Structural modification of BODIPY: Improve its applicability

The synthesis of biocompatibility and tissue penetrating BODIPY dyes have been summarized.     

Structural modification of BODIPY: Improve its applicability

BODIPY has been considered a potential scaffold because of their neutral total charge, sharp absorption,and emission with high fluorescence quantum yield. However, the drawback of emission wavelength at less than 600 nm and hydrophobicity limit its application. One of the extremely interesting properties of BODIPY is that small modifications to their structures could be able to tune their properties, mainly including the absorption/emission wavelength and the hydrophilicity. This review focuses on the modification at different positions of BODIPY to improve the water-solubility and emission wavelength that describe their spectral, photophysical properties and applicability, which is helpful for the researchers to rationally design BODIPY dyes to adapt a wide range of applications.     

新型含双酚衍生物三枝氟硼二吡咯染料的合成及其光物理性能

以三聚氯氰为原料合成含醛基的二酚氧基取代中间体（1）; 1分别与酚衍生物（2a~2e）经取代反应制得三酚氧基中间体（3a~3e）; 3a~3e经缩合、氧化和配位等反应合成了5个新型的含双酚衍生物三枝氟硼二吡咯（BODIPY）荧光染料（4a~4e）,其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。4a~4e的最大吸收波长和发射波长分别位于499 nm和508 nm,荧光量子产率为0.41~0.55,显示出BODIPY荧光核典型的光物理性能。     

Synthesis and Properties of Symmetrical Aryl Linked BODIPY Dyads

Three novel symmetrical 4.4＇-difluoro-4-bora-3a,4a-diaza-sindacene（BODIPY） derivatives were synthesized via a general and efficient protocol. These BODIPY dyads bear a diverse aryl linker bridge in the middle and two BODIPY units at the termini. The photophysical properties of these dyads were investigated by ultravioletvisible（UV-Vis） absorption and emission spectroscopy. And their electrochemical properties were studied by cyclic voltammetry. The absorption of these dyads showed slightly blue shift and the intramolecular charge transfer（ICT） state under,vent ultrafast direct surface crossing to the ground state with high degree of rotational freedom. The results will be useful for the further functionalization of these novel symmetrical BODIPY derivatives.     

Synthesis,optical, and electrochemical properties,and theoretical calculations of BODIPY containing triphenylamine

The boron dipyrromethene (BODIPY) triads consisting of two triphenylamine units as electron donor (D) and BODIPY core as electron acceptor (A; B3 , and B4 ) have been synthesized using facile palladium cross‐coupling reactions to broaden the absorption of the BODIPY dyes. All dyes and intermediates were characterized by ¹H NMR, ¹¹B NMR, ¹³C NMR, and ¹⁹F NMR spectroscopies, UV–Vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and time‐dependent density functional theory calculations. It was found that an increase in conjugation to the BODIPY core systematically extended the absorption and emission wavelength maxima. As a consequence, B4 containing the D–π–A–π–D structure, exhibited the longest absorption and emission maxima at 597 and 700 nm, respectively, with 1.8 eV in optical bandgap. The 96 nm red‐shifted absorption of B4 as compared to the unsubstituted BODIPY ( B1 ) indicated the effective electronic communication between triphenylamine and BODIPY. This suggested that the proper alignment of triphenylamine and BODIPY triad could lead to broader absorption and suitable low energy bandgap. Furthermore, the molecular modeling has been employed to analyze the electronic and optical properties of the dyes. We found that the optical, electrochemical, and theoretical bandgaps of all dyes were in good agreement.     

Long-lived room-temperature near-IR phosphorescence of BODIPY in a visible-light-harvesting N^C^N Pt(II)-acetylide complex with a directly metalated BODIPY chromophore

