Discovery, structure-activity relationship studies, and crystal structure of nonpeptide inhibitors bound to the Shank3 PDZ domain

Shank is the central scaffolding protein of the postsynaptic density (PSD) protein complex found in cells of the central nervous system. Cellular studies indicate a prominent role of the protein in the organization of the PSD, in the development of neuronal morphology, in neuronal signaling, and in synaptic plasticity, thus linking Shank functions to the molecular basis of learning and memory. Mutations in the Shank gene have been found in several neuronal disorders including mental retardation, typical autism, and Asperger syndrome. Shank is linked to the PSD complex via its PDZ domain that binds to the C‐terminus of guanylate‐kinase‐associated protein (GKAP). Here, small‐molecule inhibitors of Shank3 PDZ domain are developed. A fluorescence polarization assay based on an identified high‐affinity peptide is established, and tetrahydroquinoline carboxylates are identified as inhibitors of this protein–protein interaction. Chemical synthesis via a hetero‐Diels–Alder strategy is employed for hit optimization, and structure–activity relationship studies are performed. Best hits possess K_i values in the 10 μM range, and binding to the PDZ domain is confirmed by ¹H,¹⁵N HSQC NMR experiments. One of the hits crystallizes with the Shank3 PDZ domain. The structure, analyzed at a resolution of 1.85 Å, reveals details of the binding mode. Finally, binding to PDZ domains of PSD‐95, syntrophin, and DVL3 was studied using ¹H,¹⁵N HSQC NMR spectroscopy.     

Development of linseed oil based polyesteramide without organic solvent at lower temperature

Linseed oil based polyesteramide was synthesized at lower temperature in the absence of organic solvent through condensation polymerization reaction [Sf‐LPEA]. In this reaction N,N‐bis(2‐hydroxyethyl) linseed oil fatty amide and phthalic anhydride were heated at temperature lower than their onset of melting points and the by‐product, such as water was removed by application of vacuum technique. This approach was employed to overcome the use of volatile organic solvents used during processing and application of resin, which are ecologically harmful. The solubility of Sf‐LPEA was checked in different polar and nonpolar solvents. The FTIR, ¹H NMR, and ¹³C NMR spectral techniques were used to confirm the structure of Sf‐LPEA. The physicochemical, physicomechanical, and chemical resistance properties of the resin were investigated by standard methods. DSC and TGA were used to determine, respectively, the curing behavior and thermal stability of the resin. The comparative study of these properties of Sf‐LPEA with reported polyesteramide [LPEA], which are normally synthesized at higher temperature in organic solvent, was done. It was found that Sf‐LPEA exhibited improved physicomechanical, chemical resistance properties, and higher thermal stability compared with LPEA, and hence can find application as corrosion protective coating. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1143–1148, 2007     

Synthesis,characterization, and in vitro drug‐release properties of 2‐hydroxyethyl methacrylate copolymers

2‐Hydroxyethyl methacrylate was copolymerized with acrylamide, N‐vinyl‐2‐pyrrolidone, and n‐butyl methacrylate by free‐radical solution polymerization with α,α′‐azobisisobutyronitrile as an initiator at 70 ± 1°C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and ¹H‐NMR spectroscopy data, respectively. Diclofenac or 2‐[(2,6‐dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti‐inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N′‐dicyclohexylcarbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, ¹H‐, and ¹³C‐NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37°C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled‐release systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2403–2409, 2007     

Synthesis,photochemical characterization,and thermal stability of a series of substituted formamidines as ultraviolet light absorbers

The three‐step reactions of ethyl 4‐aminobenzoate, formic acid, and halohydrocarbons afforded 10 N‐substituted‐N,N′‐diaryl‐formamidine derivatives ( F1 – 10 ) as ultraviolet absorbers. These N‐substituted formamidines were characterized by ¹H NMR, ¹³C NMR, FT‐IR, and ESI‐MS spectroscopies. The UV–vis absorbance and fluorescence properties of the compounds F1 – 10 were investigated in different solvents and in the presences of different metal ions. The effects of the amount of Al³⁺, Pb²⁺, Zr⁴⁺ ions on the UV–vis absorbance and fluorescence properties of compound F1 were also investigated. Moreover, the thermal stability of the compounds F1 – 10 was evaluated as well as the intermediate N,N′‐bis(4‐ethoxycarbonylphenyl)‐formamidine. J. VINYL ADDIT. TECHNOL., 25:E108–E113, 2019. © 2019 Society of Plastics Engineers     

