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COVID-19 has caused severe consequences in terms of public health and economy worldwide since its outbreak in December 2019. SARS-CoV-2 3C-like protease (3CL pro ), crucial for the viral replications, is an attractive target for the development of antiviral drugs. In this study, several kinds of Michael acceptor warheads were utilized to hunt for potent covalent inhibitors against 3CL pro . Meanwhile, novel 3CL pro inhibitors with the P3-3,5-dichloro-4-(2-(dimethylamino)ethoxy)phenyl moiety were designed and synthesized which may form salt bridge with residue Glu166. Among them, two compounds 12b and 12c exhibited high inhibitory activities against SARS-CoV-2 3CL pro . Further investigations suggested that 12b with an acrylate warhead displayed potent activity against HCoV-OC43 (EC 50  = 97 nM) and SARS-CoV-2 replicon (EC 50  = 45 nM) and low cytotoxicity (CC 50  > 10 μM) in Huh7 cells. Taken together, this study devised two series of 3CL pro inhibitors and provided the potent SARS-CoV-2 3CL pro inhibitor (12b) which may be used for treating coronavirus infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study, it is aimed to prepare a polymer composite between styrene, acrylic acid, and ZnO and to measure the radiation shielding of the synthesized polymer composite. Firstly poly(styrene-co-acrylic acid) (P(S-co-AA)) copolymer was synthesized using the emulsion polymerization method between styrene and acrylic acid. Then, P(S-co-AA)-ZnO composites were prepared with different percentages of ZnO. For preparing these composites, the materials were mixed in a 60 °C ultrasonic bath. P(S-co-AA)-ZnO was poured into Petri dishes to form a film. When the TG curves were examined, it was not found a significant difference between the copolymer composite and the copolymer. The molecular weight of the copolymer was found to be 120000. SEM images show zinc fragments located between the polymer chains. The potential for radiation capture against gamma was determined using a NaI scintillation detector. The linear gamma attenuation coefficients for P(S-co-AA)-ZnO samples were calculated to Lambert's Beer Law and measured for 662 keV. Theoretical gamma attenuation coefficient values were calculated by multiplying the density of the composite with the mass attenuation coefficients. The absorption parameters of polymer composites are directly proportional to the increasing amount of zinc oxide. P(S-co-AA)-ZnO-15% was the best absorber at 662 keV energy compared to other polymer composites., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This work focuses on the extrusion of a brittle, tacky, cationic copolymer i.e. Eudragit® E-100 to prepare filament and subsequent 3D printing of hollow capsular device using the extruded filament. An optimum amount of talc and triethyl citrate was used for the possible extrusion of the polymer. There was no thermal and chemical degradation of the polymer observed after extrusion confirmed by DSC and FTIR analysis. Microscopic analysis of the printed capsule showed the layer-by-layer manner of 3D printing. Capsule parts were printed according to the set dimensions (00 size) with minimal deviation. Printed capsule showed the soluble behaviour in gastric fluid pH 1.2 where within 15 min the encapsulated drug encounters with the dissolution medium and almost 70% drug was dissolved within 4 hr. In case of phosphate buffer pH 6.8, the printed capsule showed a longed swelling behaviour up to 12 hr and then gradually bursting of capsule occurred wherein more than 90% encapsulated drug was dissolved within 36 hr. Enteric coating of the printed capsule showed similar behaviour in alkaline medium that observed with non-enteric capsule. This indicates the potential application of this printed capsules for both gastric and intestinal specific delayed drug delivery by a single step enteric coating process.

Protein crystallography (PX) is widely used to drive advanced stages of drug optimization or to discover medicinal chemistry starting points by fragment soaking. However, recent progress in PX could allow for a more integrated role into early drug discovery. Here, we demonstrate for the first time the interplay of high throughput synthesis and high throughput PX. We describe a practical multicomponent reaction approach to acrylamides and -esters from diverse building blocks suitable for mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding and to provide meaningful strategies for medicinal chemistry projects., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen ( 1 O 2 )-sensitive aminoacrylate linkers into amphiphilic mPEG- b -PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1 O 2 -responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NP BDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1 O 2 , which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NP BDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NP BDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

A rationally designed series of 2-(N-cyclicamino)quinolines coupled with methyl (E)-3-(2/3/4-aminophenyl)acrylates was synthesized and subjected to in vitro screening bioassays for potential antiplasmodial and antitrypanosomal activities against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum and nagana Trypanosoma brucei brucei 427, respectively. Substituent effects on activity were evaluated; meta-acrylate 24 and the ortho-acrylate 29 exhibited the highest antiplasmodial (IC 50  = 1.4 µM) and antitrypanosomal (IC 50  = 10.4 µM) activities, respectively. The activity against HeLa cells showed that the synthesized analogs are not cytotoxic at the maximum tested concentration. The ADME (absorption, distribution, metabolism, and excretion) drug-like properties of the synthesized compounds were predicted through the SwissADME software., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Donor-π-acceptor (D-π-A) fluorophores consisting of a donor unit, a π linker, and an acceptor moiety have attracted attention in the last decade. In this study, we report the synthesis, characterization, optical properties, TD-DFT, and cytotoxicity studies of 17 near infrared (NIR) D-π-A analogs which have not been reported so far to the best of our knowledge. These fluorophores have chloroacrylic acid as the acceptor unit and various donor units such as indole, benzothiazole, benzo[e]indole, and quinoline. The fluorophores showed strong absorption in the NIR (700-970 nm) region due to their enhanced intramolecular charge transfer (ICT) between chloroacrylic acid and the donor moieties connected with the Vilsmeier-Haack linker. The emission wavelength maxima of the fluorophores were in between 798 and 870 nm. Compound 20 with a 4-quinoline donor moiety showed an emission wavelength above 1000 nm in the NIR II window. The synthesized fluorophores were characterized by 1H NMR and 13C NMR, and their optical properties were studied. Time dependent density functional theory (TD-DFT) calculations showed that the charge transfer occurs from the donor groups (indole, benzothiazole, benzo[e]indole, and quinoline) to the acceptor chloroacrylic acid moiety. Fluorophores with [HOMO] to [LUMO+1] transitions were shown to possess a charge separation character. The cytotoxicity of selected fluorophores, 4, 7, 10 and 12 was investigated against breast cancer cell lines and they showed better activity than the anti-cancer agent docetaxel.

