4-4-difluoro-4-bora-3a-4a-diaza-s-indacene and dipyrromethene

Boron-dipyrromethene (BODIPY) and its derivatives play an important role in the area of organic fluorophore chemistry. Recently, the water-soluble boron-dipyrromethene dyes have increasingly received interest. The structural modification of the BODIPY core by incorporating different neutral and ionic hydrophilic groups makes it water-soluble. The important hydrophilic groups, such as quaternary ammonium, sulfonate, oligoethylene glycol, dicarboxylic acid, and sugar moieties significantly increase the solubility of these dyes in water while preserving their photophysical properties. As a result, these fluorescent dyes are utilized in aqueous systems for applications such as chemosensors, cell imaging, anticancer, biolabeling, biomedicine, metal ion detection, and photodynamic treatment. This review covers the most current developments in the design and synthesis of water-soluble BODIPY derivatives and their wide applications since 2014.

Topics: Boron; Fluorescent Dyes; Water

We present an overview of the state of the art in long-wavelength boron-dipyrromethene (BODIPY) fluorophores, focusing on strategies to shift the absorption and emission bands into the red/near-infrared (NIR) range of the spectrum. This report also discusses chemical modifications of the chromophoric core to obtain analyte-responsive fluorophores, including examples of pH and metal ion indicators. Finally, we present a new series of phenanthrene-fused BODIPY dyes, emitting with high efficiency in the red/NIR region of the spectrum, as well as discussing potential applications thereof as probes.

Topics: Boron; Boron Compounds; Fluorescent Dyes; Hydrogen-Ion Concentration; Ions; Metals; Models, Chemical; Molecular Structure; Phenanthrenes; Porphobilinogen; Solvents; Spectrophotometry; Spectroscopy, Near-Infrared; Temperature

Topics: Boron; Boron Compounds; Cysteine; Fluorescent Dyes; Glutathione; Hep G2 Cells; Humans; Spectrometry, Fluorescence; Sulfhydryl Compounds

A low-cost and simple boron-dipyrromethene (BODIPY)-labeled aptasensor (B-aptamer) was designed for rapid, sensitive and turn-on catechin detection. B-aptamer as signal indicator and recognition element initially stacked on the surface of multi-walled carbon nanotubes (MWCNTs) via π-π conjugation, resulting in efficient quenching of the fluorescence of the aptasensor. Upon addition of catechin, catechin was adsorbed to B-aptamer, thereby undergoing a conformational change to form B-aptamer/catechin complex, which prompted the release of the signaling probe from the surface of MWCNTs. Hence, the fluorescence intensity (FL) of the B-aptamer was increasing with the increase of catechin concentrations with the limit of detection (LOD) of 5 ng/mL. Furthermore, the method was used to analyze catechin in food samples with the recovery rate of 92.7-107.1 %. This method provided a proper analysis method for clinical analysis and pharmaceutical quality control.

Topics: Aptamers, Nucleotide; Biosensing Techniques; Boron; Catechin; Limit of Detection; Nanotubes, Carbon

Singlet oxygen (

Topics: Alzheimer Disease; Boron; Humans; Neuronal Outgrowth; Photosensitizing Agents; Protein Aggregates; Ruthenium; Singlet Oxygen; tau Proteins

The work is devoted to preparing and characterizing the properties of photosensitive composites, based on chitosan proposed for photodynamic therapy. Chitosan films with a 5% addition of two BODIPY dyes were prepared by solution casting. These dyes are dipyrromethene boron derivatives with N-alkyl phthalimide substituent, differing in the presence of iodine atoms in positions 2 and 6 of the BODIPY core. The spectral properties of the obtained materials have been studied by infrared and UV-vis absorption spectroscopy and fluorescence, both in solutions and in a solid state. Surface properties were investigated using the contact angle measurement. The morphology of the sample has been characterized by Scanning Electron and Atomic Force Microscopy. Particular attention was paid to studying the protein absorption and kinetics of the dye release from the chitosan. Adding BODIPY to the chitosan matrix leads to a slight increase in hydrophilicity, higher structure heterogeneity, and roughness, than pure chitosan. The presence of iodine atoms in the BODIPY structure caused the bathochromic effect, but the emission quantum yield decreased in the composites. It has been found that BODIPY-doped chitosan interacts better with human serum albumin and acidic α-glycoprotein than unmodified chitosan. The release rate of dyes from films immersed in methanol depends on the iodine present in the structure.

Topics: Boron; Chitosan; Fluorescent Dyes; Humans

Antimicrobial photodynamic therapy (aPDT) is an effective strategy to eliminate bacteria without inducing bacterial resistance. As typical aPDT photosensitizers, most of boron-dipyrromethene (BODIPY) are hydrophobic, and nanometerization is imperative to render them dispersible in physiological media. Recently, carrier-free nanoparticles (NPs) are formed via the self-assembly of BODIPYs without the help of any surfactants or auxiliaries, arousing people's interest. So as to fabricate carrier-free NPs, BODIPYs usually need to be derived into dimers, trimers, or amphiphiles through complex reactions. Few unadulterated NPs were obtained from BODIPYs with precise structures. Herein, BNP1-BNP3 were synthesized by the self-assembly of BODIPY, which showed excellent anti-Staphylococcus aureus ability. Among them, BNP2 could effectively fight bacterial infections and promote wound healing in vivo.

