Poly(γ-alkyl glutamates). I

Good yields of some crystalline γ-alkyl esters of L -glutamic acid were obtained by carrying out the esterfication with a small (20–50 mole-%) excess of alcohol in aqueous hydrochloric acid or 60–80% sulfuric acid followed by neutralization with an alkaline solution. This new method made it possible to synthesize various γ-alkyl L -glutamates, including those higher than ethyl, and consequently, various poly(γ-alkyl L -glutamates) such as methyl, ethyl, n-propyl, n-butyl, isobutyl, and isoamyl. The conformation of these poly-L -glutamates in the solid state was determined by the infrared absorption method. The molecular motions of the polymers of γ-methyl, -ethyl, -n-propyl, -n-butyl, and-isoamyl L -glutamates and poly(γ-methyl-D -glutamate) in the solid state were studied by NMR, and dielectric and mechanical measurements. At temperatures up to 400°K., the NMR spectra of poly(γ-methyl D -glutamate) can be explained only by rotational motion of the side chain. Also, from NMR results, rotational motion of C?O groups in the side chain of poly(γ-methyl D -glutamate) is expected near room temperature, and such a motion was examined by dielectric measurements. Rotation of C?O groups in the side chains of polymers of γ-methyl, γ-ethyl, γ-n-propyl, γ-n-butyl, and γ-isoamyl L -glutamate was also observed near room temperature by dielectric measurements in the frequency range from 10² to 10⁶ cps. Activation energies obtained by dielectric and mechanical measurements were similar to those for the side chain motions of the corresponding esters of poly(methacrylic acid). Although it has been noted that the molecular motion of poly(γ-benzyl L -glutamate) in the solid state at room temperature may be related to the motion of its back bone, the molecular motion in these poly-L -glutamates at these temperatures can be explained only in terms of side-chain rotation.     

Crystallinity and conformational changes in poly(β-benzyl L-aspartate)

The crystallinity of poly(β-benzyl L -aspartate) is highly variable, in a series of specimens prepared under various conditions: films cast from chloroform solutions at various evaporation rates, films cast comparatively slowly from chloroform–trifluoroacetic acid solutions, films prepared from dichloroacetic acid solution by treatment with ethyl alcohol, precipitates formed from trifluoroacetic acid solution by addition of ether. Film cast slowly from chloroform is in the highly crystalline ω form. In contrast, the conformation of the benzene rings in the ω helix obtained from the α helix by heating is distorted to some extent in comparison with the structure of the highly crystalline ω form. Crystallization and conformational changes from the α to the ω form, and from the ω to the β form upon heating, are correlated with the dispositions of the side chains, the packing of the benzene rings, and the motion of the side chains. The main chain of the α helix is distorted into the ω form when its side chains are in a favorable conformation. The α helix is stable in the disordered conformation, and it is distorted to some extent at high temperature.     

Synthesis of poly-L-naphthylalanine and its secondary structure

Polypeptides derived from L -naphthylalanine and γ-benzyl L -glutamate were prepared. Conformational properties in solution were investigated by circular dichroism (CD) and infrared spectra on the soluble copolymers, and the copolymers were assumed to take the right-handed α-helical conformation. By the addition of trifluoroacetic acid, a transition of side-chain arrangement is induced simultaneously with the conformational transition of the peptide backbone for the copolymer with the highest content of L -naphthylalanine residues. Fluorescence spectra of the copolymers show no excimer emission, which is evidence for the rigid orientation of the side-chain naphthyl groups. The infrared spectrum and x-ray diagram of poly-L -naphthylalanine do not rule out the helical conformation in the solid state.     

Poly(9‐undecyl‐9‐methyl‐fluorene) and poly(9‐pentadecyl‐9‐methyl‐fluorene): Synthesis,solution structure,and effect of side chain asymmetry on aggregation behavior

