Styryl Group Research Articles

Styrylchromones: Biological Activities and Structure-Activity Relationship.

Styrylchromones (SC) are a group of oxygen-containing heterocyclic compounds, which are characterized by the attachment of a styryl group to the chromone core. SC can be found in nature or can be chemically synthesized in the laboratory. As their presence in nature is scarce, the synthetic origin is the most common. Two types of SC are known: 2-styrylchromones and 3-styrylchromones. However, 2-styrylchromones are the most common, being more commonly found in nature and which chemical synthesis is more commonly described. A wide variety of SC has been described in the literature, with different substituents in different positions, the majority of which are distributed on the A- and/or B-rings. Over the years, several biological activities have been attributed to SC. This work presents a comprehensive review of the biological activities attributed to SC and their structure-activity relationship, based in a published literature search, since 1989. The following biological activities are thoroughly revised and discussed in this review: antioxidant, antiallergic, antiviral, antibacterial, antifungal, anti-inflammatory and antitumoral, affinity and selectivity for A3 adenosine receptors, neuroprotective, and α-glucosidase inhibition. In general, SC are composed by a promising scaffold with great potential for the development of new drugs.

Comprehensive study of 1,2,4-triazolo[1,5]benzodiazepine derivatives: Synthesis, characterization, X-ray diffraction, DFT calculations, Hirshfeld surface analysis, ADMET properties, and molecular docking

In this research, the synthesis of triazolobenzodiazepine derivatives was achieved through a [3 + 2] cycloaddition reaction between N-(4-bromophenyl)-C-ethoxycarbonylnitrilimine and benzodiazepine 1. The structures of the products, denoted as 3 and 4, were determined using NMR spectroscopy (1H and 13C). However, only one single crystal, corresponding to compound 4, was successfully obtained. Single-crystal X-ray diffraction analysis of compound 4 confirms the proposed structure and accurately determines the stereochemistry, indicating that the styryl group at position 3a and the phenyl group at position 5 are on opposite sides. We compared the spectral data obtained from theoretical calculations with the experimental data. and found high correlation coefficients, indicating a satisfactory reproducibility of both the geometrical parameters and chemical shifts by the computational method used. Additionally, we used Hirshfeld surface analysis to explore the intermolecular interactions within the crystal lattice, providing further understanding of the molecular packing. Additionally, an ADMET study was performed to estimate its toxicity, excretion, metabolism, distribution, and absorption.

Phenolic Dienes as Highly Selective Dienophiles in the Asymmetric Organocatalyzed Three-Component Vinylogous Povarov Reaction.

Our study presents a novel enantioselective route for the synthesis of 1,2,3,4-tetrahydroquinolines via a chiral phosphoric acid-catalyzed three-component Povarov reaction, employing phenolic dienes as dienophiles. This approach produces a diverse array of 2,3,4-trisubstituted tetrahydroquinolines, each featuring a styryl group at position 4, in high yields with excellent regio-, diastereo-, and enantioselectivities (>95:5 dr and up to >99% ee).

Synthesis, optical properties and self-assemblies of a new halogenated BODIPY dye with long alkoxy chain

A new boron-dipyrromethene (BODIPY) dye modified with two bromine atoms at the 2,6-positions and three hydrophobic p-(dodecyloxy)styryl groups at 3,5,8-positions was designed and synthesized. Its molecular structure was characterized by 1HNMR and MALDI-TOF-MS. The photophysical properties and aggregate behavior of dye 3 in solution were studied by UV–visible absorption and fluorescence spectroscopy. The dye 3 exhibited strong absorption and a high fluorescence quantum yield in different solvents. The self-assembly behaviors were investigated in THF and water mixtures, and the J-aggregates can be formed. Supramolecular self-assembly behavior of dye 3 was confirmed by temperature-dependent UV−Vis absorption. In addition, the self-assembly behavior of dye 3 in liquid-solid interface was studied using scanning tunneling microscopy (STM) and displays highly ordered linear arrangement on HOPG. The self-assembly processes are found to be adjusted by halogen bonding as well as π−π stacking.

