BODIPY Research Articles

A boron dipyrromethene chiral at boron and carbon with a bent geometry: synthesis, resolution and chiroptical properties.

We report a boron dipyrromethene that is chiral at boron and carbon (B*C*-BODIPY) and accessible through a two-pot, one-step synthesis-an interrupted Knoevenagel condensation. The electronic circular dichroism spectra of chiral high performance liquid chromatography-resolved enantiomers show clear Cotton effects (∣gabs∣ ∼ 2.0 × 10-4) in the visible region, suggesting efficient chirality induction to the otherwise achiral BODIPY. The dye's unusually weak fluorescence (Φfl < 0.01) is attributed partly to vibrational relaxations, as revealed by viscosity experiments, and partly to probable intersystem crossing that may be facilitated by the reduced symmetry of the bent-shaped molecular geometry.

Near-infrared irradiation controlled thermo-switchable polymeric photosensitizer against β-amyloid fibrillation.

Photothermal therapy (PTT) is an emerging paradigm for the degradation of amyloid-β (Aβ) aggregations and has become an effective way of treating Alzheimer's disease (AD). A promising PTT therapeutic option requires control of at least two key functional aspects: controllable photoactivity and specific activation. In this work, a near-infrared (NIR)-activated thermo-switchable biopolymeric PTT agent was designed and synthesized by conjugating a molecular rotor-based boron dipyrromethene photosensitizer (BDP) to a temperature-responsive polymer backbone of biopolymeric hydroxypropyl cellulose (HPC). The as-synthesized BDP-HPC exhibited an ultra-high PCE of 78.1% along with prominent cycling stability of phase-transition behavior under NIR irradiation in the light of the lower critical solution temperature (LCST at 42.5 °C). Importantly, the NIR irradiation can manipulate the reversible phase transition behavior of the resultant BDP-HPC that reveals high effectiveness in inhibiting Aβ aggregation together with the obvious ability to dissociate Aβ aggregations. Our work reveals an accurate modulation strategy for versatile and high-performance AD treatment.

BODIPY-based metal-organic frameworks as efficient electrochemiluminescence emitters for telomerase detection.

A boron dipyrromethene (BODIPY)-based metal-organic framework (MOF) nanoemitter was for the first time designed with enhanced electrochemiluminescence (ECL) intensity due to the suppression of non-radiative dissipation originating from the ordered arrangement of BODIPY molecules in the framework. Thus, an ECL biosensor was developed for telomerase detection with excellent performance in real samples.

Progress in the Synthesis of Boron Dipyrromethene (BODIPY) Fluorescent Dyes

Progress in the Synthesis of Boron Dipyrromethene (BODIPY) Fluorescent Dyes

Exploring halogen⋯halogen interactions in supramolecular self-assemblies of BODIPY networks

In this study, the efficiency of halogen⋯halogen interactions to control supramolecular assemblies of boron dipyrromethene (BODIPY) (B1–B5) derivatives was explored.

Photo-induced Morphological Changes of Lipid Bilayer Vesicles Enabled by a Visible-Light-Responsive Azo Compound.

Living cells and organelles are separated by a lipid membrane bilayer. It is possible to induce morphological changes in this membrane by disturbing the order of the membrane using external stimuli and understanding the details of this mechanism is expected to be applicable to intracellular transport. DBA (DBAB-BODIPY-aminopropyl), which contains (1) a DBAB (4-[di(biphenyl-4-yl)amino]azobenzene) moiety that undergoes photo-isomerization under visible light irradiation, and (2) a BODIPY (borondipyrromethene) fluorophore was synthesized. The π-π* transition absorptions of both the azo moiety and that of BODIPY moiety in DBA were observed, independently. The photo-isomerization rate constant of the DMSO solution of DBA at 299K is 5.5 ×10-3/s. The structure of the fluorescent group in DBA did not readily influence the isomerization. Upon introducing DBA into the lipid bilayer membranes of a vesicle suspension and irradiating the vesicles with visible light to isomerize the azo group, a morphological change in of the vesicles was observed due to the disturbance of the membrane order. Thus, DBA is a useful molecule for artificial modulation of the lipid membrane morphology.

