Boron Dipyrrin Research Articles

Tilianin alleviates lipid deposition and fibrosis in mice with nonalcoholic steatohepatitis by activating the PPARα/Nnat axis.

The understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low-dose streptozotocin combined with a high-fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)-1β, IL-6, transforming growth factor β1 (TGF-β1), and tumor necrosis factor α (TNF-α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator-activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element-binding protein 1 (SREBP-1), TGF-β1, nuclear factor (NF)-κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock-down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF-κB signaling pathway.

Variety of steady and excited state interactions in BODIPY aggregates: Photophysics in antisolvent systems and floating layers

Associative behavior of geometrically anisotropic meso-(4-octadecyloxy-phenyl)-boron-dipyrrin (BODIPY) studied spectroscopically in binary solvent mixtures and upon compression in Langmuir floating layers. Different steady and excited state species were found upon monolayer compression and facilitated aggregation in water/ acetonitrile systems. This discrepancy points to a big concern in possibility of commonly applied generalizations across different aggregating systems. Broad range of decay fitting models were examined to reveal their benefits and pitfalls specific to examination of dye aggregates. Radiative constant gamma-distribution approach and free form fluorescence lifetime distribution with maximum entropy method (MEM) outperformed multiple common techniques for analysis of complex fluorescence decays. MEM could be recommended for analysis of systems where complicated lifetime distributions appear over time or upon external stimuli. Findings and protocols could be utilized as tools in studies of steady and excited-state photophysics of BODIPY aggregates.

Earring Porphyrins Bearing 1,9‐Di(pyrid‐2‐yl)dipyrromethene Unit and Their BODIPY Conjugates

AbstractSuzuki–Miyaura coupling reactions of 2,18‐di(6‐bromopyrid‐2‐yl)‐substituted NiII porphyrin and 2,8,12,18‐tetrakis(6‐bromopyrid‐2‐yl)‐substituted NiII porphyrin with 1,9‐biboryl‐5‐mesityl dipyrromethene and subsequent oxidation with p‐chloranil gave single earring and double earring NiII porphyrins, respectively, which bear 1,9‐(dipyrid‐2‐yl)dipyrromethene unit. These NiII complexes were converted to free base porphyrins and then to ZnII porphyrins. Treatment of earring NiII and earring ZnII porphyrins with BF3⋅Et2O afforded the corresponding BODIPY (boron dipyrrin) conjugates and the ZnII porphyrin‐BODIPY conjugates were converted to free base porphyrin‐BODIPY conjugates. Bent structures of earring NiII porphyrins and the corresponding BODIPY conjugates have been revealed by X‐ray diffraction analysis. ZnII porphyrin‐BODIPYs show efficient fluorescence quenching, which is ascribed to fast intramolecular electron transfer from the ZnII porphyrin to the BODIPY moiety.

Molecular and electronic structure of substituted BODIPY dyes: Quantum chemical study

Boron dipyrrins, otherwise known as BODIPY, are an actively investigated group of fluorescent dyes. Their main appeal comes from the variance of their spectral properties with substitution. In this work, we focus on a series of different meso-substituted BODIPY dyes. We tested the effect of substituents on the structure and spectroscopic properties of BODIPY. The following substitutes were examined: pentil, 4-dibutylaminophenyl, phenyl, 3,5-dimethylphenyl, 4-hydroxyphenyl, 4-dihydroxyphenyl, 4-carboxyphenyl, 4-dimethylaminophenyl, 4-dibutylaminophenyl, biphenyl, 9-anthryl, 2-thiophenyl and 2-furanyl. At the same time, higher prospects for directional changing in the optical properties of BODIPYs through the addition of aryl groups in position 3 were noted. An investigation of vibrationally-resolved absorption and emission spectra is presented. Subset of compounds was used to compare the most and the least involved (adiabatic hessian and vertical gradient respectively) models and have shown the wider applicability and better accuracy in experimental reproduction of the latter.

