Asymmetric Cationic Polymerization of Benzofuran through a Reversible Chain-Transfer Mechanism: Optically Active Polybenzofuran with Controlled Molecular Weights.

Benzofuran (BzF) is a prochiral, 1,2-disubstituted, unsymmetric cyclic olefin that can afford optically active polymers by asymmetric polymerization, unlike common acyclic vinyl monomers. Although asymmetric cationic polymerization of BzF was reported by Natta et al. in the 1960s, the polymer structure has not been clarified, and there are no reports on molecular weight control. Herein, we report dual control of the optical activity and molecular weight of poly(BzF) using thioether-based reversible chain-transfer agents for asymmetric cationic polymerization with ß-amino acid derivatives as chiral additives and aluminum chloride as a catalyst. This asymmetric moderately living cationic polymerization leads to an increase in molecular weight and specific optical rotation with monomer conversion. In addition, asymmetric block polymers consisting of opposite absolute configurational segments were synthesized using both enantiomers sequentially as chiral additives. Finally, a comprehensive analysis of the polymerization products and the model reaction revealed that the optical activity of poly(BzF) originates from the threo-diisotactic structure, which occurs by regio-, trans-, and enantioselective propagation.

Hybridization of Step-/Chain-Growth and Radical/Cationic Polymerizations Using Thioacetals as Key Components for Triblock, Periodic and Random Multiblock Copolymers with Thermoresponsiveness.

A novel strategy for synthesizing a series of multiblock copolymers is developed by combining radical/cationic step-growth polymerizations of dithiols and divinyl ethers and chain-growth cationic degenerative chain-transfer (DT) polymerizations of vinyl ethers using thioacetals as key components. The combination of radical step-growth polymerization and a cationic thiol-ene reaction or cationic step-growth polymerization enables the synthesis of a series of macro chain-transfer agents (CTAs) composed of poly(thioether) and thioacetal groups at different positions. The resulting products are 1) bifunctional macro CTAs with thioacetal groups at both chain ends, 2) periodic macro CTAs periodically having thioacetal groups in the main chain, and 3) random macro CTAs randomly having thioacetal groups in the main chain. Subsequently, the obtained macro CTAs are used for chain-growth cationic DT polymerization of methoxyethyl vinyl ether (MOVE) to result in 1) triblock, 2) periodic, and 3) random multiblock copolymers consisting of poly(thioether) and poly(MOVE) segments. All these triblock and multiblock copolymers composed of hydrophobic poly(thioether) and hydrophilic poly(MOVE) segments show an amphiphilic tendency to form characteristic micelles in aqueous solutions. In addition, due to the thermoresponsive poly(MOVE) segments, the obtained copolymers exhibit lower critical solution temperatures that depend on the segment sequences and lengths.

Biobased Polymers via Radical Homopolymerization and Copolymerization of a Series of Terpenoid-Derived Conjugated Dienes with exo-Methylene and 6-Membered Ring.

A series of exo-methylene 6-membered ring conjugated dienes, which are directly or indirectly obtained from terpenoids, such as ß-phellandrene, carvone, piperitone, and verbenone, were radically polymerized. Although their radical homopolymerizations were very slow, radical copolymerizations proceeded well with various common vinyl monomers, such as methyl acrylate (MA), acrylonitrile (AN), methyl methacrylate (MMA), and styrene (St), resulting in copolymers with comparable incorporation ratios of bio-based cyclic conjugated monomer units ranging from 40 to 60 mol% at a 1:1 feed ratio. The monomer reactivity ratios when using AN as a comonomer were close to 0, whereas those with St were approximately 0.5 to 1, indicating that these diene monomers can be considered electron-rich monomers. Reversible addition fragmentation chain-transfer (RAFT) copolymerizations with MA, AN, MMA, and St were all successful when using S-cumyl-S'-butyl trithiocarbonate (CBTC) as the RAFT agent resulting in copolymers with controlled molecular weights. The copolymers obtained with AN, MMA, or St showed glass transition temperatures (Tg) similar to those of common vinyl polymers (Tg ~ 100 °C), indicating that biobased cyclic structures were successfully incorporated into commodity polymers without losing good thermal properties.

