Brominated boron dipyrrins: synthesis, structure, spectral and electrochemical properties

meso-Anisyl boron dipyrrins (BODIPYs) 1-6 containing one to six bromines at the pyrrole carbons have been synthesized by treating meso-anisyl dipyrromethane with 'n' equivalents of N-bromosuccinimide in THF at room temperature followed by oxidation with DDQ, neutralization with triethylamine and further complexation with BF(3)·OEt(2). The brominated compounds were characterized by HR-MS mass, detailed (1)H, (19)F and (11)B NMR and X-ray diffraction studies. The crystal structures solved for compounds 2-6 indicate that the boron dipyrrinato framework comprised two pyrrole rings and one six membered boron containing ring in one plane like other reported BODIPYs. However, the dihedral angle between the BODIPY core and the meso-anisyl group varied from 48° to 88° and the meso-anisyl ring has an almost perpendicular orientation in penta 5 and hexabrominated 6 BODIPYs. The absorption and emission studies showed a bathochromic shift and reached a maximum for tetrabrominated derivative 4, after which there was no change in the peak maxima for penta 5 and hexabrominated 6 derivatives. However, the quantum yields were reduced with the increasing number of bromines. The electrochemical studies revealed that brominated BODIPY compounds 1-6 are easier to reduce compared to unsubstituted meso-anisyl BODIPY 8 and the reduction potential is linearly related to the number of Br groups.     

3,5-Diformylboron dipyrromethenes as fluorescent pH sensors

A series of boron dipyrromethene (BODIPY) dyes containing two aldehyde functional groups at the 3 and 5 positions have been synthesized in low-to-decent yields in two steps. In the first step, the meso-aryl dipyrromethanes were treated with POCl(3) in N,N-dimethylformamide to afford 1,9-diformylated dipyrromethanes. In the second step, the diformylated dipyrromethanes were first in situ oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and then reacted with BF(3)·OEt(2) to afford 3,5-diformylboron dipyrromethenes. The X-ray structural analysis indicated that the aldehyde groups are involved in intramolecular hydrogen bonding with fluoride atoms, which may be responsible for the stability of the diformylated BODIPY compounds. The presence of two formyl groups significantly alters the electronic properties, which is clearly evident in downfield shifts in the (1)H and (19)F NMR spectra, bathochromic shifts in the absorption and fluorescence spectra, better quantum yields, and increased lifetimes compared to 3,5-unsubstituted BODIPYs. Furthermore, 3,5-diformylboron dipyrromethenes are highly electron-deficient and undergo facile reductions compared to unsubstituted BODIPYs. These compounds exhibit pH-dependent on/off fluorescence and thus act as fluorescent pH sensors.     

Synthesis,Structure, and Optical Studies of Donor–Acceptor‐Type Near‐Infrared (NIR) Aza–Boron‐Dipyrromethene (BODIPY) Dyes

Six donor–acceptor‐type near‐infrared (NIR) aza–boron‐dipyrromethene (BODIPY) dyes and their corresponding aza–dipyrrins were designed and synthesized. The donor moieties at the 1,7‐positions of the aza–BODIPY core were varied from naphthyl to N‐phenylcarbazole to N‐butylcarbazole. The 3,5‐positions were also substituted with phenyl or thienyl groups in the aza–BODIPYs. Photophysical, electrochemical, and computational studies were carried out. The absorption and emission spectra of aza–BODIPYs were significantly redshifted (≈100 nm) relative to the parent tetraphenylaza–BODIPY. Fluorescence studies suggested effective energy transfer (up to 93 %) from donor groups to the aza–BODIPY core in all of the compounds under study. Time‐dependent (TD)‐DFT studies indicated effective electronic interactions between energy donor groups and aza–dipyrrin unit in all the aza–BODIPYs studied. The HOMO–LUMO gap (ΔE) calculated from cyclic voltammetry data was found to be lower for six aza–BODIPYs relative to their corresponding aza–dipyrrins.     

