BODIPY Derivatives Research Articles

The multifunctional BODIPY@Eu-MOF nanosheets as bioimaging platform: A ratiometric fluorescencent sensor for highly efficient detection of F-, H2O2 and glucose

The highly emissive BODIPY (boron-dipyrromethene) have been grafted on the Eu-based metal-organic frameworks (Eu-MOFs) via the covalent F-B bonding using a facile one-pot solvothermal reaction. The fluorescence emission ratio of BODIPY@Eu-MOF has been applied to construct the ratiometric fluorescence sensor for the F-, H2O2 and glucose detection in water solution and living cells. The produced BODIPY@Eu-MOF probe provided enhanced sensitivity, higher selectivity and lower lower limits of detection (LOD) for the detection of F- (0.1737 μM), H2O2 (6.22 nM) and glucose (6.92 nM), and 5.96, 6.52 and 6.95 times lower than that for single Eu-MOF, respectively. More importantly, the probe also exhibited the lower biotoxic in living cells for bioimaging and the better visualization performance with multiplex channels. The results indicated the π-conjugated BODIPY derivative not only acted as the surfactant molecule or template agent for preferred growth, but also modulated the fluorescent emissions drastically, and thus induced excellent fluorescent detecting performances.

Syntheses and Investigations of Conformationally Restricted, Linker-Free α-Amino Acid-BODIPYs via Boron Functionalization.

A series of α-amino acid–BODIPY derivatives were synthesized using commercially available N-Boc-l-amino acids, via boron functionalization under mild conditions. The mono-linear, mono-spiro, and di-amino acid–BODIPY derivatives were obtained using an excess of basic (histidine, lysine, and arginine), acidic (aspartic acid), polar (tyrosine, serine), and nonpolar (methionine) amino acid residues, in yields that ranged from 37 to 66%. The conformationally restricted mono-spiro- and di-amino acid–BODIPYs display strong absorptions in the visible spectral region with high molar extinction coefficients and significantly enhanced fluorescence quantum yields compared with the parent BF2–BODIPY. Cellular uptake and cytotoxicity studies using the human HEp2 cell line show that both the presence of an N,O-bidentate spiro-ring and basic amino acids (His and Arg) increase cytotoxicity and enhance cellular uptake. Among the series of BODIPYs tested, the spiro-Arg- and spiro-His-BODIPYs were found to be the most cytotoxic (IC50 ∼ 22 μM), while the spiro-His-BODIPY was the most efficiently internalized, localizing preferentially in the cell lysosomes, ER, and mitochondria.

Synthesis, Reactivity, and Properties of a Class of π-Extended BODIPY Derivatives.

A new family of π-extended BODIPY derivatives were obtained through the condensation of aldehyde and pyrrole in aqueous solution in the presence of HCl. The new rigid π-framework extends beyond the dipyrromethene unit, which is significantly different from classical BODIPYs in the electronic configuration. Both π-extended BODIPYs displayed intense absorption and moderate emission with maxima around 565 and 620 nm, respectively, and showed interesting reactivity toward various nucleophiles. Moreover, these π-extended BODIPYs were developed as fluorescent probes for rapid and selective detection of GSH and were successfully applied for live-cell imaging.

BODIPY derivatives as fluorescent reporters of molecular activities in living cells

Fluorescent compounds have become indispensable tools for imaging molecular activities in the living cell. 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) is currently one of the most popular fluorescent reporters due to its unique photophysical properties. This review provides a general survey and presents a summary of recent advances in the development of new BODIPY-based cellular biomarkers and biosensors. The review starts with the consideration of the properties of BODIPY derivatives required for their application as cellular reporters. Then review provides examples of the design of sensors for different biologically important molecules, ions, membrane potential, temperature and viscosity defining the live cell status. Special attention is payed to BODPY-based phototransformable reporters.The bibliography includes 339 references.

