Synthesis of linear poly(ethylenimine) containing nucleic acid pendants as polynucleotide analogs

Polynucleotide analogs with a linear poly(ethylenimine) (PEI) backbone and adenine, cytosine, and hypoxanthine pendants were synthesized. Linear PEI was synthesized by the cationic ring-opening polymerization of 2-H-2-oxazoline, followed by acid hydrolysis. 2-(Adenin-9-yl)- and 2-(N⁶-benzyladenin-9-yl)-, 2-(cytosin-1-yl)propanoic acids in addition to 2-(adenin-9-yl)-3-methyland 3-(cytosin-1-yl)butanoic acids were synthesized from their respective nucleic acid bases. 2-(Hypoxanthin-9-yl)propanoic acid and 3-(hypoxanthin-9-yl)butanoic acid were converted from the corresponding adenine derivatives by reaction with nitrous acid. Grafting reactions of pendant groups onto various molecular weight PEI backbones were carried out at room temperature, using the coupling agent norborn-5-ene-2,3-carboximido diphenyl phosphate (PPONB), generally resulting in percent graft values greater than 90%. PPONB showed selectivity against the amino group of adenine and cytosine rings. The appropriate model compounds were also prepared.     

Synthesis of poly(ethylene glycol methyl ether)-b-poly(ethylenimine) and its derivatives containing thymine and amino acids as pendants

Poly(ethylene glycol methyl ether)tosylate was prepared and used to initiate the polymerization of 2-methyl-2-oxazoline. The resulting poly(ethylene glycol methyl ether)-b-poly(N-acetyl ethylenimine) was hydrolyzed and neutralized to give poly(ethylene glycol methyl ether)-b-poly(ethyl-enimine) (PEO–PEI). 2-(thymin-1-yl)propionic acid, N-Cbz-alanine, N-Cbz-proline, N-Cbz-O-t-Bu-serine. and N-FMOC-proline were grafted onto the PEO–PEI copolymer; attempts were then made to remove the Cbz and FMOC protecting groups.     

Nucleic acid base grafted polyethylenimine. Cytosyl pendant groups: Elucidation of structure with solution spectroscopy

In a previous paper, potassium 2-(cytos-1-yl)propanoate was grafted onto polyethylenimine of various molecular weights. These water-soluble polynucleotide analogs exhibited remarkable properties in their solution ultraviolet spectra. High hypochromicity values of 50% and 54% have been observed in alkaline aqueous solution and 50% trifluoroethanol solution, respectively. Percent hypochromicity value was observed to be directly proportional to percent graft. Red shift and hyperchromicity as a function of pH were observed for both the monomer model and the graft polymers. Light-scattering experiments on nucleic acid base grafted hydrophilic polymer backbones were carried out. Radius of gyration and second virial coefficient values indicated stiff macromolecules, rodlike in nature. Therapeutic potential of cytosyl grafted polyethylenimine was suggested by the results from continuous mixing experiments with polyinosinic acid and polyguanylic acid. Job plots showed enhanced hypochromicity, whose magnitude was dependent upon the polynucleotide and the base-base distance.     

Syntheses of poly[N-(1-pyrenyl)acetyl ethylenimine] [pyrene-substituted linear poly(ethylenimine)] and poly[methyl 2-(1-pyrenyl)acetamidopropenoate] [pyrene-substituted poly(dehydroalanine methyl ester)]

The syntheses of two new pyrene-containing monomers—2-(1-pyrenyl)methyl-2-oxazoline ( 6 ) and methyl 2-(1-pyrenyl)acetamidopropenoate ( 12 )—and their polymerization are described. Cationic isomerization polymerization of 6 with ethylene glycol ditosylate initiator gave poly[N-(1-pyrenyl)acetyl ethylenimine] ( 7 ) and free-radical polymerization of 12 with AIBN initiator gave poly[methyl 2-(1-pyrenyl)acetamidopropenoate] ( 15 ). The monomer model compounds of the two polymers, namely, N,N-diethyl(1-pyrenyl)acetamide ( 9 ) and methyl 2-methyl-2-(1-pyrenyl)acetamidopropanoate ( 14 ), were also synthesized. The polymers were characterized by elemental analysis, IR spectroscopy, and a comparison of their ¹H-NMR spectra with those of the respective monomer model compounds.     

