Cross-linking-induced permanently perpendicular helix orientation in surface-grafted polyglutamate films

Using a chemical cross-linking procedure, surface-grafted polyglutamate films with a permanently perpendicular helix orientation were prepared. A surface-grafted alpha-helical polyglutamate film containing polymerizable side groups was synthesized by ring-opening terpolymerization of 50 molar% gamma-methyl-L-glutamate N-carboxyanhydride (NCA), 30% gamma-stearyl-L-glutamate NCA and 20% gamma-4-vinylbenzyl-L-glutamate NCA initiated from a silicon substrate functionalized with primary amino groups. The average tilt angle of the end-grafted helices in this film is approximately 66 degrees , indicating a nearly parallel helix orientation with respect to the substrate surface. After swelling of the grafted terpolyglutamate film in stearyl methacrylate and subsequent radical cross-linking, the average helix tilt angle decreases to about 11 degrees, indicating an almost perpendicular helix orientation. The film thickness increases accordingly from 151 A before to approximately 390 A after cross-linking. Extensive solvent treatment of the cross-linked film shows that the perpendicular helix orientation is permanent.     

Chiral induction in quinoline-derived oligoamide foldamers: assignment of helical handedness and role of steric effects

Chiral groups attached to the end of quinoline-derived oligoamide foldamers give rise to chiral helical induction in solution. Using various chiral groups, diastereomeric excesses ranging from 9% to 83% could be measured by NMR and circular dichroism. Despite these relatively weak values and the fact that diastereomeric helices coexist and interconvert in solution, the right-handed or left-handed helical sense favored by the terminal chiral group could be determined unambiguously using X-ray crystallography. Assignment of chiral induction was performed in an original way using the strong tendency of racemates to cocrystallize, and taking advantage of slow helix inversion rates, which allowed one to establish that the stereomers observed in the crystals do correspond to the major stereomers in solution. The sense of chiral helical induction was rationalized on the basis of sterics. Upon assigning an Rs or Ss chirality to the stereogenic center using a nomenclature where the four substituents are ranked according to decreasing sizes, it is observed that Rs chirality always favors left-handed helicity and Ss chirality favors right-handed helicity (P). X-ray structures shed some light on the role of sterics in the mechanism of chiral induction. The preferred conformation at the stereocenter is apparently one where the bulkiest group should preferentially point away from the helix, the second largest group should be aligned with the helix backbone, and the smallest should point to the helix.     

Conformational transitions of poly(β-benzyl L-aspartate)

Conditions that affect the conformation of poly(β-benzyl L-aspartate) in films have been studied. A slow transition from the left-handed to the right-handed α-helical form is observed under certain conditions in half-dried film cast from chloroform solutions and after exposure of amorphous films of the left-handed β-helical form to chloroform vapor. This transition is caused by adsorption of moisture. Thermal transitions of these films were examined by differential scanning calorimetry and infrared spectroscopy. The right-handed α-helices change to left-handed ω-helices around 140°C, and sharp exothermic peak is observed in this region for some films.     

Control of peptide helix sense by temperature tuning of noncovalent chiral domino effect

We have investigated temperature effect on control of a peptide helix sense through the noncovalent chiral domino effect (NCDE: Inai, Y. et al., J. Am. Chem. Soc. 2003, 125, 8151-8162). Nonapeptide (1: Inai, Y.; Komori, H. Biomacromolecules 2004, 5, 1231-1240), which alone prefers a right-handed helix, maintained a screw-sense balance or a small imbalance at room temperature in the presence of Boc-d-amino acid. Cooling of the solution induced a left-handed helix more clearly. Conversely, heating from room temperature recovered the original right-handed sense. This helix-helix transition was essentially reversible in cooling-heating cycles. An increase in the Boc-d-amino acid concentration elevated temperature for switching CD signs based on the conformational transition. A similar thermal-driven inversion of helix sense was observed for 1 at other initial concentrations, suggesting that this behavior is insensitive to some peptide aggregation. NMR study provided direct evidence for the domino-type control of helix sense, in which Boc-Leu-OH is mainly located at the N-terminal segment. In addition, a left-handed helix induced by the d-isomer was shown to participate in equilibrium with a right-handed helix, whereas the right-handed helix was predominant in the presence of l-isomer. Consequently, we here have proposed a model for controlling a peptide helix sense (or its screw-sense bias) through temperature tuning of the external chiral interaction specific to the N-terminal sequence.     