We report on solution aggregates and backbone conformation of poly(9‐undecyl‐9‐methyl‐fluorene) (PF1‐11) and poly(9‐pentadecyl‐9‐methyl‐fluorene) (PF1‐15), having two different side chains compared with poly(9,9‐dihexylfluorene) (PF6) and poly(9,9‐dioctylfluorene) (PF8) with two identical side chains. In the poor solvent methylcyclohexane (MCH), X‐ray scattering indicates that PF1‐11 and PF1‐15 appear as three‐dimensional aggregates (5–10 nm wide and thick), forming ribbon‐like agglomerates (correlation lengths of 100 nm). PF6 and PF8 appear as two‐dimensional aggregates (>10 nm wide and 2–3 nm thick) involving ribbon‐like agglomerates (correlation lengths much greater than 100 nm). Upon heating, all aggregates undergo a gel–sol transition which occurs at lower temperatures for PF1‐11 and PF1‐15 (<60°C) than for PF6 and PF8 (>80°C). In the good solvent toluene, PF1‐11 and PF1‐15 form networks of cylindrical particles. The mesh size and the cylinder radius are smaller in 24°C toluene (60 nm, 0.5 nm) than in 60°C MCH (300 nm, 1–2 nm). Nuclear magnetic resonance spectra in toluene‐d₈ together with density functional theory calculations suggest higher torsion angles between polymer repeat units for PF6, PF8, and PF1‐11 (less planar conformation) and a gauche arrangement of the dihedral angles between the bridge carbon atom and the side chain methylene groups in PF1‐15. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 826–837     

Thermal stabilities of homopolymers of amino acids

In order to study the thermal stabilities of the α-helical polyamino acids in the solid state, measurements of the infrared spectra at high temperature, weight loss by thermogravimetry, and the expansion of the α-helix by x-ray diffractometry were carried out on poly(γ-methyl D -glutamate), poly(γ-benzyl L -glutamate), poly-L -alanine, poly(β-benzyl L -aspartate), poly-δ-carbobenzoxy-L -ornithine and poly-ε-carbobenzoxy-L -lysine. The thermal degradation temperatures of these polymers lie between 140°C and 230°C. The α-helical conformation is stable at high temperature in these polyamino acids, except for poly(β-benzyl L -asparatate), unless thermal degradation takes place. As temperature rises, the amide A and the amide I bands of the infrared spectra shift slightly to higher frequencies and the amide II band to lower frequencies. At the same time, the intensities of these amide bands decrease. These changes differ among the different molecules. From the x-ray measurement, it was found that the α-helix expands along the helical axis with temperature. It is expected that the intramolecular hydrogen bonds of the α-helix become weak with increasing temperature and that the state of the hydrogen bonds of the α-helices depends upon the molecules.     

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.     

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.     

Functional monomers and polymers. LXXI. Conformation and interaction studies of poly-L-lysine derivatives with pendant nucleic acid bases

Copolymers of L -lysine and L -lysine derivatives which contained nucleic acid bases substituted on the N^ε position were synthesized by grafting nucleic acid derivatives onto poly-L -lysine. The conformation and interaction of these copolymers in solution were studied by using spectroscopic measurements. They existed in helical conformation at neutral pH values, and the polymer complex formation among them was examined by ultraviolet (UV) measurements in organic solvents. A decrease in the nucleic acid base content of the copolymers resulted in a decrease in helical structures and also in interactions with the polymer-containing complementary bases.     

Preparation and Conformational Properties of Benzylpenicilloyl-oligo-L-lysine Conjugates

Selected oligo-L -lysine carriers and a poly-L -lysine were penicilloylated with benzylpenicillin. The resulting conjugates 2 – 6 were studied by IR. absorption in the solid state and circular dichroism measurements in solution. The IR. data demonstrate the lack of β-structure formation even in medium-sized peptides where such structures might be expected on the basis of previous studies on differently substituted oligo-L -lysines. Considerable proportions of right-handed α -helical conformation are exhibited by the icosa-L -lysine and poly-L -lysine conjugates 5 and 6 in water and 2,2,2-trifluoroethanol. Difficulties in obtaining fully penicilloylated conjugates are not related to the extent of α-helical conformation in aqueous solution.     

Grafting of poly(sodium styrenesulfonate) onto gold surface from NaNO<Subscript>3</Subscript> solution

The chemical grafting of thiol terminated poly(sodium styrenesulfonate)(HS-PSSS) chains from sodium nitrate (NaNO_3) salt solution to a gold surface was investigated with a quartz crystal microbalance with dissipation monitoring (QCM-D) in different salt concentrations.It was found that at low salt concentration grafting density of HS-PSSS was low and the grafted chains adopted a mushroom conformation.With the increase of salt concentration polyelectrolyte chains underwent a transition toward coiled stat...     

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).     

Photochromic polymers: effects of structure and environment on photoresponsiveness

In this review paper the photoresponsiveness of photochromic macromolecules under different structural and environmental conditions is discussed with reference to results from the authors' laboratories. Polypeptides, in particular poly(L -glutamic acid) and poly(L -lysine), with spirobenzopyrane side chains show photoinduced conformational variations which are amplified by addition of organic acids or bases to hexafluoro-2-propanol (HFP) solutions. Thus combination of light and environment effects allows modulation of order–disorder conformational transitions. Such photoindiced conformational changes are not observed in the case of macromolecules with a hydrocarbon main chain and azobenzene or stilbene side chains, obtained by polymerization of acrylic monomers. However, even in these systems structural variations affect the dependence of optical properties on irradiation. Moreover, the combination of organic solvents and water shows that polymer solubility can be modulated by light.     