Room-temperature long-lived near-IR phosphorescence of boron-dipyrromethene (BODIPY) was observed (λ(em) = 770?nm, Φ(P) = 3.5?%, τ(P) = 128.4?μs). Our molecular-design strategy is to attach Pt(II) coordination centers directly onto the BODIPY π-core using acetylide bonds, rather than on the periphery of the BODIPY core, thus maximizing the heavy-atom effect of Pt(II). In this case, the intersystem crossing (ISC) is facilitated and the radiative decay of the T(1) excited state of BODIPY is observed, that is, the phosphorescence of BODIPY. The complex shows strong absorption in the visible range (ε = 53,800 M(-1) cm(-1) at 574?nm), which is rare for Pt(II)-acetylide complexes. The complex is dual emissive with (3)MLCT emission at 660?nm and the (3)IL emission at 770?nm. The T(1) excited state of the complex is mainly localized on the BODIPY moiety (i.e. (3)IL state, as determined by steady-state and time-resolved spectroscopy, 77?K emission spectra, and spin-density analysis). The strong visible-light-harvesting ability and long-lived T(1) excite state of the complex were used for triplet-triplet annihilation based upconversion and an upconversion quantum yield of 5.2?% was observed. The overall upconversion capability (η = ε×Φ(UC)) of this complex is remarkable considering its strong absorption. The model complex, without the BODIPY moiety, gives no upconversion under the same experimental conditions. Our work paves the way for access to transition-metal complexes that show strong absorption of visible light and long-lived (3)IL excited states, which are important for applications in photovoltaics, photocatalysis, and upconversions, etc.     

Synthesis of Luminescent Ethynyl‐Extended Regioisomers of Borate Complexes Based on 2‐(2′‐Hydroxyphenyl)benzoxazole

A series of thirteen luminescent tetrahedral borate complexes based on the 2‐(2′‐hydroxyphenyl)benzoxazole (HBO) core is presented. Their synthesis includes the incorporation of an ethynyl fragment by Sonogashira cross‐coupling reaction, with the goal of extending the conjugation and consequently redshifting their emission wavelength. Different regioisomers, substituted in the 3‐, 4‐, or 5‐position of the phenolate side of the HBO core, were studied in order to compare their photophysical properties. The complexes were characterized by X‐ray diffraction and NMR, UV/Vis, and emission spectroscopy in solution and in the solid state. In all cases, complexation to boron leads to a donor–acceptor character that impacts their photophysical properties. Complexes with a 3‐ or 5‐substituted fragment display mild to pronounced internal charge transfer (ICT), a feature strengthened by the presence of p‐dibutylaminophenylacetylene in the molecular structure, protonation of the nitrogen atom of which leads to a significant blueshift and an increase in quantum yield. On the contrary, when the ethynyl module is grafted on the 4‐position, narrow, structured, symmetrical absorption/emission bands are observed. Moreover, the fact that protonation has little effect on the emission maximum wavelength reveals singlet excited‐state decay. Solid‐state emission properties reveal a redshift compared to solution, explained by tight packing of the π‐conjugated systems and the high planarity of the dyes. Subsequent connection of these complexes to other photoactive subunits (BODIPY, Boranil) provides dyads in which efficient cascade energy transfer is observed.     

Heavy atom free singlet oxygen generation: doubly substituted configurations dominate S1 states of bis-BODIPYs

S(0), S(1), and T(1) states of various orthogonal 8,8' and 8,2'-bis-boradiaza-s-indacene (BODIPY) dyes, recently (Angew. Chem., Int. Ed.2011, 50, 11937) proposed as heavy atom free photosensitizers for O(2)((1)Δ(g)) generation, were studied by multireference quantum chemical approaches. S(0)→S(1) excitation characteristics of certain bis-BODIPYs are shown to be drastically different than the parent BODIPY chromophore. Whereas a simple HOMO→LUMO-type single substitution perfectly accounts for the BODIPY core, S(1) states of certain orthogonal bis-BODIPYs are described as linear combinations of doubly substituted (DS) configurations which overall yield four electrons in four singly occupied orbitals. Computed DS character of S(1), strongly correlated with facile (1)O(2) production, was presumed to occur via S(1)→T(1) intersystem crossing (ISC) of the sensitizer. Further confirmation of this relation was provided by newly synthesized BODIPY derivatives and comparison of spectroscopic properties of their dimers and monomers. Near-IR absorption, desired for potential photodynamic therapy applications, was not pursuable for bis-chromophores by the standard strategy of π-extension, as DS singlet states are destabilized. Decreased exchange coupling in π-extended cases appears to be responsible for this destabilization. Comparisons with iodine incorporated bis-BODIPYs suggest that the dynamics of (1)O(2) generation via DS S(1) states are qualitatively different from that via ISC originating from heavy atom spin-orbit coupling. Although red-shifting the absorption wavelength to enter the therapeutic window does not seem attainable for orthogonal bis-BODIPYs with DS S(1) states, modifications in the chromophore cores are shown to be promising in fine-tuning the excitation characteristics.     

