Synthesis and chiral recognition of helical poly(phenylacetylene)s bearing l‐phenylglycinol and its phenylcarbamates as pendants

A series of novel stereoregular one‐handed helical poly(phenylacetylene) derivatives ( PPA‐1 and PPA‐1a～g ) bearing l ‐phenylglycinol and its phenylcarbamate residues as pendants was synthesized for use as chiral stationary phases (CSPs) for HPLC, and their chiral recognition abilities were evaluated using 13 racemates. The phenylcarbamate residues include an unsubstituted phenyl, three chloro‐substituted phenyls (3‐Cl, 4‐Cl, 3,5‐Cl₂), and three methyl‐substituted phenyls (3‐CH₃, 4‐CH₃, 3,5‐(CH₃)₂). The acidity of the phenylcarbamate N‐H proton and the hydrogen bonds formed between the N‐H groups of the phenylcarbamate residues were dependent on the type, position, and the number of substituents on the phenylcarbamate residues. The chiral recognition abilities of these polymers significantly depended on the dynamic helical conformation of the main chain with more or less regularly arranged pendants. The chiral recognition abilities seem to be improved by the introduction of substituents on the phenylcarbamate residues, and PPA‐1d bearing the more acidic N‐H groups due to the 3,5‐dichloro substituents, exhibited a higher chiral recognition than the others. PPA‐1d showed an efficient chiral recognition for some racemates, and baseline separation was possible for racemates 5 , 11 , 12 , and 15 . © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 809–821     

Influence of stereoregularity and linkage groups on chiral recognition of poly(phenylacetylene) derivatives bearing L‐leucine ethyl ester pendants as chiral stationary phases for HPLC

Stereoregular poly(phenylacetylene) derivatives bearing L ‐leucine ethyl ester pendants, poly‐1 and poly‐2a , were, respectively, synthesized by the polymerization of N‐(4‐ethynylphenylcarbamoyl)‐L ‐leucine ethyl ester ( 1 ) and N‐(4‐ethynylphenyl‐carbonyl)‐L ‐leucine ethyl ester ( 2 ) using Rh(nbd)BPh₄ as a catalyst, while stereoirregular poly‐2b was synthesized by solid‐state thermal polymerization of 2 . Their chiral recognition abilities for nine racemates were evaluated as chiral stationary phases (CSPs) for high‐performance liquid chromatography (HPLC) after coating them on silica gel. Both poly‐1 and poly‐2a with a helical conformation showed their characteristic recognition depending on coating solvents and the linkage groups between poly(phenylacetylene) and L ‐leucine ethyl ester pendants. Poly‐2a with a shorter amide linkage showed higher chiral recognition than poly‐1 with a longer urea linkage. Coating solvents played an important role in the chiral recognition of both poly‐1 and poly‐2a due to the different conformation of the polymer main chains induced by the solvents. A few racemates were effectively resolved on the poly‐2a coated with a MeOH/CHCl₃ (3/7, v/v) mixture. The separation factors for these racemates were comparable to those obtained on the very popular CSPs derived from polysaccharide phenylcarbamates. Stereoirregular poly‐2b exhibited much lower chiral recognition than the corresponding stereoregular, helical poly‐2a , suggesting that the regular structure of poly(phenylacetylene) main chains is essential to attain high chiral recognition. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Remarkable Structure Effects on Chiroptical Properties of Polyisocyanides Carrying Proline Pendants

Chiral polymers with simple chemical structures and high helical conformation stabilities are important for their applications as chiral supports and asymmetrical catalysts. We report herein the synthesis of a series of aliphatic polyisocyanides carrying proline pendants of different chiralities, and an investigation of the effects of the chemical structures of these pendants on the chiroptical properties of the polymers. The configuration of the chiral center at the 4‐position of the proline pendants was changed from S to R to check its effect on the handedness of the helical conformation. To examine the effects of steric hindrance on the stabilities of the helical conformation for these aliphatic representatives, proline pendants with various substituents at both the carboxyl and amine terminals were designed. To further examine the steric effects of the proline pendants, aromatic counterparts were also prepared. In the latter case, the effects of hydrogen bonds between pendant units on the enhancement and stabilities of the helical conformation were investigated by switching from the ester to an amide linkage. The Cotton effects and signal intensities of both aliphatic and aromatic polyisocyanides from circular dichroism spectroscopy were compared based on the bulkiness of the pendant groups, solvent polarities, and solution temperatures. It was found that highly stable helical conformations of polyisocyanides could be imposed by small bulky monoproline pendants.     

