BODIPY Compound Research Articles

Optical sensor properties of a novel BODIPY compound for non-enzymatic detection of glucose

This work demonstrated the preparation and characterization of a novel 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative containing boronic acid group and investigation of its non-invasive/non-enzymatic fluorescence sensor behavior for determination of glucose. The novel BODIPY derivative bearing boronic acid pinacol ester (BODIPY-1) was synthesized by Sonogashira coupling reaction between Iodo-BODIPY and 4-ethynylphenylboronic acid pinacol ester. The target novel BODIPY-2 compound which was used as a fluorescence probe for the determination of glucose was synthesized from BODIPY-1by changing the pinacol ester group to the boric acid moieties. The fluorescence intensity of the BODIPY-2 fluorophore decreased when it interacted with the glucose. Sensing performance towards to glucose of this probe was evaluated in detail concerning the suitable solvent, linear concentration range, convenient pH, limit of detection (LOD), limit of quantification (LOQ) and selectivity. The LOD value of BODIPY-2 was found 0.19 mM toward glucose. Also, the complex stoichiometry between the BODIPY-2 and glucose molecules was determined by Job’s plot technique.

The ultrasound and light combination as a new approach for BODIPY dyes with the enhanced singlet oxygen formation

Sonophotodynamic Therapy (SPDT) is a new approach that uses the light of photodynamic therapy (PDT) and ultrasound of sonodynamic therapy (SDT) together. Although it is known that singlet oxygen production in phthalocyanine-derived photosensitizers increases significantly with the use of the SPDT method, there is no study in the literature investigating the singlet oxygen generating capacity of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) compounds with the SPDT method. This study was motivated by the desire to evaluate the singlet oxygen production capacity of BODIPY compounds by using SPDT method. For this reason, in this study, we present the synthesis of novel BODIPY derivative withmeso-dibenzothienyl segment, diiodine moieties at 2-,6-positions and distyryl structure at 3-,5-positions. The resulting compound was illuminated by applying spectroscopic techniques including 1H-NMR, UV–Vis, MS and elemental analysis. This study aimed to demonstrate and compare the potentials of BODIPY compound in PDT and SPDT applications based on the photochemical and sonophotochemical measurements. While the calculated ΦΔ value was 0.34 for BDPY4 after light irradiation, this value increased to 0.76 after combination of light and ultrasound irradiation used together. Based on the fact that the synthesized BDPY4 may be a suitable agent in SPDT applications, this study will be a precursor in understanding the sonophotochemical measurements of BODIPY compounds for in vivo or in vitro studies in the future.

A new approach for BODIPY derivatives: Increasing the singlet oxygen formation by sonophotochemical technique

Research to explore the therapeutic capacities of sensitizers in Photodynamic Therapy (PDT) has been among the topics that have been frequently explored in recent years. In this context, studies that improve the ability of sensitizers to produce singlet oxygen with the help of ultrasound draw so much attention. In addition, the importance of BODIPYs used as sensitizers in photodynamic and/or sonodynamic therapy (SDT) is increasing. Although the positive effect of sonophotodynamic therapy (SPDT) on phthalocyanine derivatives has been shown in both photophysicochemical and in vivo studies, according to the best of our knowledge, the effect of sonophotochemical measurements for BODIPY derivatives has not been reported in the literature yet. Evaluation of the sonophotochemical potentials of BODIPY derivatives and meeting this need in the literature are the biggest impetus of this study.In this context, we have synthesized a new BODIPY compound (BDPY2) with methoxystyryl substituents to evaluate the capability of singlet oxygen production by sonophotochemical method. Synthesized compound was illuminated using different spectroscopic techniques encompassing 1H-NMR, 13C-NMR,19F-NMR, UV-Vis, MS, and elemental analysis. ΦΔ value of BDPY2 was calculated by the photochemical method as 0.33, while ΦΔ value reached 0.68 by applying the sonophotochemical method. The obtained data proved that the singlet oxygen production increased considerably by changing the method from light irradiation to ultrasound/light. This result will be a pioneer study to comprehend the sonophotochemical measurements of BODIPY derivatives for in vivo or in vitro studies in the future.