Topics: Anti-Bacterial Agents; Boron; Humans; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Staphylococcal Infections; Wound Healing

In vivo optical imaging is an important application value in disease diagnosis. However, near-infrared nanoprobes with excellent luminescent properties are still scarce. Herein, two boron-dipyrromethene (BODIPY) molecules (BDP-A and BDP-B) were designed and synthesized. The BODIPY emission was tuned to the near-infrared (NIR) region by regulating the electron-donating ability of the substituents on its core structure. In addition, the introduction of polyethylene glycol (PEG) chains on BODIPY enabled the formation of self-assembled nanoparticles (NPs) to form optical nanoprobes. The self-assembled BODIPY NPs present several advantages, including NIR emission, large Stokes shifts, and high fluorescence quantum efficiency, which can increase water dispersibility and signal-to-noise ratio to decrease the interference by the biological background fluorescence. The in vitro studies revealed that these NPs can enter tumor cells and illuminate the cytoplasm through fluorescence imaging. Then, BDP-B NPs were selected for use in vivo imaging due to their unique NIR emission. BDP-B was enriched in the tumor and effectively illuminated it via an enhanced penetrability and retention effect (EPR) after being injected into the tail vein of mice. The organic nanoparticles were metabolized through the liver and kidney. Thus, the BODIPY-based nanomicelles with NIR fluorescence emission provide an effective research basis for the development of optical nanoprobes in vivo.

Topics: Animals; Boron; Fluorescence; Mice; Nanoparticles

Phototheranostics integrating optical imaging and phototherapy has attracted extensive attention. Achieving nanophototherapeutics with near infrared (NIR)-light synchronously triggered photodynamic therapy (PDT) and photothermal therapy (PTT) is challenging. Herein, we develop a multifunctional theranostic nanoplatform prepared from the co-assembly of NIR boron dipyrromethene (BODIPY) with a cooperative D-π-A structure of a thiophene-BODIPY core and benzene-diethylamino, and a choline phosphate lipid. The as-fabricated nanoparticles (DBNPs) exhibited desirable NIR absorption, uniform spherical morphology and good colloidal stability. The elaborate molecular design and supramolecular assembly endowed DBNPs with desirable PDT and PTT activities. Upon 808 nm laser irradiation, the DBNPs efficiently generated active singlet oxygen and regional hyperpyrexia, with a photothermal conversion efficiency of 37.6%. The excellent PDT and PTT performance of DBNPs boosted the potent

Topics: Boron; Humans; Lipids; Nanoparticles; Neoplasms; Optical Imaging; Phosphorylcholine

Heavy-atom-free photosensitizers are envisioned as the next generation of photoactive molecules for photo-theragnosis. In this approach, and after suitable irradiation, a single molecular scaffold is able to visualize and kill tumour cells by fluorescence signalling and photodynamic therapy (PDT), respectively, with minimal side effects. In this regard, BODIPY-based orthogonal dimers have irrupted as suitable candidates for this aim. Herein, we analyse the photophysical properties of a set of formyl-functionalized BODIPY dimers to ascertain their suitability as fluorescent photosensitizers. The conducted computationally aided spectroscopic study determined that the fluorescence/singlet oxygen generation dual performance of these valuable BODIPY dimers not only depends on the BODIPY-BODIPY linkage and the steric hindrance around it, but also can be modulated by proper formyl functionalization at specific chromophoric positions. Thus, we propose regioselective formylation as an effective tool to modulate such a delicate photonic balance in BODIPY-based dimeric photosensitizers. The taming of the excited-state dynamics, in particular intramolecular charge transfer as the key underlying process mediating fluorescence deactivation vs. intersystem crossing increasing, could serve to increase fluorescence for brighter bioimaging, enhance the generation of singlet oxygen for killing activity, or balance both for photo-theragnosis.

Topics: Boron; Boron Compounds; Photochemotherapy; Photosensitizing Agents; Singlet Oxygen

Topics: Boron; Cisplatin; Ligands; Light; Mitochondria; Photochemotherapy; Photosensitizing Agents; Platinum

A boron dipyrromethene (BODIPY) derivative bearing a

Topics: Boron; Boron Compounds; Porphobilinogen; Proline

We report N,O-boron-chelated dipyrromethene derivatives exhibiting circularly polarized luminescence (CPL) in the red/near-infrared region, both in solution and the aggregated state. The CPL is originated from the helical chirality through intramolecular substitution of fluorine by an alkenolic substituent. The self-assembly of the fluorophores significantly enhances the |