Design and synthesis of semiflexible substituted polyacetylenes with helical conformation

In this review article, we summarize our recent efforts on the design and synthesis of helical polymers from propiolic esters. Stereoregular cis-transoidal poly(propiolic esters) prepared with Rh catalysts have proven to possess semiflexible main chain, which drives the main chain to the helical conformation with long persistence length. Based on the chiroptical properties of poly(propiolic esters) bearing various chiral pendants, we established the design strategy for the production of well-ordered helical poly(propiolic esters). NMR study of various poly(propiolic esters) enabled estimation of not only the activation energy of helix reversal, but also the free energy difference between the helical and disordered states. The helix sense of poly(propiolic esters) is determined by the configuration of the chiral center, structure of the pendant groups, temperature, and solvent.     

Synthesis and radical ring‐opening polymerization of vinylcyclopropanes derived from amino acids with hydrophobic moieties

Six 1,1‐disubstituted vinylcyclopropanes (VCP) were synthesized from glycine and amino acids bearing hydrophobic moieties, l ‐alanine, l ‐valine, l ‐leucine, l ‐isoleucine, and l ‐phenylalanine. These VCP derivatives efficiently underwent radical ring‐opening polymerization to afford the corresponding polymers bearing trans‐vinylene moiety in the main chains and the amino acid‐derived chiral moieties in the side chains. The polymers were film‐formable, and in the films of polymers bearing the glycine‐ and alanine‐derived side chains, presence of hydrogen bonding was confirmed by IR analysis. Thermogravimetric analysis of the polymers revealed that the temperatures of 5% weight loss were higher than 300 °C. Differential scanning calorimetry clarified that the polymers were amorphous ones showing glass transition temperatures in a range of 48–80 °C. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3996–4002     

The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell Adhesion

Although helical nanofibrous structures have great influence on cell adhesion, the role played by chiral molecules in these structures on cells behavior has usually been ignored. The chirality of helical nanofibers is inverted by the odd–even effect of methylene units from homochiral l ‐phenylalanine derivative during assembly. An increase in cell adhesion on left‐handed nanofibers and weak influence of cell behaviors on right‐handed nanofibers are observed, even though both were derived from l ‐phenylalanine derivatives. Weak and negative influences on cell behavior was also observed for left‐ and right‐handed nanofibers derived from d ‐phenylalanine, respectively. The effect on cell adhesion of single chiral molecules and helical nanofibers may be mutually offset.     

Two modes of asymmetric polymerization of phenylacetylenes having an L‐amino alcohol residue and two hydroxy groups

Four novel chiral phenylacetylenes having an L ‐amino alcohol residue and two hydroxymethyl groups were synthesized and polymerized by an achiral catalyst ((nbd)Rh⁺[η⁶‐(C₆H₅)B^?(C₆H₅)₃]) or a chiral catalytic system ([Rh(nbd)Cl]₂/(S)‐ or (R)‐phenylethylamine ((S)‐ or (R)‐PEA)). The two resulting polymers having an L ‐valinol or L ‐phenylalaninol residue showed Cotton effects at wavelengths around 430 nm. This observation indicated that they had an excess of one‐handed helical backbones. Positive and negative Cotton effects were observed only for the polymers having an L ‐valinol residue produced by using (R)‐ and (S)‐PEA as a cocatalyst, respectively, although the monomer had the same chirality. Even when the achiral catalyst was used, the two resulting polymers having an L ‐valinol or L ‐phenylalaninol residue showed Cotton effects despite the long distance between the chiral groups and the main chain. We have found the first example of a new type of chiral monomer, that is, a chiral phenylacetylene monomer having an L ‐amino alcohol residue and two hydroxy groups that was suitable for both modes of asymmetric polymerization, that is, the helix‐sense‐selective polymerization ( HSSP ) with the chiral catalytic system and the asymmetric‐induced polymerization ( AIP ) with the achiral catalyst. The other two monomers having L ‐alaninol and L ‐tyrosinol were found to be unsuitable to neither HSSP nor AIP because of their polymers' low solubility. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Chiral Isocamphoric Acid: Founding a Large Family of Homochiral Porous Materials

Homochiral metal–organic frameworks (MOFs) are an important class of chiral solids with potential applications in chiral recognition; however, relatively few are available. Of great importance is the availability of low‐cost, racemization‐resistant, and versatile enantiopure building blocks. Among chiral building blocks, d ‐camphoric acid is highly prolific, yet, its trans‐isomer, l ‐isocamphoric acid, has remained unknown in the entire field of solid‐state materials. Its rich yet totally untapped synthetic and structural chemistry has now been investigated through the synthesis of a large family of homochiral metal isocamphorates. The first observation of diastereoisomerism in isostructural MOFs is presented. Isocamphorate has a powerful ability to create framework topologies unexpected from common inorganic building blocks, and isocamphoric acid should allow access to hundreds of new homochiral materials.     

