Aniline Moiety Research Articles

Electrografting and electropolymerization of nanoarrays of PANI filaments through silica mesochannels

Vertically aligned mesoporous silica films electrogenerated on indium-tin oxide (ITO) electrodes are used as hard templates for the electrochemical growth of polyaniline (PANI) nanofilaments. To ensure proper adhesion of PANI to the underlying ITO surface, aniline moieties are first covalently attached to the bottom of mesochannels via electrografting of aminophenyl diazonium cations, serving in a second step as precursors for PANI growth by electropolymerization of aniline through the silica mesochannels. This was achieved by cyclic voltammetry or potentiostatically at an applied potential of +0.85 V (vs. Ag/AgCl), the latter offering a better control of the nanofilaments length by tuning the electropolymerization time. PANI wires remain attached to ITO after etching of the silica membrane, confirming the importance of initial electrografting. Although PANI nanofilaments in the silica membrane remain electroactive, enhanced peak currents were observed after silica removal as PANI nanofilaments offer a larger effective surface area to the electrolyte solution.

Nitrite Detection: Ultrasensitive, Specific, and Rapid Fluorescence Turn‐On Nitrite Sensor Enabled by Precisely Modulated Fluorophore Binding (Adv. Sci. 24/2020)

In article number advs. 2002991, Xincun Dou and co-workers report the precise regulation of the benzothiazole (BT) binding sites, including the para-, meso-, and ortho-positions on the aniline moiety and the sensing performance toward nitrite. This unique design enables an ultra-sensitive, specific, and rapid response of ortho-BT to nitrite, and favors a robust green emission signal for on-site and semiquantitative nitrite detection.

Ultrasensitive, Specific, and Rapid Fluorescence Turn-On Nitrite Sensor Enabled by Precisely Modulated Fluorophore Binding.

The precise regulation of fluorophore binding sites in an organic probe is of great significance toward the design of fluorescent sensing materials with specific functions. In this study, a probe with specific fluorescence properties and nitrite detection ability is designed by precisely modulating benzothiazole binding sites. Only the fluorophore bond at the ortho‐position of the aniline moiety can specifically recognize nitrite, which ensures that the reaction products displays a robust green emission. The unique 2‐(2‐amino‐4‐carboxyphenyl) benzothiazole (ortho‐BT) shows superior nitrite detection performance, including a low detection limit (2.2 fg), rapid detection time (<5 s), and excellent specificity even in the presence of >40 types of strong redox active, colored substances, nitro compounds, and metal ions. Moreover, the probe is highly applicable for the rapid on‐site and semiquantitative measurement of nitrite. The proposed probe design strategy is expected to start a new frontier for the exploration of probe design methodology.

Polymerization mechanism of 1,3-benzoxazine catalyzed by PCl5 and rearrangement of chemical structures

Ring-opening polymerization of benzoxazine monomers is a complex process and various chemical structures including N,O-acetal structures, phenolic Mannich structures and arylamine Mannich structures are formed in polybenzoxazines. To understand the polymerization mechanism, the effects of temperature, time and solvent polarity on the polymerization routes, chemical structures and thermal properties were studied. It was discovered that the N,O-acetal structures and the phenoxy structures can be obtained in a low-polarity solvent like dichloromethane at low temperature (−20 °C) with the aid of PCl5, while the arylamine Mannich structures can be readily generated in polar solvent like N,N-Dimethylformamide at high temperature (>80 °C) in the presence of PCl5. However, the phenolic Mannich structures can be directly formed at high temperature (>180 °C) without any catalysts. Upon prolonging the reaction time or elevating the temperature, the phenoxy structures easily rearranged into the N,O-acetal structures or the arylamine Mannich structures. Further increasing the temperature will cause the arylamine Mannich structures to rearrange into the phenolic Mannich structures and even the phenolic methylene structures. Therefore, both phenoxy structures and N,O-acetal structures showed poor thermal stability; while the arylamine Mannich structures possessed lower initial decomposition temperature but higher char yield compared with the phenolic Mannich structures because of the formation of thermally unstable iminium ions and the anchoring of dangling aniline moieties.

Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity.