Porphyrin-BODIPY light harvesting [3]rotaxane

The innovation of new synthetic strategies to assemble functional materials is of the utmost importance. Herein, a light harvesting [3]rotaxane 7 was designed and synthesized by threading alkyne-functionalized dibenzyl ammonium 5 into dibenzo-24-crown-8 ether macrocycles of Zn porphyrin 4 followed by stoppering the resulting [3]pseudorotaxane 8 with four azide-functionalized boron-dipyrrin (BODIPY) 6 moieties through the copper(I)-catalyzed Huisgen alkyne-azide 1,3-dipolar cycloaddition (CuAAC “click” reaction). The photophysical properties of the resulting [3]rotaxane were investigated by UV-Vis absorption and fluorescence spectroscopy. The absorption spectrum of 7 demonstrated that both Zn porphyrin and BODIPY moieties of 7 retain their spectroscopic properties thus indicating negligible interaction between them in the ground state. In addition, fluorescence studies of the resulting [3]rotaxane 7 showed that the selective excitation of BODIPY moieties of 7 resulted in an efficient photo-induced energy transfer from the four peripheral BODIPY to the central Zn porphyrin thus imitating the natural photosynthesis processes.

Selective, Rapid, and Ratiometric Fluorescence Sensing of Homocysteine in Live Neurons via a Reaction-Kinetics/Sequence-Differentiation Strategy Based on a Small Molecular Probe.

Small molecular biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play essential roles in maintaining the redox homeostasis of biological systems, the disorders of which are closely associated with neuropathology. To date, many probes have been developed to identify Cys and GSH; however, due to the relatively low content and the high structural homology with Cys, there is still a lack of effective strategies to design probes enabling Hcy detection in physiological environments with high selectivity, high sensitivity, and rapid response. Herein, we developed a reaction-kinetics/sequence-differentiation strategy based on a dual-binding-site boron-dipyrrin (BODIPY) fluorophore, which was able to selectively distinguish Hcy from Cys and GSH within 50 s though a ratiometric fluorescence response mode. Benefiting from these features, the probe is capable of real-time imaging and quantitative analysis of intracellular Hcy in living neurons. Moreover, results of the disease-model experiments at the cellular level indicated a gradual increase of the Hcy level in neurons during the processes of aggregated amyloid-β (Aβ) peptide or ischemia treatment, which would further promote the neuron apoptosis. These findings provide the first direct experimental evidence for the impact of Alzheimer's disease and ischemic stroke on the Hcy metabolism of brain neurons and the associated neuron injury.

Essential effect of proton coupled electron sequent transfer on photocatalytic water complete dissociation: A DFT study

Photocatalytic water splitting for hydrogen energy is one of the most promising ways to solve the energy crises. The mechanism is unclear on the sequence of proton coupled electron transfer (PCET) in photocatalytic water dissociation catalyzed by organic material. Here, the water splitting catalyzed by zinc porphyrin with boron dipyrrin (ZnPP-BDP) is systematically investigated by density functional theory (DFT) calculations. The H2O/ZnPP in valence state based on the electron transfer pulls the trigger on the water splitting process. For the oxygen evolution reaction (OER) step on ZnPP, the processes for the two H ions dissociate from water are exothermic with the −1.06 and −0.95 eV energies respectively, and the O/ZnPP system is formed. The second H2O molecule on O/ZnPP system can provide the extra oxygen atom to produce the free O2 with 1.22 eV energy barrier. For the hydrogen evolution reaction (HER) step on BDP, the H ions dissociated from OER process can be captured by BDP to form free H2 with 2.24 eV/molecule energy released. In this attractive clean cyclic process, the ZnPP-BDP can continuously catalyze the H2O dissociated into free H2 and O2 by the shifting potential barrier. Besides, the proton coupled electron sequent transfer possess an essential role in photocatalytic water dissociation. It is very instructive to design sustainable photodecomposition catalysts for both OER and HER, and to design extraordinary biomimetic photosynthesizers for clean energy.

COMPARATIVE IN VITRO ANALYSIS OF CYTOTOXICITY OF BODIPY-LUMINOPHERS AS POTENTIAL FLUORESCENT SENSORS FOR BIOLOGICAL SYSTEMS

Boron dipyrrin (BODIPY) based luminophores are of considerable interest as promising components of optically active molecular devices for sensing, visualization, and theranostics of biological systems. However, the toxic effect of boron dipyrrin based luminophores of various structure have not been systematically studied until now. In this regard, the work shows the spectral characteristics of the main groups of BODIPY luminophores, which differ in the nature of substituents in the structure of the dipyrrine ligand, as well as in the length of the aromatic system, which can be used to solve practical problems of molecular sensorics of biosystems. The cytotoxicity of the compounds was evaluated. In the study within the framework of an integrated approach, two groups of methods were used to study the effect of the compounds under study at the cellular level: assessment of the cytotoxic effect on the morphological characteristics of blood cells using phase contrast microscopy with detection of altered cells and the intensity of free radical processes of cell membrane degradation. The results of the study of changes in the antioxidant system of blood samples during incubation with all dyes did not reveal significant differences. do not show cytotoxic effect. It was found that BODIPY has a potential membrane-protective effect, which was shown in this study for the first time.

