Acrylonitrile Moiety Research Articles

Design and Synthesis of Novel HIV-1 NNRTIs with Bicyclic Cores and with Improved Physicochemical Properties.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent cornerstones of current regimens for treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, NNRTIs usually suffer from low aqueous solubility and the emergence of resistant viral strains. In the present work, novel bicyclic NNRTIs derived from etravirine (ETV) and rilpivirine (RPV), bearing modified purine, tetrahydropteridine, and pyrimidodiazepine cores, were designed and prepared. Compounds 2, 4, and 6 carrying the acrylonitrile moiety displayed single-digit nanomolar activities against the wild-type (WT) virus (EC50 = 2.5, 2.7, and 3.0 nM, respectively), where the low nanomolar activity was retained against HXB2 (EC50 = 2.2-2.8 nM) and the K103N and Y181C mutated strains (fold change, 1.2-6.7×). Most importantly, compound 2 exhibited significantly improved phosphate-buffered saline solubility (10.4 μM) compared to ETV and RPV (≪1 μM). Additionally, the binding modes of compounds 2, 4, and 6 to the reverse transcriptase were studied by X-ray crystallography.

Polyacrylonitrile-containing amphiphilic block copolymers: self-assembly and porous membrane formation

Porous nanostructures were derived after self-assembly of amphiphilic poly(acrylonitrile)-containing block copolymers. The introduction of acrylonitrile moieties within the membrane matrix was shown to improve the membranes’ mechanical properties.

Crystal structure of 2-(benzo[d]thia-zol-2-yl)-3,3-bis-(ethyl-sulfan-yl)acrylo-nitrile.

In the title compound, C14H14N2S3, the double-bond system of the acrylo-nitrile moiety is significantly non-planar, with absolute cis torsion angles of 13.9 (2) and 15.1 (2)°. The ring system and the double bond system subtend an inter-planar angle of 11.16 (4)°. The wide angle C-C(CN)=C of 129.40 (12)° may be associated with a balance between planarity and avoidance of a very short S⋯S contact.

Discovery of Sortase A covalent inhibitors with benzofuranene cyanide structures as potential antibacterial agents against Staphylococcus aureus

Sortase A (SrtA) is a cysteine transpeptidase of most gram-positive bacteria that is responsible for the anchoring of many surface protein virulence factors to the cell wall. SrtA ablation has demonstrated to alleviate the infection without affecting the viability of bacteria. Herein, a series of benzofuran cyanide derivatives were synthesized and evaluated. Several compounds exhibited excellent inhibitory activity against SrtA with IC50 values from 3.3 μM to 21.8 μM compared with the known SrtA inhibitor pHMB (IC50 = 130 μM). Ⅲ-1, Ⅲ-15, Ⅲ-34 and V-1 showed potent inhibitory effects on biofilm formation with IC50 values from 2.1 μM to 54.2 μM. Invasion assays showed the four compounds caused a decrease of 4%–24.0% in the uptake of the S. aureus strain by 293T cells. Further assay showed that compound Ⅲ-15 decreased the amount of cell wall-associated protein A by 26.5%. Structure-activity relationship and docking studies demonstrated that the acrylonitrile moiety of the compounds played an important role in enhancing the activity. When the double bond of acrylonitrile changed to single bond, the activity was decreased significantly. This indicates that acrylonitrile, which is a Michael receptor, can inhibit the activity of SrtA by covalent binding effectively to the thiol group of Cys184.

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives.

Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.

Adjustment of electronic and emissive properties of indolocarbazoles for non-doped OLEDs and cholesteric liquid crystal lasers

Derivatives of indolo[3,2-b]carbazole containing differently substituted triphenyl ethenyl moieties were synthesized and characterized as multifunctional materials for optoelectronic devices. A structure-properties relationship of the compounds was studied. Alteration of the substituents of triphenyl ethenyl moiety (H-, Ph-, CN-) afforded to modify thermal, photophysical and charge-transporting properties of the compounds. The synthesized compounds demonstrated high thermal stability with the 5% weight loss temperatures reaching 453 °C. Indolo[3,2-b]carbazoles mono- and disubstituted with tetraphenyl ethenyl groups exhibited polymorphism with two melting peaks at 211/216 °C and 236/245 °C, respectively. Modification of the substitution pattern resulted in the changes of emission of the solid films from blue centered at 471 nm to yellow peaking at 583 nm. Addition of the tetraphenylethylene and triphenyl acrylonitrile fragments resulted in aggregation induced emission (AIE) or aggregation enhanced emission (AEE). The solutions of AIE/AEE-active compounds exhibited low photoluminescence quantum yields which did not reach 1%, while the solid films demonstrated the highly boosted values of 23–35%. Hole mobilities of ca. 10−3 cm2/V × s were observed for tri(tetra)phenyl ethenyl substituted indolo[3,2-b]carbazoles compounds. The compounds containing acrylonitrile moieties exhibited bipolar charge transport with drift mobilities of ca. 10−5 cm2/V × s. The synthesized compounds showed promising electroluminescent properties as fluorescent emitters. OLEDs containing these emitters showed maximum external fluorescent quantum efficiency up to 3.0% and maximum brightness up to 18 800 cd/m2. They also demonstrated lasing properties. Using the most promising compound dissolved in cholesteric liquid crystal, laser beam at 515 nm with full width at half maximum of ca. 3.5 nm was generated.

Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates.

An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to an acrylate or acrylonitrile aza-Michael acceptor as well as an aromatic ring activated toward SNAr ring closure. A control experiment established that the initial reaction was an SN2′-type displacement of the side chain acetate by the amine to generate the alkene product with the added nitrogen nucleophile positioned trans to the SNAr aromatic ring acceptor. Thus, equilibration of the initial alkene geometry is required prior to cyclization. A further double bond migration was observed for several reactions targeting dihydronaphthyridines from substrates with a side chain acrylonitrile moiety. MBH acetates incorporating a 2,5-difluorophenyl moiety were found to have dual reactivity in these annulations. In the absence of O2, the expected dihydroquinolines were formed, while in the presence of O2, quinolones were produced. All of the products were isolated in good to excellent yields (72–93%). Numerous cases (42) are reported, and mechanisms are discussed.

Single-chain polymer nanoparticles carried cuprous catalysts

A feasible method to prepare single-chain polymer nanoparticles (SCNPs) loading metal catalysts via intramolecular collapse of the linear polymers is proposed. Styrene sulfonyl azide/acrylonitrile copolymers are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Acrylonitrile moieties in the copolymers can adsorb cupric ions and form SCNPs via the thermal decomposition of pendant sulfonyl azide and subsequent intramolecular cross-linking. Then L(+)-ascorbic acid sodium salt is used to reduce these cupric ions into cuprous nanoparticles in SCNPs. The mean diameter of composite SCNPs is in the range of 10–30 nm, in which cuprous moieties (diameter 5–10 nm) are implanted. The size of SCNPs has significant influences on the diameter of loaded cuprous moieties. It is indicated that these single-chain polymer nanoparticles carried cuprous exhibit better catalytic properties for the click reaction of alkyne and azide.

Thermally Activated Delayed Fluorescence Behavior Investigation in the Different Polarity Acceptor and Donor Molecules

To investigate the influence of intramolecular charge transfer (CT) characteristics, rigidity, and polarity of a molecule on photophysical properties, we designed and synthesized two types of thermally activated delayed fluorescence (TADF) emitters with malononitrile and acrylonitrile moieties as electron accepting units. Their photophysical properties such as singlet–triplet energy split (ΔEST), photoluminescence quantum yields (PLQYs), and electronic structures were theoretically and experimentally evaluated. Among the synthesized materials, the emitters with an acrylonitrile moiety as an acceptor and phenoxazine, dimethylacridine, and tert-butylcarbazole as a donor revealed small ΔEST values, good PLQYs, and efficient TADF performances. In contrast, the malononitrile derivatives demonstrated high ΔEST values, very low PLQYs, and relatively poor TADF performances even though they have strong intramolecular CT characteristics and high polarity. We found that high molecular polarity and strong intramolecular CT characteristics are not essential factors for attaining good TADF performances over molecular rigidity.

Synthesis of highly water selective copolymer membranes for pervaporative dehydration of acetonitrile

Pervaporative dehydration of highly concentrated (90–99.9%) acetonitrile needs a chemically resistant membrane having high water selectivity. Crosslinking is the usual practice of controlling excessive swelling in solvent and increasing selectivity of a hydrophilic membrane at the cost of flux. A membrane prepared from a copolymer of acrylonitrile and itaconic acid would be chemically resistant due to its acrylonitrile moiety and also hydrophilic due to the presence of bicarboxylic itaconic acid in its structure. Further, crosslinking is not required for preparing this copolymer membrane. Thus, in the present work several hydrophilic membranes were prepared by copolymerizing acrylonitrile (AN) and itaconic acid (IA) at varied molar ratios depending on their relative reactivity ratios. The structure of the copolymer was characterized by FT-IR, XRD and TG-DTA. The membranes prepared with an AN: IA molar ration of 15:1, 12:1 and 10:1 and noted as PANIA1, PANIA2 and PANIA3, respectively showed optimum properties, viz., mechanical stability, flux and selectivity. Thus, for 99wt% acetonitrile in feed at 30°C, these membranes showed a thickness normalized flux of 1.7, 1.8 and 1.9kgμm/m2h and a high water selectivity of 459, 429 and 409, respectively.

