Growth mechanism of crystals of glycine-L-alanine copolymer in the course of polymerization

In order to examine the growth mechanism of copolymer crystals formed during polymerization, the heterogeneous copolymerization of glycine N-carboxy anhydride (NCA) and L -alanine NCA has been studied in acetonitrile. In the polymerization systems with higher contents of glycine, the crystal growth occurs through formation of the cross-β type structure as proposed previously for poly(S-methyl-L -cysteine), giving rise to chain-folded crystals and rather high conversions. The high conversion is accounted for by the widening of the cross-section of the β-chains in the backbone crystal, due to the introduction of L -alanine residues into the polyglycine chain. Copolymerization at higher contents of L -alanine leads to conversions over 90% and extended chain crystals, due to the formation of α-helices on the ribbon-like crystals composed of the β-structure just as in the case of L -alanine NCA homopolymerization, indicating the occlusion of the glycine residues into the helices.     

15N NMR spectroscopy, 13. Copolymerization of glycine-N-carboxyanhydride and β-alanine-N-carboxyanhydride

In contrast to ¹³C NMR spectra, ¹⁵N NMR spectra allow one to characterize the sequence of copolypeptides built up by glycyl and β-alanyl residues, because the shifts of the Gly-Gly, β-Ala-Gly, Gly-β-Ala, and β-Ala-β-Ala bonds differ from each other by several p.p.m. Hence, the copolymerization of glycine-NCA and β-Alanine-NCA can be investigated by quantitative evaluation of the ¹⁵N NMR spectra obtained from the resulting copolymers. The copolymerization of these two amino acid NCAs initiated by primary amines leads to random sequences; the copolymerization is azeotropic in nature, and both copolymerization reactivity ratio parameters are near 1. If aprotic bases like pyridine and triethylamine are used as catalysts, the rate of incorporation of glycine is higher than that of β-alanine and the copolymers possess a block structure.     

Polymers containing enzymatically degradable bonds, 1. Chymotrypsin catalyzed hydrolysis of p-nitroanilides of phenylalanine and tyrosine attached to side-chains of copolymers of N-(2-hydroxypropyl)methacrylamide

A series of copolymers of N-(2-hydroxypropyl)methacrylamide were prepared, which contained side chains of the general formula -Gly-X-Y-NAp, where Gly ¨ glycine; X ¨ glycine, alanine, β-alanine, valine, leucine, isoleucine, phenylalanine; Y ¨ phenylalanine or tyrosine; NAp ¨ p-nitroanilide, the latter modelling biologically active compounds. The rates of chymotrypsin-catalyzed hydrolysis of p-nitroanilide groups at pH = 8,0 and 25°C were determined over a range of substrate concentrations to derive values for k_cat and K_M. The results allowed us to determine the influence of the structure of side chains on the rate of cleavage of Y-NAp. The increase in the susceptibility to chymotrypsin attack with an increasing spacing of the Y-NAp residue from the backbone of the polymer chains is demonstrated by comparing the kinetic data of copolymers containing -Gly-Gly-Phe-Phe-NAp, -Gly-Gly-Phe-NAp and -Gly-Phe-NAp side chains. Results obtained with α-chymotrypsin were compared with the cleavage of the above polymer substrates with chymotrypsin covalently bound to a copolymer of N-(2-hydroxypropyl)methacrylamide.     

Growth mechanism of crystals of glycine/S-methyl-L-cysteine copolymer in the course of polymerization

In order to examine the growth mechanism of copolymer crystals formed during polymerization, the heterogeneous copolymerization of glycine N-carboxy anhydride (2,5-dioxo-1-oxa-3-azacyclopentane) and S-methyl-L -cysteine N-carboxy anhydride (4-methylthiomethyl-2,5-dioxo-1-oxa-3-azacyclopentane) was studied in acetonitrile. In all the polymerization systems, the crystal growth occurs through formation of the cross-β-type structure. The high conversion in the glycine-rich systems is accounted for by the widening of the cross-section of the β-chain in the backbone crystal, due to the introduction of S-methyl-L -cysteine residues into the polyglycine chain. On the other hand, the narrowing of the cross-sectional area per chain in the skeleton crystals of the oligomer gave rise to the lowering of the conversion in the S-methyl-L -cysteine-rich systems. This shows the importance of the effect of the cross-sectional area of the oligomer chain (of the β structure) in the crystal formed in the begining relative to that of the growing (α-helical) chain. The glycine residue seems to be incorporated into the crystalline lattice of the S-methyl-L -cysteine and vice versa.     