Herein, we report the synthesis and evaluation of novel analogues of UK-5099 both in vitro and in vivo for the development of mitochondrial pyruvate carrier (MPC) inhibitors to treat hair loss. A comprehensive understanding of the structure-activity relationship was obtained by varying four positions of the hit compound, namely, the alkyl group on the N1 position, substituents on the indole core, various aromatic and heteroaromatic core structures, and various Michael acceptors. The major discovery was that the inhibitors with a 3,5-bis(trifluoromethyl)benzyl group at the N1 position were shown to have much better activity than JXL001 (UK-5099) to increase cellular lactate production. Additionally, analogue JXL069 , possessing a 7-azaindole heterocycle, was also shown to have significant MPC inhibition activity, which further increases the chemical space for drug design. Finally, more than 10 analogues were tested on shaved mice by topical treatment and promoted obvious hair growth on mice.

A green approach has been developed for the synthesis of a series of benzylidene acrylate 3(a-p) from differently substituted aromatic/heterocyclic aldehydes and ethyl cyanoacetate in excellent yields (90-98%), and employing silica bonded N-(Propylcarbamoyl)sulfamic acid as a recyclable catalyst under solvent-free condition. The molecular structure of compounds 3b, 3d and 3i were well supported by single-crystal X-ray crystallographic analysis. The present protocol bears wide substrate tolerance and is believed to be more practical, efficient, eco-friendly, and compatible as compared to existing methods. In-silico approaches were implemented to find the biochemical and physiological effects, toxicity, and biological profiles of the synthesized compounds to determine the expected biological nature and confirm a drug-like compound. A molecular docking study of the expected biologically active compound was performed to know the hypothetically binding mode with the receptor. Also, reverse docking is applied to recognize receptors from unknown protein targets for drug-like compounds to explain poly-pharmacology and binding postures with different receptors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of novel phenyl methoxyacrylate derivatives containing a 2-alkenylthiopyrimidine substructure were designed, synthesized, and evaluated in terms of acaricidal activity. The structures of the title compounds were identified by 1 H NMR, 13 C NMR and high-resolution mass spectra (HRMS). Compound ( E )-methyl 2-(2-((2-(3,3-dichloroallylthio)-6-(trifluoromethyl)pyrimidin-4-yloxy)methyl)phenyl)-3-methoxyacr-ylate ( 4j ) exhibited significant acaricidal activity against Tetranychus cinnabarinus ( T. cinnabarinus ) in greenhouse tests possessing nearly twice the larvicidal and ovicidal activity compared to fluacrypyrim. Furthermore, the results of the field trials demonstrated that compound 4j could effectively control Panonychuscitri with long-lasting persistence and rapid action. The toxicology data in terms of LD 50 value confirmed that compound 4j has a relatively low acute toxicity to mammals, birds, and honeybees.

