Substituted Phenyl Groups Research Articles

In Search of Visible Light Activatable Photocages: Structure‐Activity Relationship Study on C‐8 Substituted Indene‐Fused‐Coumarinyl Photoremovable Protecting Groups

AbstractA series of C‐8 substituted indeno[1,2‐g]coumarin‐based photoremovable protecting groups (PPGs) were synthesized. para‐Substituted benzoic acids were employed as leaving groups to evaluate their photolytic efficiency. Substitution of phenyl groups was proved to have negative impacts on photochemical properties of the PPGs, including but not limited to: retarded photolysis course, decreased uncaging quantum yield, and unsatisfactory cargo release yield. Electron‐donating diethylamino substituted PPG 3 d, a structural analogue of the widely used 7‐diethylaminocoumarin PPG (DEACM), exhibited red‐shifted absorption maximum and improved optical properties. Photochemical characterization revealed that PPG 3 d not only showed comparable photolytic efficiency to DEACM at 365 nm and 405 nm, but also demonstrated superior sensitivity towards 465 nm wavelength, to which DEACM is unable to absorb and therefore, non‐responsive. The >450 nm photosensitivity makes 3 d a complement to DEACM for long wavelength excitation and a promising PPG for biological applications.

Increasing enantioselectivity and reactivity in Ir-Catalysed intramolecular hydroamination reactions

A series of axially chiral NHC ligands bearing dialkylated naphthyl side arms and electron-rich substituted phenyl groups in the backbone have been employed in the synthesis of neutral NHC-Ir(COD)Cl complexes. When the halide ligand was abstracted from these compounds by appropriate silver salts AgX (X = PF6, NTf2), chiral cationic, formally 14-electron iridium complexes [(NHC)Ir(COD)][X] were formed. When these species were applied as catalysts for asymmetric intramolecular hydroamination of unactivated, amino-olefin substrates, chiral 5- and 6- membered N-heterocyclic products were obtained with moderate to excellent enantioselectivities. By tuning the substrate through variation of the N-protecting group on the amino-olefin substrates, remarkable improvements in enantioselectivity were obtained.

Rotational order-disorder and spin crossover behaviour in a neutral iron(II) complex based on asymmetrically substituted large planar ionogenic ligand.

Octahedrally coordinated spin crossover (SCO) FeII complexes represent an important class of switchable molecular materials. This study presents the synthesis and characterisation of a novel complex, [FeII(ppt-2Fph)2]0·2MeOH, where ppt-2Fph is a new asymmetric ionogenic tridentate planar ligand 2-(5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)-6-(1H-pyrazol-1-yl)pyridine. The complex exhibits a hysteretic thermally induced SCO transition at 285 K on cooling and at 293 K on heating, as well as light induced excited spin state trapping (LIESST) at lower temperatures with a relaxation T(LIESST) temperature of 73 K. Single crystal analysis in both spin states shows that the compound undergoes an unusual partial (25%) reversible order-disorder of the asymmetrically substituted phenyl group coupled to the thermal SCO. The highly cooperative SCO transition, analysed by structural energy framework analysis at the B3LYP/6-31G(d,p) theory level, revealed the co-existence of stabilising and destabilising energy variations in the lattice. The observed antagonism of intermolecular interactions and synchronous rotational disorder, which contributes to the overall entropy change, is suggested to be at the origin of the cooperative SCO transition.

Design, Synthesis, in Silico and in Vitro Evaluation of New Combretastatin A-4 Analogs as Antimitotic Antitumor Agents.