Synthesis of Nitrostyrylthiazolidine-2,4-dione Derivatives Displaying Antileishmanial Potential.

A series of 61 thiazolidine-2,4-diones bearing a styryl group at position 5 was synthesized in 2-5 steps and their structure was proved by elemental and spectral analyses. The compounds obtained were evaluated in vitro against the promastigote stage of the kinetoplastid parasite Leishmania infantum and the human HepG2 cell line, to determine selectivity indices and to compare their activities with those of antileishmanial reference drugs. The study of structure-activity relationships indicated the potential of some derivatives bearing a nitro group on the phenyl ring, especially when located at the meta position. Thus, among the tested series, compound 14c appeared as a hit compound with good antileishmanial activity (EC50 = 7 µM) and low cytotoxicity against both the hepatic HepG2 and macrophage THP-1 human cell lines (CC50 = 101 and 121 µM, respectively), leading to good selectivity indices (respectively, 14 and 17), in comparison with the reference antileishmanial drug compound miltefosine (EC50 = 3.3 µM, CC50 = 85 and 30 µM, SI = 26 and 9). Regarding its mechanism of action, among several possibilities, it was demonstrated that compound 14c is a prodrug bioactivated, predominantly by L. donovani nitroreductase 1, likely leading to the formation of cytotoxic metabolites that form covalent adducts in the parasite. Finally, compound 14c is lipophilic (measured CHI LogD7.7 = 2.85) but remains soluble in water (measured PBS solubility at pH7.4 = 16 µM), highlighting the antileishmanial potential of the nitrostyrylthiazolidine-2,4-dione scaffold.

Electrofluorochromic Switching of Heat-Induced Cross-Linkable Multi-Styryl-Terminated Triphenylamine and Tetraphenylethylene Derivatives.

High-performance electrochromic (EC) and electrofluorochromic (EFC) materials have garnered considerable interest due to their diverse applications in smart windows, optoelectronics, optical displays, military camouflage, etc. While many different EC and EFC polymers have been reported, their preparation often requires multiple steps, and their polymer molecular weights are subjected to batch variation. In this work, we prepared two triphenylamine (TPA)-based and two tetraphenylethylene (TPE)-based derivatives functionalized with terminal styryl groups via direct Suzuki coupling with (4-vinylphenyl)boronic acid and vinylboronic acid pinacol ester. The two novel TPE derivatives exhibited green-yellow aggregation-induced emission (AIE). The EC and EFC properties of pre- and post-thermally treated derivatives spin-coated onto ITO-glass substrates were studied. While all four derivatives showed modest absorption changes with applied voltages up to +2.4 V, retaining a high degree of optical transparency, they exhibited obvious EFC properties with the quenching of blue to yellow fluorescence with IOFF/ON contrast ratios of up to 7.0. The findings therefore demonstrate an elegant approach to preparing optically transparent, heat-induced, cross-linkable styryl-functionalized EFC systems.

Stable 2-Azaallyl Salts as a Bridge between 2H-Azirines and Densely Functionalized 2H-Pyrroles.

An efficient protocol for the synthesis of stable 2-azaallyl anion salts by the reaction of alkyl 2-bromo-2H-azirine-2-carboxylates with trimethylsilyl cyanide/Bu4NF has been developed. The domino reaction proceeds in four steps via the cleavage of the azirine C-C bond to provide the tetrabutylammonium salts of stereochemically pure 2-azaallyl anions having U-configuration relative to the cyano groups. The anions with an ortho-substituted aryl group or styryl group exist as a mixture of two geometrical isomers across the N2-C3 bond. 2-Azaallyl anion salts have been shown to be convenient substrates for the one-pot synthesis of densely functionalized 2H-pyrroles by the alkylation-cyclization sequence.