A series of novel 4-aminobenzofuroxan derivatives containing aromatic/aliphatic amines fragments was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan. The quantum chemistry calculations were performed to identify the factors affecting the regioselectivity of the reaction. The formation of 4-substituted isomer is favored both by its greater stability and the lower activation barrier. Antimicrobial activity of the obtained compounds has been evaluated and some of them were found to suppress effectively bacterial biofilm growth. Fungistatic activity of 4-aminobenzofuroxans were tested on two genetically distinct isolates of M. nivale. The effect of some benzofuroxan derivatives is likely to be more universal against different varieties of M. nivale compared with benzimidazole and carbendazim. Additionally, their anti-cancer activity in vitro has been tested. 4-aminofuroxans possessing aniline moiety showed a high selectivity towards MCF-7 and M-HeLa tumor cell lines. Moreover, they exhibit a significantly lower toxicity towards normal liver cells compared to Doxorubicin and Tamoxifen. Thus, benzofuroxans containing aromatic amines fragments in their structure are promising candidates for further development both as anti-cancer and anti-microbial agents.

Electrochemical Ring Expansion to Synthesize Medium-Sized Lactams Through C–C Bond Cleavage

Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products. Owing to the unfavorable enthalpic and entropic barriers during the transition sta...

An aniline trimer-based multifunctional sensor for colorimetric Fe3+, Cu2+ and Ag+ detection, and its complex for fluorescent sensing of L-tryptophan

The detection of metal ions and amino acids by the aniline oligomer-based receptor has not been reported yet, to the best of our knowledge. In this study, an efficient multifunctional cation-amino acid sensor (CAS) with aniline moiety and chiral thiourea binding site was synthesized by the reaction of aniline trimer and (S)-(+)-1-phenyl ethyl isothiocyanate. CAS can sense Fe3+, Cu2+, Ag+ ions, and L-tryptophan. These results can be recognized by the naked eye. The appropriate pH range for the quantitative analysis of Fe3+, Cu2+, and Ag+ by CAS in DMSO/water (30vol% water) was evaluated. The interaction between CCS and metal ions was analyzed by 1H NMR titration. The detection limits of CAS for the Cu2+, Ag+, and Fe3+ were 0.214, 0.099, and 0.147μM, respectively. Moreover, the CASCu2+ complex can act as a turn-on fluorescence sensor for L-tryptophan. On the contrary, there is no response upon the addition of other amino acids, such as L-histidine, L-proline, L-phenylalanine, L-threonine, L-methionine, L-tyrosine, and L-cystine to CASCu2+ complex.

Design, synthesis and molecular modeling studies of 2-styrylquinazoline derivatives as EGFR inhibitors and apoptosis inducers

Herein, we report the synthesis of novel 2-substituted styrylquinazolines conjugated with aniline or sulfonamide moieties, anticipated to act as potent anticancer therapeutic agents through preferential EGFR inhibition. In doing so, all the synthesized compounds were screened for their in vitro anticancer activities (nine subpanels) at the National Cancer Institute (NCI), USA. The resulting two most active anticancer compounds (7b and 8c) were then chemically manipulated to investigate feasible derivatives (12a-e and 15a-d). MTT cytotoxicity, in vitro cell free EGFR and anti-proliferative activity against EGFR/ A549 cell line evaluation for the most active broadly spectrum candidates (7a/b, 8c/e, 12b and 15d) was conducted. Promising results were obtained for the styrylquinazoline-benzenesulfonamide derivative 8c (IC50 = 8.62 µM, 0.190 µM and = 79.25%), if compared to lapatanib (IC50 = 11.98 µM, 0.190 µM, and 79.25%), respectively. Moreover, its apoptotic induction potential was studied through cell cycle analysis, Annexin-V and caspase-3 activation assays. Results showed a clear cell arrest at G2/M phase, a late apoptotic increase (76 folds) and a fruitful caspase-3 expression change (8 folds), compared to the control. Finally, molecular docking studies of compounds 7a/b, 8c/e, 12b and 15d revealed proper fitting into the active site of EGFR with a low binding energy score for compound 8c (−13.19 Kcal/mole), compared to lapatanib (−14.54 Kcal/mole).

Oligo(ethylene glycol) (OEG) functionalized 2-(2′-Hydroxy benzofuranyl) benzoxazole (HBBO) derivatives: Synthesis, photophysical properties and biomolecules binding studies

