BODIPY Research Articles

Photophysical properties of furan-bridged dimeric boron-dipyrromethene derivatives (BODIPYs)

In order to investigate the changes in the spectroscopic properties of dimeric boron-dipyrromethenes (BODIPYs), four BODIPY derivatives are synthesized, including a monomer BODIPY in which a furyl group is substituted at the meso position and a dimer BODIPY with a furan group as a bridge. The four synthesized BODIPY derivatives are characterized through nuclear magnetic resonance and mass spectrometry. Photophysical properties such as ultraviolet–visible absorbance and the fluorescence emission of monomers (mT1 and mT2) and dimers (biT1 and biT2) are studied in eight different solvents. In addition, the relationship of their structural properties and optical properties are also considered through density functional theory calculations. The covalent link between the two BODIPY units using a furan group has a profound effect on the optical properties of the dimeric BODIPYs. We believe that an understanding of the synthesis and physical properties of dimeric BODIPYs will have a promising perspective in designing new BODIPY derivatives and predicting their spectroscopic characteristics in the future.

Special issue on enhanced photodynamic therapy: Part II

Special issue on enhanced photodynamic therapy: Part II

Detection of wheat toxigenic Aspergillus flavus based on nano-composite colorimetric sensing technology

Volatile organic compounds (VOCs) are an important indicator for fungal-infected wheat identification. This work proposes a novel approach for toxigenic Aspergillus flavus infected wheat identification through characteristic VOCs analyzed by nano-composite colorimetric sensors. Nanoparticles of poly styrene-co-acrylic acid (PSA), porous silica nanoparticles (PSN), and metal–organic framework (MOF) were combined with boron dipyrromethene (BODIPY) to fabricate nano-composite colorimetric sensors. The combination mechanisms for nanoparticles and the information extracted from nano-colorimetric sensors by digital images were analyzed in the current work. Furthermore, linear discriminant analysis (LDA) and k-nearest neighbor (KNN) were used comparatively to analyze the data from images, and toxigenic Aspergillus flavus infected wheat samples could be 100.00% correctly identified when using the optimal KNN model. This research contributes to the practical analysis of VOCs and the detection of toxigenic Aspergillus flavus infected wheat.

Development of Meso‐Substituted Heterocyclic BODIPY‐Based Polymeric Nanoparticles for Pathogen Inhibition using Photodynamic Therapy**

AbstractIn this work, a series of novel small fluorophores, meso‐substituted heterocyclic BODIPYs were designed and synthesized as phototherapeutic agents. Boron dipyrromethene (BODIPY) dyes are promising chromophores and currently used as a sensitizers in photodynamic therapy (PDT). However, BODIPY as an organic photosensitizer (PS), suffers from poor hydrophilicity resulting in low efficiency in biological applications. To overcome these problems, biopolymer (gelatin) based nanoparticles are developed to incorporate BODIPYs, to achieve phototherapeutic nanoagents (BODIPY‐GNPs) in the aqueous system. More importantly, BODIPY‐GNPs have better in vitro physicochemical properties in the aqueous medium than native BODIPYs. The BODIPY‐GNPs were further explored for their photo‐inhibition activity towards Gram‐positive and Gram‐negative bacteria and fungi using LED as the light source. These BODIPY molecules also showed the ability to intercalate the DNA in vitro. This study provides a new avenue to design therapeutic agents for biomedical applications in photodynamic therapy.

Fluoroalkylated BODIPY nanoparticles for photodynamic sterilization and cancer therapy

Microbial infection often accompanies most diseases such as cancer, which has been testified to severely decrease the efficacy of cancer therapy. It is imperative and significant to develop the single therapeutic agents with high antimicrobial and antitumor efficacy. Herein, fluoroalkylated boron dipyrromethene (BDP) (named as B-F) and its counterpart alkylated BDP (named as B-H) were synthesized. Fluoroalkylation could facilitate the spontaneous self-assembly of B-F into nanoparticles (NPs) and dramatically enhance its intracellular delivery efficiency. Furthermore, compared with B-H NPs, B-F NPs possessed enhanced capacity of generating reactive oxygen species (ROS) upon irradiation, which endowed B-F NPs with photodynamic destroying Gram-positive bacteria and cancer cells. This work contributes to strategical design of the nanoscale photosensitizers (PSs) for antimicrobial photoinactivation and photodynamic therapy (PDT).