Three undescribed dimeric ferulates from the culture broth of Phellinus linteus and their dengue virus type-2 inhibition activity

Several members of the genus Phellinus have been used as traditional medicine for treating various diseases. They produce unique yellow pigments composed of a styrylpyrone class of compounds. Styrylpyrones exhibit various biological activities. The styryl group is derived from phenylalanine via cinnamic acid, p-coumaric acid, and caffeoyl-CoA pathways, whereas the pyrone ring is derived from acetate. In a feeding experiment using ferulic acid, a phenylpropanoid, three undescribed dimeric ferulates designated as phellidiferulates A-C were isolated from culture broth of P. linteus. Their structures were determined by spectroscopic methods. These compounds exhibited anti-viral activities against dengue virus type 2 (DENV-2) with IC50 values ranging from 0.12 to 0.18 µg/mL.

In vitro demetalation of central magnesium in various chlorophyll derivatives using Mg-dechelatase homolog from the chloroflexi Anaerolineae.

In the metabolic pathway of chlorophylls (Chls), an enzyme called STAY-GREEN or SGR catalyzes the removal of the central magnesium ion of Chls and their derivatives to their corresponding free bases, including pheophytins. The substrate specificity of SGR has been investigated through in vitro reactions using Chl-related molecules. However, information about the biochemical properties and reaction mechanisms of SGR and its substrate specificity remains elusive. In this study, we synthesized various Chl derivatives and investigated their in vitro dechelations using an SGR enzyme. Chl-a derivatives with the C3-vinyl group on the A-ring, which is commonly found as a substituent in natural substrates, and their analogs with ethyl, hydroxymethyl, formyl, and styryl groups at the C3-position were prepared as substrates. In vitro dechelatase reactions of these substrates were performed using an SGR enzyme derived from an Anaerolineae bacterium, allowing us to investigate their specificity. Reactivity was reduced for substrates with an electron-withdrawing formyl or sterically demanding styryl group at the C3-position. Furthermore, the Chl derivative with the C8-styryl group on the B-ring was less reactive for SGR dechelation than the C3-styryl substrate. These results indicate that the SGR enzyme recognizes substituents on the B-ring of substrates more than those on the A-ring.

Microwave-assisted synthesis, photochemical and electrochemical studies of long-wavelength BODIPY dyes

Novel BODIPY derivatives possessing different styryl substituents were synthesized using different methods of Knoevenagel-type condensation with conventional heating and microwave radiation in two conditions. Microwave-assisted synthesis significantly reduces reaction time while enhancing its efficiency. The introduction of styryl substituents at the 3 and 5 positions of the BODIPY core resulted in a substantial bathochromic shift, which was affected by the substituents within styryl groups. Depending on the solvents, the BODIPY with unsubstituted styryl groups possesses absorption maxima (λAbs) between 616 and 626 nm. While the analogs containing electron-donating methoxy and methylthio groups exhibited bathochromically shifted bands with λAbs values in the 633-654 nm range. Fluorescence studies revealed intensive emission of tested BODIPYs with fluorescence quantum yields at the 0.41-0.83 range. On the other hand, singlet oxygen quantum yields were very low. In the electrochemical studies, the CV and DPV scans showed the presence of three redox processes. The calculated electrochemical gaps were in the range of 1.71-1.87 V.

Styryl-extended Azopyrroles and their boron difluoride complexes: Synthesises, structures, spectra, and DFT calculation

Three styryl-extended azopyrrole compounds (2–4) with different substituents (-H, -NO2, and -N(CH3)2) have been synthesized by Knoevenagel condensation reaction between azopyrrole and substituted benzaldehyde. Their BF2 complexes (5–7) were also synthesized. The planar structure of compound 3 was characterized by X-ray crystallographic study. Hirshfeld surface analysis reveals that van der Waals interactions and hydrogen-bonding are the dominant interactions in the crystal packing. All compounds have λmax absorption greatly red-shift even to deep-red light region (646 nm) due to the extended π-conjugation by styryl group and the introduction of BF2 group. The structures, frontier molecular orbitals (FMOs), energy gaps (ΔE) and UV–Vis spectra of these compounds were evaluated by DFT calculations. The results reveal that the styryl, electron donating and withdrawing groups, and BF2 group all can reduce the energy gap (ΔE) of the compounds, and finally cause their long-wavelength absorption.