Two molecular fluorophores based on a 2-(2′-Hydroxybenzofuranyl) benzoxazole (HBBO) scaffold and presenting an Excited-State Intramolecular Proton Transfer (ESIPT) process are reported herein. These dyes incorporate strongly electrodonating aromatic amino groups on the benzofuranyl side, enabling the appearance of a dual fluorescence emission corresponding to the radiative decay of the excited enol (E*) and keto (K*) tautomers at high and low energy respectively. It was previously demonstrated that dual E*/K* emission could originate from a beneficial decrease of phenolic acidity upon absorption of light leading to a thermodynamic stabilization of the first excited-state. The innovation within these dyes lies in the double functionalization of the aniline moiety with 2-(2-methoxyethoxy)ethyl units which allowed a better solubilization in protic solvents, as compared to their butyl analogs while keeping strong electrodonating capacity. Their intrinsic amphiphilic character leads to a good vectorization in a wide range of solvents from toluene to PBS buffer. The investigation of the photophysical properties of these dyes in solution showed a clear dual emission in apolar solvents with the E* band gradually red-shifting along with the dipole moment of the solvent. Dual emission is also observed in the solid-state when these dyes are doped as 1% wt in PMMA or PS films. Finally, the interactions of one dye with calf-thymus (ct)-DNA and Bovine Serum Albumin (BSA) have been explored and reveal pronounced modifications of the UV–Vis profile of the dye. Additionally, a gradual hypsofluorochromic shift and narrowing of the K* band along with the appearance of the E* fluorescence band upon addition of ct-DNA or BSA is also observed, presumably evidencing an intercalation mode of binding.

Design and efficient synthesis of novel vitamin D analogues bearing an aniline moiety in their side chains

Six novel vitamin D analogues bearing an aniline moiety in their side chains were designed and synthesized using a convergent route. The CD ring fragments were prepared from Inhoffen-Lythgoe diol in five- or six-steps with high yields. Secondary amines were obtained via a one-pot, two-step transformation with excellent yields.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Copper‐Catalyzed Modular Access to N‐Fused Polycyclic Indoles and 5‐Aroyl‐pyrrol‐2‐ones via Intramolecular N—H/C—H Annulation with Alkynes: Scope and Mechanism Probes

Summary of main observation and conclusionCopper‐catalyzed intramolecular N—H/C—H annulation with alkynes has been developed. A variety of densely functionalized heterocycles, such as pyrrolo[1,2‐a]indoles, indolo[1,2‐c]quinazolin‐2‐ones, oxazolo[3,4‐a]indoles, and imidazo[1,5‐a]indoles, were synthesized in an atom‐ and step‐economical manner, owing to the high modularized feature of aniline moiety, the linker moiety, as well as the alkyne moiety. By simply changing the oxidant from di‐tert‐butyl peroxide (DTBP) to 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO), the reaction could readily be transformed to the aminooxygenation pathway, which grabs one oxygen atom from the TEMPO to generate 5‐aroyl‐pyrrol‐2‐ones. Mechanistic experiments indicate that vinyl radical is involved in this reaction and an amidyl‐radical‐initiated radical cascade might be responsible for this transformation.

Degradation of sulfamethoxazole by Co3O4-palygorskite composites activated peroxymonosulfate oxidation

In this study, a simple hydrothermal method was used to synthesize Co3O4-palygorskite composites. Transmission electron microscopy, X-ray spectroscopy and X-ray diffraction analysis showed that Co3O4 nanoparticles with diameters of approximately 3–5 nm were uniformly distributed on the surface of palygorskite fibers. Co3O4-palygorskite composites were outstanding catalyst for activating peroxymonosulfate (PMS) to degrade the antibiotic sulfamethoxazole (SMX). Complete removal of 30 μM SMX at pH 3–5 was achieved with doses of 0.3 mM PMS and 125 mg/L Co3O4-palygorskite composites. The composites exhibited higher catalytical activity than unsupported Co3O4. The removal rate of SMX was accelerated under acidic conditions (pH 3–5), while was significantly inhibited under basic conditions (pH 11–12). Radical quenching tests revealed that SO4− and OH were responsible for the degradation. The oxidative degradation was initiated at either isoxazole or aniline moiety of the SMX molecule. Using solid phase extraction-liquid chromatography-time-of-flight-tandem mass spectrometry, a total of six transformation products formed from benzene ring hydroxylation, S-N bond cleavage, aniline moiety oxidation and coupling reactions were identified. Based on the products, three transformation pathways are proposed for the catalytic degradation of SMX in the Co3O4-palygorskite/PMS system.