Combretastatin A-4 (CA-4) binds β-tubulin at the colchicine-binding site preventing tubulin from polymerizing into microtubules. CA-4 and cis combretastatin analogs isomerize to the trans form resulting in decreased cytotoxicity and anti-tubulin activity. However, the excellent anti-cancer potential and relatively simple molecular structure of CA-4, provide an encouraging starting point for the development of new, more stable and more potent anti-tubulin compounds. To synthesize a new series of 4-(3,4,5-trimethoxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives (compounds 10-12) as analogs of CA-4, with different alkyl, and aryl side chain substituents at the triazole moiety (B-ring), resulting in permanent cis form. The newly synthesized CA-4 analogs were characterized by FT-IR, 1HNMR, 13CNMR, and HR-MS(ESI) techniques. Molecular docking studies including docking score (G) ADMET, DFT, and mlocular similarities were performed. The anti-proliferative activity of the new compounds against three human cancer cell lines was evaluated using the MTT assay, and their ability to inhibit tubulin polymerization, and consequently their effects on cell cycle progression and induction of apoptois were assessed. Molecular docking studies showed that compounds 11b and 11d exhibited the highest docking scores (-13.30 and -14.01 Kcal/mol, respectively) into colchicine-binding site, scores very close to the reference drug colchicine (-13.50 Kcal/mol), and that hydrogen bonding and hydrophobic interaction are essential for binding. The most active cytotoxic compound 11b had potent IC50 values ranging from 3.83 to 10.67 µM against the three human cancer cell lines, while exhibiting low cytotoxicity against non-cancer human WI-38, suggesting that compound 11b targets rapidly growing cancer cells. Moreover, compound 11b exhibited potent anti-tubulin activity which was comparable to CA-4. Targeting microtubules caused cell cycle arrest at the G2/M phase resulting in induction of apoptosis. These findings indicate that compound 11b is a promising β-tubulin-binding compound with antimitotic action that has the potential to treat cancer.

Battling colorectal cancer via s-triazine-based MMP-10/13 inhibitors armed with electrophilic warheads for concomitant ferroptosis induction; the first-in-class dual-acting agents

There is an increasing interest in halting CRC by combining ferroptosis with other forms of tumor cell death. However, ferroptosis induction is seldom studied in tandem with inhibiting MMPs. A combination that is expected to enhance the therapeutic outcome based on mechanistic ferroptosis studies highlighting the interplay with MMPs, especially MMP-13 associated with CRC metastasis and poor prognosis. Herein, we report new hybrid triazines capable of simultaneous MMP-10/13 inhibition and ferroptosis induction bridging the gap between their anticancer potentials. The MMP-10/13 inhibitory component of the scaffold was based on the non-hydroxamate model inhibitors. s-Triazine was rationalized as the core inspired by altretamine, an FDA-approved ferroptosis inducer. The ferroptosis pharmacophores were then installed as Michael acceptors via triazole-based spacers. The electrophilic reactivity was tuned by incorporating cyano and/or substituted phenyl groups influencing their electronic and steric properties and enriching the SAR study. Initial screening revealed the outstanding cytotoxicity profiles of the nitrophenyl-tethered chalcone 5e and the cyanoacrylohydrazides bearing p-fluorophenyl 9b and p-bromophenyl 9d appendages. 9b and 9d surpassed NNGH against MMP-10 and −13, especially 9d (IC50 = 0.16 μM). Ferroptosis studies proved that 9d depleted GSH in HCT-116 cells by a relative fold decrement of 0.81 with modest direct GPX4 inhibition, thus inducing lipid peroxidation, the hallmark of ferroptosis, by 1.32 relative fold increment. Docking presumed that 9d could bind to the MMP-10 S1′ pocket and active site His221, extend through the MMP-13 hydrophobic pocket, and interact covalently with the GPX4 catalytic selenocysteine. 9d complexed with ferrous oxide nanoparticles was 7.5 folds more cytotoxic than its free precursor against HCT-116 cells. The complex-induced intracellular iron overload, depleted GSH with a relative fold decrement of 0.12, consequently triggering lipid peroxidation and ferroptosis by a 3.94 relative fold increment. Collectively, 9d could be a lead for tuning MMPs selectivity and ferroptosis induction potential to maximize the benefit of such a combination.