Probing the role of the C-H...O hydrogen bond stabilized polypeptide chain reversal at the C-terminus of designed peptide helices. Structural characterization of three decapeptides

The structural characterization in crystals of three designed decapeptides containing a double d-segment at the C-terminus is described. The crystal structures of the peptides Boc-Leu-Aib-Val-Xxx-Leu-Aib-Val-(D)Ala-(D)Leu-Aib-OMe, (Xxx = Gly 2, (D)Ala 3, Aib 4) have been determined and compared with those reported earlier for peptide 1 (Xxx = Ala) and the all l analogue Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe, which yielded a perfect right-handed alpha-helical structure. Peptides 1 and 2 reveal a right-handed helical segment spanning residues 1 to 7, ending in a Schellman motif with (D)Ala(8) functioning as the terminating residue. Polypeptide chain reversal occurs at residue 9, a novel feature that appears to be the consequence of a C-H.O hydrogen bond between residue 4 C(alpha)H and residue 9 CO groups. The structures of peptides 3 and 4, which lack the pro R hydrogen at the C(alpha) atom of residue 4, are dramatically different. Peptide 3 adopts a right-handed helical conformation over the 1 to 7 segment. Residues 8 and 9 adopt alpha(L) conformations forming a C-terminus type I' beta-turn, corresponding to an incipient left-handed twist of the polypeptide chain. In peptide 4, helix termination occurs at Aib(6), with residues 6 to 9 forming a left-handed helix, resulting in a structure that accommodates direct fusion of two helical segments of opposite twist. Peptides 3 and 4 provide examples of chiral residues occurring in the less favored sense of helical twist; (D)Ala(4) in peptide 3 adopts an alpha(R) conformation, while (L)Val(7) in 4 adopts an alpha(L) conformation. The structural comparison of the decapeptides reported here provides evidence for the role of specific C-H.O hydrogen bonds in stabilizing chain reversals at helix termini, which may be relevant in aligning contiguous helical and strand segments in polypeptide structures.     

Photoinduced conformational changes of azoaromatic polyaspartates containing octadecyl side chains

Copolymers of p-(phenylazo)benzyl-L-aspartate and n-octadecyl-L-aspartate exist as right- and left-handed α-helices in solution at 25°C depending on the copolymer composition: the reversal of helix sense from a right- to left-handed one occurs with increasing the azobenzene content. The α-helices of the copolymers are very sensitive to trifluoroacetic acid (TFA), and are converted into random coil below 2.0% of TFA. Among the copolymers, the copolymer containing 47% azobenzene groups is unique since it exhibits a TFA-induced conformational change from right-handed α-helix to random coil via left-handed α-helix. Upon UV light irradiation at 25°C, the copolymers containing 68 and 89% azobenzene groups caused the reversal in helix sense from a left- to right-handed one. The conformations of the copolymers were dependent on temperature, mostly right-handed and left-handed α-helices at lower and higher temperatures, respectively. On this basis, the copolymer containing 47% azobenzene groups could be made to undergo a photoinduced helix reversal at high temperatures.     

Heat capacity and vibrational dynamics of α poly(β-benzyl-L-aspartate)

Poly(β-benzyl-L-aspartate) (PBLA) is an unusual polypeptide, which is capable of going into four different conformations, namely, left-handed α helix, right-handed α helix, ω helix, and β pleated sheet. The present work is a complete study of normal modes and their dispersion in the unusual left-handed α form. A special feature of some of the dispersion curves is their tendency to bunch in the neighborhood of helix angle. This is attributed to the presence of strong intramolecular interactions. Crossing and repulsion between the dispersion curves is also observed. The N-deuterated analogue of PBLA has been studied to check the validity of assignments and force field (Urey Bradley). Specific heat has been obtained from dispersion curves via density of states. A comparative study of left-handed and right-handed forms is presented. © 1996 John Wiley & Sons, Inc.     