In this work, we report the preparation of a novel partially aminated and inexpensive water-soluble acrylic acid grafted activated carbon represented as C-g-AA-NH 2 for efficient inhibition of shale hydration. The as-prepared C-AA-NH 2 was subjected to Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR), and thermal gravimetric analysis (TGA). This was followed by an evaluation of the capability of the material to inhibit shale through various tests including anti-swelling, shale recovery, and immersion tests. Our results indicated that 2% of C-g-AA-NH 2 drastically reduced water invasion into shale by combining plugging property of the core-centered carbon nanoparticles with the inhibition ability of the partially aminated acrylic acid component by adsorption on the clay surface through hydrogen bonding. In this manner, the plugging of the pore throat of the interlayer spacing of the shale formation could easily be achieved. This approach could significantly control fluid loss, reduce permeability and filtrate volume of drilling mud by forming a thin film on the formation surface due to the nano-nature of the carbon component of the polymer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A new phosphine is proposed as efficient coinitiator for camphorquinone (CQ)-based photoinitiating systems for the free radical polymerization of (meth)acrylates. Remarkably, this new co-initiator can exhibit two functionalities: a phosphine moiety to overcome oxygen inhibition and an iodonium salt moiety as counter cation to initiate the polymerization process. Excellent polymerization performances in the presence of CQ for the free radical polymerization of methacrylates under blue light are observed, and amine-free systems can be easily developed from the proposed structure. The photopolymerization of composites is also investigated in the presence of the new phosphine (without iodonium counter cation) and very interesting depth of cure can be obtained from the new developed photoinitiating system after only 20 s of irradiation with a blue light-emitting diode., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study aimed to synthesize novel polymeric nanoparticles (NPs) bound with cisplatin for the treatment of oral cancer. The NPs were synthesized from N-vinylpyrrolidone (NVP) and acrylic acid (AA) using 2 different methods based on a surfactant-free emulsion polymerization reaction. An azo initiator (V 50 ) and bisacrylamide crosslinker were used in the reaction to create the NPs. The morphology, physicochemical characteristics, drug loading, and in vitro release were evaluated. Moreover, the cytotoxicity, death induction mechanism, and in vitro intracellular accumulation of cisplatin in HN22 cells were also investigated. Relatively spherical NPs with negative charge were obtained from both synthesis methods with the size in the range of 136-183 nm. The NPs were bound to cisplatin via coordination bond which was confirmed by FT-IR. The optimal NPs to cisplatin ratio was found to be 1:10 with %entrapment efficiency and loading capacity of 12-18% and 4 mmol/g, respectively. Approximately 47-83% of cisplatin was released from the NPs in 7 days in the presence of chloride ions depending on the pH of the release medium. The novel NPs from both methods were nontoxic to gingival fibroblast cells while the IC 50 values of cisplatin-loaded NPs on HN22 cells were just above 20 μg/mL. In addition, the cisplatin-loaded NPs demonstrated a higher percentage in the early apoptotic death mechanism. Higher cellular deposition of cisplatin at the earlier period was obtained by the cisplatin-loaded NPs suggesting a slower but safer cancer-killing effect. Therefore, these novel NPs may be promising nanocarriers of cisplatin for oral cancer treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel indole derivative (N-(1H-2-phenyl-indole-3-ylmethyl) acrylamide, NPI) synthesized by a Friedel-Crafts alkylation reaction was identified using IR spectroscopy, 1 H NMR, 13 C NMR and elemental analysis. The inhibitory effect of this novel indole derivative on bacteria and marine algae was studied. The results showed that the inhibition ratios of the indole derivative against Escherichia coli and Staphylococcus aureus were 95.93% and 94.91%, respectively, and the indole derivative possessed prominent inhibitory activity against Phaeodactylum tricornutum, Nitzschia Closterium and Skeletonema costatum. These findings indicate that the indole derivative has high biological activity. Subsequently, the indole derivative was introduced to acrylate resins by free-radical polymerization. The resulting acrylate resins were subjected to self-polishing, anti-algal and antifouling test, the results of which indicated that acrylate resins containing the synthesized indole derivative could exhibit significant antifouling properties because of the combination of the biofouling resistance of the indole derivative and the self-polishing properties of acrylate. This work provides an academic foundation for studying environmentally friendly and highly efficient antifouling coatings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A near-infrared (NIR) fluorescent probe (Cys-AN) for selective and sensitive detection of cysteine (Cys) was designed and synthesized. The fluorescent probe was water-soluble and had a large Stokes shift of 150 nm, whose detection limit could reach to 0.96 μM in PBS buffer. After we analyzed the HRMS, TLC and optical data, a proposed sensing mechanism for the detection of Cys could result from the Michael addition and intramolecular cyclization reactions between the probe and Cys, followed by intramolecular charge transfer (ICT) process to afford the NIR fluorescent signal at 674 nm. Meanwhile, Cys-AN exhibited low cytotoxicity, and was successfully applied for bioimaging of Cys in living cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We developed a photoacoustic and fluorescent dual-mode imaging probe, CCYS, for the detection of cysteine with high selectivity and sensitivity in a living system for the first time. By using CCYS, we found that the limited synthesis of glutathione in pulmonary fibrosis was not caused by cysteine deficiency.

A straightforward transformation protocol combining two distinct living polymerization methods for the controlled synthesis of block copolymers is described. In the first step, bromo-terminated poly(methyl methacrylate) is prepared by atom transfer radical polymerization (ATRP). Then, a bromide end group is substituted with a triphenylmethyl (trityl) functionality under visible light irradiation using dimanganese decacarbonyl (Mn 2 (CO) 10 ) photochemistry. The resulting polymers with trityl end groups are used as macroiniferter for the polymerization of styrene and tert-butyl acrylate (tBA) to yield desired block copolymers with narrow molecular weight distribution. Moreover, the amphiphilic copolymers with acrylic acid functionalities are obtained by the hydrolyzation of poly(tert-butyl acrylate) containing block copolymers with trifluoroacetic acid., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers. The noninvasive imaging of these MCTs in cancers is regarded to be advantageous for assessing MCT-mediated effects on chemotherapy and radiosensitization using specific MCT inhibitors. Herein, we describe a method for the radiosynthesis of [ 18 F]FACH ((E)-2-cyano-3-{4-[(3-[ 18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylic acid), as a novel radiolabeled MCT1/4 inhibitor for imaging with PET. A fluorinated analog of α-cyano-4-hydroxycinnamic acid (FACH) was synthesized, and the inhibition of MCT1 and MCT4 was measured via an L-[ 14 C]lactate uptake assay. Radiolabeling was performed by a two-step protocol comprising the radiosynthesis of the intermediate (E)/(Z)-[ 18 F]tert-Bu-FACH (tert-butyl (E)/(Z)-2-cyano-3-{4-[(3-[ 18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylate) followed by deprotection of the tert-butyl group. The radiofluorination was successfully implemented using either K[ 18 F]F-K 2.2.2 -carbonate or [ 18 F]TBAF. The final deprotected product [ 18 F]FACH was only obtained when [ 18 F]tert-Bu-FACH was formed by the latter procedure. After optimization of the deprotection reaction, [ 18 F]FACH was obtained in high radiochemical yields (39.6 ± 8.3%, end of bombardment (EOB) and radiochemical purity (greater than 98%)., (© 2019 John Wiley & Sons, Ltd.)