Tailoring the cobalt porphyrin for minimal overpotential in the electrochemical oxygen evolution/reduction reactions: A density functional study

Oxygen reduction and evolution reactions (ORR/OER) have attracted tremendous attention as the means to provide sustainable energy solutions. Bifunctionality for ORR and OER is extremely crucial and relevant for regenerative fuel cell technology. Both reactions use precious metal-based electrocatalysts that are limited and expensive making a strong case to develop low-cost, active and stable electrocatalysts. We propose tailoring of Cobalt Porphyrin (Co–Pr) framework by introducing meso phenyl substituents in the Pr ligand and further substitution of phenyl group by ortho/para-anilino groups (CoTPP, CoTPP-o-NMe3, CoTPP-p-NMe3) to design an efficient and selective bifunctional catalyst. Electrocatalysis by CoTPP-o-NMe3 (ηORR/ηOER = 0.45/0.28 V) outperforms Ir/Ru and Pt based benchmark catalysts. Energy profile, scaling relationship, electrode potential, energy descriptor and FMO analysis performed in the DFT framework rationalize its excellent catalytic activity and selectivity for 4e− reduction of O2 to H2O which is vital for hydrogen production and fuel cell applications.

Photodissociative Modules that Control Dual-Emission Properties in Donor-π-Acceptor Organoborane Fluorophores.

Donor-π-acceptor fluorophores that consist of an electron-donating amino group and an electron-accepting triarylborane moiety generally exhibit substantial solvatochromism in their fluorescence while retaining high fluorescence quantum yields even in polar media. Herein, we report a new family of this compound class, which bears ortho-P(=X)R2 -substituted phenyl groups (X=O or S) as a photodissociative module. The P=X moiety that intramolecularly coordinates to the boron atom undergoes dissociation in the excited state, giving rise to dual emission from the corresponding tetra- and tricoordinate boron species. The susceptibility of the systems to photodissociation depends on the coordination ability of the P=O and P=S moieties, whereby the latter facilitates dissociation. The intensity ratios of the dual emission bands are sensitive to environmental parameters, including temperature, solution polarity, and the viscosity of the medium. Moreover, precise tuning of the P(=X)R2 group and the electron-donating amino moiety led to single-molecule white emission in solution.

14-Substituted Diquinothiazines as a New Group of Anticancer Agents.

A series of novel double-angularly condensed diquinothiazines with aminoalkyl, amidoalkyl, sulfonamidoalkyl, and substituted phenyl groups was designed, synthesized, and evaluated for their anticancer activity against four selected human tumor cell lines (HTC116, SH-SY5Y, A549, and H1299). The cytotoxicity of the novel diquinothiazines was investigated against BEAS-2B cells. The activities of the compounds were compared to etoposide. Among them, compounds with aminoalkyl and phenyl groups showed excellent broad-spectrum anticancer activity. The most active 14-(methylthiophenyl)diquinothiazine, 3c, showed low cytotoxicity against BEAS-2B cells and high activity against tumor cell lines HTC116, SH-SY5Y, A549, and H1299, with IC50 values of 2.3 µM, 2.7 µM, 17.2 µM, and 2.7 µM, respectively (etopiside 8.6 µM, 3.9 µM, 44.8 µM, and 0.6, respectively). Live long-term microscopic observations of cell survival using the starting molecule M0 were also performed. Flow cytometry showed the proapoptotic effects of the studied diquinothiazines. Inhibition of the cell cycle in the S phase was observed, which is associated with damage to nucleic acids and connected to DNA replication arrest.

Fe(II) complexes of 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups: synthesis, crystal structures and anticancer potential.