Polymerizaton of Salts of 2-Alkenyl-2-Oxazolines and Their Homologs

The present paper describes a new type of polymerization of 2-vinyl-2-oxazoline and 2-vinyl-5,6-dihydro-4H-1,3-oxazine and their salts. When these two imino ether monomers are allowed to react with Meerwein reagents or super acid esters, N-alkylation takes place first, followed by polymerization through the opening of vinyl groups to give poly [(2-oxazolinium-2-yl)ethylene] and poly [(5,6-dihydro-4H-1,3-oxazinium-2-yl)ethylene], respectively. With the corresponding 2-isopropenyl homologs, 2-isopropenyl-2-oxazoline and 2-isopropenyl-5,6-dihydro-4H-1,3-oxazine, stable N-alkylated salts are obtained, which were subjected to radical and base-catalyzed polymerizations. From the above results the reactivities of the salts are considered in terms of their ring size and the substituents on the olefinic functions.     

Selective hydrolysis of oxazoline block copolymers

Block copolymers, composed of a hydrophobic block [poly(N-t-butylbenzoyl ethylenimine) or poly(N-lauroyl ethylenimine)] and a hydrophilic block [poly(N-propionyl ethylenimine)], synthesized by cationic ring-opening polymerization of 2-substituted Δ2-oxazolines, were selectively deacylated by acid hydrolysis. The hydrolysis process was monitored by using ¹H-NMR. The results show that the propionyl groups could be removed from the hydrophilic block of the polymer chain without touching the hydrophobic block, if appropriate reaction conditions were used.     

Synthesis of silsesquioxanes having photochromic diarylethene pendant groups

Silsesquioxanes having 1-(2-methylbenzo[b]thien-3-yl)-2-[5-(4-butylphenyl)-2,4-dimethylthien-3-yl]perfluorocyclopentenes as the pendant groups were synthesized. Photochemical conversion from the open-ring to the closed-ring form of diarylethenes chemically bonded to polymers was by 15–25% lower than the conversion of the chromophores dispersed in the same matrix. No appreciable difference in the photoconversion of the fixed chromophores was observed below and above the glass transition temperature (T_g) of the polymer films.     

Synthesis of poly(styrene-tetrahydrofuran-2-methyl-2-oxazoline) triblock and graft copolymers

Poly[styrene (ST)-tetrahydrofuran (THF)-2-methyl-2-oxazoline(MeOz)] triblock and graft copolymers were prepared by ionic polymerizations. Poly(ST-THF) graft copolymers were synthesized by coupling of ST-4-vinylpyridine (4VP) copolymer with a large excess of PTHF dication. The ion coupling of PST dianion with PTHF dication was accompanied by the side reaction (abstraction of α proton of oxonium ion). After tosylation of terminal hydroxyl groups of PTHF blocks, cationic copolymerizations of MeOz with poly(ST-THF) block and graft copolymers were carried out, and characteristics of produced copolymers were investigated in some detail.     

Graft polymerization of methyl methacrylate initiated by pendant azo groups introduced onto γ-poly(glutamic acid)