Topics: Boron; Boron Compounds; Luminescence; Porphobilinogen

There is an urgent need to develop efficient and safe antimicrobials to augment traditional antibiotics for fighting drug-resistant bacteria. Antimicrobial photodynamic therapy (aPDT), is a promising antimicrobial stize antibiotic resistance and may reduce systemic side effects. Boron-dipyrromethene (BODIPY) is a type of photosensitizer (PSs) for aPDT with tunable structures and rational photophysical features. Herein, six kinds of BODIPY derivatives (BDP1-BDP6) modified with different atoms or groups such as iodine atoms, thiophene, cyano, phenyl, aldehyde and nitro groups were synthesized and their photophysical behaviors were characterized. The results indicated that BDP3, which had 2, 6-diiodo and 8-phenyl substitution, was the best PS candidate with the highest reactive oxygen species (ROS) generation efficacy. BDP3 and BDP5 could rapidly kill Staphylococcus aureus (S. aureus) with the minimum inhibitory concentration (MIC) of 10 nM upon illumination. They also possessed excellent biofilm inhibition ability against S. aureus and could efficaciously restrain the formation of bacterial biofilm. The results of Live/Dead staining assay and scanning electron microscopy (SEM) demonstrated that BDP3 destroyed the cell membrane structure of bacteria by generating ROS, which ultimately led to bacterial lysis and death. Finally, the biosafety evaluation toward the mouse fibroblasts (L929 cells) suggested BDP3 had good cytocompatibility. This work exhibits the great potential of rational designs of PS for aPDT applications.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Boron; Boron Compounds; Mice; Photochemotherapy; Photosensitizing Agents; Porphobilinogen; Reactive Oxygen Species; Staphylococcus aureus

The linear and nonlinear optical properties of two BODIPY derivatives, 1,7-Diphenyl-3,5-bis(9,9-dimethyl-9H-fluoren-2-yl)-boron-diuoride-azadipyrromethene (ZL-61) and 1,7-Diphenyl-3,5-bis(4-(1,2,2-triphenylvinyl)phenyl)-boron-diuoride-azadipyrromethene (ZL-22), were comprehensively investigated based on experimental and theoretical studies. It was found that both compounds show a strong two-photon absorption response in the near-infrared regime, and the two-photon-absorption cross-section values of ZL-61 and ZL-22 were determined to be 8321 GM and 1864 GM at 800 nm, respectively. The improvement of the two-photon absorption cross section in ZL-61 was attributed to the enhancement of the donor group, which was confirmed by transient absorption measurements and DFT calculation. Our results indicate that these BODIPY derivatives are a promising candidate for optical limiting and two-photon imaging applications.

Topics: Boron; Boron Compounds; Fluorescent Dyes; Porphobilinogen

For long-term live-cell fluorescence imaging and biosensing, it is crucial to work with a dye that has high fluorescence quantum yield and photostability without being detrimental to the cells. In this paper, we demonstrate that neutral boron-dipyrromethene (BODIPY)-based molecular rotors have great properties for high-light-dosage demanding live-cell fluorescence imaging applications that require repetitive illuminations. In molecular rotors, an intramolecular rotation (IMR) allows an alternative route for the decay of the singlet excited state (S

Topics: Boron; Boron Compounds; Molecular Probes; Oxygen; Porphobilinogen

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (

Topics: Boron Compounds; Cell Line, Tumor; Coordination Complexes; Drug Synergism; Humans; Neoplasms; Photochemotherapy; Platinum; Porphobilinogen

Hypoxia-activated prodrugs (HAPs) have drawn increasing attention for improving the antitumor effects while minimizing side effects. However, the heterogeneous distribution of the hypoxic region in tumors severely impedes the curative effect of HAPs. Additionally, most HAPs are not amenable to optical imaging, and it is difficult to precisely trace them in tissues. Herein, we carefully designed and synthesized a multifunctional therapeutic

Topics: Azo Compounds; Boron; Boron Compounds; Camptothecin; Cell Line, Tumor; Humans; Hyperthermia, Induced; Hypoxia; Nanoparticles; Neoplasms; Phototherapy; Photothermal Therapy; Porphobilinogen; Prodrugs

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.

Topics: Biosensing Techniques; Boron; Boron Compounds; Electrochemical Techniques; Limit of Detection; Luminescent Measurements; Metal-Organic Frameworks; Porphobilinogen; Telomerase

Cancer phototheranostics that combines diagnosis with phototherapy has emerged as a new mode of precise treatment. Nevertheless, taking highly effective phototheranostics into consideration, it is still a tremendous challenge to design multifunctional photothermal agents (PTAs) that combine the features of intensive near-infrared (NIR) absorption/emission, high photothermal conversion efficiency (PCE) and preferable tumor accumulation. Herein, seeking a convenient method to facilitate absorption red-shift, promote the accumulation of drugs in tumors and heighten the PCE appears to be particularly important for cancer theranostics. In this work, heavy-atom-free boron dipyrromethene (BODIPY) was assembled with F127 to fabricate ultra-small J-aggregated nanoparticles (named as BNPs). Compared to free BODIPY, BNPs exhibited 63 nm redshifted absorption, deep-tissue fluorescence imaging, enhanced cellular uptake, preferable tumor accumulation, elevated PCE, excellent photothermal stability and water dispersibility.