Synthesis, spectral, electrochemical, and anion binding properties of 3,5-bis(dipyrromethanyl) boron-dipyrromethenes

Four new boron-dipyrromethenes (BODIPYs) containing dipyrromethanyl substituents at 3,5-positions, bis(3,5-dipyrromethanyl) BODIPYs 5-8, were synthesized by treating their corresponding 3,5-diformyl BODIPYs 1-4 with excess pyrrole under mild acid catalyzed reaction conditions. The compounds 5-8 are stable and freely soluble in common organic solvents. One-dimensional, two-dimensional NMR, high resolution mass spectrometry (HRMS), absorption, fluorescence, and electrochemical techniques were used to characterize the compounds. The spectral and electrochemical studies indicated that dipyrromethanyl groups at 3,5-positions of BODIPY are less electron deficient compared to formyl groups at the same positions. The anion binding studies indicated that bis(3,5-dipyrromethanyl) BODIPY compounds containing four pyrrole NH groups showed preferential binding with F(-) ion over other anions, as confirmed by using NMR, fluorescence, and electrochemical studies.     

Synthesis,Computational Modeling,and Properties of Benzo‐Appended BODIPYs

A series of new functionalized mono‐ and dibenzo‐appended BODIPY dyes were synthesized from a common tetrahydroisoindole precursor following two different synthetic routes. Route A involved the assembly of the BODIPY core prior to aromatization, while in Route B the aromatization step was performed first. In general, Route A gave higher yields of the target dibenzo‐BODIPYs, due to the ease of aromatization of the BODIPYs compared with the corresponding dipyrromethenes, probably due to their higher stability under the oxidative conditions (2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone in refluxing toluene). However, due to the slow oxidation of highly electron‐deficient BODIPY 3 c bearing a meso‐C₆F₅ group, dibenzo‐BODIPY 4 c was obtained, in 35 % overall from dipyrromethane, only by Route B. Computational calculations performed at the 6‐31G(d,p) level are in agreement with the experimental results, showing similar relative energies for all reaction intermediates in both routes. In addition, BODIPY 3 c had the highest molecular electrostatic potential (MEPN), confirming its high electron deficiency and consequent resistance toward oxidation. X‐ray analyses of eight BODIPYs and several intermediates show that benzannulation further enhances the planarity of these systems. The π‐extended BODIPYs show strong red‐shifted absorptions and emissions, about 50–60 nm per benzoannulated ring, at 589–658 and 596–680 nm, respectively. In particular, db‐BODIPY 4 c bearing a meso‐C₆F₅ group showed the longest λ_max of absorption and emission, along with the lowest fluorescence quantum yield (0.31 in CH₂Cl₂); on the other hand monobenzo‐BODIPY 8 showed the highest quantum yield (0.99) of this series. Cellular investigations using human carcinoma HEp2 cells revealed high plasma membrane permeability for all dibenzo‐BODIPYs, low dark‐ and photo‐cytotoxicities and intracellular localization in the cell endoplasmic reticulum, in addition to other organelles. Our studies indicate that benzo‐appended BODIPYs, in particular the highly stable meso‐substituted BODIPYs, are promising fluorophores for bioimaging applications.     