A Highly Selective and High-Contrast Colorimetric “Off-On” Chemosensor for Cu2＋ Based on Boron-Dipyrromethene (BODIPY) Derivatives

A Highly Selective and High-Contrast Colorimetric “Off-On” Chemosensor for Cu^2＋ Based on Boron-Dipyrromethene (BODIPY) Derivatives

Red light active Pt(iv)-BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent.

A cisplatin-based platinum(iv) prodrug, [Pt(NH3)2Cl2(OH)(L 1 )], having L 1 as a red-light active boron-dipyrromethene (BODIPY) pendant, was synthesized and characterized and its application as a chemo-cum-photodynamic therapy agent was studied. Me-L 1 as the ligand precursor is structurally characterized. The complex displayed an intense absorption band near 650 nm (ε ∼ 8.8 × 104 dm3 mol-1 cm-1) in 1 : 1 (v/v) DMSO/DPBS. It showed an emission band at 674 nm (λ ex = 630 nm) with a fluorescence quantum yield (Φ F) value of 0.37. In red light (600-720 nm), it generated singlet oxygen as evidenced from the 1,3-diphenylisobenzofuran (DPBF) titration experiment giving a singlet oxygen quantum yield (Φ Δ) value of 0.28 in DMSO. The mechanistic pUC19 DNA photocleavage study and singlet oxygen sensor green (SOSG) assay ascertained its ability to generate singlet oxygen in both extracellular and intracellular media by a type-II photo-process. The complex exhibited high stability in the dark, but on red-light irradiation, it displayed rapid activation in the presence of a reducing environment. It displayed remarkable apoptotic photocytotoxicity with half-maximal inhibitory concentration (IC50) ranging from 0.58 to 0.76 μM in human cervical cancer (HeLa) and breast cancer (MCF-7) cells with a respective photo-cytotoxicity index value of >172 and >131. The photodynamic activity was significantly less in non-cancerous human peripheral lung epithelial (HPL1D) cells. The emissive complex showed localization in the mitochondria and endoplasmic reticulum (ER) with a similar Pearson's correlation coefficient value, making it a dual organelle-targeted therapeutic agent. JC-1, fluo-4-AM and annexin V-FITC/propidium iodide assays in HeLa cells showed cellular apoptosis by arresting cells in the sub-G1 phase via mitochondrial dysfunction and ER stress.

Design of a graphene oxide-BODIPY conjugate for glutathione depletion and photodynamic therapy

Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol derivatisation with the phenyl boronic acid moiety at the meso position of the BODIPY core, allowed to preserve the intrinsic properties of GO. We demonstrated that both chlorine atoms were substituted by GSH in the presence of glutathione transferase (GST), inducing a relevant bathochromic shift in the absorption/emission features and thus generating the active PS. Ex vitro assessment using cell lysates containing cytoplasmatic GST revealed the intracellular catalytic mechanism for the nucleophilic substitution of the GO-BODIPY adduct with GSH. Confocal microscopy studies showed important differences in the cellular uptake of free BODIPY and GO-BODIPY and revealed the coexistence of GO-BODIPY, GO-BODIPY-GS, and GO-BODIPY-GS2 species inside vesicles and in the cytoplasm of the cells after 24 h of incubation. In vitro biocompatibility and safety of GO and GO-BODIPY were evaluated in 2D and 3D models of prostate adenocarcinoma cells (PC-3), where no toxicity was observed up to 100 µg ml−1 of GO/GO-BODIPY in all treated groups 24 h post-treatment (cell viability > 90%). Only a slight decrease to 80% at 100 µg ml−1 was observed after 48 h of incubation. We demonstrated the efficacy of a GO adduct containing an α-chlorine-substituted BODIPY for the simultaneous depletion of intracellular GSH and the photogeneration of reactive oxygen species using a halogen white light source (5.4 mW cm−2) with a maximum in the range of 500–800 nm, which significantly reduced cell viability (<50%) after irradiation. Our study provides a new vision on how to apply BODIPY derivates and potentiate the toxicity of PDT in prostate and other types of cancer.

