BODIPY Dyes Research Articles

Imaging of intracellular singlet oxygen with bright BODIPY dyes

Singlet oxygen is a cytotoxic reactive species which is involved in the photodynamic therapy of cancer. It is also known to be produced endogenously in most eukaryotic cells and implicated in many biochemical processes, including apoptotic response. We now report that Bodipy based fluorescent dyes with singlet oxygen reactive modules, signal the intracellular generation of singlet oxygen through photosensitization. We believe long wavelength probes of singlet oxygen, based on this approach will be highly valuable.

Far-Red to Near Infrared Emissive Aqueous Nanoparticles Based on a New Organic Material with Three BODIPY Dyes at the Periphery of the Core: A Combined Experimental and Theoretical Study

A new organic material with three 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene dyes (BODIPYs) at the periphery of the central core is successfully synthesized (3BDP3T) and its corresponding aqueous nanoparticles are prepared via the encapsulation approach and characterized in detail both experimentally and theoretically with the aid of the Density Functional Theory (DFT). The linear and non-linear optical properties of the synthesized material are also studied. Until now, the development of organic materials with three BODIPYs as substituents is limited and their properties are not fully resolved. The obtained 3BDP3T-based nanoparticles exhibit far-red and near infrared (NIR) emission with photoluminescence quantum yields of 0.021, which is promising as a new fluorescent contrast agent in the far-red and NIR spectral regions.

A Labeling Strategy for Living Specimens in Long-Term/Super-Resolution Fluorescence Imaging.

Despite the urgent need to image living specimens for cutting-edge biological research, most existing fluorescent labeling methods suffer from either poor optical properties or complicated operations required to realize cell-permeability and specificity. In this study, we introduce a method to overcome these limits—taking advantage of the intrinsic affinity of bright and photostable fluorophores, no matter if they are supposed to be live-cell incompatible or not. Incubated with living cells and tissues in particular conditions (concentration and temperature), some Atto and BODIPY dyes show live-cell labeling capability for specific organelles without physical cell-penetration or chemical modifications. Notably, by using Atto 647N as a live-cell mitochondrial marker, we obtain 2.5-time enhancement of brightness and photostability compared with the most commonly used SiR dye in long-term imaging. Our strategy has expanded the scientist's toolbox for understanding the dynamics and interactions of subcellular structures in living specimens.

Double pH-sensitive nanotheranostics of polypeptide nanoparticle encapsulated BODIPY with both NIR activated fluorescence and enhanced photodynamic therapy.

To achieve accurate fluorescence imaging-guided cancer therapy, intelligent systems with specific responsiveness to the tumor microenvironment need to be designed. Here, we have achieved both enhanced NIR fluorescence and photodynamic therapy by introducing a dimethylamino functional group in BODIPY dyes, which can be used as a pH sensor under acidic conditions by coordinating with the proton. At pH 7.4, the fluorescence is quenched due to the photo-induced electron transfer (PET) process. After the photosensitizer is protonated in tumor cell lysosomes (pH 4.0-5.5), the PET process is inhibited and the fluorophore emission capacity is restored (fluorescence enhancement up to 10-fold), resulting in near-infrared fluorescence with the OFF/ON transition inside the tumor and enhanced singlet oxygen production for lysosome targeting capability. Due to the substitution of heavy atom iodine, the compound has a high singlet oxygen quantum yield of 81.8% in dichloromethane. In addition, using a pH-sensitive amphiphilic polypeptide (POEGMA23-PE9) as a carrier to wrap the photosensitizer BDPI can release enough drug in the acidic environment (pH 5.5-6.5) of intracellular endosomes/lysosomes, which is conducive to more adequate interactions of the photosensitizer with H+ and more effective enhancement of fluorescence emission and 1O2 production, achieving precise fluorescence imaging capability and extremely low background toxicity.

Direct C-H alkoxylation of BODIPY dyes via cation radical accelerated oxidative nucleophilic hydrogen substitution: a new route to building blocks for functionalized BODIPYs.

