect in the tumor region. We also prepared J-aggregates PAsp@Gal with non-acidic responsive polyaspartic acid benzyl esters (PAsp) encapsulated Gal-BDP, which remained "always-on" with J-aggregate characteristics. The P-ipr@Gal (or PAsp@Gal) J-aggregate has a maximum emission peak redshifted to nearly 1064 nm, with a 3.5-fold increase in the emission intensity compared to the H-aggregate at pH 7.4. Based on the effective accumulation of tumor sites and considerable PCE (>40%), P-ipr@Gal nanoparticles have a lower background and higher tumor background ratio, which makes them a potential NIR-II imaging-guided photothermal therapy agents.

Maleimide-Functionalized Bodipy Dyes: Synthesis, Structural Determination and Conjugation with Carborane Thiols

Maleimide-Functionalized Bodipy Dyes: Synthesis, Structural Determination and Conjugation with Carborane Thiols

Silver-mediated, direct phosphorylation of BODIPY dyes at the 3- or 3,5-positions with H-phosphonates.

A direct and regioselective C-H/P-H cross-coupling of dialkyl phosphites, and diphenylphosphine oxide to easily available BODIPYs through an Ag-mediated radical addition, resulted in a series of new α-phosphorylated BODIPY fluorophores under mild conditions. Hydrolysis of the phosphonate gave the corresponding BODIPY phosphoric acid, which is soluble and fluorescent in water with a high quantum yield of 0.83.

A multicomponent reaction platform towards multimodal near-infrared BODIPY dyes for STED and fluorescence lifetime imaging.

We report a platform combining multicomponent reaction synthesis and automated cell-based screening to develop biocompatible NIR-BODIPY fluorophores. From a library of over 60 fluorophores, we optimised compound NIRBD-62c as a multimodal probe with suitable properties for STED super-resolution and fluorescence lifetime imaging. Furthermore, we employed NIRBD-62c for imaging trafficking inside cells and to examine how pharmacological inhibitors can alter the vesicular traffic between intracellular compartments and the plasma membrane.