BODIPY Derivatives Research Articles

D-A-D type small molecule donors based on BODIPY skeleton for bulk heterojunction organic solar cells

In recent years, structural modification for boron-dipyrromethene (BODIPY) derivatives has been proven to be an effective way to improve their performance of organic solar cells (OSCs). Here, three D-A-D type small molecule donors BDP-1, BDP-2 and BDP-3 were synthesized based on 3,5,8-trimethyl BODIPY dye as the core by the introduction of 4-(diethylamino)phenyl, 4-diethylamino-2-methoxyphenyl and 4-(diphenylamino)phenyl at the 3, 5 and 8 positions, respectively, and used for the construction of organic solar cells. BDP-1, BDP-2, and BDP-3 are synthesized. Due to the strong electron-donating ability of the substituted groups at 3, 5, and 8 positions of BODIPY core, three donors exhibit extended π-conjugation and effective intramolecular charge transfer, resulting in the strong absorption in the range of 500–––900 nm with narrow band gaps below 1.52 eV. BDP-1, BDP-2 and BDP-3 display complementary absorption spectra and suitable highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital levels (LUMO) with fullerene derivative PC71BM. These molecules (BDP-1, BDP-2 or BDP-3) as electron donor were applied into BHJ solar cells by using PC71BM as electron acceptor. The performance of BHJ organic solar cells is systematically investigated and compared. The optimized solar cells based on BDP-1, BDP-2 and BDP-3 show high power conversion efficiencies (PCEs) of 9.52%, 11.83% and 5.27%, respectively. The OSCs based on BDP-2: PC71BM exhibited excellent short-circuit current density (Jsc), high electron mobility and open-circuit voltage (Voc). This work demonstrates that BODIPY derivatives with simple-structured show great potential for high performance OSCs.

BODIPY-Based Mitochondrial Targeted NIR-Responsive CO-Releasing Platform for the On-Demand Release of CO to Treat Cancer.

It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered meso-substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two meso-substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of ∼50 μM.

A new gold electrode modified with azido-terminal BODIPY derivative: synthesis, characterization and electrochemical property

A new gold electrode modified with azido-terminal BODIPY derivative: synthesis, characterization and electrochemical property

Colorimetric Chemosensor for Cu2+ and Fe3+ Based on a meso-Triphenylamine-BODIPY Derivative.

Optical chemosensors are a practical tool for the detection and quantification of important analytes in biological and environmental fields, such as Cu2+ and Fe3+. To the best of our knowledge, a BODIPY derivative capable of detecting Cu2+ and Fe3+ simultaneously through a colorimetric response has not yet been described in the literature. In this work, a meso-triphenylamine-BODIPY derivative is reported for the highly selective detection of Cu2+ and Fe3+. In the preliminary chemosensing study, this compound showed a significant color change from yellow to blue-green in the presence of Cu2+ and Fe3+. With only one equivalent of cation, a change in the absorption band of the compound and the appearance of a new band around 700 nm were observed. Furthermore, only 10 equivalents of Cu2+/Fe3+ were needed to reach the absorption plateau in the UV-visible titrations. Compound 1 showed excellent sensitivity toward Cu2+ and Fe3+ detection, with LODs of 0.63 µM and 1.06 µM, respectively. The binding constant calculation indicated a strong complexation between compound 1 and Cu2+/Fe3+ ions. The 1H and 19F NMR titrations showed that an increasing concentration of cations induced a broadening and shifting of the aromatic region peaks, as well as the disappearance of the original fluorine peaks of the BODIPY core, which suggests that the ligand-metal (1:2) interaction may occur through the triphenylamino group and the BODIPY core.

Near-infrared fluorescent Aza-BODIPY dyes: Rational structural design and biomedical imaging

Near-infrared dyes have attracted widespread attention due to their intense absorption and emission in the near-infrared region. As an important class of heteroatom-containing BODIPY derivatives, Aza-BODIPY dyes display excellent performances, such as red-shifted spectra, high molar extinction coefficients, and good photostability. In this review, we summarize the latest advances in Aza-BODIPY dyes. The regulation strategies for photophysical properties and their applications in biomedical imaging are highlighted. Furthermore, we discuss the versatile imaging applications of Aza-BODIPY dyes in cancer diagnoses, organ injuries, and surgical navigation. The future challenges and development prospects of Aza-BODIPY dyes in biomedical field are also presented. We aim at providing meaningful inspiration for further development of functional organic dyes with excellent properties. It is believed that this review will illuminate the way for the development of new Aza-BODIPY contrast agents as well as other organic photosensitizer-based contrast agents in future clinical practices.