Synthesis, computational modeling, and properties of benzo-appended BODIPYs

A series of new functionalized mono- and dibenzo-appended BODIPY dyes were synthesized from a common tetrahydroisoindole precursor following two different synthetic routes. Route?A involved the assembly of the BODIPY core prior to aromatization, while in Route?B the aromatization step was performed first. In general, Route?A gave higher yields of the target dibenzo-BODIPYs, due to the ease of aromatization of the BODIPYs compared with the corresponding dipyrromethenes, probably due to their higher stability under the oxidative conditions (2,3-dichloro-5,6-dicyano-1,4-benzoquinone in refluxing toluene). However, due to the slow oxidation of highly electron-deficient BODIPY 3?c bearing a meso-C(6)F(5) group, dibenzo-BODIPY 4?c was obtained, in 35?% overall from dipyrromethane, only by Route?B. Computational calculations performed at the 6-31G(d,p) level are in agreement with the experimental results, showing similar relative energies for all reaction intermediates in both routes. In addition, BODIPY 3?c had the highest molecular electrostatic potential (MEPN), confirming its high electron deficiency and consequent resistance toward oxidation. X-ray analyses of eight BODIPYs and several intermediates show that benzannulation further enhances the planarity of these systems. The π-extended BODIPYs show strong red-shifted absorptions and emissions, about 50-60?nm per benzoannulated ring, at 589-658 and 596-680?nm, respectively. In particular, db-BODIPY 4?c bearing a meso-C(6)F(5) group showed the longest λ(max) of absorption and emission, along with the lowest fluorescence quantum yield (0.31 in CH(2)Cl(2)); on the other hand monobenzo-BODIPY 8 showed the highest quantum yield (0.99) of this series. Cellular investigations using human carcinoma HEp2 cells revealed high plasma membrane permeability for all dibenzo-BODIPYs, low dark- and photo-cytotoxicities and intracellular localization in the cell endoplasmic reticulum, in addition to other organelles. Our studies indicate that benzo-appended BODIPYs, in particular the highly stable meso-substituted BODIPYs, are promising fluorophores for bioimaging applications.     

Silyl‐ and Disilanyl‐BODIPYs: Synthesis via Catalytic Dehalosilylation and Spectroscopic Properties

We describe herein the first synthesis of silyl‐ and disilanyl‐BODIPYs through transition‐metal‐catalyzed dehalosilylation of iodo‐BODIPYs using a Pd(P(t Bu)₃)₂/Et₃N/toluene system. Various mono‐ and bis‐silyl‐BODIPYs, mono‐ and bis‐disilanyl‐BODIPYs and bis‐BODIPYs linked by silylene and SiOSi groups were synthesized by using this straightforward method. Silyl‐ and disilanyl‐substitution significantly modifies the spectroscopic properties of the BODIPY, in which the fluorescence quantum yields of the silyl‐BODIPYs are remarkably increased, whereas the emission spectra of disilanyl‐BODIPYs are red‐shifted due to effective σ(SiSi)–π(BODIPY) conjugation.     

Acidic Condensation of BODIPYs with Aldehydes: A Quick and Versatile Route to Alkenyl‐BODIPYs and C(sp3)‐Connected DYEmers

The condensation of aldehydes with BODIPY (boron dipyrrin) luminophores was investigated. Formaldehyde can be used to connect two BODIPYs at each of the three pyrrolic C positions (α‐, β‐, and β′‐positions) in a quick and highly selective manner, yielding new DYEmers (di‐ and oligomeric BODIPY derivatives) with varied photophysical properties. Benzaldehydes form DYEmers only at the β‐ and the β′‐positions. For aliphatic aldehydes the DYEmer formation competes with the elimination of water from a proposed alcohol intermediate, leading to the formation of α‐ and β‐alkenyl‐BODIPYs. 2‐Phenylacetaldehyde and similar precursors exclusively yield elimination products. These acid‐mediated transformations are valuable alternatives to the well‐established, base‐promoted Knoevenagel condensation protocol that is typically employed in the preparation of BODIPYs with near infrared (NIR)‐shifted absorptions.     

