BODIPY Groups Research Articles

Synthesis of Bodipy-Tagged Galactoconjugates and Evaluation of Their Antibacterial Properties.

As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis and early bactericidal tests of two luminescent glycoconjugates whose basic structure is characterized by two boron dipyrromethene difluoride (BODIPY) moieties and three galactoside rings mounted on an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches of biology in the last few decades. In particular, molecular platforms showing two different BODIPY groups have unique photophysical behavior useful in fluorescence imaging. Construction of the complex architecture of the new probes is accomplished through a convergent route that exploits a series of copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to the proliferation of bacterial infections, in conjunction with growing antibiotic resistance, requires the production of new multifunctional drugs and efficient methods for their targeted delivery to control bacteria-associated diseases. Preliminary studies of the glycoconjugate properties as antibacterial agents against representatives of Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) pathogens, which are associated with chronic infections, indicated significant bactericidal activity ascribable to their structural features.

Visible light and pH-responsive star copolymer and doxorubicin-polymer conjugate micelles for combination drug delivery and bioimaging

Amphiphilic 3-arm star copolymer containing visible light-cleavable BODIPY group and pH-responsive imine bonds at the junction of hydrophilic poly(ethylene glycol) (PEG) and two poly(ε-caprolactone) (PCL) arms was synthesized by the combination of ring-opening polymerization (ROP) and click chemistry. The formation and stimuli-responsive disruption of micelles were analyzed using dynamic light scattering and transmission electron microscopy. Dual stimuli-responsive release of anticancer drugs Doxorubicin (Dox) and Camptothecin (CPT) from the micelles was studied. Micellar assemblies containing Dox conjugated to PEG-BODIPY through imine bonds were prepared and controlled release of Dox in response to visible light and pH was shown. CPT and Dox-loaded star copolymer micelles as well as CPT loaded Dox-conjugated micelles were used in cellular uptake studies on MDA-MB 231 cells, and the synergistic effect of the two stimuli on the release of the two drugs was demonstrated inside the cells. Micellar assemblies also showed excellent bioimaging properties in the cellular uptake studies.

Sulfonothioated meso-Methyl BODIPY Shows Enhanced Uncaging Efficiency and Releases H2Sn.

meso-Methyl BODIPY photocages stand out for their absorption properties and easy chromophore derivatization. However, their low uncaging efficiencies often hinder applications requiring release of protected substrates in high amounts. In this study, we demonstrate that the sulfonothioated BODIPY group photocleaves a sulfonylthio group from the meso-methyl position with a 10-fold higher quantum yield than the most efficient leaving groups studied to date. Photocleavage, observed in solution and in cells, is accompanied by the spatiotemporally controlled photorelease of H2Sn. For this reason, sulfonothioated BODIPY may be applied in cell signaling, redox homeostasis, and metabolic regulation studies.

Symmetry dual functional pyrimidine-BODIPY probes for imaging targeting and activity study.

Nondestructive diagnosis of tumor has always been the goal of scientists. Fluorescent dyes have become the rising star in the field of cancer diagnosis because of their excellent characteristics. Therefore, in this work, fluorescence probes d-Y-B and dO-Y-B with anti-tumor activity were constructed by introducing pyrimidine groups with high anti-tumor activity using fluorescence dye BODIPY as parent nucleus. The modified BODIPY group in the structure had the advantage of fluorescent dye, ensuring the strong fluorescence and photosensitivity of the target compound. That ethylenediamine acts as a bridge with two -NH- groups to increase molecular hydrogen bonding, and can bind firmly to multiple proteins. Co-localization of the target compounds d-Y-B and dO-Y-B with the hoechst dye for labeling living cells showed that these compounds had high biocompatibility and photostability for localization to HeLa cells. In vivo imaging in mice can realize specific localization and real-time visualization of tumor cells. The results of cytotoxicity experiments in vitro and computer software simulating molecular docking confirmed the potential of the target compounds as an anticancer agents. The bifunctional probe realized visualization of cancer cells in mice, and can kill cancer cells by anti-proliferation, which may provide a direction for future anticancer drug development.

Lipophilic probe behavior in microemulsions evaluated by fluorescence correlation spectroscopy.

