Benzothiadiazole Derivatives Research Articles

Towards the Inhibition of Protein-Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives.

Signal transducer and activator of transcription 3 (STAT3) is a validated anticancer target due to the relationship between its constitutive activation and malignant tumors. Through a virtual screening approach on the STAT3-SH2 domain, 5,6-dimethyl-1H,3H-2,1,3-benzothiadiazole-2,2-dioxide (1) was identified as a potential STAT3 inhibitor. Some benzothiadiazole derivatives were synthesized by employing a versatile methodology, and they were tested by an AlphaScreen-based assay. Among them, benzosulfamide 1 showed a significant activity with an IC50 = 15.8 ± 0.6 µM as a direct STAT3 inhibitor. Notably, we discovered that compound 1 was also able to interact with cysteine residues located around the SH2 domain. By applying mass spectrometry, liquid chromatography, NMR, and UV spectroscopy, an in-depth investigation was carried out, shedding light on its intriguing and unexpected mechanism of interaction.

Synthesis and photo-electro-thermal characterization of non-symmetrical 4,7-dibromobenzo[c][1,2,5]thiadiazole derivatives

This work describes the synthesis of new fluorophores based on non-symmetric 4,7-dibromobenzo[c][1,2,5]thiadiazole derivatives with benzene ethynyl tetrazole and propargyl carbazole as terminal groups. The new compounds were obtained using the Sonogashira cross-coupling reaction and produced good yields. The benzothiadiazole derivatives presented absorption in the ultraviolet–visible region (391–400 nm) ascribed to spin and symmetry allowed electronic transitions 1ππ*. The main fluorescence emission located at 460–500 nm was observed with solvatochromism up to 40 nm, indicating higher electronic delocalization in the excited state. Electrochemically, the compounds are electroactive in both the anodic and cathodic potential range. The magnitude of oxidation potentials ranged from 1.54 to 1.61 V vs. NHE and reduction potentials ranged from −2.00 to −2.05 V vs. NHE. The HOMO and LUMO energies were calculated using cyclic voltammetry data. HOMO energies ranged from −6.16 to −6.23 eV and EA energies ranged from −2.57 to −2.62 eV, and thus, the electrochemical band gap of compounds ranged from 3.56 to 3.66 eV. Thermogravimetric analysis showed that the compounds presented good thermal stability up to 200 °C. The DFT and TD-DFT calculations were performed at the B3LYP/6-31G level of theory. The results show that the dipole moment of the molecules varies tremendously from the electronic ground to excited state, ensuring a charge transfer character.

Synthesis and thermal, electrochemical, and photophysical investigation of carbazole/diphenyl benzothiadiazole-based fluorophores

Herein, we describe the syntheses of symmetric and asymmetric benzothiadiazole (BTD)-based fluorophores via the Sonogashira coupling reaction, using 4,7-dibromobenzothiadiazole as the central core and propargyl carbazole and/or propargyl diphenylamine as the side groups. The synthesized fluorophores exhibited absorption bands in the ultraviolet region, with a maxima between 372 and 380 nm due to the π→π* electronic transitions. Although they presented very low fluorescence quantum yields in solution, they demonstrated typical aggregation-induced emission phenomenon. Their oxidation potentials ranged from 0.91 to 1.18 V vs. NHE and reduction potentials from −1.20 to 1.26 V vs. NHE. Their HOMO energies ranged from −5.35 to 5.62 eV electron affinity from −3.18 to 3.24 eV. Thus, the electrochemical bandgap of the BTD-based fluorophores was in the range of 2.16–2.38 eV. The symmetric BTD derivatives 3 and 5 exhibited good thermal stability, with decomposition temperatures at ~330 °C and 200 °C, respectively. BTD 7 showed lower thermal stability with a decomposition temperature of ~110 °C. BTD 3 and 5 showed glass transition temperature (Tg) values of ~75 °C (first heating) and 60 °C (first and second heating), respectively. BTD 7 did not show any Tg. The density functional theory (DFT) and time-dependent DFT calculations were performed at the CAM-B3LYP/6-31G** level of theory, which corroborated with the charge transfer characteristics of these compounds.

