Studies of some new bioactive acrylic esters

Four typical bioactive esters of acrylic monomers, N-p-acryloxybenzoyloxysuccinimides, 3-ac-ryloxy-4-oxo-3,4-dihydro-1,2,3-benzotriazines, N-acryloxy-5-norbornene-2,3-dicarboximides, and I-p-acryloxybenzoyloxybenzotriazoles, were Synthesized and polymerized as reactive polymers. Twelve new monomers were prepared by coupling acrylic acid, methacrylic acid, p-acryloxybenzoic acid, or p-methacryloxybenzoic acid with four N-hydroxy compounds such as N-hydroxysuccinimide (HOSu), 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOObt), N-hydroxy-5-norbornene-2,3-dicarboximide (HONB), and I -hydroxybenzotriazole (HOBT) in the presence of dicyclohexylcarbodimide. All monomers polymerized readily in solution with azobisisobutyronitrile (AIBN) as free radical initiator. The resulting reactive polymers with reactive ? OSu, ? OObt, ? ONB, or ? OBT group on the side chain are equally reactive toward n-butylamine at room temperature in the formation of corresponding polyacrylamides. Reactive polymers were used to immobilizetrypsin. It has been found that poly(N-p-methacryloxybenzoyloxy-5-norbornene-2,3-dicarboximide)-trypsin matrix had high activity around three times that of the poly(N-methacryloxy-5-norbornene-dicarboximide)-trypsin matrix. It is proposed that this activity may be due to the presence of a long spacer arm with a hydrophobic and rigid benzene ring between the ligand and matrix. The reactive poly(N-p-methacryloxybenzoyloxysuccinimide-p-methacryloxybenzoic acid) copolymer was used to immobilize the serum protein. This immobilized protein was a hopeful bioactive solid immunoadsorbent.     

Synthesis and polymerization of optically active L-[α-(N-p-acryloxybenzoyl)alanine ethyl esters]

New optically active monomers L -[α-(N-p-acryloxybenzoyl)alanine ethyl esters] (I) and their polymers were synthesized. The title monomers (I) were prepared by the reaction of 1-p-acryloxybenzoyloxy-4-chlorobenzotriazoles (II) with L -alanine ethyl ester hydrochloride, by aminolysis of the active monoester. The new typical active ester (II) was synthesized by the N-hydroxy compound active-ester methods in excellent yield. Before the synthesis of the optically active monomers was carried out, a model study of the aminolysis of the two active esters was performed.     

New synthetic route to alternating copoly(aromatic ester–aliphatic amide)s

The preparation of three novel alternating copoly(aromatic ester–aliphatic amide)s containing the same ordered amide–amide–ester–ester (AAEE), the same para-disubstituted phenyl, and the different long methylene chain structure were described. 1,1′-(Adipoyl)bisbenzotriazole (AdBBT), 1,1′-(suberoyl)bisbenzotriazole (SuBBT), and 1,1′-(sebacoyl)bisbenzotriazole (SeBBT) were synthesized. These diacylbenzotriazoles were preferred to aminoethanol at the amino group because of the selective N-acylation of active acylamide of benzotriazole in excellent yield at room temperature to give diol monomers such as N,N′-bis(2-hydroxyethyl)adipic amide (HEAdA), N,N′-Bis(2-hydroxyethyl)subaric amide (HESuA), and N,N′-bis(2-hydroxyethyl)sebacic amide (HESeA). Polycondensation of 1,1′-(teraphthaloyl)bisbenzotrizole (tPBT) with HEAdA, HESuA, and HESeA gave the corresponding alternating copoly(aromatic ester–aliphatic amide)s: P(tPE–AdA), P(tPE–SuA), and P(tPE–SeA), respectively. The alternating copoly(aromatic ester–aliphatic amide)s were characterized by ¹H-NMR spectra. The resulting polymers have two different chain units; one is chain unit of poly(ethylene terephthalate) and the other is a chain unit of polyamide-2,6, polyamide-2,8, and polyamide-2,10; both are linked via a C? N bond.     

Homogeneous ion-exchange membranes of improved flexibility

Poly(styrenesulfonic acid) ion-exchange membranes having various degrees of porosity and flexibility have been prepared by using aliphatic and aromatic esters of p-styrenesulfonic acid. The membranes formed from the aliphatic ester monomers were found to exhibit an increase in water uptake, permeability, and flexibility with increase in the size of the alcohol group of the ester monomer. With membranes formed from the phenyl and β-naphthyl ester monomers the reverse trend was indicated. The flexibility of the membranes formed from the aromatic ester monomers was much greater than that obtained with the aliphatic esters.     