Discrete and Stereospecific Oligomers Prepared by Sequential and Alternating Single Unit Monomer Insertion.

Natural biopolymers, such as DNA and proteins, have uniform microstructures with defined molecular weight, precise monomer sequence, and stereoregularity along the polymer main chain that affords them unique biological functions. To reproduce such structurally perfect polymers and understand the mechanism of specific functions through chemical approaches, researchers have proposed using synthetic polymers as an alternative due to their broad chemical diversity and relatively simple manipulation. Herein, we report a new methodology to prepare sequence-controlled and stereospecific oligomers using alternating radical chain growth and sequential photoinduced RAFT single unit monomer insertion (photo-RAFT SUMI). Two families of cyclic monomers, the indenes and the N-substituted maleimides, can be alternatively inserted into RAFT agents, one unit at a time, allowing the monomer sequence to be controlled through sequential and alternating monomer addition. Importantly, the stereochemistry of cyclic monomer insertion into the RAFT agents is found to be trans-selective along the main chains due to steric hindrance from the repeating monomer units. All investigated cyclic monomers provide such trans-selectivity, but analogous acyclic monomers give a mixed cis- and trans-insertion.

Enantioseparation Using Cellulose Tris(3,5-dimethylphenylcarbamate) as Chiral Stationary Phase for HPLC: Influence of Molecular Weight of Cellulose.

The cellulose oligomers with different degrees of polymerization (DP), 7, 11, 18, 24, 26, 40 and 52, were prepared by hydrolysis of microcrystalline cellulose with phosphoric acid. These oligomers including the starting microcrystalline cellulose (DP 124) were converted to tris(3,5-dimethylphenylcarbamate) (CDMPC) derivatives by the reaction with an excess of 3,5-dimethylphenyl isocyanate to be used as the chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). The structures of the CDMPC derivatives were investigated by infrared spectroscopy (IR), ¹H-NMR, circular dichroism (CD) and size exclusion chromatography (SEC), and the DPs of the derivatives estimated by SEC agreed with those estimated by ¹H-NMR. After coating the derivatives on silica gel, their chiral recognition abilities were evaluated using eight racemates under a normal phase condition with a hexane-2-propanol (99/1) mixture as an eluent. The chiral recognition abilities of 7- and 11-mers, particularly the former, were lower than those of the higher oligomers from DP 18 to 52, which had rather similar abilities to that of 124-mer, although the abilities depended on the racemates. DP 18 seems to be sufficient for CDMPC to exhibit chiral recognition similar to that of the CDMPC with larger DPs.

Precision synthesis of bio-based acrylic thermoplastic elastomer by RAFT polymerization of itaconic acid derivatives.

Bio-based polymer materials from renewable resources have recently become a growing research focus. Herein, a novel thermoplastic elastomer is developed via controlled/living radical polymerization of plant-derived itaconic acid derivatives, which are some of the most abundant renewable acrylic monomers obtained via the fermentation of starch. The reversible addition-fragmentation chain-transfer (RAFT) polymerizations of itaconic acid imides, such as N-phenylitaconimide and N-(p-tolyl)itaconimide, and itaconic acid esters, such as di-n-butyl itaconate and bis(2-ethylhexyl) itaconate, are examined using a series of RAFT agents to afford well-defined polymers. The number-average molecular weights of these polymers increase with the monomer conversion while retaining relatively narrow molecular weight distributions. Based on the successful controlled/living polymerization, sequential block copolymerization is subsequently investigated using mono- and di-functional RAFT agents to produce block copolymers with soft poly(itaconate) and hard poly(itaconimide) segments. The properties of the obtained triblock copolymer are evaluated as bio-based acrylic thermoplastic elastomers.

Stereospecific cyclic poly(methyl methacrylate) and its topology- guided hierarchically controlled supramolecular assemblies.

