Polymerization of N-carboxy–amino acid anhydrides in the solid state. II. Relation between polymerizability and molecular arrangement in L-leucine NCA and L-alanine NCA crystals

The polymerizability of N-carboxy–amino acid anhydrides (NCAs) of L -leucine and L -alanine was examined in the solid state and in solution. L -leucine NCA shows much higher reactivity in the solid state (when immersed in hexane) than in solution (in acetonitrile), but the opposite is true for L -alanine NCA. However, the two NCAs give similar values of apparent activation energy in each polymerization system. Rather high-molecular-weight polypeptides were obtained in the polymerization of L -leucine NCA in the solid state compared with those obtained in solution, while the molecular weight of polymers obtained from L -alanine NCA was higher in solution than in the solid state. IR spectra showed that α helices form mainly in the polymerization of both L -leucine NCA and L -alanine NCA in the solid state; a small amount of the β structure forms in the latter polymerization. X-ray diffraction and electron microscopy revealed that L -leucine NCA polymerizes predominantly along the c axis in the crystal, while the polymer chains grow in random directions in the crystal of L -alanine NCA. The difference can be explained by the molecular arrangement in the crystal. There are two requirements for high reactivity in the solid state: the five-membered rings of the monomer must form a layer structure and the polymer must occupy nearly the same space as the reacting monomer.     

Copolymerization of N-carboxy Nϵ-carbobenzoxy L-lysine anhydride with N-carboxy β-benzyl L-aspartate anhydride in acetonitrile

Copolymerization of N-carboxy N^?-carbobenzoxy L -lysine anydride with N-carboxy β-benzyl L -aspartate anhydride was initiated with n-butylamine in acetonitrile. The copolymerization proceeded almost homogeneously except for the initial stage, when the proportion of N-carboxy anhydride (NCA) in the polymerization mixture varied from 25 to 75 mol %. This was due to the fact that the copolypeptides formed were soluble or highly swollen in the solvent, in contrast to the homopolymerization of NCAs such as N^?-carbobenzoxy L -lysine NCA and β-benzyl L -aspartate NCA in acetonitrile, which proceeds heterogeneously. The compositions of the copolymers obtained were, within experimental error, the same as their monomer feed compositions. The initial rates of copolymerization were almost the same as the rate of homopolymerization of β-benzyl L -aspartate NCA, which propagates with a nonhelical polypeptide, but were slower than the rate of homopolymerization of N^?-carbobenzoxy L -lysine NCA, which propagates with a helical polypeptide.     

Multichain copoly(α-amino acid). III. Multichain copoly(α-amino acid) prepared by the reaction of copoly(L-lysine γ-methyl-L-glutamate) with N-carboxy anhydride of β-benzyl L-aspartate

Graft copolymerization of N-carboxy anhydride of β-benzyl-L -aspartate onto copoly(L -lysine γ-methyl-L -glutamate) was carried out in N,N-dimethylformaide which contained 3 v/v% of dimethyl sulfoxide to obtain multi-N^ε-poly(β-benzyl-L -aspartyl)copoly(L -lysine γ-methyl-L gluta mate). The degree of polymerization of the branch chain attained was much influenced by the interval of the grafting sites of the copoly(L -lysine γ-methyl-L -glutamate). The solvent-induced two-step conformational transition of the multichain copoly(α-amino acid) was observed in the chloroform-dichloroacetic acid system at 25°C by the ORD technique. The stability of the α-helical conformation of the backbone polymer chain was decreased by the presence of poly(β-benzyl-L -aspartyl) branch chains that could form unstable α-helical conformations of opposite spirals.     

Study on biodegradable polymer. 3. Synthesis and characterization of poly(DL-lactic acid)-co-poly(ethylene glycol)-co-poly(L-lysine) copolymer

The synthesis of poly(DL-lactic acid)-co-poly(ethylene glycol)-co-poly(L-lysine) copolymer was investigated by the reaction of amino acid-N-carboxy anhydride with lactic acid anhydrosulphite and methoxypolyoxyethylene amine (MPEG-NH₂). The successful synthesis was obtained after adding dibutylmegnesium into the system. The product was proved to be copolymer. The solubility of the polymer revealed that it was ionic polymer.     