Appending ionic liquids to fluorescent benzothiadiazole derivatives: Light up and selective lysosome staining

We present a series of newly designed 2,1,3-benzothiadiazole (BTD)-containing imidazole(ium) derivatives that are selective live cell fluorescence imaging probes applied in bioimaging experiments. The attachment of imidazole(ium) moieties that are planar, rigid, flat and displays strong hydrogen bond sites allows modulating the physicochemical properties of the resulting fluorescent bioimaging molecular probes which are water-soluble at room temperature. The photophysical characterization revealed the high stability of those derivatives in both the ground and excited states meaning the relaxation processes take place with no degradation. DFT calculations showed the orbital behavior of the fluorescent compounds pointing to the origin of the high chemical stability of such compounds in their relaxation processes from the excited states (no degradation noted). Live cell fluorescence imaging experiments (MCF-7 breast cancer cell lineage and other types) showed a high subcellular selection inside the cells and lysosomes could be selectively stained. Bioimaging experiments also revealed that all compounds were capable of transpose the cellular membrane and one of them showed impressive selection towards lysosomes with intense, bright and green fluorescence. The BTD derivatives proved to be cell penetrating and stable in solution storage at room temperature, which represents a huge advance over the commercially available cellular markers.

Identification of the Irreversible Redox Behavior of Highly Fluorescent Benzothiadiazoles

AbstractRedox switches are applied in various fields of research, including molecular lifts, electronic devices and sensors. Switching the absorbance between UV and Vis/NIR by redox processes is of interest for applications in light harvesting or biomedicine. Here, we present a series of push‐pull benzothiadiazole derivatives with high fluorescence quantum yields in solution and in the crystalline solid state. Spectroelectrochemical analysis reveals the switching of UV‐absorption in the neutral state to Vis/NIR absorption in the reduced state. We identify the partial irreversibility of the switching process, which appears to be reversible on the cyclic voltammetry timescale.

Optoelectronic properties of cyclopentadithiophene-based donor–acceptor copolymers as donors in bulk heterojunction organic solar cells: A theoretical study

Cyclopentadithiophene and benzothiadiazole derivatives have promising characteristics for use in organic solar cells. In this study, we theoretically investigated two donor–acceptor copolymers comprising 2-(benzo[c][1,2,5]thiadiazol-4-yl)-4H-cyclopenta[2,1-b:3,4-b']dithiophen-4-one and 2-(2-(benzo[c][1,2,5]thiadiazol-4-yl)-4H-cyclopenta[2,1-b:3,4-b']dithiophen-4-ylidene)malononitrile with alternating donor–acceptor building units. Different copolymer chain lengths (n = 1–5) were extended to investigate their structural, electronic, and photo-physical properties based on density functional theory calculations. The copolymers exhibited high planarity, reduced band gap energies, and broad absorption in the visible range, and thus they may enhance the performance of organic solar cells. The transition density matrix plots were simulated for the copolymers and used to evaluate hole–electron localization interactions, donor–acceptor interactions, and the electronic excitation processes in their excited states. The charge transfer properties, fill factors, and open-circuit voltages were estimated. Based on our simulations, we found that the trimer was the most suitable conformation among the copolymers for designing high performance bulk heterojunction (BHJ) solar cells. The power conversion efficiency of the BHJ-based blended copolymers-[70]PCBM was estimated as 9.5%. Thus, the appropriate design of conjugated materials could considerably enhance the donor properties to further improve the performance of BHJ solar cells.