Computer simulation and structure analysis of polypeptide derivatives of cyclotriphosphazene

A quantum-chemical analysis and experimental investigation of the structure of poly(γ-methyl L-α-glutamate) and poly(γ-benzyl L-α-glutamate) linked with the triphosphazene ring via aminophenoxy groups were performed. The computer simulation showed that these compounds with a total degree of polymerization of amino acid sequences of n ≤ 60 are close to the rigid-rod conformation in struture, whereas the rod is distorted to the arch architecture at n > 60. According to X-ray data, the α helices of polypeptide segments are arranged into two-dimensional hexagonal packing. By means of the DSC technique, the glass transition associated with the freezing-out of the mobility of side chains was revealed, transitions to the mesophase were determined, and it was established that the helix type experiences a local change characteristic of poly(γ-benzyl glutamate) derivatives of cyclotriphosphazene in the solid state.     

Synthesis of poly(Nε-phenoxycarbonyl-l-lysine) by polycondensation of activated urethane derivative and its application for selective modification of side chain with amines

We report a methodology for the synthesis of Nε-phenoxycarbonyl-protected poly(l -lysine) on the side chain by chain growth polycondensation of Nα,Nε-bis(phenoxycarbonyl)-l -lysine proceeded through the selective elimination of phenol and CO₂ from the Nα phenoxycarbonyl moiety at 50 °C in N,N-dimethylacetamide in the presence of a primary amine used as an initiator. After optimization of reaction condition, the addition of acetic acid during polycondensation proved effective for the realization of the predicted molecular weight and narrow dispersity of the corresponding polypeptide by adjusting the feed ratio of monomer to the amine initiator because of the suppression of interchain coupling that occurs between the amino terminus of poly(l -lysine) and the Nε-phenoxycarbonyl group on the polymer side chains. Furthermore, taking advantage of the potentially reactive Nε-phenoxycarbonyl moiety on the side chain, post-polymerization modification was effectively achieved by the nucleophilic reaction of amine compounds including primary, secondary, and aromatic amines through the formation of urea linkage, providing a useful platform for synthesis of selective side chain functionalization of poly(l -lysine) samples. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2522–2530     

Side‐chain conformational changes during the thermoshrinking process: γ‐Ray polymerization and spectroscopic study of uncrosslinked poly(methacryloyl‐Ala‐OMe)

Poly(methacryloyl‐L ‐alanine‐methyl ester) (1) has an optically active side chain and consists of thermoshrinking hydrogels upon crosslinking. We synthesized an uncrosslinked polymer of 1 by the γ‐ray polymerization method. For the prepared polymer, variable‐temperature circular dichroism (CD) and ¹H NMR spectra were studied, and we found conformational changes in the optically active side chains during the thermally induced phase transition. Intense CD spectra reveal ordered conformation in the side chain of 1 below the phase transition temperature (∼28 °C). A well‐resolved ¹H NMR spectrum of 1 at 0 °C shows that the conformational angles in the polymer side chain are fixed at low‐energy minima. With increasing temperature, the frozen side chain starts rotating vigorously and takes an unordered orientation. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2671–2677, 2000     

Conformational change of proline residues observed in swollen and shrunken phases: γ‐Ray synthesis and variable temperature circular dichroism spectra of a thermo‐responding polymer,poly(acryloyl‐Pro‐OMe)

Poly(acryloyl‐L ‐proline‐methyl ester) ( 1 ) has optically active side chain, and constitutes thermoresponsive hydrogels upon crosslinking. In this study, we have prepared uncrosslinked polymer of 1 with a 10‐kGy irradiation dose of γ‐ray. For this polymer, 1 , variable temperature circular dichroism (CD) and ¹H NMR spectra have been studied in the range of 0–30 °C. The intense CD spectrum at 0 °C suggests that the side chains in 1 have an ordered orientation. The CD intensity decreases gradually with increasing temperature. The decreased intensity of CD spectra indicates that the disordering occurs for the side‐chain orientation. The CD band shape changes discontinuously at 20 °C. In the ¹H NMR spectra, signals disappear above 20 °C. These spectral change at 20 °C indicate that the phase transition occurs at around 20 °C from swollen to shrunken phase. Even after the phase transition, the CD spectra are still changing with isochromic point at 212 nm. It appears that the side‐chain conformation is still changing from one state to the other state in the shrunken phase polymers. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4524–4530, 2000     