Syntheses and radical polymerization behavior of novel optically active methacrylamides having (L)-leucine structure in the side chains

Syntheses and radical polymerizations of methacrylamides having (L)-leucine and N-methyl-(L)-leucine methyl ester structures in the side chains N-methacryloyl-(L)-leucine methyl ester (MA-L-M) and N-methyl-N-methacryloyl-(L)-leucine methyl ester (N-Me-MA-L-M) were carried out. The monomers were prepared by the reactions of methacryloyl chloride with the corresponding amino acid methyl esters. Radical polymerizations were carried out in the presence of appropriate initiators at 60°C and 120°C. MA-L-M afforded the corresponding polymer with M_ns 38,000 ∼ 372,000 in high yields, while N-Me-MA-L-M afforded a trace amount of polymer at 60°C and in a low yield even at 120°C. Both inversion and increase of absolute value of specific rotation were observed in the transformation from MA-L-M (+1.3°C) to poly(MA-L-M) (−35.7°C). Changes in the CD spectral pattern and the conformation of the leucine moiety were confirmed from the monomer to polymer. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2681–2690, 1998     

Synthesis of Novel a PEG-Lysine Polymer

Summary: A novel PEG functionalized-L-lysine-α-amino-N-carboxy anhydride monomer (L-Lys(PEG-(COOBzl))-NCA) is prepared for the synthesis of carboxylic acid terminated, PEG-sheathed poly-lysine biopolymers.     

Synthesis of poly[S-(2–9′-acridinylethyl)-L-cysteine] and its TCNQ salt

Poly[S-(2–9′-acridinylethyl)-L -cysteine] ( 5 ) was synthesized by the N-carboxy anhydride procedure. It was converted to the trifluoroacetic acid salt ( 6 ), which was treated with LiTCNQ in methanol to give the TCNQ anion radical salt ( 7 ). 7 showed electrical conductivity of 10^?8 S/cm at 295 K.     

Syntheses and radical polymerizations of novel optically active vinyl and isopropenyl carbamates having L-leucine structures

Syntheses and radical polymerizations of vinyl and isopropenyl carbamates having L -leucine methyl ester structures, N-vinyloxycarbonyl-L -leucine methyl ester (VOC-L-M) and N-isopropenyloxycarbonyl-L -leucine methyl ester (IOC-L-M), were carried out. VOC-L-M and IOC-L-M were prepared by the reactions of L -leucine methyl ester with vinyl and isopropenyl chloroformates in the presence of sodium hydrogen carbonate. The radical polymerization of VOC-L-M with AIBN (1 mol %) in bulk, chlorobenzene, methanol, and N,N-dimethylformamide afforded the corresponding polymer (poly(VOC-L-M)) with M _n 7,400–19,000. Meanwhile, IOC-L-M afforded no polymer with AIBN at 60°C but afforded a polymer having low molecular weight with BPO at 80°C. The glass transition temperatures of poly(VOC-L-M) and poly(IOC-L-M) were 53 and 65°C, respectively. The 10% weight loss temperatures of poly(VOC-L-M) and poly(IOC-L-M) under nitrogen were 255 and 173, respectively. The copolymerization parameters of VOC-L-M (M₁) and vinyl acetate (M₂) were evaluated as r₁ = 0.92 and r₂ = 0.63. © 1996 John Wiley & Sons, Inc.     

Multichain copoly(α-amino acid). I. Multichain copoly(α-amino acid) prepared by reaction of copoly(L-lysine γ-methyl-L-glutamate) with N-carboxy anhydride of Nϵ-carbobenzyloxy-L-lysine

Polymerization of the N-carboxy anhydride of N^?-carbobenzyloxy-L -lysine in the presence of multifunctional polymeric initiator, copoly(L -lysine γ-methyl-L -glutamate) was studied in N,N-dimethylformamide containing 3% (v/v) of dimethyl sulfoxide. Multichain copoly(α-amino acid), i.e., multi-N^?-poly(N^?-carbobenzyloxy-L -lysine)copoly(L -lysine γ-methyl-L -glutamate), was obtained with linear poly(N^?-carbobenzyloxy-L -lysine) as by-product that could be removed by reprecipitation as was evidenced by gel-permeation chromatography. The degree of polymerization of the branch polymer chains estimated by the osmometric molecular weight determination and amino acid analysis was between 20 and 60, which decreased with increasing lysine content of the polymeric initiator. The stability of α-helical conformation of the multichain copoly(α-amino acid) was studied in the chloroform–dichloroacetic acid system at 25°C by the ORD technique. The α-helical conformation of poly(N^?-carbobenzyloxy-L -lysine) branches was less stable than those of linear poly(N^?-carbobenzyloxy-L -lysine) and the core molecular chains of the multichain copoly(α-amino acid).     

Preparation of optically active N-bornyl maleimide and poly(N-bornyl maleimide)

Optically active N-bornyl maleimide (NBMI) was prepared with maleie anhydride and d-camphor amine and the polymerizations of N-bornyl maleimide were carried out with benzoyl peroxide (BPO), α,α′-azobisisobutyronitrile (AIBN) and n-butyllithium. The specific rotations of the polymers obtained by BPO, AIBN, and n-BuLi were +5.1 to +8.4, +10.0 to +10.1 and ?7.0 to ?9.0, respectively. The results of the x-ray analysis for the above polymers showed that these polymers had the same structure. The specific rotation of the polymer initiated by BPO increased with increasing intrinsic viscosity. The effect of the polymer endgroup on the specific rotation was discussed.     