Based on conjugate addition-cyclization reaction of Cys with acrylate and subsequent 1,6-elimination of p-hydroxybenzyl moiety, a novel colorimetric and ratiometric fluorescent probe 1 was designed and synthesized. Upon addition of Cys to the solution of 1, the absorption spectra changed from 508 nm to 452 nm (Δ56 nm) and afforded visible color change from pink to yellow. Meanwhile, the emission spectra shifted from 644 nm to 539 nm (Δ105 nm) with remarkable changes in the emission ratio of F 539 nm /F 644 nm (R/R 0 up to 760-fold), accompanying with an obvious fluorescence change from orange to green under illumination with a 365 nm UV lamp. In addition, 1 exhibited a large Stokes shift (136 nm), high sensitivity (detection limit of 46.7 nM), and excellent selectivity to Cys over Hcy and GSH. Moreover, 1 can discriminate Cys from Hcy and GSH by fluorescence spectra, even obvious visible and fluorescence color changes. Importantly, 1 can be used to image Cys in living cells by dual emission channels., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play many crucial physiological roles in organisms. Their abnormal levels can cause and indicate various diseases. In the present study, a small-molecule fluorescent probe 2-(imidazo[1,2-a]pyridin-2-yl)phenyl acrylate (IPPA) was designed, synthesized and characterized by NMR, FT-IR and HRMS. IPPA can selectively detect Cys over other analytes because of an approximately 76 times enhancement in fluorescence intensity. The limit of detection of IPPA for Cys was 0.33 μM. The pseudo-first-order rate constant of the reaction between IPPA and Cys was approximately 10 times that of the reaction between IPPA and Hcy (K Cys 3.18 × 10 -3  S -1 vs K Hcy 4.92 × 10 -4  S -1 ), indicating that Cys can be distinguished from Hcy. In addition, IPPA exhibits strong anti-interference ability, small molecular weight, high efficiency, low toxicity and good cell permeability. It was successfully used in imaging HepG2 cells and zebrafish. The fluorescence response of IPPA for calf serum are powerful proofs for practical application. Therefore, IPPA has high potential for bioassay applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The application range of hydrogels can be greatly widened by improving their mechanical properties. It is still a great challenge to develop hydrogels with good mechanical properties, reliable self-healing properties and remolding ability at the same time. Inspired by biological soft tissue with excellent mechanical properties and self-healing properties, here, a facile method to fabricate poly (styrene-acrylic acid) (P(S-AA)) core-shell nanoparticles with plenty of carboxyl groups on their surface, and their enhancement to hydrophobic association hydrogels was reported. Under stress, the dynamic physical bonds including hydrogen bonding between polymer chains and P(S-AA) core-shell nanoparticles (NPs), and entanglement of hydrophobic chains were destroyed to effectively dissipate energy, and uniform hydrogel network leads to smooth stress-transfer, which makes the core-shell nanoparticles composite hydrophobic association hydrogels (MHA gels) excellent mechanical properties, such as excellent mechanical properties, toughness and ductility, and good self-healing properties as well. These features make the MHA gels have great potential in biomedical applications such as tissue engineering, articular cartilage and artificial skin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this paper, feruloylated bagasse xylan (FBX) was synthesized with a method based on homogeneous catalytic esterification of bagasse xylan (BX) with ferulic acid (FA) in the presence of triethylamine as a catalyst, and it was further grafted with methacrylic acid (MAA) and butyl acrylate (BA) to synthesize FBX-g-MAA/BA grafted copolymer by using ammonium persulfate as initiator and N,N-methylene acrylamide as cross-linker. The effects of reaction variables including reaction time, temperature and reactant concentration on the esterification and graft reactions were investigated carefully by conducting orthogonal tests. A maximum degree of substitution (DS) of 1.76 for the esterification and a maximum graft ratio (GR) of 31% can be achieved by performing the reaction at optimized reaction parameters. The molecular docking was further performed to study the binding mode of the final product into the active site of human Caprin-2 C1q domain (4OUM, cause gastric cancer protein), liver cancer protein (1UV0) and lung cancer protein (3B9S). The software generated results were in satisfactory agreement with the evaluated biological activity. The anticancer performances of BX, FBX and FBX-g-MAA/BA copolymer were investigated by using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) method. The results indicated that the inhibition ratio of FBX-g-MAA/BA copolymer on BEL-7407 (liver cancer cells) can reach 25.28% ± 4.01%, which is two times higher than that of BX., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A hypervalent (HV) iodine(III)-containing crosslinker, (diacryloyloxyiodo)benzene, is synthesized and its crystal structure is reported. Highly branched polymers with hypervalent iodine(III) groups as the building blocks present at the branching points are synthesized by copolymerization of tert-butyl acrylate and the diacrylate crosslinker (up to 12 mol% vs the monovinyl monomer), under reversible deactivation radical polymerization (iodine transfer polymerization) conditions, which are employed to ensure that the incorporation of the crosslinker into the polymer chains is slow and gradual, that is, to limit the average number of pendant double bonds per chain and delay gelation. The branched polymers with (diacyloxyiodo)benzene-type linkers are responsive and react with monocarboxylic acids, for example, acetic acid, which participate in ligand-exchange reactions with the HV iodine(III) centers, and with reducing agents, for example, tributylphosphine, which reduce iodine(III) to iodine(I); both reactions lead to polymer degradation with the formation of random linear copolymers of tert-butyl acrylate and acrylic acid., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of novel 3-aryl-4-hydroxy-2(5 H ) furanone-acrylate hybrids were designed and synthesized based on the natural butenolides and acrylates scaffolds. The structures of the prepared compounds were characterized by ¹H-NMR, 13 C-NMR and electrospray ionization mass spectrometry (ESI-MS), and the bioactivity of the target compounds against twelve phytopathogenic fungi was investigated. The preliminary in vitro antifungal activity screening showed that most of the target compounds had moderate inhibition on various pathogenic fungi at the concentration of 100 mg·L -1 , and presented broad-spectrum antifungal activities. Further studies also indicated that compounds 7e and 7k still showed some inhibitory activity against Pestallozzia theae , Sclerotinia sclerotiorum and Gibberella zeae on rape plants at lower concentrations, which could be optimized as a secondary lead for further research.