Electric‐field‐induced chain orientation in poly(L‐lactic acid)

The orientational order was studied for melt‐state poly(L ‐lactic acid) under an external direct‐current electric field. A birefringence as high as 1.1 × 10^?2 was recorded against an external field of 1.0 MV/m at 190 °C. The evidence proved that a field–dipole interaction transferred from a randomly coiled conformation to a uniaxially drawn conformation. The field‐induced birefringence was temporally resolved, and the chain orientation and relaxation processes on the order of 100 s were observed in a real timescale after the field was turned on and off. A mechanism of chain orientation was examined with respect to the orientation polarization and viscoelasticity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4433–4439, 2004     

Zerovalent metal polymer composites. II. Metal–polymer microdispersions

Metallization of water-soluble polymers incorporating metal-binding ligand is achieved by binding palladium ions at substoichiometric quantities, followed by reduction to polymer–zero-valent palladium complex and deposition of transition metal ions by electroless plating solutions. The polymers studied include poly[N,N,N-trimethyl-N-(m- and p-vinylbenzyl)ammonium chloride], poly-L -glutamic acid, poly-L -lysine, and a copolymer of 2-phenylhydroquinone-2-amino-phthalic acid. Noble metal polyelectrolyte solutions were directly reduced with dimethylamineborane to stable microdispersions. The reactive nickel, cobalt and copper microdispersions were coated on KODAK ESTAR filmbase. Scanning electron microscopy (SEM), ESCA, and IR were used for material characterization. Conductivity and magnetic properties were also measured. Hydrophobic materials such as graphite and fluorinated graphite were metallized in organic solvents using hydrophobic trioctylammonium–tetrachloropalladate as the activating noble metal complex. The metallized conductive graphites were evaluated for their electrochemical properties.     

Aqueous solution behavior of comb‐shaped poly(2‐ethyl‐2‐oxazoline)

A series of comb polymers consisting of a methacrylate backbone and poly(2‐ethyl‐2‐oxazoline) (PEtOx) side chains was synthesized by a combination of cationic ring‐opening polymerization and reversible addition–fragmentation chain transfer polymerization. Small‐angle neutron scattering (SANS) studies revealed a transition from an ellipsoidal to a cylindrical conformation in D₂O around a backbone degree of polymerization of 30. Comb‐shaped PEtOx has lowered T_g values but a similar elution behavior in liquid chromatography under critical conditions in comparison to its linear analog was observed. The lower critical solution temperature behavior of the polymers was investigated by turbidimetry, dynamic light scattering, transmission electron microscopy, and SANS revealing decreasing T_cp in aqueous solution with increasing molar mass, the presence of very few aggregated structures below T_cp, a contraction of the macromolecules at temperatures 5 °C above T_cp but no severe conformational change of the cylindrical structure. In addition, the phase diagram including cloud point and coexistence curve was developed showing an LCST of 75 °C of the binary mixture poly[oligo(2‐ethyl‐2‐oxazoline)methacrylate]/water. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Poly(γ-alkyl L-glutamates). II. Optical rotatory dispersion studies in organic solvents

Conformations of a series of poly(γ-alkyl L -glutamates) (ethyl, n-propyl, n-butyl, isobutyl, and isoamyl) were studied by ORD and infrared absorption methods. All except the n-propyl ester were found to be in helical form in nonpolar non-aromatic solvents such as ethyl acetate, chloroform, ethylene dichloride, methylene chloride, carbon tetrachloride, 2-chloroethanol, dimethylformamide, and dioxane. In such cases, the Cotton effects due to the n–π* transition of peptide bonds occurred near 234 mμ and were of a magnitude similar to those found for poly(γ-benzyl L -glutamate) and poly-L -methionine in nonpolar non-aromatic organic solvents. These four polypeptides in aromatic nonpolar solvents, such as benzene, benzyl alcohol, pyridine, and m-cresol, were also found to be in helical form, although the ORD parameters differed considerably from the values in non-aromatic solvents. An essential cause seems to be the interaction of π electrons on peptide bonds with π electrons in the solvents. Helix-coil transitions of these esters in chloroform-dichloroacetic acid mixtures (dichloroacetic acid seems to be a random coil-forming solvent) were expressed by the Shechter-Blout formulation. This was not true, however, for helix–coil transitions in benzyl alcohol–dichloroacetic acid mixtures. The dependence of the helical stability of these polypeptides in chloroform solution upon the side-chain length and upon temperature is discussed.