Α-cyanostilbene Derivative Research Articles

Functionalized α-Cyanostilbene Derivatives for Detection of Hypoxia or Proteostasis Imbalance in Live Cells.

α-Cyanostilbene represents one of the easily functionalized aggregation-induced emission (AIE) scaffolds. It has been widely adopted for the construction of fluorescent materials for broad applications. Here, we further expanded the utilization of α-cyanostilbene derivatives for the detection of hypoxia or proteostasis imbalance in live cells. Four different amine containing donors were introduced to construct α-cyanostilbene derivatives (R-ASC) with donor-acceptor scaffolds. Equipped with the cysteine (Cys) reactive group, maleimide (MI), R-ASC-MI shows fluorescence turn-on property upon binding with unfolded proteins in vitro and in live cells under proteostatic stress. By virtue of R-ASC-MI, the level of unfolded protein loads in cells can be quantified by flow cytometry, or visualized under microscope. Furthermore, we also characterized the performance of R-ASC-NO2, synthetic precursors of R-ASC-MI, in cellular hypoxia. R-ASC-NO2 revealed upregulated activities of nitroreductase, as well as increased hydrophobicity in live cells, under either chemical (NaN3) induced or atmospheric (1% O2) hypoxia. Together, the advantages of easy modification and high signal-to-noise ratio of new α-cyanostilbene derivatives reported in this work highlight the great potential of α-cyanostilbene in constructing functional biosensors and many other domains.

Dual physical stimuli fluorescence response of an α-cyanostilbene derivative for dynamic information storage

α-cyanostilbene derivatives, known as AIE molecules, have the potential to serve as optical recorders and vapor sensor by altering the molecular aggregation and / or stacking models. Despite the significant scientific and technological importance of the correlation between molecular stacking modes and modulated optical properties, relevant research remains scarce. Herein, two thermodynamically stable crystalline phase (BCr and GCr) were found for a biphenyl-based cyanostilbenic compound, DSB-SQ, condensed from its solution. Uniquely, the BCr demonstrated reversible mechanochromism and irreversible thermalchromism, whereas GCr remained unaffected by exposure to light, heat, grinding, etc. The discoloration process was correlated with the variation of local dipole coupling modes during the phase transition, leading to a significant change in π-π overlap and delocalization of excited states. Finally, the BCr was doped with polyvinyl alcohol (PVA) to prepare a composite membrane with dynamic information storage and encryption function.

Multi-stimuli fluorescence responsiveness of α-cyanostilbene derivative: AIEE, stimuli response to polarity, acid, force and light, applications in anti-counterfeiting and single phosphor w-OLED

Recently, the small molecule functional materials with a simple synthesis have attracted more and more attention. A multi-stimuli-responsive aggregation-induced emission (AIE) molecule is expected to have great applications in the near future. Identically, the single-component white organic light diode (w-OLED) has a good application field. Herein, a cyanostilbene derivative (TSC) was efficiently synthesized by Vilsmeier and Knoevenagel reactions with only 2 steps under mild conditions. TSC was characterized by NMR (1H, 13C), FT-IR, HRMS and elemental analysis. TSC has aggregation-induced enhanced emission (AIEE) effect, and significant polar-, acid-, force- and light-stimuli fluorescence responsiveness properties. The AIE effect and four different stimulus responses are all simultaneously presented in TSC. This phenomenon is relatively rare in small molecule fluorescent compounds. The results of SEM and DLS reveal the AIEE of TSC is mainly due to the fact that molecular self-assembly into nanofiber networks in the aggregated state limiting the distortion of molecules. DFT calculations show that the polarity stimuli-response (fluorescence from green to orange) is closely related to intramolecular charge transfer (ICT). Acid/base 1H NMR titration proves that the acidochromism results from reversible protonation/deprotonation. The results of DSC, SEM, PXRD and POM prove that the essence of mechanical force stimuli-response is the change of crystallinity. The results of 1H NMR, UV–vis and fluorescence spectra, DFT calculations and SEM reveal that the light stimuli-response is attributed to the Z/E configuration transformation. Based on multi-stimuli responsive properties, TSC can be used for recognition of solvents polarity by naked eyes or fluorophotometer, used as an acid indicator and also used to quantitatively test the concentration of trace acids, used in anti-counterfeiting including safty ink, data rewriting, even can be used to construct supramolecular liquid crystals materials. In addition, TSC can be used to fabricate single phosphor w-OLED, avoiding using multicomponent composite materials.