We evaluated the dispersion and diffusion of fluorescent-labeled lipophilic vitamin E (VE) in microemulsions (MEs) including water-in-oil (W/O) type ME, oil-in-water (O/W) type ME, and bicontinuous ME (BME), using fluorescence correlation spectroscopy (FCS). We prepared a fluorescent ATTO 488 or BODIPY group labeled VE (VE-ATTO or VE-BODIPY). VE-ATTO possesses lipophilic and hydrophilic parts, while VE-BODIPY consists solely of the lipophilic part. The VE-ATTO dissolved in heptane solution as an oil phase appeared hot pink in color due to the solvatochromism effect under room light and almost no fluorescent signal, which was unlike the VE-ATTO dissolved in ME solutions and all the VE-BODIPY solutions (typical fluorescent green color). The FCS measurement proved that VE-BODIPY diffuses faster than VE-ATTO. This is presumably because the "surfactant-like" VE-ATTO is localized and trapped at the micro-water/micro-oil interface of the MEs, while the VE-BODIPY exists in the ME phase and macro-oil phase with good dispersion. These results demonstrate that FCS is a powerful tool for the rapid evaluation of the lipophilic probe behavior in heterogeneous ME solutions.

Give or Take: Effects of Electron-Accepting/-Withdrawing Groups in Red-Fluorescent BODIPY Molecular Rotors.

Mapping microviscosity, temperature, and polarity in biosystems is an important capability that can aid in disease detection. This can be achieved using fluorescent sensors based on a green-emitting BODIPY group. However, red fluorescent sensors are desired for convenient imaging of biological samples. It is known that phenyl substituents in the position of the BODIPY core can shift the fluorescence spectra to longer wavelengths. In this research, we report how electron-withdrawing (EWG) and -donating (EDG) groups can change the spectral and sensory properties of -phenyl-substituted BODIPYs. We present a trifluoromethyl-substituted (EWG) conjugate with moderate temperature sensing properties and a methoxy-substituted (EDG) molecule that could be used as a lifetime-based polarity probe. In this study, we utilise experimental results of steady-state and time-resolved fluorescence, as well as quantum chemical calculations using density functional theory (DFT). We also explain how the energy barrier height () for non-radiative relaxation affects the probe’s sensitivity to temperature and viscosity and provide appropriate ranges for the best possible sensitivity to viscosity and temperature.

Designing a Red-Emitting Viscosity-Sensitive BODIPY Fluorophore for Intracellular Viscosity Imaging.

Viscosity imaging at a microscopic scale can provide important information about biosystems, including the development of serious illnesses. Microviscosity imaging is achievable with viscosity-sensitive fluorophores, the most popular of which are based on the BODIPY group. However, most of the BODIPY probes fluoresce green light, whereas the red luminescence is desired for the imaging of biological samples. Designing a new viscosity probe with suitable spectroscopic properties is a challenging task because it is difficult to preserve viscosity sensitivity after modifying the molecular structure. Here we describe how we developed a new red-emitting, viscosity-sensitive, BODIPY fluorophore BP-PH-2M-NO2 that is suitable for reliable intracellular viscosity imaging of lipid droplets in MCF-7 breast cancer cells. The design of BP-PH-2M-NO2 was aided by DFT calculations that allowed a successful prediction of the viscosity sensitivity of fluorophores before synthesis. In summary, we report a new red viscosity probe possessing monoexponential fluorescence decay that makes it attractive for lifetime-based viscosity imaging.

Synthesis and biological evaluation of cationic TopFluor cholesterol analogues

Cholesterol is not only a major component of the cell membrane, but also plays an important role in a wide range of biological processes and pathologies. It is therefore crucial to develop appropriate tools for visualizing intracellular cholesterol transport. Here, we describe new cationic analogues of BODIPY-Cholesterol (TopFluor-Cholesterol, TF-Chol), which combine a positive charge on the sterol side chain and a BODIPY group connected via a C-4 linker. In contrast to TF-Chol, the new analogues TF-1 and TF-3 possessing acetyl groups on the A ring (C-3 position on steroid) internalized much faster and displayed slightly different levels of intracellular localization. Their applicability for cholesterol monitoring was indicated by the fact that they strongly label compartments with accumulated cholesterol in cells carrying a mutation of the Niemann-Pick disease-associated cholesterol transporter, NPC1.

Design of novel conjugated systems bearing donor-acceptor groups (pyrene-bodipy): Optical, photophysical properties and energy transfer

Herein, we report the design and characterization of a novel series of systems bearing pyrene units as donors and a bodipy group with extended degree of π-conjugation as acceptor, as well as model bodipy compounds bearing only methoxy groups. The optical and photophysical properties of all obtained compounds were studied by absorption and fluorescence spectroscopies. Molecular orbitals and electronic transitions were simulated by means of Density Functional Theory (DFT) methodologies and the obtained results showed good accuracy with respect to the experimental values. The compounds bearing pyrene-bodipy donor-acceptor pair exhibited optimal results for fluorescence resonance energy transfer (FRET) applications, since both chromophores displayed high quantum yields and elevated extinction coefficients, as well as emission in the visible region. High FRET efficiencies were obtained for these dyads making them potential candidates as molecular antennae.