Sulfamide-substituted-BODIPY based fluorescence drugs: Synthesis, spectral characteristics, molecular docking, and bioactivity

BODIPY derivatives have attracted much attention in the field of biological probes, but probes with a single imaging function are no longer innovative. In this paper, two multifunctional sulfonamide-BODIPY derivatives were designed and synthesized. Photophysical properties, cytotoxicity, in vitro and in vivo imaging, apoptosis, cell cycle, and molecular docking simulation were studied. The results showed that the compound had low cytotoxicity to normal cells, but had strong inhibitory effect on tumor cells. The IC 50 value of compound 3 on HCT-116 cells was 58.61 ± 4.91 μmol/L, and 4 on HeLa cells was 52.29 ± 10.93 μmol/L. Cell imaging and mice experiments demonstrated that the probe had excellent biocompatibility and potential tumor targeting; and in vivo imaging of mice at different time periods showed that the fluorescence intensity of probes in subcutaneous lung tumor gradually increased with the extension of time. In addition, the flow cytometry analysis of 3 showed that the G1 phase of HCT-116 cells was inhibited and apoptosis of tumor cells was promoted. In molecular docking simulation, sulfonamide-BODIPY derivatives had high affinity scores with CDK2: −8.0 and −8.4 kcal·mol −1 , and the multiple interactions with receptors provided conditions for the probes to recognize tumor cells.

Fluorescence quenching-based bodipy-boronic acid linked viologen dual system for potential glucose sensing applications

PurposeThe purpose of this study is to develop a non-enzymatic based glucose-sensing platform composed of Bodipy-BBV dual system which can be monitored by a photodetector under the blue LED excitation.Design/methodology/approachThe sensor has been developed from a dual system including a fluorescent dye, an aldehyde derivative of boron dipyrromethene (Bodipy) and a quencher, orto-boronic acid linked viologen (o-BBV) where their combination resulted in a ratiometric fluorescence quenching in ethanol: PBS (1:1, pH:7.4) solution under UV light excitation. By glucose addition, o-BBV has been released from the Bodipy and binded to cis-diol groups of glucose, thereby fluorescence emission of Bodipy has been regained. Furthermore, a setup consisting of a light emitting diode (LED) and a photodiode (PD) was used to prove electrical detection of glucose without the need for expensive and bulky optical equipment, enabling the development of a miniaturized and low-cost glucose-sensing platform.FindingsThe fluorescence intensity of the Bodipy derivative in the solution (2 × 10−6 M) was diminished by 93% in the presence of o-BBV solution (5 × 10−3 M). Upon the glucose addition, 81% of the Bodipy fluorescence intensity has been recovered after introduction of 30 mM of glucose, where the ratio of o-BBV/Bodipy was 35:1. A linear response between 10 and 30 mM glucose concentration was obtained, which covers the biologically significant range. A high correlation between the photodiode current and Bodipy fluorescence intensity was achieved.Originality/valueEven though Bodipy molecules are known with their superior optical properties and applied to the fluorescence-based detection of glucose, to the best of the authors’ knowledge, no work has been reported on Bodipy-BBV dual system to detect glucose molecules as a non-enzymatic based method. This design enables the dye and the quencher to independently coexist in the solution, allowing for tuning of their individual concentrations to optimize the glucose sensitivity. Furthermore, an electrical light detection scheme consisting of a LED and a photodiode has been implemented to eliminate the bulky optical equipment from the measurement setup and further this work for the development of a compact and inexpensive sensor. The results presented here demonstrate the feasibility of this system for the development of a novel glucose sensor.

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

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

Theoretical Investigation of the Effect of Alkylation and Bromination on Intersystem Crossing in BODIPY-Based Photosensitizers.

Halogenated and alkylated BODIPY derivatives are reported as suitable candidates for their use as photosensitizers in photodynamic therapy due to their efficient intersystem crossing (ISC) between states of different spin multiplicities. Spin-orbit couplings (SOCs) are evaluated using an effective one-electron spin-orbit Hamiltonian for brominated and alkylated BODIPY derivatives to investigate the quantitative effect of alkyl and bromine substituents on ISC. BODIPY derivatives containing bromine atoms have been found to have significantly stronger SOCs than alkylated BODIPY derivatives outside the Frank-Condon region while they are nearly the same at local minima. Based on calculated time-dependent density functional theory (TD-DFT) vertical excitation energies and SOCs, excited-state dynamics of three BODIPY derivatives were further explored with TD-DFT surface hopping molecular dynamics employing a simple accelerated approach. Derivatives containing bromine atoms have been found to have very similar lifetimes, which are much shorter than those of the derivatives possessing just the alkyl moieties. However, both bromine atoms and alkyl moieties reduce the HOMO/LUMO gap, thus assisting the derivatives to behave as efficient photosensitizers.