Functional-group-regulated stimuli-responsive banana-shaped α-cyanostilbene derivatives: Dual-state emission, AIEE, acidochromism and their applications in anti-counterfeiting, fingerprint recognition and OLEDs

The research of structure-property relationships is of great significance for exploring the luminescent mechanism, the design of functional materials with desired photoelectric properties and facilitating practical applications. In this paper, a series of cyanostilbene derivatives (TS-R) with different functional groups were synthesized by one step under mild conditions and characterized. Their photoelectric properties and structure-property relationships have been researched. The results indicate that TS-R have solution and solid dual-state emission (DSE) property, aggregation-induced emission enhancement (AIEE) effect, solvatochromism behavior and stimuli-responsive fluorescence characteristic for acid. The photoelectric properties can be changed by introducing different functional groups at the molecular same position of TS-R. The applications of TS-R were also investigated. The results indicate that TS-R can be used in fluorescent anti-counterfeiting, fingerprint recognition and light emitting diode (LED).

Versatile side chain turns property and functions of α-cyanostilbene derivatives with near-infrared emission and two-photon property for mitochondrial imaging

Developing red materials with bright near-infrared emission and excellent two-photon performance by a simple preparation process is a meaningful and challenging work. Herein, a series of nitro functionalized D-π-A type α-cyanostilbene derivatives with different side chains (ZH, ZOM, ZOE, and ZOB) have been designed and synthesized by a one-pot method. The compounds show weak emissions and almost the same photophysical properties in solutions. In contrast, in the aggregation state, ZOM, ZOE, and ZOB with side chains of methoxy, ethoxy and benzyloxy emit strong fluorescence, while ZH with no side chain shows weak emission. The aggregate emission mechanism is ascribed to the side chain induced the molecular planarization, and formation of unique “bricks” H-aggregates and “staircase” J-aggregates, investigated by single-crystal analysis and DFT calculations. Considering the excellent photophysical properties of the side chain modified compounds, the triphenylphosphonium is employed to the side chain to obtain a mitochondrial targeting probe Z-TPP, which performs high fluorescence and selectively targeted the mitochondria in live cell and zebrafish under one/two-photon excitation, and further successfully applied to observe the complex mitochondrial network with high signal-to-noise ratio under stimulated emission depletion (STED) nanoscopy.

A cyanostilbene derivative containing –CF3: Synthesis and applications in sensors, information rewritable, encryption and LED

An organic small molecule fluorescent material α-cyanostilbene derivative (2) containing trifluoromethyl (electron acceptor) and dimethylamino (electron donor) has been designed and synthesized by a simple two-step reaction and mild conditions. The structure of target product 2 was characterized using elemental analysis, FT-IR and NMR (1H, 13C, 19F) methods. Compound 2 has strong luminescence in solution and solid states (i.e., dual-state emission, DSE) and aggregation-induced enhanced emission, (AIEE) effect. 2 can be used to recognition the polarity of solvents by “naked eye” under a UV lamp or by fluorescence spectrometer because of its obvious solvatochromic behaviour. 2 can be applied in information rewritable storage, encryption and acid/base sensor, owing to its colour and emission wavelength/intensity can be switched under grinding and acid/base stimulation. The acid/base titration 1H NMR spectra of 2 prove that acidichromism results from the conversion of protonation (2-H+)/deprotonation (2). The results of powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) confirm that the mechanochromic is caused by the morphological transition of 2. Moreover, 2 can be used in light emitting diode (LED) due to its desirable solid-state luminescence performance.