In this study, the stereocomplexation between a novel stereospecific cyclic vinyl polymer, that is, cyclic syndiotactic poly(methyl methacrylate) (st-PMMA), with the complementary linear isotactic (it-) PMMA was investigated. Surprising new insight into the effects of the topology (i.e., end groups), size, and tacticity of the assembling components on stereocomplex formation was obtained. Characterization of the stereocomplexes revealed that the self-assembly of cyclic st-PMMAs and linear it-PMMAs resulted in the formation of an unprecedented "polypseudorotaxane-type" supramolecular assembly. This stereocomplex exhibited remarkably different physical properties as compared to the conventional PMMA triple-helix stereocomplex as a result of the restricted topology imposed by the cyclic st-PMMA assembling component.

Design and synthesis of self-degradable antibacterial polymers by simultaneous chain- and step-growth radical copolymerization.

Self-degradable antimicrobial copolymers bearing cationic side chains and main-chain ester linkages were synthesized using the simultaneous chain- and step-growth radical polymerization of t-butyl acrylate and 3-butenyl 2-chloropropionate, followed by the transformation of t-butyl groups into primary ammonium salts. We prepared a series of copolymers with different structural features in terms of molecular weight, monomer composition, amine functionality, and side chain structures to examine the effect of polymer properties on their antimicrobial and hemolytic activities. The acrylate copolymers containing primary amine side chains displayed moderate antimicrobial activity against E. coli but were relatively hemolytic. The acrylate copolymer with quaternary ammonium groups and the acrylamide copolymers showed low or no antimicrobial and hemolytic activities. An acrylate copolymer with primary amine side chains degraded to lower molecular weight oligomers with lower antimicrobial activity in aqueous solution. This degradation was due to amidation of the ester groups of the polymer chains by the nucleophilic addition of primary amine groups in the side chains resulting in cleavage of the polymer main chain. The degradation mechanism was studied in detail by model reactions between amine compounds and precursor copolymers.

Hydrophilic bio-based polymers by radical copolymerization of cyclic vinyl ethers derived from glycerol.

In this study, novel functional polymers were obtained by using glycerol as a bio-based precursor, which is abundant and inexpensive renewable feedstock with a polyol skeleton. Cyclic vinyl ethers with acetal linkage were derived from glycerol to yield well-defined copolymers by reversible addition-fragmentation chain transfer (RAFT) radical copolymerization with common vinyl monomers. The resulting acetal-containing copolymers could be hydrolyzed under acidic conditions to afford water-soluble functional polymers with pendent diols.

Biocompatible thermoresponsive N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide-based random copolymer: synthesis and studies of its composition dependent properties and anticancer drug delivery efficiency.

A new acrylamide monomer, N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide (M3i), consisting of both isopropyl and isopropylamidopropyl moieties, has been synthesized from isopropylamine and N-isopropylacrylamide via an aza-Michael addition reaction followed by amidation with acryloyl chloride. The homopolymer of M3i (polyM3i) and a series of random copolymers of M3i and poly(ethylene glycol)methyl ether acrylate (PEGA: CH2CHCO2(CH2CH2O)nMe, Mn = 480, n = 9 on average) with varying compositions have been synthesized via reversible addition-fragmentation chain transfer polymerization using 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as well as 1-phenylethyl phenyl dithioacetate (PEPD) as a RAFT agent. These polymers have been characterized by 1H NMR, FTIR, GPC, UV-Vis, fluorescence, TGDTA, DSC, DLS, and TEM techniques. A lower critical solution temperature (LCST) and glass transition temperature (Tg) for polyM3i prepared using DDMAT were observed at 17 and 133 °C, respectively, while for a polymer formed using PEPD, no LCST was observed until 0 °C and its observed Tg was found at 127.3 °C. The polymers are thermally stable up to 300 °C. Upon an increase in the M3i content in the copolymers, LCST decreases, Tg increases, and the apparent hydrodynamic diameter decreases. Moreover, the effects of concentration and the addition of urea and sodium chloride on the LCST of the copolymer with an LCST close to body temperature were studied. Owing to the incorporation of PEGA, a higher critical micellar concentration and larger TEM particle size of this copolymer were observed with respect to those of polyM3i. The usefulness of the micelles of the copolymers as nano-carriers for the drug doxorubicin was explored. The in vitro tumoricidal activity of the micelles of the doxorubicin-loaded copolymers was also assessed against Dalton's lymphoma cells.

