BODIPY Dyes Research Articles

Colorimetric and fluorescent detection of synthetic cathinones in oral fluid with meso-aryl BODIPYs and Cu(ii).

Synthetic cathinones are a class of new psychoactive substances whose consumption has increased a lot and is widespread throughout the world. Thus, there is currently a need for rapid and simple detection of these drugs. In particular, detection of synthetic cathinones in oral fluid in drivers can be of great importance in preventing traffic accidents. Herein, we report two probes, based on BODIPY derivatives combined with Cu(ii), which are able to detect these drugs both in water and in oral fluid, by changes in color and fluorescence. The determined limits of detection for ephedrone (as a model drug) are lower than the usual concentrations in saliva after intake of this type of drug. The sensing mechanism seems to be related to the cathinone induced reduction of Cu(ii) to Cu(i) with concomitants changes in the BODIPY structure.

Utilization of BODIPY-based redox events to manipulate the Lewis acidity of fluorescent boranes.

This report describes the implementation of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye into the ligand framework of a borane. The redox-active nature of the BODIPY dye is utilized to generate a family of molecular boranes that are capable of exhibiting tunable Lewis acidities through BODIPY-based redox events.

Unlocking the Potential of Ru(II) Dual-action Compounds with the Power of the Heavy-atom Effect.

We report the synthesis, photochemical and biological characterization of two new Ru(II) photoactivated complexesbased on [Ru(tpy)(Me2 bpy)(L)]2+ (tpy = 2,2':6',2''-terpyridine, Me2 bpy = 6,6'-dimethyl-2,2'-bipyridine), where L = pyridyl-BODIPY (pyBOD). Two pyBOD ligands were prepared bearing flanking hydrogen or iodine atoms. Ru(II)-bound BODIPY dyes show a red-shift of absorption maxima relative to the free dyes and undergo photodissociation of BODIPY ligands with green light irradiation. Addition of iodine into the BODIPY ligand facilitates intersystem crossing, which leads to efficient singlet oxygen production in the free dye, but also enhances quantum yield of release of the BODIPY ligand from Ru(II). This represents the first report of a strategy to enhance photodissociation quantum yields through the heavy-atom effect in Ru(II) complexes. Furthermore, Ru(II)-bound BODIPY dyes display fluorescence turn-on once released, with a lead analog showing nanomolar EC50 values against triple negative breast cancer cells, >100-fold phototherapeutic indexes under green light irradiation, and higher selectivity toward cancer cells as compared to normal cells than the corresponding free BODIPY photosensitizer. Conventional Ru(II) photoactivated complexes require nonbiorthogonal blue light for activation and rarely show submicromolar potency to achieve cell death. Our study represents an avenue for the improved photochemistry and potency of future Ru(II) complexes.

Amphiphilic Fullerene-BODIPY Photosensitizers for Targeted Photodynamic Therapy.

Nanotheranostic tailor-made carriers are potent platforms for the treatment of cancer that propound a number of advantages over conventional agents for photodynamic therapy (PDT). Herein, four new heavy atom free amphiphilic glucose-BODIPY-fullerene dyads (14-17) endowed with carbohydrate units in the styryl units, which can also form nanomicelles (14-17NM) with Tween 80 for PDT are reported. Glucose-BODIPY-fullerene systems (14-17) and related nanomicelles (14-17NM) have been prepared to emcee efficient singlet oxygen generation upon light irradiation. In vitro anti-tumor effects of the compounds 14-17 and 14-17NM in the presence of light and in darkness have been investigated with K562 human chronic myelogenous leukemia suspension cells. Anti-tumor toxicity upon light irradiation was due to the formation of singlet oxygen and reactive oxygen species (ROS). This study may provide an accomplished example of efficient PDT applications based on nanovehicles fabricated with universal spin converter, fullerene, light harvesting unit, BODIPY dyes conjugated with targeting units to fight against cancer.