Cascades of energy and electron transfer in a panchromatic absorber.

The investigation of molecular model systems is fundamental towards a deeper understanding of key photochemical steps in natural photosynthesis. Herein, we report an entirely non-covalent triad consisting of boron dipyrromethene (BDP), porphyrin (ZnP), and fullerene (C60). Non-covalent binding motifs such as an amidinium-carboxylate salt bridge as well as axial pyridyl-metal coordination offer substantial electronic coupling and establish efficient pathways for photoactivated energy and electron transfer processes along a well-tuned gradient. Experimental findings from steady-state and time-resolved spectroscopic assays, as well as (spectro-)electrochemical measurements corroborate the formation of BDP|ZnP|C60 in solution, on one hand, and significant communication in the excited states, on the other hand. BDP acts as an energy harvesting antenna towards ZnP, which eventually undergoes charge separation with C60 by electron transfer from ZnP to C60. Notably, full spectral deconvolution of the transient species was achieved, supporting the successful self-assembly as well as giving a clear view onto the occurring photophysical processes and their spectral footprints upon photoexcitation.

Ruthenium-catalyzed acceptorless dehydrogenative coupling of amino alcohols and ynones to access 3-acylpyrroles.

Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones via ruthenium-catalyzed acceptorless dehydrogenative coupling has been demonstrated. This developed methodology proceeds in an atom- and step-economic fashion together with the merits of broad substrate scope, operational simplicity, and water and hydrogen gas as the sole by-products, which provides an alternative and sustainable way to access functionalized pyrroles. Further, this method was applied to the rapid synthesis of the COX-1/COX-2 inhibitor and boron dipyrromethene derivative successfully.

Using BODIPY FL-Sphingolipid Analogs to Study Sphingolipid Metabolism in Mouse Embryonic Stem Cells.

Sphingolipids are important structural components of cellular membranes. They also function as prominent signaling molecules to control a variety of cellular events, such as cell growth, differentiation, and apoptosis. Impaired sphingolipid metabolism, particularly defects in sphingolipid degradation, has been associated with many human diseases. Fluorescence sphingolipid analogs have been widely used as efficient probes to study sphingolipid metabolism and intracellular trafficking in living mammalian cells. Compared with nitrobenzoxadiazole fluorophores (NBD FL), the boron dipyrromethene difluoride fluorophores (BODIPY FL) have much higher absorptivity and fluorescence quantum. These features allow more intensive labeling of cells for fluorescence microscopy imaging and flow cytometry analysis. Here, we describe a protocol employing BODIPY FL-labeled sphingolipid analogs to elucidate sphingolipid internalization, trafficking, and endocytosis in mouse embryonic stem cells. This protocol was validated in: eLife (2022), DOI: 10.7554/eLife.67452 Graphical abstract.

Galactose conjugated boron dipyrromethene and hydrogen bonding promoted J-aggregates for efficiently targeted NIR-II fluorescence assistant photothermal therapy