Acceleration of Nonradiative Charge Recombination Reactions at Larger Distances in Kinked Donor-Bridge-Acceptor Molecules.

Photoinduced electron transfer in donor-bridge-acceptor (D-B-A) molecular systems can occur via tunneling over long distances (rDA) of well over 10 Å. We commonly observe decreasing rates of electron transfer with increasing distances, a result of a decrease in the electronic coupling of the donor and acceptor moiety. In the study of D-B-A molecules with Ru(bpy)32+ as a bridge/core, Kuss-Petermann and Wenger observed the opposite trend (J. Am. Chem. Soc.2016, 138, 1349); a maximum rate constant of electron transfer was observed at an intermediate electron transfer distance. Within the high-temperature limit of the classical Marcus equation, their observation was qualitatively explained by a sharp distance dependence of outer sphere (or solvent) reorganization energy, as predicted by Sutin and co-workers (J. Am. Chem. Soc.1984, 106, 6858), and almost distance-independent electronic couplings. Here, we report another example of such an underexplored behavior with three kinked D-B-A systems of rDA ∼ 10-19 Å, showing increasing rates of nonradiative charge recombination with increasing rDA. The three D-B-A systems are based on boron dipyrromethene and triphenylamine as electron acceptor and donor groups, respectively, with aryl bridges where the donor and acceptor moieties are connected at meso-positions. These D-B-A molecules exhibit radiative electron transfer reactions (or charge-transfer emission), which enables us to experimentally determine the solvent reorganization energy and the electronic couplings. The analysis of charge-transfer emission that explicitly considers electron-vibration coupling, in conjunction with the temperature-dependent analysis and computational method, revealed that the solvent reorganization energy indeed increases with distance, and at the same time, the electronic coupling decreases with distance expectedly. Therefore, under the right conditions for solvent reorganization energy and electronic coupling values, our results show that we can observe the acceleration of electron transfer reactions with increasing distance, even when we have the expected distance dependence of electronic coupling. This work indicates that the acceleration of electron transfer with increasing distance may be achieved with a fine-tuning of molecular design.

Dynamic Fluorescent Patterning Based on Visible-Light-Responsive Diselenide Metathesis.

A diselenide bond, as a dynamic covalent bond, is a versatile tool to construct smart interfaces, which can respond to visible light. In this work, we used microcontact printing (μCP) to construct diselenide patterns on quartz substrates. Fluorescent patterns were obtained on the modified surfaces via the visible-light-induced diselenide metathesis reaction, which allowed the patterning process to be fast, dynamically erasable, and compatible with different fluorescent molecules including rhodamine B and boron-dipyrromethene (BODIPY) used in this work. A variety of analytical methods offered comprehensive evidence for the success of the printing of diselenides here. We further printed diselenide and disulfide intersecting stripes on one single quartz substrate layer by layer and introduced rhodamine B and BODIPY to obtain a multicolored pattern simultaneously. By taking advantage of their responsiveness to different wavelengths, the composite pattern of disulfides and diselenides could be erased by two stepwise stages. The fluorescent images of the modified substrate showed a good agreement with the pattern of the poly(dimethylsiloxane) (PDMS) stamp, indicating the methodology with a potential application for information storage.

Novel Meso-Benzothiazole-Substituted BODIPY-Based AIE Fluorescent Rotor for Imaging Lysosomal Viscosity and Monitoring Autophagy.

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.

Integrating a Far-Red Fluorescent Probe with a Microfluidic Platform for Super-Resolution Imaging of Live Erythrocyte Membrane Dynamics.

Living erythrocyte (red blood cell, RBC) membranes present rich ultrastructural and dynamic details, which require synchronous super-resolution imaging and single-molecule tracking to be revealed. Yet, it poses a serious challenge to achieve these dual functions in a single probe, due to the rigid and conflicting photophysical demands of the different techniques. Herein, we rationally developed a far-red boron dipyrromethene membrane probe with blinking capability and persistent single-molecule emission, and constructed a microfluidic platform for noninvasive trapping and long-term imaging of RBCs. By combining them, multi-dimensional super-resolution reconstructions and single-molecule tracking were achieved at the molecular scale on living human RBC membranes in a high-throughput manner. Our integrated system defines a quantitative method for analyzing RBC membranes under physiological and pathological conditions, improving precision and revealing new perspectives for future disease diagnostics.