Highly efficient synthesis of low polydispersity core cross-linked star polymers by Ru-catalyzed living radical polymerization.

The efficient formation of low polydispersity core cross-linked star (CCS) polymers via controlled/living radical polymerization (LRP) and the arm-first approach was found to be dependent on the mediating catalyst system. The Ru catalyst, Ru(Ind)Cl(PPh3)2 Cat. 1, and tertiary amine co-catalyst were used to synthesize highly living poly(methyl methacrylate) (PMMA) macroinitiators, which were then linked together with ethylene glycol dimethacrylate (EGDMA) to form PMMA(arm)PEGDMA(core) CCS polymers. The quantitative and near-quantitative synthesis of CCS polymers were observed for low to moderate molecular weight macroinitiators (M(n) = 8 and 20 kDa), respectively. Lower conversions were observed for high-molecular weight macroinitiators (M(n) ≥ 60 kDa). Overall, an improvement of between 10 and 20% was observed when comparing the Cat. 1 system to a conventional Cu-catalyzed system. This significant improvement in macroinitiator-to-star conversion is explained in the context of catalyst system selection and CCS polymer formation.

AAB-sequence living radical chain copolymerization of naturally occurring limonene with maleimide: an end-to-end sequence-regulated copolymer.

Sequence control in chain-growth polymerization is still one of the most challenging topics in synthetic polymer chemistry in contrast to natural macromolecules with completely sequence-regulated structures like proteins and DNA. Here, we report the quantitative and highly selective 1:2 sequence-regulated radical copolymerization of naturally occurring (+)-d-limonene (L) and a maleimide (M) in fluoroalcohol giving chiral copolymers with high glass transition temperatures (220-250 degrees C) originating from the specific rigid cyclic structures of the monomers. Furthermore, the combination with a reversible addition-fragmentation chain transfer (RAFT) agent (C-S) via the controlled/living radical polymerization resulted in end-to-end sequence-regulated copolymers [C-(M-M-L)(n)-M-S] with both highly sequenced chain ends and main-chain repeating units as well as controlled molecular weights.

Immobilized-type chiral packing materials for HPLC based on polysaccharide derivatives.

The polysaccharide-based chiral packing materials (CPMs) for high-performance liquid chromatography (HPLC) have been recognized as the most powerful ones for the analyzing and preparative separating of the chiral compounds. These CPMs have been conventionally prepared by coating polysaccharide derivatives on a silica gel support. This means that the solvents, which swell or dissolve the derivatives on the silica gel and reduce the performance of the chiral columns, do not allow to be applied as components of the eluents. Therefore, the polysaccharide-based CPMs can be used with a rather limited number of eluents. In order to enhance the versatility of the eluent selection for more practical and economical chromatographic enantioseparations, the polysaccharide derivatives must be immobilized onto the silica gel. This review summarizes our latest studies on the development of the immobilized-type CPMs via the radical copolymerization and the polycondensation of the polysaccharide derivatives bearing small amounts of vinyl groups and alkoxysilyl groups, respectively.

Sequence-regulated vinyl copolymers by metal-catalysed step-growth radical polymerization.

Proteins and nucleic acids are sequence-regulated macromolecules with various properties originating from their perfectly sequenced primary structures. However, the sequence regulation of synthetic polymers, particularly vinyl polymers, has not been achieved and is one of the ultimate goals in polymer chemistry. In this study, we report a strategy to obtain sequence-regulated vinyl copolymers consisting of styrene, acrylate and vinyl chloride units using metal-catalysed step-growth radical polyaddition of designed monomers prepared from common vinyl monomer building blocks. Unprecedented ABCC-sequence-regulated copolymers with perfect vinyl chloride-styrene-acrylate-acrylate sequences were obtained by copper-catalysed step-growth radical polymerization of designed monomers possessing unconjugated C=C and reactive C-Cl bonds. This strategy may open a new route in the study of sequence-regulated synthetic polymers.

