Metal-free Ring-opening Polymerization Research Articles

Metal-Free Ring-Opening Polymerization of Propylene Oxide: Synthesis and Characterization of Polyether in the Undergraduate Organic Chemistry Laboratory

Metal-Free Ring-Opening Polymerization of Propylene Oxide: Synthesis and Characterization of Polyether in the Undergraduate Organic Chemistry Laboratory

Access to Functionalized Materials by Metal-Free Ring-Opening Metathesis Polymerization of Active Esters and Divergent Postpolymerization Modification.

Metal-free ring-opening metathesis polymerization (MF-ROMP) is an emerging polymerization strategy that provides access to ROMP materials by using organic initiators and photoredox catalysts. Unlike metal-mediated ROMP, MF-ROMP is not highly tolerant toward functionalized monomers. Herein, we report that pentafluorophenyl esters are polymerizable under MF-ROMP conditions to produce homopolymers, statistical copolymers, and block copolymers. Amine coupling agents were then used to install a range of functional groups via acyl substitution including alkynes, amino acid derivatives, fluorophores, and redox active moieties. Overall, these findings provide a framework to prepare functionalized ROMP polymers without the risk of metal contamination.

Flow Optimization of Photoredox-Mediated Metal-Free Ring-Opening Metathesis Polymerization.

Photoredox-mediated metal-free ring-opening metathesis polymerization (MF-ROMP) is a convenient metal-free method to produce a variety of ROMP polymers. Transitioning MF-ROMP from a batch to a continuous flow process has yet to be demonstrated and could potentially benefit the production efficiency, safety, and modularity of reaction conditions. We designed and evaluated continuous flow and droplet flow setups and compared the results for MF-ROMP across a short series of common monomers. By using the droplet flow reactor setup, we achieved flow conversions comparable to that of batch and circumvented issues with diffusion-limited mixing and air exposure.

Highly tunable metal-free ring opening polymerization of glycidol into various controlled topologies catalyzed by frustrated lewis pairs

In this work, we investigated the metal-free frustrated Lewis pair (FLP) catalyzed ring-opening polymerization of glycidol. It was observed that the type of Lewis bases influences on the polymer topologies and unique physical properties.

Precise synthesis of α,ω-chain-end functionalized poly(dimethylsiloxane) with azide groups based on metal-free ring-opening polymerization and a quantitative azidation reaction

We have so far developed a method for the controlled ring-opening polymerization of cyclotrisiloxane catalyzed by strong organobasic compounds to produce various chain-end functionalized polysiloxanes with controlled number-average molar mass (Mn) and narrow molar-mass dispersity (ÐM) values. In this study, well-defined α,ω-chain-end functionalized poly(dimethylsiloxane) with azide groups (N3-PDMS-N3) possessing a narrow ÐM range (ÐM = 1.04) and a relatively high Mn of up to 28.2 kg mol−1 was precisely synthesized in a mixed solvent of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF) in the presence of quaternary ammonium salts as catalysts; N3-PDMS-N3 was obtained by converting α,ω-chain-end functionalized PDMS with bromomethyl groups (Br-PDMS-Br), which was prepared by polymerizing hexamethylcyclotrisiloxane (D3), water, and 1,3-trimethylene-2-n-propylguanidine (TMnPG) as the monomer, the initiator, and the catalyst, respectively. It was necessary to choose proper solvents depending on the Mn of Br-PDMS-Br to achieve the complete conversion of the bromomethyl groups by the azidation reaction. Moreover, we demonstrate the model reaction of copper-catalyzed 1,3-dipolar cycloaddition between N3-PDMS-N3 and phenylacetylene. As a result, the cycloadducted compound was exclusively obtained while maintaining a low ÐM value of 1.06 by employing copper(I) bromide and triethylamine as the catalyst and the ligand, respectively. This system was also effective for a polymer-polymer coupling reaction. Indeed, we successfully synthesized an ABA-type triblock copolymer where A and B are polystyrene (PS) and PDMS segments by reacting N3-PDMS-N3 with ω-chain-end functionalized PS with an alkynyl group.