Large red-shifted NIR absorption in azulenyl- and iodinated-modified BODIPYs sensitive to aggregation and protonation stimuli

Pushing forward the red-shifting of electronic transitions in organic dyes is potentially important for applications in photodynamical chemistry and therapies. In this work, a series of BODIPY derivatives conjugated with azulene at different substituent positions were synthesized and investigated in depth. These compounds are shown to exhibit varying bathochromic shifts of their electronic transitions, as well as a further red-shift of the absorption by the modification of the compounds with iodine. Moreover, self-assembly and protonation of these compounds lead to hundreds of nanometer red-shifted electronic transitions, up to NIR-II window, relative to traditional BODIPYs. On this basis, a unique photoproduction of singlet oxygen species can be achieved under corresponding long-wavelength irradiation both in organic solution and in water, featuring a superior photosensitivity and photodynamic potential of the molecular design.

Facile Construction of Covalent Organic Framework Nanozyme for Colorimetric Detection of Uranium.

2D covalent organic frameworks (2D COFs) have been recognized as a novel class of photoactive materials owing to their extended π-electron conjugation and high chemical stabilities. Herein, a new covalent organic framework (Tph-BDP) is facilely synthesized by using a porphyrin derivative and an organic dye BODIPY derivative (5,5-difluoro-2,8-diformyl-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabori-nin-4-ium-5-uide) as monomers for the first time, and their unique photosensitive properties endow them excellent simulated oxidase activity under 635 nm laser irradiation that can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Further findings demonstrate that the presence of uranium (UO22+ ) can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading. This research provides a preparation strategy for COFs with excellent photocatalytic properties and nanozyme activity, and broadens the applications of the simple colorimetric methods for sensitive and selective radionuclide detection.

New BODIPY derivatives with triarylamine and truxene substituents as donors for organic bulk heterojunction photovoltaic cells

We have designed two new BODIPY derivatives, denoted as 6a and 6b, substituted with truxene moiety and triphenylamine (TPA) unit groups and have investigated their optical and electrochemical properties. Dyes 6a and 6b were employed as donor along with PC71BM or Y6 as acceptor for the fabrication of binary and ternary organic solar cells. After optimization of the binary and ternary active layers, we have achieved over all power conversion efficiency (PCE) of 11.37 % and 13.32% for 6a:PC71BM:Y6 and 6b:PC71BM:Y6 ternary organic solar cells, respectively, which are higher than the binary organic solar cells based on PC71BM or Y6 acceptor. The higher power conversion efficiency for ternary OSC is possibly attributed to the better exciton generation rate, exciton dissociation and charge collection.

BODIPY trimer with 1,3,5-triazine core: Facile synthesis and crystal structure

Trimerization reaction of 8-(4′-cyanophenyl)-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (CN-BODIPY) led to the isolation of a new triazine-based BODIPY trimer 2,4,6-tris(8′-phenyl-1′,3′,5′,7′-tetramethyl-4′,4′-difluoro-4′-bora-3a′,4a′-diaza-s-indacene)-1,3,5-triazine (1). This BODIPY trimer 1 have been characterized by a series of spectroscopic methods including MALDI-TOF mass, 1H NMR, electronic absorption, IR and fluorescence spectroscopy. In particular, the single crystals of 1 have be obtained by slow diffusion of methanol into the solution of this compound in CHCl3. The BODIPY trimer structure of 1 with a triazine core has been directly revealed on the basis of single crystal X-ray diffraction analysis with the intermolecular interactions investigated by Hirshfeld surface analysis. This work will be helpful for the design and synthesis of new multiple BODIPY derivatives with various application.

Nido-carborane encapsulated by BODIPY zwitterionic polymers: Synthesis, photophysical properties and cell imaging

Carborane encapsulation was visualized by using fluoroboropyrrole (BODIPY) zwitterionic polymer as fluorescence marker. Firstly, a water-soluble fluorescent probe carrier was prepared by combining the BODIPY derivatives with poly (carboxybetaine methacrylate) (p-CBMA). Two oil-in-water carborane polymers were self-assembled in organic solvents by means of dual ion hydrogen bonding. The ultraviolet and fluorescence spectra were measured with different organic solvents, and the spectra ranged from 531 to 555 nm. The dynamic self-assembly effect was tested by TEM, and the internal microscopic phenomena of the water-soluble polymer were further observed. It was confirmed that two kinds of BODIPY zwitterionic polymers were firmly encase the fat-soluble carborane, forming an oval shape. Carboranes are water-soluble, can achieve biocompatible expression, and can visualize the degree of aggregation in the targeted cells through its own fluorescence effect. Subsequent imaging of the cells showed that both polymers entered the targeted cells.