Integrating a Far‐Red Fluorescent Probe with a Microfluidic Platform for Super‐Resolution Imaging of Live Erythrocyte Membrane Dynamics**

AbstractLiving erythrocyte (red blood cell, RBC) membranes present rich ultrastructural and dynamic details, which require synchronous super‐resolution imaging and single‐molecule tracking to be revealed. Yet, it poses a serious challenge to achieve these dual functions in a single probe, due to the rigid and conflicting photophysical demands of the different techniques. Herein, we rationally developed a far‐red boron dipyrromethene membrane probe with blinking capability and persistent single‐molecule emission, and constructed a microfluidic platform for noninvasive trapping and long‐term imaging of RBCs. By combining them, multi‐dimensional super‐resolution reconstructions and single‐molecule tracking were achieved at the molecular scale on living human RBC membranes in a high‐throughput manner. Our integrated system defines a quantitative method for analyzing RBC membranes under physiological and pathological conditions, improving precision and revealing new perspectives for future disease diagnostics.

Tetracyanobutadiene Bridged Push-Pull Chromophores: Development of New Generation Optoelectronic Materials.

This review describes the design strategies used for the synthesis of various tetracyanobutadiene bridged donor-acceptor molecular architectures by a click type [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction sequence. The photophysical and electrochemical properties of the tetracyanobutadiene bridged molecular architectures based on various moieties including diketopyrrolopyrrole, isoindigo, benzothiadiazole, pyrene, pyrazabole, truxene, boron dipyrromethene (BODIPY), phenothiazine, triphenylamine, thiazole and bisthiazole are summarized. Further, we discuss some important applications of the tetracyanobutadiene bridged derivatives in dye sensitized solar cells, bulk heterojunction solar cells and photothermal cancer therapy.

Bichromophoric BODIPY and Biotin Tagged Terpyridyl Ruthenium(II) Complexes for Cellular Imaging and Photodynamic Therapy

AbstractA perceived drawback of ruthenium(II) polypyridyl photosensitizers for phototherapeutic applications is their inadequate absorption in the visible region. Ru(II) dyads attached to light‐harvesting organic chromophores are studied to address this issue. Biotin‐appended compounds having one chromophore, namely BODIPY (boron‐dipyrromethene) (1) and Ru(II)‐(tpy)2 (2), or a dyad system containing BODIPY linked to Ru(II)‐(tpy)2 via a diphenylacetylene linker (3) were prepared and studied as photodetection agent and photosensitizes for Photodynamic Therapy (PDT) applications. The bichromophoric 3 with a strong absorption profile (ϵ≈71000 M−1 cm−1 at λmax=503 nm) and high singlet oxygen quantum yield (ΦΔ=0.63 in DMSO) was studied for PDT activity. This complex produced a superoxide anion radical via type‐I and singlet oxygen via type‐II photosensitization processes on light exposure, as evidenced from DNA photo‐cleavage experiments and in vitro DCFDA assay using reactive oxygen species scavengers/quenchers. Dyad 3 displayed an apoptotic photo‐cytotoxic effect against HeLa and H1299 cancer cells with a photocytotoxicity index (PI) value of >625 in HeLa cells with a PDT efficacy much superior to those of its monochromophoric analogs 1 and 2. The intrinsic emission of complex 3, utilized for cellular imaging, showed selectivity towards lysosomes. Finally, the remarkable potential of complex 3 was evidenced using a clinically relevant 3D multicellular tumor spheroid model.

Structure and Conformation of Novel BODIPY Ugi Adducts.