A near IR di-styryl BODIPY-based ratiometric fluorescent chemosensor for Hg(II)

A novel BODIPY-based near-IR emitting probe as a selective and sensitive fluorophore for Hg(II) is synthesized. This versatile BODIPY fluorophore is functionalized for long wavelength emission at the 3 and 5 positions via a condensation reaction in which two dithiodioxomonoaza-based crown-containing phenyl units are conjugated to the BODIPY core as a chelating unit. This designed fluorophore, employing an ICT sensor can be used effectively to detect Hg(II) cations by way of a hypsochromic shift (∼90 nm) in both the absorption and emission spectra.     

Novel fluorescent dyes with fused perylene tetracarboxlic diimide and BODIPY analogue structures

Two novel fluorescent dyes based on perylene tetracarboxylic diimides and BODIPY were designed and synthesized. Significant features, such as longer wavelength absorption and emission, high fluorescence quantum yields, and strong electron accepting abilities, are observed for these compounds.     

Deep‐red emissive conjugated poly(2,6‐BODIPY‐ethynylene)s bearing alkyl side chains

Novel deep‐red emissive poly(2,6‐BODIPY‐ethynylene)s bearing dodecyl side chains (polymers A , B , and C ) have been prepared by palladium‐catalyzed Sonogashira polymerization of 2,6‐diiodo‐functionalized BODIPY monomers with 2,6‐diethynyl‐functionalized BODIPY monomers. These polymers emit in the deep‐red region with emission maxima at up to 690 nm, and exhibit significant red shifts (up to 166 and 179 nm) of both absorption and emission maxima compared with their parent BODIPY dyes due to significant extension of π‐conjugation. These polymers possess good thermal stability with decomposition temperature between 270 and 360 °C. The polymers exhibit a little larger Stokes shifts and shorter lifetime than their corresponding BODIPY dyes. The solid state thin films of polymers A , B , and C emit in near‐infrared region between 723 and 743 nm, and show significantly red shifts (up to 57 nm) in absorption and emission maxima relative to their polymer solution. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5354–5366, 2009     

A Quencher-Based Blood-Autofluorescence-Suppression Strategy Enables the Quantification of Trace Analytes in Whole Blood

Precise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence-suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood. Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPY quencher with an absorption wavelength ranging from 600–700 nm was selected for its superior quenching efficiency and high brightness. Two 7-nitrobenzo[c] [1,2,5] oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H₂S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal-to-back ratio, the probe thus achieved the accurate quantification of endogenous H₂S in 20-fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H₂S in whole blood. Moreover, this autofluorescence-suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.     

取代基对3(5)-(9-蒽基)吡唑光学性质的影响

使用密度泛函理论(DFT)B3LYP/6-31G(d)方法优化得到了3(5)-(9-蒽基)吡唑及其衍生物的基态(S₀)分子结构, 使用单激发组态相互作用(CIS)/6-31G(d)方法优化得到这些分子的第一单重激发态(S₁)的几何结构, 并使用含时密度泛函理论(TD-DFT)B3LYP/6-311++G(d,p)方法计算了它们的吸收和发射光谱. 计算结果表明, 与3(5)-(9-蒽基)吡唑相比, 无论取代基是吸电子基团还是供电子基团, 衍生物的吸收和发射峰均发生红移, 并且当取代基―R=―BH₂, ―CCl₃, ―CHO, ―NH₂时衍生物有较长的吸收波长和发射波长.     