Exploring the optical and nonlinear optical features of heteroleptic complexes with BODIPY and amido-BODIPY substitutions; A comparative theoretical study

In this study, special attention has been paid to understanding the structural effect on electronic structure, absorption spectra and nonlinear optical (NLO) response for a series of heteroleptic diimine dithiolate complexes [M(bpy)(bdt)] (M = Ni, Pd and Pt; bpy = 2,2′-bipyridine, bdt = 1,2-benzenedithiolate) attached to BODIPY and amido-BODIPY dyes through density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods. Natural bond orbital (NBO) analyses are also performed for scrutinizing the structural properties of the considered heteroleptic complexes. The calculated energy gaps show that the substitution of BODIPY or amido-BODIPY groups on the diimine ligand (bpy) leads to reduce of HLG. In contrast, these substitutions on the dithiolate ligand (bdt) are slightly increased energy gap. Moreover, the entitled substitutions at the diimine position can be red-shifted, and the expansion of absorption range to the near-IR region. It is interesting to note that the BODIPY and amido-BODIPY substitutions dramatically increase the static first hyperpolarizability (β0) value. The results suggest that structural modifications on the diimine and dithiolate ligands using BODIPY and amido-BODIPY dyes can finely tune their linear and nonlinear optical properties.

Detection of toxic fluoride ion via chromogenic and fluorogenic sensing. A comprehensive review of the year 2015-2019.

Fluoride ion (F-) contamination can be accumulated along the water and the food chain and cause serious risk to public health. It is of the greatest importance that selects the suitable chromophores and fluorophores for the design and synthesis of outstanding selective, sensitive chromogenic and fluorogenic probes for detection of fluoride ion. In this review is mainly focused on the current progress of fluoride ion detection according to their receptors into several categories like anthracene, azo, benzothiazole, BODIPY, calixarene, coumarin, imidazole, diketopyrrolopyrrole, hydrazone, imidazole, naphthalene, naphthalimide, quantum dots, Schiff base and urea group sensing in the year 2015-2019.

Purple silicon(IV) phthalocyanine axially substituted with BODIPY groups

A novel silicon(IV) phthalocyanine axially substituted with iodine containing BODIPY groups was synthesized. Surprisingly, this novel phthalocyanine is colored as purple in solution due to the mixture of pink and blue colours of BODIPY and phthalocyanine units, respectively. Additionally, the photophysical and photochemical properties of this silicon(IV) phthalocyanine were investigated for the determination of its photodynamic therapy (PDT) ability. This phthalocyanine generated approximately 12 times higher singlet oxygen compared to axially non-iodinated BODIPY substituted silicon(IV) phthalocyanine counterpart.

Spectroscopic and 1O2 Sensitization Characteristics of a Series of Isomeric Re(bpy)(CO)3Cl Complexes Bearing Pendant BODIPY Chromophores.

Two new Re(I)bipyridyltricarbonyl chloride complexes, Re(BB3)(CO)3Cl and Re(BB4)(CO)3Cl, featuring BODIPY groups appended to the 5,5'- or 6,6'-positions of the bipyridine ligand, respectively, were synthesized as structurally isomeric compliments to a previously reported 4,4'-substituted homologue, Re(BB2)(CO)3Cl. X-ray crystal structures of the compounds show that the 4,4'-, 5,5'-, and 6,6'-substitution patterns place the BODIPY groups at progressively shorter distances of 9.43, 8.39, and 5.56 Å, respectively, from the complexes' Re centers. The photophysical properties of the isomeric complexes were investigated to ascertain the manner in which the heavy rhenium atom might induce intersystem crossing of the pendant BODIPY moieties positioned at progressively shorter through-space distances. Electronic absorption spectroscopy revealed that the three metal complexes retain the strong visible absorption features characteristic of the bpyBODIPY (BB2-BB4) ligands; however, the fluorescence of the parent borondipyrromethane appended ligands is attenuated by more than an order of magnitude in Re(BB2)(CO)3Cl and Re(BB3)(CO)3Cl and by more than two orders of magnitude in Re(BB4)(CO)3Cl. Furthermore, phosphorescence from Re(BB4)(CO)3Cl is observed under a nitrogen atmosphere, consistent with highly efficient ISC to the triplet-excited state. Singlet oxygen sensitization studies confirm that all three complexes produce singlet oxygen with quantum yields that increase as the distance of the BODIPY groups to the heavy rhenium center is decreased. The trends observed across the series of rhenium complexes with respect to emission and 1O2 sensitization properties can be rationalized in terms of the varied distal separation between the metal center and BODIPY groups in each system.