Nir mono and bi 2-vinylthiophene substituted boron dipyrrin dyes: from practice to theory to further practice

Boron dipyrrin (BODIPY) family is one of the most studied collection of fluorophores, many of which are specifically designed for vital medical uses, such as cell imaging. In this research area, near-infrared absorbing and emitting compounds play the key role. Because of their long wavelength of absorption, they can be effectively excited by taking advantage of therapeutic window of human tissues. Herein we report the repeat of the synthesis of two vinylthiophene-substituted derivatives with extended π-electron systems and their computational investigation. Those dyes were prepared starting from methyl-substituted ones via addition reaction of aldehyde-containing thiophene following the literature. Obtained experimental and theoretical data will allow us to design promising tools not only for cell imaging, but also for fluorescent detection of heavy cations via coordination and possibly more.

BODIPY Dyes as Probes and Sensors to Study Amyloid-β-Related Processes.

Amyloid formation plays a major role in a number of neurodegenerative diseases, including Alzheimer’s disease. Amyloid-β peptides (Aβ) are one of the primary markers associated with this pathology. Aβ aggregates exhibit a diverse range of morphologies with distinct pathological activities. Recognition of the Aβ aggregates by using small molecule-based probes and sensors should not only enhance understanding of the underlying mechanisms of amyloid formation, but also facilitate the development of therapeutic strategies to interfere with amyloid neurotoxicity. BODIPY (boron dipyrrin) dyes are among the most versatile small molecule fluorophores. BODIPY scaffolds could be functionalized to tune their photophysical properties to the desired ranges as well as to adapt these dyes to various types of conditions and environments. Thus, BODIPY dyes could be viewed as unique platforms for the design of probes and sensors that are capable of detecting and tracking structural changes of various Aβ aggregates. This review summarizes currently available examples of BODIPY dyes that have been used to investigate conformational changes of Aβ peptides, self-assembly processes of Aβ, as well as Aβ interactions with various molecules.

Electrochemical B-H Nitrogenation: Access to Amino Acid and BODIPY-Labeled nido-Carboranes.

Electrocatalyzed oxidative B−H nitrogenations of nido‐carborane (nido‐7,8‐C2B9H12 −) with N‐heterocycles have been established, enabling the preparation of various N‐substituted nido‐carboranes without chemical oxidants or metal catalyst under ambient conditions. The electrolysis manifold occurred with high levels of efficiency as well as chemo‐ and position‐ selectivity, employing sustainable electricity as the sole oxidant. The strategy set the stage for a user‐friendly access to novel amino acid and fluorogenic boron‐dipyrrin (BODIPY)‐labeled nido‐carborane hybrids.

DDAO Controlled Synthesis of Organo-Modified Silica Nanoparticles with Encapsulated Fluorescent Boron Dipyrrins and Study of Their Uptake by Cancerous Cells.

The design of cargo carriers with high biocompatibility, unique morphological characteristics, and capability of strong bonding of fluorescent dye is highly important for the development of a platform for smart imaging and diagnostics. In this paper, BODIPY-doped silica nanoparticles were prepared through a “one-pot” soft-template method using a sol-gel process. Several sol-gel precursors have been used in sol-gel synthesis in the presence of soft-template to obtain the silica-based materials with the most appropriate morphological features for the immobilization of BODIPY molecules. Obtained silica particles have been shown to be non-cytotoxic and can be effectively internalized into the cervical cancer cell line (HeLa). The described method of synthesis allows us to obtain silica-based carriers with an immobilized fluorescent dye that provide the possibility for real-time imaging and detection of these carriers.