BODIPY doping of covalent organic frameworks-based nanomaterials: A novel strategy towards biomedical applications

Covalent organic Frameworks (COFs) are a class of crystalline macromolecular materials build-up by monomers with specific symmetries or functionalities. There are important limitations in the synthesis of highly ordered COFs, such as the shape and packing of the building blocks. Thus, the presence of fluorine atoms that lie perpendicular to the bisecting plane of BODIPY derivatives together with the presence of four bulky methyl groups could hinder the crystallization process in COF synthesis. For that reason, BODIPY-based COFs are rarely incorporated to COF networks. In this work, following the mixed linker strategy, a pre-synthetic method to dope COF structures with BODIPY units was developed. The materials have been processed into fluorescent Covalent Organic Nanosheets (CONs) with defined particle-size distributions around 100 nm, suitable for cellular biomedical applications. The viability of the CONs was evaluated using Sk-Mel-103 cells, demonstrating the internalization showing 100% cell viability. We envisage that this work could accelerate the discovery of new COF-based materials for biomedical sciences.

BODIPY‐based Fluorescent Indicators for Lipid Droplets

AbstractLipid droplets are essential for cellular lipid storage, playing critical roles in cellular lipid metabolism. Although lipid droplets have drawn intense research in recent years, much remains to be uncovered about the roles of this organelle in biology. Lipid droplet indicators exhibiting large Stokes shifts and improved brightness are therefore in demand. We report two asymmetric BODIPY derivatives, BoL1 and BoL2 bearing a benzothiazole group at the 6‐position, which led to bathochromic shifts of 62 nm for BoL1 and 37 nm for BoL2 in fluorescence emission when compared to the reference molecules without the benzothiazole group. The incorporation of the benzothiazole moiety also resulted in a large Stokes shift of 40 nm. BoL1 and BoL2 have been demonstrated to operate as lipid droplet indicators in both confocal and STED imaging. BoL2 showed particularly good cellular retention and was further applied to explore the impact of cellular starvation on the trafficking of lipid droplets.

Recent Developments in the Design of New Water-Soluble Boron Dipyrromethenes and Their Applications: An Updated Review.

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.

Synthesis and characterization of novel BODIPYs and their antioxidant, antimicrobial, photodynamic antimicrobial, antibiofilm and DNA interaction activities.

In the current study, we synthesized and characterized new BODIPY derivatives (1-4) having pyridine or thienyl-pyridine substituents at meso- position and 4-dibenzothienyl or benzo[b]thien-2-yl moieties at 2-,6- positions. We investigated fluorescence properties and the ability to form singlet oxygen. In addition, various biological activities of BODIPYs such as DPPH scavenging, DNA binding/cleavage ability, cell viability inhibition, antimicrobial activity, antimicrobial photodynamic therapy (aPDT) and biofilm inhibition properties were performed. BODIPY derivatives BDPY-3 (3) and BDPY-4 (4) have high fluorescence quantum yields as 0.50 and 0.61 and 1 O2 quantum yields were calculated as 0.83 for BDPY-1 (1), 0.12 for BDPY-2 (2), 0.11 for BDPY-3 and 0.23 for BDPY-4. BODIPY derivatives BDPY-2, BDPY-3 and BDPY-4 displayed 92.54 ± 5.41%, 94.20 ± 5.50%, and 95.03 ± 5.54% antioxidant ability, respectively. BODIPY compounds showed excellent DNA chemical nuclease activity. BDPY-2, BDPY-3 and BDPY-4 also exhibited 100% APDT activity against E. coli at all tested concentrations. In addition to these, they demonstrated a highly effective biofilm inhibition activity against Staphyloccous aureus and Pseudomans aeruginosa. BDPY-4 showed the most effective antioxidant and DNA cleavage activity, while BDPY-3 exhibited the most effective antimicrobial and antibiofilm activity.