The grafting of poly(methyl methacrylate) (PMMA) onto biosynthesized γ-poly(glutamic acid) (γ-PGA) initiated by pendant azo groups introduced onto γ-PGA was performed. The introduction of pendant azo groups onto γ-PGA was achieved by the reaction of carboxyl groups of γ-PGA with azo initiators having hydroxyl or amino groups, such as 2,2-azobis[2-(hydroxymethyl)propionitrile] (AHP), 2,2′-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (AMHP), and 2,2′-azobis[2-(2-imidazolin-2-yl)propane] (AIP), using N,N′-dicyclohexylcarbodiimide. The amount of pendant AHP groups introduced onto γ-PGA was estimated to be 0.15 mmol/g. Untreated γ-PGA failed to initiate the polymerization of MMA. On the contrary, the polymerization of MMA was found to be initiated in the presence of γ-PGA having azo groups: the polymerization rate was proportional to the square root of the concentration of γ-PGA having pendant azo groups. During the polymerization PMMA was grafted onto γ-PGA; the percentage of grafting of PMMA onto γ-PGA obtained from the graft polymerization initiated by pendant AHP, AMHP, and AIP groups was evaluated to be 65.0, 53.1, and 29.0%, respectively. Differential scanning calorimetric analysis shows that the endotherm transition point of γ-PGA at 220°C disappears by the grafting of PMMA onto the polymer. © 1993 John Wiley & Sons, Inc.     

Effect of pendant groups on the blood compatibility and hydration states of poly(2-oxazoline)s

Poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx), poly(2-n-butyl-2-oxazoline) (PBuOx), and poly(2-phenyl-2-oxazoline) (PPhOx) are selected as poly(2-oxazoline) (POX) models to study the effect of pendant groups on their blood compatibility and hydration states. A comprehension of this can provide a perspective for understanding the biocompatibility of PMeOx and PEtOx in water-polymer interactions and may inspire the development of novel blood-compatible POX derivatives. The aforementioned four POXs are grafted onto glass substrates via photo-grafting, and their blood compatibility is estimated via platelet adhesion and the degree of denaturation of the adsorbed fibrinogen. The hydration states of the POXs are investigated using differential scanning calorimetry and attenuated total reflection infrared spectroscopy. Intermediate water is found to be present in hydrated PMeOx and PEtOx, but is observed to be scarce in hydrated PBuOx and PPhOx. This could be the reason for the biocompatibility of PMeOx and PEtOx. The carbonyl groups in PMeOx and PEtOx can be fully hydrated. However, in PBuOx and PPhOx, water mainly exists as bulk water. The hydration of the carbonyl groups is hindered by the bulky side chains, and IW cannot be generated.     

Syntheses of Conjugated Polymers for Photonics

Summary: By the Suzuki coupling reaction of 9,9-dioctyl-2,7-bis(1,3,2-dioxaborinan-2-yl)fluorene ( I ) and 3,5-di-tert-butylphenyl 2,5-dibromobenzenesulfonate ( II ) the alternating poly{[9,9-dioctylfluoren-2,7-diyl]-alt-[2-(3,5-di-tert-butyl-phenoxysulfonyl)-1,4-phenylene]} ( III ) was synthesized. Alkaline hydrolysis of III gave a conjugated polyelectrolyte carrying sulfonic acid groups ( IV ). Monomers 2,5-dibromo-3-[2-(pyren-1-yl)vinyl]thiophene and 2,5-dibromo-3-[2-(quinolin-4-yl)vinyl)thiophene were prepared and copolymerized with I to afford poly{[9,9-dioctylfluoren-2,7-diyl]-alt-[3-(2-(pyren-1-yl)vinyl)thiophen-2,5-diyl]} ( V ) and poly{[9,9-dioctylfluoren-2,7-diyl]-alt-[3-(2-(quinolin-4-yl)-vinyl)thiophen-2,5-diyl] ( VI ), respectively. Conjugated backbone of V contains the conjugated pyrene unit in the side chain. Similarly the side chain of VI contains the conjugated quinoline structure unit which can be for instance protonated. By the Suzuki polycondensation reaction of I and of the prepared methyl 3-(2,7-dibromocarbazole-9-yl)propionate ( VII ) the new poly{[9,9-dioctylfluorene-2,7-diyl]-alt-[9-(2-methoxycarbonylethyl)carbazole-2,7-diyl]} ( VIII ) was synthesized and characterized.     