Dual Chromophoric Meso-Aryl BODIPYs with Aggregation Induced Red-Emission Characteristics: Optical Properties and their Application in Fe3+ Detection

Herein, we report the design of meso-aryl BODIPYs as a structural motif for aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) transformation. A series of meso-aryl BODIPY derivatives were synthesized, by systematically increasing the size of the chromophore at the meso-position from phenyl to pyrene. The effect of various factors, such as the aryl ring size, solvents, viscosity, and metal cations, on the photophysical properties was analyzed. The emission properties are well correlated with the flexibility of the aromatic ring for free rotation around the C_aryl−C_BODIPY bond. Accordingly, meso-phenanthrene BODIPY ( PhB ) has the highest emission characteristics. The emission property of less bulky aryl-substituted BODIPYs increases by increasing the solvent viscosity. The interaction of Fe³⁺ ions with aryl-BODIPYs provides a prominent photophysical response based on Lewis-acid supported decomplexation of BF₂ in aryl-BODIPYs. The bichromophoric meso-aryl BODIPYs exhibit notable intramolecular excitation energy transfer from the aromatic ring to the BODIPY core, which is higher in meso-anthracene BODIPY( AB ). Hence, decorating BODIPYs with polycyclic aromatic systems generates a twisted structure, which inhibits the π-π stacking between the planar aromatic molecules. This can be proposed as an effective approach at the molecular level to convert planar aryl luminophores having ACQ to AIEgens. Besides, the meso-pyrene BODIPY derivative shows excellent mechanofluorochromic behaviour.     

Conformationally Restricted Aza‐Dipyrromethene Boron Difluorides (Aza‐BODIPYs) with High Fluorescent Quantum Yields

A simple approach to the highly fluorescent near‐infrared aza‐BODIPY dyes with higher fluorescence quantum yields (up to 0.81 in toluene) in comparison with their known analogues is presented. Our approach is based on the restricted rotations of the 1,7‐phenyl groups to the mean plane of the aza‐BODIPYs, which is achieved through the installation of bulky substituents on the 1,7‐phenyl groups of aza‐BODIPYs and results in a reduced nonradiative relaxation process in solution. The large torsion angles between the 1,7‐phenyl groups and the aza‐BODIPY core (?₁ and ?₂ in these novel conformationally restricted aza‐BODIPYs) were confirmed by X‐ray diffraction studies.     

Synthesis of directly connected BODIPY oligomers through Suzuki-Miyaura coupling

Treatment of a meso-arylboron dipyrrin (BODIPY) with NBS provides mono- and dibrominated BODIPYs at the 2- and 6-positions in excellent yields with high regioselectivity. Brominated products can be employed as a nice building block for the synthesis of a variety of BODIPY derivatives through Suzuki-Miyaura coupling. Because of a lack of substituents at the 1,3,5,7-positions, a directly β-β-linked BODIPY dimer exhibits a completely coplanar conformation of BODIPY units, offering effective π-conjugation.     

Bis(BF2)-2,2'-bidipyrrins (BisBODIPYs): highly fluorescent BODIPY dimers with large stokes shifts

Four new dimeric bis(BF(2))-2,2'-bidipyrrins (bisBODIPYs), and their corresponding BODIPY monomers, have been prepared and studied with respect to their structural and photophysical properties. The solid-state molecular structure of the dimers and the relative orientation of the subunits have been revealed by an X-ray diffraction study, which showed that the molecules contain two directly linked BODIPY chromophores in a conformationally fixed, almost orthogonal arrangement. Two of the fluorine atoms are in close contact with each other and the (19)F NMR spectra show a characteristic through-space coupling in solution. The new chromophores all exhibit a clear exciton splitting in the absorption spectra with maxima at about 490 and 560 nm, and are highly luminescent with an intense emission band at around 640 nm. The Stokes shift, which is the difference between the maximum of the lowest-energy absorption band and the maximum of the emission band, has a typical value of 5 to 15 nm for simple BODIPYs, whereas this value increases to 80 nm or more for the dimers, along with a slight decrease in fluorescence quantum yields and lifetimes. These properties indicate potential uses of these new fluorophoric materials as functional dyes in biomedical and materials applications and also in model compounds for BODIPY aggregates.     