Two novel BODIPY‐Ugi (boron dipyrromethene) adducts exhibit peculiar room temperature (T=20 °C) H‐1 NMR spectra in that several protons located at the aromatic aniline‐type ring are lost in the baseline. This observation revealed the existence of a dynamic conformational process where rotation around the C−N bond is hindered. Variable‐temperature H‐1 and C‐13 NMR spectroscopic analysis confirmed this conclusion; that is, low‐temperature spectra show distinct signals for all four aromatic protons below coalescence, whereas average signals are recorded above coalescence (T=+120 °C). Particularly interesting was the rather large difference in chemical shifts for the ortho protons below coalescence, Δδ=1.45 ppm, which was explained based on DFT computational analysis. Indeed, the calculated lowest‐energy gas‐phase conformation of the BODIPY Ugi adducts locates one half of the aniline‐type ring in the shielding anisotropic cone of the bridge phenyl ring in the BODIPY segment. This is in contrast to the solid‐state conformation established by X‐ray diffraction analysis that shows a nearly parallel arrangement of the aromatic rings, probably induced by crystal packing forces.

Synthesis and photophysical investigations of pyridine-pyrazolate bound boron(III) diaryl complexes

This study presents the design and synthetic pathway of unsymmetric ligands based on pyridine-pyrazolate scaffold with Donor–Acceptor (D–A) molecular arrays and their boron complexes to achieve a large Stokes shift. Intermolecular charge transfer (ICT) triggered by the uneven molecular charge distribution from electronically dense pyrazolate (donor) part of the ligands to electron-deficient boron centre (acceptor) resulted in a mega Stokes shift up to 263 nm for selected compounds while retaining the characteristic quantum efficiency and chemical stability. The photophysical properties of derivatization of pyrazolate group in the pyridine-pyrazolate scaffold of diaryl boron complexes were explored based on UV–Visible, steady-state and time-resolved fluorescence spectroscopy. An interesting dual emission along with quenching behaviour was also observed for 2-(6-methoxynaphthelene) 5-(2-pyridyl) pyrazolate boron complex (P5) due to the formation of a twisted intermolecular charge transfer (TICT) state from a locally excited (LE) state rendering it a potential candidate for sensing applications based on H-Bond quenching. In addition, the extended excited state lifetime of the reported compounds compared to classical boron-dipyrromethene (BODIPY) makes them suitable as potential probes for analytical applications requiring a longer excited state lifetime.

Stabilization of Artificial Viral Capsid Using Surface Modification with BODIPY

This study shows that β-annulus peptide modified with boron-dipyrromethene (BODIPY) at the C-terminal self-assembled into stable artificial viral capsid even at 1 µM, in contrast to unmodified or N-terminally modified peptides, which cannot self-assemble. Even when sodium dodecyl sulfate was present, the artificial viral capsid, which was stabilized by presumably π–π stacking interactions between BODIPYs at the surface, nearly retained the apparent diameter and formation ratio.

Accurate Vertical Excitation Energies of BODIPY/Aza-BODIPY Derivatives from Excited-State Mean-Field Calculations.

We report a benchmark study of vertical excitation energies and oscillator strengths for the HOMO → LUMO transitions of 17 boron–dipyrromethene (BODIPY) structures, showing a large variety of ring sizes and substituents. Results obtained at the time-dependent density functional theory (TDDFT) and at the delta-self-consistent-field (ΔSCF) by using 13 different exchange correlation kernels (within LDA, GGA, hybrid, and range-separated approximations) are benchmarked against the experimental excitation energies when available. It is found that the time-independent ΔSCF DFT method, when used in combination with hybrid PBE0 and B3LYP functionals, largely outperforms TDDFT and can be quite competitive, in terms of accuracy, with computationally more costly wave function based methods such as CC2 and CASPT2.

Thiazole Boron Difluoride Dyes with Large Stokes Shift, Solid State Emission and Room-Temperature Phosphorescence.

The small Stokes shift and weak emission in the solid state are two main shortcomings associated with the boron-dipyrromethene (BODIPY) family of dyes. This study presents the design, synthesis and luminescent properties of boron difluoro complexes of 2-aryl-5-alkylamino-4-alkylaminocarbonylthiazoles. These dyes display Stokes shifts (Δλ, 77-101 nm) with quantum yields (ϕFL ) up to 64.9 and 34.7 % in toluene solution and in solid state, respectively. Some of these compounds exhibit dual fluorescence and room-temperature phosphorescence (RTP) emission properties with modulable phosphorescence quantum yields (ϕPL ) and lifetime (τp up to 251 μs). The presence of intramolecular H-bonds and negligible π-π stacking revealed by X-ray crystal structure might account for the observed large Stokes shift and significant solid-state emission of these fluorophores, while the enhanced spin-orbit coupling (SOC) of iodine and the self-assembly driven by halogen bonding, π-π and C-H… π interactions could be responsible for the observed RTP of iodine containing phosphors.