A BODIPY derivative for colorimetric fluorescence sensing of Hg2+, Pb2+ and Cu2+ ions and its application in logic gates

A BODIPY-based colorimetric and fluorescent chemosensor 1 anchored with dipyridylamino (DPA) receptor has been designed, synthesized and characterized. It exhibited a simultaneous sensitive recognition for Cu2+, Hg2+ and Pb2+ ions. With the addition of these three kinds of metal ions into 1 in CH3CN, its initial absorption maximum displayed obvious blue shifts, and the color changes of the solution could be clearly observed by naked eyes. Besides, the fluorescence intensity was significantly enhanced accompanied with the appearance of new emission peaks at 587 nm for Pb2+ and Hg2+ ions and 545 nm for Cu2+ ions. These results were attributed to the π-deconjugation between N-pyridyl and the BODIPY group due to the binding of metal ions with the BODIPY and DPA groups. Based on the sensing behaviors of 1, three logic gates (OR, INHIBT and combinational logic gate) were constructed correspondingly.

Synthesis and properties of octa-distyryl-BODIPY substituted zinc(II) phthalocyanines

A novel type octa-distyryl-BODIPY substituted zinc(II) phthalocyanines 9 and 10 were prepared by the copper-free Sonogashira coupling and “Click” reactions, respectively. The terminal ethynyl functionalized BODIPY (4,4’-difluoro-8-(4-propynyloxy)-phenyl-1,7-dimethyl-3,5-bis(4-4″-diethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene, 8) compound was reacted with octakis (iodo) zinc(II) phthalocyanine (2) for the synthesis of BODIPY substituted zinc(II) phthalocyanine 9. On the other hand, the same BODIPY compound (8) was used to the synthesis of BODIPY substituted zinc(II) phthalocyanine 10 by the reaction of this BODIPY with octakis-(2-azidoethoxy) zinc(II) phthalocyanine (7). While eight distyryl-BODIPY groups were linked to the phthalocyanine core through ethynyl bonds for phthalocyanine 9, these BODIPY groups were connected to the phthalocyanine core via triazole ring for phthalocyanine 10. All newly synthesized compounds were characterized by elemental analysis and general spectroscopic methods such as 1H NMR, mass, FT-IR, UV–Vis and fluorescence. Moreover, the photophysical and photochemical properties of these conjugates were investigated for determination of their photosensitizer and fluorescence abilities for photodynamic therapy.

Novel aluminum-BODIPY dyads: intriguing dual-emission via photoinduced energy transfer.

Three novel BODIPY-based heterodinuclear complexes, [salen(3,5-(t)Bu)2Al-(OC6H4-BODIPY)] (6), [salen(3,5-(t)Bu)2Al-(OC6F2H2-BODIPY)] (7), and [(mq)2Al-(OC6H4-BODIPY)] (8) (salen = N,N'-bis(salicylidene)ethylenediamine, BODIPY = 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, and mq = methyl-8-quinolinolato) were prepared and characterized by multinuclear NMR spectroscopy. The specific structures of 6-8 were also determined by single crystal X-ray analysis. In particular, the salen-based heterodinuclear complexes 6 and 7 exhibited higher thermal stability (Td5 = 309 and 306 °C, respectively) than that of the closely related mononuclear aluminum or BODIPY compounds, except for 8. The UV/vis absorption and PL spectra for 6 and 7 indicated a significant photoinduced energy transfer from the aluminum-salen moiety to the BODIPY group in an intramolecular manner. Theoretical calculations revealed independent transition states of the aluminum-salen moiety or the BODIPY group in the Al(III)-BODIPY dyads, further supporting these experimental results.