Organic-inorganic hybrid materials for efficient enantioseparation using cellulose 3,5-dimethylphenylcarbamate and tetraethyl orthosilicate.

The hybrid bead-type chiral packing material (CPM) for preparative enantioseparation has been prepared from the cellulose 3,5-dimethylphenylcarbamate containing a small number of 3-(triethoxysilyl)propyl groups in the presence of tetraethyl orthosilicate, by a sol-gel reaction in an aqueous surfactant solution. The obtained hybrid bead-type CPM was packed into a column and evaluated by high-performance liquid chromatography. When compared with the commercially available Chiralpak IB, which is prepared by the immobilization of cellulose 3,5-dimethylphenylcarbamate on silica gel, the hybrid bead-type CPM was shown to exhibit a similar chiral recognition and possess a higher loading capacity.

Preparation and chiral recognition ability of crosslinked beads of polysaccharide derivatives.

The spherical beads consisting of cellulose 3,5-dimethylphenylcarbamate with partial hydroxyl groups were prepared to be used as chiral packing materials (CPMs) for HPLC. The beads were obtained without using macroporous silica gel, which is usually used as the support of the CPMs based on the polysaccharide derivatives. After the crosslinking in the bead with diisocyanates, such as 4,4'-diphenylmethane diisocyanate (MDI), 4,4'-dibenzyl diisocyanate (DBDI), tolylene-2,4-diisocyanate (TDI), and m-xylylene diisocyanate (XDI), the obtained beads were packed into an HPLC column. As the content of the hydroxyl groups of the cellulose derivatives decreased, the obtained CPM exhibited a higher chiral recognition ability. The beads possessed a higher loading capacity than the CPM prepared by coating the cellulose derivative on silica gel. The crosslinked beads could be used with the eluent containing chloroform. The amylose derivative beads were also prepared as a CPM for chiral HPLC.

Immobilized polysaccharide derivatives: chiral packing materials for efficient HPLC resolution.

Polysaccharide-based chiral packing materials (CPMs) for high-performance liquid chromatography have frequently been used not only to determine the enantiomeric excess of chiral compounds but also to preparatively resolve a wide range of racemates. However, these CPMs can be used with only a limited number of solvents as mobile phases because some organic solvents, such as tetrahydrofuran, chloroform, and so on, dissolve or swell the polysaccharide derivatives coated on a support, e.g., silica gel, and destroy their packed columns. The limitation of mobile phase selection is sometimes a serious problem for the efficient analytical and preparative resolution of enantiomers. This defect can be resolved by the immobilization of the polysaccharide derivatives onto silica gel. Efficient immobilizations have been attained through the radical copolymerization of the polysaccharide derivatives bearing small amounts of polymerizable residues and also through the polycondensation of the polysaccharide derivatives containing a few percent of 3-(triethoxysilyl)propyl residue.

High-performance liquid chromatographic enantioseparations on capillary columns containing crosslinked polysaccharide phenylcarbamate derivatives attached to monolithic silica.

Monolithic capillary columns containing native silica gel were covalently modified with 3,5-disubstituted phenylcarbamate derivatives of cellulose and amylose and applied for enantioseparations in capillary LC. The method previously used for covalent immobilization of polysaccharide phenylcarbamate derivatives onto the surface of microparticulate silica gel was successfully adapted for in situ modification of monolithic fused-silica capillary columns. The effects of the nature of polysaccharide and the substituents, as well as of multiple covalent immobilization of polysaccharide derivative on chromatographic performance of capillary columns were studied. The capillary columns obtained using this technique are stable in all solvents commonly used in LC and exhibit promising enantiomer resolving ability.