Organic LEDs Based on Bis(8-hydroxyquinoline) Zinc Derivatives with a Styryl Group.

For the first time, organic light-emitting diodes (OLEDs) based on bis(8-hydroxyquinoline) zinc with a styryl group (ZnStq) dispersed in poly(N-vinylcarbazole) matrix (ZnStq_R:PVK, where R = H, Cl, OCH3) were fabricated. The ZnStq_R:PVK films made via the spin-coating method were used as the active layer in these devices. The produced OLEDs showed strong electroluminescence with yellow emissions at 590, 587 and 578 nm for the ZnStq_H:PVK, ZnStq_Cl:PVK and ZnStq_OCH3:PVK, respectively. For all the studied thin films, the main photoluminescence emission bands were observed between 565 and 571 nm. The OLED with the ZnStq_OCH3:PVK layer with a narrow electroluminescence spectrum was found to have sufficient color purity to produce ultra-high-resolution displays with reduced power consumption (full width at half maximum of 59 nm, maximum brightness of 2244 cd/m2 and maximum current efficiency of 1.24 cd/A, with a turn-on voltage of 6.94 V and a threshold voltage of 7.35 V). To characterize the photophysical properties of the active layer, the ZnStq_R:PVK layers samples were additionally deposited on glass and silicon substrates. We found that the obtained results predestine ZnStq_R:PVK layers for use in the lighting industry in the future.

Transparent Recombination Electrode with Dual-Functional Transport and Protective Layer for Efficient and Stable Monolithic Perovskite/Organic Tandem Solar Cells.

Rational selection and design of recombination electrodes (RCEs) are crucial to enhancing the power conversion efficiency (PCE) and stability of monolithic tandem solar cells (TSCs). Sputtered indium tin oxide (ITO) with high conductivity and excellent transmittance is introduced as RCE in perovskite/organic TSCs. To prevent high-energy ITO particles destroy the underlying material during sputtering, dual-functional transport and protective layer (C1) is employed. The styryl group in C1 can be thermally crosslinked to serve as a sputtering protective layer. Meanwhile, the conjugated phenanthroline skeleton in C1 shows high electron mobility and hole blocking capability to promote the electron transport process at the interfaces and effectively reduce charge accumulation. Monolithic perovskite/organic TSC with high PCE of 24.07% and excellent stability is demonstrated by stacking a 1.77eV bandgap perovskite layer and a 1.35eV bandgap organic active layer. This strategy provides new insights for overcoming the fundamental efficiency limits of single-junction devices and promotes the further development of TSC devices.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Synthesis of the proposed structure of enhypyrazinone A, a rare marine-derived 3,5,6-tri-substituted pyrazinone secondary metabolite

Herein, we report the first total synthesis of enhypyrazinone A, a rare tri-substituted pyrazinone secondary metabolite that is isolated from the marine-derived myxobacterium Enhygromyxa sp. The key features of the synthesis involve a Horner-Wadsworth-Emmons (HWE) olefination to provide a crucial C5-substituted (E)-styryl group and the construction of a 3,5,6-tri-substituted pyrazinone skeleton from a highly functionalized dipeptide intermediate via pyridine-promoted cyclization and subsequent spontaneous aerobic oxidation. Although the 13C NMR spectra of the synthetic enhypyrazinone A slightly differed from those reported previously, the structure was confirmed by comprehensive 2D NMR analysis, including 1H–1H COSY, 1H–13C HSQC, and 1H–13C HMBC. Our concise and straightforward synthetic route provides the proposed structure of enhypyrazinone A with eight linear steps in 27.4% overall yield from commercially available Boc-Trp-OMe.