Oxidative nucleophilic α-hydrogen substitution is a direct method for BODIPY functionalization. However, it was hampered by the low reactivity of BODIPYs toward weak nucleophiles. Herein, we develop a cation radical accelerated oxidative nucleophilic α-hydrogen substitution reaction between BODIPY dyes and a variety of alcohols. This direct C-H alkoxylation presented a wide substrate scope and high site selectivity, providing a series of α-alkoxylated BODIPYs with diverse functional groups. Moreover, a BODIPY derivative with a pyridinium ion was developed as a new mitochondria-targeting fluorescent probe with favorable photophysical properties.

Design of BODIPY dyes as triplet photosensitizers: electronic properties tailored for solar energy conversion, photoredox catalysis and photodynamic therapy.

BODIPYs are renowned fluorescent dyes with strong and tunable absorption in the visible region, high thermal and photo-stability and exceptional fluorescence quantum yields. Transition metal complexes are the most commonly used triplet photosensitisers, but, recently, the use of organic dyes has emerged as a viable and more sustainable alternative. By proper design, BODIPY dyes have been turned from highly fluorescent labels into efficient triplet photosensitizers with strong absorption in the visible region (from green to orange). In this perspective, we report three design strategies: (i) halogenation of the dye skeleton, (ii) donor–acceptor dyads and (iii) BODIPY dimers. We compare pros and cons of these approaches in terms of optical and electrochemical properties and synthetic viability. The potential applications of these systems span from energy conversion to medicine and key examples are presented.

J-aggregation induced emission enhancement of BODIPY dyes via H-bonding directed supramolecular polymerization: the importance of substituents at boron

For uracil-functionalized BODIPY dyes 1a–c, AIEE upon H-bonding directed J-aggregation was observed for the two dyes bearing alkyne groups at boron while the BF2-chelated dye displayed ACQ, indicating the crucial role of the substituents at boron.

From photosensitizers to light harvesters adapting the molecular structure in all-BODIPY assemblies.

Herein we detail a protocol to design dyads and triads based solely on BODIPY dyes as halogen-free singlet oxygen photosensitizers or energy transfer molecular cassettes. The conducted photonic characterization reveals the key role of the BODIPY-BODIPY linkage to finely modulate the balance between the triplet state population and fluorescence decay.

Voltage-induced fluorescence lifetime imaging of a BODIPY derivative in giant unilamellar vesicles as potential neuron membrane mimics.

Fluorescence lifetime imaging (FLIM) was used to study the behaviour of a BODIPY dye in a giant unilamellar vesicle (GUV) in the presence of an electric field. The modulation of the electric field resulted in distinctive fluorescence lifetime changes in line with environment alterations within the membrane mimic.

Radiative lifetime of a BODIPY dye as calculated by TDDFT and EOM-CCSD methods: solvent and vibronic effects.

The radiative emission lifetime and associated S1 excited state properties of a BODIPY dye are investigated with TDDFT and EOM-CCSD calculations. The effects of a solvent are described with the polarizable continuum model using the linear response (LR) approach as well as state-specific methods. The Franck-Condon (FC), Herzberg-Teller (HT) and Duschinsky vibronic effects are evaluated for the absorption and emission spectra, and for the radiative lifetime. The transition energies, spectra shapes and radiative lifetime are assessed with respect to experimental results. It is found that the TDDFT transition energies are overestimated by about 0.4-0.5 eV, whereas EOM-CCSD improves the vertical emission energy by about 0.1 eV in comparison to TDDFT. The solvatochromic and Stokes shifts are better reproduced by the state-specific solvation methods, which show that these methods are more suited than the LR model to describe the solvent effects on the BODIPY dye. The vibronic effects lead to an increase of the radiative lifetime of about 0.4 to 1.0 ns depending on the theoretical approach, which highlights the importance of such effects. Moreover, the HT effects are negligible on both the spectra and lifetime, which demonstrates that the FC approximation is accurate for the BODIPY dye. Finally, the comparison with experimental data shows that the radiative lifetimes predicted by EOM-CCSD and TDDFT have comparable accuracy.

Wavelength dependent photochemistry of BODIPY-phenols and their applications in the fluorescent labeling of proteins.