An aggregation-induced emission luminophore with multi-stimuli single- and two-photon fluorescence switching and large two-photon absorption cross section

A novel aggregation- and crystallization-induced emission luminophore (ENPOMe) containing tetraphenylethene and acrylonitrile moieties with high fluorescence efficiency (Φ(F) of up to 0.85) has been easily synthesized. ENPOMe has an exceptionally large two-photon absorption cross section (σ) of 5548 GM, and exhibits striking multi-stimuli-responsive single- and two-photon fluorescence switching with excellent reversibility in the solid state.

Central Nervous System Disposition and Metabolism of Fosdevirine (GSK2248761), a Non-Nucleoside Reverse Transcriptase Inhibitor: An LC-MS and Matrix-Assisted Laser Desorption/Ionization Imaging MS Investigation into Central Nervous System Toxicity

The CNS disposition and metabolism of Fosdevirine (FDV), an HIV non-nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV-1 treatment experienced study. In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies. LC-MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid (seizure patients, rabbit, and monkey) and brain homogenate (rabbit, minipig, and monkey). The application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) provided the spatial distribution of FDV and its metabolites in brain tissue (rabbit, minipig, and monkey). A cysteine conjugate metabolite resulting from an initial glutathione (GSH) Michael addition to the trans-phenyl acrylonitrile moiety of FDV was the predominant drug-related component in the samples from seizure patients, rabbits, and minipigs. This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs. Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS. In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter. On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity/seizures observed after FDV dosing.

(E)-2-(4-tert-Butylphenyl)-2-cyano-1-(3-methyl-1-vinyl-1H-pyrazol-5-yl)vinyl 2,2-dimethylpropanoate

In the title compound, C24H29N3O2, the dihedral angle between the benzene and pyrazole rings is 80.55 (7)°. The mol­ecule contains an acrylonitrile moiety and exists in an E conformation. Bioassay tests showed that the title compound exhibited higher acaricidal activity than its Z isomer.

Synthesis and in vitro antimicrobial activity of new 3-(2-morpholinoquinolin-3-yl) substituted acrylonitrile and propanenitrile derivatives

AbstractA series of new 3-(2-morpholinoquinolin-3-yl)acrylonitrile derivatives (IVa-IVf) has been synthesised by the base-catalysed condensation reaction of 2-morpholinoqionoline-3-carboxaldehydes (IIa-IIc) and 2-cyanomethylbenzimidazoles (IIIa-IIIb). Subsequent regiospecific reduction of the C—C double bond in acrylonitrile moiety afforded 3-(2-morpholinoquinolin-3-yl)propanenitrile derivatives (Va-Vf). All the compounds synthesised were subjected to in vitro antimicrobial screening against some representatives of bacteria and fungi. The majority of the compounds were found to be active against Gram-positive bacteria Bacillus subtilis and Clostridium tetani as well as against the fungal pathogen Candida albicans.

Synthesis and characterization of soft polymeric nanoparticles and composites with tunable properties

Polymeric particles comprising acrylonitrile (AN)-based core and acrylamide derivative–based shell in the submicron range with positive and negative charges were synthesized via microemulsion polymerization. 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) and 3-(acrylamidopropyl)-trimethyl ammonium chloride (APTMACl) were used as shell-forming charged monomers onto AN core for the synthesis of p(AN-co-AMPS) and p(AN-co-APTMACl), respectively, using an oil-in-water emulsion system. To tune the characteristics of the core–shell particles, AN moieties in the core were amidoximated to change the nature of the core from hydrophobic (nitrile) to hydrophilic (amidoxime) nature. Additionally, colloidal magnetite particles (Fe3O4) produced by chemical coprecipitation technique under alkaline and inert conditions were also included inside p(AN-co-AMPS) and p(AN-co-APTMACl) particles as dual-responsive nanocomposites against pH and magnetic field. With the magnetic properties, AN-based core with modifiable characteristics and acrylamide-based polyelectrolyte shells with variable charges and sizes were further used as drug carriers. For potential targeted drug delivery application of the synthesized soft particles and their composites Naproxen and Trimethoprim were used as model drugs, and he release studies were carried in phosphate buffer saline (pH = 7.4) at ambient temperature. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

ChemInform Abstract: Rearrangements and Intramolecular Diels—Alder Reactions of Normal and Vinylogous Aza‐Morita—Baylis—Hillman Products Leading to Isoindoline Derivatives.

AbstractThe reactions allow a convenient access to diverse substituted isoindoline derivatives.