In the present investigation we report the first target specific, highly diastereoselective synthesis of new class of pyranoquinolinyl/furoquinolinyl-acrylic acid diastereomers and evaluation of their invitro α-glucosidase inhibitory activity. All the products were thoroughly characterized by 1 H NMR, 13 C NMR, FT-IR, Mass spectral and CHN analysis. A highly diastereoselective target specific route of synthesis for the biologically active diastereomers were developed by usingchiral catalyst Europium tris[3-heptafluoropropylhydroxyl methylene]-(-)-camphorate (A) or Europiumtris[3-(trifluoromethyl)hydroxylmethylene]-(+)-camphorate (B). It was found that among a set of 4 diastereomeric products obtained, exodiasteromers of pyranoquinolinyl acrylic acid adducts exhibited relatively high α-glucosidase inhibitory activity. The newly synthesized compounds exhibited IC 50 values in the range of (0.40 ± 0.02-30.3 ± 0.84 μM) as compared to standard acarbose (IC 50  = 0.65 ± 0.02 μM). It was found that compounds 11a, 11c, 11d and 12d were found to be more active than standard acarbose. It was also found that unsubstituted compound (11a) or compounds with chlorine or methoxy substituent (11c, 11d, 12d) showed potential α-glucosidase inhibitory activity. However a reversal in activity was observed with Nitro substituent (11b, 13b) wherein the endodiastereomers were found to be more active than exodiastereomers. Molecular docking studies were used for design of the compound and understand the mode of binding between the compound and target enzyme. A plausible mechanism for the diastereoselective synthesis was also proposed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The adaptability, joint with a large surface area, electronic flexibility, high intrinsic mobility, high mechanical strength and supreme thermal conductivity have condensed graphene family materials attractive as technological tools of the drug delivery system. In this present study, investigate a modified graphene oxide-methyl acrylate (GO-g-MA) nanocarrier for targeted anti-cancer drug delivery in breast cancer cells and the GO-g-MA fascinated with folic acidas a targeting ligand to target the cancer cells. Paclitaxel (PTX) was assembled through π-π stacking, hydrophophic interaction on the surface of the GO-g-MA/FA carrier. Structural modification of GO-g-MA, functionalization of targeting ligands GO-g-MA/FA and drug loaded GO-g-MA/FA-PTX was characterized and confirmed through FTIR, XRD, SEM,TEM and AFM analysis. The in-vitro drug release pattern of PTX from the GO-g-MA/FA was examined in different pH ranges. An MTT assay was performed to evaluate the cytotoxicity behaviour of the carrier and PTX loaded nanocarrier in the human breast cancer cell line (MDA-MB-231). GO-g-MA/FA-PTX carrier showed that 39% of cytotoxic effect. Furthermore, the in-vivo (DMBA induced breast cancer rats) studies were carried out and treatment with PTX- loaded GO-g-MA/FA nanocarrier attenuates the levels of mitochondrial citric acids enzymes to near normal., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hydrogel with good mechanical and biological properties has great potential and promise for biomedical applications. Here we fabricated a series of novel cytocompatible chitosan (CS) based double-network (DN) and triple-network (TN) hydrogels by physically-chemically crosslinking methods. Natural polysaccharide CS with abundant resources was chosen as the first network due to its good antimicrobial activity, biocompatibility and easy cross-linking reaction. Zwitterionic sulfopropylbetaine (PDMAPS) was chosen as the second network due its good biocompatibility, antimicrobial and antifouling properties. And nonionic poly(2-hydroxyethyl acrylate) (PHEA) was chosen as the final network due to its good biocompatibility, excellent nonfouling and mechanical properties. Cross-section SEM images showed that both CS/PHEA (DN 1 , the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) and CS/PDMAPS/PHEA (TN 1 , the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) hydrogels exhibited a smooth and uniformly dispersed porous microstructures with pore size distribution in the range of 20∼100 μm. The largest compressive stress and tensile stress of DN 1 hydrogels reached 84.7 MPa and 292 kPa, respectively, and largest compressive stress and tensile stress of TN 1 hydrogels could reach 81.9 MPa and 384 kPa, respectively. Moreover, the value of failure strain for TN 1 gels reached 1020%. Besides excellent mechanical properties, DN 1 and TN 1 gels exhibited good antimicrobial, cytocompatible and antifouling properties due to introduction of antimicrobial chitosan, cell anti-adhesive PDMAPS and PHEA. The combination of the excellent mechanical and biological properties of multiple network hydrogels can provide a potential pathway to develop biomedical hydrogels as promising bioapplications in wound dressing and other biomedical applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cysteine (Cys) plays crucial roles in physiological and pathological processes, and is related to many diseases. Selective monitoring of Cys over its analogues homocysteine (Hcy) and glutathione (GSH) is of great significance. A probe named ANT with an acrylate group as a recognizing moiety and a red-emission dye with a large Stokes shift (160 nm) as a fluorophore was designed and synthesized. The acrylate group can quench the fluorescence of ANT by a photoinduced electron transfer (PET) process. However, in the presence of Cys, the emission was switched on by the cleavage of the quencher through a concerted reaction including Michael addition and intramolecular cyclization. Furthermore, solution experiments showed that ANT exhibited high sensitivity and selectivity towards Cys with the maximum emission at 640 nm. Besides, ANT was successfully applied to specifically map endogenous Cys in living MCF-7 cells with low toxicity, despite the interference of Hcy and GSH. We hope that such a prepared novel probe will bring advancement in specifically differentiating Cys, Hcy and GSH.

In this study, we developed a multi-signal mitochondria-targeted fluorescent probe (NIR-Cys) for simultaneous detection of Cys and its metabolite, SO2. In the design of the probe, the acrylate group and the C[double bond, length as m-dash]C of the coumarin ring were used as the recognizing moiety for Cys and SO2, respectively. The probe exhibited high sensitivity, excellent specificity, and fast response. NIR-Cys was found to precisely target and visualize Cys metabolism in mitochondria of living cells with a multi-fluorescence signal. This probe is expected to be a useful tool for understanding Cys metabolism.

DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecules that rapidly and specifically bind and inhibit electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type enzyme. Thus, this approach can be used to systematically generate small molecule-sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition and functional characterization of members of this enzyme family.

A series of 16 new ethyl [Formula: see text]-amino benzimidazole acrylate derivatives 12(a-p) with a (2E)-s-cis/trans conformation and bearing two points of diversity was designed and synthesized by using a multi-step strategy (reductive amination, deprotection in acidic media and transamination) in moderate to good yields from ethyl 3-dimethylamino-2-(1H-benzimidazol-2-yl)acrylate (5) and monosubstituted N-Boc diamines (7a,7b) as starting building blocks. Products 12 were evaluated for their in vitro cytotoxic potential against six selected human cell lines (Huh7-D12, Caco2, MDA-MB231, HCT116, PC3 and NCI-H727). Compounds 12a, 12e and 12l exhibited selective and micromolar antitumor activities against Huh7-D12 and Caco2 cell lines.

The beneficial use of computer simulations to track the microstructural evolution of individual species is highlighted in view of macromolecular engineering and design, considering two case studies on catalytic polymerization, and both "low" (<100) and "high" (>100) chain lengths, that is, i) atom transfer radical copolymerization of n-butyl acrylate and styrene aiming at the synthesis of functional macrospecies of "identical' chain length; and ii) chain shuttling polymerization of ethylene and 1-octene toward the production of segmented block copolymers with "soft" and "hard" segments. Model parameters are validated and/or tuned based on literature data. The modeling strategy supports the future identification of chemical structure-polymer property relationships and is based on the combination of principles from polymer reaction engineering, chemistry, and physics., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Organic matters in wastewater dramatically impaired the removal capability of adsorbents to heavy metal ions, thus greatly limited their applications for real systems. Here we fabricated the F127/PAA hydrogels that could effectively remove Cu 2+ and Hg 2+ from organic wastewater due to their anti-fouling properties against organic matters. The F127/PAA hydrogels performed high swelling ratio and mechanical stress, showing maximum adsorption capacities of Cu 2+ and Hg 2+ at 283.4 and 222.1 mg/g, respectively. For the BSA containing water, the removal ratio of Cu 2+ and Hg 2+ by F127/PAA hydrogels could reach to 94.0% and 70.2%, respectively. For the humic acid containing water, the corresponding data were 89.5% and 72.1%. Besides, five cyclic adsorption-desorptions in humic acid solution and simulated cosmetic wastewater only slightly decreased the removal efficiencies of F127/PAA hydrogels to Cu 2+ and Hg 2+ . Our results suggested the potential application of the F127/PAA hydrogels in treatment of real organic wastewater., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A series of inhibitors targeting human cathepsins have been designed and synthesized following a combinatorial approach. The compounds bear an α,β-unsaturated phenyl vinyl sulfone or ethyl acrylate warhead and a peptidomimetic portion aligned to the non-primed binding region. Biochemical evaluation toward four human cathepsins was carried out and the kinetic characterization confirmed an irreversible mode of inhibition. Compound 6c combining the most advantageous building blocks for cathepsin S inhibition was identified as a potent cathepsin S inactivator exhibiting a second-order rate constant of 30600 M -1  s -1 ., (Copyright © 2018. Published by Elsevier Ltd.)

A mixed-mode polymer monolithic column functionalized by arsonic acid groups was prepared by single-step in situ copolymerization of monomers p-methacryloylaminophenylarsonic acid (p-MAPHA) and pentaerythritol triacrylate (PETA). The prepared poly(p-MAPHA-co-PETA) monolithic column has a homogeneous monolithic structure with good permeability and mechanical stability. Zeta potential measurements reveal that the monolithic stationary phase holds a negative surface charge when the mobile phase resides in the pH range of 3.0-8.0. The retention mechanisms of prepared monolithic column are explored by the separation of selected polycyclic aromatic hydrocarbons (PAHs), nucleosides, and three basic compounds. The results indicate that the column functions in three different separation modes associated with reversed-phase chromatography based on hydrophobic interaction, hydrophilic interaction chromatography, and cation-exchange chromatography. The column efficiency of prepared monolithic column is estimated to be 70,000 and 76,000 theoretical plates/m for thiourea and naphthalene, respectively, at a linear flow velocity of 0.85 mm/s using acetonitrile/H 2 O (85/15, v/v) as the mobile phase. Furthermore, an analysis of the retention factors obtained for the PAHs indicates that the prepared monolithic column exhibits good reproducibility with relative standard deviations of 2.9%, 4.0%, and 4.7% based on run-to-run injections, column-to-column preparation, and batch-to-batch preparation, respectively. Finally, we investigate the separation performance of the proposed monolithic column for select phenols, sulfonamides, nucleobases and nucleosides., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Site-selective chemical conjugation of synthetic molecules to proteins expands their functional and therapeutic capacity. Current protein modification methods, based on synthetic and biochemical technologies, can achieve site selectivity, but these techniques often require extensive sequence engineering or are restricted to the N- or C-terminus. Here we show the computer-assisted design of sulfonyl acrylate reagents for the modification of a single lysine residue on native protein sequences. This feature of the designed sulfonyl acrylates, together with the innate and subtle reactivity differences conferred by the unique local microenvironment surrounding each lysine, contribute to the observed regioselectivity of the reaction. Moreover, this site selectivity was predicted computationally, where the lysine with the lowest p K a was the kinetically favored residue at slightly basic pH. Chemoselectivity was also observed as the reagent reacted preferentially at lysine, even in those cases when other nucleophilic residues such as cysteine were present. The reaction is fast and proceeds using a single molar equivalent of the sulfonyl acrylate reagent under biocompatible conditions (37 °C, pH 8.0). This technology was demonstrated by the quantitative and irreversible modification of five different proteins including the clinically used therapeutic antibody Trastuzumab without prior sequence engineering. Importantly, their native secondary structure and functionality is retained after the modification. This regioselective lysine modification method allows for further bioconjugation through aza-Michael addition to the acrylate electrophile that is generated by spontaneous elimination of methanesulfinic acid upon lysine labeling. We showed that a protein-antibody conjugate bearing a site-specifically installed fluorophore at lysine could be used for selective imaging of apoptotic cells and detection of Her2+ cells, respectively. This simple, robust method does not require genetic engineering and may be generally used for accessing diverse, well-defined protein conjugates for basic biology and therapeutic studies.

