Zwitterionic Ring-opening Polymerization Research Articles

Zwitterionic ring-opening polymerization of macrocyclic ethyleneoxy-substituted carbonate: Access to cyclic PEG-like polycarbonate

The innovation in polymer design to rival conventional polyethylene glycol (PEG) is an important approach to achieving a more sustainable society. Here, cyclic PEG-like polycarbonates having high molecular weight (4.4–49.5 kg/mol) were enabled through zwitterionic ring-opening polymerization (ZROP) of macrocyclic carbonates (MCs) mediated by N-heterocyclic carbene (NHC). The thermodynamic behavior of polymerization depends on the ring size of monomers. During this process, the ZROP of 11-membered MC was driven by the change of enthalpy (ΔHp) which differed from the ZROP of 14-membered MC driven by the entropic change (ΔSp). Cyclic polycarbonates depicted improved thermostability (Td5% ≥ 204 °C) and higher glass transition temperatures (Tg > ‒40 °C) in comparison to their linear analogues (Td5% ≤ 185 °C, Tg ∼‒50 °C). In addition, the mechanism of ZROP of MC was addressed through computational study. A distinct mechanism of polymerization distinguishable from the well-known NHC-mediated ZROP of cyclic esters was revealed, where the zwitterion from nucleophilic addition to MC, i.e. tetrahedral intermediate, cannot be ring-opened probably due to the delocalization of negative charge on the carbonate group, but serves as an active center for the polymerization. In comparison to PEG, the attained polymer demonstrated comparable hydrophilic and biocompatible properties, as revealed by the results of contact angle and in vitro cytotoxicity studies, suggesting that cyclic polycarbonate hold the promise as the alternative of PEG.

1,1,3,3-Tetramethylguanidine-Mediated Zwitterionic Ring-Opening Polymerization of Sarcosine-Derived N-Thiocarboxyanhydride toward Well-Defined Polysarcosine.

Zwitterionic ring-opening polymerization (ZROP) of sarcosine-derived N-thiocarboxyanhydrides (Me-NNTAs) can be induced by using 1,1,3,3-tetramethylguanidine (TMG) initiators in CH2Cl2 at 25 °C, rapidly producing well-defined polysarcosine polymers with controlled molecular weights (Mn = 1.9–37 kg/mol) and narrow molecular weight distributions (Đ = 1.01–1.12). The reaction exhibits characteristics of a living polymerization, evidenced by pseudo-first-order polymerization kinetics, the linear increase of polymer molecular weight (Mn) with conversion, and the successful chain extension experiments. The polymerization is proposed to proceed via propagating macro-zwitterions bearing a cationic 1,1,3,3-tetramethylguanidinium and an anionic thiocarbamate chain end. The TMG not only initiates the polymerization but also serves to stabilize the thiocarbamate chain end where the monomer addition occurs. Because of the enhanced hydrolytic stability of Me-NNTA, the polymerization can be conducted without the rigorous exclusion of moisture, further enhancing the appeal of the method to access well-defined polysarcosine.

Stereoselective zwitterionic ring-opening polymerization of rac-lactide

Stereoselective zwitterionic ring-opening polymerization (ZROP) poses a potentially great challenge in polymer chemistry because of its unique ion-pairing catalysis mechanism. Herein, a stereoselective ZROP of rac-lactide (rac-LA) was explored for synthesis of isotactic cyclic polylactides by using commercially available N-heterocyclic carbene (NHC) catalysts at low temperature in tetrahydrofuran. The epimerization of lactide during ZROP can be inhibited at low temperature. The best isoselectivity can reach to a high value of Pm = 0.91 associated with a high melting point (Tm) of 193 °C. The resulting polylactides exhibit narrow molecular weight distributions (Mw/Mn < 1.2) and inhibited transesterification as evidenced by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The resulting polylactide is predominantly cyclic as evidenced by 1H NMR and MALDI-TOF MS analyses.