Synthesis of fluorene-thiophene-benzothiadiazole (D-π-A) molecules by direct arylation reactions: Formation of nanoparticles and their fluorescence study by one- and two-photon absorption

This work presents the synthesis of Donor-π-Acceptor (D-π-A) systems including the monomer (M1), dimer (O1b), oligomer (O1aH, O1aT) and polymers (P1bT, P1cT), which are derived from fluorene-thiophene and benzothiadiazole (BT) using direct arylation reactions under different conditions. These compounds have a structure with fluorene moieties as D groups, benzothiadiazole derivatives as A groups and the thiophene moiety acting as a polarizable π bridge. Their structures and properties were spectroscopically and physicochemically characterized and analyzed. These D-π-A molecules were encapsulated into silica nanoparticles (NPs) to provide possible biocompatibility. Doped silica NPs were synthesized by the microemulsion method and their morphology was analyzed by Field Emission Scanning Electron Microscopy (FESEM). The optical properties of the solution, suspension of NPs and solid-state thin films of the title compounds were investigated by UV–vis absorption and photoluminescence spectroscopies. Fluorescence quantum yields of monomer (M1) and dimer (O1b) in THF solutions were 92% and 75%, respectively, while for the higher molecular weight polymer (P1cT) was 38%. Two-photon absorption (TPA) cross-sections were measured for O1b NPs by two-photon excited fluorescence (TPEF) method, which gave a maximum value of 55 GM (1 GM = 10−50 cm4s) at 750 nm.

Palladium-Catalyzed Direct Mono- or Polyhalogenation of Benzothiadiazole Derivatives.

An unprecedented method for the palladium (II)-catalyzed direct halogenation of benzothiadiazole derivatives is reported here, which would allow the rational tuning of their electronic properties by further transformations. The key strategy is the combination of the double functions of benzothiadiazole as both an important moiety of functional materials and modifiable directing group. Various mono/polychlorinated, brominated, or iodinated benzothiadiazole products could be prepared efficiently, which can be converted into a wide range of valuable polyaromatic compounds with potential applications in material chemistry.

Highly fluorescent solid-state benzothiadiazole derivatives as saturated red emitters for efficient solution-processed non-doped electroluminescent devices

Benzothiadiazole derivatives exhibit strong solid-state red fluorescence emission with bipolar properties.

High efficiency and low efficiency roll-off hole-transporting layer-free solution-processed fluorescent NIR-OLEDs based on oligothiophene–benzothiadiazole derivatives

Two D–A–D type emitters exhibited superior simple hole-transporting free solution-processed OLEDs with maximum EQE of 1.52%, low efficiency roll-off and maximum radiance of 4463 mW Sr−1 m−2, which is one the best solution-processed NIR-OLEDs.

Preventive Effects of Fluoro-Substituted Benzothiadiazole Derivatives and Chitosan Oligosaccharide against the Rice Seedling Blight Induced by Fusarium oxysporum.

Rice seedling blight, caused by Fusarium oxysporum, significantly affects global rice production levels. Fluoro-substituted benzothiadiazole derivatives (FBT) and chitosan oligosaccharide (COS) are elicitors that can enhance plant resistance to pathogen infection. However, there is a lack of information regarding FBT and COS used as elicitors in rice seedlings blight. Therefore, the aim of this study was to evaluate the effect of FBT and COS treatments on rice seedling blight and elucidate the molecular mechanisms of the two elicitors for inducing resistance using proteomic technique. Results indicated that FBT and COS significantly reduced the disease incidence and index, and relived the root growth inhibition caused by F. oxysporum (p < 0.05). Biochemical analyses demonstrated that these two elicitors effectively enhanced activities of defense enzymes. Moreover, the proteomic results of rice root tissues disclosed more differentially expressed proteins in diterpenoid biosynthesis pathway that were particularly stimulated by two elicitors compared to the other pathways studied, resulting in the accumulation of antimicrobial substance, momilactone. Findings of this study could provide sound theoretical basis for further applications of FBT and COS used as rice elicitors against seedling blight.