With the aim of developing potential anticancer drug candidates, a series of Fe(II) complexes were synthesized using nine 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups, and their biological activities were systematically investigated. Their bis-terpyridine sandwich-like structures were determined by single crystal X-ray crystallography. In vitro antiproliferative experiments based on three human cancer cell lines, including human hepatoma cancer cell line (Bel-7402), human esophageal cancer cell line (Eca-109), and human cervical squamous cancer cell line (SiHa), indicate the high antiproliferation activities of these complexes compared with commercial cisplatin. And their toxicity to normal cells was estimated based on human normal hepatocyte (HL-7702) cell line. In particular, when the phenyl in terpyridine ligand was modified by a carboxyl group, the corresponding complex 3 exhibited much higher antiproliferation to cancer Bel-7402 cells (IC50 = 3.653 μmol L-1) than cisplatin and low toxicity to normal HL-7702 cells (IC50 = 99.92 μmol L-1), implying a significant selectivity for 3 in killing hepatoma cancer cells. Combined with the fact that iron element is more accessible than platin, this series of Fe(II) complexes comprises potential candidates for anticancer drugs with specific inhibition of hepatoma cancer. UV titration experiments and circular dichroism (CD) showed a strong binding affinity between these nine complexes and CT-DNA. However, molecular docking simulation revealed the competitive binding of DNA and protein to these complexes. Further, the interactions between these complexes and bovine serum albumin (BSA) have been studied by fluorescence titration and CD spectroscopy.

Substitution reactions of cis-platinum(II) complexes containing bidentate N,N-donor pyridinecarboxamide ligands with different substituents

Substitution reactions of [2-(pyridinecarboxamide)dichloride Pt(II)] [PtCl2 ], [N-phenyl-(2-pyridinecarboxamide)dichloride Pt(II)] [PhPtCl2 ], [N-(4-methylphenyl)-2-pyridinecarboxamide)dichloride Pt(II)] [CH3PhPtCl2 ], [N-(4-methoxyphenyl)-(2-pyridine-carboxamide)dichloride Pt(II)] [CH3OPhPtCl2 ] and [N-(4-fluorophenyl)-(2-pyridinecarboxamide)dichloride Pt(II)] [FPhPtCl2 ], with nucleophiles; thiourea (TU), N,N′-dimethylthiourea (DMTU) and N,N,N′,N′-tetramethylthiourea (TMTU) were studied under pseudo first-order conditions. The rates of substitution were investigated as a function of nucleophile concentration and temperature using stopped-flow and UV-visible absorption spectrophotometers. Substitutions of the two coordinated chloride ligands of the Pt(II) complexes occur consecutively, with the first substitution occurring opposite the coordinated pyridyl. The observed pseudo first-order rate constants regressed linearly with concentration of the incoming nucleophiles according to the equation k obs = k 2[Nu]. The highest substitution rates were measured for PtCl2, which is attributed to the unsubstituted non-leaving carboxamide ligand. The Pt(II) center of this complex is the most electrophilic as a result of the strong withdrawal of electron density through π-resonance by the carboxamide group. The introduction of a 4′-substituted phenyl group on the amido N of the carboxamide reduces the reactivity of the complexes due to proportional electronic effects from the ancillary substituents on the phenyl ring as well as its conformational disposition with respect to the plane of the complex. The order of reactivity of studied nucleophiles is TU > DMTU > TMTU. The substitution is associatively activated as supported by the negative entropy of activation values for the reactions.

Synthesis, crystal structures, and Hirshfeld analysis of three hexa-hydro-quinoline derivatives.

Three hexa-hydro-quinoline derivatives were synthesized and crystallized in an effort to study the structure-activity relationships of these calcium-channel antagonists. The derivatives are ethyl 4-(2-meth-oxy-phen-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, C22H27NO4, (I), ethyl 4-(4-meth-oxy-phen-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carb-ox-yl-ate, C22H27NO4, (II), and ethyl 4-(3,4-di-hydroxy-phen-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, C21H24NO5, (III). In these hexa-hydro-quinoline derivatives, common structural features such as a flat-boat conformation of the 1,4-di-hydro-pyridine (1,4-DHP) ring, an envelope conformation of the fused cyclo-hexa-none ring, and a substituted phenyl group at the pseudo-axial position are retained. Hydrogen bonds are the main contributors to the packing of the mol-ecules in these crystals.