Small molecules block the interaction between porcine reproductive and respiratory syndrome virus and CD163 receptor and the infection of pig cells

BackgroundPorcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the pork industry globally. PRRS is caused by PRRS virus (PRRSV). Currently there are no effective treatments against this swine disease.MethodsThrough artificial intelligence molecular screening, we obtained a set of small molecule compounds predicted to target the scavenger receptor cysteine-rich domain 5 (SRCR5) of CD163, which is a cell surface receptor specific for PRRSV infection. These compounds were screened using a cell-based bimolecular fluorescence complementation (BiFC) assay, and the function of positive hit was further evaluated and validated by PRRSV-infection assay using porcine alveolar macrophages (PAMs).ResultsUsing the BiFC assay, we identified one compound with previously unverified function, 4-Fluoro-2-methyl-N-[3-(3-morpholin-4-ylsulfonylanilino)quinoxalin-2-yl]benzenesulfonamide (designated here as B7), that significantly inhibits the interaction between the PRRSV glycoprotein (GP2a or GP4) and the CD163-SRCR5 domain. We further demonstrated that compound B7 inhibits PRRSV infection of PAMs, the primary target of PRRSV in a dose-dependent manner. B7 significantly inhibited the infection caused by both type I and type II PRRSV strains. Further comparison and functional evaluation of chemical compounds structurally related to B7 revealed that the 3-(morpholinosulfonyl)aniline moiety of B7 or the 3-(piperidinylsulfonyl)aniline moiety in a B7 analogue is important for the inhibitory function against PRRSV infection.ConclusionsOur study identified a novel strategy to potentially prevent PRRSV infection in pigs by blocking the PRRSV-CD163 interaction with small molecules.

A long-wavelength turn-on fluorescent probe for intracellular nanomolar level peroxynitrite sensing with second-level response

As a typical kind of endogenous reactive nitrogen species, peroxynitrite (ONOO−) is believed heavily involved in the pathogenesis of many diseases such as inflammation, neurodegenerative conditions, and cardiovascular disorders. Precisely estimating ONOO− level in cell compartments is crucial for unraveling the biological relevance of ONOO− and enabling effective control of ONOO−-associated pathogenicity but suffers from serious difficulty owing to the daunting elusive features of ONOO−, namely nanomolar level physiological concentration and millisecond level biological half-life. A new fluorescent probe capable of detecting ONOO− with limit of detection down to 1.2 nM, response time less than 1s, and high recognition specificity over other similarly interfering species was developed in this work. For the probe constructed by conjugating an isatin moiety with an electron-withdrawing tricyanofuran (TCF) moiety, the former enabled a highly selective ONOO−-mediated oxidative decarbonylation reaction while the latter significantly improved the electrophilicity of the 3-position carbonyl group of isatin moiety and therefore accelerate the ONOO−-mediated nucleophilic attack, which eventually enabled prompt and efficient recognition reaction. For the decarbonylated product featured with a released primary aniline moiety, TCF acted as an acceptor for enabling an intramolecular charge transfer (ICT) process and the remarkable change in electronic feature upon reaction with ONOO−, which generated turn-on fluorescence with large contrast and therefore the basis for ONOO− sensing. The cell fluorescence imaging performed in this work definitely verified the capability of the probe for mapping intracellular ONOO−, despite the daunting elusive features of such physiological species.

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions.

A simple photocatalytic method was developed for the synthesis of unsymmetrical 1,2-diamines by the unprecedented reductive coupling of N-benzylidene-[1,1'-biphenyl]-2-amines with an aliphatic amine. The presence of a phenyl substituent in the aniline moiety of the substrate was critical for the reactivity. The reaction proceeded via radical–radical cross-coupling of α-amino radicals generated by proton-coupled single-electron transfer in the presence of an Ir photocatalyst. On the other hand, symmetrical 1,2-diamines were selectively produced from the same starting materials by the judicious choice of the reaction conditions, showcasing the distinct reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines. The developed method can be employed for the synthesis of various bulky vicinal diamines, which are potential ligands in stereoselective synthesis.

Copper(II) complexes containing N′-aromatic group substituted N,N′,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amines: Synthesis, structures, polymerization of methyl methacrylate and ring opening polymerization of rac-lactide

A series of Cu(II) complexes, [LnCuCl2] (Ln = LA–LF), supported by N′-aromatic-group-substituted N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methylamine ligands have been synthesized. Variations of substituents at the ortho position of the aniline moiety influenced the solid-state structures of these complexes. The X-ray structures of [LnCuCl2] (Ln = LA–LC and LF) revealed that ligands are coordinated in a N,N,N-tridentate fashion to Cu(II) center and adopted a distorted square-pyramidal geometry, while [LDCuCl2] with N,N-bidentate coordination adopts distorted tetrahedral geometry. These complexes were capable of polymerizing methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO), with [LFCuCl2] displaying the highest activity (2.81 × 104 g PMMA (mol Cu)−1h−1). Regardless of ligand architecture, syndio-enriched PMMAs have been furnished with a slightly broader polydispersity index (PDI). Additionally, the in situ generated dimethyl derivatives, polymerized rac-LA and furnished PLA with mediocre heterotacticities at room temperature. Importantly, the catalytic efficiencies of the Cu(II) complexes studied have been found to be influenced by the steric and electronic properties of ligand.