A series of BODIPY dyes were synthesized, that were at the 3, or 3 and 5 positions, substituted by photochemically reactive quinone methide (QM) precursor moieties. Fluorescence properties of the molecules were investigated and we demonstrated that the molecules undergo wavelength dependent photochemistry. Photodeamination to deliver QMs takes place only upon excitation to higher excited singlet states, showing unusual anti-Kasha photochemical reactivity. The findings were corroborated by TD-DFT computations. Laser flash photolysis experiments could not reveal QMs due to the low efficiency of their formation, but enabled the detection of phenoxyl radicals. The applicability of the molecules for the fluorescent labeling of bovine serum albumin as a model protein upon photoexcitation at 350 nm was demonstrated.

Photolysis of the BODIPY dye activated by pillar[5]arene.

Here, a pseudo[3]rotaxane comprising a fluorescent BODIPY derivative and pillar[5]arene was conveniently fabricated via host–guest complexation. Importantly, in this system, the efficient photodecomposition of the BODIPY derivative in the presence of pillar[5]arene was witnessed upon irradiation at 311 nm light, which was demonstrated via UV-Vis absorption, fluorescence emission, NMR and HR-MS spectroscopy techniques, but the only BODIPY dye in the absence of pillar[5]arene couldn't undergo photodegradation. We demonstrated that pillar[5]arene could act as an activator to trigger the photodegradation reaction of BODIPY derivatives via free radical reactions even without supramolecular interactions. The present results provide a new strategy for the efficient photolysis of organic dyes.

Si-Bridged annulated BODIPYs: synthesis, unique structure and photophysical properties.

Two novel Si-bridged meso-annulated BODIPY dyes have been prepared through intermolecular C-I silylation and subsequent intramolecular C-H silylation in a one-pot reaction. A marked redshift of the main spectral bands was observed since the efficient σ*-π* conjugation results in a notable stabilization of the LUMOs. Si-annulation blocks the non-radiative decay and contributes to higher fluorescence quantum yields. This strategy is very attractive for the construction of highly emissive polycyclic aromatic hydrocarbons.

Tuning the optical properties of BODIPY dyes by N-rich heterocycle conjugation using a combined synthesis and computational approach

We report a systematic tuning of optical properties of BODIPY dyes by conjugation of nitrogen-rich heterocycles, and underlying nitrogen influence by TDDFT calculations.

Supramolecular polymerization of BODIPY dyes extended with rationally designed pyrazole-based motifs

Two distinct aggregation pathways during the supramolecular polymerization of BODIPY dyes functionalized with rationally designed pyrazole-based motifs have been investigated.

Sensitive and effective imaging of carbon monoxide in living systems with a near-infrared fluorescent probe.

CO, a gas molecule that is harmful to living organisms, has a high affinity with hemoglobin, which will cause severe hypoxia. However, in recent years, researchers have discovered that endogenous CO, similar to NO, is one of the messenger molecules, which has a certain regulatory effect in many physiological and pathological processes in the respiratory system, cardiovascular system, and nervous system. Therefore, it is urgent to explore an effective method to monitor the role of CO under physiological and pathological conditions. Herein, we designed and synthesized a near-infrared small-molecule fluorescent probe for the detection of CO in living cells. In this design, a two-site BODIPY dye was introduced as the fluorophore, and the allyl chloroformate part as the CO reactive group. The probe displays excellent sensitivity, selectivity, and a good linear relationship to CO. Furthermore, it shows good biocompatibility and low cytotoxicity. This probe has been successfully applied to the detection of CO in a variety of cells. The developed fluorescent probe can serve as a potential molecular imaging tool for in vivo imaging and detection of CO.