Optical rotatory dispersion and circular dichroism studies of copoly(propyl-L-aspartate-benzyl-L-aspartate)

Copoly(propyl-L -aspartate-benzyl-L -aspartate)s with various compositions were synthesized by propylation of a parent poly(β-benzyl-L -Aspartate). The variation of helix sense of copolyaspartate obtained against a degree of propylation and temperature was examined by optical rotatory dispersion and circular dichroism method. Copolyaspartate of propylation less than about 70% is in a left-handed α helix conformation and its Moffitt parameter b₀ and molecular ellipticity [θ]₂₂₂ decreased gradually with increasing propylation. On the other hand, a different temperature dependence of b₀ and [θ]₂₂₂ was observed for copolyaspartate of propylation more than about 80%, i.e., the reversible transition of the helix sense from right- to left-handed α helix took place by temperature increasing. These features were basically similar to the variation in helix sense of copoly(ethyl-L -aspartate-benzyl-L -aspartate), although a slight difference was seen for copoly(propyl-L -aspartate-benzyl-L -aspartate). The thermodynamic treatment indicating larger entropy of right-handed α helix suggests much mobile side chain of the right-handed α helix than the left handed one.     

Spectroscopic evidence for diastereomeric helical segments of polysilane bearing enantiopure (S)- and (R)-3,7-dimethyloctyl groups

We synthesized two optically active helical polysilanes, poly[(S)-3,7-dimethyloctyl-3-phenylpropylsilane] (PS1) and poly[(R)-3,7-dimethyloctyl-3-phenylpropylsilane] (PS2), bearing a flexible and rodlike silicon main chain and enantiopure alkyl side chains with (S)- and (R)-chiral centers, respectively, at the γ-positions. PS1 and PS2 underwent a thermodriven helix–helix transition at 10 °C in isooctane. Circular dichroism (CD) and UV studies demonstrated the transition characteristics, such as the transition temperature, population of right- and left-handed helical motifs, global shape, and screw pitch. At −80 °C, the dissymmetry ratio suggested that a preferential right-handed or left-handed screw sense was present in the polymer chains of PS1 and PS2, respectively. However, above the transition temperature, the appearance of a bisignate cotton band in the CD spectra suggested that both right-handed screw-sense, tight helical segments and left-handed screw-sense, loose helical segments coexisted in the same chains of PS1 and PS2. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4518–4527, 2004     

Handedness enantioselection of carbon nanotubes using helical assemblies of flavin mononucleotide

In order to truly unlock advanced applications of single-walled carbon nanotubes (SWNTs), one needs to separate them according to both chirality and handedness. Here we show that the chiral d-ribityl phosphate chain of flavin mononucleotide (FMN) induces a right-handed helix that enriches the left-handed SWNTs for all suspended (n,m) species. Such enantioselectivity stems from the sp(3) hybridization of the N atom anchoring the sugar moiety to the flavin ring. This produces two FMN conformations (syn and anti) analogous to DNA. Electrostatic interactions between the neighboring uracil moiety and the 2'-OH group of the side chain provide greater stability to the anti-FMN conformation that leads to a right-handed FMN helix. The right-handed twist that the FMN helix imposes to the underlying nanotube, similar to "Indian burn", causes diameter dilation of only the left-handed SWNTs, whose improved intermolecular interactions with the overlaying FMN helix, impart enantioselection.     

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.     

Amplification of chirality of the majority-rules type in helical supramolecular polymers: the impact of the presence of achiral monomers

We present a theoretical treatment describing the conformational state of helical supramolecular polymers that consist of three types of monomer: right-handed and left-handed chiral monomers and achiral ones. We find that chirality amplification of the majority-rules type, that is, a disproportionately large shift in the helix screw sense due to a small enantiomeric excess, can occur in these polymers. The strength of the chirality amplification depends on the free-energy penalty of a helix reversal along the self-assembled chain and on that of a mismatch between the conformation of a bond and the preferred conformation of the preceding monomer. It turns out that the impact of achiral monomers also depends on these two parameters. For high values of these free energies, the net helicity does not change much from the situation where no achiral material is present. However, if the free-energy penalties are not both large, the impact of the achiral monomers on the conformational state of the aggregates can be quite substantial.     

Effect of molecular weight on conformation of poly(β-benzyl L-aspartate) in films

In order to study the effect of the molecular weight on the crystallinity and conformational changes of poly(β-benzyl L aspartate) in films, a previous study on high molecular weight samples has been extended to included polymers of low molecular weight, about 3.3 × 10³. Films were prepared from chloroform solution by quick or slow evaporation at room temperature. The conformation and the thermal behavior were studied by means of infrared spectroscopy and differential scanning calorimetry. All films dried quickly are composed of polymer in the left-handed α-helical form. All samples studied which have molecular weights above 2.3 × 10⁴ are similar in crystallinity and the left-handed α-helices in them crystallize to ω-helices during slow evaporation. In the low molecular weight region, however, the left-handed α-helices reverse to right-handed α-helices during slow evaporation, and the right-handed α-helices, in turn, reverse and crystallize to highly ordered ω-helices upon heat treatment, although there is some simultaneous conversion to the β-form. The transition temperatures of the quick-dried films for conversion from the left-handed α-helix to the ω-helix and from the ω-helix to the β-form increase linearly with increasing molecular weight up to about 2 × 10⁴, but no large molecular weight dependence is observed beyond that region.     