Influence of iodine substitution on electrochemical properties and energy levels of BODIPY derivatives

Four boron-dipyrromethene derivatives (BODIPYs) were investigated to assess the influence of the iodine substitution on their electrochemical properties. The performed CV and DPV scans revealed an increase in the number of redox pairs in iodine-substituted derivatives compared to unsubstituted ones, from one reduction and one or two oxidations to two reductions and two oxidations. The calculated electrochemical energy band gap was decreased by approx. 0.6 eV in the case of neutral iodinated derivative 3 compared to parent compound 1, indicating the possible future application of substituted species as semiconductors. The electrolysis of 3 and 4 showed the formation of anion radicals of BODIPYs. The additional DFT studies confirmed the decrease of the HOMO-LUMO energy band gap when the halide atom was inserted into the core and allowed to locate the orbitals.

Dual Chromophoric Meso‐Aryl BODIPYs with Aggregation Induced Red‐Emission Characteristics: Optical Properties and their Application in Fe3+ Detection

AbstractHerein, we report the design of meso‐aryl BODIPYs as a structural motif for aggregation‐caused quenching (ACQ) to aggregation‐induced emission (AIE) transformation. A series of meso‐aryl BODIPY derivatives were synthesized, by systematically increasing the size of the chromophore at the meso‐position from phenyl to pyrene. The effect of various factors, such as the aryl ring size, solvents, viscosity, and metal cations, on the photophysical properties was analyzed. The emission properties are well correlated with the flexibility of the aromatic ring for free rotation around the Caryl−CBODIPY bond. Accordingly, meso‐phenanthrene BODIPY (PhB) has the highest emission characteristics. The emission property of less bulky aryl‐substituted BODIPYs increases by increasing the solvent viscosity. The interaction of Fe3+ ions with aryl‐BODIPYs provides a prominent photophysical response based on Lewis‐acid supported decomplexation of BF2 in aryl‐BODIPYs. The bichromophoric meso‐aryl BODIPYs exhibit notable intramolecular excitation energy transfer from the aromatic ring to the BODIPY core, which is higher in meso‐anthracene BODIPY(AB). Hence, decorating BODIPYs with polycyclic aromatic systems generates a twisted structure, which inhibits the π‐π stacking between the planar aromatic molecules. This can be proposed as an effective approach at the molecular level to convert planar aryl luminophores having ACQ to AIEgens. Besides, the meso‐pyrene BODIPY derivative shows excellent mechanofluorochromic behaviour.

Cationic BODIPY Photosensitizers for Mitochondrion-Targeted Fluorescence Cell-Imaging and Photodynamic Therapy.

The straightforward synthesis of three cationic boron-dipyrromethene (BODIPY) derivatives and their mitochondria-targeting and photodynamic therapeutic (PDT) capabilities are reported. Two cancer cell lines (HeLa and MCF-7) were used to investigate the PDT activity of the dyes. Compared to their non-halogenated counterparts, halogenated BODIPY dyes exhibit lower fluorescence quantum yields and enable the efficient production of singlet oxygen species. Following LED light irradiation at 520 nm, the synthesized dyes displayed good PDT capabilities against the treated cancer cell lines, with low cytotoxicity in the dark. In addition, functionalization of the BODIPY backbone with a cationic ammonium moiety enhanced the hydrophilicity of the synthesized dyes and, consequently, their uptake by the cells. The results presented here collectively demonstrate the potential of cationic BODIPY-based dyes as therapeutic drugs for anticancer photodynamic therapy.

Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents.

Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives (1-3) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and 1 O2 emission were obtained only under acidic conditions inducing amine protonation. The pKa values and pH-dependent emissive properties of 1-3 being established, their cellular uptake and activation in the lysosomal vesicles (pH≈4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC50 between 0.16 and 0.06 μM) against HeLa cancer cells.

Neutral BODIPY derivatives as photosensitizers

A series of 2,6-dibromo-, 2,6-diiodo-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, together with the 4,4-dicyano analogs were synthesized. The photostability of these BODIPY derivatives and their efficiencies in generating singlet oxygen species were determined. Among these, 2,6-dibromo-4,4-dicyano-4-bora-3a,4a-diaza-s-indacene (BODIPY 6) was found to be similarly photostable as Rose Bengal, while 2,6-diiodo-8-iodomethyl-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY 10) and 1,3,5,7,8-pentamethyl-2,6-diiodo-4,4-dicyano-4-bora-3a,4a-diaza-s-indacene (BODIPY 5) were found to be the least stable. For the ability to generate singlet oxygen species, 2,6-dibromo- (BODIPY 3) and 2,6-diiodo-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY 2) were found to be more efficient than Rose Bengal, while BODIPY 10 and 1,3,5,7,8-pentamethyl-2,6-diiodo-4,4-dicyano-4-bora-3a,4a-diaza-s-indacene (BODIPY 5) were quite poor photosensitizers. When Bacillus subtilus cultures were supplemented with the photosensitizers and exposed to light, it was found that the presence of a positive charge in the photosensitizers was essential in order for them to be effective bacterialcidal agents.