NMR studies of DOXP reductoisomerase and its inhibitor complex

1‐Deoxy‐D ‐xylulose 5‐phosphate (DOXP) reductoisomerase (EC1.1.1.267) catalyses the second step of the 2‐C‐methyl‐D ‐erythritol 4‐phosphate (MEP) pathway of isoprenoid biosynthesis. The enzyme is used by most bacteria, apicomplexan parasites and the plastids of plants, but not by humans, and therefore represents an attractive target for antibacterial, antiparasitic and herbicidal compounds. Fosmidomycin, an inhibitor of DXR, has been found to be active against bacterial infections and malaria in early clinical studies. Here, we report sample optimisation, partial backbone assignment and secondary‐structure prediction of E. coli DXR by heteronuclear NMR analysis for further NMR‐aided drug discovery. Perdeuterated ¹⁵N,¹³C‐labelled samples were prepared under oxygen exclusion in the presence of Mg²⁺, NADPH and the inhibitor FR‐900098, a close derivative of fosmidomycin. ¹H and ¹⁵N backbone assignment was achieved for 44 % of the primary structure, and ¹³C backbone assignment was achieved for 50 % of the primary structure. Comparison with previously solved crystal structures revealed that the assigned fragments were located mainly in helical regions on the solvent‐exposed surface of the enzyme. Torsion angle likelihood obtained from shift and sequence similarity (TALOS) was used for secondary structure prediction, resulting in agreement with eight available crystal structures; deviations could be observed for the catalytic loop region.     

Synthesis and properties of polymeric complexes containing bithiazole rings and carbazole units

A novel polymer (poly[2,2'‐(4,4'‐bithiazolylene)][N‐(2‐ethylhexyl)‐3,6‐carbazylene] (PBTCA) was first synthesized from 2,2′‐diamino‐4,4′‐bithiazole and N‐(2‐ethylhexyl)‐3,6‐diformylcarbazole. The structure of the polymer was determined with IR and ¹H‐NMR spectroscopy. The PBTCA–Nd³⁺ complex was prepared via the mixing of neodymium trichloride hexahydrate and PBTCA in dimethyl sulfoxide under a nitrogen atmosphere. The magnetic behaviors of the Nd³⁺ complex of a poly(Schiff base) were measured as a function of the magnetic field strength (0–50 kOe) at 4 K and as a function of the temperature (4–300 K). The results show that PBTCA–Nd³⁺ is a ferromagnet when the temperature is below 15 K, and above that, it is a diamagnet. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 443–446, 2006     

Natural abundance 15n solid‐state nmr study of nylon‐6 in blends

Natural abundance solid‐state nuclear magnetic resonance spectroscopy (NMR) of nitrogen‐15 (¹⁵N) was applied to investigate the films of nylon‐6 and their blends with poly(propylene oxide) (PPO). The NMR ¹⁵N results allowed us to identify the crystalline forms present in these blends and also confirmed the previous NMR results obtained by ¹³C‐NMR study. From all NMR data the antiplasticization phenomena and plasticization effects caused by PPO content, in the blends were characterized. The polyoxide action is a function of its proportion. However, because the samples were prepared by solution casting, the residual solvent action cannot be ignored. The ¹⁵N chemical shift changes were influenced by both PPO and residual solvent. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3872–3875, 2003     

Structural development Of TMMA and SSQXN‐8 as porous chelating resins

Superfast kinetics of Nd⁺³, Eu⁺³, and Gd⁺³ ions were studied on the surfaces of N,N,N^\,N^\‐tetramethylmalonamide (TMMA) and silsesquioxane (SSQXN‐8) resins. TMMA and SSQXN‐8 were prepared by suspension polymerization and sol–gel routes, respectively. They were identified using elemental analysis, FTIR, H‐NMR, ¹³C‐NMR, MIP, and BET surface area. Kinetic investigations were performed in batch conditions and different models were used to fit the data; Boyd and Helfferich models were found the best. The diffusion of the ions through the resins were very fast and found to be in the order of 10^?16 m²/S. Effective diffusions of the studied ions were found to be 10^?15 order of magnitude and directly proportional to the kinetic energy of the transition state. ΔS* values from ?166.044 to ?179.297 J mol^?1 K^?1 were estimated as entropy stability factors of the system. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