Development of alkyne-BODIPYs as viscosity sensitive fluorescent probes for enumeration of bacterial cells

We report a series of alkyne-functionalized meso-aryl boron dipyrrin (BODIPY) molecular rotors sensitive to viscosity. The planar and twisted conformation within the molecular structure decides the viscosity-dependent behavior. The variations in fluorescence lifetime and intensity were appreciable to the local viscosity. Hence, the dye has been successfully employed in the enumeration of microbes by considering the proportionate fluorescence intensity of the BODIPYs as an index of the number of cells per mL. With increasing cells per mL, the viscosity of the bacterial solution is increased. Consequently, the fluorescence intensity of the sample containing BODIPY tends to increase due to the restricted rotation in the viscous medium. The BODIPY probe offers high sensitivity and is easier than other conventional techniques of colony-forming unit (CFU) determination. The theoretical studies indicate that intramolecular charge transfer is responsible for the enhanced fluorescence intensity in a highly viscous solvent.

Synthesis and Functions of Oligomeric and Multidentate Dipyrrin Derivatives and their Complexes

The dipyrrin–metal complexes and especially the boron complex 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) have recently attracted considerable attention because of their interesting properties and possible applications. We have developed two unique and useful ways to extend versatility and usefulness of the dipyrrin complexes. The first one is the linear and macrocyclic oligomerization of the BODIPY units. These arrangements of the B–F moieties of the oligomerized BODIPY units provide sophisticated functions, such as unique recognition ability toward cationic guest, associated with changes in the photophysical properties by utilizing unprecedented interactions between the B–F and a cationic species. The second one is introduction of additional ligating moieties into the dipyrrin skeleton. The multidentate N2Ox dipyrrin ligands thus obtained form a variety of complexes with 13 and 14 group elements, which are difficult to synthesize using the original N2 dipyrrin derivatives. Interestingly, these unique complexes exhibit novel structures, properties, and functions such as guest recognition, stimuli-responsive structural conversion, switching of the optical properties, excellent stability of the neutral radicals, etc. We believe that these multifunctional dipyrrin complexes will advance the basic chemistry of the dipyrrin complexes and develop their applications in the materials and medicinal chemistry fields.1 Introduction2 Linear Oligomers of Boron–Dipyrrin Complexes3 Cyclic Oligomers of Boron–Dipyrrin Complexes4 A Cyclic Oligomer of Zinc–Dipyrrin Complexes5 Group 13 Element Complexes of N2Ox Dipyrrins6 Chiral N2 and N2Ox Dipyrrin Complexes7 Group 14 Element Complexes of N2O2 Dipyrrins8 Other N2O2 Dipyrrin Complexes with Unique Properties and Functions9 Conclusion

Synthesis, spectral and crystal structures of gem-dibromovinyl boron dipyrrins

A series of BODIPYs (boron-dipyrromethene dyes; 4,4-difluoro-5-aryl-4-bora-3a,4a-diaza-s-indacene) derivatives, bearing an aldehyde group at different pyrrole positions, were transformed into gem-dibromovinyl analogs using the Corey-Fuchs or Lautens olefination method. The gem-dibromovinyl moieties (one or two) are symmetric/asymmetric and attached at α- or β-positions of the pyrrole ring, directly or through the extension of a β-position substituted phenyl spacer ring. The molecular structures of the resultant dyes were assigned using MS, 1H, 13C, 19F NMR, X-ray diffraction and for some compounds 2D HSQC and 11B NMR. The absorption, fluorescence and solvatochromism properties were investigated in different solvents. The highest absorption and emission maxima were obtained for compounds having two gem-dibromovinyl groups attached directly at the α-positions. The best correlation (R-coefficient) of absorption between the solvents and spectral properties of the BODIPYs was obtained using the refractive index of the solvent. The R-coefficient of emission was obtained only for compounds having gem-dibromo vinyl moieties at α-positions. Their solid states clearly reveal distinct patterns of gem-dibromovinyl orientation, torsion angles of the 5-phenyl ring and the indacene plane. Hirshfeld surface analyses were used to visualize various intermolecular interactions.

Boron Dipirrins: Mechanism of Formation, Spectral and Photophysical Properties, and Directions of Functionalization

Boron dipyrrins (Bodipy) are unique complexes occupying an intermediate position between classical coordination and organometallic compounds. The enormous interest of researchers from all over the world to the compounds of this class has by now provided an endless stream of publications that requires generalization. Existing reviews and original publications do not fully cover the structural diversity of Bodipy and their possible applications in engineering, medicine, analytical chemistry, optics, photonics, etc. In this paper, w e present the results, mainly of our own research, which for the first time allowed us to establish the physicochemical principles of the formation of Bodipy (the reasons for the low rates of complexation of ligands with boron trifluoride), changes in the spectral and photophysical properties of alkylated Bodipy complexes with the separation of contributions from universal and specific solvation, and examples of functionalization of inorganic and organic polymer materials based on Bodipy of different structures. Examples of the current team’s Bodipy research in different practical areas are presented.

