Enzymatic polymerization: A new method of polymer synthesis

Enzymatic polymerization denotes an in vitro polymerization via nonbiosynthetic pathways catalyzed by an isolated enzyme. This article describes the recent progress of this polymerization technique, developed mainly during this decade. The polymerization utilizes enzymes of hydrolases and oxidoreductases as catalysts. This new method of polymer synthesis provided natural polysaccharides like cellulose, amylose, xylan, and chitin, and unnatural polysaccharides catalyzed by a glycosidase from well-designed monomers, various functionalized polyesters catalyzed by lipase from a variety of monomers, and polyaromatics materials catalyzed by an oxidoreductase and an enzyme model complex from phenols and anilines. An oxidoreductase also initiated vinyl polymerizations. Characteristic features of enzymatic polymerizations are discussed, including the importance of the combination of substrate monomer and enzyme. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3041–3056, 1999     

Synthesis and reaction of β‐hydroxyaspartic acid‐based polymethacrylate

O‐Methacryloyl‐N‐(tert‐butoxycarbonyl)‐β‐hydroxyaspartic acid dimethyl ester was synthesized by methyl esterification of β‐hydroxyaspartic acid, followed by protection of the amino group with the tert‐butoxycarbonyl group and then the reaction of the hydroxyl group with methacryloyl chloride. The monomer efficiently underwent radical polymerization to afford the corresponding polymer with a number‐average molecular weight of 42,000 in good yields. The alkaline hydrolysis of the polymer occurred not only at the methyl ester but also at the ester moiety between the main and side chains of the polymer. The methyl ester‐free polymer gradually released β‐hydroxyaspartic acid moiety in a phosphate buffer solution with pH = 7.3 and 7.8. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2782–2788, 2002     

Synthesis of polymers by template polymerization. I. Template polymerization of poly(methacrylic acid) with β‐cyclodextrin

A novel template monomer with multiple methacryloyl groups was synthesized with β‐cyclodextrin by the acetylation of primary hydroxyl groups and the esterification of secondary hydroxyl groups with methacrylic acid anhydride. The average number of methacryloyl groups in the monomer was 11. The radical polymerization of the monomer was carried out with the following initiators: α,α′‐azobisisobutylonitrile, H₂O₂? Fe²⁺ redox initiator, p‐xylyl‐N,N‐dimethyldithiocarbamate (XDC), and α‐bromo‐p‐xylyl‐N,N‐dimethyldithiocarbamate (BXDC). When the concentration of the monomer was less than 4.12 × 10^?3 M, polymerization was limited inside the molecule, and gelation of the system was hindered. For controlled radical photopolymerization with XDC and BXDC, the methacryloyl groups of the monomer were homogeneously polymerized, and poly(methacrylic acid) with a narrow molecular weight distribution was obtained by the hydrolysis of the polymerized products. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3539–3546, 2001     

Asymmetric cyclopolymerization of N‐tert‐butyl‐N‐allylacrylamide in the presence of β‐cyclodextrin

The radical polymerization of N‐tert‐butyl‐N‐allylacrylamide (t‐BAA) was carried out in a dimethyl sulfoxide/H₂O mixture in the presence of β‐cyclodextrin (β‐CD). The polymerization proceeded with the complete cyclization of the t‐BAA unit and yielded optically active poly(t‐BAA). The IR spectrum of the obtained polymer showed that the cyclic structure in the polymer was a five‐membered ring. The optical activity of poly(t‐BAA) increased with an increasing molar ratio of β‐CD to the t‐BAA monomer. The interaction of β‐CD with t‐BAA was confirmed by ¹H NMR and ¹³C NMR analyses of the polymerization system. It is suggested that interaction of the t‐BAA monomer with the hydrophobic cavity of β‐CD plays an important role in the asymmetric cyclopolymerization of t‐BAA. The radical copolymerization of t‐BAA with styrene (St), methyl methacrylate, ethyl methacrylate, or benzyl methacrylate (BMA) also produced optically active copolymers with a cyclic structure from the t‐BAA unit. St and BMA carrying a phenyl group were predicted to compete with t‐BAA for interaction with β‐CD in the copolymerization system. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2098–2105, 2000     

High‐molecular‐weight poly(1,5‐dioxepan‐2‐one) via enzyme‐catalyzed ring‐opening polymerization