[3H]UR‐DE257: Development of a Tritium‐Labeled Squaramide‐Type Selective Histamine H2 Receptor Antagonist

A series of new piperidinomethylphenoxypropylamine‐type histamine H₂ receptor (H₂R) antagonists with different substituted “urea equivalents” was synthesized and characterized in functional in vitro assays. Based on these data as selection criteria, radiosynthesis of N‐[6‐(3,4‐dioxo‐2‐{3‐[3‐(piperidin‐1‐ylmethyl)phenoxy]propylamino}cyclobut‐1‐enylamino)hexyl]‐(2,3‐³H₂)propionic amide ([³H]UR‐DE257) was performed. The radioligand (specific activity: 63 Ci mmol^?1) had high affinity for human, rat, and guinea pig H₂R (hH₂R, Sf9 cells: K_d, saturation binding: 31 nM , kinetic studies: 20 nM ). UR‐DE257 revealed high H₂R selectivity on membranes of Sf9 cells, expressing the respective hH_xR subtype (K_i values: hH₁R: >10 000 nM , hH₂R: 28 nM , hH₃R: 3800 nM , hH₄R: >10 000 nM ). In spite of insurmountable antagonism, probably due to rebinding of [³H]UR‐DE257 to the H₂R (extended residence time), the title compound proved to be a valuable pharmacological tool for the determination of H₂R affinities in competition binding assays.     

Discovery of Non‐ATP‐Competitive Inhibitors of Polo‐like Kinase 1

Polo‐like kinase 1 (Plk1) is an evolutionarily conserved serine/threonine kinase, and its N‐terminal kinase domain (KD) controls cell signaling through phosphorylation. Inhibitors of Plk1 are potential anticancer drugs. Most known Plk1 KD inhibitors are ATP‐competitive compounds, which may suffer from low selectivity. In this study we discovered novel non‐ATP‐competitive Plk1 KD inhibitors by virtual screening and experimental studies. Potential binding sites in Plk1 KD were identified by using the protein binding site detection program Cavity. The identified site was subjected to molecular‐docking‐based virtual screening. The activities of top‐ranking compounds were evaluated by in vitro enzyme assay with full‐length Plk1 and direct binding assay with Plk1 KD. Several compounds showed inhibitory activity, and the most potent was found to be 3‐((2‐oxo‐2‐(thiophen‐2‐yl)ethyl)thio)‐6‐(pyridin‐3‐ylmethyl)‐1,2,4‐triazin‐5(4H)‐one (compound 4 ) with an IC₅₀ value of 13.1±1.7 μm . Our work provides new insight into the design of kinase inhibitors that target non‐ATP binding sites.     

Carrier‐bound methotrexate. I. Water‐soluble polyaspartamide–methotrexate conjugates with ester links in the polymer–drug spacer

The antifolate‐type anticancer drug methotrexate (MTX) has for many years, in numerous laboratories, been a “workhorse” drug for conjugation with natural and synthetic macromolecular carriers for the purpose of enhancing bioavailability and lowering toxic side effects. In the project here described the polymer–drug conjugation strategy is utilized for the preparation of water‐soluble polyaspartamide–methotrexate conjugates in which the drug is carrier‐anchored through short spacers containing ester groups as biofissionable links. To this end, polyaspartamide carriers 1, poly‐α,β‐D,L ‐N‐(2‐hydroxyethyl)aspartamide, and 2, poly‐α,β‐D,L ‐N‐[2‐(2‐hydroxyethoxy)ethyl]aspartamide, are treated with MTX in DMF solution in the presence of a carbodiimide coupling agent and 4‐(dimethylamino)pyridine catalyst. The molar MTX/OH feed ratios, 0.28 and lower, are chosen in these coupling reactions so as to provide conjugates featuring drug‐loading levels in the approximate range of 3–16 mol % MTX, roughly corresponding to 6–28% by mass. The water‐soluble product polymers are purified by aqueous dialysis, collected in the solid state by freeze‐drying, and structurally characterized by ¹H–NMR spectroscopy. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1844–1849, 2001     

Novel and Mild Route to Phthalocyanines and 3‐Iminoisoindolin‐1‐ones via N,N‐Diethylhydroxylamine‐Promoted Conversion of Phthalonitriles and a Dramatic Solvent‐Dependence of the Reaction