Adsorption of enantiomeric poly(lactide)s on surface-grafted poly(L-lactide)

We show that resistance of densely grafted polymer layers to adsorption of chemically identical free chains, which is known to be caused by entropic expulsion of free chains from the grafted layer, can be suppressed using the grafted and free chains of opposite stereoconfiguration. Specifically, we study adsorption of poly(L-lactide) (PLLA) and its enantiomer poly(D-lactide) (PDLA) onto layers of surface-grafted PLLA in acetonitrile and chloroform by infrared spectroscopy (IR). The grafted layers with thicknesses ranging from 7 to 35 nm are produced by ring-opening polymerization of L-lactide from hydroxyl end-groups of a self-assembled monolayer on gold. The IR data indicate that adsorption on the bare gold surface is the same for the L- and D-form of the polymer. However, covering the gold with the surface-grafted PLLA produces a significant decline in the adsorption of free PLLA and, by contrast, a strong enhancement in the adsorption of free PDLA. In addition, the IR data indicate that the adsorbed PDLA chains are stereocomplexed with the grafted PLLA chains. Thus, entropic expulsion of free chains from the grafted layer, which is responsible for the resistance of surface-grafted PLLA to adsorption of free PLLA, is suppressed in the case of free PDLA by stereocomplexation between the grafted and free chains.     

Biodegradability of poly(3-hydroxybutyrate) film grafted with vinyl acetate: Effect of grafting and saponification

Radiation-induced graft polymerization of vinyl acetate (VAc) onto poly(3-hydroxybutyrate) (PHB) film was carried out. At a degree of grafting higher than 5%, the grafted films (PHB-g-VAc) completely lost the enzymatic degradability that is characteristic of PHB due to the grafted VAc covering the surface of the PHB film. However, the biodegradability of the PHB-g-VAc films was recovered when the films were saponified in alkali solution under optimum conditions. Graft chains of the PHB-g-VAc film reacted selectively to become biodegradable polyvinyl alcohol (PVA). The biodegradability of the saponified PHB-g-VAc film increased rapidly with time.     

Fabrication of shape-controllable polyaniline micro/nanostructures on organic polymer surfaces: obtaining spherical particles, wires, and ribbons

A novel strategy was developed in order to prepare various micro/nanostructured polyanilines (PANI) on polymer substrates. The strategy involved two main steps, i.e., a grafting polymerization of acrylate acid (AA) onto the surface of a polypropylene (PP) film and subsequently an oxidative polymerization of aniline on the grafted surface. By tuning the conformation of the surface-grafted poly acrylate acid (PAA) brushes, as well as the ratio of AA to aniline, the shape of the PANIs fixated onto the surfaces of the polymer substrate could be controlled to go from spherical particles to nanowires and eventually to nanoribbons. In these structures, the PAA brushes not only acted as templates but also as dopants of PANI, and thereby, the nanostructured PANIs could be strongly bonded with the substrate. In addition, the surface of the PP films grafted with polyaniline nanowires and nanoribbons displayed superhydrophobicity with contact angles for water of approxiamtely 145 and 151 degrees , respectively.     

Homo-N-oligonucleotides (N1/N9-C1' methylene bridge oligonucleotides): nucleic acids with left-handed helicity

Oligonucleotides containing a methylene bridge between N1 or N9 of the heterocyclic base and C1' of the pentofuranosyl ring (homo-N-oligonucleotides) were synthesized. Melting curves revealed that such homo-type oligomers could cross-pair with complementary homo-type or natural oligomers. Circular-dichroic studies provide evidence that the homo-type dimers have a left-handed stacked conformation and further suggest that single-stranded and double-stranded homo-type oligomers adopt a left-handed conformation, while duplexes with natural oligomers or nucleic acids form RNA-like right-handed helices. NMR spectroscopy (NOESY) provides supporting evidence for a left-handed stacked conformation of the homo-type dimer, while atomic force microscopy indicates a left-handed helical conformation of homo-type dsDNA. Homo-type dimers and oligomers showed high resistance to digestion by snake-venom and calf-spleen phosphodiesterases and nuclease S1.     