Mechanofluorochromism and mechanical force-triggered solid-state [2+2] photocycloaddition in α-cyanostilbene derivatives

α-Cyanostilbene derivatives are known as fluorescent photochromic molecules that could be used to realize emission colour change or on/off switching via photo-induced isomerization or cycloaddition. Comparing with isomerization, photocycloaddition is less studied due to its critical molecular position and alignment requirement for molecular packing. In this work, biphenyl-based cyanostilbenic compounds 1–3 were synthesized, which exhibit characteristic mechanofluorochromic (MFC) response behaviour. Under force stimuli, the luminescent colour has bathochromic shift from blue to green, together with the phase transition from crystal to amorphous state. Photochromic fluorescent response attributed to photo-induced [2 + 2] cycloaddition could take place instantly in amorphous state, rather than crystals. The MFC response can be successfully used to monitor the photoreaction process, giving rise to quantitative dimerized product. The single crystal structure of compound 2 revealed its photostable feature. The formation of excimers in ground amorphous state, together with the mechanical shearing, facilitates the occurrence of cycloaddition. Subsequently, the recovery process could be achieved thermally or under UV irradiation.

A π-conjugated α-cyanostilbene dimer emitting strongly red fluorescence with a large Stokes’ shift of ca. 300 nm and used as a probe for selective detection of Cu2+

The first π-conjugated α-cyanostilbene dimer, bearing double excited-state intramolecular proton transfer (ESIPT) segments was designed and synthesized via the Schiff's base condensation rection of benzil hydrazone and the individually aldehyde-functionalized α-cyanostilbene derivative. It could emit extraordinary red-fluorescence with a large Stokes' shift of ca. 300 nm in solution, and generate an enhanced red-emission in the aggregated process due to the synergistic effect of the ESIPT and the aggregation-induced emission (AIE). In view of the binging sites of ESIPT segments, it exhibited highly sensitive and selective detection of Cu2+ in THF/water mixtures (v/v, 1:9), and accompanied by a visual and spectro-photometrical fluorescence quenching with the limit of detection (LOD) calculation of 1.55 × 10−8 M. Mechanistic studies indicated that the ESIPT segments participated in coordination function of Cu2+. The real-time and visible monitoring of Cu2+ could be achieved on the red silica gel testing strip due to its excellent AIE nature.

Pyrene and triphenylamine substituted cyanostyrene and cyanostilbene derivatives with dual-state emission for high-contrast mechanofluorochromism and cell imaging

Two α-cyanostilbene derivatives exhibiting bright emission in both well-dissolved solutions (Φ > 49%) and the solid state (Φ > 95%) have been synthesized as novel DSEgens for high-contrast mechanofluorochromism (>50 nm) and live cell imaging.

A competitive effect of acceptor substitutions on the opto-electronic features of triphenylamine cored di α-cyanostilbene derivatives

Acceptor strength regulates the ICT mechanism via AIE or ACQ processes.

Engineering an AIE N2H4 fluorescent probe based on α-cyanostilbene derivative with large Stokes shift and its versatile applications in solution, solid-state and biological systems

Developing effect methods for sensing N2H4 in the environmental and biological systems is particularly important as its terrible toxicity. However, most of the reported N2H4 fluorescent probes have aggregation-caused quenching (ACQ) effect, limited Stokes shift and short emission wavelengths, and thus these shortcomings restrain their comprehensive applications. In this work, we designed a first AIE N2H4 fluorescent probe Co-NH based on the α-cyanostilbene derivative. This probe Co-NH integrated intramolecular charge transfer (ICT) and AIE mechanisms. The probe Co-NH has remarkable aggregations with increasing proportion of water, and these aggregates show obviously redshift in emission with large Stokes shift (170 nm and 205 nm in 1,4-dixoane and pure water respectively). Importantly, Co-NH can sense N2H4 in 1,4-dioxane/H2O (v/v = 9/1) solution with low LOD (0.101 μM), high selectivity and photostability. With the aids of fluorescence in solid-states, Co-NH has achieved in detecting N2H4 in TLC plates. In addition, Co-NH exhibits the ability for tracing N2H4 in living cells and zebrafish. We hope Co-NH is a useful tool for detection of N2H4 in various environments.