Refluxing a mixture of phthalonitrile C₆R¹R²R³R⁴(CN)₂ 1 (R¹–R⁴=H), or its substituted derivatives 2 (R¹, R³, R⁴=H, R²=Me), or 3 (R¹, R⁴=H, R², R³=Cl) (1 equiv.) and N,N‐diethylhydroxylamine, Et₂NOH, (4 equivs.) in methanol for 4 h results ( Route A ) in precipitation of the symmetrical ( 6 and 8 ) and an isomeric mixture of unsymmetrical ( 7 ) phthalocyanines, isolated in good (55–65 %) yields. The reaction of phthalonitriles 1 , 2 , or 4 (R¹, R³, R⁴=H, R²=NO₂) (4 equivs.) with Et₂NOH (8 equivs.) in the presence of a metal salt MCl₂ (M=Zn, Cd, Co, Ni) (1 equiv.) in n‐BuOH or without solvent results in the formation of metallated phthalocyanine species ( 9 – 17 ). Upon refluxing in freshly distilled dry chloroform, phthalonitrile 1 or its substituted analogues 2 , 3 or 5 (R¹–R⁴=F) (1 equiv.) react with N,N‐diethylhydroxylamine (2 equivs.) affording 3‐iminoisoindolin‐1‐ones 18 – 21 ( Route B ) isolated in good yields (55–80 %). All the prepared compounds were characterized with C, H, and N elemental analyses, ESI‐MS, IR, and compounds 18 – 21 also by 1D (¹H, ¹³C{¹H}), and 2D (¹H,¹⁵N‐HMBC and ¹H,¹³C‐HMQC, ¹H,¹³C‐HMBC) NMR spectroscopy.     

Synthesis,characterization, and drug‐release behavior of amphiphilic quaternary ammonium chitosan derivatives

A new type of amphiphilic quaternary ammonium chitosan derivative, 2‐N‐carboxymethyl‐6‐O‐diethylaminoethyl chitosan (DEAE–CMC), was synthesized through a two‐step Schiff base reaction process and applied to drug delivery. In the first step, benzaldehyde was used as a protective agent for the incorporation of diethylaminoethyl groups to form the intermediate (6‐O‐diethylaminoethyl chitosan). On the other hand, NaBH₄ was used as a reducing agent to reduce the Schiff base, which was generated by glyoxylic acid, for the further incorporation of carboxymethyl groups to produce DEAE–CMC. The structure, thermal properties, surface morphology, and diameter distribution of the resulting chitosan graft copolymers were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, thermogravimetric analysis, differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy, and laser particle size analysis. Benefiting from the amphiphilic structure, DEAE–CMC was able to be formed into microspheres in aqueous solution with an average diameter of 4.52 ± 1.21 μm. An in vitro evaluation of these microspheres demonstrated their efficient controlled release behavior of a drug. The accumulated release ratio of vitamin B₁₂ loaded DEAE–CMC microspheres were up to 93%, and the duration was up to 15 h. The grafted polymers of DEAE–CMC were found to be blood‐compatible, and no cytotoxic effect was shown in human SiHa cells in an MTT [3‐(4, 5‐dimethyl‐thiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide] cytotoxicity assay. These results indicate that the DEAE–CMC microspheres could be used as safe, promising drug‐delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39890.     

Synthesis and characterization of AB‐type copolymers poly(L‐lactide)‐block‐poly(methyl methacrylate) via a convenient route combining ROP and ATRP from a dual initiator

Diblock copolymers of poly(L ‐lactide)‐block‐poly(methyl methacrylate) (PLLA‐b‐PMMA) were synthesized through a sequential two‐step strategy, which combines ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP), using a bifunctional initiator, 2,2,2‐trichloroethanol. The trichloro‐terminated poly(L ‐lactide) (PLLA‐Cl) with high molecular weight (M_n,GPC = 1–12 × 10⁴ g/mol) was presynthesized through bulk ROP of L ‐lactide (L ‐LA), initiated by the hydroxyl group of the double‐headed initiator, with tin(II) octoate (Sn(Oct)₂) as catalyst. The second segment of the block copolymer was synthesized by the ATRP of methyl methacrylate (MMA), with PLLA‐Cl as macroinitiator and CuCl/N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA) as catalyst, and dimethyl sulfoxide (DMSO) was chosen as reaction medium due to the poor solubility of the macroinitiator in conventional solvents at the reaction temperature. The trichloroethoxyl terminal group of the macroinitiator was confirmed by Fourier transform infrared spectroscopy (FTIR) and ¹H‐NMR spectroscopy. The comprehensive results from GPC, FTIR, ¹H‐NMR analysis indicate that diblock copolymers PLLA‐b‐PMMA (M_n,GPC = 5–13 × 10⁴ g/mol) with desired molecular composition were obtained by changing the molar ratio of monomer/initiator. DSC, XRD, and TG analyses establish that the crystallization of copolymers is inhibited with the introduction of PMMA segment, which will be beneficial to ameliorating the brittleness, and furthermore, to improving the thermal performance. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Anticancer Potency Studies of Coordination Driven Self‐Assembled Arene–Ru‐Based Metalla‐Bowls