To avoid organometallic catalysts in the synthesis of poly(1,5‐dioxepan‐2‐one), the enzymatic ring‐opening polymerization of 1,5‐dioxepan‐2‐one (DXO) was performed with lipase CA (derived from Candida antarctica) as a biocatalyst. A linear relationship between the number‐average molecular weight and monomer conversion was observed, and this suggested that the product molecular weight could be controlled by the stoichiometry of the reactants. The monomer consumption followed a first‐order rate law with respect to the monomer, and no chain termination occurred. Water acted as a chain initiator, but it could cause polymer hydrolysis when it exceeded an optimum level. An initial activation via the heating of the enzyme was sufficient to start the polymerization, as the monomer conversion occurred when samples were left at room temperature after an initial heating at 60 °C. A high lipase content led to a high monomer conversion as well as a high molecular weight. An increase in the monomer conversion and molecular weight was observed when the polymerization temperature was increased from 40 to 80 °C. A further increase in the polymerization temperature led to a decrease in the monomer conversion and molecular weight because of the denaturation of the enzyme at elevated temperatures. The polymerization behavior of DXO under lipase CA catalysis was compared with that of ε‐caprolactone (CL). The rate of monomer conversion of DXO was much faster than that of CL, and this may have been due to differences in their specificity toward lipase CA. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4206–4216, 2005     

Ring‐opening polymerization of 1,4‐dioxan‐2‐one initiated by lanthanum isopropoxide in bulk

Lanthanum isopropoxide (La(OiPr)₃) has been synthesized and employed for ring‐opening polymerization of 1,4‐dioxan‐2‐one in bulk as a single‐component initiator. The influences of reaction conditions such as initiator concentration, reaction time, and reaction temperature on the polymerization were investigated. The kinetics indicated that the polymerization is first‐order with respect to the monomer concentration. The Mechanistic investigations according to ¹H NMR spectrum analysis demonstrated that the polymerization of PDO proceeded through a coordination‐insertion mechanism with a rupture of the acyl‐oxygen bond of the monomer rather than the alkyl‐oxygen bond cleavage. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5214–5222, 2008     

Toward the design of LPEI containing block copolymers: Improved synthesis protocol,selective hydrolysis,and detailed characterization

The synthesis of poly(2‐ethyl‐2‐oxazoline)‐b‐linear poly(ethylenimine) (PEtOx‐b‐LPEI) copolymers by selective basic hydrolysis of PEtOx‐b‐poly(2‐H‐2‐oxazoline) (PEtOx‐b‐PHOx) is described. For this purpose, an easy method for the preparation of the 2‐H‐2‐oxazoline (HOx) monomer was developed. Based on the microwave‐assisted polymerization kinetics for this monomer, PEtOx‐b‐PHOx copolymers were prepared. Subsequently, the block copolymers were selectively hydrolyzed to PEtOx‐b‐LPEI under basic conditions. The success of the polymerizations and subsequent post‐polymerization reactions was demonstrated by ¹H NMR spectroscopy and MALDI‐TOF‐MS investigations of the obtained polymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Organosoluble star polymers from a cyclodextrin core

Well‐defined star polymers were synthesized with a combination of the core‐first method and atom transfer radical polymerization. The control of the architecture of the macroinitiator based on β‐cyclodextrin bearing functional bromide groups was determined by ¹³C NMR, fast atom bombardment mass spectrometry, and elemental analysis. In a second step, the polymerization of the tert‐butyl acrylate monomer was optimized to avoid a star–star coupling reaction and allowed the synthesis of a well‐defined organosoluble polymer star. The determination of the macromolecular dimensions of these new star polymers by size exclusion chromatography/light scattering was in agreement with the structure of armed star polymers in a large range of predicted molecular weights. This article describes a new approach to polyelectrolyte star polymers by postmodification of poly(tert‐butyl acrylate) by acrylic arm hydrolysis in a water‐soluble system. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5186–5194, 2005     

Polymerization of β‐pinene with Schiff‐base nickel complexes catalyst: Synthesis of relatively high molecular weight poly(β‐pinene) at high temperature with high productivity