Morphogenic effect of common solvent in the self-assembly behavior of amphiphilic PEO-b-PLA

The formation of block copolymer nanoparticles is commonly obtained by switching solvent quality from good solvent for both blocks to a selective solvent for one block. The effect of the selective solvent on particle dimension, shape and inner structure has been analyzed in detail, instead less attention has been focused on the role of the common solvent. Poly(ethylene oxide)-block-poly(lactic acid) (PEO-b-PLA) is widely used for the preparation of nanometric drug delivery systems and the control of the particle morphology has relevant effects on bioactivity. In this work we investigate the effect of using different common solvents (acetone, dioxane, tetrahydrofuran, dimethylformamide) on the self-assembly behavior of narrowly dispersed PEO-b-PLA copolymers, synthesized by metal free ring-opening polymerization, with large variation of molecular weight of the hydrophobic block (from 65 to 1300 lactic units). Dynamic light scattering (DLS) and cryo-electron microscopy (cryo-EM) analyses of PEO-b-PLA nanoparticles reveal that their size and shape are strongly dependent on the hydrogen bonding ability of the common solvent used in the self-assembly process. As consequence of these variations, also the cytoxicity of the nanoparticles is affected.

A highly efficient metal-free protocol for the synthesis of linear polydicyclopentadiene

We have developed a highly efficient synthesis of linear polydicyclopentadiene (pDCPD) via photoredox mediated metal-free ring-opening metathesis polymerization (MF-ROMP) and investigated the Tg–Mn dependence of linear pDCPD.

Visible light-regulated organocatalytic ring-opening polymerization of lactones by harnessing excited state acidity

A metal-free ring-opening polymerization of lactones has been developed using PyOH as a photocatalyst under visible light mediation.

Block Copolymers of Poly(ε-caprolactone) with pH-Responsive Side-Chain Amino Acid Moieties

To prepare amphiphilic block copolymers consisting of biocompatible and biodegradable segments, herein we report synthesis of diblock copolymers having e-caprolactone (e-CL) repeating units in one block and amino acid-based acrylate monomers in another segment. The block copolymers were prepared by a combination of metal-free ring-opening polymerization (ROP) of e-CL and reversible addition-fragmentation chain transfer (RAFT) polymerization of tert-butyloxycarbonyl (Boc)-alanine/Boc-leucine based acrylate monomers. The ROP of e-CL was initiated with diphenyl phosphate (DPP) as a metal-free catalyst in conjunction with a heterofunctional initiator, benzyl-2-hydroxyethyl carbonotrithioate, produced trithiocarbonate terminated poly(e-caprolactone) (PCL). This was further employed as macro-chain transfer agent for the synthesis of side chain amino acid containing block via RAFT. Deprotection of Boc group pendants from the block copolymers under acidic conditions at room temperature provided pH responsive block copolymers with positively charged cationic primary amine functionalities. Furthermore, self-assembling nature of these block copolymers in aqueous medium was examined through dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM).

Biodegradable pH-responsive micelles loaded with 8-hydroxyquinoline glycoconjugates for Warburg effect based tumor targeting

Biodegradable triblock copolymer poly(ethylene glycol)-b-polycarbonate-b-oligo([R]-3-hydroxybutyrate) was prepared via metal-free ring-opening polymerization of ketal protected six-membered cyclic carbonate followed by esterification with bacterial oligo([R]-3-hydroxybutyrate) (oPHB). Amphiphilic triblock copolymer self-organizes into micelles with a diameter of ~25 nm. Acid-triggered hydrolysis of ketal groups to two hydroxyl groups causes an increase in hydrophilicity of the hydrophobic micelle core, resulting in the micelles swell and drug release. oPHB was added as core-forming block to increase the stability of prepared micelles in all pH (7.4, 6.4, 5.5) studied. Doxorubicin and 8-hydroxyquinoline glucose- and galactose conjugates were loaded in the micelles. In vitro drug release profiles in PBS buffers with different pH showed that a small amount of loaded drug was released in PBS at pH 7.4, while the drug was released much faster at pH 5.5. MTT assay showed that the blank micelles were non-toxic to different cell lines, while glycoconjugates-loaded micelles, showed significantly increased ability to inhibit the proliferation of MCF-7 and HCT-116 cells compared to free glycoconjugates. The glycoconjugation of anti-cancer drugs and pH-responsive nanocarriers have separately shown great potential to increase the tumor-targeted drug delivery efficiency. The combination of drug glycoconjugation and the use of pH-responsive nanocarrier opens up new possibilities to develop novel strategies for efficient tumor therapy.