A water caged BODIPY as fluorescence sensor of phthalates

Abstract Phthalates esters (PAEs) have been used as plasticizers, which contributes to some cancers and endocrine dyscrasia. Here we reported a BODIPY fluorescent dye ((3-(4-(5,5-difluoro-2-(4-(hydroxymethyl)phenyl))-1,3,7,9-tetramethyl-5H-5l4,6l4-Bispyrrole[1,2-c:2′,1′-f] [1,3,2]borothiaserine-10-yl)phenyl)-2-(4-nitro)phenylnier (BCNOH)) modified with p-nitrodiphenylacrylonitrile, and hydroxymethyl phenyl group for the affinity and sensing of PAEs. BCNOH formed non-emission water caged BCNOH, which was turned on by PAEs. Fluorescence, UV and Density functional theory (DFT) calculation were performed to research the mechanism. Results demonstrate that PAEs assembled with water caged BCNOH producing nano fluorescence dyes (nano-BCNOH), in which BCNOH is E isomerization. The binding ratio of BCNOH and DBP is 1:10, and the detection limit of PAEs is related to the chain length of phthalates. Hydroxymethyl phenyl group of BCNOH increased the attachment with DBP, and the interaction of DBP and p-nitrodiphenylacrylonitrile was the trigger to turn on the fluorescence emission. Moreover, the water caged BCNOH was used for the detection of PAEs in rice yellow wine and liquor and spirits. Results indicate that attenuating the isomerization of water caged BODIPY dyes will be a potential strategy for the development of turn-on fluorescence sensors.

Detection of volatile marker in the wheat infected with Aspergillus flavus by porous silica nanospheres doped Bodipy dyes

Abstract Current work presented a new colorimetric sensor based on nano-porous modified NO2BDP pigment for the detection of volatile markers in wheat infected by Aspergillus flavus (A. flavus). Firstly, principal component analysis (PCA) load factor analysis was performed on each volatile organic compounds (VOCs) detected by gas chromatography-mass spectrometry (GC–MS) from the infected wheat samples. It was found that the content of 1-Octen-3-ol increased with the rise of the A. flavus number (Pearson Correlation of 0.983). The synthesized porous silica nanosphere was modified to fabricate the colorimetric sensor. The content of 1-Octen-3-ol could be accurately quantified within 6 ppm using nano-porous modified NO2BDP pigments in the gas mixture from the infected wheat, which was more sensitive than the conventional boron-dipyrromethene (Bodipy) pigment. Finally, the proposed colorimetric sensor was applied to analyze 108 wheat samples with different degrees of A. flavus infection. As a result, 98 % of infected wheat samples (with the concentration of A. flavus from 3.0–7.0 lgCFU/g) were correctly identified using linear discriminant analysis (LDA) model. Based on the achieved results, this work demonstrated that nano-porous modified NO2BDP pigment was an effective way for non-destructive detection of A. flavus infection in wheat.

High-Efficiency FRET Processes in BODIPY-Functionalized Quantum Dot Architectures.

Efficient FRET systems are developed combining colloidal CdSe quantum dots (QDs) donors and BODIPY acceptors. To promote effective energy transfer in FRET architectures, the distance between the organic fluorophore and the QDs needs to be optimized by a careful system engineering. In this context, BODIPY dyes bearing amino-terminated functionalities are used in virtue of the high affinity of amine groups in coordinating the QD surface. A preliminary QD surface treatment with a short amine ligand is performed to favor the interaction with the organic fluorophores in solution. The successful coordination of the dye to the QD surface, accomplishing a short donor-acceptor distance, provides effective energy transfer already in solution, with efficiency of 76 %. The efficiency further increases in the solid state where the QDs and the dye are deposited as single coordinated units from solution, with a distance between the fluorophores down to 2.2 nm, demonstrating the effectiveness of the coupling strategy.

Pathway and Length Control of Supramolecular Polymers in Aqueous Media via a Hydrogen Bonding Lock.

Programming the organization of π‐conjugated systems into nanostructures of defined dimensions is a requirement for the preparation of functional materials. Herein, we have achieved high‐precision control over the self‐assembly pathways and fiber length of an amphiphilic BODIPY dye in aqueous media by exploiting a programmable hydrogen bonding lock. The presence of a (2‐hydroxyethyl)amide group in the target BODIPY enables different types of intra‐ vs. intermolecular hydrogen bonding, leading to a competition between kinetically controlled discoidal H‐type aggregates and thermodynamically controlled 1D J‐type fibers in water. The high stability of the kinetic state, which is dominated by the hydrophobic effect, is reflected in the slow transformation to the thermodynamic product (several weeks at room temperature). However, this lag time can be suppressed by the addition of seeds from the thermodynamic species, enabling us to obtain supramolecular polymers of tuneable length in water for multiple cycles.