Oligo(p-phenylene ethynylene)-BODIPY derivatives: synthesis, energy transfer, and quantum-chemical calculations

The synthesis and energy‐transfer properties of a series of oligo(p‐phenylene ethynylene)–BODIPY ( OPEB ) cassettes are reported. A series of oligo(p‐phenylene ethynylene)s ( OPE s) with different conjugated chain lengths as energy donor subunit in the energy‐transfer system were capped at both ends with BODIPY chromophores as energy‐acceptor subunits. The effect of the conjugated chain of OPE s on energy transfer in the OPEB cassettes was investigated by UV/Vis and fluorescence spectroscopy and modeling. With increasing number n of phenyl acetylene units (n=1–7), the absorption and emission maxima of OPEn are bathochromically shifted. In the OPEBn analogues, the absorption maximum assigned to the BODIPY moieties is independent of the length of the OPE spacer. However, the relative absorption intensity of the BODIPY band decreases when the number of phenyl acetylene units is increased. The emission spectra of OPEBn are dominated by a band peaking at 613 nm, corresponding to emission of the BODIPY moieties, regardless of whether excitation is at 420 or 550 nm. Furthermore, a very small band is observed with a maximum between 450 and 500 nm, and its intensity relative to that of the BODIPY emission increases with increasing n, that is, the excited state of OPE subunits is efficiently quenched in OPEBn by energy transfer to the BODIPY moieties. Energy transfer (ET) from OPEn to BODIPY in OPEBn is very efficient (all Φ_ET values are greater than 98 %) and only slightly decreases with increasing length of the OPE units. These results are supported by theoretical studies that show very high energy transfer efficiency (Φ_ET>75 %) from the OPE spacer to the BODIPY end‐groups for chains with up to 15–20 units.     

Synthesis of non-covalent BODIPY–metalloporphyrin dyads and triads

Boron-dipyrromethenes (BODIPY) containing oxypyridine substituents at 3- and 3,5-positions and metalloporphyrins (Zn(II), Ru(II)) were used to synthesize four non-covalent BODIPY–metalloporphyrin dyads and four BODIPY–metalloporphyrin triads assembled using metal–pyridine ‘N’ interaction. The formation of BODIPY–metalloporphyrin assemblies was confirmed by 1D and 2D NMR methods and X-ray crystal structure obtained for one of the BODIPY–metalloporphyrin dyad. In ¹H NMR, the signals of oxypyridine group(s) of BODIPY unit showed significant upfield shifts supporting the coordination of oxypyridine group of BODIPY unit to metalloporphyrin unit. The NMR study also indicated that Zn(II) porphyrin forms relatively weak BODIPY–Zn(II) porphyrin conjugates, whereas Ru(II) porphyrin forms strong BODIPY–Ru(II) porphyrin conjugates. The X-ray structure solved for BODIPY–Zn(II)porphyrin dyad revealed that the Zn(II) porphyrin coordinated to the BODIPY unit obliquely and the angle between the Zn(II) porphyrin and the pyridyl ring is 70°. The absorption properties of stable BODIPY–Ru(II) porphyrin conjugates showed the overlapping absorption features of both the components and the fluorescence studies indicated that the BODIPY unit emission was significantly quenched on coordination with RuTPP(CO) unit. The electrochemical studies exhibited the features of both BODIPY and metalloporphyrin units in dyads and traids.     

A New Ratiometric Fluorescent Probe Based on BODIPY for Highly Selective Detection of Hydrogen Sulfide

Hydrogen sulfide (H₂S) as small molecular signal messenger plays key functions in numerous biological processes. The imaging detection of intracellular hydrogen sulfide is of great significance. In this work, a ratiometric fluorescent probe BH based on an asymmetric BODIPY dye for detection of H₂S was designed and synthesized. After the interaction with hydrogen sulfide, probe display colorimetric and ratiometric fluorescence response, with its maximum emission fluorescence wavelength red-shifted from 542 nm to 594 nm, which is attributed to the sequential nucleophilic reaction of H₂S leading to enhanced molecular conjugation after ring formation of the BODIPY skeleton. A special response mechanism has been fully investigated by NMR titration and MS, so that the probe has excellent detection selectivity. Furthermore, probe BH has low cytotoxicity and fluorescence imaging experiments indicate that it can be used to monitor hydrogen sulfide in living cells.     

Absorption and Fluorescence Emission Spectra of Molecules Containing Azo and/or Oxadiazole Units

The ground state structures of a series of organic molecules containing azo and/or oxadiazole units were obtained by means of density functional theory B3LYP/6-31G(d) method. The first singlet excited state structures were optimized by virtue of singlet-excitation configuration interaction CIS/6-31G(d) method. The absorption and fluorescence emission spectra were then evaluated via the time-dependent density functional theory B3LYP and PBE1PBE methods with 6-311++G(3df,2p) basis set. The calculation results show that compared with those of their parent molecules A-H, B-H, C-H, D-H, the absorption and emission wavelength values of all the derivatives show red shifts. The derivatives containing both the oxadiazole and methoxyl units are good candidates for longer absorption wavelength materials. The effects of azo, oxadiazole, and methoxyl units on the absorption and emission wavelength were discussed.     