Synthesis of 3,8‐Dichloro‐6‐ethyl‐1,2,5,7‐tetramethyl–BODIPY from an Asymmetric Dipyrroketone and Reactivity Studies at the 3,5,8‐Positions

The asymmetric BODIPY 1 a (BODIPY=4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene), containing two chloro substituents at the 3,8‐positions and a reactive 5‐methyl group, was synthesized from the asymmetric dipyrroketone 3 , which was readily obtained from available pyrrole 2 a . The reactivity of 3,8‐dichloro‐6‐ethyl‐1,2,5,7‐tetramethyl‐BODIPY 1 a was investigated by using four types of reactions. This versatile BODIPY undergoes regioselective Pd⁰‐catalyzed Stille coupling reactions and/or regioselective nucleophilic addition/elimination reactions, first at the 8‐chloro and then at the 3‐chloro group, using a variety of organostannanes and N‐, O‐, and S‐centered nucleophiles. On the other hand, the more reactive 5‐methyl group undergoes regioselective Knoevenagel condensation with an aryl aldehyde to produce a monostyryl‐BODIPY, and oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) gives the corresponding 5‐formyl‐BODIPY. Investigation of the reactivity of asymmetric BODIPY 1 a led to the preparation of a variety of functionalized BODIPYs with λ_max of absorption and emission in the ranges 487–587 and 521–617 nm, respectively. The longest absorbing/emitting compound was the monostyryl‐BODIPY 16 , and the largest Stokes shift (49 nm) and fluorescence quantum yield (0.94) were measured for 5‐thienyl‐8‐phenoxy‐BODIPY 15 . The structural properties (including 16 X‐ray structures) of the new series of BODIPYs were investigated.     

meso‐Ester and Carboxylic Acid Substituted BODIPYs with Far‐Red and Near‐Infrared Emission for Bioimaging Applications

A series of meso‐ester‐substituted BODIPY derivatives 1–6 are synthesized and characterized. In particular, dyes functionalized with oligo(ethylene glycol) ether styryl or naphthalene vinylene groups at the α positions of the BODIPY core ( 3 – 6 ) become partially soluble in water, and their absorptions and emissions are located in the far‐red or near‐infrared region. Three synthetic approaches are attempted to access the meso‐carboxylic acid (COOH)‐substituted BODIPYs 7 and 8 from the meso‐ester‐substituted BODIPYs. Two feasible synthetic routes are developed successfully, including one short route with only three steps. The meso‐COOH‐substituted BODIPY 7 is completely soluble in pure water, and its fluorescence maximum reaches around 650 nm with a fluorescence quantum yield of up to 15 %. Time‐dependent density functional theory calculations are conducted to understand the structure–optical properties relationship, and it is revealed that the Stokes shift is dependent mainly on the geometric change from the ground state to the first excited singlet state. Furthermore, cell staining tests demonstrate that the meso‐ester‐substituted BODIPYs ( 1 and 3 – 6 ) and one of the meso‐COOH‐substituted BODIPYs ( 8 ) are very membrane‐permeable. These features make these meso‐ester‐ and meso‐COOH‐substituted BODIPY dyes attractive for bioimaging and biolabeling applications in living cells.     

Tuning the solid-state luminescence of BODIPY derivatives with bulky arylsilyl groups: synthesis and spectroscopic properties

Boron dipyrromethenes (BODIPYs) with bulky triphenylsilylphenyl(ethynyl) and triphenylsilylphenyl substituents on pyrrole sites were prepared via Hagihara-Sonogashira and Suzuki-Miyaura cross-coupling with ethynyl-terminated tetraphenylsilane and boronic acid-terminated tetraphenylsilane. The chromophores are designed to prevent intermolecular π-π stacking interaction and enhance fluorescence in the solid state. Single crystals of 1?a and 2?b for X-ray structural analysis were obtained, and weak π-π stacking interactions of the neighboring BODIPY molecules were observed. Spectroscopic properties of all of the dyes in various solvents and in films were investigated. Triphenylsilylphenyl-substituted BODIPYs generally show more pronounced increases in solid-state emission than triphenylsilylphenyl(ethynyl)-substituted BODIPYs. Although the simple BODIPYs do not exhibit any fluorescence in the solid state (Φ=0), arylsilyl-substituted BODIPYs exhibit weak to moderate solid-state fluorescence with quantum yields of 0.03, 0.07, 0.10, and 0.25. The structure-property relationships were analyzed on the basis of X-ray crystallography, optical spectroscopy, cyclic voltammetry, and theoretical calculations.     