A new 3-substituted BODIPY dye: Synthesis, crystal structure, photophysical, non-linear optic and OLED properties

A BODIPY derivative (compound 2), substituted with 4-nitrophenyl at the meso position and its 3-pyrrole substituted derivative (compound 3) were synthesized and characterized. The structure of compound 3 was elucidated by single crystal X-ray diffraction study. The Photophysical properties of compounds 2 and 3 were studied in various solvents with different polarities. The expansion of the π-conjugation by introduction of the pyrrole ring to 3-position of the BODIPY core results in a considerable red shift in the absorption and emission bands. Also, photophysical properties of compounds 2 and 3 was affected by the solvent polarity. Compound 3 showed stronger fluorescence in non-polar solvents (ΦF = 0.049 in Hexane). In order to establish the effect of the pyrrole attachment, the synthesized compounds 2 and 3 were optimized at the level of computational chemistry, DFT/B3LYP/6–31+G(d,p). The highest occupied molecular orbital energy (EHOMO), the lowest unoccupied molecular orbital (ELUMO), the energy gap (ΔE) parameters and contour diagrams obtained from the optimized structures were investigated. The nonlinear optical (NLO) and light emission (OLED) properties of the compounds were investigated computationally on the basis of polarizability parameters and Marcus theory, respectively.

Red haloBODIPYs as theragnostic agents: The role of the substitution at meso position

Three different molecular designs based on BODIPY dye have been proposed as photosensitizers (PSs) for photodynamic therapy (PDT) by the inclusion of halogen atoms (Iodine) at 2,6-positions and with extended conjugation at 3, 5-positions and varying the substitution at meso position. The synthesis is described and their main photophysical features including singlet oxygen production and triplet states were characterized by absorption and fluorescence spectroscopy (steady-state and time-correlated) and nanosecond transient absorption spectroscopy. The results were compared with the commercial Chlorin e6. The three new red-halogen-BODIPYs showed a great balance between singlet oxygen generation (ΦΔ≥0.40) and fluorescence (Φfl≥0.22) for potential application on PDT, and particularly in theragnosis. In vitro experiments in HeLa cells were done to study their performance and to elucidate the best potential candidate for PDT.

Conjugated Porous Polymers Based on BODIPY and BOPHY Dyes in Hybrid Heterojunctions for Artificial Photosynthesis (Adv. Funct. Mater. 51/2021)

Artificial Photosynthesis In article number 2105384, Laura Collado, Marta Liras, Javier Marugán, Víctor A. de la Peña O'Shea, and co-workers investigate hybrid heterostructures containing highly tuneable and photostable conjugated porous polymers (CPPs) coupled to inorganic semiconductors for solar fuel production via H2 evolution and CO2 photoreduction under UV/visible illumination. Photophysical studies reveal the potential of these hybrids to facilitate charge separation and transfer, considerably improving the photocatalytic activities for artificial photosynthesis or other light-mediated energy solutions.

Quinoline-functionalized BODIPY dyes: Structural and photophysical properties

BODIPYs at different positions of quinolines show similar absorption spectra but very different visible emission efficiency. Single-crystal structures show different tilting angles of quinoline groups and BODIPY core structure. The emission efficiency decreases as the torsion angle between BODIPY core and quinoline becomes smaller in the order of 4-Q-BDP > 3-Q-BDP > 2-Q-BDP ≈ 2,9-Phen-BDP. The restoration of fluorescence in the presence of methanol and theoretical calculations indicate the photoinduced electron transfer from quinoline N to BODIPY core could be responsible for such a gradual fluorescence change.

Characterization of cellular development and fatty acid accumulation in thraustochytrid Aurantiochytrium strains of Taiwan

Abstract Long-chain saturated and polyunsaturated fatty acids of two new thraustochytrid isolates cultured from Taiwan mangroves, Aurantiochytrium sp. IMB169 and Aurantiochytrium sp. IMB171, were characterized through their cell growth and development in relation to their intracellular lipid accumulation using transmission electron microscopy. Flow cytometry in combination with the lipophilic fluorescent dye BODIPY 505/515 was used to stain and characterize intracellular lipid bodies in the two isolates. The transmission electron microscopy and flow cytometry analyses revealed a progressive accumulation of lipid products in IMB169 and IMB171. Further, selective BODIPY stained cells were successfully separated and enriched using flow cytometry at single cell level. Among the two isolates, IMB169 was found to produce a high level of docosahexaenoic acid. The qualitative and analytical results obtained using electron microscopy and flow cytometry studies were validated by gas chromatography (GC). In addition, a quantitative baseline was established using cell growth, flow cytometry and GC analyses for developing an efficient bioprocessing methodology to selectively enrich thraustochytrids phenotypes with desirable characteristics.