It is essential to develop novel multifunctional and easily synthesized stable NIR-II fluorescent probes to guide photothermal therapy for tumors. Here, we propose a new strategy to construct boron dipyrromethene (BODIPY) J-aggregates by intermolecular hydrogen bonding (H-bond) and π-π stacking interactions to achieve fluorescence emission in the second near-infrared window (NIR-II, 1000–1700 nm). A novel meso-benzamide galactose hexanoate-BODIPY (Gal-OH-BDP) amphiphilic small molecular dye was synthesized and it formed nanoparticles spontaneously in aqueous solution with a maximum emission wavelength near 1060 nm, which works as a smart nanomedicine for targeting NIR-II imaging-guided photothermal therapy (PTT) of hepatocellular carcinoma. Galactose not only provided hydrogen bonds to regulate the aggregation pattern of the molecules but also effectively targeted hepatocellular carcinoma cells and promoted the formation of well-dispersed nanoparticles of dye molecules due to their hydrophilicity. Moreover, due to high photothermal conversion efficiency (PCE = 55%), Gal-OH-BDP NPs achieve galactose-targeted NIR-II imaging and PTT, which is important for the precise diagnosis and treatment of tumors (Scheme 1). In the present research work, H-bond was introduced for the first time into BODIPY for building J-aggregates to achieve the NIR-II fluorescence.

Fluorescence Sensing of Glutathione Thiyl Radical by BODIPY‐Modified β‐Cyclodextrin

Comprehensive SummaryThe fluorescence sensing of intracellular glutathione thiyl radical (GS•) is in great demand to seek the GS•‐related pathophysiological events. Herein, boron−dipyrromethene (BODIPY)‐modified β‐cyclodextrin was developed for high‐efficiency sensing of GS•, accompanied by a fast response time (t1/2 = 218 s), with the detection limit of 468 nmol/L. Cell experiments indicated that the BODIPY‐ modified β‐cyclodextrin could be applied to detect the GS• in live A549 cells.

Stereoselective Cyclopropanation of Boron Dipyrromethene (BODIPY) Derivatives by an Organocascade Reaction

AbstractThe synthesis of enantiopure chiral boron dipyrromethenes (BODIPYs) is of importance due the intrinsic properties of BODIPYs as fluorophores that could be used as probes for molecular sensing. The present study reports an asymmetric organocatalytic cascade reaction of meso‐chloromethyl BODIPY derivatives with α,β‐unsaturated aldehydes catalyzed by a chiral secondary amine. The corresponding BODIPY‐derived cyclopropanes were produced in isolated yields 66–98%, and with diastereomeric ratios 3/2–&gt;20/1, and 92–99% ee for major diastereomer. The synthetic utility of the protocol was exemplified on a set of additional transformations of the corresponding optically pure compounds. In addition, a study explaining the reaction mechanism (DFT computations) and photophysical characterization of all enantioenriched products were accomplished.magnified image

Identification of diverse lipid-binding modes in the groove of zinc α2 glycoprotein reveals its functional versatility.

ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16 -BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16 -BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related Cluster of differentiation 1 proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16 -BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16 -BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16 -BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16 -BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16 -BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand.

Tracking Labile Copper Fluctuation In Vivo/Ex Vivo: Design and Application of a Ratiometric Near-Infrared Fluorophore Derived from 4-Aminostyrene-Conjugated Boron Dipyrromethene.

Specimen differences, tissue-dependent background fluorescence and scattering, and deviated specimen position and sensor concentration make optical imaging for labile copper fluctuation in animals questionable, and a signal comparison between specimens is infeasible. We proposed ratiometric optical imaging as an alternative to overcome these disadvantages, and a near-infrared (NIR) ratiometric sensor, BDPS1, was devised therefore by conjugating boron dipyrromethene (BODIPY) with 4-aminostyrene and modifying the 4-amino group as a Cu+ chelator. BDPS1 possessed an excitation ratiometric copper-sensing ability to show the ratio of NIR emission (710 nm) upon excitation at 600 nm to that at 660 nm, Fex600/Fex660, increasing from 2.8 to 10.7. This sensor displayed still the opposite copper response of its internal charge transfer (ICT; 670 nm) and local (581 nm) emission bands. Ratiometric imaging with this sensor disclosed a higher labile copper region near the nucleus apparatus, and HEK-293T cells were more sensitive to copper incubation than MCF-7 cells. Dual excitation ratiometric imaging with this sensor realized tracking of labile copper fluctuation in mice, and the whole-body imaging found that tail intravenous injection of CUTX-101, a therapeutical agent for Menkes disease, led to a distinct labile copper increase in the upper belly. The ex vivo imaging of the resected viscera of mice revealed that CUTX-101 injection enhanced the labile copper level in the liver, intestine, lung, and gall bladder in sequence, yet the kidney, heart, and spleen showed almost no response. This study indicated that modifying BODIPY as an extended ICT fluorophore, with its electron-donating group being derived as a metal chelator, is an effective design rationale of NIR ratiometric sensors for copper tracking in vivo/ex vivo.