Effect of Molecular Structure on Complexation Between Acidic- and Basic-Polypeptides in Solution

Abstract

Interpolymer complex formation between basic polypeptides, poly(L- proline) Form I [PLP(I)], Form II [PLP(II)] and poly-4-hydroxy-L-proline (PHLP), and acidic polypeptides, poly(L-glutamic acid) (PLGA), poly(D- glutamic acid) (PDGA) and poly(L-aspartic acid) (PLAA), has been studied in water-methanol (1:2 v/v) mixed-solvent by viscometry, potentiometry, light scattering and circular dichroism (CD) measurements. It has been found that polymer complexes between basic- and acidic- polypeptides are formed via hydrogen bonding with a stoichiometric ratio of basic/acidic polypeptides =1:2 (in unit mole ratio) and that PLP(II) forms polymer complex more favorably with PLGA than with PLAA, and the complex of PLP(II) with PLGA is also more favorable than the complex formation of PHLP with PLGA. In addition, the complex formation is highly dependent on the conformation, especially the optical structure of the component polymers, i.e., the stereoselective complexation is observed. The PLGA having a right-handed helix at pH 3.2 formed the complex favorably and quickly with left-handed helix PLP(II), whereas PDGA having a left-handed helix at pH 3.2 favorably formed the complex with right-handed helix PLP(I).     

Noncovalent domino effect on helical screw sense of chiral peptides possessing C-terminal chiral residue

Recently, a novel chiral intermolecular interaction was found in an N-deprotected achiral nonapeptide that undergoes the predominance of one-handed screw sense through the addition of chiral small carboxylic acid (Inai, Y.; Tagawa, K.; Takasu, A.; Hirabayashi, T.; Oshikawa, T.; Yamashita, M. J. Am. Chem. Soc. 2000, 122, 11731). We here clarify to what extent such noncovalent chiral domino effect affects the helical screw sense of an N-deprotected chiral peptide. Two chiral peptides consisting of C-terminal L-Leu (1) or L-Leu(2) (2) and the preceding achiral helical octapeptide segment were employed. NMR and IR spectroscopy, and energy calculation indicated that both peptides adopt a helical conformation in chloroform. Peptide 1 showed a small excess of a left-handed screw sense for the achiral helical octapeptide, but peptide 2 strongly preferred a right-handed screw sense. The addition of chiral Boc amino acid to a chloroform solution of peptide 1, depending on its chirality, underwent a unique helix-to-helix transition or led to remarkable stabilization of the original left-handed screw sense. Peptide 2 retained the original right-handed screw sense on addition of chiral Boc-amino acid, but its helical stability changed to some extent depending on its added chirality. Therefore, the importance of noncovalent domino effect for controlling the helical screw sense or helical stability of a chiral peptide has been demonstrated here for the first time. In addition, we here have presented a unique system that both N-terminal noncovalent and C-terminal covalent domino effects operate simultaneously on the helical screw sense of a single achiral segment and have compared both powers for inducing the screw sense bias.     

Anion-coordination-driven single–double helix switching and chiroptical molecular switching based on oligoureas

Synthetic foldamers with helical conformation are widely seen, but controllable interconversion amongst different geometries (helical structure and sense) is challenging. Here, a family of oligourea (tetra-, penta-, and hexa-) ligands bearing stereocenters at both ends are designed and shown to switch between single and double helices with concomitant inversion of helical senses upon anion coordination. The tetraurea ligand forms a right-handed single helix upon chloride anion (Cl⁻) binding and is converted into a left-handed double helix when phosphate anion (PO₄³⁻) is coordinated. The helical senses of the single and double helices are opposite, and the conversion is further found to be dependent on the stoichiometry of the ligand and phosphate anion. In contrast, only a single helix is formed for the hexaurea ligand with the phosphate anion. This distinction is attributed to the fact that the characteristic phosphate anion coordination geometry is satisfied by six urea moieties with twelve H-bonds. Our study revealed unusual single–double helix interconversion accompanied by unexpected chiroptical switching of helical senses.

Two-in-one switching of single–double helical forms and helicities is demonstrated using anion-coordination-driven oligourea foldamers.