In this article, hydrogen polysulfide (H 2 S n )-mediated Michael addition/cyclization cascade reactions toward acrylate ester analogues were exploited and utilized to construct novel and robust H 2 S n -specific fluorescence probe for the first time. Through rational molecular engineering of the α-substituted acrylate ester template, the optimal candidate probe FP-CF 3 containing trifluoromethyl-substituted acrylate ester group as recognition unit and 3-benzothiazol-7-hydroxycoumarin dye BHC as signal reporter can highly selectively detect H 2 S n over other reactive sulfur species, especially biothiols including cysteine (Cys) and homocysteine (Hcy)/glutathione (GSH), with a rapid and significant turn-on fluorescence response (less than 60 s for response time and over 44-fold for signal-to-background ratio). The fast response and high selectivity of FP-CF 3 for H 2 S n could be attributed to a kinetically and spatially favored pentacyclic addition produced by the dual nucleophilic reaction of H 2 S n with the CF 3 -substituted acrylate group. The big off-on fluorescence response is due to the pentacyclic intermediate results in the release of the highly fluorescent BHC. Moreover, it has been successfully applied in imaging of endogenous H 2 S n fluctuation in living cells.

Cysteine (Cys), as an important biothiol, plays a major role in many physiological processes like protein synthesis, detoxification and metabolism, and also is closely associated with a variety of diseases; thus the design of novel highly selective and sensitive near-infrared (NIR) fluorescent probes for Cys detection in vivo is of great significance. Herein, we report a selective and sensitive NIR turn-on fluorescent probe (CP-NIR) with large Stokes shift for detecting Cys in vivo. Upon addition of Cys to the solution of the probe, it is absorption wavelength shifts from 550 to 600 nm, accompanying with an obvious enhancement of NIR fluorescence emission centering around 760 nm. This Michael-addition reaction-based probe shows a large Stokes shift (160 nm), low detection limit (48 nM), fast response time, and low toxicity. Moreover, this novel NIR probe with good cell permeability was successfully applied to monitoring endogenous Cys in living cells and in a mouse model.

Octocrylene (OC) is an emerging UV filter, which is used in the majority of sunscreens as well as other personal care products (PCP) and consumer products. Its presence in various environmental matrices has been reported. However, information on the internal OC exposure in humans is not available, due to the lack of appropriate biomarkers of exposure and analytical methods. Here, we describe a rugged, precise, and accurate analytical method for the determination of three OC metabolites (ester hydrolysis and alkyl chain oxidation products) in human urine by stable isotope dilution analysis. Urine samples are incubated with β-glucuronidase (E. coli K12) and then analyzed by liquid chromatography-electrospray ionization-triple quadrupole-tandem mass spectrometry with online turbulent flow chromatography for sample cleanup and analyte enrichment (online-SPE-LC-MS/MS). Syntheses of analytical standards, including deuterium-labeled internal standards, are also described. In a pilot study, we investigated the applicability of the metabolites as biomarkers of exposure in urine samples from the general population (n = 35). OC metabolites were detected in 91% of the samples, with the highest concentrations for three individuals having used sunscreen within 5 days prior to sample collection. We will apply the method in future human biomonitoring studies for OC exposure and risk assessment.

A binary grafted copolymer of Psyllium mucilage (Psy) with acrylic acid (AA) and acrylonitrile (An) has been successfully synthesized under microwave conditions for in vitro drug release study. The grafting was confirmed by FTIR spectroscopy, XRD, SEM, EDX, TGA analytical techniques and the intrinsic viscosity study. The swelling behavior of grafted material has been studied in solution of different pH and time. We also prepare Psy-g-Poly (AA-co-An) based beads with anti-cancer drug [(2-Chloro-3-(4-hydroxyphenylamino) naphthalene-1, 4-dione)]. The drug release behavior of Psy-g-Poly (AA-co-An) based beads has been determined in aqueous medium at different pH. It has been observed that highest drug release at pH 1.6. The drug release kinetics was analysed using the different models. This study demonstrates that the release of drug depends on the composition of beads and pH of release medium. Kinetics of drug release from beads is best fitted by zero order and first order model., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

There is a clinical need for a synthetic bone graft substitute that can be used at sites of surgical intervention to promote bone regeneration. Poly(vinylphosphonic acid-co-acrylic acid) (PVPA-co-AA) has recently been identified as a potential candidate for use in bone tissue scaffolds. It is hypothesized that PVPA-co-AA can bind to divalent calcium ions on bone mineral surfaces to control matrix mineralization and promote bone formation. In this study, hydrogels of PVPA-co-AA have been produced and the effect of copolymer composition on the structure and properties of the gels was investigated. It was found that an increase in VPA content led to the production of hydrogels with high porosities and greater swelling capacities. Consequently, improved cell adhesion and proliferation was observed on these hydrogels, as well as superior cell spreading morphologies. Furthermore, whereas poly(acrylic acid) gels were shown to be relatively brittle, an increase in VPA content created more flexible hydrogels that can be more easily molded into bone defect sites. Therefore, this work demonstrates that the mechanical and cell adhesion properties of PVPA-co-AA hydrogels can be tuned for the specific application by altering the copolymer composition. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 255-264, 2018., (© 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.)