The multifunctional BODIPY@Eu-MOF nanosheets as bioimaging platform: A ratiometric fluorescencent sensor for highly efficient detection of F-, H2O2 and glucose

The highly emissive BODIPY (boron-dipyrromethene) have been grafted on the Eu-based metal-organic frameworks (Eu-MOFs) via the covalent F-B bonding using a facile one-pot solvothermal reaction. The fluorescence emission ratio of BODIPY@Eu-MOF has been applied to construct the ratiometric fluorescence sensor for the F-, H2O2 and glucose detection in water solution and living cells. The produced BODIPY@Eu-MOF probe provided enhanced sensitivity, higher selectivity and lower lower limits of detection (LOD) for the detection of F- (0.1737 μM), H2O2 (6.22 nM) and glucose (6.92 nM), and 5.96, 6.52 and 6.95 times lower than that for single Eu-MOF, respectively. More importantly, the probe also exhibited the lower biotoxic in living cells for bioimaging and the better visualization performance with multiplex channels. The results indicated the π-conjugated BODIPY derivative not only acted as the surfactant molecule or template agent for preferred growth, but also modulated the fluorescent emissions drastically, and thus induced excellent fluorescent detecting performances.

Synthesis of Functionalized Silsesquioxane Nanomaterials by Rhodium-Catalyzed Carbene Insertion into Si-H Bonds.

We report carbene insertion into Si-H bonds of polyhedral oligomeric silsesquioxanes (POSS) for the synthesis of highly functionalized siloxane nanomaterials. Dirhodium(II) carboxylates catalyze insertion of aryl-diazoacetates as carbene precursors to afford POSS structures containing both ester and aryl groups as orthogonal functional handles for further derivatization of POSS materials. Four diverse and structurally varied silsesquioxane core scaffolds with one, three, or eight Si-H bonds were evaluated with diazo reactants to produce a total of 20 new POSS compounds. Novel diazo compounds containing a fluorinated octyl group and boron-dipyrromethene (BODIPY) chromophore demonstrate the use of highly functionalized substrates. Transformations of aryl(ester)-functionalized POSS compounds derived from this method are demonstrated, including ester hydrolysis and Suzuki-Miyaura cross-coupling.

Synthesis of Functionalized Silsesquioxane Nanomaterials by Rhodium‐Catalyzed Carbene Insertion into Si−H Bonds

AbstractWe report carbene insertion into Si−H bonds of polyhedral oligomeric silsesquioxanes (POSS) for the synthesis of highly functionalized siloxane nanomaterials. Dirhodium(II) carboxylates catalyze insertion of aryl‐diazoacetates as carbene precursors to afford POSS structures containing both ester and aryl groups as orthogonal functional handles for further derivatization of POSS materials. Four diverse and structurally varied silsesquioxane core scaffolds with one, three, or eight Si−H bonds were evaluated with diazo reactants to produce a total of 20 new POSS compounds. Novel diazo compounds containing a fluorinated octyl group and boron‐dipyrromethene (BODIPY) chromophore demonstrate the use of highly functionalized substrates. Transformations of aryl(ester)‐functionalized POSS compounds derived from this method are demonstrated, including ester hydrolysis and Suzuki–Miyaura cross‐coupling.