Selenophene-Modified Boron Dipyrromethene-Based Photosensitizers Exhibit Photodynamic Inhibition on a Broad Range of Bacteria.

Microorganisms are crucial for human survival in view of both mutualistic and pathogen interactions. The control of the balance could be achieved by use of the antibiotics. There is a continuous arms race that exists between the pathogen and the antibiotics. The emergence of multidrug-resistant (MDR) bacteria threatens health even for insignificant injuries. However, the discovery of new antibiotics is not a fast process, and the healthcare system will suffer if the evolution of MDR lingers in its current frequency. The cationic photosensitizers (PSs) provide a unique approach to develop novel, light-inducible antimicrobial drugs. Here, we examine the antimicrobial activity of innovative selenophene-modified boron dipyrromethene (BODIPY)-based PSs on a variety of Gram (+) and Gram (−) bacteria. The candidates demonstrate a level of confidence in both light-dependent and independent inhibition of bacterial growth. Among them, selenophene conjugated PS candidates (BOD-Se and BOD-Se-I) are promising agents to induce photodynamic inhibition (PDI) on all experimented bacteria: E. coli, S. aureus, B. cereus, and P. aeruginosa. Further characterizations revealed that photocleavage ability on DNA molecules could be potentially advantageous over extracellular DNA possessing biofilm-forming bacteria such as B. cereus and P. aeruginosa. Microscopy analysis with fluorescent BOD-H confirmed the colocalization on GFP expressing E. coli.

A novel BODIPY-based nano-photosensitizer with aggregation-induced emission for cancer photodynamic therapy

The discovery of aggregation-induced emission (AIE) effect provides opportunities for the rapid development of fluorescence imaging-guided photodynamic therapy (PDT). In this work, a boron dipyrromethene (BODIPY)-based photosensitizer (ET-BDP-O) with AIE characteristics was developed, in which the two linear arms of BODIPY group were linked with triphenylamine to form an electron Donor–Acceptor–Donor (D–A–D) architecture while side chain was equipped with triethylene glycol group. ET-BDP-O was able to directly self-assemble into nanoparticles (NPs) without supplement of any other matrices or stabilizers due to its amphiphilic property. The as-prepared ET-BDP-O NPs had an excellent colloid stability with the size of 125 nm. Benefiting from the AIE property, ET-BDP-O NPs could generate strong fluorescence and reactive oxygen species under light-emitting diode light irradiation (60[Formula: see text]mW/cm[Formula: see text]. After internalized in cancer cells, ET-BDP-O NPs were able to emit bright red fluorescence signal for bioimaging. In addition, the cell viability assay demonstrated that the ET-BDP-O NPs exhibited excellent photo-cytotoxicity against cancer cells, while negligible cytotoxicity under dark environment. Thus, ET-BDP-O NPs might be regarded as a promising photosensitizer for fluorescence imaging-guided PDT in future.

Diiodinated Mono- and Dipyridylvinyl BODIPY Dyes: Photophysicochemical Properties, invitro Antibacterial Studies, Molecular Docking and Theoretical Calculations.

In this study, novel mono- and dipyridylvinyl boron dipyrromethene dyes are prepared to compare their photodynamic antimicrobial chemotherapy (PACT) activities against Staphylococcus aureus to the corresponding core dyes. Pyridylvinyl substitution at the 3- or 3,5-positions of a meso-4-bromophenylBODIPY core dye via a Knoevenagel reaction with an aromatic 2-bromopyridinecarboxaldehyde shifts the major BODIPY spectral band to longer wavelength. The extended π-conjugation red shifts the main spectral band into the 602-618 nm region in CHCl3 , THF, ethanol and DMSO after monopyridylvinyl substitution and to 685-704 nm after dipyridylvinyl substitution. An enhancement of the population of the T1 state through the incorporation of iodine atoms at the 2,6-positions results in moderately high singlet oxygen quantum yields in DMSO. The π-extended dyes were found to have significantly lower PACT activities than the diiodinated core dye.