Background: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases., Objective: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiate the action of incretins in decreasing the blood glucose levels., Methods: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved., Results: In vitro anti-DPP-IV activity of the synthesized compounds was evaluated, where compound 3b demonstrated the best activity with a % inhibition of 41.7 at 10 µM concentration and an IC50 of 23.9 µM. Moreover, Glide docking experiments revealed that our targeted compounds accommodate the binding site of DPP-IV and tend to form H-bonding with the backbones of R125, E206, S209, D545, K554, W629, Y631, and G632., Conclusion: Modeling findings recommend the attachment of bulky hydrophobic group on the ester side of the structure in addition to harboring extra aromatic rings that might be beneficial for better binding interaction and biological activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A strategy for the synthesis of sequence-defined oligomers using a selective side-group insertion approach making use of thiophenol-catalyzed amidation reactions is herein reported. In this context, a new thiolactone-based, multistep, iterative protocol is designed, utilizing thioacrylates in combination with solid-phase synthesis for step-by-step growth, resulting in sequence-defined oligomers. Sequence definition and structure variation are introduced by substituting the thioacrylate side groups with a wide variety of amines. The step-by-step growth of the oligomers is followed by liquid chromatography-mass spectrometry and high-resolution mass spectroscopy to determine both conversion and purity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two new tricyclic β-aminoacrylate derivatives (2e and 3e) have been found to be inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) with Ki 0.037 and 0.15μM respectively. 1 H and 13 C NMR spectroscopic data show that these compounds undergo ready cis-trans isomerisation at room temperature in polar solvents. In silico docking studies indicate that for both molecules there is neither conformation nor double bond configuration which bind preferentially to PfDHODH. This flexibility is favourable for inhibitors of this channel that require extensive positioning to reach their binding site., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Poly(2-methoxyethyl acrylate) (pMEA) microspheres are prepared through facile free-radical polymerization in water without additives and impurities, such as surfactants, other polymers, and organic solvents, which are usually used to synthesize pMEA chains. Clean and pure (non-factionalized and non-cross-linking) pMEA microspheres exhibit plasma-protein adsorption resistances on their surface regardless of their charged state. They are characterized in terms of the adsorbed amounts of proteins at pH 7. In addition, these soft and deformable pMEA microspheres are suitable for forming substrates coated with pMEA microspheres and free-standing films by injecting pMEA dispersion and evaporating the aqueous medium through fusion between the pMEA chains at the surface without the precoating agent and cross-linker. These pMEA coatings have been used till now in artificial heart/lung fabrication and metal products manufacturing by casting organic solvents such as 1,4-dioxane, toluene, and methanol and dissolving pMEA chains prepared using conventional solution polymerization. In this study, bioinert coatings and adhesive and transferable films are easily obtained due to the rubber-like properties of the pMEA microspheres and stable in mild and biocompatible conditions even when these impurities are not used completely, allowing us to provide a guideline for potential pMEA bioapplications such as coatings, films, barriers, and implant devices., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Butyl acrylate is polymerized in the living way under the irradiation of purple light-emitting diode (LED) or sunlight without photocatalyst at ambient temperature. 2-((Phenoxycarbonothioyl)thio) ethyl propanoate) is exclusively added and acted as an initiator and a chain transfer agent simultaneously in the current system. Poly(butyl acrylate) with well-regulated molecular weight and relatively narrow molecular weight distribution (Ð < 1.30) is synthesized. High conversion (>95%) can be achieved within several minutes. Polymerization shows oxygen tolerance. Near quantitative end-group fidelity of polymer is demonstrated by 1 H NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectra., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Despite being a simple dehydration reaction, the industrially relevant conversion of lactic acid to acrylic acid is particularly challenging. For the first time, the catalytic cracking of lactide and poly(lactic acid) to acrylic acid under mild conditions is reported with up to 58 % yield. This transformation is catalyzed by strong acids in the presence of bromide or chloride salts and proceeds through simple S N 2 and elimination reactions., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The synthesis of the γ-secretase modulator MK-8428 (1) is described. The synthesis is highlighted by an enzyme-catalyzed reaction to access 3,4,5-trifluoro-(S)-phenylglycine, a 1-pot activation/displacement/deprotection sequence to introduce the aminooxy functionality and a dehydrative intramolecular cyclization under mild conditions to form the oxadiazine heterocycle of 1. In situ reaction monitoring was employed to understand the deleterious role of water during the formation of a methanesulfonate ester in the 1-pot activation/displacement/deprotection sequence.

A microwave induced irradiation synthesis, was proposed for the preparation of hydroxypropyl methylcellulose-graft-(polyvinylalcohal-co-acrylic acid) hydrogels. The hydrogels were separately synthesized by using microwave irradiation method and conventional water bath heating method. Moreover, the prepared hydrogels were loaded with an antihypertensive drug, captopril. Chemical groups, thermal stability and surface morphology of these hydrogels were characterized by FT-IR, DSC and SEM. Swelling ratios of the gels were measured gravimetrically at'pH 1.2 and 7.4. Results showed that micrographs obtained from scanning electron microscopy (SEM), revealed that gels synthesized using microwave irradiation had more uniformly porous network structures. The uniformity in porosity was due to rapid and instantaneous penetration of microwave energy throughout the surface and they had higher swelling ratios in comparison to hydrogels synthesized by water bath method. Thermal analysis (DCS and TGA) depicted that crosslinked polymers were more stable. FT-IR analysis had confirmed the formation of the new polymeric network. X-ray diffractogram revealed that crystallinity of HPMC was reduced in hydrogel prepared by microwave radiation. It had also been observed that high crosslinking density diminish swelling of hydrogel. A stable network of hydroxypropyl methylcellulose (HPMC), poly(vinylalcohal) (PVA) and acrylic acid was developed in shorter time period under influence of microwave radiations.