Topics: Boron; Cell Line, Tumor; Humans; Nanoparticles; Neoplasms; Theranostic Nanomedicine

A boron-dipyrromethene (BODIPY) derivative reactive towards amino groups of proteins (

Topics: Amines; Boron; Fluorescent Dyes; Molecular Docking Simulation; Serum Albumin, Bovine; Solvents

We disclose an interesting concept for developing heavy atom-free chemiluminogenic photosensitizers. To accomplish this, conjugates

Topics: Boron; Boron Compounds; Luminol; Photochemotherapy; Photosensitizing Agents; Porphobilinogen; Singlet Oxygen

Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N

Topics: Boron; Boron Compounds; Cell Line, Tumor; ErbB Receptors; Fluorescent Dyes; Humans; Ligands; Peptides, Cyclic; Porphobilinogen; Protein Binding; Surface Plasmon Resonance

A series of fluorescent boron-dipyrromethene (BODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have been designed to participate, as aglycons, in synthetic oligosaccharide protocols. As such, they served a dual purpose: first, by being incorporated at the beginning of the process (at the reducing-end of the growing saccharide moiety), they can function as fluorescent glycosyl tags, facilitating the detection and purification of the desired glycosidic intermediates, and secondly, the presence of these chromophores on the ensuing compounds grants access to fluorescently labeled saccharides. In this context, a sought-after feature of the fluorescent dyes has been their chemical robustness. Accordingly, some BODIPY derivatives described in this work can withstand the reaction conditions commonly employed in the chemical synthesis of saccharides; namely, glycosylation and protecting-group manipulations. Regarding their photophysical properties, the BODIPY-labeled saccharides obtained in this work display remarkable fluorescence efficiency in water, reaching quantum yield values up to 82 %, as well as notable lasing efficiencies and photostabilities.

Topics: Boron; Boron Compounds; Fluorescence; Fluorescent Dyes; Glycosylation; Light; Porphobilinogen

Boron-dipyrromethenes (Bodipys), since first reported in 1968, have emerged as a fascinating class of dyes in the past few decades due to their excellent photophysical properties including bright fluorescence, narrow emission bandwidth, resistance to photobleaching, and environment insensitivity. However, typical Bodipys are highly lipophilic, which often results in nonfluorescent aggregates in aqueous solution and also severely limits their bioavailability to cells and tissues. In this work, based on a simple one-atom B → C replacement in the Bodipy scaffold, we present a new class of carbon-dipyrromethenes (Cardipys for short) fluorescent dyes with tunable emission wavelengths covering the visible and near-infrared regions. These Cardipys not only retain the excellent photophysical properties of conventional Bodipys but also show improved water solubility and photostability due to their cationic character. Moreover, the cationic character also makes them extremely easy to penetrate the cell membrane and specifically accumulate into mitochondria without resorting to any mitochondria-targeted groups. Interestingly, several Cardipys bearing active styryl groups could serve as fluorescent indicators to map cellular trafficking of the glutathione conjugates produced within mitochondria under the catalysis of glutathione S-transferase (GST), thus showing potential in either exploring the detoxification mechanism of the mitochondrial GST/GSH system or evaluating the drug resistance of cancer cells that is closely related with GST activity.

Topics: A549 Cells; Boron Compounds; Carbon; Cations; Cell Membrane; Cell Movement; Electrochemical Techniques; Fluorescent Dyes; Glutathione; Glutathione Transferase; Humans; Mitochondria; Molecular Structure; Optical Imaging; Photochemical Processes; Porphobilinogen; Solubility; Solvents; Spectrometry, Fluorescence

This study focuses on the behavior of a new fluorescent marker for labeling individual biomolecules and staining cell organelles developed on a

Topics: Boron; Boron Compounds; Candida albicans; Cell Line, Tumor; Crystallography, X-Ray; Diagnostic Imaging; Doxorubicin; Electrons; Fusarium; Humans; Porphobilinogen; Solvents; Spectrometry, Fluorescence; Subcellular Fractions; Ultraviolet Rays

We report a new boron dipyrromethene (BODIPY)-bridged bisphenoxyl diradicaloid (

Topics: Boron Compounds; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Porphobilinogen

Recently, 3-dimensional supramolecular coordination complexes of the metallacage type have been shown to hold promise as drug delivery systems for different cytotoxic agents, including the anticancer drug cisplatin. However, so far only limited information is available on their uptake and sub-cellular localisation in cancer cells. With the aim of understanding the fate of metallacages in cells by fluorescence microscopy, three fluorescent Pd

Topics: Antineoplastic Agents; Boron Compounds; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Coordination Complexes; Glutathione; Humans; Magnetic Resonance Spectroscopy; Microscopy, Confocal; Microscopy, Fluorescence; Palladium; Porphobilinogen

Boron-dipyrromethene (BODIPY) chromophores have a wide range of applications, spanning areas from biological imaging to solar energy conversion. Understanding the ultrafast dynamics of electronically excited BODIPY chromophores could lead to further advances in these areas. In this work, we characterize and compare the ultrafast dynamics of halogenated BODIPY chromophores through applying two-dimensional electronic spectroscopy (2DES). Through our studies, we demonstrate a new data analysis procedure for extracting the dynamic Stokes shift from 2DES spectra revealing an ultrafast solvent relaxation. In addition, we extract the frequency of the vibrational modes that are strongly coupled to the electronic excitation, and compare the results of structurally different BODIPY chromophores. We interpret our results with the aid of DFT calculations, finding that structural modifications lead to changes in the frequency, identity, and magnitude of Franck-Condon active vibrational modes. We attribute these changes to differences in the electron density of the electronic states of the structurally different BODIPY chromophores.