Polymeric amines and their copper(II) complexes: Catalysts for the hydrolysis of organophosphate esters

Catalysis of the solvolysis of organophosphorus esters by polymers of aliphatic amines, imidazole, pyridine, 2,2′-bipyridine, and their copper(II) complexes was studied using diisopropyl fluorophosphate (DEP) as a model substrate. The polymeric catalysts were synthesized either by (1) derivation of available polymers, including polyethylenimine, polyvinyl amine, polyvinyl alcohol, polystyrene, and poly-4-vinylpyridine or (2) by polymerization of functionalized monomers such as 4(5)-vinylimidazole and 4-vinyl-4′-methyl-2,2′-bipyridine. Polymer hydrophilicity was controlled by partial quaternization of amine groups with different alkyl halides. The greatest catalytic activity was exhibited by copper(II) complexes of polymers containing the 2,2′-bipyridine group. At pH 7.6 and 3.7 × 10^?3M, the most active of these catalysts reduced the half-life of DFP from 800 to 9 min. The rate was largely independent of the pH in the range 6.5–8.5 but was limited by the aqueous solubility of the catalyst. Heterogeneous catalysis by some polymers was observed but was less effective. A Lineweaver-Burk plot of V₀^?1 versus [DFP]^?1 for a soluble polymeric 2,2′-bipyridine-copper(II) catalyst was linear. There was no correlation between catalysis of solvolysis of DFP and the carboxylic ester, p-nitrophenyl acetate.     

Study of photopolymer. XVII. Synthesis of novel photosensitive polymers with pendant photosensitive group and photosensitizer groups

Novel photosensitive polymers with pendant photosensitive group, such as cinnamic ester, and photosensitizer groups, such as N-carbamoyl-p-nitroaniline and N-carbamoly-4-nitro-1-naphthylamine, were synthesized from radical copolymerizations of (2-cinnamoyloxy)ethylmethacrylate with photosensitizer monomers, such as p-nitrophenylmethacrylamide and 4-nitro-1-na-phthylmethacrylamide, by using asobisisobutyronitrile (AIBN) in benzene and from the copolymerizations of (2-hydroxy)ethylmethacrylate or (2-hydroxy)ethylacrylate with photosensitizer monomers by using AIBN in DMF. This procedure was followed by condensation reactions of the copolymers with cinnamoyl chloride with pyridine as HCL acceptor in the same reaction flask. The photoreactivities of the polymers obtained were influenced by the concentration of photosensitive group and photosensitizer groups and their ratio in the polymer matrix. In addition, the photosensitivity of cinnamic ester groups attached to a soft polymer segment was higher than that of cinnamic ester group attached to a hard polymer segment when these polymers had the same pendant N-carbamoyl-p-nitroaniline group as photosensitizer. Furthermore, the spacer length between the polymer chain and photosensitizer group was important for increasing the photoreactivity of the photosensitive group in the polymers with pendant cinnamic ester and N-carbamoyl-p-nitroaniline groups.     

Reactivity of polymer substituents. Aminolysis of p-nitrophenyl ester residues attached to various polymer backbones

Styrene, methyl acrylate, and N,N-dimethylacrylamide were copolymerized with small proportions of p-nitrophenyl acrylate or p-nitrophenyl esters of CH₂?CHCONH(CH₂)_nCOOH (n = 1,3,5). The aminolysis of these copolymers in dioxane and chlorobenzene solution was compared with the corresponding reaction of low molecular weight analogs. The ratio of the reactivity of the polymer substituent and its analog was found to be insensitive to the nature of the amine but strongly dependent on the nature of the polymer backbone. Poly(dimethylacrylamide) chains carrying active ester substituents were in some cases much more reactive than their analogs due to the activating effect of the dimethylamide groups. In the case of the p-nitrophenyl acrylate–styrene copolymer, the aminolysis exhibited a dispersion of the rate constant due to its sensitivity to stereoisomerism in the vicinity of the active ester, but no similar effects were observed with the other copolymers.     