A series of easily accessible and stable Schiff‐base nickel complexes (complex 1 – 4 ) in conjunction with methylaluminoxane (MAO) were employed for the synthesis of relatively high molecular weight β‐pinene polymers at high temperature with high productivity. The ligand structure of the complex had a substantial effect on the polymerization in terms of the productivity and the molecular weight. With complex 4 in the presence of MAO, high molecular weight polymers of β‐pinene (M_n ～ 10,900) were obtained at 40 °C with an extremely high productivity up to 1.25 × 10⁷ g polyβ‐pinene/mol of Ni. ¹H NMR analyses showed that the obtained β‐pinene polymer was structurally identical to that formed by conventional cationic Lewis acid initiators. The polymerization was presumably initiated by the nickel cation formed by the reaction of the schiff‐base nickel complex and MAO, while the propagation proceeded in a manner typical for a conventional carbocationic polymerization process. Direct evidence for the carbocationic polymerization was offered by the fact that quenching of the polymerization with methanol at a low monomer conversion resulted in incorporation of a methoxyl end group into the polymer chain. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3739–3746, 2007     

Chemical Synthesis of Native-Type Cellulose and Its Analogues via Enzymatic Polymerization

Abstract

The first successful chemical synthesis of cellulose was achieved by a polycondensation of β-cellobiosyl fluoride monomer catalyzed with cellulase, an extracellular hydrolytic enzyme of cellulose, in a mixed solvent of acetonitrile and acetate buffer. The product, synthetic cellulose, was the crystalline allomorph cellulose II, a thermodynamically more stable form. More detailed examinations of the polymerization conditions led to the formation of the native cellulose I, a metastable allomorph, for the first time. The key to the success was to use partially purified cellulase and an appropriate mixed solvent of acetonitrile/buffer. The formation of the two allomorphs of cellulose implies that the polarity of the glucan chain ordering can be controlled in a test tube. Based on these findings, a new concept “choroselectivity,” meaning spacial control in ordering the macromolecular chain, has been proposed. Cellulose analogues, 6-O-methylated cellulose and xylan, have been synthesized regio- and stereoselectively by using the enzymatic polymerization technique.     

Controlled radical copolymerization of β‐pinene and acrylonitrile

The feasibility of the radical copolymerization of β‐pinene and acrylonitrile was clarified for the first time. The monomer reactivity ratios evaluated by the Fineman–Ross method were r_β‐pinene = 0 and r_{acrylonitrile} = 0.66 in dichloroethane at 60 °C with AIBN, which indicated that the copolymerization was a simple alternating copolymerization. The addition of the Lewis acid Et₂AlCl increased the copolymerization rate and enhanced the incorporation of β‐pinene. The first example for the synthesis of an almost perfectly alternating copolymer of β‐pinene and acrylonitrile was achieved in the presence of Et₂AlCl. Furthermore, the possible controlled copolymerization of β‐pinene and acrylonitrile was then attempted via the reversible addition–fragmentation transfer (RAFT) technique. At a low β‐pinene/acrylonitrile feed ratio of 10/90 or 25/75, the copolymerization with 2‐cyanopropyl‐2‐yl dithiobenzoate as the transfer agent displayed the typical features of living polymerization. However, the living character could be observed only within certain monomer conversions. At higher monomer conversions, the copolymerizations deviated from the living behavior, probably because of the competitive degradative chain transfer of β‐pinene. The β‐pinene/acrylonitrile copolymers with a high alternation degree and controlled molecular weight were also obtained by the combination of the RAFT agent cumyl dithiobenzoate and Lewis acid Et₂AlCl. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2376–2387, 2006     

Ring‐opening polymerization of L‐lactide by rare‐earth tris(4‐tert‐butylphenolate) single‐component initiators

The ring‐opening polymerization of L ‐lactide initiated by single‐component rare‐earth tris(4‐tert‐butylphenolate)s was conducted. The influences of the rare‐earth elements, solvents, temperature, monomer and initiator concentrations, and reaction time on the polymerization were investigated in detail. No racemization was found from 70 to 100 °C under the examined conditions. NMR and differential scanning calorimetry measurements further confirmed that the polymerization occurred without epimerization of the monomer or polymer. A kinetic study indicated that the polymerization rate was first‐order with respect to the monomer and initiator concentrations. The overall activation energy of the ring‐opening polymerization was 79.2 kJ mol^?1. ¹H NMR data showed that the L ‐lactide monomer inserted into the growing chains with acyl–oxygen bond cleavage. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6209–6215, 2004     