Topics: Boron; Boron Compounds; Electrons; Porphobilinogen; Quantum Theory; Solubility; Solvents; Spectrum Analysis; Vibration

Evaluation of three subclasses of boron difluoride formazanate complexes bearing o-, m-, and p-anisole N-aryl substituents (Ar) as readily accessible alternatives to boron dipyrromethene (BODIPY) dyes for cell imaging applications is described. While the wavelengths of maximum absorption (λmax ) and emission (λem ) observed for each subclass of complexes, which differed by their carbon-bound substituents (R), were similar, the emission quantum yields for 7 a-c (R=cyano) were enhanced relative to 8 a-c (R=nitro) and 9 a-c (R=phenyl). Complexes 7 a-c and 8 a-c were also significantly easier to reduce electrochemically to their radical anion and dianion forms compared to 9 a-c. Within each subclass, the o-substituted derivatives were more difficult to reduce, had shorter λmax and λem , and lower emission quantum yields than the p-substituted analogues as a result of sterically driven twisting of the N-aryl substituents and a decrease in the degree of π-conjugation. The m-substituted complexes were the least difficult to reduce and possessed intermediate λmax , λem , and quantum yields. The complexes studied also exhibited large Stokes shifts (82-152 nm, 2143-5483 cm(-1) ). Finally, the utility of complex 7 c (Ar=p-anisole, R=cyano), which can be prepared for just a few dollars per gram, for fluorescence cell imaging was demonstrated. The use of 7 c and 4',6-diamino-2-phenylindole (DAPI) allowed for simultaneous imaging of the cytoplasm and nucleus of mouse fibroblast cells.

Topics: Anisoles; Boron Compounds; Crystallography, X-Ray; Diagnostic Imaging; Diamines; Fibroblasts; Fluorescence; Indoles; Models, Molecular; Molecular Structure; Porphobilinogen

A simple approach to the highly fluorescent near-infrared aza-BODIPY dyes with higher fluorescence quantum yields (up to 0.81 in toluene) in comparison with their known analogues is presented. Our approach is based on the restricted rotations of the 1,7-phenyl groups to the mean plane of the aza-BODIPYs, which is achieved through the installation of bulky substituents on the 1,7-phenyl groups of aza-BODIPYs and results in a reduced nonradiative relaxation process in solution. The large torsion angles between the 1,7-phenyl groups and the aza-BODIPY core (ϕ1 and ϕ2 in these novel conformationally restricted aza-BODIPYs) were confirmed by X-ray diffraction studies.

Topics: Aza Compounds; Boron Compounds; Fluorescence; Fluorescent Dyes; Fluorides; Molecular Conformation; Molecular Structure; Porphobilinogen; Quantum Theory; Solvents

We synthesized benzimidazole substituted boron-dipyrromethene 1 (BODIPY 1) by treating 3,5-diformyl BODIPY 2 with o-phenylenediamine under mild acid catalyzed conditions and characterized by using various spectroscopic techniques. The X-ray structure analysis revealed that the benzimidazole NH group is involved in intramolecular hydrogen bonding with fluoride atoms which resulted in a coplanar geometry between BODIPY and benzimidazole moiety. The presence of benzimidazole moiety at 3-position of BODIPY siginificantly altered the electronic properties, which is clearly evident in bathochromic shifts of absorption and fluorescence bands, improved quantum yields, increased lifetimes compared to BODIPY 2. The anion binding studies indicated that BODIPY 1 showed remarkable selectivity and specificity toward F(-) ion over other anions. Addition of F(-) ion to BODIPY 1 resulted in quenching of fluorescence accompanied by a visual detectable color change from fluorescent pink to nonfluorescent blue. The recognition mechanism is attributed to a fluoride-triggered disruption of the hydrogen bonding between BODIPY and benzimidazole moieties leading to (i) noncoplanar geometry between BODIPY and benzimidazole units and (ii) operation of photoinduced electron transfer (PET) from benzimidazole moiety to BODIPY unit causing quenching of fluorescence. Interestingly, when we titrated the nonfluorescent blue 1-F(-) solution with TFA resulted in a significant enhancement of fluorescence intensity (15-fold) because the PET quenching is prevented due to protonation of benzimidazole group. Furthermore, the reversibility and reusability of sensor 1 for the detection of F(-) ion was tested for six cycles indicating the sensor 1 is stable and can be used in reversible manner.

Topics: Benzimidazoles; Boron; Boron Compounds; Crystallography, X-Ray; Fluorescent Dyes; Fluorides; Models, Molecular; Phenylenediamines; Porphobilinogen; Spectrometry, Fluorescence

Caged compounds are useful tools for precise spatiotemporal modulation of cell functions, but in most cases uncaging requires ultraviolet (UV) light, which is cytotoxic and has limited tissue penetration. Therefore, caged compounds that can be activated by longer-wavelength light are required. Here we describe a novel photoelimination reaction of 4-aryloxy boron dipyrromethene (BODIPY) derivatives and show that BODIPY can function as a caging group for phenol groups. We developed a novel BODIPY-caged histamine compound, which is photoactivatable with blue-green visible light to stimulate cultured HeLa cells in a spatiotemporally well-controlled manner. This caging strategy is expected to be widely applicable to develop tools for probing various cellular functions.