Zwitterionic Ring-Opening Polymerization of N-Substituted Eight-Membered Cyclic Carbonates to Generate Cyclic Poly(carbonate)s.

The zwitterionic ring-opening polymerization of N-functionalized eight-membered cyclic carbonates with N-heterocyclic carbenes (NHC) in the absence of alcohol initiators generates cyclic polycarbonates of Mn ∼ 30-100 kDa. The polymerization behavior of these eight-membered cyclic azacarbonates depends sensitively on the nature of the nitrogen substituent. The N-benzyl-substituted eight-membered cyclic carbonate (8CCBn) polymerizes readily with 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene to generate cyclic polycarbonates with molecular weights of Mn = 14 000 to 96 000 Da. In contrast, the N-phenyl-substituted cyclic carbonate (8CCPh) catalytically dimerizes in the presence of the NHC to afford the crystalline cyclic dimer. The zwitterionic ring-opening copolymerization of δ-valerolactone (VL) and the cyclic carbonates afford gradient cyclic copolymers. The cyclic topology of both the homopolymers and copolymers was supported by MALDI-TOF MS and intrinsic viscosity measurements. 13C NMR and differential scanning calorimetry of the cyclic copolymers are indicative of a gradient sequence distribution as a consequence of the more rapid enchainment of the cyclic carbonates relative to valerolactone.

Amidine-Mediated Zwitterionic Ring-Opening Polymerization of N-Alkyl N-Carboxyanhydride: Mechanism, Kinetics, and Architecture Elucidation

Zwitterionic ring-opening polymerization (ZROP) of N-butyl N-carboxyanhydrides (Bu-NCAs) has been investigated using 1,8-diazabicycloundec-7-ene (DBU), a bicyclic amidine initiator. It was found that poly(N-butylglycine)s (PNBGs) with molecular weight (Mn) in the 3.5–32.4 kg mol–1 range and polydispersity index (PDI) in the 1.02–1.12 range can be readily obtained by systematically varying the initial monomer to initiator feed ratio. The polymerization exhibits characteristics of a controlled polymerization, as evidenced by the linear increase of polymer molecular weight with conversion and the successful enchainment experiments. Kinetic studies revealed that the reaction is first-order dependent on the monomer and the DBU concentration. The rate of initiation is comparable to that of the propagation. Random copolypeptoids of poly[(N-propargylglycine)-r-(N-butylglycine)]s [P(NPgG-r-NBG)s] were also synthesized by DBU-mediated copolymerization of Bu-NCA and N-propargyl N-carboxyanhydride (Pg-NCA). Subsequen...

Merging of Zwitterionic ROP and Photoactivated Thiol–Yne Coupling for the Synthesis of Polyether Single-Chain Nanoparticles

Preparation of polyether single-chain nanoparticles (SCNPs) has remained as an elusive issue in spite of the significant interest in the synthesis of polyether derivatives with complex architectures (i.e., star-shaped, cyclic, multicyclic, and supramolecular structures). In this work, we report the facile access to polyether SCNPs by combining zwitterionic ring-opening polymerization (ZROP) and thiol–yne coupling (TYC) techniques. Linear copolymers of tetrahydrofuran (THF) and glycidyl propargyl ether (GPgE), P(GPgE-co-THF), and terpolymers of THF, GPgE, and glycidyl phenyl ether (GPE), P(THF-GPgE-GPE), having naked alkyne functional groups (10–21 mol %) were synthesized through ZROP at high content of THF in the feed. Only P(THF-GPgE-GPE) terpolymers were found to give polyether SCNPs upon photoactivated TYC reaction by working at appropriate dilution conditions (0.5 mg/mL) and using 3,6-dioxa-1,8-octane-dithiol as homobifunctional cross-linker. The different monomer sequence distribution in the copolymers when compared to that in the terpolymers was the responsible for this behavior, as revealed by in situ polymerization 13C nuclear magnetic resonance measurements. A significant reduction in intrinsic viscosity was observed upon SCNP formation. Analysis of hydrodynamic data from size exclusion chromatography with triple detection in terms of Mark–Houwink–Sakurada plots revealed that the degree of compaction increases upon increasing the alkyne content in the SCNP precursor. Polyether SCNPs were found to be noncrystalline rubbery materials at room temperature.