Isoquinolone derivatives as lysophosphatidic acid receptor 5 (LPA5) antagonists: Investigation of structure-activity relationships, ADME properties and analgesic effects

Blockade of lysophosphatidic acid receptor 5 (LPA5) by a recently reported antagonist AS2717638 (2) attenuated inflammatory and neuropathic pains, although it showed moderate in vivo efficacy and its structure-activity relationships and the ADME properties are little studied. We therefore designed and synthesized a series of isoquinolone derivatives and evaluated their potency in LPA5 calcium mobilization and cAMP assays. Our results show that substituted phenyl groups or bicyclic aromatic rings such as benzothiophenes or benzofurans are tolerated at the 2-position, 4-substituted piperidines are favored at the 4-position, and methoxy groups at the 6- and 7-positions are essential for activity. Compounds 65 and 66 showed comparable in vitro potency, excellent selectivity against LPA1-LPA4 and >50 other GPCRs, moderate metabolic stability, and high aqueous solubility and brain permeability. Both 65 and 66 significantly attenuated nociceptive hypersensitivity at lower doses than 2 and had longer-lasting effects in an inflammatory pain model, and 66 also dose-dependently reduced mechanical allodynia in the chronic constriction injury model and opioid-induced hyperalgesia at doses that had no effect on the locomotion in rats. These results suggest that these isoquinolone derivatives as LPA5 antagonists are of promise as potential analgesics.

Potential Functional Role of Phenethylamine Derivatives in Inhibiting Dopamine Reuptake: Structure-Activity Relationship.

Numerous psychotropic and addictive substances possess structural features similar to those of β-phenethylamine (β-PEA). In this study, we selected 29 β-PEA derivatives and determined their structure-activity relationship (SAR) to their ability to inhibit dopamine (DA) reuptake; conducted docking simulation for two selected compounds; and identified their potential functionals. The compounds were subdivided into arylethylamines, 2-(alkyl amino)-1-arylalkan-1-one derivatives and alkyl 2-phenyl-2-(piperidin-2-yl)acetate derivatives. An aromatic group, alkyl group, and alkylamine derivative were attached to the arylethylamine and 2-(alkyl amino)-1-arylalkan-1-one derivatives. The inhibitory effect of the compounds on dopamine reuptake increased in the order of the compounds substituted with phenyl, thiophenyl, and substituted phenyl groups in the aromatic position; compounds with longer alkyl groups and smaller ring-sized compounds at the alkylamine position showed stronger inhibitory activities. Docking simulation conducted for two compounds, 9 and 28, showed that the (S)-form of compound 9 was more stable than the (R)-form, with a good fit into the binding site covered by helices 1, 3, and 6 of human dopamine transporter (hDAT). In contrast, the (R, S)-configuration of compound 28 was more stable than that of other isomers and was firmly placed in the binding pocket of DAT bound to DA. DA-induced endocytosis of dopamine D2 receptors was inhibited when they were co-expressed with DAT, which lowered extracellular DA levels, and uninhibited when they were pretreated with compound 9 or 28. In summary, this study revealed critical structural features responsible for the inhibition of DA reuptake and the functional role of DA reuptake inhibitors in regulating D2 receptor function.

Oleanane-Type Triterpene Conjugates with 1H-1,2,3-Triazole Possessing of Fungicidal Activity.

The triazole pesticide is an organic nitrogen-containing heterocyclic compound with a 1,2,3-Triazole ring. In order to develop a potential glucosamine-6-phosphate synthase (GlmS) inhibitor bactericide, 18 triazole-derivative compounds were synthesized efficiently. In addition, these compounds have not been reported in the literature. The structure was confirmed by high-resolution mass spectrometry (HRMS), H NMR and C NMR. The potential use of the most promising derivatives has been investigated by testing their antifungal activity and enzyme inhibitory activity, revealing inhibitory activities in the low micromolar range. Among them, the antifungal effects of compounds 1e, 1f, 1g, 2e, 2f, and 2g on Sclerotinia sclerotiorum were particularly significant, all of which were above 83%. These compounds will be further investigated as potential antifungal lead compounds. Their structure–activity relationships are discussed based on the effects of substituted phenyl groups on compounds.