Impact of the Arylation of Fused N-bridged BODIPY Dyes in Photophysical Properties.

Functionalization of BODIPY dyes is commonly used to modulate photophysical properties. Among the chemical modification of these dyes, ring fusion indifferent faces of dipyrromethene cores is gaining attention in the literature, due to the modulation of emission/absorption properties and fluorophores with increased bright. N-bridged arylated BODIPYs were recently synthesized and shows intense bright and blu shifted emission. However, few examples of substituted compounds are described and none involving arylation with extention of the π-conjugation. In this manuscript, it is shown an optimized method for the synthesis of N-bridged arylated BODIPYs, including arylated derivatives, and the studies of molecular properties. It is also shown that fluorinated aryl substituted N-bridged arylated BODIPYs show high quantum yields and are red-shifted compared to unsubstituted examples. The work open opportunities for application of the new developed compounds as probes.

Hydrophobic Cargo Encapsulation into Virus Protein Cages by Self-Assembly in an Aprotic Organic Solvent.

While extensive studies of virus capsid assembly in environments mimicking in vivo conditions have led to an understanding of the thermodynamic driving forces at work, applying this knowledge to virus assembly in other solvents than aqueous buffers has not been attempted yet. In this study, Brome mosaic virus (BMV) capsid proteins were shown to preserve their self-assembly abilities in an aprotic polar solvent, dimethyl sulfoxide (DMSO). This facilitated protein cage encapsulation of nanoparticles and dye molecules that favor organic solvents, such as β-NaYF4-based upconversion nanoparticles and BODIPY dye. Assembly was found to be robust relative to a surprisingly broad range of DMSO concentrations. Cargos with poor initial stability in aqueous solutions were readily encapsulated at high DMSO concentrations and then transferred to aqueous solvents, where they remained stable and preserved their function for months.

Inositol-Requiring Enzyme 1α-Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus-like Autoimmune Disease.

To explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE). B cells in peripheral blood from patients with SLE and healthy controls were stained with BODIPY dye for detection of lipids. Mice with targeted knockout of genes for B cell-specific inositol-requiring enzyme 1α (IRE-1α) and stearoyl-coenzyme A desaturase 1 (SCD-1) were used for studying the influence of the IRE-1α/SCD-1/SCD-2 pathway on B cell differentiation and autoantibody production. The preclinical efficacy of IRE-1α suppression as a treatment for lupus was tested in MRL.Faslpr mice. In cultures with mouse IRE-1α-null B cells, supplementation with monounsaturated fatty acidslargely rescued differentiation of plasma cells from B cells, indicating that the compromised capacity of B cell differentiation in the absence of IRE-1α may be attributable to a defect in monounsaturated fatty acidsynthesis. Moreover, activation with IRE-1α/X-box binding protein 1 (XBP-1) was required to facilitate B cell expression of SCD-1 and SCD-2, which are 2 critical enzymes that catalyze monounsaturated fatty acidsynthesis. Mice with targeted Scd1 gene deletion displayed a phenotype that was similar to that of IRE-1α-deficient mice, with diminished B cell differentiation into plasma cells. Importantly, in B cells from patients with lupus, both IRE-1α expression and Xbp1 messenger RNA splicing were significantly increased, and this was positively correlated with the expression of both Scd1 and Scd2 as well as with the amount of B cell lipid deposition. In MRL.Faslpr mice, both genetic and pharmacologic suppression of IRE-1α protected against the pathologic development and progression of lupus-like autoimmune disease. The results of this study reveal a molecular link in the dysregulation of lipid metabolism in the pathogenesis of lupus, demonstrating that the IRE-1α/XBP-1 pathway controls plasma cell differentiation through SCD-1/SCD-2-mediated monounsaturated fatty acidsynthesis. These findings provide a rationale for targeting IRE-1α and monounsaturated fatty acidsynthesis in the treatment of patients with SLE.