Zwitterionic ring-opening polymerization for the facile, efficient and versatile grafting of functional polyethers onto graphene sheets

Zwitterionic ring-opening polymerization is used as a strategy to covalently anchor polyethers of different chemical nature and polarity onto thermally reduced graphene oxide (rGO) sheets. This versatile strategy involves the generation of a macrozwitterionic propagating species by reaction of a functional epoxide monomer with a Lewis acid catalyst, B(C6F5)3. Upon addition of rGO sheets, the polyether propagating species react with available nucleophilic groups on the rGO surface to generate graphene sheets decorated with functional polyether chains in amounts as large as 30wt%. Polyethers obtained from glycidyl monomers carrying hydroxyl, hexadecyl and fluorinated groups, as well as a copolyether of tetrahydrofuran and glycidyl phenyl ether, were successfully grafted to rGO sheets. Surprisingly, grafting was found to increase the degree of hydrophilicity of the rGO sheets, irrespective of the hydrophobic or hydrophilic character of the side groups attached to the main polyether chain, as determined from contact angle measurements in both macroscopic and microscopic experiments. Properties such as the degree of crystallization of poly(tetrahydrofuran) grafted onto rGO sheets and the transparency of polymer films containing polyether-grafted rGO sheets were also evaluated in this study.

Ion pairing effects in the zwitterionic ring opening polymerization of δ-valerolactone

The effect of LiCl additive on the N-heterocyclic carbene mediated zwitterionic ring-opening polymerization of δ-valerolactone was investigated.

Synthesis and Topological Trapping of Cyclic Poly(alkylene phosphates)

The zwitterionic ring-opening polymerization of 2-isopropoxy-2-oxo-1,3,2-dioxaphospholane (iPP) with N-heterocyclic carbenes (NHC) generates poly(alkylene phosphate)s with molecular weights of Mn = 55000–202000 Da. MALDI-TOF mass spectrometry provided clear evidence for cyclic poly(alkylene phosphate)s (poly(iPP)) for lower molecular weight fractions (m/z ≤ 3000). The cyclic topology of the higher molecular weight fractions was inferred by trapping of poly(iPP) in cross-linked 2-hydroxyethyl methacrylate (HEMA) hydrogels. Cross-linked HEMA hydrogels were generated in the presence of a high molecular weight (Mn = 202000 Da) poly(iPP) generated from the zwitterionic ring-opening polymerization of iPP with the NHC 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene 2. Extraction of the resulting gel with methanol for 11 days revealed that 36% of the poly(iPP) was retained in the gel, whereas a linear poly(iPP) was completely extracted under similar conditions. The retention of the poly(iPP)s in the gels is attrib...

Zwitterionic Ring-Opening Polymerization: Models for Kinetics of Cyclic Poly(caprolactone) Synthesis

Investigations of the kinetics of zwitterionic ring-opening polymerization of e-caprolactone by N-heterocyclic carbenes (NHC) were carried out to illuminate the key reaction steps responsible for the formation of high molecular weight cyclic poly(caprolactones). Modeling of both the decay in monomer concentration as well as the evolution of molecular weights and polydispersities were necessary to identify the key reaction steps responsible for initiation, propagation, cyclization and chain-transfer. Nucleophilic attack of the NHC on e-caprolactone to generate reactive zwitterions is slow and reversible. The modeling indicates that less than 60% of the carbenes are transformed to active zwitterions, but that these zwitterions rapidly add monomer and cyclize by intramolecular backbiting of the terminal alkoxides on internal esters of the zwitterions. This cyclization event maintains the concentration of active zwitterions. The reactivation of cyclized chains by active zwitterions is a key step that leads to...