Topics: Boron; Boron Compounds; Fluorescent Dyes; HeLa Cells; Humans; Light; Molecular Structure; Photons; Porphobilinogen

We present the development of the thiophene-fused boron dipyrromethene derivatives as efficient light absorbers. The two strategies for the evolution of the optical properties such as the peak positions of absorption wavelengths and molar extinct coefficients were established by the substituent effects: by introducing iodine groups, the bathochromic shifts of the peak positions (+15 nm) and the enhancement of molar extinct coefficients were simultaneously received owing to the heavy atom effect. Next, it was found that the modification with the trifluoromethyl group contributed to the large bathochromic shift (+60 nm) because of the lowering effect on the lowest unoccupied molecular orbital of the dye by the substituent. Finally, we obtained the dyes with large molar extinct coefficients (184,140 M(-1) cm(-1) at 592 nm, 72,180 M(-1) cm(-1) at 623 nm), sharp absorption bands, and low emissions.

Topics: Boron Compounds; Fluorescent Dyes; Molecular Structure; Porphobilinogen; Spectrometry, Fluorescence

Near-infrared (NIR) fluorescence probes are especially useful for simple and noninvasive in vivo imaging inside the body because of low autofluorescence and high tissue transparency in the NIR region compared with other wavelength regions. However, existing NIR fluorescence probes for matrix metalloproteinases (MMPs), which are tumor, atherosclerosis, and inflammation markers, have various disadvantages, especially as regards sensitivity. Here, we report a novel design strategy to obtain a NIR fluorescence probe that is rapidly internalized by free diffusion and well retained intracellularly after activation by extracellular MMPs. We designed and synthesized four candidate probes, each consisting of a cell permeable or nonpermeable NIR fluorescent dye as a Förster resonance energy transfer (FRET) donor linked to the NIR dark quencher BHQ-3 as a FRET acceptor via a MMP substrate peptide. We applied these probes for detection of the MMP activity of cultured HT-1080 cells, which express MMP2 and MT1-MMP, by fluorescence microscopy. Among them, the probe incorporating BODIPY650/665, BODIPY-MMP, clearly visualized the MMP activity as an increment of fluorescence inside the cells. We then applied this probe to a mouse xenograft tumor model prepared with HT-1080 cells. Following intratumoral injection of the probe, MMP activity could be visualized for much longer with BODIPY-MMP than with the probe containing SulfoCy5, which is cell impermeable and consequently readily washed out of the tissue. This simple design strategy should be applicable to develop a range of sensitive, rapidly responsive NIR fluorescence probes not only for MMP activity, but also for other proteases.

Topics: Animals; Boron Compounds; Cell Line, Tumor; Cell Membrane Permeability; Cell Survival; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Humans; Matrix Metalloproteinases; Mice; Microscopy, Fluorescence; Neoplasms; Porphobilinogen; Whole Body Imaging

A series of six Bodipy derivatives, namely 4,4-difluoro-8-(4-amidophenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (1), 4,4-difluoro-8-(4-methylphenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (2), 4,4-difluoro-8-(4-nitrylphenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (3), 4,4-difluoro-8-(4-amidophenyl)-3,5-dimethyl-4-bora-3a,4a-diaza-s-indacene (4), 4,4-difluoro-8-(4-methylphenyl)-3,5-dimethyl-4-bora-3a,4a-diaza-s-indacene (5), and 4,4-difluoro-8-(4-nitrylphenyl)-3,5-dimethyl-4-bora-3a,4a-diaza-s-indacene (6) were structurally characterized by single crystal X-ray diffraction analysis. Two methyl substituents attached at C-1 and C-7 positions of boron-dipyrromethene (Bodipy) moiety in compounds 1-3 were revealed to prevent the free rotation of the benzene moiety, resulting in a molecular configuration with an almost orthogonal dihedral angle between the Bodipy and benzene moieties with the dihedral angle in the range of 81.14-88.56°. This is obviously different from that for 4-6 with a free-rotating benzene moiety relative to the Bodipy core due to the lack of two methyl substituents in the latter series of compounds, leading to an enhanced interaction between the Bodipy and benzene moieties for 4-6 in comparison with 1-3. The resulting larger HOMO-LUMO gap for 1-3 than 4-6 results in a blue-shifted absorption band for 1-3 relative to that for 4-6. Comparative studies over their fluorescence properties also disclose the blue-shifted fluorescence emission band and corresponding higher fluorescence quantum yield for 1-3 relative to those of 4-6, revealing the effect of molecular configuration on the spectroscopic properties of Bodipy derivatives. Comparison of the redox behaviors of these two series of Bodipy compounds provides additional support for this point. In addition, the electron-donating/withdrawing property of the para substituent of the benzene moiety was shown to exhibit a slight influence on the electronic absorption and fluorescence emission properties of the Bodipy compounds.