Stereochemical Control of Secondary Benzamide-based BODIPY Emitters.

Aromatic amides can be used to construct light-harvesting materials with valuable optical properties. The amide bond is formed using well-known coupling agents in near quantitative yield, as illustrated here through the synthesis of two boron dipyrromethene derivatives bearing an amide linkage. The primary concern with acyl amides is rotation around the C-N bond, leading to cis and trans isomers. Using NMR spectroscopy, quantum chemical calculations and critical comparison to simpler benzamides, the stereochemistry of the target compounds has been addressed. The N-cyclohexyl derivative gave diffraction quality crystals that established a trans geometry for the amide bond. Quantum chemical calculations support the trans geometry as being the lowest-energy structure in solution but indicate that inversion of the aryl ring is an important structural feature. Indeed, rotation around the C(sp2 )-C(aryl) bond has a strong influence on the solution-phase NMR spectra. The amide connection has minimal effect on the photophysical properties.

Conformational effect on the photophysics of two BODIPY dyes in a mixture of butanol and acetonitrile: Insight from the steady-state, fluorescence time-resolved spectroscopy and TD-DFT calculations

We studied the effect of acetonitrile-butanol-1 mixture composition on the photophysics (absorption, fluorescence emission spectra, the quantum yield as well as the relaxation of the excited state) of two BODIPY derivatives with an aryl and pyridine substituent in the meso position and methyl (ethyl) in α,β-position. The behavior of these photophysical properties (fluorescence quantum yields, fluorescence lifetimes, radiative and nonradiative constants) as a function of the mixture composition points to its correlation with the rotation of the phenyl group that is possible in BDP2 while it is hindered in BDP1 as a channel of the excited state energy relaxation. As a consequence, the photophysical properties of BDP1 are weakly dependent on the mixture composition while those of BPD2 undergo two stages of variation. In the low mole fraction of Butanol-1 (lower than 0.48), where the viscosity changes by 0.8 MPa.s, the BDP2 photophysical properties are slightly dependent on the mixture composition. We conjecture that the free rotation of the phenyl group allows both radiative and nonradiative excited state relaxation to occur. This is shown by a relatively high fluorescence quantum yield and nonradiative constant values that remain constant in this range of butanol-1 mol fraction. For its further increase, the photophysical properties become strongly dependent on the change of the mixture composition and this was associated with the gradual increase of the viscosity by a factor of 1.7 MPa.s that results in a hindrance of the rotation of the phenyl group. This makes 8-phenyl substituted BDP2 a sensitive molecular rotor for small changes in viscosity between 0.2 and 3 MPa.s.

A BODIPY-based fluorescent chemosensor with 2, 6-substitution for visual and highly selective detection of S2–

BODIPY derivatives have often been employed as fluorescent sensors to probe toxic ions in environment and living systems, such as sulfide ion (S2−). Whilst many structure modifications have been exploited on groups at the 3, 5, 8-positions, there are quite few examples on tailoring the 2,6-substituents for chemosensor investigations. Herein, we design and synthesize a 2,6-substituted BODIPY molecule, LM-BDP, to use as a fluorescent probe for detecting S2− in aqueous media. The electronic and crystal structures of the probe are studied by density functional theory (DFT) calculations and single-crystal X-ray diffraction analysis. Spectroscopy investigations are performed in a variety of conditions, showing that LM-BDP exhibits a noticeable color change from pink to dark red and a fluorescence shift from yellow to pink channel with decreased intensity upon addition of S2−. The selectivity and sensitivity measurements show that LM-BDP can only response to S2− with a detection limit of 0.29 μM in less than 100 s. The remarkable contrast in fluorescence images in test-stripe and RAW 264.7 cell experiments indicates that the probe is a proper candidate for the application in detecting exogenous S2−.