Exploring anticancer properties of novel Nano-Formulation of BODIPY Compound, Photophysicochemical, in vitro and in silico evaluations

A new BODIPY complex (C4) composed of meso- thienyl-pyridine substituted core unit diiodinated from 2- and 6- positions and distyryl moieties at 3- and 5- positions is synthesized. Nano-sized formulation of C4 is prepared by single emulsion method using poly(ε-caprolactone)(PCL) polymer. Encapsulation efficiency and loading capacity values of C4 loaded PCL nanoparticles (C4@PCL-NPs) are calculated and in vitro release profile of C4 is determined. The cytotoxicity and anti-cancer activity are conducted on the L929 and MCF-7 cell lines. Cellular uptake study is performed and interaction between C4@PCL-NPs and MCF-7 cell line is investigated. Anti-cancer activity of C4 is predicted with molecular docking studies and the inhibition property on EGFR, ERα, PR and mTOR are investigated for its anticancer properties. Molecular interactions, binding positions and docking score energies between C4 and EGFR, ERα, PR and mTOR targets are revealed using in silico methods. The druglikeness and pharmacokinetic properties of C4 are evaluated using the SwissADME and its bioavailability and toxicity profiles are assessed using the SwissADME, preADMET and pkCSM servers. In conclusion, the potential use of C4 as an anti-cancer agent is evaluated in vitro and in silico methods. Also, photophysicochemical properties are studied to investigate the potential of using Photodynamic Therapy (PDT). In photochemical studies, the calculated singlet oxygen quantum yield (ΦΔ) value was 0.73 for C4 and in photopysical studies, the calculated fluorescence quantum yield ΦF value was 0.19 for C4.

One- and two-electron reductions of a bulky BODIPY compound.

The redox reaction between a bulky BODIPY and a magnesium(I) reducing agent leads to the formal one-electron reduction of the BODIPY, initially generating a dipyrromethene-centred radical compound that dimerises via C-C bond formation. In contrast, reduction with magnesium anthracene leads to the formal two-electron reduction of the BODIPY, resulting in the formation of the corresponding anion.

Improvement of photochemical and enzyme inhibition properties of new BODIPY compound by conjugation with cisplatin

In this study, new BODIPY complexes were synthesized, characterized and investigated for their some metabolic enzyme inhibition and photophysicochemical properties. BODIPY central core unit was synthesized by using conventional method followed by Suzuki-Miyaura Cross-Coupling reaction. After converting the obtained compound into the diiodinated derivative in the presence of HIO3/I2, quaternization of BODIPY derivative was achieved with cisplatin [cis-PtCl(NO3)(NH3)2] over the pyridine segment. Characterizations of all intermediates and the target compound were determined by 1H-NMR, 13C-NMR and MS spectroscopic methods. The potentials of the synthesized compounds in photodynamic therapy applications were determined by calculating the fluorescence, singlet oxygen and photodegradation quantum yields. Also, all complexes were screened for human carbonic anhydrase I, II (hCAs I and II), acetylcholinesterase (AChE), butyryl cholinesterase (BChE), and α-glucosidase inhibitory activities. Results indicated that all the synthesized complexes exhibited potent inhibitory activities against standard inhibitors, revealed by IC50 values.

Inhibiting Radiative Transition-Mediated Multifunctional Polymeric Nanoplatforms for Highly Efficient Tumor Phototherapeutics.

It is highly desired to explore ideal phototherapeutic nanoplatforms, especially containing satisfactory phototherapeutic agents (PTAs), for potential cancer therapies. Herein, we proposed an effective strategy for designing a highly efficient PTA through inhibiting radiative transition (IRT). Specifically, we developed an ultralow radiative BODIPY derivative (TPA-IBDP) by simply conjugating two triphenylamine units to iodine-substituted BODIPY, which could simultaneously facilitate the nonradiative decay channels of singlet-to-triplet intersystem crossing and intramolecular charge transfer. In comparison to the normal BODIPY compound, TPA-IBDP exhibited an outstanding singlet oxygen yield (31.8-fold) and a higher photothermal conversion efficiency (PCE; over 3-fold), respectively, benefiting from the extended π-conjugated donor-to-accepter (D-A) structure and the heavy atom effect. For tumor phototherapy using TPA-IBDP, TPA-IBDP was conjugated with a H2O2-responsive amphiphilic copolymer POEGMA10-b-[PBMA5-co-(PS-N3)2] to construct a multifunctional phototherapeutic BODIPY-based nanoplatform (PB). PB produced abundant singlet oxygen (1O2) and heat along with negligible fluorescence emission under near-infrared laser irradiation. Additionally, PB could generate a GSH-depletion scavenger (quinone methide, QM) after reacting with the abundant intracellular H2O2 in tumor for the cooperative enhancement of IRT-mediated phototherapy. We envision that this highly efficient multifunctional phototherapeutic nanoplatform cooperated by GSH-depletion could be a valuable paradigm for tumor treatments.

