aza-BODIPY Dyes Research Articles

Multifunctional organic nanomaterials with ultra-high photothermal conversion efficiency for photothermal therapy and inhibition of cancer metastasis

Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low-toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photothermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE−mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of ∼72.0% and ∼79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti-metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment.

Naphthodipyrrolopyrrole-based Aza-BODIPY dye for N-type organic field-effect transistors

To date, n-type semiconductor designs are less investigated than their p-type counterparts, due to the fact that the charge transport mobility and the stability of the n-type materials are generally lower than those of the p-type ones. Well-defined n-type semiconductors often require low lowest unoccupied molecular orbital (LUMO) levels that facilitate the electron injection from the electrode into the semiconductors. Therefore, it is of significance to explore novel chromophores with strong electron-deficient properties, yet it is still challenging. Herein, a naphthodipyrrolopyrrole-based dimeric aza-boron dipyrromethene (Aza-BODIPY) dye (NDP-AB) is designed and synthesized. The optical studies indicate that NDP-AB presents a blue spectral shift (111 nm) in solution phase compared to the thin film state, while exhibiting a photoluminescence emission quenching. The NDP-AB semiconductor demonstrates strong acceptor properties with a low LUMO energy level of only −4.25 eV, owing to the multi-fluorine atoms, unsaturated nitrogen atoms, as well as the amide functional groups. Moreover, the large conjugation system, highly planar core, along with the large transition dipole on the line that links 2-position with 6-position of the BODIPY core, result in NDP-AB with a strong H-aggregation. As a consequence, the NDP-AB-based semiconductors show a good n-type behavior with an average electron mobility of 0.16 cm2 V−1 s−1. Our work, proposes a strong electron-deficient chromophore that is a promising candidate as building block of organic field-effect transistors. Our design strategy paves the way for the identification of more n-type semiconductor materials with high-performance.

J- and H-aggregates of heavy-atom-free Aza-BODIPY dyes with high 1O2 generation efficiency and photodynamic therapy potential

Aggregation of molecules offers a facile way to tune the optical properties of dyes, thus providing a design platform for organic nano-photosensitizers (PSs) with the potential in photodynamic therapy (PDT). However, it is still a great challenge to control the molecular organization of dye monomers to form a specific aggregation to maximize the efficiency of PDT. Herein, we present a novel supramolecular strategy to build nano-PSs from metastable aggregation of heavy-atom-free Aza-BODIPY dyes (BDP-1 and BDP-2) bearing pyridine units, which represented high singlet oxygen (1O2) generation efficiency (up to 0.85–0.89) to overcome the several intrinsic drawbacks of traditional heavy-atom Aza-BODIPY PSs. X-ray crystallographic analysis and theoretical calculations revealed that multiple intermolecular electrostatic interactions triggered the formation of J- and H-aggregates, which transformed excited state properties of the chromophores and promoted the intersystem crossing (ISC) process by reducing singlet-triplet energy gaps (ΔEST) and radiative decay. This study provides insights for clarifying the relationship between molecular structure and aggregates properties by ingenious molecular design and engineering, which should open up new opportunities to construct functional aggregates for PDT.

Ratiometric Detection of H2S in Liver Injury by Activated Two-Wavelength Photoacoustic Imaging.

Metformin is commonly used for clinical treatment of type-2 diabetes, but long-term or overdose intake of metformin usually causes selective upregulation of H2S level in the liver, resulting in liver injury. Therefore, tracking the changes of H2S content in the liver would contribute to the prevention and diagnosis of liver injury. However, in the literature, there are few reports on ratiometric PA molecular probes for H2S detection in drug-induced liver injury (DILI). Accordingly, here we developed a H2S-activated ratiometric PA probe, namely BDP-H2S, based Aza-BODIPY dye for detecting the H2S upregulation of metformin-induced liver injury. Due to the intramolecular charge transfer (ICT) effect, BDP-H2S exhibited a strong PA signal at 770 nm. Following the response to H2S, its ICT effect was recovered which showed a decrement of PA770 and an enhancement of PA840. The ratiometric PA signal (PA840/PA770) showed excellent H2S selectivity response with a low limit of detection (0.59 μM). Bioimaging experiments demonstrated that the probe has been successfully used for ratiometric PA imaging of H2S in cells and metformin-induced liver injury in mice. Overall, the designed probe emerges as a powerful tool for noninvasive and accurate imaging of H2S level and tracking its distribution and variation in liver in-real time.