New tetranuclear cationic metalla‐bowls 5 – 7 with the general formula [Ru₄(p‐cymene)₄(N∩N)₂(OO∩OO)₂]⁴⁺ (N∩N=2,6‐bis(N‐(4‐pyridyl carbamoyl)pyridine, OO∩OO=2,5‐dihydroxy‐1,4‐benzoquinonato ( 5 ), OO∩OO=5,8‐dioxydo‐1,4‐naphthaquinonato ( 6 ), OO∩OO=hoxonato ( 7 )) were prepared by the reaction of the respective dinuclear ruthenium complexes 2 – 4 with a bispyridine amide donor ligand 1 in methanol in the presence of AgO₃SCF₃.These new molecular metalla‐bowls were fully characterized by analytical techniques including elemental analysis as well as ¹H and ¹³C NMR and HR‐ESI‐MS spectroscopy. The structure of metalla‐bowl 6 was determined from X‐ray crystal diffraction data. A UV/visible study was also carried out for the entire suite of new complexes. As with recent studies of similar arene–Ru complexes, the inhibition of cell growth by metalla‐bowls was established against SK‐hep‐1 (liver cancer), AGS (gastric cancer), and HCT‐15 (colorectal cancer) human cancer cell lines. Inhibition of cell growth by 6 was found to be considerably stronger against all cancer cell lines than the anticancer drugs, doxorubicin and cisplatin. In particular, in colorectal cancer cells, expression of the cancer suppressor genes APC and p53 was increased following exposure to 6 .     

Water‐soluble copolymers of 1‐vinyl‐2‐pyrrolidone and acrylamide derivatives: synthesis,characterization, and metal binding capability studied by liquid‐phase polymer‐based retention technique

Radical copolymerizations of 1‐vinyl‐2‐pyrrolidone with acrylamide and N,N′‐dimethylacrylamide at different feed ratios were investigated. The copolymers were characterized by Fourier transform infrared spectroscopy, ¹H NMR, and ¹³C NMR spectroscopy. The copolymer composition was determined from the ¹H NMR spectra and found to be statistical. The metal complexation of poly(acrylamide‐co‐1‐vinyl‐2‐pyrrolidone) and poly(N,N′‐dimethylacrylamide‐co‐1‐vinyl‐2‐pyrrolidone) for the metal ions Cu(II), Co(II), Ni(II), Cd(II), Zn(II), Pb(II), Fe(III), and Cr(III) were investigated in an aqueous phase. The liquid‐phase polymer‐based retention method is based on the retention of inorganic ions by soluble polymers in a membrane filtration cell and subsequent separation of low‐molecular compounds from the polymer complex formed. The metal ion interaction with the hydrophilic polymers was determined as a function of the pH and the filtration factor. Poly(N,N‐dimethylacrylamide‐co‐1‐vinyl‐2‐pyrrolidone) showed a higher affinity for the metal ions than poly(acrylamide‐co‐1‐vinyl‐2‐pyrrolidone). According to the interaction pattern obtained, Cr(III) and Cu(II) formed the most stable complexes at pH 7. Pb(II) and Zn(II) were not retained. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 741–750, 1999     

Aromatic polyimides from m‐phenylene diamines containing pendant groups: Synthesis and characterization