Twisted Bodipy Derivative as a Heavy-Atom-Free Triplet Photosensitizer Showing Strong Absorption of Yellow Light, Intersystem Crossing, and a High-Energy Long-Lived Triplet State.

A Bodipy derivative with twisted π-conjugation system is demonstrated that shows efficient intersystem crossing (ISC) (singlet oxygen quantum yield ΦΔ = 55%) and a long-lived triplet state (τT = 197.5 μs) with high energy (ET1 = 1.44-1.53 eV). This is superior to the conventional heavy-atom-enhanced ISC in a reference Bodipy compound, which results in much shorter triplet state lifetime (3.3 μs) and lower triplet-state energy (1.2 eV).

Two Novel BODIPY-Functional Magnetite Fluorescent Nano-Sensors for Detecting of Cr(VI) Ions in Aqueous Solutions.

In this study, we developed two different very sensitive magnetite fluorescent Fe3O4@SiO2-TPED-BODIPY and Fe3O4@SiO2-TMPTA-BODIPY nano-sensors for the selective detection of Cr(VI) ions. The Cr(VI) metal ions sensing is based on the fluorescent quenching of BODIPY functionalized with Fe3O4@SiO2-TPED and Fe3O4@SiO2-TMPTA nanoparticles in the ethanol-water environment. Characterization of the newly synthesized fluorescent BODIPY compound was performed on a 1H and 13C-NMR spectrometer. The morphology, chemical and physical properties of the sensing nano-sensors were studied by transmission thermogravimetric analysis (TGA), X-ray diffraction (XRD), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), FT-IR spectroscopy, and transmission electron microscopy (TEM). UV-visible and fluorescent spectroscopy were used to characterize BODIPY functionalized magnetite fluorescent nano-sensors. Characterization measurements revealed that the mean particle diameter of magnetite fluorescent Fe3O4@SiO2-TPED-BODIPY and Fe3O4@SiO2-TMPTA-BODIPY nano-sensors was 18.5 and 19nm, respectively. The magnetite fluorescent Fe3O4@SiO2-TPED-BODIPY and Fe3O4@SiO2-TMPTA-BODIPY nano-sensors (0.1 gL-1 in EtOH/H2O, v/v (3/7)) showed fluorescence quenching responses towards Cr(VI) ions in the medium at pH:1. The fluorescence quenches of the magnetite fluorescent Fe3O4@SiO2-TPED-BODIPY and Fe3O4@SiO2-TMPTA-BODIPY nano-sensors by Cr(VI) were completed in first 5 and 3min. Respectively. These features provide potential uses of BODIPY functionalized magnetite fluorescent nano-sensors (Fe3O4@SiO2-TPED-BODIPY and Fe3O4@SiO2-TMPTA-BODIPY) as a new class of non-toxic sensors for environmental applications. Graphical Abstract.

A highly sensitive and selective ON-OFF fluorescent sensor based on functionalized magnetite nanoparticles for detection of Cr(VI) metal ions in the aqueous medium

Herein, we developed a very sensitive and selective fluorescent magnetic nanoparticle sensor for the selective detection of Cr(VI) metal ions in aqueous solutions. Detection of Cr(VI) metal ions is based on fluorescence quenching mechanism of the BODIPY compound bearing magnetic nanoparticles in aqueous media. The newly synthesized BODIPY compound was characterized by 1H and 13C NMR. The morphology, chemical and physical properties of the prepared nanoparticles were performed by energy-dispersive X-ray (EDX), thermo gravimetric analysis (TGA), transmission electron microscopy (TEM), FT-IR spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Fluorescence and UV–visible spectroscopies were used to investigate the selectivity of the BODIPY immobilized magnetic nanoparticle and used to detect Cr(VI) metal ion in aqueous solutions. According to the characterization, the magnetic fluorescent super magnetic iron oxide nanoparticles (F-SPION) were revealed that the average particle diameter was about 18 nm. The newly prepared fluorescent superparamagnetic nanoparticle (F-SPION) showed a fluorescence quenching response against Cr(VI) metal ions at pH 1 medium. The response of the magnetic fluorescent nanoparticle to target metal ion, Cr(VI), was highly selective, while possible interactions from other metal cations were insignificant. The fluorescence quenching of F-SPION in presence of Cr(VI) was completed in the first 5 min. These features provide potential uses of the prepared F-SPION as a new class of useful sensors for environmental applications.