Exploration of Two Different Strategies in Near IR Absorbing Boron Dipyrromethene Derivatives for Photodynamic and Bioimaging Purposes

AbstractPhotodynamic therapy (PDT) is a method for the treatment of non‐oncological diseases and different types of cancers. Here, we report the synthesis and photophysical investigations of two different near IR absorbing classes of Boron dipyrromethene (Bodipy) photosensitizers to be used in PDT and for fluorescent bioimaging purposes. Successful utilization of benzofused Bodipy derivatives in other areas have encouraged us to exploit singlet oxygen generation abilities in comparison to a unique distyryl derivative (STBOD). In vitro cytotoxicity and fluorescence microscopy studies revealed that benzofused derivative (BFBOD) is an effective PDT agent at concentrations as low as 40 nM. Analysis with singlet oxygen trap molecule shows that distyryl derivative is more effective in terms of singlet oxygen formation ability. Furthermore, the same compound has higher fluorescence quantum yield. Novel agents including benzofused Bodipy derivatives are used for the first time by this study to expand the photosensitizer pool so to be used for various applications.

Synthesis and characterization of aryl-substituted BODIPY dyes displaying distinct solvatochromic singlet oxygen photosensitization efficiencies

Three BODIPY derivatives substituted at meso position by aryl (phenyl or N,N-dimethylaminonaphthyl) groups and functionalized at position 2 with electron-withdrawing formyl or electron deficient benzimidazole heterocycle were synthesized and completely characterized by the usual spectroscopic techniques. A comprehensive photophysical study showed a remarkable enhancement of the singlet oxygen sensitization quantum yield for meso-substituted dimethylaminonaphthyl BODIPY with the decrease of the dielectric constant of the solvent (0.02–0.04 for dimethylsulfoxide vs. 0.84 in toluene). In toluene the triplet state formation for the aminonaphthyl substituted BODIPY's was found to be mediated by the intramolecular charge transfer state (ICT), whereas in polar solvents triplet state formation is hindered by fast recombination of the ICT state. Pump-probe transient absorption spectroscopy was used to characterize the photoinduced dynamics of the BODIPY derivatives from the femtosecond to the nanosecond time scale.

Seleno-Functionalization of BODIPY Fluorophores Assisted by Oxidative Nucleophilic Hydrogen Substitution

Background: The most current reported methods of chalcogen insertion into BODIPY’s nuclei are based on nucleophilic substitution reactions of halogenated derivatives, metal-catalyzed cross-coupling reactions, or assistance by radical mechanisms. Recent reports describe Oxidative Nucleophilic Hydrogen Substitution (ONHS) reactions involving the functionalization of BODIPY nuclei by thiols, but the generalities of the strategy for other chalcogens was not yet demonstrated. Herein we report our contribution on the selenium-functionalization of BODIPY by ONHS in high yield. Objective: Aryl-Se-functionalization of 2,6-brominated BODIPY’s nuclei by ONHS reaction. Method: The procedure consists of a direct reaction of 2,6-brominated BODIPYs with in situ generated PhSeH in THF, at room temperature, under a nitrogen atmosphere. The corresponding products were isolated and purified by conventional flash column chromatography. Full structure characterization was performed by 1H, 13C, 19F, and 77Se NMR and DFT calculation. Results: Densely functionalized 2,6-dibrominated/3,5-diseleno-BODIPYs were obtained as corresponding products, leading to versatile molecular scaffolds. Their structural features were contrary to those initially expected by the original experimental applied conditions. A mechanistic investigation was performed to conclude that ONHS reaction is governing the transformation, thereby damaging the nucleophilic substitution of the halogen atoms. Conclusion: To sum up, new densely functionalized BODIPY derivatives were synthesized by a highly selective, simple, fast, metal-free, and efficient insertion of PhSe- residues into the 3,5-positions, governed by an Oxidative Nucleophilic Hydrogen Substitution (ONHS) reaction in high yields. It was observed that the presence of halogen (Br) into the 2,6-positions of the BODIPY core is mandatory for the ONHS reaction, which is completely inert when the 2,6-hydrogenated analogues are used in the same experimental conditions.