Advances in the Applications of Boron Tetrapyrrole and Dipyrrin Complexes

Over the years we have developed the chemistry of boron complexes of porphyrins and corroles, and have recently made the first examples of boron calixphyrin and porphyrazine complexes. The unifying motifs are the coordination of two borons per tetrapyrrole macrocycle, with both the structural stereochemistry and the chemical reactivity dictated by the steric demands of incorporating two boron atoms within a tightly defined cavity. We are now exploring the physical properties of these classes of complexes with a view to developing applications, for example in PDT. We have also explored new chemistry of the well-known boron dipyrrins (or BODIPYs) and have developed new chemistry for directly attaching BODIPY groups to substrates that are useful in biology and materials science. Figure 1

Macromolecular Crowding Effects on Two Homologs of Ribosomal Protein S16: Protein-Dependent Structural Changes and Local Interactions

Proteins function in cellular environments that are crowded with biomolecules, and in this reduced available space, their biophysical properties may differ from those observed in dilute solutions in vitro. Here, we investigated the effects of a synthetic macromolecular crowding agent, dextran 20, on the folded states of hyperthermophilic (S16Thermo) and mesophilic (S16Meso) homologs of the ribosomal protein S16. As expected for an excluded-volume effect, the resistance of the mesophilic protein to heat-induced unfolding increased in the presence of dextran 20, and chemical denaturation experiments at different fixed temperatures showed the macromolecular crowding effect to be temperature-independent. Förster resonance energy transfer experiments show that intramolecular distances between an intrinsic Trp residue and BODIPY-labeled S16Meso depend on the level of the crowding agent. The BODIPY group was attached at three specific positions in S16Meso, allowing measurements of three intraprotein distances. All S16Meso variants exhibited a decrease in the average Trp-BODIPY distance at up to 100 mg/mL dextran 20, whereas the changes in distance became anisotropic (one distance increased, two distances decreased) at higher dextran concentrations. In contrast, the two S16Thermo mutants did not show any changes in Trp-BODIPY distances upon increase of dextran 20 concentrations. It should be noted that the fluorescence quantum yields and lifetimes of BODIPY attached to the two S16 homologs decreased gradually in the presence of dextran 20. To investigate the origin of this decrease, we studied the BODIPY quantum yield in three protein variants in the presence of a tyrosine-labeled dextran. The experiments revealed distinct tyrosine quenching behaviors of BODIPY in the three variants, suggesting a dynamic local interaction between dextran and one particular S16 variant.

Fluorescent fatty acid analogs as a tool to study development of the picornavirus replication organelles

Genome replication of positive strand RNA viruses of eukaryotes is universally associated with specialized membranous structures referred to as replication organelles. Accumulating evidence show that new membrane synthesis is important for the development of the replication organelles of diverse picornaviruses and likely for other positive strand RNA viruses as well. The hydrophobic part of the structural phospholipid molecules defining the barrier properties of biological membranes consists of two long chain fatty acid moieties attached to the glycerol backbone. Fluorescent long chain fatty acid analogs represent a very convenient tool to monitor membrane synthesis in infected cells offering significant advantages over conventional radioactively labeled compounds. Bodipy-containing fatty acid analogs are readily imported from the extracellular media and utilized in lipid synthesis by cellular machinery. The strong fluorescence of the Bodipy group allows monitoring the molecules in situ by fluorescent microscopy as well as provides an opportunity for quantitative assessment of fatty acid import in a multi-well plate format. Moreover lipids with incorporated fluorescent fatty acid chain can be resolved by thin layer chromatography and easily identified using conventional UV imaging systems thus providing a simple and convenient way of monitoring the perturbation of the lipid synthesis pathways upon infection.

Photocatalytic Conversion of CO2 to CO using Rhenium Bipyridine Platforms Containing Ancillary Phenyl or BODIPY Moieties.

Harnessing of solar energy to drive the reduction of carbon dioxide to fuels requires the development of efficient catalysts that absorb sunlight. In this work, we detail the synthesis, electrochemistry and photophysical properties of a set of homologous fac-ReI(CO)3 complexes containing either an ancillary phenyl (8) or BODIPY (12) substituent. These studies demonstrate that both the electronic properties of the rhenium center and BODIPY chromophore are maintained for these complexes. Photolysis studies demonstrate that both assemblies 8 and 12 are competent catalysts for the photochemical reduction of CO2 to CO in DMF using triethanolamine (TEOA) as a sacrificial reductant. Both compounds 8 and 12 display TOFs for photocatalytic CO production upon irradiation with light (λex ≥ 400 nm) of ~5 hr-1 with TON values of approximately 20. Although structural and photophysical measurements demonstrate that electronic coupling between the BODIPY and fac-ReI(CO)3 units is limited for complex 12, this work clearly shows that the photoactive BODIPY moiety is tolerated during catalysis and does not interfere with the observed photochemistry. When taken together, these results provide a clear roadmap for the development of advanced rhenium bipyridine complexes bearing ancillary BODIPY groups for the efficient photocatalytic reduction of CO2 using visible light.