Synthesis and properties of alkylene-linked aromatic polyimides

Alkylene-linked aromatic polyimides were prepared from a family of new dianhydride monomers and aromatic diamines. The dianhydrides were synthesized by Friedel-Crafts catalysis of the condensation of ditertiary alcohols with o-xylene, subsequent oxidation of the aryl methyl groups to carboxy, and finally, dehydration of the ortho-carboxy substituents to anhydride groups. Alkylene-linked aromatic polyimides, with up to 8 methylene groups in the polymer chain, are stable to 400°C in air and can be extruded or compression-molded at 300°C. In addition, these polymers are soluble in solvents within the solubility parameter range of 10.4 ± 1.2.     

Asymmetric interaction of optically active polymers with asymmetric small molecules. IV. Effect of hydrophobic groups on asymmetric interaction

In order to investigate the mechanism of the asymmetric interaction between optically active polymers and small molecules, optically active copolymers of N-acrylyl L-amino acids(N-acrylyl-L -phenylalanine, N-acrylyl-L -tryptophan, and N-acrylyl-L -leucine, respectively) and N,N′-hexamethylene diacrylylamide were synthesized, and interaction of these polymers with the optical isomers of phenylalanine and tryptophan was investigated. In the interaction of these acidic polymers with amino acids performed at pH 5.0, significant difference in amount of adsorption between the D and L isomers of amino acids were observed, and the L form of amino acids was adsorbed preferentially. The interaction between optically active small molecules was also investigated: these results showed a similarity to the results for interaction between optically active polymers and amino acids. In some instances of asymmetric interaction the influence of hydrophobic interaction between a polymer and substrate was clearly perceived. The stereoselective effects on the asymmetric interaction are discussed.     

Multichain copoly(α-amino acid). II. Preparation and properties of multi-Nϵ-poly(γ-benzyl-L-glutamyl)copoly(L-lysine γ-methyl-L-glutamate)

A number of multi-N^?-poly(γ-benzyl-L -glutamyl)copoly(L -lysine γ-methyl-L -glutamate)s with branches having various degrees of polymerization and with various intervals of the grafting sites in the core molecule were prepared in N,N-dimethylformamide containing dimethyl sulfoxide by the reaction of N-carboxy anhydride of γ-benzyl L -glutamate with random copoly(L -lysine γ-methyl-L -glutamate)s of different composition with various anhydride-initiator ratios. The relationship between the intrinsic viscosity measured in a coil solvent, dichloroacetic acid (DCA), and the number-average molecular weight determined by osmometry was found to be expressed by the Mark–Houwink–Sakurada equation for the multichain copoly(α-amino acid)s which were made from the same polymeric initiator. The observed α values of the multichain copoly(α-amino acid)s in the equation were lower than that of linear poly(γ-benzyl-L -glutamate). The solvent induced helix–coil transition of the multichain copolymer was investigated in the chloroform?DCA system by the ORD technique. Two kinds of transition regions were clearly distinguished: The α-helices of the core molecules underwent the transition at lower DCA concentration and those of the branch chains at higher DCA concentration. The reduced viscosity of the multichain copoly-(α-amino acid) increased slightly between the two transition regions, in contrast to the large decrease in the reduced viscosity of linear poly(γ-benzyl-L -glutamate) during the helix–coil transition.     

Size-Selective Encapsulation Property of Unimolecular Reverse Micelle Consisting of Hyperbranched D-Glucan Core and L-Leucine Ethyl Ether Shell

The synthesis of a unimolecular reverse micelle ( 3 ) consisting of hyperbranched D -glucan as the core and L -leucine ethyl ester as the shell was accomplished through the carbamation reaction of the hyperbranched D -glucan ( 1 ) with the N-carbonyl L -leucine ethyl ester ( 2 ) in pyridine at 100 °C. The polymer 3 was soluble in a large variety of organic solvents, such as methanol, acetone, chloroform, and ethyl acetate, and insoluble in water, which remarkably differed from the solubility of 1 . The solubilities of 3 were also changed by the substitution degrees of the L -leucine moiety. The encapsulation ability of 3 toward water-soluble dyes has been investigated. These results indicated that 3 was a unimolecular reverse micelle with an encapsulation ability toward hydrophilic dye molecules. In addition, 3 showed an molecular size-selective encapsulation ability.     