Near-infrared aza-BODIPYs bearing tetraphenylethylene: Synthesis, photophysical studies, and cell imaging application

We provide a simple method to synthesize tetraphenylethylene-modified aza-BODIPY dyes (AZB-TPE1 and AZB-TPE2) with aggregation-enhanced emission. Single-crystal X-ray method, electrochemical experiments, and TD-DFT calculations were used to understand more about their electronic and photophysical properties. The intramolecular energy transfer between the TPE donor and the aza-BODIPY acceptor was observed from both dyes, with 84–97% energy transfer efficiencies and large pseudo-Stokes shifts of 395 – 406 nm. Aggregation studies in THF/water solution showed increased fluorescence in the aggregated form. X-ray crystal structure of AZB-TPE2 suggested the reduction of intermolecular pi-pi interactions between the structures. Finally, these NIR-emitting particles with superior water dispersion and biocompatibility demonstrated amazing features in bioimaging applications.

Synthesis and application of aromatic rings fused AzaBODIPY

<p indent="0mm">Aromatic rings fused BF₂ azadipyrromethenes (AzaBODIPY) exhibit wide applications in frontier fields such as biomedicine and materials science due to their unique near-infrared absorption, emission, simple synthesis, modification and derivatization. Based on the modified strategies of aromatic rings fused AzaBODIPY dyes, this review mainly focuses on the latest research progress of the construction strategy, the regulatory of optoelectronic properties and the application of near-infrared AzaBODIPY dyes made by our group in recent years. Among those, [<italic>a</italic>]-aromatic rings fused AzaBODIPYs are mainly conducted by phthalodinitrile route and the route of totally synthetic aromatic pyrroles by nitrosation, condensation, and BF₂ chelation. And [<italic>b</italic>]-aromatic rings and [a,b]-aromatic rings annularly fused AzaBODIPYs are conducted by metal-catalyzed C–H activation or intramolecular dehydrogenation oxidation coupling reactions. Further researches indicate that these novel near infrared dyes exhibit advantageous bioimaging, therapy and semiconducting characteristics. Finally, the synthesis, application and development of these dyes have been discussed.

Design of Promising aza-BODIPYs for Bioimaging and Sensing

The obtainment of new luminophores for molecular sensorics of biosystems is becoming one of the urgent tasks in the field of chemical synthesis. The solution to each practical problem imposes its own limitations in the design of new structures with practically useful properties. The relationship between the structure and spectral properties is still to be unveiled. Three aza-BODIPY complexes with substituents of different natures were studied using time-resolved and steady-state fluorescence and absorption spectroscopy. The solvatochromic properties of aza-BODIPYs were studied with the use of a combined polyparametric approach and analysis by chemoinformatics methods for the first time. It was found that red shift of aza-BODIPY dyes was due to the increase of their structural lability. Predictive and experimental methods showed that the investigated aza-BODIPYs exhibited a positive solvatochromic effect, in contrast to classic BODIPYs (bearing C in the meso-position of the dipyrromethene core), which represents the negative solvatochromic properties. Spectral maxima in the area of the therapeutic window, low and predictable solvatochromism, and the ability to fine-tune the spectral characteristics make the investigated aza-BODIPYs promising scaffolds for the construction of bioengineering devices. Generalizations on the aza-BODIPYs’ design patterns were made in accordance with further bioimaging applications.

Lipoprotein interactions with water-soluble NIR-II emitting aza-BODIPYs boost the fluorescence signal and favor selective tumor targeting.

Following intravenous administration, the interaction of fluorescent exogenous molecules with circulating endogenous transporters can influence their photophysical properties as well as their fate and distribution, and possibly their recognition by different cell types. This type of interaction can be used to optimize the drug delivery but also the imaging properties of a compound of interest. In this study, we investigated the behavior of SWIR-WAZABY-01 fluorophore, a water-soluble aza-BODIPY dye emitting in the NIR-II region, both in vitro and in vivo. While the fluorescence emission of SWIR-WAZABY-01 was weak in aqueous solutions, it was intensely magnified in plasma (∼ ×30). Further analyses using lipoprotein gel electrophoresis and ultracentrifugation revealed interactions between SWIR-WAZABY-01 and plasma lipoproteins in vitro and ex vivo, in particular with LDL. The tumor uptake mechanism of SWIR-WAZABY-01 was investigated based on the presence of low-density lipoprotein (LDL) receptors and passive tumor uptake. Overall, we found that SWIR-WAZABY-01 interacts with lipoproteins enhancing their NIR-II fluorescence emission, and driving the tumor accumulation with regards to the expression of lipoprotein receptors (LDLR, SR-BI). Moreover, SWIR-WAZABY-01, by exploiting endogenous lipoproteins, arises as a new, potent and relevant tool to efficiently label LDL involved in pathologies.