Cover Picture: Bringing Color to Sugars: The Chemical Assembly of Carbohydrates to BODIPY Dyes (Chem. Rec. 11/2021)

Cover Picture: Bringing Color to Sugars: The Chemical Assembly of Carbohydrates to BODIPY Dyes (Chem. Rec. 11/2021)

Rapid and Highly Selective BODIPY Based Turn‐Off Colorimetric Cyanide Sensor**

AbstractCyanide ion (CN− ion) is one of the most harmful inorganic pollutants wasted by various industrial processes. Although some spectroscopic methods are being used, these methods need advanced instrumentation and have high detection limits. Because of this, rapid, low‐cost and sensitive methods are highly required to detect CN− ion. Chemosensor application is one of the most useful methods for selective detection of the target analyte. BODIPY (boradiazaindacene) dyes are one of the promising candidates for these types of applications because of the unique optical and photophysical properties. Here, we report the first application of the meso‐formyl‐BODIPY dye‐based, rapid and naked‐eye CN− ion sensor application depending on the reaction of CN− ion and aldehyde functionality of the meso‐formylated BODIPY derivative (BODIPY‐BAL). Absorption and emission experiments were successfully conducted. Additionally, colorimetric tests were performed in solution and on test strips. The limit of detection of the chemosensor was calculated as 10.4 μM. Real sample experiments in seawater were also performed and CN− ion was detected at 50 μM concentration, which is the limit level of CN− ion concentration causes acute effects determined by the U.S. Environmental Protection Agency (EPA).

Effect of meso-substituents and solvent on the photo- and thermal stability of BODIPY dyes

In this paper, the effect of meso-substituents nature and solvent properties on the photo- and thermal stability of BODIPYs, was studied. It was found that the replacement of the hydrogen atom in the methine bridge by CH3 group, carboxylic acid residues (CH2)nCOOH or their esters (CH2)nCOOCH3 (where n = 3, 4) significantly increases the photo- and thermal stability of meso-substituted dyes compared to meso-unsubstituted analog that is in good agreement with the results of NBO analysis. It has been established that the photooxidation process of dyes in solutions proceeds more efficiently in aromatic toluene (in ∼2–3 times) and, especially, in the electron donor DMSO (in ∼10 times) compared to non-polar cyclohexane, which is due to the specific solvation of dye molecules by aromatic and polar solvents.

Isotretinoin-Delonix polymeric nanoparticles: Potentials for skin follicular targeting in acne treatment

In acne management, oral isotretinoin (IST) is associated with various untoward systemic effects, while its topical formulation has irritation side effects. Delonix (DLX) is a natural galactomannan derived from Delonix regia seed that can fabricate nanoparticles for topical skin delivery. This study aims to develop IST-DLX nanoparticles and assess their prospects for acne treatment. Fluorescent-DLX nanoparticles (made with a lipophilic BODIPY dye) or IST-DLX nanoparticles were prepared and characterized. BODIPY-DLX nanoparticles’ skin distribution and IST-DLX nanoparticles’ in-vitro targeting were assessed in pig ear skin, inflammatory modulation was assessed in AMJ-2 macrophage cells, while skin penetration and irritation were assessed in Wistar rats. IST-DLX nanoparticles had ≈230 nm, negative zeta potential, and ≈30% encapsulation efficiency. Confocal showed BODIPY in DLX nanoparticles accumulated in hair follicles as compared to BODIPY solution. IST-DLX nanoparticles released ≈37% IST over 48 h and increased IST 3-fold in hair follicles compared to IST solution. IST-DLX nanoparticles suppressed IL-6 expression in cells and reduced photo-irritation in Wistar rats compared to IST solution. In conclusion, IST-DLX nanoparticles may target and deliver adequate IST to skin layers associated with acne, avoid systemic penetration, modulate inflammatory pathogenic acne stage and prevent IST topical photo-irritation.