One-Handed Helical Polyacetylenes Bearing Axially-Chiral 2-Arylpyridyl-N-Oxide Units for Efficient Chromatographic Enantioseparation of Chiral Aromatic and Aliphatic Alcohols

A series of poly(biarylylacetylene)s (PBAs) bearing axially-chiral (S)-and (R)-pyridyl-N-oxide residues with a methoxy, propoxy, or acetyloxy substituent at the 3-position of the biaryl units was synthesized. All the PBAs formed a preferred-handed helix, while the helical sense preference was varied depending on the substituents despite the same twist-sense of the biaryl units. Among them, the propoxy-bound helical PBA showed an exceptionally high chiral recognition ability as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) and efficiently resolved not only various chiral aromatic alcohols, but also a variety of chiral aliphatic alcohols; the latter still remains difficult to resolve by commercially-available CSPs in HPLC. Such practically-useful both handed helical PBA-based CSPs can be produced from the racemic PBA composed of fully racemic monomer units through deracemization of the biaryl units with a chiral alcohol.     

Host–guest complexation‐triggered chiroptical change of poly(phenylacetylene)s bearing binaphthocrown ether moieties on the main chain

Diacetylene monomers with respective lengths of the oxyethylene chains were cyclopolymerized with a rhodium catalyst to produce novel poly(phenylacetylene)s bearing a different cavity size of the chiral crown ether in the repeating units ( 2a – c ). In the circular dichroism spectra of the resulting polymers, characteristic Cotton effects were observed in the range from 350 to 500 nm corresponding to the absorption of the conjugated polymer backbone, indicating that the polymers possessed a helical structure with an excess single screw sense induced by the covalently bonded binaphthyl units. The host–guest complexation of 2a – c with achiral guests produced a chiroptical change based on the fluctuation in the main chain conformation. The behavior of the complexation‐induced chiroptical change was essentially dictated by the cavity size of the binaphthocrown ether units. Additionally, a chirality‐responsive helicity change was observed in the case of the complexation of 2a – c with chiral guests, which also depended on the crown ether size. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1197–1206, 2010     

Synthesis and property of helical poly(phenylacetylene)s bearing chiral ruthenium complexes and real space imaging of meso- and nanoscopic structures by atomic force microscopy

Novel sets of helical poly(phenylacetylene)s bearing a chiral ruthenium (Ru) complex with opposite chirality (Δ and Λ forms) as a bulky pendant (poly- 1 and poly- 2 ) were synthesized through the polymerization of the corresponding optically pure phenylacetylenes with a rhodium catalyst, and their structures in solution and morphology on solid substrates were investigated with NMR, ultraviolet–visible, and circular dichroism (CD) spectroscopies and with atomic force microscopy (AFM), respectively. The obtained cis–transoidal polymers (poly- 1 and poly- 2 ) showed characteristic Cotton effects in the region of metal-to-ligand charge transfer of the chiral Ru pendants. Poly- 1 and poly- 2 were thought to have a predominantly one-handed helical conformation induced by the chiral pendants. However, the apparent Cotton effects derived from the helically twisted π-conjugated polymer backbone could not be observed, probably because of the strong chiral chromophoric pendants. However, in the AFM images, the helical polymers adsorbed on mica could be easily discerned as isolated strands, and the visualization and discrimination of the right- and left-handed helical structures of the chiral polymers were achieved by high-resolution AFM imaging. On the basis of the AFM observations together with the CD measurements and computational calculation results, possible structures of poly- 1 and poly- 2 were examined. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4621–4640, 2004     

Glycosyl‐Templated Chiral Helix Stapling of Ethynylpyridine Oligomers by Alkene Metathesis between Inter‐Pitch Side Chains

Ethynylpyridine polymers and oligomers consisting of 4‐substituted pyridine rings linked by acetylene bonds at the 2‐ and 6‐positions have been investigated. Ethynylpyridine oligomers covalently linked with a glycosyl chiral template form chiral helical complexes by intramolecular hydrogen bonding, in which the chirality of the template is translated to the helix. With a view to fixation of the chiral architecture, D /L ‐galactosyl‐ and D /L ‐mannosyl‐linked ethynylpyridine oligomers have been developed with 4‐(3‐butenyloxy)pyridine units having alkene side chains. The helical structures are successfully stapled by alkene metathesis of the side chains. Subsequent removal of the chiral templates by acidolysis produces template‐free stapled oligomers. The chiral, template‐free, stapled oligomers show chiral helicity, which is resistant to polar solvents and heating.     