Supramolecular J-aggregates of aza-BODIPY by steric and π-π nteractions for NIR-II phototheranostics.

Achieving J-aggregation of a molecule is a fascinating way to construct fluorescent imaging and photothermal therapy agents in the second near-infrared window. Modulation of the balance between intermolecular π-π stacking and steric interactions is an elegant method to acquire J-aggregation dyes. Herein, we succeeded in synthesizing an aza-BODIPY dye with J-aggregation characteristics by introducing steric hindrance (TPA) and a π-bridge (thiophene) in the aza-BODIPY skeleton. In aqueous solutions, supramolecular J-aggregates with a regular lamellar stacking structure could quickly be formed by the dye-templated self-assembly and longer absorption (λmax = 939 nm) and emission (λmax = 1039 nm) bands were observed. After co-assembly of the dye and an amphiphilic polypeptide (POEGMA23-PAsp20), the obtained J-aggregation nanoparticles (J-NPs) with good water solubility and smaller size were more suitable for application in living organisms. In addition, the J-NPs exhibited good stability, considerable photothermal conversion capacity (η = 35.6%), and excellent resistance to pH, H2O2, and photobleaching. In vitro and in vivo experiments revealed that the J-NPs show great NIR-II fluorescence imaging capabilities and anti-tumor effects under 915 nm irradiation (1 W cm-2). This is a rare example of using BODIPY dyes to perform NIR-II fluorescence imaging-guided photothermal therapy under NIR-II irradiation.

Asymmetric living supramolecular polymerization of an achiral aza-BODIPY dye by solvent-mediated chirality induction and memory

Chiral aggregates of achiral aza-BODIPY 1 was obtained in a nearly achiral medium, i.e. a limonene/MCH mixed solvent with a chiral limonene ratio &lt;1% (v/v), by living supramolecular polymerization exploiting the chirality memory of dye 1 aggregates.

Living supramolecular polymerization of an amphiphilic aza-BODIPY dye realized by water-assisted kinetic trapping.

The kinetic assembly pathways of a newly synthesized amphiphilic aza-BODIPY dye 1 were tuned by using H2O as a co-solvent in MeOH. Accordingly, the biphasic aggregation pathways resulting in kinetically-trapped and thermodynamically stable aggregates of 1 were established and the multiple cyclic seeded living supramolecular polymerization of this dye was realized.

Bimolecular Interactions Between Graphene Oxide and a New Aza-BODIPY Derivative

Fluorescent dyes are optical devices which are commonly used in medical and technical applications. Graphene-oxide, on the other hand, is a unique structure in nanotechnology with its oxygen-containing functional groups, high solubility, optical, electronic and thermal properties. Here we report photophysical properties of a newly synthesized fluorescent aza-BODIPY dye and dye-graphene oxide (GO) composite in aqueous media. Quantum yields were determined in both ethanol and chloroform medias according to Perker-Rees equation. Also quenching mechanism was discussed in the light of Stern-Volmer parameters.

BODIPY dyes: Versatile building blocks to construct multiple types of self-assembled structures