Synthesis of methylene butyrolactone polymers from itaconic acid

Herein, we report the transformation of β‐monomethyl itaconate, an inexpensive and biorenewable alternative to petroleum feedstocks, to the high‐value monomer α‐methylene‐γ,γ‐dimethyl‐γ‐butyrolactone (Me₂MBL) through a selective addition strategy. This strategy is also applied to the synthesis of α‐methylene‐γ‐butyrolactone (MBL, tulipalin A), a monomer that can be polymerized to give materials with desirable properties (high decomposition temperature, glass transition temperature, and refractive index). Subsequent polymerization of both Me₂MBL and MBL through reversible addition‐fragmentation chain‐transfer polymerization generates well‐defined poly(Me₂MBL) and poly(MBL) (PMBL). Physical characterization of poly(Me₂MBL) shows good physical properties comparable with known PMBL materials. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2730–2737     

Chemistry of 2‐oxazolines: A crossing of cationic ring‐opening polymerization and enzymatic ring‐opening polyaddition

Chemistry of 2‐oxazolines is involved in the polymer synthesis fields of cationic ring‐opening polymerization (CROP) and enzymatic ring‐opening polyaddition (EROPA), although both polymerizations look like a quite different class of reaction. The key for the polymerization to proceed is combination of the catalyst (initiator) and the design of monomers. This article describes recent developments in polymer synthesis via these two kinds of polymerizations to afford various functional polymers having completely different structures, poly(N‐acylethylenimine)s via CROP and 2‐amino‐2‐deoxy sugar unit‐containing oligo and polysaccharides via EROPA, respectively. From the viewpoint of reaction mode, an acid‐catalyzed ring‐opening polyaddition (ROPA) is considered to be a crossing where CROP and EROPA meet. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1251–1270, 2010     

New aliphatic poly(ester‐carbonates) based on 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one

The synthesis, characterization, and ring‐opening polymerization of a new cyclic carbonate monomer containing an allyl ester moiety, 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one (MAC), was performed for the first time. MAC was synthesized in five steps in good yield beginning from the starting material, 2,2‐bis(hydroxymethyl)propionic acid. Subsequent polymerization and copolymerizations of the new cyclic carbonate with rac‐lactide (rac‐LA) and ?‐caprolactone (CL) were attempted. Rac‐LA copolymerized well with MAC, but CL copolymerizations produced insoluble products. Oligomeric macroinitiators of MAC and rac‐LA were synthesized from stannous ethoxide, and both macroinitiators were used for the controlled ring‐opening polymerization of rac‐LA. The polymerization kinetics were examined by monitoring the disappearance of the characteristic C? O ring stretch of the monomer at 1240 cm^?1 with real‐time in situ Fourier transform infrared spectroscopy. Postpolymerization oxidation reactions were conducted to epoxidize the unsaturated bonds of the MAC‐functionalized polymers. Epoxide‐containing polymers may allow further organic transformations with various nucleophiles, such as amines, alcohols, and carboxylic acids. NMR was used for microstructure identification of the polymers, and size exclusion chromatography and differential scanning calorimetry were used to characterize the new functionalized poly(ester‐carbonates). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1978–1991, 2003     

Thermal polycondensation of sugar fluoride to form highly branched polysaccharide

Sugar fluorides were found to undergo powder‐to‐powder polycondensation without any catalyst at 110–160 °C under vacuum, giving highly branched polysaccharides (Conv. = 40–95%, M_w = 1400–20,000). The cross‐polarized optical microscopy at 110 °C disclosed that the crystal shape of α‐glucosyl fluoride ( FGlc ) was unchanged throughout the polymerization in spite of producing the amorphous polymer ( Poly‐FGlc ). The solid‐state post polymerization of Poly‐FGlc (M_w: 2700) at 180 °C increased the higher molecular weight (M_w: 8900). The product polysaccharide was per‐O‐methylated and subjected to structure analyses. Acid‐hydrolysis, which gave a variety of the partially O‐methylated monosaccharides, suggested that the product polysaccharides had a highly branched structure consisting of all of the possible glycosidic linkages. MALDI‐TOF mass analysis revealed that the 1,6‐anhydride terminal unit was formed and participated to the polymerization. Interestingly, α‐maltosyl fluoride hydrate ( FMal·H ₂ O ) was polymerized at the lower temperature (100 °C) than the anhydrate ( FMal ), which required 160 °C for the polymerization. They produced different structure polymers even from the same monomer. The polymer from the former consisted of the disaccharide‐repeating unit, while the repeating unit of the polymer from the latter was the monosaccharide, which was formed by the acetal exchange reaction. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3851–3860, 2007     

Two‐dimensional polymer synthesis through the topochemical polymerization of alkylenediammonium muconate as a multifunctional monomer