N-Heterocyclic carbene/Lewis acid-mediated ring-opening polymerization of propylene oxide. Part 2: Toward dihydroxytelechelic polyethers using triethylborane

Propylene oxide (PO) is polymerized by metal-free ring-opening polymerization (ROP) at 25 °C using N-heterocyclic carbenes (NHCs) and triethylborane (Et3B) as a bicomponent catalytic system. Poly(propylene oxide)s with predictable molar mass up to 60 000 g·mol−1 and low dispersity (Ð < 1.10) were obtained without the occurrence of undesirable transfer reaction to the monomer. In presence of an alcohol as the initiator, the ROP of PO follows an anionic mechanism assisted by monomer activation improving the efficiency of NHCs for the polymerization of substituted epoxides. Et3B is involved both in the formation of a complexed active center and in the activation of PO. Interestingly, dihydroxytelechelic PPOs can be readily synthesized not only using 1,4-benzenedimethanol but also water, both serving as difunctional initiators. Block copolyethers are also prepared by PPO chain extension experiments. All (co)polyethers have been thoroughly characterized by 1H NMR spectroscopy, SEC and MALDI-TOF mass spectrometry as means to elucidate the reaction mechanisms involved in this chemistry.

Linear- and star-brush poly(ethylene glycol)s: Synthesis and architecture-dependent crystallization behavior

Linear-brush and star-brush poly(ethylene glycol)s (PEGs) with tunable branching degree and side chain length were successfully obtained via metal-free ring-opening polymerization of ethylene oxide using hydroxylated polybutadiene (HPB) as a macroinitiator and t-BuP4 as a catalyst. The branching degree and side chain length of brush PEGs can be tailored simply by controlling the number of hydroxyl groups ([OH]) on backbone and the feed ratio of ethylene oxide/[OH], respectively. The effects of molecular weight and macromolecular architecture on crystallization behavior were systematically investigated through crystallization kinetics and morphologies. In all cases, the thermal parameters, including Tc, ΔHc, and ΔHm, increase with increasing molecular weight of side chains, while decrease with an increasing the branching degree, suggesting an increased or reduced crystallinity. According to the Avrami equation, the rate constant K decreases while the n values increase with branching degree increasing. POM observations suggested that the spherulites growth rate G decreases with branching degree increasing under the same supercooling. Nonetheless, with increasing the side chain length, the spherulites growth rate G decreases for linear and star PEGs while increases instead for brush PEGs, suggesting that the crystal growth rate of PEGs is influenced by topological structure and supercooling simultaneously. Consequently, with increasing the side chain length, Kg and σe increase for linear and star PEGs, while Kg and σe decrease for brush structures. Both Kg and σe increase regardless of macromolecular architecture with an increasing branching degree. Based on Hoffman-Lauritzen analysis, the transition of regime II to regime III for brushed PEG (ΔT = 15 K) require larger supercooling than linear and star PEGs (ΔT = 10 K).

Integration of metal-free ring-opening metathesis polymerization and organocatalyzed ring-opening polymerization through a bifunctional initiator

We demonstrate the first integration of metal-free ROMP and organocatalyzed ROP to provide entirely metal-free syntheses of block copolymers.

Fast, selective and metal-free ring-opening polymerization to synthesize polycarbonate/polyester copolymers with high incorporation of ethylene carbonate using an organocatalytic phosphazene base

Polycarbonate/polyester copolymers with high incorporation of EC were realized by a fast and selective process using a metal-free catalyst.

Nanoparticles Based on Poly(trimethylene carbonate) Triblock Copolymers with Post-Crystallization Ability and Their Degradation in vitro

Aliphatic polycarbonate-based block copolymers have received considerable attention as carriers for targeted drug and gene delivery because of their biocompatibility and biodegradability. However, there is little understanding of their phase behaviour and physicochemical characterization of the particles made from them. Here, we prepared a series of well-defined poly(trimethylene carbonate) (PTMC)-based copolymers with molar masses of 3–9 kg·mol-1 by metal-free ring-opening polymerization using dihydroxy-terminated poly(ethylene oxide) as a macroinitiator. Micellar nanoparticles self-assembled from copolymers had a size of less than 130 nm. They were degraded by the action of a model lipase from Mucor Miehei at 37 °C, which is of high importance for biodegradability in the living organism. X-ray diffraction and differential scanning calorimetry proved that amorphous copolymers with more than 39 mol% of carbonate units and representative particles were prone to the rearrangement of PTMC chains during storage and to thus undergo post-crystallization. Our findings can contribute to the comprehensive characterization of polycarbonate biomaterials for medical applications.