Amino Acid Ionic Liquids as Chiral Ligands in Ligand‐Exchange Chiral Separations

Recently, amino acid ionic liquids (AAILs) have attracted much research interest. In this paper, we present the first application of AAILs in chiral separation based on the chiral ligand exchange principle. By using 1‐alkyl‐3‐methylimidazolium L ‐proline (L ‐Pro) as a chiral ligand coordinated with copper(II), four pairs of underivatized amino acid enantiomers—dl ‐phenylalanine (dl ‐Phe), dl ‐histidine (dl ‐His), dl ‐tryptophane (dl ‐Trp), and dl ‐tyrosine (dl ‐Tyr)—were successfully separated in two major chiral separation techniques, HPLC and capillary electrophoresis (CE), with higher enantioselectivity than conventionally used amino acid ligands (resolution (R_s)=3.26–10.81 for HPLC; R_s=1.34–4.27 for CE). Interestingly, increasing the alkyl chain length of the AAIL cation remarkably enhanced the enantioselectivity. It was inferred that the alkylmethylimidazolium cations and L ‐Pro form ion pairs on the surface of the stationary phase or on the inner surface of the capillary. The ternary copper complexes with L ‐Pro are consequently attached to the support surface, thus inducing an ion‐exchange type of retention for the dl ‐enantiomers. Therefore, the AAIL cation plays an essential role in the separation. This work demonstrates that AAILs are good alternatives to conventional amino acid ligands for ligand‐exchange‐based chiral separation. It also reveals the tremendous application potential of this new type of task‐specific ILs.     

Chiral discrimination of a helically organized crown ether array parallel to the helix axis of polyisocyanate

The asymmetric polymerization of 4′‐isocyanatobenzo‐18‐crown‐6 with the lithium amide of (S)‐(2‐methoxymethyl)pyrrolidine successfully proceeded to afford end‐functionalized poly(4′‐isocyanatobenzo‐18‐crown‐6) with (S)‐(2‐methoxymethyl)pyrrolidine (polymer 2 ). In the circular dichroism (CD) spectrum of 2 , a clear positive Cotton effect was observed in the range of 240–350 nm corresponding to the absorption of the polymer backbone, indicating that 2 partially formed a one‐handed helical structure, which was preserved by the chirality of (S)‐(2‐methoxymethyl)pyrrolidine bonding to the terminal end in 2 . In the titration experiments for the CD intensity of 2 in the presence of D ‐ and L ‐Phe·HClO₄ (where Phe is phenylalanine), a small but remarkable difference was observed in the amount of the chiral guest needed for saturation of the CD intensity and in the saturated CD intensity, indicating that the extremely stable, one‐handed helical part should exist in the main chain of 2 , which was not inverted even when the unfavorable chiral guest for the predominant helical sense, L ‐Phe·HClO₄, was added. In addition, helical polymer 2 exhibited a chiral discrimination ability toward racemic guests; that is, the guests were extracted from the aqueous phase into the organic phase with enantiomeric excess. The driving force of the chiral discrimination ability of 2 should certainly be attributed to the one‐handed helical structure in 2 . © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 325–334, 2006     

Unexpected stereomutation dependence on the chemical structure of helical vinyl glycopolymers

A small change in chemical structure causes a remarkable influence on the stereostructure stability and mutarotational rate of helical vinyl polymers bearing laterally attached p-terphenyl pendants with an achiral butoxy terminal and a chiral galactosyloxy terminal.     

Synthesis and characterization of chiral poly(l‐lactide‐b‐hexyl isocyanate) macromonomers with norbornenyl end groups and their homopolymerization through ring opening metathesis polymerization to afford polymer brushes

We report the synthesis of the novel half‐titanocene alkoxide complex bischloro‐η⁵‐cyclopentadienyl(bicyclo[2.2.1]‐hept‐5‐en‐2‐oxy) titanium (IV), [CpTiCl₂(O‐NBE)]. This complex was employed for the synthesis of chiral poly(l ‐lactide‐b‐hexyl isocyanate) diblock copolymer bearing a norbornene end group with sequential addition of monomers. The poly(hexyl isocyanate) block is chiral due to the last l ‐lactide unit of the poly(l ‐lactide) block. This macromonomer was polymerized towards a chiral polymer brush structure with polynorbornene backbone and chiral poly(l ‐lactide‐b‐hexyl isocyanate) side chains using Grubbs first‐generation catalyst. The polymers were characterized using size exclusion chromatography (SEC), nuclear magnetic resonance (NMR), and circular dichroism (CD) spectroscopy and their thermal properties were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1102–1112     