Multi-functional materials based on α-cyanostilbene: Response to mechanical stimuli and selective detection of PNA

Two α-cyanostilbene derivatives NCS1 and NCS2 were designed and synthesized. Both two compounds exhibited AIE properties. Solid compounds showed excellent mechanochromism with 29/26 nm redshift and distinct acid-base vapor chromotropism, which could be applied for relevant sensors. XRSD and PXRD spectra revealed the intrinsic relationship between mechanochromism and molecular packing mode. The twisted molecular conformation became more planar with an increase in conjugation after grinding, resulting in the redshift in fluorescence spectra. Moreover, the emission spectra of NCSs showed obvious fluorescence quenching for p-nitroaniline (PNA) with excellent selectivity. The fluorescence intensity showed better linear relationship at low concentration of PNA. The limit of detections were as low as 0.42 μmol L−1 and 0.60 μmol L−1, respectively. DFT theory proved that this sensing mechanism was attributed to the process of photoinduced electron transfer (PET). Importantly, NCSs were successfully used for PNA detection in real environments. We provide the working basis for developing high-performance multi-functional materials.

An α-Cyanostilbene Derivative for the Enhanced Detection and Imaging of Amyloid Fibril Aggregates.

The aggregation of proteins into amyloid fibrils has been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Benzothiazole dyes such as Thioflavin T (ThT) are well-characterized and widely used fluorescent probes for monitoring amyloid fibril formation. However, existing dyes lack sensitivity and specificity to oligomeric intermediates formed during fibril formation. In this work, we describe the use of an α-cyanostilbene derivative (called ASCP) with aggregation-induced emission properties as a fluorescent probe for the detection of amyloid fibrils. Similar to ThT, ASCP is fluorogenic in the presence of amyloid fibrils and, upon binding and excitation at 460 nm, produces a red-shifted emission with a large Stokes shift of 145 nm. ASCP has a higher binding affinity to fibrillar α-synuclein than ThT and likely shares the same binding sites to amyloid fibrils. Importantly, ASCP was found to also be fluorogenic in the presence of amorphous aggregates and can detect oligomeric species formed early during aggregation. Moreover, ASCP can be used to visualize fibrils via total internal reflection fluorescence microscopy and, due to its large Stokes shift, simultaneously monitor the fluorescence emission of other labelled proteins following excitation with the same laser used to excite ASCP. Consequently, ASCP possesses enhanced and unique spectral characteristics compared to ThT that make it a promising alternative for the in vitro study of amyloid fibrils and the mechanisms by which they form.

Fabrication of deoxycholic acid tethered α-cyanostilbenes as smart low molecular weight gelators and AIEE probes for bio-imaging

Four novel deoxycholic acid tethered α-cyanostilbenes were designed, synthesized and characterized using detailed spectroscopic analysis. The synthesized deoxycholic acid tethered α-cyanostilbene derivatives formed stable gels with a variety of solvents, such as xylene, toluene, mesitylene, decane, dodecane etc. The stable gels showed lamellar sheet type structures stacked over each other, consisting of entangled fibres as evident from SEM, TEM and Fluorescence Microscopy images; The synthesized compounds exhibited AIEE behaviour in H2O/THF mixture, with the maximum emission observed in 70% H2O/THF fraction along with a bathochromic shift. A solvent thickening experiment was perform to establish the mechanism of AIEE and the AIEE property was explored for bacterial bio-imaging. The synthesized derivatized steroids proved their potential as multifunctional organic materials.

Emission shift of an amphiphilic α-cyanostilbene derivative through concentration-driven two-step assembly with cucurbit[7]uril

In this study, we synthesized an amphiphilic α-cyanostilbene derivative (E-form)-1-(12-(2-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)-5-(diethylamino)phenoxy)dodecyl)pyridin-1-ium bromide (denoted by BCPB). As being dissolved in aqueous solution, BCPB shows strong emission of excimers at around 660 nm due to the formation of aggregates. Addition of different amount of CB[7] into the solution leads to the emission shift from 660 nm, firstly to 540 nm and then to 588 nm. The emission shift is attributed to the two-step assembly driven by the concentration of CB[7], and the molar ratios of CB[7]/BCPB (denoted by Rm) play a critical role for the shift. As Rm ≤ 4, CB[7] mainly interacts with the cationic pyridinium group of BCPB to form BCPB@CB[7] complex. As Rm > 4, another CB[7] binds to the diethylamino group at one end of α-cyanostilbene to form BCPB@CB[7]2 complex. The two-step assembly well explains the emission shift of BCPB.