Lipase‐Catalyzed Ring‐Opening Polymerization of Lactones in the Presence of Aliphatic Polyesters to Ester Copolymers

Ring‐opening polymerization of macrolides in the presence of aliphatic polyesters has been performed using Pseudomonas lipase as catalyst to produce ester copolymers with molecular weights of several thousands. The polymerization behavior was monitored by SEC and NMR. ¹³C NMR analysis showed that the resulting polymer was not a mixture of the starting polyester and the polymer from the macrolide, but a random copolymer consisting of both units. These data indicate that the lipase catalyzed the polymerization of the macrolide as well as the intermolecular transesterification of the starting and resulting polymers. The random copolymer was found to be highly crystalline by DSC and WAXD measurement. The present specific catalysis of the lipase was applied to the synthesis of ester copolymers by transesterification between two different polyesters.     

The hyperpolarization of spinal motoneurones by glycine and related amino acids

Summary Electrophoretically administered glycine, -alanine and GABA hyperpolarize spinal motoneurones in cats anaesthetized with pentobarbitone. The reversal potential for these hyperpolarizations is similar to that of inhibitory postsynaptic potentials. Alterations in intracellular K⁺ and Cl^– ion concentrations, and intracellular injection of a series of anions of different hydrated ion size, affect inhibitory and amino acid potentials in the same fashion. Hence it is probable that glycine, -alanine and GABA produce an alteration in membrane permeability similar to that produced by spinal inhibitory synaptic transmitters. Strychnine reversibly blocks the action of inhibitory transmitters, glycine and -alanine, but is without effect on the hyperpolarizing action of GABA.These results indicate that glycine may be a major spinal inhibitory transmitter, in which case strychnine affects spinal postsynaptic inhibition by limiting the action of glycine upon subsynaptic inhibitory receptors.Supported by a grant from the Swiss Academy of Medical Sciences.     

Preparation and characterization of poly(methyl-3,3,3-trifluoropropylsiloxane-co-dimethylsiloxane)

Methyl-3,3,3-trifluoropropylsiloxane (F)-dimethylsiloxane (D) random and block copolymers were prepared. The random copolymers were prepared by equilibrium copolymerization starting from a mixture of cyclic F and D siloxanes with potassium silanolate as the catalyst. The F-D block copolymer was prepared by sequential anionic living polymerization of strained cyclic trisiloxanes using butyllithium as initiator, first polymerizing D₃ then adding F₃ after consumption of D₃. The copolymer microstructure was established by means of ²⁹Si NMR, differential scanning calorimetry (DSC), and gel-permeation chromatography (GPC). Characteristic glass transition temperature (T_g) shifts were observed depending on the F:D ratio of the random copolymers. It was demonstrated that the tensile strength of the poly(methyl-3,3,3-trifluoropropylsiloxane)-poly(dimethylsiloxane) (PTFPMS-PDMS) blend system was improved when either of the copolymers was added.     

Effect of Crosslinking on Block and Random Copolymers of Styrene and Butadiene

The effect of crosslinking on the molecular dynamics of two triblock copolymers and a random copolymer is investigated and compared. Dynamic‐mechanical measurements were done to evaluate both real and imaginary parts (J′, J″) of shear compliance in wide temperature and frequency windows, –95 to 120°C and 10^–4 to 10 Hz, respectively. Moreover, DSC as well as stress‐strain measurements were carried out. The materials used in this study are two triblock copolymers, mainly styrene‐butadiene‐styrene, (SBS) triblock copolymer, in addition to styrene‐butadiene‐rubber (SBR) random copolymer. The materials were crosslinked by means of dicumylperoxide (DCUP) up to 10 parts per hundred of rubber (phr) to obtain different crosslinking concentrations. Complete master curves were constructed for all samples and analyzed using Cole‐Cole processes. It is shown that crosslinking of block copolymers has a much stronger effect on the dynamics of the polybutadiene (PB) phase in block copolymers than in random copolymers having the same styrene content. The results were discussed using the meander model of Pechhold, and the Mooney‐Rivlin and Mullins equations.     

Characterization of ethylene-propene copolymers prepared with heterogeneous titanium-based catalysts

Ethylene-propene (EP) copolymers prepared with various heterogeneous titanium-based Ziegler-Natta catalysts, i. e., δ-TiCl₃, β-TiCl₃, and MgCl₂-supported titanium catalysts were fractionated by successive solvent extraction. Wide composition distributions were observed for all samples. Composition distributions of some samples were investigated precisely by temperature-programmed elution column fractionation. The fractionation data showed that these copolymers are a mixture of polyethylene and of copolymers with different structures, i. e., random and block copolymers. In every sample random copolymers were found most abundantly, the propylene sequences being present only as mmmm pentads. These data suggest that random copolymer is formed on an isospecific site.     