Tetraphenylethene-substituted benzothiadiazoles: AIE and TICT properties, tunable intramolecular conjugation and application in detecting trace water in organic solvents

A series of tetraphenylethylene-based benzothiadiazole derivatives (TPEB-o-NO2, TPEB-m-NO2, and TPEB-p-NO2) were designed and synthesized by adjusting the linkage model of nitro group. Different substituent positions of nitro group lead to different intramolecular conjugation of compounds TPEB-o-NO2, TPEB-m-NO2, and TPEB-p-NO2, thus resulting in different photophysical properties. Their maximum emission gradually red-shifted when changing the connected position of nitro group from ortho-position to meta-position and to para-position. TPEB-o-NO2, TPEB-m-NO2, and TPEB-p-NO2 exhibit interesting solvatochromic effects and “on–off–on” optical switch behavior owing to the combined action of AIE and TICT. Moreover, TPEB-m-NO2 and TPEB-p-NO2 were successfully applied as highly sensitive sensors in quantitatively detecting trace water in tetrahydrofuran (THF), dioxane (Diox) and ethyl acetate (EA). The DL of TPEB-m-NO2 and TPEB-p-NO2 are, 0.039% and 0.014% for THF, 0.021% and 0.009% for EA, 0.033% and 0.018%(v/v) for Diox, respectively. It is worth mentioning that TPEB-m-NO2, and TPEB-p-NO2 can act as sensitive indicator for monitoring trace water fraction in organic solvent rectification, which is much more convenient and intuitive to estimate the real-time water content approximately than traditional method.

Hybrid Azo-fluorophore Organic Nanoparticles as Emissive Turn-on Probes for Cellular Endocytosis.

The development of fluorescent organic nanoparticles, serving as bioimaging agents or drug cargos, represents a buoyant field of investigations. Nevertheless, their ulterior fate and structural integrity after cell uptake remain elusive. Toward this aim, we have elaborated original photoactive organic nanoparticles (dTEM ∼ 35-50 nm wide) with an off-on signal upon cellular internalization. Such nanoparticles are based on the noncovalent association of red-emitting benzothiadiazole (BDZ) derivatives and azo dyes, acting as fluorescence quenchers. Upon varying the azo/BDZ ratio, we found that quantitative emission quenching could be obtained with only a 0.2:1 azo/BDZ ratio and originated from exergonic oxidative and reductive photoinduced electron transfer from the azo units (ΔelG0 = -0.21 and -0.29 eV, respectively). Such results revisited the origin of emission quenching, often confusedly ascribed to Förster resonance energy transfer. A nonlinear and sharp drop of the emission intensity with the increase in the azo unit density n was observed and presents comparable evolution to a n-1/3 mathematical law. Thorough biological examinations involving cancer cells prove a receptor-independent endocytosis pathway, leading to progressive cell lighting upon nanoparticle accumulation in the late endosomal/lysosomal compartments. Complete emission recovery of the initially quenched azo/BDZ nanosystems could be achieved by using mefloquine, which caused endosomal/lysosomal disruption, and release of their content in the cytoplasm. Such results demonstrate that the dotlike emission from endosomes actually stems from fully dissociated individual dyes and not integer nanoparticles. They conclude on the high spatial confinement promoted by organelles and finally question its severe impact on functional compounds or nanoparticles whose properties are strongly distance dependent.

Synthesis by direct arylation reaction of photovoltaic D–π–A polymers based on fluorene-thiophene- fragment and fluorinated benzothiadiazole derivatives