Functionalized BODIPYs as Fluorescent Molecular Rotors for Viscosity Detection.

Abnormal changes of intracellular microviscosity are associated with a series of pathologies and diseases. Therefore, monitoring viscosity at cellular and subcellular levels is important for pathological research. Fluorescent molecular rotors (FMRs) have recently been developed to detect viscosity through a linear correlation between fluorescence intensity or lifetime and viscosity. Recently, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (boron dipyrrins or BODIPY) derivatives have been widely used to build FMRs for viscosity probes due to their high rotational ability of the rotor and potentially high brightness. In this minireview, functionalized BODIPYs as FMRs for viscosity detection were collected, analyzed and summarized.

BODIPY-Labeled Cyclobutanes by Secondary C(sp3 )-H Arylations for Live-Cell Imaging.

Arylated cyclobutanes were accessed by a versatile palladium-catalyzed secondary C(sp3 )-H activation, exploiting chelation assistance by modular triazoles. The C-H arylation led to cyclobutane natural product derivatives in a highly regioselective fashion, setting the stage for the easy access to novel fluorogenic boron-dipyrrin (BODIPY)-labeled probes for live-cell imaging.

Bichromophoric Properties of Ruthenium(II) Polypyridyl Complexes Bridged by Boron Dipyrromethenes: Synthesis, Electrochemical, Spectroscopic, Computational Evaluation, and Plasmid DNA Photoreactions

Two new π‐extended dipyrrins containing isoquinolpyrrole and phenanthro‐fused pyrrole have been synthesized by solvent free reactions with trifluoroacetic acid (TFA) as a catalyst. The boron‐dipyrrin (BDP) of the isoquinolpyrrole was synthesized by standard procedures followed by synthesis of the bis‐ruthenium(II) BDP analog. The spectroscopic properties of this complex were investigated, showing the typical intra‐ligand charge transfer transitions (ILCT) along with the Ru(dπ) to ligand(π*) metal to ligand charge transfer (MLCT) transitions. An intense transition at 608 nm with molar absorptivity greater than 100,000 m–1 cm–1 associated with the ππ* transition of the BDP‐core is observed. The less stable bis‐RuII BDP complex from the phenanthro‐fused dipyrrin was also synthesized giving the typical spectra associated with RuII‐phenanthroline complexes in addition an intense absorption at 618 nm from ππ* transition of the BDP‐core. The spectroscopic properties of this complex were correlated to density functional theory (DFT) and time‐dependent density functional theory (TDDFT) theoretical calculations. This complex shows interesting dual emission of both the Ru(bpy)2phen and the BDP‐core components at 601 nm and 641 nm respectively upon excitation of the lower energy MLCT transition at 453 nm. In acetonitrile solutions both bis‐RuII‐BDP complexes generate significant singlet oxygen when irradiated with low energy light. In aqueous solutions both complexes are capable of photo‐nicking plasmid DNA when irradiated within the photodynamic therapy (PDT) window with the phenanthrol‐fused bis‐RuII‐BDP complex showing greater photoreactivity.

Quantum-chemical study of oxophosphorus dipyrromethene (PODIPY) fluorophore coordination environment

Boron dipyrrin (BODIPY) fluorophores possess a range of excellent spectral characteristics, making their parent structure a useful scaffold for design of optically active molecules. Recently, new oxophosporus dipyrrin (PODIPY) compounds were introduced. They were shown to possess spectroscopic properties similar to those of corresponding BODIPY dyes. However, better solubility in polar solvents makes PODIPY better candidate for in vitro and in vivo fluorescent diagnostics. Here we give further insight into the structure and spectroscopic properties of the PODIPY dye. Theoretically predicted coordination center geometries correspond to the ones found experimentally for phosphorus phthalocyanines, corrolazines and other known P(V) heterocyclic complexes. DFT and WFT methods are employed to study geometrical, energetical and resulting spectral characteristics of the structural isomers.