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

Experimental and computational investigations of the zwitterionic ring-opening polymerization (ZROP) of δ-valerolactone (VL) catalyzed by the N-heterocyclic carbenes (NHC) 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (1) and 1,3,4,5-tetramethyl-imidazol-2-ylidene (2) were carried out. The ZROP of δ-valerolactone generates cyclic poly(valerolactone)s whose molecular weights are higher than predicted from [VL]0/[NHC]0. Kinetic studies reveal the rate of polymerization is first order in [VL] and first order in [NHC]. Density functional theory (DFT) calculations were carried out to elucidate the key steps involved in the ring-opening of δ-valerolactone and its subsequent oligomerization. These studies have established that the initial steps of the mechanism involve nucleophilic attack of the NHC on δ-valerolactone to form a zwitterionic tetrahedral intermediate. DFT calculations indicate that the highest activation barrier of the entire mechanism is associated with the ring-opening of the tetrahedral intermediate formed from the NHC and δ-valerolactone, a result consistent with inefficient initiation to generate reactive zwitterions. The large barrier in this step is due to the fact that ring-opening requires a partial positive charge to develop next to the directly attached NHC moiety which already bears a delocalized positive charge.

Synthesis and new application of green and recyclable cyclic poly(L -lactide)-clay hybrid

We report on the application of biodegradable cyclic poly(L-lactide) (PLLA) as new stabilizer; synthesis and application of a cyclic PLLA-clay hybrid material as recyclable catalyst support. Cyclic PLLAs were used to stabilize palladium nanoparticles synthesized by a wet chemical method. It was found that the palladium particles were smaller with cyclic PLLA stabilizer (∼5–10 nm) than the particles obtained from linear PLLA. The cyclic PLLA-clay hybrid was prepared by a zwitterionic ring-opening polymerization catalyzed by in situ-generated N-heterocyclic carbene catalyst. Palladium (0) nanoparticles were supported and well dispersed on the cyclic PLLA-clay hybrid to form a new nanocomposite. The nanocomposite was found to be a highly efficient and recyclable catalyst for the aminocarbonylation reactions of aryl halides with various amines. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4167–4174

Zwitterionic Ring-Opening Polymerization for the Synthesis of High Molecular Weight Cyclic Polymers

Cyclic polymers are an intriguing class of macromolecules. Because of the constraints of the cyclic topology and the absence of chain ends, the properties of these molecules differ from those of linear polymers in ways that remain poorly understood. Cyclic polymers present formidable synthetic challenges because the entropic penalty of coupling the chain ends grows exponentially with increasing molecular weight. In this Account, we describe recent progress in the application of zwitterionic ring-opening polymerization (ZROP) as a strategy for the synthesis of high molecular weight, cyclic polymers. Zwitterionic ring-opening polymerization involves the addition of neutral organic nucleophiles to strained heterocyclic monomers; under appropriate conditions, cyclization of the resultant macrozwitterions generates cyclic macromolecules. We discuss the mechanistic and kinetic features of these zwitterionic ring-opening reactions and the conditions that influence the efficiency of the initiation, propagation, and cyclization to generate high molecular weight cyclic polymers. N-Heterocyclic carbenes (NHC) are potent nucleophiles and relatively poor leaving groups, two features that are important for the generation of high molecular weight polymers. Investigations of the nature of the monomer and nucleophile have helped researchers understand the factors that govern the reactivity of these systems and their impact on the molecular weight and molecular weight distributions of the resulting cyclic polymers. We focus primarily on ZROP mediated by N-heterocyclic carbene nucleophiles but also discuss zwitterionic polymerizations with amidine, pyridine, and imidazole nucleophiles. The ZROP of N-carboxyanhydrides with N-hetereocyclic carbenes generates a family of functionalized cyclic polypeptoids. We can synthesize gradient lactone copolymers by exploiting differences in relative reactivity present in ZROP that differ from those of traditional metal-mediated polymerizations. These new synthetic methods have allowed us to investigate the influence of topology on the crystallization behavior, stereocomplexation, and solution properties of cyclic macromolecules.

