BODIPY Research Articles

BODIPY-based monofunctional Pt (II) complexes for specific photocytotoxicity against cancer cells

Photodynamic therapy (PDT) has attracted extensive attention in cancer treatment because of its minimum trauma, less side effects, and so on. Photosensitizers, as one of the core elements of PDT, usually have to face problems such as poor water solubility and light stability, lack of targeting, and other problems, which seriously affect the therapeutic effect. In this work, two BODIPY (boron-dipyrromethene)-based monofunctional Pt (II) complexes, 1a and 2a, were designed and synthesized, and their PDT effect was studied. The Pt atom improved the singlet oxygen quantum yield (0.19 for 1a and 0.14 for 2a, respectively), which effectively improves the efficiency of PDT. MTT assay confirmed that the short time photo-irradiation distinctly promoted antitumor cytotoxicity of Pt (II) compounds against different cell lines. For 1a under irradiation, the IC50 value of cancer cell lines were 13.1 μM for HeLa cells and 7.6 μM for MCF-7 cells, while those of normal cell lines were 32.4 μM for HBL-100 cells and 48.6 μM for L02 cells. The results demonstrated that 1a showed specific phototoxicity to cancer cells. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake (determined by ICP-MS) and higher ROS generation (detected by Cell ROX Deep Red) in cancer cells after irradiation. This study laid the foundation for the future design and synthesis of effective PDT photosensitizers.

Red light triggered photodynamic-chemo combination therapy using a prodrug caged by photosensitizer.

Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.

Ultrafast Electron/Energy Transfer and Intersystem Crossing Mechanisms in BODIPY-Porphyrin Compounds

Meso-substituted borondipyrromethene (BODIPY)-porphyrin compounds that include free base porphyrin with two different numbers of BODIPY groups (BDP-TTP and 3BDP-TTP) were designed and synthesized to analyze intramolecular energy transfer mechanisms of meso-substituted BODIPY-porphyrin dyads and the effect of the different numbers of BODIPY groups connected to free-base porphyrin on the energy transfer mechanism. Absorption spectra of BODIPY-porphyrin conjugates showed wide absorption features in the visible region, and that is highly valuable to increase light-harvesting efficiency. Fluorescence spectra of the studied compounds proved that BODIPY emission intensity decreased upon the photoexcitation of the BODIPY core, due to the energy transfer from BODIPY unit to porphyrin. In addition, ultrafast pump-probe spectroscopy measurements indicated that the energy transfer of the 3BDP-TTP compound (about 3 ps) is faster than the BDP-TTP compound (about 22 ps). Since the BODIPY core directly binds to the porphyrin unit, rapid energy transfer was seen for both compounds. Thus, the energy transfer rate increased with an increasing number of BODIPY moiety connected to free-base porphyrin.

Neural and behavioral control in Caenorhabditis elegans by a yellow-light–activatable caged compound

Caenorhabditis elegans is used as a model system to understand the neural basis of behavior, but application of caged compounds to manipulate and monitor the neural activity is hampered by the innate photophobic response of the nematode to short-wavelength light or by the low temporal resolution of photocontrol. Here, we develop boron dipyrromethene (BODIPY)-derived caged compounds that release bioactive phenol derivatives upon illumination in the yellow wavelength range. We show that activation of the transient receptor potential vanilloid 1 (TRPV1) cation channel by spatially targeted optical uncaging of the TRPV1 agonist N-vanillylnonanamide at 580 nm modulates neural activity. Further, neuronal activation by illumination-induced uncaging enables optical control of the behavior of freely moving C. elegans without inducing a photophobic response and without crosstalk between uncaging and simultaneous fluorescence monitoring of neural activity.

Molecular engineering of near-infrared active boron dipyrromethene moiety with various donors and acceptors for tuning the absorption behavior and electron injection of the resultant dyes

Small molecules having an absorption band beyond 750 nm for DSSC applications are scarce in the literature. Derivatives of boron dipyrromethane (BODIPY) are popular fluorophores in life sciences and hence used in fluorescent microscopy for staining different intracellular organelles, and BODIPY-based dye molecules have been known for the strong absorption in the visible and near IR regions. A series of twelve (Donor-π-linker)2-Ancillary Acceptor-Acceptor ((D-π)2-An-A)) based metal-free organic dyes comprising BODIPY moiety as an ancillary acceptor (An) were designed to fine-tune the panchromatic behavior of BODIPY dyes. Based on the density-functional theory (DFT) and time-dependent DFT, the photophysical and photoelectrochemical properties of the dyes were investigated. To convey the objective of the work, several photovoltaic parameters, such as dye regeneration driving force (ΔGreg), reorganization energy (Λ), chemical reactivity parameters, dye adsorption energy (Eads), and the density of states were calculated to justify the suitability of the dyes for the DSSCs application. This study identified six dyes with carbazole and phenothiazine-based donors as DSSC suitable panchromatic dyes.