Synthesis of dimethyl‐ and diphenylsilane‐based oligo(azine)s: Thermal, optical, electronic, and morphological properties

AbstractFour new oligo(azine)s were synthesized from dimethyldiphenylsilane and tetraphenylsilane core‐based dialdehydes and hydrazine by high‐temperature polycondesation and proposed as materials for optoelectronic applications. The oligo(azine)s were characterized by EA, FT‐IR, and NMR. Although most of samples were poorly soluble, TPS‐containing PAZ‐4 was soluble in aprotic polar solvents. According to SEC and FT‐IR studies, the samples were oligomers with up to five repeating units long. TGA showed highly stable samples with TDT10% over 420°C except for PAZ‐1 that contains a DMS core along with phenyl units, and thus, the lowest carbon content in the series. From DSC analysis, the substitution of phenyl groups in PAZ‐1/3 by biphenyl moieties in PAZ‐2/4 allowed to obtain oligo(azine)s with lower Tg values. PAZ‐4 showed a UV‐A absorption with optical band‐gap values of 2.91 and 2.65 eV from UV–vis (solution) and DRS (films), respectively. PL analysis showed a violet emission. PAZ‐4 showed resistivity of 29.24 Ω cm, similar to wide‐band gap materials. Their contact angle measurements showed a critical surface tension of 42.29 dynes/cm, revealing its hydrophobicity. AFM analysis indicated that the PAZ‐4 films had homogeneous surfaces. Young's modulus close to 4.46 GPa was established by microindentation for the PAZ‐4 thin‐films.

Design and synthesis of novel benzimidazole-iminosugars linked a substituted phenyl group and their inhibitory activities against β-glucosidase

A series of novel benzimidazole-iminosugars linked a (substuituted) phenyl group on benzene ring of benzimidazole 5(a-p) and 6(a-p) have been rationally designed and conveniently synthesized through Suzuki coupling reaction in high yields. All compounds have been evaluated for their inhibitory activities against β-glucosidase (almond). Six compounds 5d, 6d, 6e, 6i, 6n, and 6p showed more significant inhibitory activities with IC50 values in the range of 0.03–0.08 μM, almost 10-fold improved than that of the parent analogue 4, and much higher than that of the positive control castanospermine. The additional phenyl ring and the electron donating groups on it would be beneficial for the activity. Compounds 6d, 6n, and 4 had been chosen to be tested for their inhibition types against β-glucosidase. Interestingly, three compounds have different inhibition types although they had very similar structure. Their Ki values were calculated to be 0.02 ± 0.01 μM, 0.02 ± 0.01 μM, and 0.66 ± 0.14 μM, respectively. The equilibrium dissociation constant (KD) for 6d, 6n, and 4 and β-glucosidase was 0.04 μM, 0.03 μM and 0.45 μM by the ITC-based assay, respectively. Molecular docking work suggests that such benzimidazole-iminosugars derivatives might bind to the active site of β-glucosidase mainly through hydrogen bonds, the additional phenyl ring towards the solvent-exposed region played an important effect on their inhibitory activity against β-glucosidase.

Endowing deep-red BODIPY luminophors with enhanced aggregation-induced emission by installing miniature rotor of trifluoromethyl for solution-processed OLEDs