Syntheses of cyclic poly(lactones) by zwitterionic ring opening polymerization catalyzed by N‐heterocyclic carbene

AbstractSynthesis of cyclic biopolymers from renewable monomers remains a big challenge because of lack of efficient catalysts. The organocatalyst of N‐heterocyclic carbene (NHC), (+)‐1‐methyl‐3‐menthoxymethyl imidazol‐2‐ylidene, is used to prepare cyclic polylactones including poly(ε‐caprolactone) (poly(ε‐CL)), poly(δ‐valearolactone) (poly(δ‐VL)), and poly(ε‐caprolactone‐co‐δ‐valearolactone) (poly(ε‐CL‐co‐δ‐VL)) via zwitterionic ring opening polymerization. The NHC catalyst is founded a highly efficient organic catalyst for the polymerization. The resulting cyclic polymers show a melting temperature (Tm) in a range of 20–60°C, which is dramatically lower than the Tm of cyclic poly(lactide) (Tm = 120–150°C). The resulting copolymer, cyclic poly(ε‐CL‐co‐δ‐VL) owns high molecular weight comparing with corresponding linear poly(ε‐CL‐co‐δ‐VL) produced by other catalysts. The synthesized cyclic homo and copolymers were characterized by 1H‐, 13C‐NMR spectroscopy, gel permeation chromatography, differential scanning calorimetry–thermogravimetric analysis and matrix‐assisted laser desorption ionization‐time of flight mass spectrometry. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Synthesis and Characterization of Cyclic Brush-Like Polymers by N-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Propargyl N-Carboxyanhydride and the Grafting-to Approach

Cyclic brush-like polymers were synthesized by tandem organo-mediated zwitterionic polymerization and a grafting-to approach. The cyclic polymer backbone, consisting of poly(N-propargylglycine) (c-PNPG), was synthesized by an N-heterocyclic carbene (NHC)-mediated zwitterionic ring-opening polymerization of N-propargyl N-carboxyanhydride. The polymerization proceeds in a quasi-living manner, allowing access to c-PNPG of well-defined chain length. The cyclic architecture of the polymers was verified by size exclusion chromatography (SEC) and mass spectroscopy (MS), as well as scanning probe characterization. Poly(ethylene glycol) functionalized with azido end-groups was subsequently grafted onto the c-PNPG by the copper-mediated azide/alkyne cycloaddition reaction (CuAAC). The side chain grafting density was determined by 1H NMR spectroscopy and SEC analysis. The grafting efficiency is low (<19%) when the cyclic backbone is comprised of a c-PNPG homopolymer. The efficiency can be significantly improved (up ...

Zwitterionic ring opening polymerization of lactide by metal free catalysts: Production of cyclic polymers

AbstractTailor made N‐heterocyclic carbene (NHC) catalyst precursors namely (+) and (−) 1‐methyl‐3‐menthoxymethyl imidazolium chloride have been synthesized in high yield with a literature modified procedure. A reaction of catalyst precursor with potassium tert butoxide in situ generates the NHC catalyst. The zwitterionic ring opening polymerization of lactide (LA) mediated by a catalytic system composed of NHC catalyst at 25°C under argon atmosphere led to a cyclic poly(lactide) of a high molecular weight with a narrow molecular weight distribution. The cyclic poly(lactide) was characterized by NMR spectroscopy, Gel Permeation Chromatography (GPC) and Matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF MS). The NHC catalysts are active for lactide polymerization in the presence of air and elevated temperatures at 55°C. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Top-Down Multidimensional Mass Spectrometry Methods for Synthetic Polymer Analysis