Synthesis and UCST‐type phase behavior of OEGylated poly(γ‐benzyl‐l‐glutamate) in organic media

A series of OEGylated poly(γ‐benzyl‐l ‐glutamate) with different oligo‐ethylene‐glycol side‐chain length, molecular weight (MW = 8.4 × 10³ to 13.5 × 10⁴) and narrow molecular weight distribution (PDI = 1.12–1.19) can be readily prepared from triethylamine initiated ring‐opening polymerization of OEGylated γ‐benzyl‐l ‐glutamic acid based N‐carboxyanhydride. FTIR analysis revealed that the polymers adopted α‐helical conformation in the solid‐state. While they showed poor solubility in water, they exhibited a reversible upper critical solution temperature (UCST)‐type phase behavior in various alcoholic organic solvents (i.e., methanol, ethanol, 1‐propanol, 1‐butanol, 1‐pentanol, and isopropanol). Variable‐temperature UV–vis analysis revealed that the UCST‐type transition temperatures (T_pts) of the resulting polymers were highly dependent on the type of solvent, polymer concentration, side‐ and main‐chain length. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1348‐1356     

Induction of Preferential Helical Screw Senses in Optically Inactive Polysilanes via Chiral Solvation

Two optically active solvents were synthesised, (S)‐(–)‐2‐methyl‐1‐propoxybutane and (S)‐(–)‐(2‐methylbutoxymethyl)benzene. The main chain conformations of poly(methylphenylsilane) and poly(hexylmethylsilane) in these solvents were investigated using optical UV‐visible and circular dichroism spectroscopy. It was observed that dissolving these inherently achiral polysilanes in optically active solvents induces the polymer chains to adopt preferred helical screw senses. This is the first example of induction of optical activity in conjugated polymers through chiral solvation.     

侧链带有L-氨基酸乙酯的螺旋聚苯乙炔衍生物的手性识别能力研究

采用Rh(nbd)BPh4催化剂合成了3种侧链带有L-氨基酸乙酯的螺旋聚苯乙炔衍生物PPA-S-Phe、PPA-S-Leu和PPA-A-Leu,并将其涂覆在氨丙基硅胶上制备高效液相色谱(HPLC)手性固定相(CSP),研究其对7种对映体的手性识别能力.由于侧链手性基团或主链与手性基团之间的链接基团不同,PPA-S-Phe、PPA-S-Leu和PPA-A-Leu形成了不同的螺旋构象,并表现出对对映体不同的手性识别能力.PPA-S-Phe和PPA-S-Leu的主链与手性基团之间的链接基团均为磺酰胺基,侧链手性基团为L-亮氨酸乙酯的PPA-S-Leu的手性识别能力优于侧链手性基团为L-苯丙氨酸乙酯的PPA-S-Phe.PPA-S-Leu和PPA-A-Leu的侧链手性基团均为L-亮氨酸乙酯,以酰胺基为链接基团的PPA-A-Leu的手性识别能力明显优于以磺酰胺基为链接基团的PPA-S-Leu.螺旋聚苯乙炔主链与侧链手性基团之间的链接基团、侧链手性基团在手性识别中均发挥十分着重要作用.     

乙烯基二联苯单体的螺旋选择性自由基聚合

为了深入理解乙烯基二联苯单体自由基聚合过程中的手性传递,进行了手性单体(+)-2-[(S)-异丁氧羰基-5-(4′-己氧基苯基)苯乙烯、非手性单体2-丁氧羰基-5-(4′-己氧基苯基)苯乙烯的均聚反应及它们二者的共聚反应,探讨了聚合温度和溶剂性质对手性单体均聚物旋光活性、手性单体含量对共聚物旋光活性以及聚合反应溶剂的超分子手性对共聚物旋光活性的影响.研究发现,降低聚合温度、采用液晶性反应介质有利于得到旋光度大的聚合物;少量手性单体的引入即可诱导共聚物形成某一方向占优的螺旋构象,比旋光度随手性单体的含量增加呈线性增长;在胆甾相液晶中制备的非手性单体聚合物不具有光学活性.这些结果表明,该类乙烯基二联苯聚合物具有动态螺旋构象,其光学活性主要依赖于主链的立构规整度和侧基不对称原子的手性.