Synthesis and chiroptical properties of phenanthrene-fused N2O-type BODIPYs

A series of phenanthrene-fused N₂O-type boron-dipyrrin complexes (BODIPYs) with various substituents were synthesized. The synthesized BODIPYs show light absorption and emission in the red to near-infrared region due to their extended π-system. Furthermore, the first optical resolution of the N₂O-type BODIPY was achieved using the phenyl-substituted complex. The separated enantiomers are stable to racemization at room temperature, and exhibited a Cotton effect in the deep-red region.     

Substituents modification of meso-aryl BODIPYs for tuning photophysical properties

We successfully synthesized eight meso-aryl BODIPYs with 2,6-diethyl- or 1,2,6,7-tetraethyl substituents and characterized their photophysical properties. The steric hindrance resulting from the phenolic group in the meso-aryl moiety and the ethyl groups on the BODIPY core affected the synthesis of dipyrromethanes as an intermediate as well as the UV–Vis absorption and fluorescence emission of the BODIPYs due to the constrained rotation of the aryl ring. The potential use of the meso-hydroxyphenyl BODIPY as a pH sensor was also shown by the pH-dependent fluorescence emissions.     

Benzo[c,d]indole‐Containing Aza‐BODIPY Dyes: Asymmetrization‐Induced Solid‐State Emission and Aggregation‐Induced Emission Enhancement as New Properties of a Well‐Known Chromophore

A series of symmetric and asymmetric benzo[c,d]indole‐containing aza boron dipyrromethene (aza‐BODIPY) compounds was synthesized by a titanium tetrachloride‐mediated Schiff‐base formation reaction of commercially available benzo[c,d]indole‐2(1H)‐one and heteroaromatic amines. These aza‐BODIPY analogues show different electronic structures from those of regular aza‐BODIPYs, with hypsochromic shifts of the main absorption compared to their BODIPY counterparts. In addition to the intense fluorescence in solution, asymmetric compounds exhibited solid‐state fluorescence due to significant contribution of the vibronic bands to both absorption and fluorescence as well as reduced fluorescence quenching in the aggregates. Finally, aggregation‐induced emission enhancement, which is rare in BODIPY chromophores, was achieved by introducing a nonconjugated moiety into the core structure.     

A nitroolefin functionalized BODIPY chemodosimeter for biothiols driven by an unexpected conjugated addition mechanism

A weakly fluorescent nitroolefin functionalized BODIPY 1 was prepared and rapidly reacted with thiols through an unexpected conjugated addition to the azafulvene ring of BODIPY to generate highly fluorescent BODIPYs 4 and 5. This reaction was applied for the highly selective and sensitive detection of Cys in living cells.     

基于新型不对称BODIPY的GSH荧光探针

本文通过在BODIPY母体中引入丙二腈,设计合成了一个新型不对称BODIPY荧光染料CN-B-Cl。由于丙二腈强吸电作用,荧光染料CN-B-Cl具有优异的化学活性,能够与含巯基的化合物在buffer体系中迅速发生芳香亲核取代反应;与GSH反应生成硫取代BODIPY,而与Cys/Hcy反应生成氮取代BODIPY。根据不同取代基BODIPY化合物发光性能的不同,该荧光探针可选择性区分GSH与Cys/Hcy。