Topics: Boron Compounds; Crystallography, X-Ray; Electrochemical Techniques; Fluorescent Dyes; Molecular Conformation; Oxidation-Reduction; Porphobilinogen; Quantum Theory; Spectrometry, Fluorescence

A series of boron dipyrromethene (BODIPY) dyes containing two aldehyde functional groups at the 3 and 5 positions have been synthesized in low-to-decent yields in two steps. In the first step, the meso-aryl dipyrromethanes were treated with POCl(3) in N,N-dimethylformamide to afford 1,9-diformylated dipyrromethanes. In the second step, the diformylated dipyrromethanes were first in situ oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and then reacted with BF(3)·OEt(2) to afford 3,5-diformylboron dipyrromethenes. The X-ray structural analysis indicated that the aldehyde groups are involved in intramolecular hydrogen bonding with fluoride atoms, which may be responsible for the stability of the diformylated BODIPY compounds. The presence of two formyl groups significantly alters the electronic properties, which is clearly evident in downfield shifts in the (1)H and (19)F NMR spectra, bathochromic shifts in the absorption and fluorescence spectra, better quantum yields, and increased lifetimes compared to 3,5-unsubstituted BODIPYs. Furthermore, 3,5-diformylboron dipyrromethenes are highly electron-deficient and undergo facile reductions compared to unsubstituted BODIPYs. These compounds exhibit pH-dependent on/off fluorescence and thus act as fluorescent pH sensors.

Topics: Benzoquinones; Biosensing Techniques; Boron; Boron Compounds; Crystallography, X-Ray; Dimethylformamide; Fluorescence; Fluorescent Dyes; Formamides; Hydrogen Bonding; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Molecular Structure; Porphobilinogen; Pyrroles; Spectrometry, Fluorescence; Thermodynamics

A rapid synthetic route for polyarylated boron-dipyrromethenes using hexabromo boron-dipyrromethene as the key synthon is described. The X-ray structure revealed that the polyarylated BODIPY adopts a propeller-like conformation. These compounds exhibit red-shifted absorption and fluorescence bands with decent quantum yields and reversible oxidation and reduction waves when compared to unsubstituted boron-dipyrromethenes.

Topics: Boron; Boron Compounds; Crystallography, X-Ray; Fluorescence; Fluorescent Dyes; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Imaging; Molecular Probes; Oxidation-Reduction; Porphobilinogen; Spectrometry, Fluorescence

BODIPY-Le, a colorimetric and ratiometric fluorescent probe based on boron-dipyrromethene for selective detection sulfite ion, was investigated. Boron-dipyrromethene levulinyl ester (BODIPY-Le) is composed of an indole-based BODIPY dye and the levulinyl protective group, which could be easily and selectively deprotected by sulfites. As a result, the absorption and emission spectra show a dramatic red shift, and the development of a colorimetric and ratiometric fluorescent sulfite probe could be achieved. Besides, BODIPY-Le also exhibited prominent turn-on or turn-off type fluorogenic signaling toward sulfite ions once excited at 510 and 620 nm, respectively.

Topics: Boron; Boron Compounds; Colorimetry; Fluorescent Dyes; Porphobilinogen; Spectrometry, Fluorescence; Sulfites

A panchromatic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-zinc phthalocyanine conjugate (Bodipy-ZnPc) 1 was synthesized starting from phthalocyanine aldehyde 4, via dipyrromethane 3 and dipyrromethene 2. Conjugate 1 represents the first example in which a Bodipy unit is tethered to the peripheral position of a phthalocyanine core. Electrochemical and optical measurements provided evidence for strong electronic interactions between the Bodipy and ZnPc constituents in the ground state of 1. When conjugate 1 is subjected to photoexcitation in the spectral region corresponding to the Bodipy absorption, the strong fluorescence characteristic of the latter subunit is effectively quenched (i.e., > or = 97%). Excitation spectral analysis confirmed that the photoexcited Bodipy and the tethered ZnPc subunits interact and that intraconjugate singlet energy transfer occurs with an efficiency of ca. 25%. Treatment of conjugate 1 with N-pyridylfulleropyrrolidine (8), an electron-acceptor system containing a nitrogen ligand, gives rise to the novel electron donor-acceptor hybrid 1<-->8 through ligation to the ZnPc center. Irradiation of the resulting supramolecular ensemble within the visible range leads to a charge-separated Bodipy-ZnPc(*+)-C(60)(*-) radical-ion-pair state, through a sequence of excited-state and charge transfers, characterized by a remarkably long lifetime of 39.9 ns in toluene.

Topics: Boron Compounds; Dimerization; Electrochemistry; Fluorescence; Fullerenes; Indoles; Isoindoles; Models, Chemical; Organometallic Compounds; Photochemistry; Porphobilinogen; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Zinc Compounds

To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.