Two diamine monomers, 4‐[4‐(1‐methyl‐1‐phenylethyl)phenoxy]‐1,3‐diamino benzene and 4‐{4‐[(4‐methylphenyl)sulfonyl]phenoxy}‐1,3‐diamino benzene, were synthesized, and both diamines were polycondensed with three commercial dianhydrides to obtain aromatic polyimides containing pendant groups. The polyimides were characterized by solubility tests, viscosity measurements, IR, ¹H‐NMR, and ¹³C‐NMR spectroscopy, X‐ray diffraction studies, and thermogravimetric analysis. The polyimides had inherent viscosities of 0.33–0.58 dL/g in m‐cresol at 30 ± 0.1°C. All the polyimides were amorphous and were soluble in solvents such as N,N‐dimethylacetamide, N‐methyl‐2‐pyrrolidone, N,N‐dimethylformamide, and m‐cresol. Thermogravimetric analysis of the polyimides indicated no weight loss below 410°C under a nitrogen atmosphere. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1377–1384, 2005     

Synthesis and characterization of novel polyimides containing triazoles units in the main chain by click chemistry

In this study, some polyimides containing triazoles units in the main chain was prepared from the polymerization of dialkynes including imide linkages and diazides in the presence of Cu (I) catalyst in yield of 76.2–87.6%, with inherent viscosity of 0.37–0.53 dL g^?1. The obtained polymers are soluble in polar aprotic solvents such as N,N‐dimethyformamide (DMF), N,N‐dimethyacetamide (DMAc), dimethyl sulfoxide (DMSO), and N‐methyl‐2‐pyrrolidone (NMP). These polymers were characterized using FT‐IR, ¹H‐NMR, and elemental analysis techniques. Their thermal stability was evaluated with thermogravimetric (TGA) analysis and differential scanning calorimetry (DSC) techniques under a nitrogen atmosphere which is indicative of their good thermal stability. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Stereochemical assignments of the nuclear magnetic resonance spectra of isobornyl acrylate/methacrylonitrile copolymers

Isobornyl acrylate (B)/methacrylonitrile (N) copolymers with different compositions were synthesized by the free‐radical bulk polymerization with azobisisobutyronitrile as the initiator under a nitrogen atmosphere at 70°C. The copolymer compositions were calculated from quantitative ¹³C(¹H)NMR spectra. The reactivity ratios of the comonomers in the B/N copolymers determined from the linear Kelen–Tudos method and nonlinear error‐in‐variable method were r_B = 0.66 ± 0.11 and r_N = 1.54 ± 0.22 and r_B = 0.74 and r_N = 1.65, respectively. The complete spectral assignments of the ¹H‐NMR and ¹³C(¹H)‐NMR spectra were carried out with the help of distortionless enhancement by polarization transfer, two‐dimensional (2D) heteronuclear single quantum coherence, and 2D total correlation spectroscopy. The nitrile carbon of the N unit and the methine and OCH carbons of the B unit were assigned to triad compositional sequences, whereas the β‐methylene carbons of the B and N units were assigned to the tetrad compositional and configurational sequences. The α‐methyl carbon of the N unit was also assigned to the triad level of configurational and compositional sequences. Similarly, the nitrile and quaternary carbon resonances with the methine, methylene, and methyl protons were studied in detail with 2D heteronuclear multiple‐bond correlation spectra. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Thermoresponsive and biocompatible poly(vinyl alcohol)‐graft‐poly(N,N‐diethylacrylamide) copolymer: Microwave‐assisted synthesis,characterization, and swelling behavior

Novel thermoresponsive poly(vinyl alcohol)‐graft‐poly(N,N‐diethylacrylamide) (PVA‐g‐PDEAAm) copolymers were prepared by microwave‐assisted graft copolymerization using a potassium persulfate/N,N,N′,N′‐tetramethylethylenediamine (KPS/TEMED) initiator system. The structures of PVA‐g‐PDEAAm copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, differential scanning calorimetry/thermogravimetric analysis, gel permeation chromatography, X‐ray diffraction, and scanning electron microscopy. The effects of various process parameters on grafting were systematically studied: microwave power, KPS, monomer and PVA concentrations, and ultraviolet irradiation. Under optimal conditions, the maximum grafting percent and graft efficiency were 101% and 93%, respectively. Furthermore, a lower critical temperature of copolymers was measured in the range 29–31 °C by ultraviolet spectroscopy. The swelling behavior of graft membranes was carried out at various temperatures, and the results showed that the swelling behavior of membranes was dependent on the temperature. In vitro cell culture studies using L929 fibroblast cells confirmed cell compatibility with the PVA‐g‐PDEAAm copolymer and its membrane, making them an attractive candidate for drug delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45969.