Copolymerization of amino acid and amino ester functionalized norbornenes via living ring‐opening metathesis polymerization

The block and random copolymerization of a series of amino acid and amino ester functionalized norbornenes by ring‐opening metathesis polymerization (ROMP) induced by the well‐defined molybdenum [Mo(?N‐2,6‐ⁱPr? C₆H₃)(?CHCMe₂)Ph)(OCMe₃)₂] or ruthenium [Ru(PCy)₂Cl₂(?CHPh)] based initiators is described. The monomers are derived from the amino acids glycine, alanine, and isoleucine or the methyl esters of these amino acids and either endo‐ or exo‐norborn‐5‐ene‐2,3‐dicarboxylic anhydride. Enantiomerically pure monomers afforded optically active polymers, and the mechanism and kinetics of the copolymerizations are investigated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7985–7995, 2008     

Aminimides. XII. Synthesis,homo- and copolymerization studies of trialkylamine N-acryloyl or N-methacryloyl glycinimides and β-aminopropanimides

Some representative examples of a new family of aminimide monomers, i.e., trialkylamine N-acryloyl or N-methacryloyl glycinimides and β-aminopropanimides have been prepared and studied. These are the first examples of a possible large family of primary aminimide monomers. With radical initiators, the acryloyl and monosubstituted methacryloyl monomers readily homopolymerize. The disubstituted methacryloyl aminimides do not homopolymerize under the same conditions. All of the new monomers copolymerize with styrene, methyl methacrylate, and n-butyl acrylate. The various polymers were characterized by IR, DTA, TGA, GPC and inherent viscosities. When heated (160°C) the polymers liberate amine and crosslink in the presence of active hydrogen moieties to give resins with carbamate, urea, allophonate, etc., residues. When no active hydrogens are available during heating, polymers can be prepared with pendent primary isocyanate groups. This preliminary work shows these monomers to be highly useful for preparing a wide variety of reactive copolymers.     

Synthesis of Amino Acid Derivatives of Neamine and 2-Deoxystreptamine to be used as Mutasynthons

ABSTRACT

6′-N derivatives of neamine with alanine, phenylalanine and lysine were synthesized either using an active esters method in one step under controlled conditions, or using a mixed anhydride method after blocking every functional group of neamine and leaving the 6′-amino group free to react. Similarly N,N′-diamino acid and monoamino acid derivatives of 2-deoxystreptamine were synthesized.     

Synthesis of polynucleotide analogs by grafting optically active adenine,cytosine, and hypoxanthine derivatives onto polytrimethylenimine

A new family of polynucleotide analogs were prepared by grafting nucleic acid base derivatives onto polytrimethylenimine. Several new optically pure α-nucleic acid base substituted propanoic acids were prepared as pendant groups. The (R)-ethyl adeninylpropanoate was obtained from adenine and (S)-ethyl lactate by utilizing a diethyl azodicarboxylate-triphenyl phosphine method. Subsequent hydrolysis of the ester in aqueous acid gave the (R)-adeninylpropanoic acid without racemization. The reaction of cytosine sodium salt with (S)-ethyl 2-[(methylsulfonyl)oxy] propanoate produced the 20% racemized (R)-ethyl 2-(cytosin-1-yl)propanoate. The optically pure ester was obtained by recrystallization from ethyl alcohol, which was hydrolyzed in aqueous acid to give the (R)-acid with 66% enantiomeric excess. The (R)-2-(hypoxanthin-9-yl)propanoic acid was prepared by reaction of (R)-2-(adenin-9-yl)propanoic acid with sodium nitrite. The pendant groups were allowed to react with N-hydroxy compounds in the presence of dicyclohexylcarbodiimide to give the active esters. These active esters underwent reaction with N,N-dipropylamine to provide monomer model compounds. The pendant groups were grafted onto polytrimethylenimine by using the active ester method. The racemization reactions were observed in the grafting reactions. The resulting polymers showed a range of percent grafting from 60 to 80%.     

Prodendronic polyamines from stable or labile methacrylates obtained by selective Michael addition onto asymmetric diacrylic compounds

A new synthetic strategy for the preparation of methacrylic monomers and polymers carrying acyl β‐amino groups is presented. The approach is based on the Michael addition of aliphatic amines onto asymmetric acrylic/methacrylic compounds, reacting the amine highly selectively with the acrylic unit while leaving the methacrylic moiety unreacted. The corresponding polymers are then obtained by conventional radical polymerization. The use of N,N,N′,N′‐tetraethyldiethylenetriamine (TEDETA) as the secondary amine leads to TEDETA moieties supported on polymeric chains. The new aminopolymers are sensitive to pH and to temperature exhibiting a lower critical solution temperature of between 50 and 90 °C. A further interesting feature of the new approach is that the stability toward hydrolysis of the side β‐amino acyl compounds was found to be dependent on whether an acrylamide or an acrylate is employed as the acrylic group of the asymmetric starting material. The esters exhibit an enhanced sensitivity to hydrolysis, compared to standard aliphatic esters, and decompose releasing a derivative of the amine precursor, within hours or weeks, depending on the pH and temperature conditions. The use of the amides leads to stable polymers when the same experimental conditions are applied. The novel dendronic polyamines have been proven to interact with DNA and to transfect cells with efficiency close to that obtained with polyethyleneimine vectors used as positive controls. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2297–2305     