Synthesis of polyesters by an efficient heterogeneous phosphazene (P1)-Porous Polymeric Aromatic Framework catalyzed-Ring Opening Polymerization of lactones

A novel phosphazene superbase (P1) organocatalyst heterogenized on a Porous Polymeric Aromatic Framework (PPAF) based on an adamantine node catalyzed metal-free ring-opening polymerization (ROP) of lactones to yield polyesters, showing a 7.7-fold increase in the turnover number for δ-valerolactone (δ-VL) and 3.3-fold increase in the case of ε-caprolactone (ε-CL) as comparing with its soluble counterpart. The heterogeneous catalyst can be reused until four times without loss of activity.

Investigation of Tacticity and Living Characteristics of Photoredox-Mediated Metal-Free Ring-Opening Metathesis Polymerization.

This study investigated the microstructures of polymers produced via photoredox-mediated metal-free ring-opening metathesis polymerization. Polynorbornene, poly(exo-dihydrodicyclopentadiene), and poly(endo-dicyclopentadiene) were found to have cis olefin contents of 23%, 24%, and 28%, respectively. Additionally, the cis/trans ratio remained consistent during the course of norbornene polymerization. Polymer tacticity was evaluated by quantitative 13 C NMR spectroscopy, which revealed each polymer to be largely atactic. Specifically, the three polymers were estimated to be 33%, 58%, and 55% syndiotactic, respectively. In parallel, this study also explored the ability to produce diblock copolymers from norbornene and exo-dihydrodicyclopentadiene. Successful diblock copolymerization was achieved using either monomer order. In each case, however, the results suggested to us that chain-chain coupling (increased molecular weight) and irreversible termination (dead chains observed during attempted chain extension) occurred when reaction times were extended.

Expanded Functionality of Polymers Prepared Using Metal-Free Ring-Opening Metathesis Polymerization

Photoredox-mediated metal-free ring-opening metathesis polymerization (MF-ROMP) is an alternative to traditional metal-mediated ROMP that avoids the use of transition metal initiators while also enabling temporal control over the polymerization. Herein, we explore the effect of various additives on the success of the polymerization in order to optimize reaction protocols and identify new functionalized monomers that can be utilized in MF-ROMP. The use of protected alcohol monomers allows for homo- and copolymers to be prepared that contain functionality beyond simple alkyl groups. Several other functional groups are also tolerated to varying degrees and offer insight into future directions for expansion of monomer scope.

Phosphazene-Promoted Metal-Free Ring-Opening Polymerization of 1,2-Epoxybutane Initiated by Secondary Amides

The in situ generation of an anionic initiator X– obtained by the deprotonation of various secondary amides with tBuP4 phosphazene base was tested as possible way to initiate the polymerization of 1,2-epoxybutane. The initiation efficiency of different amide-containing molecules was investigated. Particular attention was given to the detection of eventual transfer or side reactions, especially due to nucleophilic attacks on the initiator moiety at the α-chain end. In all cases, the initiation of the polymerization by the amidate anion was effective. And in most cases, the polymerization proceeded in a controlled manner to afford amide end-capped poly(butylene oxide) with narrow molar mass distribution and expected molar masses.

Metal-Free Preparation of Linear and Cross-Linked Polydicyclopentadiene

Metal-free ring-opening metathesis polymerization (ROMP) utilizes organic photoredox mediators as alternatives to traditional metal-based ROMP initiators to allow the preparation of polymers without residual metal contamination. Herein we report studies exploring the use of endo-dicyclopentadiene (DCPD), a common ROMP monomer, to form linear polyDCPD and copolymers with norbornene. Subsequent cross-linking of the linear polyDCPD using thiol-ene chemistry allows for a completely metal-free preparation of cross-linked polyDCPD. Furthermore, the examination of a number of structurally related monomers offers insights into mechanistic details of this polymerization and demonstrates new monomers that can be utilized for metal-free ROMP.