Hydrogen peroxide enhanced photoinactivation of Candida albicans by a novel boron-dipyrromethene (BODIPY) derivative.

Photodynamic inactivation (PDI) has received increasing attention as a promising approach to combat Candida albicans infections. This study aimed to evaluate the synergistic effect of a new BODIPY (4,4-difluoro-boradiazaindacene) derivative and hydrogen peroxide on C. albicans. BDP-4L in combination with H2O2 demonstrated enhanced photokilling efficacy. In suspended cultures of C. albicans, the maximum decrease was 6.20 log and 2.56 log for PDI using BDP-4L (2.5μM) with or without H2O2, respectively. For mature C. albicans biofilms, 20μM BDP-4L plus H2O2 eradicated C. albicans, causing an over 6.7 log count reduction in biofilm-associated cells, while only a reduction of ~ 1 log count was observed when H2O2 was omitted. Scanning electron microscopy analysis and LIVE/DEAD assays suggested that PDI using BDP-4L plus H2O2 induced more damage to the cell membrane. Correspondingly, amplification of nucleic acids release was observed in biofilms treated with the combined PDI. Additionally, we also discovered that the addition of hydrogen peroxide potentiated the generation of 1O2 in PDI using the singlet oxygen sensor green probe. Collectively, BDP-4L combined with H2O2 presents a promising approach in the treatment of C. albicans infections.

An oxygen-carrying and lysosome-targeting BODIPY derivative for NIR bioimaging and enhanced multimodal therapy against hypoxic tumors.

Cancer treatment modalities have gradually shifted from monotherapies to multimodal therapies. It is still a challenge to develop a synergistic chemo-phototherapy system with relieving tumor hypoxia, specific targeting, and real-time fluorescence tracking. In this study, we designed a multifunctional BODIPY derivative, FBD-M, for synergistic chemo-phototherapy against hypoxic tumors. FBD-M was composed of four parts: 1) The BODIPY fluorophore selected as a theranostic core, 2) A pentafluorobenzene group modified on meso-BODIPY to carry oxygen, 3) A morpholine group hooked to one side of BODIPY served as a lysosome-targeting unit for enhancing antitumor effect, and 4) An aromatic nitrogen mustard group introduced on other side of BODIPY to achieve chemotherapy. After introducing the morpholine and aromatic nitrogen mustard in BODIPY, the conjugate system of BODIPY was also expanded to realize near-infrared (NIR) phototherapy. Finally, FBD-M was obtained by a rational design, which possessed with NIR absorbance and emission, photosensitive activity, oxygen-carrying capability for relieving tumor hypoxia, high photothermal conversion efficiency, good photostability, lysosome targeting, low toxicity, and synergistic chemo-phototherapy against hypoxic tumors. FBD-M had been successfully applied for anticancer in vitro and in vivo. Our study demonstrates that FBD-M can serve as an ideal multifunctional theranostic agents.

BODIPY-Perylene Charge Transfer Compounds; Sensitizers for Triplet-Triplet Annihilation Up-conversion.

BODIPY heterochromophores, asymmetrically substituted with perylene and/or iodine at the 2 and 6 positions were prepared and investigated as sensitizers for triplet-triplet annihilation up conversion (TTA-UC). Single-crystal X-ray crystallographic analyses show that the torsion angle between BODIPY and perylene units lie between 73.54 and 74.51, though they are not orthogonal. Both compounds show intense, charge transfer absorption and emission profiles, confirmed by resonance Raman spectroscopy and consistent with DFT calculations. The emission quantum yield was solvent dependent but the emission profile remained characteristic of CT transition across all solvents explored. Both BODIPY derivatives were found to be effective sensitizers of TTA-UC with perylene annihilator in dioxane and DMSO. Intense anti-Stokes emission was observed, and visible by eye from these solvents. Conversely, no TTA-UC was observed from the other solvents explored, including from non-polar solvents such as toluene and hexane that yielded brightest fluorescence from the BODIPY derivatives. In dioxane, the power density plots obtained were strongly consistent with TTA-UC and the power density threshold, the Ith value (the photon flux at which 50 % of ΦTTAUC is achieved), for B2PI was observed to be 2.5x lower than of B2P under optimal conditions, an effect ascribed to the combined influence of spin-orbit charge transfer intersystem crossing (SOCT-ISC) and heavy metal on the triplet state formation for B2PI.