New Idea for Narrowing an Energy Gap by Selective Perturbation of One Frontier Molecular Orbital

Abstract In this manuscript, we will illustrate a new idea for narrowing energy gaps between frontier molecular orbitals (FMOs) by selectively perturbing the levels of highest occupied molecular orbitals (HOMOs) and/or lowest unoccupied molecular orbitals (LUMOs). Initially, the basic concept of the isolated FMOs is explained by employing pentaazaphenalene (5AP) derivatives. It was found that electronic structures of the isolated LUMO of 5AP can be preserved even when incorporated into polymer chains if the connecting points are separated from the isolated LUMO. The mechanism and their unique electronic properties are summarized. Next, conversely, isolated HOMO and LUMO can be perturbed by conjugation effects independently. On the basis of this fact, near infrared (NIR)-absorbing molecules can be obtained by selectively elevating HOMO and lowering LUMO energy levels. We also mention strategies for enhancing luminescent properties of 5AP derivatives. Finally, we demonstrate that the isolated LUMO can be found in commodity luminescent dyes, such as boron dipyrromethene (BODIPY). By selectively lowering the LUMO energy level through the aza-substitution at the skeletal carbon where the isolated LUMO is distributed, NIR-emissive polymers can be obtained. Versatility of the isolated FMOs for obtaining optoelectronic organic materials is explained in this review.

Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides.

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(N3)LARLLT and its cyclic analog cyclo(K(N3)larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70–82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm−2) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein.

A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes

AbstractInstallation of a carbanionic substituent, that is strongly stabilized by two (trifluoromethyl)sulfonyl (Tf=SO2CF3) groups, into several fluorescence dyes including boron‐dipyrromethenes (BODIPYs), fluoresceins, and aminocoumarins has been achieved by the 2,2‐bis(triflyl)ethylation reaction of the dye frameworks with highly electrophilic Tf2C=CH2, followed by neutralization with NaHCO3. Despite the contradiction between water solubility and lipophilicity, the carbanion‐decorated dyes thus obtained showed significant enhancement of not only water solubility but also lipophilicity. This work clearly demonstrates that the fluorinated, highly stabilized carbanionic substituent is a new option for controlling the macroscopic property of chemical materials.

A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes.

Installation of a carbanionic substituent, that is strongly stabilized by two (trifluoromethyl)sulfonyl (Tf=SO2 CF3 ) groups, into several fluorescence dyes including boron-dipyrromethenes (BODIPYs), fluoresceins, and aminocoumarins has been achieved by the 2,2-bis(triflyl)ethylation reaction of the dye frameworks with highly electrophilic Tf2 C=CH2 , followed by neutralization with NaHCO3 . Despite the contradiction between water solubility and lipophilicity, the carbanion-decorated dyes thus obtained showed significant enhancement of not only water solubility but also lipophilicity. This work clearly demonstrates that the fluorinated, highly stabilized carbanionic substituent is a new option for controlling the macroscopic property of chemical materials.

A Fluorescent Visual Proton Donor and Photoacid Sterilant Based on Sulfonate-conjugated BODIPY.

Increasing acidity is an effective method for bacterial inactivation by inhibiting the synthesis of intracellular proteins at low pH. Photo-driven proton release probe can be used for the measurement of proton in hydrophobic condition. To develop fluorescent proton donor, two boron dipyrromethene derivatives (BDP-S and BDP-S2) were characterized by spectroscopic methods. Irradiation of BDP-S by white LED light resulted in efficient generation of acidic species with changes of fluorescence emission. The linear relationship between the pH value and the fluorescence intensity of BDP-S was obtained, indicating that BDP-S is a fluorescent visual proton donor. Light-induced antibacterial results indicate that BDP-S can significantly inhibit the growth of E. coli. The results prove that BDP-S is a very promising photoacid sterilant.

Near-Infrared-II Nanoparticles for Cancer Imaging of Immune Checkpoint Programmed Death-Ligand 1 and Photodynamic/Immune Therapy.