Polypeptides containing adenine and uracil residues

Amino acids containing uracil, adenine and imidazole residues were prepared and polymerized by reacting with phosgene in ethylene carbonate. The polymers did not have a simple polypeptidic structure but were soluble in aqueous dimethylformamide and interacted with complementary polynucleotides. Alternative polymerization of amino acids by N,N′-carbonyldiimidazole in aqueous neutral buffers proceeded with very low conversion but pure polypeptides resulted from the reaction. The following amino acids were prepared: β-adenin-9-yl-α-alanine ( 1a ), N-methyl-β-(adenin-9-yl)-α-alanine ( 1b ), β-(uracil-1-yl)-α-alanine, ( 2a ), N-methyl-β-(uracil-1-yl)-α-alanine ( 2b ), β-(5,6-trimethyleneuracil-1-yl)-α-alanine ( 3 ), and β-(imidazol-1-yl)-α-alanine.     

Study of diethyl 3,12-diaza-4,11-dioxotetradecanedioate as a model compound of poly(ester amide)s derived from glycine

The conformation of the molecule of diethyl 3,12-diaza-4,11-dioxotetradecanedioate (EtGSGEt) has been investigated in the crystalline state by X-ray analysis. EtGSGEt crystallizes in the monoclinic system, space group P112₁/n with a = 4.8174(7) Å, b = 4.9008(5) Å, c = 43.616(5) Å and γ = 112.854(10)°. 965 independent reflections were used in the refinement to the final agreement factor of R = 8.36%. The glycine residues of EtGSGEt are related by an inversion center and adopt a conformation, which slightly deviates from that characteristic of the polyglycine II structure. An all-trans conformation was deduced for the suberamide unit. The packing characteristics of the diamide are similar to that found in the α form of nylons.     

Condensation polymerization of N-dithiocarbonyl alkoxycarbonyl-amino acids. Part I. Synthesis and condensation polymerization of N-dithiocarbonyl ethoxycarbonyl-amino acids

N-dithiocarbonyl ethoxycarbonyl-amino acids (III), were synthesized in crystalline form from various amino acids by the addition of ethyl chlorocarbonate to dithiocarbamic acid salt obtained from amino acid and CS₂ at low temperature. When the reaction was performed above room temperature, polypeptides could directly be obtained without getting III. Compounds such as III were synthesized from glycine, DL -α-alanine, DL -valine, DL-methionine, L-leucine, glycylglycine, β-alanine, γ-amino-n-butyric acid and ε-amino-n-caproic acid in this paper. III were polymerized to polypeptides in high yields in the presence of a basic catalyst or by heating; acid inhibited the polymerization of III.     

Asymmetric synthesis catalyzed by oligo((S)-alanine)

In the asymmetric addition of 1-dodecanethiol to isopropenyl methyl ketone catalyzed by the terminal primary amino group of oligo((S)-alanine) ( 1c ), the trimer and the tetramer in β-conformation gave much higher optical yield than the monomer and the dimer in random conformation. A similar result was obtained in the catalysis by β-alanyl-poly((S)-alanine) ( 3 ).     

Sodium Poly(α,L‐glutamate)/Ethylene Oxide‐Propylene Oxide (Block and Random) Copolymer Macromolecular Complexes. Method of Preparation and Structure of Complex