Asymmetric selective polymerization of racemic methacrylates with the cyclohexylmagnesium bromide-(−)-sparteine system

Asymmetric selective (or stereoelective) polymerization of various racemic methacrylates with cyclohexylmagnesium bromide (c-HexMgBr)-(-)sparteine (1/1.2) catalyst was studied in toluene at ?78°C. The methacrylates of α-ethylbenzyl (EBMA), α-isopropylbenzyl (i-PBMA), α-tert-butylbenzyl (t-BBMA), sec-butyl (s-BuMA), 1-methylallyl (1-MAMA), 2,3-epoxypropyl (2,3-EPMA), 2-phenylpropyl (2-PPMA), and menthyl (MentMA) alcohols were used as racemic monomers. In the polymerization of EBMA and i-PBMA (S) enantiomers were consumed preferentially and the optical purity of initially polymerized i-PBMA was as high as 97%. Optically pure (R) monomers were recovered at about 60% conversion for i-PBMA and 80% for EBMA. In t-BBMA, however, the (R) monomer was consumed preferentially over the (S) isomer. In the polymerization of s-BuMA and 1-MAMA (S) monomers were consumed in excess and the optical purity of the polymers formed in the early stage was about 30%. In 2,3-EPMA and 2-PPMA, which have asymmetric centers at the β position from the ester oxygen, (R) antipodes were more reactive. MentMA did not polymerize at ?78°C. Enantiomer selectivity ratios r_S and r_R were determined in the polymerization of EBMA, i-PBMA, and 1-MAMA. All polymers except poly(t-BBMA) were highly isotactic, but the tacticity of poly(t-BBMA) could not be estimated. Circular dichroism spectra of optically active polymers of α-substituted benzyl esters were measured.     

Reactions of 2-Arylhydrazono-1,3-dicarbonyl Compounds with Ethylenediamine

2-Arylhydrazono-1,3-diketones react with ethylenediamine to give, depending on the substituents, dihydro-1,4-diazepine derivative or N,N'-ethylenebis(1,3-aminovinyl ketones). Treatment of the latter with nickel(II) or copper(II) acetate results in formation of the corresponding metal chelates. Nickel complexes of N,N'-ethylenebis(1,3-aminovinyl ketones) can also be synthesized from 2-arylhydrazono-1,3-diketones and ethylenediamine on a metal template. Reactions of 2-arylhydrazono-3-oxo esters with ethylenediamine yield N,N'-ethylenebis(3-alkyl-2-arylhydrazono-3-oxopropionamides). Ethyl 2-arylhydrazonoacetoacetate reacts with ethylenediamine under mild conditions, affording ethyl 2-p-tolylazo-3-[2-(2-p-tolylhydrazono-1,3-dioxobutylamino)ethylamino]-2-butenoate.     

Poly(DCAQI): Synthesis and characterization of a new redox‐active polymer

Redox‐active anthraquinone based polymers are synthesized by the introduction of a polymerizable vinyl and ethynyl group, respectively, resulting in redox‐active monomers, which electrochemical behaviors are tailored by the modification of the keto groups to N‐cyanoimine moieties. These monomers can be polymerized by free radical polymerization and Rh‐catalyzed polymerization methods, respectively. The resulting polymers are obtained in molar masses (M_n) of 4,400 to 16,800 g mol^?1 as well as high yields of up to 97%. The monomers and polymers are furthermore electrochemically characterized by cyclic voltammetry. The monomers exhibit two one‐electron redox reactions at about ?0.6 and ?1.0 V versus Fc⁺/Fc. The N‐cyanoimine units are, however, partially hydrolyzed during the polymerization step or during the electrochemical measurements and degenerate to carbonyl groups, resulting in a new reduction signal at ?1.26 V versus Fc⁺/Fc. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1998–2003     

Polyurethanes and polyureas having long methylene chain units

Polyurethanes and polyureas containing long methylene chain units have been prepared from the following six series of monomer combinations; aliphatic diisocyanates with aliphatic glycols or diamines, methylene bis(4-phenyl isocyanate) with aliphatic glycols or diamines, and p-xylylene diisocyanate with aliphatic glycols or diamines. A good linear relationship was noted between the polymer melting points of each series against the concentration of functional groups. Both polyurethanes and polyureas from p-xylylene diisocyanate showed higher melting points than those from methylene bis(4-phenyl isocyanate) with corresponding aliphatic monomers. The relations between the melting points of these polymers with long methylene chains, including polyamides which were previously reported, and the chain components were discussed. The higher melting points of polymers containing p-xylylene group are attributed to the high rigidity of this group.     

Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethane-phosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I)

Summary The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.     

Preparation and polymerization of thyroxine methacrylate monomers

Thyroxine methyl ester amides of mono-, di-, and tri-glycyl methacrylates have been prepared. Water-soluble polymers formed from thyroxine methacrylate monomers by free-radical copolymerization with acrylamide had molecular weights of (2–4) × 10⁴ (by viscometry). A fluorescent polymer was prepared by copolymerization with a fluorescein methacrylate monomer. Similarly, a polymeric thyroxine material was prepared with amine functionality by copolymerization with N-3-aminopropylmethacrylamide. These polymers may have interesting biological and immunochemical properties.     

Use of N‐methyliminodiacetic acid boronate esters in suzuki‐miyaura cross‐coupling polymerizations of triarylamine and fluorene monomers

Polytriarylamine copolymers can be prepared by Suzuki‐Miyaura cross‐coupling reactions of bis N‐methyliminodiacetic acid (MIDA) boronate ester substituted arylamines with dibromo arenes. The roles of solvent composition, temperature, reaction time, and co‐monomer structure were examined and (co)polymers prepared containing 9, 9‐dioctylfluorene (F8), 4‐sec‐butyl or 4‐octylphenyl diphenyl amine (TFB), and N, N′‐bis(4‐octylphenyl)‐N, N′‐diphenyl phenylenediamine (PTB) units, using a Pd(OAc)₂/2‐dicyclohexylphosphino‐2′,6′‐dimethoxybiphenyl (SPhos) catalyst system. The performance of a di‐functionalized MIDA boronate ester monomer was compared with that of an equivalent pinacol boronate ester. Higher molar mass polymers were produced from reactions starting with a difunctionalized pinacol boronate ester monomer than the equivalent difunctionalized MIDA boronate ester monomer in biphase solvent mixtures (toluene/dioxane/water). Matrix‐assisted laser desorption/ionization mass spectroscopic analysis revealed that polymeric structures rich in residues associated with the starting MIDA monomer were present, suggesting that homo‐coupling of the boronate ester must be occurring to the detriment of cross‐coupling in the step‐growth polymerization. However, when comparable reactions of the two boronate monomers with a dibromo fluorene monomer were completed in a single phase solvent mixture (dioxane + water), high molar mass polymers with relatively narrow distribution ranges were obtained after only 4 h of reaction. © 2017 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2798–2806     

Thermally stable silarylene-1,3,4-oxadiazole polymers

The effects of incorporating a p-phenylene- (or m-phenylene)-1,3,4-oxadiazole fragment into the backbone of poly[1,4-phenylene(diphenylsilyl)-1,4-phenylene-2,5-(1,3,4-oxadiazole)], which was developed by the authors, was investigated. Bis[(p-carbohydrazidophenyl)]diphenylsilane was copolymerized with dipentachlorophenyl terephthalate or isophthalate to produce the prepolymers poly[N-(p-diphenylsilylbenzoyl)-N′N″-(terephthaloyl)-N″′-(p-benzoyl)dihydrazide] and poly[N-(p-diphenylsilylbenzoyl)-N′,-N″-(isophthaloyl)-N″′-p-(benzoyl) dihydrazide], respectively. The polyhydrazides were converted by thermal dehydration into poly[1,4-phenylene(diphenylsilyl)-1,4-phenylene-(1,3,4-oxadiazole-2,5-diyl)-1,4-phenylene-2,5-(1,3,4-oxadiazole)] and poly[1,4-phenyl-ene(diphenylsilyl)-1,4-phenylene-(1,3,4-oxadiazole-2,5-diyl)-1,3,4-(oxadiazole)]. The new polymers were soluble in organic solvents. Films cast from these solutions exhibited good adhesion to glass and metal surfaces. Thermal analysis showed that the heat stability of all these polymers was about the same and that they were resistant to decomposition when heated in air to about 400°C. The results also indicated that these polymers were somewhat less heat-resistant than samples of poly-[1,4-phenylene(diphenylsilyl)-1,4-phenylene-2,5-]1,3,4-(oxadiazole) synthesized from bis(p-carbohydrazidophenyl)diphenylsilane and bis-(p-carbopentachlorophenoxy-phenyl)diphenylsilane.