5-Aryl-2,2′-bipyridines bearing fluorinated anilines residues at C6 position: synthesis and photophysical properties

A convenient synthetic approach to 5-aryl-2,2′-bipyridines bearing a (poly)fluorine-containing aniline residue at position C6 based on sequential ipso-substitution of the cyano group at position C5 of 3-(2-pyridyl)-1,2,4-triazines and the aza-Diels–Alder reaction has been proposed. The influence of the number and the position of the fluorine atoms on the reactivity of fluoroanilines has been estimated by means of DFT calculations. It was shown that the reaction cannot be realized if a nitro group is present in the ortho-position or two fluorine atoms occupied the ortho-positions in aniline. Photophysical properties of prospective “push–pull” fluorophores have been studied. Incorporation of fluorine atom into position 4 of aniline fragment in 5-p-tolylbipyridines causes small bathochromic shift of emission maximum, whereas the replacement of the methoxy group at the position C4 of the aniline moiety in 5-(4-methoxyphenyl)-2,2′-bipyridine with fluorine atom leads to a significant hypsochromic shift of emission maximum and to significant increase in quantum yield; the positive solvatochromism has been observed.

Synthesis, Characterization of sym-2,4,6-trisubstituted-s-Triazine Derivatives and Their Effects on Flame Retardancy of Polypropylene Composites

Polypropylene (PP) is flammable material, which brings latent danger to the environment and human society. Therefore, developing new environmentally friendly and effective flame-retardant is one of the most important ways to improve the flame retardancy of PP and improve safety during its lifetime. Herein, we describe the synthesis of five sym-2,4,6-trisubstituted-s-triazine derivatives, namely, N2,N4,N6-triphenyl-1,3,5-triazine-2,4,6-triamine (TAT), N2,N4,N6-tris(4-bromophenyl)-1,3,5-triazine-2,4,6-triamine (TBAT), N2,N4,N6-tris(4-chlorophenyl)-1,3,5-triazine-2,4,6-triamine (TCAT), 4,4′,4″-((1,3,5-triazine-2,4,6-triyl) tris(azanediyl)) triphenol (THAT), and N2,N4,N6-tris(4-methoxyphenyl)-1,3,5-triazine-2,4,6-triamine (TMAT), from the reaction of cyanuric chloride and p-substituted aniline employing conventional heating or microwave irradiation. The prepared compounds characterized by different techniques, such as Fourier-transform infrared (FTIR), Ultra-Violet and Visible (UV-Vis), Nuclear Magnetic Resonance spectroscopy (1H-NMR and 13C-NMR), Thermogravimetric Analysis (TGA), and differential scanning calorimetry (DSC). The effect of substituent on the aniline moiety has great impact on its thermal stability, as observed from the TGA and DSC data. Based on the TGA and DSC results, three triazine derivatives TAT, TBAT, and TMAT were used as charring agents in the presence of different proportions of ammonium polyphosphate (APP) to form an intumescent flame-retardant (IFR) system, to improve the flame retardancy of PP. The flammability property of PP was investigated by a vertical burning test (UL94). The results of UL94 revealed that the TXAT/APP (IFR) system influence the PP and could improve the flame retardancy of PP. Best results were obtained with the mass ratio of APP and TXAT 2:1. When the IFR loading was 25 wt%, it displayed great influence and passed V-0 with TMAT, and V-1 with both TAT and TBAT in the UL94 test.

N-Acylcarbazole as a Selective Transamidation Reagent

Abstract N-acylation reaction offers an opportunity to develop an efficient synthesis of amide group-containing molecules. We found that N-acyl carbazoles showed remarkable selectivity in transamidation. Sterically less hindered primary amines are selectively acylated with N-acyl carbazoles without any additives. Various functional groups such as alcohol, phenol, indole, and aniline moieties are tolerated under mild conditions. The synthetic utility was displayed in one-pot synthesis of an N-acyl polyamine natural product. The terminal amines of spermidine were selectively benzoylated with N-benzoyl carbazole, followed by acetylation reaction accomplished the total synthesis in a highly efficient manner.