Rearrangements and Intramolecular Diels−Alder Reactions of Normal and Vinylogous Aza-Morita−Baylis−Hillman Products Leading to Isoindoline Derivatives

Aza-Morita-Baylis-Hillman (aza-MBH) products derived from arylimines and methyl acrylate or acrylonitrile were N-alkylated with (E)-5-bromopenta-1,3-diene, and the resulting trienes were subjected to intramolecular Diels-Alder (IMDA) cyloadditions to afford the corresponding trans- and cis-fused tetrahydroisoindolines as the major and minor products, respectively. Catalysis with boron trichloride improved the IMDA diastereoselectivities of the nitrile derivatives, while yields were improved in both the nitrile and ester series. Treatment of the nitrile-substituted trienes with DABCO in DMF resulted in unexpected transposition of the N-(pentadienyl)sulfonamide group to the beta-position of the acrylonitrile moiety. Subsequent IMDA cycloadditions produced cis-fused positional isomers of the previous tetrahydroisoindolines. When the products of vinylogous aza-MBH reactions in the nitrile series were N-propargylated, the resulting dienynes underwent a similar transposition and IMDA reaction, producing trans and cis diastereomers of the corresponding dihydroisoindolines as the major and minor products, respectively. In all but one case, only the former products were observed in the presence of methylaluminum dichloride, while the corresponding aromatized isoindolines were obtained when the IMDA reactions were carried out in the presence of DDQ. Thus, a variety of aryl-substituted isoindoline products with different levels of unsaturation and complementary substitution patterns and stereochemistry are readily available through these processes.

The effect of distribution of monomer moiety on the pH response and mechanicalproperties of poly(acrylonitrile-co-acrylic acid) copolymers

The pH response and mechanical properties of copolymer-based hydrogels such aspoly(acrylonitrile-co-acrylic acid) are usually attributed to their chemical composition. In thisstudy, it has been shown that the architecture of the polymer chains, i.e. the distribution ofcomonomers in the macromolecules, also plays a major role in controlling these properties.A series of four poly(acrylonitrile-co-acrylic acids) with fixed composition (i.e. ∼30 mol% acrylic acid moieties) were synthesized, where the block lengths of both AN(acrylonitrile) and AAc (acrylic acid) moieties in the copolymers were varied by controllingthe feeding pattern of the monomers during free radical copolymerization. Thesecopolymers were then converted into fine fibers of the same dimensions. The monomerdistribution in the four copolymers was estimated using quantitative carbon 13C nuclear magnetic resonance (NMR) and related to the mechanical and pH responseproperties of the resultant fibers. The pH response of the fibers with similar compositionincreased dramatically as the block length of the AAc moiety was increased, while themechanical properties increased as a direct function of the block length of the AN moieties.The fiber’s response at pH 10 in terms of the change in length increased by∼four times while its responserate increased by ∼50 times with the increase in block length of the AAc moiety. On theother hand, the tensile properties and retractive stress increased by∼four times with the increase in the block length of the AN moiety.

Effects of Lewis acid-type transition metal chloride additives on the thermal degradation of ABS

The thermal degradation of ABS in the presence of Lewis acid-type transition metal chloride additives has been studied by thermogravimetric analysis. The reaction of transition metal chlorides (NiCl 2, CoCl 2, ZnCl 2 and FeCl 3) and ABS has been found to occur during the thermal degradation of ABS. In an inert atmosphere, char formation is observed, and some 10–30% of the reaction product is non-volatile at 600 °C. From model studies, it was found that the interaction of transition metal chloride and the acrylonitrile moieties of ABS at elevated temperatures leads to crosslinking of the polymer. The resulting enhancement of char formation in an inert atmosphere has been explained as a catalytic crosslinking effect of transition metal chloride compounds via a macroradical coupling mechanism. Although this crosslinking does not increase the threshold temperature for decomposition of ABS, it decreases the formation of flammable small molecules. On the other hand, transition metal chloride catalysed char formation of ABS in air was unsuccessful due to the oxidative degradation of the char at a higher temperature.

Separation of uranyl ions with amidoximated poly(acrylonitrile/N-vinylimidazole) complexing sorbents

Abstract Acrylonitrile (AN)/N-vinylimidazole (VIm) copolymeric hydrogels were synthesized by irradiating their binary mixtures. The AN moieties of copolymers were amidoximated using hydroxylamine hydrochloride in basic medium. The amidoximated hydrogels were used for separating uranyl ions from aqueous solutions by a complexation process. Uranyl ion adsorption studies were conducted from different UO22+ ion solutions (650–1850 ppm). The result of all UO22+ ion adsorption studies complied with the L-type isotherm. The adsorption capacity was found as high as 0.64 g UO22+ g−1 dry amidoximated copolymer.