Polymerization of DL-alanine NCA and L-alanine NCA

The polymerization of N-carboxy-DL -alanine anhydride and N-carboxy-L -alanine anhydride were carried out in various solvents such as acetonitrile, dimethyl sulfoxide (DMSO), and nitrobenzene. The x-ray diffraction diagram and the infrared spectra of the polymers of DL - and L -alanine were obtained. The polypeptides obtained in acetonitrile and in nitrobenzene were in the α conformation, and the conformation of polypeptide obtained in acetonitrile was not influenced by its molecular weight. The polypeptide obtained in DMSO was essentially in the β conformation. It was observed that the α and β forms of polyalanine were altered on treatment of the polymer with m-cresol, dichloroacetic acid, or formic acid.     

Functionalization of a poly(vinyl alcohol) in the solid state with a swelling agent by methacrylic anhydride

Poly(vinyl alcohol‐co‐vinyl acetate) was functionalized by methacrylic anhydride to introduce functional groups by a new process that consisted of modifying a polymer directly from a powder form in the solid state. To favor the diffusion of the reagents, a swelling agent composed by a mixture of ethylene carbonate and propylene carbonate was used. N‐methylimidazole was used as a basic catalyst of the esterification reaction, adjusting the reaction times. This work presents the process and the effects of the formulation on anhydride conversion. The side reactions were also determined; they all involved N‐methylimidazole. Decarboxylation reactions of the carbonates were characterized, that is, going from ethylene carbonate to ethylene glycol, which is able to react with two anhydride molecules by esterification reactions to, respectively, form 2‐hydroxyethyl 2‐methylpropenoate and ethyl 1,2‐bis(2‐methyl propenoate). The same side reactions are possible with propylene carbonate but are less reactive than the starting ethylene carbonate. Model anhydrides such as hexanoic and heptanoic anhydrides, less reactive than methacrylic anhydride, were used to characterize a new anhydride decarboxylation reaction. The homogeneity of the grafting is also discussed, especially its dependence on the polymer properties, the diffusion modes of the reagents (carbonate mixture and the anhydride), and the competition between the diffusional and chemical kinetics of methacrylic anhydride. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1618–1629, 2004     

Solution properties of poly(4,4′-oxydiphenylene)-4-amidophthalamic acid

A series of polymers based on 4-chloroformyl phthalic anhydride (TMAC) and 4,4′-diaminodi-phenylether (DAPE) was prepared and shown to be soluble in N, N-dimethylacetamide which contained 0.1N LiBr. These solutions were characterized by light scattering, membrane osmometry, and viscosity. A relationship between the viscosity and molecular weight was formulated and the nature of the polymer chain in solution was postulated.     

5,6-Dimethylbenz[c]acridine functionalized in the 7-position

5,6-Dimethylbenz[c]acridines, functionalized in the 7-position by the carboxy, carbomethoxy, carboxamido, N-ethylcarboxamido, acetyl, cyano, chloro, methoxy or amino group are reported for the first time. Also various related 5,5-dimethyl-5,6-dihydrobenz[c]acridines including the 7-carbomethoxy, 6-hydroxy-7-carboxy, 6-bromo-7-carbomethoxy, 6-methoxy-7-carboxy, 6-methoxy-7-carbomethoxy, and 6-hydroxy-7-N-ethylcarboxamido derivatives which serve as precursors to the completely aromatized 5,6-dimethylbenz[c]acridines are also reported for the first time.     

Study on biodegradable polymers: synthesis and characterization of poly(DL-lactic acid-co-l-lysine) random copolymer

Poly(DL-lactic acid-co-l-lysine) (PLAL) random copolymer was obtained by copolymerization of amino acid-N-carboxy anhydride with lactic acid anhydrosulphite in the presence of an initiator. The structures of the poly(DL-lactic acid-co-ε-cbz-l-lysine) and PLAL were characterized by IR, ¹H-NMR, ¹³C-NMR and elemental analysis. Different initiators were used to initiate the ring-opening copolymerization. Good agreement between calculated and actual compositions was observed in most cases when using dibutylzinc as initiator. The solubility of PLAL was discussed.     

Novel polybenzoxazinones with tricyclic fused-rings

A series of polybenzoxazinones containing phenoxathiin and phenoxaphosphine units were prepared from tricyclic diacid chlorides and 4,4′-diaminobiphenyl-3,3′-dicarboxylic acid and 4,4′-diamino-3,3′-diphenylmethane dicarboxylic acid. The low temperature solution polymerization technique afforded polyamic acid which subsequently underwent cyclization along the polymer chain in a solvent mixture of refluxing N,N′-dimethylacetamide, acetic anhydride, and pyridine to give polybenzoxazinones in moderate yields. The polymers thus obtained had inherent viscosities in the range of 0.15–0.23 dL/g, were sparingly soluble in N-methyl-2-pyrrolidone, and were found to be thermally more stable than the corresponding open-chain polymer with diphenylether linkage.