The ability of multidimensional mass spectrometry (MS) approaches, interfacing different ionization methods with tandem mass spectrometry (MS2) fragmentation and ion mobility (IM) separation, to characterize synthetic polymers is demonstrated for poly(α-peptoid)s synthesized by N-heterocyclic carbene (NHC)-mediated zwitterionic ring-opening polymerization. Matrix-assisted laser desorption ionization (MALDI) causes elimination of the NHC initiator, if performed in the presence of cationizing salts. Electrospray ionization (ESI) is softer, allowing for the detection of the intact sample. It also shows that in proper solvents self-assembly of the poly(α-peptoid) occurs to form supramacromolecules; since these noncovalent self-assemblies overlap with the main product, separation by IM MS is essential for their conclusive identification. MS2 confirms the connectivity of the poly(α-peptoid)s, whereas MS2 combined with IM separation renders valuable insight into the binding interactions in the supramolecular assemblies and on the structures and conformations of the poly(α-peptoid) resulting after NHC elimination. Performing all analyses inside the mass spectrometer (“top-down”) enables fast, sensitive, and cost-effective analysis of polymer composition, structure, and architecture without prior derivatization, separation, or degradation.

Zwitterionic Polymerization: A Kinetic Strategy for the Controlled Synthesis of Cyclic Polylactide

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between M(n) = 5000 and 30,000 g/mol with narrow polydispersities (M(w)/M(n) < or = 1.31). These zwitterionic polymerizations are extremely rapid (k(p) = 48.7 M(-1) s(-1)), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order in [M]), a propagation step (first order in [M]) that is much faster than initiation (k(i) = 0.274 M(-2) s(-1)), cyclization (k(c) = 0.0575 s(-1)), and depropagation (k(d) = 0.208 s(-1)). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters.

N-Heterocyclic Carbene-Induced Zwitterionic Ring-Opening Polymerization of Ethylene Oxide and Direct Synthesis of α,ω-Difunctionalized Poly(ethylene oxide)s and Poly(ethylene oxide)-b-poly(ε-caprolactone) Block Copolymers

An N-heterocyclic carbene (NHC), namely, 1,3-bis-(diisopropyl)imidazol-2-ylidene (1), was demonstrated to bring about the metal-free ring-opening polymerization of ethylene oxide at 50 degrees C in dimethyl sulfoxide, in absence of any other reagents. Poly(ethylene oxide) (PEO) of polydispersities <1.2 and molar masses perfectly matching the [monomer]/[(1)] ratio could thus be obtained in quantitative yields, attesting to the controlled/living character of such carbene-initiated polymerizations. It is argued that (1) adds to ethylene oxide to form a zwitterionic species, namely 1,3-bis-(diisopropyl)imidazol-2-ylidinium alkoxide, that further propagates by a zwitterionic ring-opening polymerization (ZROP) mechanism. Through an appropriate choice of terminating agent NuH or NuSiMe(3) at the completion of the polymerization, a variety of end-functionalized PEO chains could be generated. In particular, alpha,omega-bis(hydroxy)-telechelic PEO, alpha-benzyl,omega-hydroxy, and alpha-azido,omega-hydroxy-difunctionalized PEOs were synthesized by NHC (1)-initiated ZROP, using H(2)O, PhCH(2)OH, and N(3)SiMe(3) as terminating agent, respectively. Characterization of these alpha,omega-difunctionalized PEOs by techniques such as (1)H NMR spectroscopy, MALDI-TOF spectrometry, and size exclusion chromatography confirmed the quantitative introduction of functional groups at both alpha and omega positions of the PEO chains and the formation of very narrow molar mass polymers. Finally, the synthesis of a poly(ethylene oxide)-b-poly(epsilon-caprolactone) diblock copolymer by sequential ZROP of the corresponding monomers was successfully achieved using (1) as organic initiator without isolation of the PEO block intermediate.