Topics: Animals; Apoptosis; Biological Transport; Blood Vessels; Boron; Boron Compounds; Cell Cycle; Cell Line, Tumor; Chickens; Chorioallantoic Membrane; Humans; Intracellular Space; Photochemotherapy; Photosensitizing Agents; Porphobilinogen; Singlet Oxygen; Structure-Activity Relationship

Chromophore-assisted light inactivation is a promising technique to inactivate selected proteins with high spatial and temporal resolution in living cells, but its use has been limited because of the lack of a methodology to prevent nonspecific photodamage in the cell owing to reactive oxygen species generated by the photosensitizer. Here we present a design strategy for photosensitizers with an environment-sensitive off/on switch for singlet oxygen ((1)O(2)) generation, which is switched on by binding to the target, to improve the specificity of protein photoinactivation. (1)O(2) generation in the unbound state is quenched by photoinduced electron transfer, whereas (1)O(2) generation can occur in the hydrophobic environment provided by the target protein, after specific binding. Inositol 1,4,5-trisphosphate receptor, which has been suggested to have a hydrophobic pocket around the ligand binding site, was specifically inactivated by an environment-sensitive photosensitizer-conjugated inositol 1,4,5-trisphosphate receptor ligand without (1)O(2) generation in the cytosol of the target cells, despite light illumination, demonstrating the potential of environment-sensitive photosensitizers to allow high-resolution control of generation of reactive oxygen species in the cell.

Topics: Animals; Boron; Boron Compounds; Cell Line; Chickens; Cytosol; Fluorescent Dyes; Inositol 1,4,5-Trisphosphate Receptors; Light; Models, Biological; Oxygen; Photochemistry; Photosensitizing Agents; Porphobilinogen; Protein Binding; Singlet Oxygen

Substitution of F-Bodipy with alkynylaryl residues at boron, at the pyrrolic core or at the meso position, provides unique tri-, tetra-, and pentasubstituted dyes. Substitution at the (pyrrolic) 2,6-positions provides substantial red shifts with quantum yields in the 40-90% range and excited-state lifetimes of 3-7 ns. ON/OFF fluorescence switching can be produced by protonation of dibutylamino subunits.

Topics: Acetylene; Boron Compounds; Fluorescent Dyes; Porphobilinogen

Novel fluorescent, conformationally restricted dipyrromethene boron difluoride (BODIPY) dyes have been prepared by introducing a naphthalenyl group at the meso position of the BODIPY core. These BODIPY dyes exhibit increased fluorescence quantum yields compared with dyes that have a meso-position phenyl group with internal rotation. The absorption and emission wavelengths of such conformationally restricted BODIPY dyes can be easily tuned to the near-IR range by derivatization through a condensation reaction with benzaldehyde derivatives. The two-photon absorption properties of these BODIPY dyes were also investigated and the results show that they exhibit increased two-photon excited fluorescence compared to analogue dyes that contain a phenyl group. The one- and two-photon fluorescence imaging of living cells by using selected BODIPY dyes has been successfully demonstrated.

Topics: Boron Compounds; Cells; Crystallography, X-Ray; Fluorescent Dyes; Image Interpretation, Computer-Assisted; Molecular Conformation; Porphobilinogen; Spectrometry, Fluorescence

The intracellular distribution of synthetic glycosphingolipids (GSLs) bearing a fluorophore can be monitored in living cells by fluorescence microscopy. We reported previously that variation in the length of the long-chain base and in the structure of the carbohydrate-containing polar head group of (2S,3R) (or D-erythro-)-beta-lactosylceramide (LacCer) did not alter the mechanism of endocytic uptake from the plasma membrane of various mammalian cell types [Singh, R.D., Puri, V., Valiyaveettil, J.T., Marks, D.L., Bittman, R., Pagano, R.E., 2003. Selective caveolin-1-dependent endocytosis of glycosphingolipids. Mol. Biol. Cell 14, 3254-3265]. To extend our examination of the molecular features in LacCer that are responsible for its uptake by the caveolar-requiring endocytic pathway, we have synthesized the three unnatural stereoisomers [(2R,3R)-, (2S,3S)-, and (2R,3S)] of dipyrromethene difluoride (BODIPY)-LacCer. These analogues will be used to probe the role of stereochemistry in the long-chain base of LacCer in the mechanism of endocytic uptake.

Topics: Animals; Antigens, CD; Boron Compounds; Caveolae; Cell Membrane; Endocytosis; Fluorescent Dyes; Glycosphingolipids; Lactosylceramides; Microscopy, Fluorescence; Models, Chemical; Porphobilinogen; Stereoisomerism

Boron dipyrromethene dyes bearing nitro, amino, isocyanate and isothiocyanate functions were readily prepared under mild conditions. Various combinations allow to produce urea, diurea, thiourea, dithiourea in the 3, 4 and 5-substitution positions of the appended phenyl group. Condensation of the 3,4-substituted diamino derivative with 1,10-phenanthroline-5,6-dione and 6-formyl-2-methylpyridine allow to prepare dipyridophenazine and indole derivatives. The 3,5-dinitro-substituted indacene dye was characterized by an X-ray molecular structure showing a pronounced tilt angle of the dinitrophenyl group relative to the indacene core (approximately 84 degrees) whereas one nitro groups is basically coplanar with the phenyl ring and the second titled by approximately 21 degrees. The optical properties of these dyes reveals on/off switching of the fluorescence from the nitro to the amino compounds and further to the urea likely understood in the framework of an photoinduced electron transfer process.

Topics: Boron; Boron Compounds; Chemistry; Electrons; Fluorescence; Fluorescent Dyes; Light; Models, Chemical; Molecular Structure; Nitrobenzenes; Photochemistry; Porphobilinogen; X-Rays