Design of large π-conjugated α-cyanostilbene derivatives as colorimetric sensors for volatile acids and organic amine gases

Two large π-conjugated α-cyanostilbene derivative isomers (M-PDC and P-PDC) could sensitively and continuously detect volatile acids and organic amine gases.

Abstract 4788: Novel hybrid benzothiazole screening in U87-MG glioblastoma cell line

Abstract Benzothiazole is a heteroaromatic compound known for its wide range of bioactivities including anticancer, antiviral, antimicrobial, anti-inflammatory, anticonvulsant, antidiabetic, antihelminthic, and antitubercular activities. Research has shown that derivatives of benzothiazole exhibit inhibition of proliferation via apoptosis in various human cancer cell lines, such as liver cancer (Wang, et. al., 2010). In this study, a series of novel hybrid benzothiazole α-cyanostilbene derivatives and styrylbenzothiazole derivatives containing boronic acid and non-boronic acid pharmacophores were synthesized and their anti-cancer properties on U87-MG glioblastoma cells were investigated in vitro. U87-MG cells were incubated with synthesized novel hybrid compounds at varying concentration to determine the inhibitory concentration 50 (IC50) of the compounds. Most hybrid compounds displayed inhibitory effects on cell growth and the IC50 of the compounds varied depending on the nature of the pharmacophores. Moreover, boronic acid-containing compounds exhibit lower IC50 than nonboronic acid-containing compounds. Cell mobility has been investigated and we have found that treated cells were less mobile than untreated cells. In the future, we will be further screening for mobility, invasiveness, and mode of death of these novel hybrid benzothiazole treated glioblastoma cells. Citation Format: Priscilla Kyi, Desmond H. Murray, Denise L. Smith. Novel hybrid benzothiazole screening in U87-MG glioblastoma cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4788.

Fast photoinduced deformation of hydrogen-bonded supramolecular polymers containing α-cyanostilbene derivative

This is the first example of photoinduced deformation displayed by α-cyanostilbene-based supramolecular polymers.

Two AIEE-active α-cyanostilbene derivatives containing BF2 unit for detecting explosive picric acid in aqueous medium.

Two novel α-cyanostilbene derivatives bearing triphenylamine and BF2 groups are synthesized (named TPE-B and TPE-BN). The fluorescent emissions of compounds TPE-B and TPE-BN are hypochromatically shifted and bathochromically shifted, respectively, with increasing polarity of the solvents, suggesting that the two compounds have characteristic polarity-dependent solvatochromic effects. Furthermore, they show obvious aggregation-induced emission enhancement (AIEE) phenomenon in THF/water mixture solutions. Meanwhile, compounds TPE-B and TPE-BN emit orange and yellow fluorescence in their solid states, respectively. Most significantly, in aqueous medium, compounds TPE-B and TPE-BN can selectively and sensitively detect picric acid (PA) among a number of nitroaromatic compounds, and their limits of detection (LOD) are calculated as 1.26 × 10−6 M and 1.51 × 10−6 M, respectively. The recognition mechanism for PA can be attributed to the photo-induced electron transfer (PET) process and this is supported by density functional theory (DFT) calculation. This research provides two novel compounds for the rational design of AIEE-active materials for sensing systems.

Substituent Effect on the Solid-State Photoinduced Luminescence of α-Cyanostilbene Derivatives

A series of α-cyanostilbene derivatives with aggregation-induced enhanced emission （AIEE） was obtained. All the compounds were characterized by UV−vis spectroscopy, fluorescence and nuclear magnetic resonance. These compounds exhibited blue, green and yellow color emission in solid state but non-fluorescent in dilute solutions. The electronic characteristics were examined by GAMESS Interface software package. The results indicate that the luminescence properties are affected by the substituents.