Pyridine substituted BODIPYs: synthesis, characterization and cholinesterease, α-glucosidase inhibitory, DNA hydrolytic cleavage effects

In this study, the synthesis of new monostyryl (BDPY-2) and distyryl BODIPY dyes (BDPY-4, BDPY-5) containing pyridine groups has been reported for the first time. The acetylcholinesterase from Electrophorus electricus (AChE), butyrylcholinesterase from equine serum (BuChE), α-glucosidase from Saccharomyces cerevisiae and DNA hydrolytic cleavage actions of BDPY-2, BDPY-4, BDPY-5 were investigated using various techniques. The results indicated that the compounds had varying inhibition properties against AChE, BuChE, and α-glucosidase. BDPY-4 was the most potent compound on AChE with IC50 of 54.78 ± 4.51 µM, and Lineweaver–Burk plots indicated that the compound is bound to a site other than the active site as a noncompetitive inhibitor. The compound-protein binding experiment showed that BDPY-4 changed the microenvironment around AChE. On the other hand, the compounds showed lower α-glucosidase inhibition than the positive control. The DNA hydrolytic cleavage effects were not observed on supercoiled plasmid DNA in the presence of the compounds as compared to negative controls. These findings suggested that BDPY-4 might be a promising compound to treat Alzheimer’s diseases.

Novel BODIPY-based fluorescent Lycopodium clavatum sporopollenin microcapsules for detection and removal of Cu(II) ions

In this study, microcapsules of L. clavatum sporopollenin (f-sporopollenin) immobilized with BODIPY were developed. XRD, SEM, and FTIR did characterization of f-sporopollenin, showing that the BODIPY dye was successfully introduced, and the microcapsule structure of f-sporopollenin microcapsules was well preserved after the post-grafting procedure. When Cu(II) was added to the f-sporopollenin suspension, the fluorescence intensity gradually decreased at ~541 nm. Furthermore, adding Cu(II) to suspension mixtures in the presence of other cations resulted in dramatic fluorescent quenching, which showed that it was excellent selectivity for Cu(II) ions. The linear detection range for low concentration Cu(II) detection was 1 – 10 µM, and the detection limit was 7.41 × 10−7 M (0.741 µM). Prepared f-sporopollenin was also used as an adsorbent to remove Cu(II) ions from aqueous solutions. The adsorption study showed that the optimum adsorption conditions were pH = 6.0, amount of adsorbent 0.04 g, initial Cu(II) concentration at 25 mg/L, and contact time of 120 min. Adsorption isotherms and kinetics have been studied and found to fit the Langmuir isotherm model and the pseudo-second-order kinetic. The theoretical maximum Langmuir adsorption capacity of Cu(II) towards f-sporopollenin was 22.71 mg/g. Therefore, f-sporopollenin shows promise for removing and detecting Cu(II) ions in water.

Palladium(II)-Catalyzed Dehydrogenative Strategy for Direct and Regioselective Oligomerization of BODIPY Dyes.

A family of directly β,γ-linked BODIPY oligomers up to pentamers were regioselectively prepared via Pd(II)-catalyzed oxidative C-H cross-coupling. The structural integrity of β,γ-linked dimers was unambiguously confirmed by X-ray crystallography. These structurally unprecedented oligomers showed red-shifted absorptions and near-infrared emissions along with efficient intersystem crossing, giving ΦΔ in the range of 12-43%, for potential use as heavy-atom-free photosensitizers.

One-Pot Access to Ethylene-Bridged BODIPY Dimers and Trimers through Single-Electron Transfer Chemistry.

A Cu(I)-promoted oxidative dimerization of BODIPY dyes was developed to give a series of α,α- ethylene-bridged BODIPY dimers and trimers for the first time. This methodology does not need harsh conditions but relies on the singlet-electron-transfer process between alkylated BODIPYs and Cu(I) salt to generate BODIPY-based radical species, which undergo a selective radical homocoupling reaction. Moreover, these resultant dimers and trimers showed high attenuation coefficients, small line widths of the absorption and emission, and intense fluorescence.