More than 50 years have passed since the discovery of boradiazaindacenes by Treibs and Kreuzer [Liebigs Ann. Chem. 718, 208 (1968)]. Since then, the number of research articles related to their synthesis, properties, and applications has not stopped growing. Not without reason, borondipyrromethene (BODIPY) dyes are one of the most versatile chromophores in terms of photophysical and chemical properties and multiple potential applications. For many applications, control over the properties in the aggregated state is necessary, and understanding the interactions that take part in the self-assembly of dye molecules is crucial. In this review, recent developments on the self-assembly of BODIPY dyes, as well as their potential applications, are discussed, highlighting the versatility of the BODIPY chromophore. In the first section, recent strategies to obtain solid-state emissive BODIPY dyes based on the introduction of different non-covalent interactions are presented. In a subsequent section, we discuss recent work on self-assembly and supramolecular polymerization of BODIPY dyes in aqueous and organic media with particular focus on pathway complexity—the analysis of different aggregation pathways by the same building block. In addition, given the high relevance of BODIPY dyes in biomedicine, a short overview of new BODIPY-based structures with interesting applications in biomedicine is presented. This section is followed by the discussion of recent work on metallosupramolecular assemblies of BODIPY dyes. Finally, a brief overview of other structurally related BODIPY-based analogs is given with particular focus on self-assembled structures of aza-BODIPY dyes.

Activity-based photoacoustic probe for biopsy-free assessment of copper in murine models of Wilson’s disease and liver metastasis

The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson's disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson's disease animals from healthy control mice in each instance.

The synthesis and characterization of ylideneisoindolinones

1,3-Diiminoisoindoline (DII) and the closely related molecule, iminoisoindolinone are important precursors in the synthesis of macrocycles and chelates such as phthalocyanines, and bis(arylimino)isoindolines, as well as chromophores including aza-BODIPY dyes. A series of seven ylideneisoindolinones are presented in this report. The reaction of various organic CH acids and iminoisoindolinone produce compounds that show strong [Formula: see text]* transitions in the UV region. The chromophores have been characterized spectroscopically and the X-ray structures show electronic delocalization across the chromophore. Additionally, DFT and time-dependent DFT calculations confirm the lower energy absorbances are primarily HOMO-LUMO transitions.

Near-infrared Aza-BODIPY Dyes Through Molecular Surgery for Enhanced Photothermal and Photodynamic Antibacterial Therapy

Near-infrared Aza-BODIPY Dyes Through Molecular Surgery for Enhanced Photothermal and Photodynamic Antibacterial Therapy

NIR absorbing dimeric aza-BODIPY dye with J-type aggregation and photothermal properties

A novel amphiphilic dimeric aza-BODIPY dye was synthesized by oxidative coupling and characterized by 1H NMR, 13C NMR, MS, and UV/Vis absorption and fluorescence spectroscopy. In comparison with its precursor, the dimeric dye displayed a bathochromically shifted absorption band with maximum at 731 nm and an emission maximum at 768 nm. In addition, the dimeric dye formed stable J-type aggregates in DMSO/H2O. The morphology of nanowire was observed for the aggregates by AFM and TEM. Furthermore, the J-type aggregates of the dimeric aza-BODIPY exhibited promising photothermal conversion efficiency (38.7%).

Development of Receptor-sensitive Near-infrared Absorbing azaBODIPY Dye for Glucose Sensors

Development of Receptor-sensitive Near-infrared Absorbing azaBODIPY Dye for Glucose Sensors

Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment

BackgroundThe aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy.ResultsA class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza–boron–dipyrromethene (aza-BODIPY) dyes with donor–acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity.ConclusionsUtilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.

Synthesis and optical properties of 1-ethyl-indol-3-yl-substituted aza-BODIPY dyes at the 1,7-positions

New aza-BODIPYs with significant bathochromic shifts in their UV–vis absorption spectrum were synthesized by the installation of 1-ethyl-indol-3-yl moieties at the 1,7-positions of the aza-BODIPY core bearing 4-substituted phenyl or thien-2-yl groups at the 3,5-positions. The compounds described herein show strong NIR absorptions up to 779 nm, and emissions up to 805 nm in chloroform solution, and present large molar extinction coefficients. The absorption and emission bands of aza–BODIPYs were significantly red-shifted, by ca 100 nm, relative to the 3,5-dianisyl-1,7-diphenyl aza-BODIPY. TD-DFT calculations indicate an effective electronic conjugation between the aza-BODIPY core and the substituents. Absorption of the studied aza-BODIPY derivatives corresponds to a charge transfer from donor substituents toward the boron-centered core. Moreover, computational results show that all the compounds present HOMO–LUMO band gap values that are in the organic semiconductor range. • A series of new aza-BODIPYs with 1-ethyl-indol-3-yl substituents were synthesized. • These dyes show strong NIR absorptions up to 779 nm, and emissions up to 805 nm in chloroform solution. • DFT-calculated and optical band gap values are found to lie in the organic semiconductor range.