Nucleic acid base grafted imino polyurethane

Preparation of two model polymers of polynucleotides with linear polyurethane backbone and 2-(thymin-1-yl)propionyl or 2-(uracil-1-yl)propionyl group as grafted pendant are described. 2-(Thymin-1-yl)propionic acid (TPA) and 2-(uracil-1-yl)propionic acid (UPA) were grafted into partial imino functionalized polyurethane, poly[(β,β′-diethylene)amine methylene bis(4-phenylcarbamate)]-75 (PU-NH-75), at the secondary amino group through amide bonds with 1-hydroxybenzotriazole (HOBT) using the active ester technique. Two novel polymer models of polynucleotides, poly[(N-(2-(thymin-1-yl)propionyl)-β,β′-diethylene)amine methylene bis(4-phenylcarbamate)]-75 (PU-NT-75) and poly[(N-(2-(uracil-1-yl)propionyl)-β,β′-diethylene)amine methylene bis(4-phenylcarbamate)]-75 (PU-NU-75) were obtained. The imino polyurethane PU-NH-75 was produced from the partially deprotected N-Cbz imino polyurethane, poly[N-(benzyloxycarbonyl-β,β′-diethylene)amine methylene bis(4-phenylcarbamate)] (PU-NCbz) which was prepared by the polyaddition of 4,4′-diphenylmethane diisocyanate (MDI) with diol monomer N-benzyloxycarbonyl-β,β′-dihydroxyethylamine (CbzHEA). Selective N-protection of N-benzyloxycarbonyloxy-5-norbornene-2,3-bicarboximide (CbzONB) with β,β′-dihydroxyethylamine (HEA) gave the N-Cbz protected diol monomer HEA. The related monomer model compounds were also prepared by the same methods.     

Synthesis of novel glycopeptide-polyoxazoline block copolymers by direct coupling between living anionic and cationic polymerization systems

A novel glycopeptide-containing block copolymer, poly[O-(tetra-O-acetyl-β-D -glucopyranosyl)-L -serine]-block-poly(2-methyl-2-oxazoline) ( 5 ), was synthesized by mutual termination of living polymerizations of a sugar-substituted α-amino acid N-carboxyanhydride (NCA) ( 1 ) and 2-methyl-2-oxazoline ( 3 ). 5 was deacetylated to provide the glycopeptide-polyoxazoline block copolymer, poly[O-(β-D -glucopyranosyl)-L -serine]-block-poly(2-methyl-2-oxazoline) ( 6 ).     

Polyethene with pendant 3-thienyl functionalities

Polyethene with 3-thienyl functionalities pendant on short-chain branches was prepared by catalytic random copolymerisation of ethene and 3-(penten-1-yl)thiophene; the functionalities can be used to graft poly(3-hexylthiophene) onto the polyethene surface.     

Photochemische Synthesen potentiell hypoglykämisch wirkender 3-Oxazoline

Photochemical Syntheses of 3-Oxazolines which Possibly Exhibit Hypoglycemic Activity Reactions of photochemically generated benzonitrile methylides 2 with carbonyl compounds 3 yielded 3-oxazolines of the types 5 and 6 (Scheme 1). Photooxidation of 5-[p-(dimethylamino)phenyl]-2,2-dimethyl-4-phenyl-3-oxazoline ( 5a ) gave 4′-(2,2-dimethyl-4-phenyl-3-oxazolin-5-yl)-N-methylformanilide ( 6r ) which could be transformed to 2,2-dimethyl-5-[p-(methylamino)phenyl]-4-phenyl-3-oxazoline ( 6s ) by photodecarbonylation. Thirty 3-oxazolines of types 5 and 6 have been synthesized and tested by oral and/or intraperitoneal administration to starved rats and obese-hyperglycemic mice.     