Synthesis of three photovoltaic polymers PFBT-HH, PFBT-HF and PFBT-FF based on benzothiadiazole derivatives and fluorene ring was carried out by direct arylation reaction. The polymers were designed to have a donor–π–acceptor –(D–π–A)n– structure, PFBT derivatives were synthetized employing similar reaction conditions to evaluate the effect of fluorine atoms into the acceptor moiety. For synthesis of PFBT-polymers via direct arylation reaction, the presence of fluorine atoms promotes materials with lower molecular weight and with deep HOMO and LUMO energy levels. An expected increment of photochemical stability with the substitution of fluorine atoms on polymers was observed for its pristine films, and the reduction of polymers photodegradation due to presence of PC61BM fullerene derivative. Photovoltaic characteristics of PFBT-polymers were evaluated into Polymer Solar Cell with bulk- heterojunction architecture fabricated under the configuration glass/ITO/PEDOT:PSS/polymer:PC61BM/PFN/FM. Devices were fabricated at room atmospheric conditions, using an easy-to-manufacture superior electrode (FM = Field’s metal) which was free vacuum deposited by melting it about 90 °C, average power conversion efficiencies of 2.3, 1.1 and 1.2% were reached for high molecular weight fractions of polymers PFBT-HH, PFBT-HF and PFBT-FF, respectively.

Fluorine-Mediated Benzothiadiazole Derivatives for Second-Order Nonlinear Optics

With increasing research interests in the field of light-matter interactions, various methods have been developed for regulating nonlinear optical (NLO) materials. However, the design and synthesis of organic molecular materials for second-order nonlinear optics remain a great challenge because of the strict requirement of the materials to possess a noncentrosymmetric structure. In this work, two benzothiadiazole (BTD) derivatives referred to as BTD-H and BTD-F were synthesized, and their NLO properties in the crystalline states were studied. It was found that introducing fluorine into the BTD backbone effectively tuned the crystal packing styles of BTD derivatives to a noncentrosymmetric system for effective second-order NLO responses. Such a strategy to induce the noncentrosymmetric structure by introducing the fluorine atoms and halogen interactions may provide guidance for future engineering of organic NLO molecular materials.

(Invited) Understanding Benzothiadiazole Based Anolyte Materials for Nonaqueous Redox Flow Cells

Redox-active organic materials (ROMs) have shown great promise for redox flow battery applications but generally encounter limited cycling efficiency and stability at relevant redox material concentrations in nonaqueous systems. In this talk, a new family of heterocyclic organic anolyte molecules, 2,1,3-benzothiadiazole (BZNSN) and derivatives,1-2 will be discussed, which demonstrated high solubility, low redox potential, and fast electrochemical kinetics. By coupling BZNSN with a benchmark catholyte ROM (DBMMB), the nonaqueous organic flow battery delivered significant improvement in cyclable redox material concentrations and cell efficiencies compared to the state-of-the-art nonaqueous systems. In order to obtain an insightful understanding of this family of molecules, a series of derivatives have been developed by varying the 5-position substitutions with tunable electronic accepting/withdrawing features. The substituent effects on their properties of interest have been examined, including redox potentials, calendar lives of charged ROMs in an electrolyte, and the flow cell cycling performance. While the calendar life of energized fluids can be tuned in a predictable fashion over a wide range, the improvements in the calendar life do not directly translate into the enhanced cycling performance. This finding strongly indicates the significant role of structural engineering in achieving improvement of radical ion stability, suggesting a generic guidance for developing long-cycling ROM-based flow cells. Figure 1 Structures and cyclic voltammogram of benzothiadiazole derivatives and the correlation of the half-decay lifetime of the radical anions with the redox potentials. Mind the logarithmic vertical scale. Duan, W.; Huang, J.; Kowalski, J. A.; Shkrob, I. A.; Vijayakumar, M.; Walter, E.; Pan, B.; Yang, Z.; Milshtein, J. D.; Li, B.; Liao, C.; Zhang, Z.; Wang, W.; Liu, J.; Moore, J. S.; Brushett, F. R.; Zhang, L.; Wei, X.,. ACS Energy Letters 2017, 2(5), 1156-1161. 2. Huang, J.; Duan, W.; Zhang, J.; Shkrob, I. A.; Assary, R. S.; Pan, B.; Liao, C.; Zhang, Z.; Wei, X.; Zhang, L..Journal of Materials Chemistry A 2018, 6 (15), 6251-6254. Figure 1

Thiophene Disubstituted Benzothiadiazole Derivatives: An Effective Planarization Strategy Toward Deep-Red to Near-Infrared (NIR) Organic Light-Emitting Diodes.