Development of second near-infrared (NIR-II) nanoparticles (NPs) with high biocompatibility, low toxicity, and high singlet oxygen quantum yield (ΦΔ) to prevent tumor recurrence is highly desirable in molecular imaging and photodynamic/immune combination therapy. Here, theranostic photosensitizer BODIPY (BDP)-I-N-anti-PD-L1 NPs were developed by encapsulating the photosensitizer BDP-I-N with amphipathic poly(styrene-co-chloromethylstyrene)-graft-poly(ethylene glycol) nanocarriers through self-assembly functionalization with programmed cell death-ligand 1 (PD-L1) monoclonal antibody. These NPs exhibit highly intensive luminescence in the NIR-II window (1000-1700 nm) to real-time imaging of immune checkpoint PD-L1, high singlet oxygen quantum yield (ΦΔ = 73%), and an eliminating effect of primary cancers. The NPs also allow for profiling PD-L1 expression as well as accumulating in MC38 tumor and enabling molecular imaging in vivo. Upon an 808 nm laser excitation, the targeted NPs produce an emission wavelength above 1200 nm to image a tumor to a normal tissue signal ratio (T/NT) at an approximate value of 14.1. Moreover, the MC38 tumors in mice are eliminated by combining photodynamic therapy and immunotherapy within 30 days, with no tumor recurrence within a period of 40 days. In addition, the tumors do not grow in the rechallenged mice within 7 days of inoculation. Such a strategy shows a durable immune memory effect against tumor rechallenging without toxic side effects to major organs.

Thiophene Donor for NIR-II Fluorescence Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared windows. However, their applications in the second near-infrared (NIR-II) windows are still limited primarily owing to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) as the molecularly engineered thiophene donor unit with high QYs to the redshift is created. Thiophene insertion initiates substantial redshifts of the absorbance, as compared to its counterparts that introduce iodine. The fluorescent molecule can be triggered by a NIR laser with a single wavelength, producing emission in the NIR-II windows. Single NIR laser triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and chemotherapy drug docetaxel (DTX) using a synthetical amphiphilic poly(styrene- co -chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen quantum yield (ΦΔ =62%), but also demonstrate a single NIR laser-triggered multifunctional characteristics. After intravenous injection of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor presented a high signal-to-background ratio (11.8). Furthermore, the 4T1 tumors in mice were almost eradicated by released DTX and PDT/PTT combination therapy from the BDP-T-N-DTX-FA NPs under the single NIR laser excitation.

Construction of ultrasensitive devices for visualization and quantification of phosgene based on FRET-mediated two-photon chemosensor

As a widely used but highly toxic chemical species, phosgene is threatening to human health because of possible accidental leakage during industrial manufacture. Herein, we exploited a turn-on fluorescent sensor F671 for phosgene detection. The exact distance of nitro benzoxadiazole (NBD) and boron dipyrromethene (BODIPY) in F671 was changed from 5.027 Å to 15.535 Å after reaction with phosgene, accompanied with obvious fluorescence enhancement, which is attributed to the inhibition of Förster resonance energy transfer (FRET) process. The FRET-associated strategy possesses the capacity of detecting phosgene with a rapid response time (<6 s), ultra-sensitivity (LOD = 0.36 nM in solution and 0.14 ppm in gas phase) and remarkable selectivity to phosgene in solutions and in gas phase. Furthermore, the F671-embedded degreasing cotton, has been fabricated to serves as a specific gaseous phosgene device, for facile, selective and visual detection of phosgene gas. Confocal imaging of F671-embedded degreasing cotton displayed increasing emission intensity in the presence of phosgene in both of one-photon and two-photon patterns. It is envisioned that the developed convenient device is a promising tool for phosgene gas detection and quantification in real industrial and environmental applications.

Unique PDT and PTT synergistic effect between TPE and BODIPY.

A novel intermolecular system D-π⋯π'-A was constructed with tetraphenylethylene (TPE) and borondipyrromethene (BODIPY), which had a synergistic effect on PDT and PTT (1 + 1 > 2). The PTT effect of TPD-BOA(D/A) was 1.7 times the sum of BOA + TPD; the effect of PDT(TPA+BOD) was 1.45 times the sum of TPA + BOD.

Leveraging BODIPY nanomaterials for enhanced tumor photothermal therapy.

In the past ten years, photothermal therapy (PTT) has attracted widespread attention in tumor treatment due to its non-invasiveness and little side effects. PTT utilizes heat produced by photothermal agents under the irradiation of near-infrared light to kill tumor cells. Boron-dipyrromethene (BODIPY), an organic phototherapy agent, has been widely used in tumor phototherapy due to its higher molar extinction coefficient, robust photostability and good phototherapy effect. However, there are some issues in the application of BODIPY for tumor PTT, such as low photothermal conversion efficiency and short absorption wavelength. In this review, we focus on the latest development of BODIPY nanomaterials for overcoming the above problems and enhancing the PTT effect.