A Nano-BODIPY Encapsulated Zeolitic Imidazolate Framework As Photoresponsive Integrating Antibacterial Agent.

Drug-resistant bacteria challenge the antimicrobial agents and antibacterial strategy. To develop environmental friendly smart technology for treating pathogens, we report a kind of photoactivated nano-BODIPY (BCNBA@ZIF). First BODIPY compound (BC) was synthesized by coupling phenethyl caffeate (CAPE) with brominated BODIPY through B-O bonds. Next, BC was encapsulated in ZIF-8 together with 2-nitrobenzaldehyde (o-NBA) to form photoactivated BCNBA@ZIF nanoparticles. TEM confirm the structural change of BCNBA@ZIF after illumination. BCNBA@ZIF is less toxic to cells without illumination. Under illumination of blue LED light, the BCNBA@ZIF worked as a photoacid generator initiating the damage of ZIF shell with the release of BC, metal ions, and the production of singlet oxygen for achieving multifunctional antibacterial uses. Therefore, BCNBA@ZIF is a kind of photodriven smart "Domino" agent for bacterial inhibition.

Insight into the optical properties of meso-pentafluorophenyl(PFP)-BODIPY: An attractive platform for functionalization of BODIPY dyes

The pentafluorophenyl (PFP) moiety is an important and versatile substituent in the chemistry of BODIPYs, porphyrins and corroles. The widespread use of PFP meso-substituted compounds, as intermediates in the synthesis of more complex pyrrole derivatives, is the motivation behind this work, which investigates the optical properties of the meso-PFP-BODIPY from a theoretical point of view. From the panoply of computational tools available for this purpose, we have considered the MS-CASPT2//CASSCF multiconfigurational protocol, and other monoreference methods, including time dependent density functional theory, TD-DFT, the second order approximate couple cluster, CC2, and the algebraic diagrammatic construction scheme of the polarization propagator in its second order, ADC(2). We have identified ADC(2) as the most suited method for the characterization of the absorption properties of BODIPYs. Besides its computational efficiency and the small dependence shown towards the basis set flexibility, the results obtained with this method are independent from the preexisting knowledge of the system and its properties to be calculated by the user. In general, all the methods evaluated show a good performance when compared with experimental results, especially if implicit solvent effects are taken into account, delivering errors which amount to 0.05 eV. Finally, we discuss the effect of the electron-withdrawing PFP substituent at the meso-position on the absorption and emission energies of the boron-dipyrromethene core. The comparison of the PFP-substituted and core BODIPY spectroscopic properties reveals that this substituent red-shifts both the absorption and the emission of the parent dye. On the one hand, the incorporation of this substituent was found to reduce the HOMO-LUMO gap, and on the other it induces a strong destabilization of the electronic ground state along the global coordinate leading the system from the Franck-Condon region to the position of the first excited state, S1, minimum, suggesting a lower S1/S0 internal conversion funnel compared to the parent BODIPY compound.

An unprecedented oxidised julolidine-BODIPY conjugate and its application in real-time ratiometric fluorescence sensing of sulfite.

Reaction of a julolidine-based BODIPY compound with silver(i) ions in the presence of white light produced the oxidised julolidine version (OXJUL) containing a quaternary nitrogen. The oxidation of one ring at the julolidine site is highly unusual and there is no other reported literature example. The fluorescence maximum of OXJUL is altered from 648 nm to 608 nm by the addition of an aqueous solution of Na2SO3 over several minutes. In the presence of a large excess of sulfite a further slower reaction is observed which further shifts the emission maximum to 544 nm. The alterations form the basis of a real-time ratiometric sensor for sulfite and its detection in a white wine.