Highly efficient deep-red (DR) organic materials in aggregated state are fundamentally restricted by the serious nonradiative decay rates (k nr ) due to the energy gap law, and the aggregation induced quenching in view of significant intermolecular interaction. Here, two new BODIPY chromophores owning donor−acceptor−donor (D−A−D) structure, namely CF 3 -2TPA and 2CF 3 -2TPA, were designed and synthesized. Trifluoromethyl (CF 3 )-substituted phenyl group was introduced to the meso-position of the BODIPY core, tuning red to DR emission and suppressing intermolecular interaction with the utilization of the steric hindrance of CF 3 . Besides, CF 3 -2TPA and 2CF 3 -2TPA show enhanced aggregation-induced emission (AIE) characteristic, which was ascribed to the CF 3 rotor dissipating the excited-state energy. The OLEDs are fabricated by combining a thermally assisted delayed fluorescence host with a deep-red dye, showing a DR cut-on wavelength of 668 nm and external quantum efficiency of 2.3%. This work provided a rotor strategy to convert BODIPY molecule with obvious AIE property, providing their promising applications in DR-OLEDs. The miniature rotor of trifluoromethyl (CF 3 ) introduced to the meso-position of BODIPY, induced redshifted to deep-red emission, prevented obvious intermolecular interaction and achieved remarkably enhanced aggregation induced emission feature. Deep-red OLED showed an emission wavelength of 668 nm and an EQE max of 2.3%. • The CF 3 units, modifying the meso position of BODIPY, assisted in the deep-red emission. • Depending on the steric hindrance of CF 3 groups, the intermolecular interaction and packing were suppressed. • The enhanced AIE feature of BODIPYs was realized due to the miniature rotor of CF 3 substitutes. • Deep-red OLED showed an emission wavelength of 668 nm and an external quantum efficiency of 2.3%.

Synthesis, optical properties and self-organization of blue-emitting butterfly-shaped dithienobenzosiloles

Ten novel butterfly-shaped dithienobenzosilole-based luminogens, which are peripherally installed with a variety of substituents including hydrogen, phenyl and substituted phenyl groups, have been readily prepared via an iodine-induced intramolecular electrophilic double-cyclisation reaction and subsequent deiodination or coupling reactions. The optical and electrochemical properties of these compounds were systematically investigated to clarify the relationships between their structures and properties, supported by theoretical calculations. These compounds exhibit deep-blue to sky-blue emissions and high photoluminescence quantum yields up to 0.84 in solution and solid states which are regulated by the functional blades and their steric hindrance on the α– and β–positions of thiophene rings. Their high thermal- and photo- stabilities have been revealed and mainly attributed to the dithienobenzosilole core.

Nickel‐Catalyzed Decarbonylative Cycloaddition of Benzofuran‐2,3‐diones with Alkynes to Flavones

AbstractUsing dppe as the ligand, the Nickel‐catalyzed decarbonylative cycloaddition of benzofuran‐2,3‐diones with alkynes was established, and a variety of functional flavones were synthesized in 65–99% yields. Terminal alkynes with substituted phenyl groups and internal alkynes such as aryl acyl acetylenes and diphenylacetylenes are suitable for this reaction. The effects of bases on the reactions of different types of alkyne substrates were also investigated and discussed.magnified image

2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies

• 2-methylindole analogs were designed, synthesized and characterized. • The target 2-methylindole analogs ( 4a–4j ) were evaluated for their inhibitory potential against glutathione S-transferase (GST), acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory activities. • Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interactions at the active pocket site of the receptors. • The pharmacokinetic studies of 2-methylindole analogs were carried out using SwissADMET analyses. In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assessing enzyme inhibitory activity against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), (iii) predict ADMET and pharmacokinetic properties of the synthesized 2-methylindole analogs, (iv) reveal the possible interactions between the synthesized 2-methylindole analogs with GST, AChE, and BChE enzymes using several molecular docking software. In vitro enzyme inhibition assays showed that the synthesized indole analogs exhibited moderate to good inhibitory activities against GST, AChE, and BChE enzymes. Briefly, the inhibitory activities of the analogs 4b and 4i against AChE, 4a and 4b against BChE, and analogs 1 and 4i against GST were detected to be higher or close to the standard inhibitor compounds. The analog 4b was detected to have the best inhibitory activity against both AChE and BChE enzymes with the lowest IC 50 values as 0.648 µM for AChE and 0.745 µM for BChE. The analyses of enzyme inhibition relationship with the synthesized analogs could help to design new analogs for the inhibitors of cholinergic and glutathione pathways based on the indole derivatives.