Macromolecular complexes of sodium poly(α,L ‐glutamate) (PGNA) (molecular weight (MW) 1, 49 and 71 k) and ethylene oxide‐propylene oxide tri‐block copolymer (MW 8 400) have been prepared by a novel method involving dehydration of reverse micelles (DRM method). This series of complexes was compared with the complexes of PGNA (MW 1, 49 and 71 k)/ethylene oxide‐propylene oxide random and tri‐block copolymers prepared by the common method involving evaporation of aqueous mixtures (EAM method). By the DRM process fifteen times more copolymer was incorporated in the pure macromolecular complex than by the EAM process. CD spectra of the EAM series of complexes showed formation of α‐helical PGNA conformation as evidenced by the observation of +ve peak at 194 nm and two –ve peaks at 201 and 221 nm. Formation of the α‐helical conformation is further supported by FT‐IR spectroscopy. On the other hand, CD spectra of the DRM macromolecular complexes showed neither α‐helical nor random conformation, and the spectra may be attributed to a distorted helical PGNA conformation. DSC studies revealed that the copolymers in EAM macromolecular complexes were intimately blended with PGNA, while in the DRM series only 65% of the copolymer were blended at the molecular level, with the rest present as a pure copolymer domain. ²³Na NMR spectra of both series of complexes showed presence of free sodium ions indicative of dissociated Na⁺—O dipolar interactions in aqueous solution. Hydrophobic interaction between PGNA and copolymer remained intact even in very dilute solutions of both series of complexes as observed by strong 2D‐NOESY ¹H NMR correlation between β and γ CH₂ groups of PGNA and CH₂ groups of copolymers. However, in the DRM series, only the CH₂ groups of PEO blocks of the PEO‐PPO‐PEO copolymer showed the 2D‐NOESY ¹H NMR correlation indicating that only the PEO blocks are involved in the complex formation. The PPO block that had no interaction with PGNA may have formed pure PPO domains. NMR data combined with the DSC, CD and FT‐IR data suggest that the structure of both series of macromolecular complex is a composite composed of copolymer molecules intimately interacting with PGNA chains. Interactions between β and γ groups of PGNA side groups with CH₂ groups of the copolymer are involved in forming the complex. 2D‐NOESY ¹H NMR correlation further indicate that both the DRM and EAM series of macromolecular complexes are stable in water for at least seven weeks.     

Polymerization of β-aminopropionitrile

The polymerization of β-aminopropionitrile (β-APN) was carried out by using basic catalysts such as sodium sec-butoxide in organic solvents and gave polyamidine which was converted to poly-β-alanine by hydrolysis. Poly-β-alanine was identified by IR and ¹H -NMR spectra and elemental analysis. The degree of polymerization was determined to 9,1 by vapor pressure osmometry. Free β-alanine was obtained by hydrolysis of the poly-β-alanine. From a kinetic study of this polymerization, it was found that the rate of polymerization was The polymerization mechanism of β-APN is discussed.     

Microstructure of poly[polytetrahydrofuran-block-poly(sebacoylchloride-alt-hexamethylenediamine)] and its role in blood compatibility

The microstructure of poly[polytetrahydrofuran-block-poly(sebacoyl chloride-alt-hexamethylenediamine)]s 1–4 , containing polytetrahydrofuran (PTHF) blocks of various molecular weights, and their blood compatibility were studied. These multiblock copolymers were prepared by interfacial polycondensation. The characterization of these copolymers was carried out by means of transmission electron microscopy (TEM), differential scanning calorimetry (DSC), dynamic mechanical measurements, wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS), and electron spectroscopy for chemical analysis (ESCA). The TEM observation revealed the formation of a spherulitic structure at the copolymer surfaces, which is closely related to the homopolymer, polyamide (PA) 610. The DSC and dynamic mechanical measurements indicate the presence of distinct phase separation between PTHF and PA 610 blocks, and of the PTHF block in the copolymer being partially crystallized. The WAXD and SAXS indicate the formation of microstructures composed of crystalline and amorphous phases in the copolymer. Moreover, ESCA measurements verify that the surface chemical composition of the copolymer is identical to their bulk composition. Blood compatibility of these copolymers was evaluated by estimating platelet adhesion on the copolymer surfaces. Platelet adhesion was found to be affected by the PA 610 crystallinity, including the size and distribution of the crystalline phase in the case of the copolymers in which the PTHF blocks are completely amorphous (M?_n = 980). On the contrary, platelet adhesion at the copolymers in which the PTHF blocks are partially crystallized (M?_n ≥ 1560) depends upon the crystallinity of both PA 610 and PTHF, including the balance of crystalline (PA 610 and PTHF) and amorphous (mainly PTHF) phases. This result suggests that the balance of the crystalline and amorphous phase distribution in the copolymer is the most determinative factor for suppressing platelet adhesion at the copolymer surface.     