As one of the three primary colors that are indispensable in full-color displays, the development of red emitters is far behind the blue and green ones. Here, three novel orange-yellow to near-infrared (NIR) emitters based on 5,6-difluorobenzo[c][1,2,5]thiadiazole (BTDF) namely BTDF-TPA, BTDF-TTPA, and BTDF-TtTPA were designed and synthesized. Density functional theory analysis and photophysical characterization reveal that these three materials possess hybridized local and charge-transfer (HLCT) state feature and a feasible reverse intersystem crossing (RISC) from the high-lying triplet state to the singlet state may conduce to an exciton utilization exceeding the limit of 25% of traditional fluorescence materials under electrical excitation. The insertion of thiophene with small steric hindrance as π-bridge between the electron-donating (D) moiety triphenylamine (TPA) and the electron-accepting (A) moiety BTDF not only results in a remarkable 67 nm red-shift of the emission peak but also brings about a large overlap of frontier molecular orbitals to guarantee high radiative transition rate that is of great significance to obtain high photoluminescence quantum yield (PLQY) in the “energy-gap law” dominated long-wavelength emission region. Consequently, an attractive high maximum external quantum efficiency (EQE) of 5.75% was achieved for the doped devices based on these thiophene π-bridged emitters, giving a deep-red emission with small efficiency roll-off. Remarkably, NIR emission could be obtained for the non-doped devices, achieving an excellent maximum EQE of 1.44% and Commission Internationale de l'Éclairage (CIE) coordinates of (0.71, 0.29). These results are among the highest efficiencies in the reported deep-red to NIR fluorescent OLEDs and offer a new π-bridge design strategy in D-π-A and D-π-A-π-D red emitter design.

Palladium Catalyst with Task-Specific Ionic Liquid Ligands: Intracellular Reactions and Mitochondrial Imaging with Benzothiadiazole Derivatives.

A water-soluble and charge-tagged palladium complex (PdMAI) was found to function inside breast cancer live cells of the MCF-7 lineage as an efficient catalyst for cross-coupling reaction. PdMAI, bearing two ionophilic task-specific ionic liquids as ligands, efficiently catalyzed both in cellulo Suzuki and Buchwald-Hartwig amination reactions. For the first time, therefore, the Buchwald-Hartwig amination is described to occur inside the highly complex cellular environment. The 2,1,3-benzothiadiazole (BTD) core was used as the base for the syntheses, and two π-extended fluorescent derivatives (BTD-2APy) and (BTD-1AN), which were found to emit in the green and red channels, had impressive mitochondrial affinity. These chromophores allowed for selective mitochondrial imaging and tracking.

Efficient Föster Resonance Energy Transfer between Semiconducting Polymer and Benzothiadiazole Derivatives

The efficient foster resonance energy transfer (FRET) between a semiconducting polymer such as an iptycene polymer and benzothiadiazole derivatives was investigated. The iptycene polymer whose emission wavelength is 450 nm acts as an electron donor and the benzothiadiazole derivatives, which emits at 590 nm, act as electron acceptors. The photoluminescence properties of the iptycene polymer/benzothiadiazole - donor/acceptor were studied. FRET from the donor/acceptor was used to detect explosives. Detection efficiencies were measured through quenching PL measurements on FRET materials with explosives added. The detection mechanism was analyzed using Stern-Volmer plots.

Tetracyanobutadiene (TCBD) functionalized benzothiadiazole derivatives: effect of donor strength on the [2+2] cycloaddition–retroelectrocyclization reaction

A series of unsymmetrical and symmetrical mono/di 1,1,4,4-tetracyanobutadiene (TCBD) substituted benzothiadiazoles (BTDs) 2a–2g was synthesized by [2+2] cycloaddition–retroelectrocyclization reaction.