Synthesis of Bis(amino acids) Containing the Styryl-cyclobutane Core by Photosensitized [2+2]-Cross-cycloaddition of Allylidene-5(4H)-oxazolones.

The irradiation of 2-aryl-4-(E-3'-aryl-allylidene)-5(4H)-oxazolones 1 with blue light (456 nm) in the presence of [Ru(bpy)3](BF4)2 (bpy = 2,2'-bipyridine, 5% mol) gives the unstable cyclobutane-bis(oxazolones) 2 by [2+2]-photocycloaddition of two oxazolones 1. Each oxazolone contributes to the formation of 2 with a different C=C bond, one of them reacting through the exocyclic C=C bond, while the other does so through the styryl group. Treatment of unstable cyclobutanes 2 with NaOMe/MeOH produces the oxazolone ring opening reaction, affording stable styryl-cyclobutane bis(amino acids) 3. The reaction starts with formation of the T1 excited state of the photosensitizer 3[Ru*(bpy)3]2+, which reacts with S0 of oxazolones 1 through energy transfer to give the oxazolone T1 state 3(oxa*)-1, which is the reactive species and was characterized by transient absorption spectroscopy. Measurement of the half-life of 3(oxa*)-1 for 1a, 1b and 1d shows large values for 1a and 1b (10-12 μs), while that of 1d is shorter (726 ns). Density functional theory (DFT) modeling displays strong structural differences in the T1 states of the three oxazolones. Moreover, study of the spin density of T1 state 3(oxa*)-1 provides clues to understanding the different reactivity of 4-allylidene-oxazolones described here with respect to the previously reported 4-arylidene-oxazolones.

2-Styrylchromones Prevent IL-1β-Induced Pro-Inflammatory Activation of Fibroblast-like Synoviocytes while Increasing COX-2 Expression

Rheumatoid arthritis (RA) is characterized by systemic immune and chronic inflammatory features, leading to the destruction of the joints. Presently, there are no effective drugs able to control synovitis and catabolism in the process of RA. 2-Styrylchromones (2-SC) are a small group of compounds characterized by the attachment of a styryl group to the chromone core that have already been associated to a wide range of biological activities, including antioxidant and anti-inflammatory activities. The present study investigated the effect of a set of six 2-SC on the interleukin-1β (IL-1β)-induced increase of nitric oxide (•NO), inducible form of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-3 (MMP-3) expression levels in human fibroblast-like synoviocytes (HFLS), pointing to the role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in the process. From a set of six 2-SC, presenting hydroxy and methoxy substituents, the one presenting two methoxy substituents at C-5 and C-7 of A ring and a catechol group on B ring, significantly reduced •NO production and the expression of its inducible synthase (iNOS). It also significantly reduced the catabolic MMP-3 protein expression. This 2-SC inhibited the NF-κB pathway by reversing the IL-1β - induced levels of cytoplasmatic NF-kB inhibitor alpha (IκBα), and decreasing the p65 nuclear levels, suggesting the involvement of these pathways in the observed effects. The same 2-SC significantly increased the COX-2 expression, which may indicate a negative feedback loop mechanism of action. The properties of 2-SC may be of great value in the development of new therapies with improved efficacy and selectivity towards RA, and thus deserve further exploitation and evaluation to disclose the full potential of 2-SC.