New amphiphilic copolymers of N-phenylmaleimides and vinyl ethers: thermal properties,Langmuir and Langmuir-Blodgett films,gas permeation

Amphiphilic copolymers 1 a–1d were prepared by radical copolymerization of hydrophilic N-phenylmaleimide derivatives and lipophilic vinyl ethers in dichloromethane. Though the starting concentrations of the two monomers were always equimolar, none of the copolymers had a strictly alternating structure. Molecular weights were between 10⁴ and 9 · 10⁴. The copolymers prepared from ethyl 4-maleimidobenzoate ( 2a ) and isobutyl vinyl ether ( 3a ) (copolymer 1a ), and 2a and isooctyl vinyl ether ( 3b ) (copolymer 1b ) were thermally stable up to 300°C and showed glass transitions at about 150°C, while the copolymers prepared from 2a and octadecyl vinyl ether ( 3c ) (copolymer 1c ), and 4-maleimidobenzoic acid ( 2b ) and 3c (copolymer 1 d ) were considerably less stable. All copolymers formed stable, condensed monomolecular layers at the air-water interface, which could be transferred onto hydrophobic supports by the Langmuir-Blodgett (LB) technique. Up to the 20th dipping cycle, a Y-type deposition was found, while further dipping predominantly led to Z-type deposition. Nitrogen and oxygen permeabilities (p) were studied after depositing the LB films onto porous Celgard membranes. Permeability and selectivity were dependent on the nature of the alkyl substituent group of the polymer. Copolymer 1a with the isobutyl group showed higher permeabilities than copolymer 1c with the octadecyl group, but no selectivity. The copolymer with the small alkyl group showed no selectivity of oxygen over nitrogen (α = )P_O2/P_N2 while for the copolymer with the long alkyl chain the α-value was 1,3.     

Syntheses and Properties of Novel Copolymers of Poly(1,4‐dioxane‐2‐one) and Aliphatic Polycarbonate Based on Ketal‐Protected Dihydroxyacetone

Novel random copolymers of 1,4‐dioxane‐2‐one (DON) and 2,2‐ethylenedioxy‐1,3‐propanediol carbonate (EOPDC) are synthesized in bulk at 120 °C using Sn(Oct)₂ as a catalyst. The effects of different molar feed ratios of EOPDC/DON on the yield and molecular weight of the copolymers are investigated. The copolymers are obtained with a yield of 55.4–98%. The number‐average molecular weight of the copolymer is 0.49–4.18 × 10⁴ g mol^?1 with a polydispersity of 1.52–1.68. The poly(DON‐co‐EOPDC)s obtained are characterized by FTIR, ¹H NMR, and ¹³C NMR spectroscopy, gel‐permeation chromatography (GPC), and DSC. The hydrolytic degradation of the copolymer in phosphate buffered saline (PBS) is also investigated. The results show that both the hydrophilicity and the degradation rate of the copolymers increase with increasing copolymer DON content.     

Asymmetric copolymerization of styrene homologues with oxygen

Styrene homologues (styrene, α-methylstyrene, and β-methylstyrene) were copolymerized with oxygen to produce optically active copolymers in the presence of a chiral Co(II) (Schiffbase) complex. The absolute configuration of the carbon atom in the copolymer chain was determined by hydrogenolysis of the copolymer to phenylethanediol derivatives. In the cases of styrene and α-methylstyrene, (R)-(+)-1-phenylethanediol and (R)-(+)-2-phenyl-1,2-propanediol were preferentially formed, respectively. In the reaction of β-methylstyrene, the preferential formation of (1S, 2R)-(?)- and/or (1R, 2R)-(?)-1-phenyl-1,2-propanediol was observed. The chiral Co(II) (Schiff-base) complex seems to stabilize both the peroxy-and the peroxyalkyl radical.     

Heterogeneous polymerization of L-alanine N-carboxy anhydride initiated by amines having primary and tertiary amino groups

Various amines such as aniline (A), N,N-diethyl-1,3-propanediamine (DPD), and pamino-N,N-diethylaniline (ADA), were used as initiators in the heterogeneous polymerization of L -alanine N-carboxy anhydride (L -alanine NCA), (4-methyl-2,5-dioxo-1-oxa-3-azacyclopentane). When ADA is used as initiator, the initiation reaction proceeds via normal amine initiation as for primary monoamines. On the other hand, in the polymerization initiated by DPD, the initiation reaction takes place from both the primary and tertiary amino groups of the initiator. In all systems, the propagation proceeds by nucleophilic attack of the amino groups of the growing chains on the C⁽⁵⁾ of the L -alanine NCA ring. The resultant polymers obtained in the case of the initiators A or ADA had wider molecular weight distributions than those from DPD-initiated polymerization. Oligomers and polymers obtained using DPD as initiator were in the form of β-and α-conformations, respectively. However, mixtures of both β-structure and α-helix were formed in the polymerization initiated by A or ADA. It is suggested that the number of the growing chain ends occluded in the precipitate is increasing in the following order with respect to the initiator used: DPD<A≈ADA. The morphologies of the resultant polymer crystals were in good agreement with the results from IR and X-ray analysis.