A Photoactivatable BODIPY Probe for Localization‐Based Super‐Resolution Cellular Imaging

AbstractThe synthesis and application of a photoactivatable boron‐alkylated BODIPY probe for localization‐based super‐resolution microscopy is reported. Photoactivation and excitation of the probe is achieved by a previously unknown boron‐photodealkylation reaction with a single low‐power visible laser and without requiring the addition of reducing agents or oxygen scavengers in the imaging buffer. These features lead to a versatile probe for localization‐based microscopy of biological systems. The probe can be easily linked to nucleophile‐containing molecules to target specific cellular organelles. By attaching paclitaxel to the photoactivatable BODIPY, in vitro and in vivo super‐resolution imaging of microtubules is demonstrated. This is the first example of single‐molecule localization‐based super‐resolution microscopy using a visible‐light‐activated BODIPY compound as a fluorescent probe.

Fluorescent Sensing of Cesium Ions by an Amide‐Linked BODIPY Dye: Synthesis and Photophysical Properties

AbstractIn this study, a new fluorescent sensor for Cs+ ion was designed and synthesized from the combination of pyridine‐2,6‐dicarboxamide and 4,4‐difluoro‐4‐borata‐3a,4a‐diaza‐s‐indacene (BODIPY) scaffolds. The sensing capability of the target compound against a variety of ions was investigated. The structure of the target compound was proved by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, and 1H and 13C NMR spectroscopies. Photophysical properties of the amide‐linked BODIPY compound were studied by utilizing fluorescence spectroscopies in DMSO/water (9:1, v/v) solution. It was found that the final amide‐linked BODIPY compound showed exclusively selective and sensitive turn‐off sensor behavior for Cs+ ion over other metal ions (Li+, Na+, K+, Cs+, Mg2+, Ca2+, Ba2+, Hg2+, Pb2+, Mn2+, Cd2+, Ag+, Ni2+, Cu2+, Zn2+, Co2+, Cr3+ and Fe3+). The addition of Cs+ resulted in quenching of fluorescence intensity and the detection limit was calculated to be 0.273 μM. According to Job's Plot, binding stoichiometry ratio of the target compound with Cs+ was 1:1.

Utilization of a Fluorescent Dye Molecule as a Proton and Electron Reservoir.

Fluorescent dyes have been widely utilized as chemical sensors and in photodynamic therapy, but exploitation of their redox-active nature in chemical reactions has remained mostly unexplored. This report describes the isolation of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based radical. The redox-active nature of the BODIPY compound can be utilized in combination with a guanidine center, the basicity of which can be manipulated by greater than 14 pKa units, to promote the conversion of protons and electrons into H-atoms for transfer to substrate molecules.

Utilization of a Fluorescent Dye Molecule as a Proton and Electron Reservoir

AbstractFluorescent dyes have been widely utilized as chemical sensors and in photodynamic therapy, but exploitation of their redox‐active nature in chemical reactions has remained mostly unexplored. This report describes the isolation of a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY)‐based radical. The redox‐active nature of the BODIPY compound can be utilized in combination with a guanidine center, the basicity of which can be manipulated by greater than 14 pKa units, to promote the conversion of protons and electrons into H‐atoms for transfer to substrate molecules.

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.

New Meso-ortho-hydroxy-decorating Fluorescent ON-OFF Bodipy sensor to Cu2 +

A new meso-ortho-hydroxy-modifying Bodipy compound (o-OH-Bodipy) has been designed and synthesized. Single crystal X-ray diffraction analysis reveals the slight lean of the meso-phenyl moiety to the o-OH side due to the effect of the o-OH substituent. Systematic optical studies indicate that introduction of the o-OH group onto the meso-phenyl moiety of this compound induces an increased binding affinity and in particular an obvious fluorescence quenching response to Cu2+ on the basis of the photo-induced electronic transition process, endowing o-OH-Bodipy a great potential as highly sensitive fluorescence ONOFF detector for Cu2+ even in the acidic condition.

Near IR emitting BODIPY fluorophores with mega-stokes shifts

A novel Near Infra-Red emitting BODIPY derivative is presented which exhibits the largest Stokes shift thus far reported for a BODIPY compound.