Effect of pyrrole substitution on the optical limiting properties of 3,5-distyrylBODIPYdyes

The optical limiting properties of three meso-pyridyl-distyrylBODIPY dyes with differing alkyl substitution patterns at the 2,6- and 1,7-positions on the pyrrole moieties are investigated. Styryl groups are introduced at the 3,5-positions to form dyes with strong donor-[Formula: see text]-acceptor (D-[Formula: see text]-A) properties. Favorable optical limiting properties are obtained for all three dyes, with the highest second-order hyperpolarizability obtained for a dye that is unsubstituted at both the 2,6- and 1,7-positions suggesting that the optical limiting properties are enhanced when the meso-aryl ring can freely rotate into the plane of the BODIPY core.

Exploring the potential of anthracene derivatives as fluorescence emitters for biomedical applications.

Two novel anthracene derivatives were synthesized, and detailed photo-physical and biological investigations were carried out using a variety of spectroscopy techniques. The effect of cyano (-CN) substitution was found to be effective to alter the charge population and frontier orbital energy levels via Density Functional Theory (DFT) calculations. Particularly, the introduction of styryl and triphenylamine groups attached to the anthracene core helped to increase the conjugation relative to the anthracene moiety. The results revealed that the molecules have intramolecular charge transfer (ICT) properties, occurring from the electron donating triphenylamine to the electron accepting anthracene moiety in solutions. In addition, the photo-physical properties are strongly cyano-dependent, where the cyano-substituted (E/Z)-(2-anthracen-9-yl)-3-(4'-(diphenylamino)biphenyl-4yl)acrylonitrile molecule showed stronger electron affinity due to the enhanced internal steric hindrance compared to the (E)-4'-(2-(anthracen-9-yl)vinyl)-N,N-diphenylbiphenyl-4-amine molecule, which resulted in a lower photoluminescence quantum yield (PLQY) value and a shorter lifetime in the molecule. Besides, the Molecular Docking approach was used to investigate possible cellular staining targets to confirm cellular imaging potential of the compounds. Moreover, cell viability analyses put forth that synthesized molecules do not exhibit significant cytotoxicity under 125 μg mL-1 concentration on the human dermal fibroblast cell line (HDFa). Moreover, both of the compounds showed great potential in cellular imaging of HDFa cells. Compared to Hoechst 33258, a common fluorescent dye used for nuclear staining, the compounds showed higher magnification of cellular structure imaging capacity by staining the whole cellular compartment. On the other hand, bacterial staining showed that ethidium bromide has higher resolution in monitoring Staphylococcus aureus (S. aureus) cell culture.

Acrolein evokes inflammation and autophagy-dependent apoptosis through oxidative stress in vascular endothelial cells and its protection by 6-C-(E-2-fluorostyryl)naringenin

• Acrolein induced mitochondrial dysfunction, apoptosis, and inflammation in HUVECs. • Acrolein induced apoptosis was partially dependent on the activation of autophagy. • The addition of styryl group contributed to the protective potential of 6- C -( E -fluorostyryl)naringenin. • The protective effects of 6- C -( E -fluorostyryl)naringenin is via Nrf2 activation. Acrolein is a common dietary and environmental toxicant. Evidence suggests that acrolein can increase the risk of cardiovascular diseases in which endothelial cells are the sensitive targets. In human umbilical vein endothelial cells (HUVECs), acrolein treatment induced mitochondrial dysfunction, which subsequently triggered apoptosis and inflammation. Acrolein also upregulated autophagy, which possibly resulted from negative regulation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway via reactive oxygen species (ROS). Inhibition of autophagy by 3-methyladenine reduced acrolein-evoked apoptosis, implying a pro-death role of autophagy. In addition, the protective potential of 6- C -( E -2-fluorostyryl)naringenin (6-CEFN) against acrolein was examined. 6-CEFN exhibited higher efficacy than its parental compound naringenin in preventing acrolein-caused damages, where nuclear factor erythroid 2-related factor (Nrf2)-mediated up-regulation of phase II enzymes was involved. Altogether, our findings offer new mechanistic insights into acrolein-induced endothelial injury and demonstrate the therapeutic potential of 6-CEFN for acrolein-related cardiovascular toxicities.