Accelerated discovery of boron-dipyrromethene sensitizer for solar cells by integrating data mining and first principle

Boron-dipyrromethene (BODIPY) is one promising class of sensitizers for dye-sensitized solar cells (DSSCs) due to unique merits of high absorption coefficient and versatile structural modification capability. However, such derivatives usually suffer from limited power conversion efficiencies (PCEs) because of narrow light absorption band and low electron injection. To aid the discovery of BODIPY sensitizers, we employ an inverse design method to design efficient sensitizers by integrating data mining and first-principle techniques. We establish robust data-mining models using genetic algorithm and multiple linear regression, where the features are filtered from 5515 descriptors and their meanings are explicitly explored for next inverse designs. Based on the features’ understanding, we design candidates NH1-6 and predict their PCEs, demonstrating remarkable enhancements (58% maximum) compared to previous works. Furthermore, their optoelectronic properties including maximum absorption wavelengths, oscillator strengths, bandgaps, transferred charges, charge transferred distances, TiO2 conduction band shifts, short-circuit currents and electron injection efficiencies simulated via first-principle calculations indicate significant increasements (93 nm, 122.41%, 23.70%, 36.36%, 471.17%, 63.64%, 28.55%, 107.86% maximum), which testifies the corresponding highly predicted PCEs and may overcome BODIPY dyes’ shortcomings. The as-designed BODIPY sensitizers can be promising candidates for DSSCs, and such method could help accelerate the discovery of other energy materials.

A boron dipyrromethene (BODIPY) based probe for selective passive sampling of atmospheric nitrous acid (HONO) indoors.

People spend up to 90% of their time indoors, and yet our understanding of indoor air quality and the chemical processes driving it are poorly understood, despite levels of key pollutants typically being higher indoors compared to outdoors. Nitrous acid (HONO) is a species that drives these indoor chemical processes, with potentially detrimental health effects. In this work, a BODIPY-based probe was synthesized with the aim of developing the first selective passive sampler for atmospheric HONO. Our probe and its products are easily detected by UV-Vis spectroscopy with molar extinct coefficients of 37 863 and 33 787 M-1 cm-1, respectively, and a detection limit of 14.8 ng mL-1. When protonated, the probe fluoresces with a quantum yield of 33%, which is turned off upon reaction. The synthesized BODIPY probe was characterized using NMR and UV-Vis spectroscopy. Products were characterized by UV-Vis and ultra high-resolution mass spectrometry. The reaction kinetics of the probe with nitrite was studied using UV-Vis spectroscopy, which had a pseudo-first-order rate of k = 7.7 × 10-4 s-1. The rapid reaction makes this probe suitable for targeted ambient sampling of HONO. This was investigated through a proof-of-concept experiment with gaseous HONO produced by a custom high-purity calibration source delivering the sample to the BODIPY probe in an acidic aqueous solution in clean air and a real indoor air matrix. The probe showed quantitative uptake of HONO in both cases to form the same products observed from reaction with nitrite, with no indication of interferences from ambient NO or NO2. The chemical and physical characteristics of the probe therefore make it ideal for use in passive samplers for selective sampling of HONO from the atmosphere.

Excited state dynamics of BODIPY-based acceptor-donor-acceptor systems: a combined experimental and computational study.

Donor-bridge-acceptor systems based on boron dipyrromethene (BODIPY) are attractive candidates for bio-imagining and sensing applications because of their sensitivity to temperature, micro-viscosity and solvent polarity. The optimization of the properties of such molecular sensors requires a detailed knowledge of the relation between the structure and the photophysical behavior in different environments. In this work we have investigated the excited-state dynamics of three acceptor-donor-acceptor molecules based on benzodithiophene and BODIPY in solvents of different polarities using a combination of ultrafast spectroscopy and DFT-based electronic structure calculations. Transient absorption spectra show that upon photoexcitation an initial excited species with an induced absorption band in the near-infrared regime is formed independent of the solvent polarity. The subsequent photophysical processes strongly depend on the solvent polarity. In non-polar toluene this initial excited state undergoes a structural relaxation leading to a delocalized state with partial charge transfer character, while in the more polar tetrahydrofuran a fully charge separated state is formed. The results clearly show how factors such as donor-acceptor distance and restricted rotational motion by steric hindrance can be used to tune the excited state photophysics to optimize such systems for specific applications.

Modulation of supramolecular self-assembly of BODIPY tectons via halogen bonding

In this study, the efficiency of halogen bonding strategies to control over the supramolecular assemblies of boron dipyrromethene (BODIPY) (B-1, B-2, and B-3) derivatives was explored.

Coherent internal conversion from high lying electronic states to S1 in boron-dipyrromethene derivatives.

Internal conversion is the first step after photoexcitation to high lying electronic states, and plays a central role in many photoinduced processes. In this report, we demonstrate a truly ultrafast internal conversion (IC) in large molecules by time-resolved fluorescence (TF). Following photoexcitation to the Sn (n ≥ 2) state, TF of the S1 state was recorded for two boron-dipyrromethene (BODIPY) derivatives in solution. IC to S1 takes place nearly instantaneously within 20 fs for both molecules. Abundant nuclear wave packet motions in the S1 state are manifest in the TF signals, which demonstrates that the IC in these BODIPY molecules is coherent with respect to most of the vibrational modes. Theoretical calculations assuming impulsive IC to S1 account for the wave packet dynamics accurately.