Development of Carbazole and Bipyridine Copolymers as Novel Photovoltaic Materials

Summary: A novel acrylate polymer with a carbazole pendant group and bipyridine derivatives as side chains was synthesized, in which derivatives of bipyridine as electro-optic chromophores and carbazole as photoconductive moiety were covalently linked to the acrylate backbone. 2–(Carbazol-9-yl)ethyl methacrylate (CEM) and methacrylic 2-[5-(2-{5,5′-dimethyl-6′-[2-(5-pentylthiophen-2-yl)vinyl]-3,3′-bipyridin-6-yl}vinyl)thiophen-2-yl]ethyl methacrylate (BiPy) were synthesized and then copolymerized to give 99:1, 98:2, 92:8 (mol/mol) CEM/BiPy copolymers. Films of the copolymers blended with poly(3-octylthiophene) (P3OT) or poly(3-decylthiophene) (PDT) and sandwiched between the transparent ITO and Al electrode were examined for photovoltaic properties.     

Investigation of the reaction of N-substituted indolylborates: Palladium catalyzed cross-coupling reactions and intramolecular alkyl migration reactions

The palladium catalyzed cross-coupling reaction of indolylborates with various N-protecting groups was investigated, where N-Methyl, N-methoxy, and N-tert-butoxycarbonyl groups were found to be useful. However, triethyl(1-methoxymethylindol-2-yl)borate could not be used for this reaction. It was also found that the alkyl migration reaction of trialkyl(1-methoxymethylindol-2-yl)borate produced 2-alkyl-1-methyl-indole accompanied by the unexpected reduction of 1-methoxymethyl group to 1-methyl group.     

Synthesis and characterization of liquid crystalline poly(N-acylethyleneimine)s

The synthesis of three cyclic imino ethers containing mesogenic groups attached to the heterocyclic unit through flexible spacers is described. Cationic ring-opening isomerization polymerization of two of them, i.e., 2-[4-(4-methoxy-4′-biphenyloxy)butyl]-2-oxazoline (MeOBiph-4-Oxz) and 2-[6-(4-methoxy-4′-biphenyloxy)hexyl]-2-oxazoline (MeOBiPh-6-Oxz) provided thermotropic liquid crystalline (LC) poly(N-acylethyleneimine)s, whereas the polymerization of 2-[4-(4-phenylphenoxy)butyl]-2-oxazoline (BiPh-4-Oxz) led to a crystalline polymer.     

Synthesis and characterization of biodegradable amphiphilic PEG-grafted poly(DTC-co-CL)

<正>A novel biodegradable copolymer,poly(5,5-dibromomethyltrimethylene carbonate-co-ε-caprolactone)(poly(DBTC-co-CL)) with pendant bromine groups,was synthesized via ring-opening polymerization(ROP) ofε-caprolactone(CL) and 5,5- dibromomethyltrimethylene carbonate(DBTC) using stannous octoate(Sn(Oct)_2) as catalyst.Then the pendant bromine groups were completely converted into azide form,which permitted"click"reaction with alkyne-terminated polyethylene(A-PEG) by Huisgen 1,3-dipolar cycloadditions preparing biodegradable amphiphilic poly(DTC-co-CL)-g-PEG graft copolymer.The graft copolymer was characterized by nuclear magnetic resonance(NMR) and size-exclusion chromatography(SEC).     

Synthesis and Functionalization of Isotactic Poly(propylene) Containing Pendant Styrene Groups

Summary: Copolymerization of propylene and 1,4‐divinylbenzene was successfully performed by a MgCl₂‐supported TiCl₄ catalyst, yielding isotactic poly(propylene) (i‐PP) polymers containing a few pendant styrene groups. With a metalation reaction with butyllithium and a hydrochlorination reaction with dry hydrogen chloride, the pendant styrene groups were quantitatively transformed into benzyllithium and 1‐chloroethylbenzene groups, respectively, which allowed the synthesis of i‐PP‐based graft copolymers by living anionic and atom transfer radical (ATRP) polymerization mechanisms.

The incorporation of styrene pendant groups into isotactic poly(propylene) using a Zeigler–Natta catalyst gave functionalized polymers able to undergo living anionic and atom transfer radical (ATRP) polymerizations.