Aggregation, energy transfer and intramolecular charge transfer in donor-acceptor-donor BODIPY derivative lead to single component white light emission

A novel donor-acceptor-donor (D-A-D’) type of BODIPY derivative BDP-1 was synthesized and its fluorescence properties were investigated. By delicate tuning various parameters, e. g. solvent, concentration, excitation wavelength, aggregates of BDP-1 display single component white light emission (WLE), and the CIE coordinate values could be optimized to (0.33, 0.32). Detailed photophysical analysis by use of time-resolved spectroscopy and model compounds demonstrated that aggregation and further balance between energy transfer (ET) and intramolecular charge transfer (CT) from different groups in BDP-1 resulted in coordinated three primary color emissions which led to single component WLE.

Functionalization of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers with Triphenylphosphonium (TPP) for mitochondria-targeted fluorescence bioimaging and photodynamic therapy

Functionalization of BODIPY dyes with TPP substituents endowed them with mitochondria-targeting capabilities. The uniodinated BODIPY control displayed good biocompatibility, low cytotoxicity in the dark, and exceptional cellular imaging capabilities; however, it did not exhibit photodynamic therapeutic properties upon excitation at 530 nm. Dual functional photosensitizers were obtained in the case of mono- and di-iodinated BODIPY derivatives, which exhibited mitochondria-targeting capabilities and provided clear fluorescence confocal bioimages, while efficiently generating high levels of singlet oxygen species and displaying photodynamic therapeutic activity toward two cancer cell lines following LED irradiation. Overall, the results presented herein demonstrate the considerable potential for the use of TPP-functionalized BODIPY dyes as viable agents for fluorescence-imaging-guided photodynamic therapy (PDT) for cancer treatment.

Effects of Intermolecular Hydrogen Bonding and Solvation on Enol-Keto Tautomerism and Photophysics of Azomethine-BODIPY Dyads.

Boron-dipyrromethene derivatives (BODIPYs) are a category of molecules with excellent photophysical properties and can be applied to various fields. This work investigates the fluorescent properties of two azomethine-BODIPY dyads in different solvents based on the time-dependent density functional theory (TD-DFT) method. The potential energy curves (PECs) show that the polar protic solvent and the enhanced π-conjugation effect can lower the proton-transfer (PT) barriers, causing the main configuration of NA-BODIPY in methanol to be the keto form, while the main configuration of NA-BODIPY in toluene and SA-BODIPY in methanol and toluene is the enol form. The keto forms of the two compounds possess the twisted intramolecular charge transfer (TICT) decay pathway in the excited state identified by the optimized twisted configurations and the appropriate barriers of the TICT process, whereas the twisted configurations of the enol forms are nonexistent. TICT successfully competes with excited-state proton transfer (ESIPT) of the keto form, which leads to the fluorescence quenching of NA-BODIPY in methanol. This work provides new ideas for the influence of enol-keto tautomerism and the competitiveness of TICT and ESIPT on the photophysical properties of BODIPYs and is expected to provide guidance for the design of new BODIPY functional molecules.

Tailoring the Solid-State Fluorescence of BODIPY by Supramolecular Assembly with Polyoxometalates.

A cationic boron dipyrromethene (BODIPY) derivative (1+) has been successfully combined with two polyoxometalates (POMs), the Lindqvist-type [W6O19]2- and the β-[Mo8O26]4- units, into three new supramolecular fluorescent materials (1)2[W6O19]·2CH3CN, (1)2[W6O19], and (1)4[Mo8O26]·DMF·H2O. The resulting hybrid compounds have been fully characterized by a combination of single-crystal X-ray diffraction, IR and UV-vis spectroscopies, and photoluminescence analyses. This self-assembly approach prevents any π-π stacking interactions not only between the BODIPY units, responsible for aggregation-caused quenching (ACQ) effects, but also between the BODIPY and the POMs, avoiding intermolecular charge-transfer effects. Noticeably, the POM units do not only act as bulky spacers, but their negative charge density drives the molecular arrangement of the 1+ luminophore, strongly modifying its fluorescence in the solid state. As a consequence, the 1+ cations are organized into dimers in (1)2[W6O19]·2CH3CN and (1)2[W6O19], which are weakly emissive at room temperature, and in a more compact layered assembly in (1)4[Mo8O26]·DMF·H2O, which exhibits a red-shifted and intense emission upon similar photoexcitation.