Here we demonstrate a unique two‐dimensional polymer synthesis through topochemical polymerization via polymer crystal engineering, which is useful for controlling and designing the polymerization reactivity as well as the polymer chain and crystal structures. We have succeeded in the synthesis of a sheet polymer through the polymerization of alkylenediammonium (Z,Z)‐muconate as a multifunctional 1,3‐diene monomer in the crystalline state under the irradiation of UV and γ‐rays or upon heating in the dark. The photopolymerization reactivity of several muconates and the structural control of the obtained polymer are described. The stereochemical structure of the polymer and the polymerization mechanism are discussed on the basis of the results of IR and NMR spectroscopy, thermogravimetric measurements, and solid‐state hydrolysis for the transformation into poly(muconic acid). © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3922–3929, 2004     

Living syndiospecific polymerization of propylene promoted by C1‐symmetric titanium complexes activated by dried MAO

A series of C₁‐symmetric titanium complexes with both salicylaldiminato and β‐enaminoketonato as the ligands have been synthesized and investigated as the catalysts for propylene polymerization. In the presence of dried methylaluminoxane (dMAO), the complex with bulky substituent tert‐butyl ortho to alkyl oxygen can promote living polymerization of propylene with improved catalytic activity at ambient temperature, producing high molecular weight syndiotactic polypropylenes (rrrr 90.2%) with narrow molecular weight distributions (M_w/M_n = 1.07–1.22), via a propagation of 1,2‐insertion of monomer and chain‐end control of stereoselectivity. The propagation of polymer chain is completely different from that mediated by FI catalysts (the titanium complexes with phenoxy‐imine chelate ligands) which favor 2,1‐insertion of monomer. The interaction between a fluorine and a β‐hydrogen of a growing polymer chain, negligible chain transfer to monomer and dMAO without any free AlMe₃ were responsible for the achievement of living propylene polymerization. The substituent ortho to alkyl oxygen determined the stereo structure of the resultant polypropylene. In the case of less steric congested complexes with two nonequivalent coordination positions, the growing polymer chain might swing back to the favorite coordination position (site‐epimerization), forming m dyads regioirregular units. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of polymeric core–shell particles using surface‐initiated living free‐radical polymerization

An easy and novel approach to the synthesis of functionalized nanostructured polymeric particles is reported. The surfactant‐free emulsion polymerization of methyl methacrylate in the presence of the crosslinking reagent 2‐ethyl‐2‐(hydroxy methyl)‐1,3‐propanediol trimethacrylate was used to in situ crosslink colloid micelles to produce stable, crosslinked polymeric particles (diameter size ～ 100–300 nm). A functionalized methacrylate monomer, 2‐methacryloxyethyl‐2′‐bromoisobutyrate, containing a dormant atom transfer radical polymerization (ATRP) living free‐radical initiator, which is termed an inimer (initiator/monomer), was added to the solution during the polymerization to functionalize the surface of the particles with ATRP initiator groups. The surface‐initiated ATRP of different monomers was then carried out to produce core–shell‐type polymeric nanostructures. This versatile technique can be easily employed for the design of a wide variety of polymeric shells surrounding a crosslinked core while keeping good control over the sizes of the nanostructures. The particles were characterized with scanning electron microscopy, transmission electron microscopy, optical microscopy, dynamic light scattering, and Raman spectroscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1575–1584, 2007     

Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization in ionic liquid

Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization has been demonstrated to be a valid method to prepare block copolymer nano‐objects. However, volatile solvents are generally involved in this preparation. Herein, the in situ synthesis of block copolymer nano‐objects of poly(ethylene glycol)‐block‐polystyrene (PEG‐b‐PS) in the ionic liquid of 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([BMIN][PF₆]) through the macro‐RAFT agent mediated dispersion polymerization is investigated. It is found that the dispersion RAFT polymerization of styrene in the ionic liquid of [BMIN][PF₆] runs faster than that in the alcoholic solvent, and the dispersion RAFT polymerization in the ionic liquid affords good control over the molecular weight and the molecular weight distribution of the PEG‐b‐PS diblock copolymer. The morphology of the in situ synthesized PEG‐b‐PS diblock copolymer nano‐objects, e.g., nanospheres and vesicles, in the ionic liquid is dependent on the polymerization degree of the solvophobic block and the concentration of the fed monomer, which is somewhat similar to those in alcoholic solvent. It is anticipated that the dispersion RAFT polymerization in ionic liquid broads a new way to prepare block copolymer nano‐objects. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1517–1525