Long‐Lived Room‐Temperature Near‐IR Phosphorescence of BODIPY in a Visible‐Light‐Harvesting N^C^N PtII–Acetylide Complex with a Directly Metalated BODIPY Chromophore

Room‐temperature long‐lived near‐IR phosphorescence of boron‐dipyrromethene (BODIPY) was observed (λ_em=770 nm, Φ_P=3.5 %, τ_P=128.4 μs). Our molecular‐design strategy is to attach Pt^II coordination centers directly onto the BODIPY π‐core using acetylide bonds, rather than on the periphery of the BODIPY core, thus maximizing the heavy‐atom effect of Pt^II. In this case, the intersystem crossing (ISC) is facilitated and the radiative decay of the T₁ excited state of BODIPY is observed, that is, the phosphorescence of BODIPY. The complex shows strong absorption in the visible range (ε=53800 M ^?1 cm^?1 at 574 nm), which is rare for Pt^II–acetylide complexes. The complex is dual emissive with ³M LCT emission at 660 nm and the ³IL emission at 770 nm. The T₁ excited state of the complex is mainly localized on the BODIPY moiety (i.e. ³IL state, as determined by steady‐state and time‐resolved spectroscopy, 77 K emission spectra, and spin‐density analysis). The strong visible‐light‐harvesting ability and long‐lived T₁ excite state of the complex were used for triplet‐triplet annihilation based upconversion and an upconversion quantum yield of 5.2 % was observed. The overall upconversion capability (η=ε×Φ_UC) of this complex is remarkable considering its strong absorption. The model complex, without the BODIPY moiety, gives no upconversion under the same experimental conditions. Our work paves the way for access to transition‐metal complexes that show strong absorption of visible light and long‐lived ³IL excited states, which are important for applications in photovoltaics, photocatalysis, and upconversions, etc.     

Hetero-Substituted αβ-Fused BODIPY

Here, we report the synthesis and properties of heterosubtituted αβ-fused BODIPY fluorophores. The compounds were obtained in good yields by sequential and selective Stille cross-coupling reactions from 2,3,5,6-tetrahalo-BODIPY, allowing the introduction of different substituents at the 3,5 and 2,6 positions of the BODIPY ring. The final fused compounds were synthesized using oxidative cyclisation with ferrous chloride. The fully fused compounds show a strong bathochromically shifted emission along with a hyperchromic shift of the absorption maxima. The fluorescence quantum yields remain relatively large for compounds emitting in this wavelength range. Computational studies have been carried out to fully understand the photophysical behaviour of these dyes.     

Fine‐Tuning Dual Emission and Aggregation‐Induced Emission Switching in NPI–BODIPY Dyads

Three new NPI–BODIPY dyads 1 – 3 (NPI=1,8‐naphthalimide, BODIPY=boron‐dipyrromethene) were synthesized, characterized, and studied. The NPI and BODIPY moieties in these dyads are electronically separated by oxoaryl bridges, and the compounds only differ structurally with respect to methyl substituents on the BODIPY fluorophore. The NPI and BODIPY moieties retain their optical features in molecular dyads 1 – 3 . Dyads 1–3 show dual emission in solution originating from the two separate fluorescent units. The variations of the dual emission in these compounds are controlled by the structural flexibilities of the systems. Dyads 1 – 3 , depending on their molecular flexibilities, show considerably different spectral shapes and dissimilar intensity ratios of the two emission bands. The dyads also show significant aggregation‐induced emission switching (AIES) on formation of nano‐aggregates in THF/H₂O with changes in emission color from green to red. Whereas the flexible and aggregation‐prone compound 1 shows AIES, rigid systems with less favorable intermolecular interactions (i.e., 2 and 3 ) show aggregation‐induced quenching of emission. Correlations of the emission intensity and structural flexibility were found to be reversed in solution and aggregated states. Photophysical and structural investigations suggested that intermolecular interactions (e.g., π–π stacking) play a major role in controlling the emission of these compounds in the aggregated state.