Ring-opening Metathesis Polymerization Research Articles

Ring Opening Metathesis Polymerization of Cyclooctadiene and Cyclooctene with Dihydrofuran: Influence of Ru Fischer Carbene.

Vinyl ethers are commonly used to deactivate Grubbs catalysts and terminate ring opening metathesis polymerization (ROMP) by forming Fischer carbene species with attenuated metathesis reactivity. However, we recently demonstrated that a cyclic enol ether, 2,3-dihydrofuran (DHF), can in fact be homopolymerized or copolymerized with norbornene derivatives. 1,5-Cyclooctadiene (COD) and cyclooctene (COE) consist of an important class of ROMP monomers, and we describe here a study of their copolymerization with DHF. Addition of DHF greatly suppressed the ROMP activity of COD and COE and resulted in significant alkene isomerization of COD. Chloranil was found to be an effective additive to prevent undesired isomerization and promote copolymerization. As a result, high molecular weight COD/COE and DHF copolymers were synthesized. Hydrolysis of the enol ether main chain linkages yields polyalkenamers with alcohol and aldehyde end groups. This study encourages further exploration of the in situ formed Ru Fischer carbene species in ROMP to access degradable polymers.

Synthesis and Characterization of Dearomatized Pyridine‐Derived Alkyl‐Amido‐tert‐Butylphosphine Iron(II) Complexes

AbstractNeutral three‐coordinate iron alkylidenes of the form PN−Fe=CHR have been proposed as viable candidates for alkene metathesis. Indeed, during the final stages of preparing this current study, a separate report disclosed that dearomatized PN−Fe‐alkyl complexes are active precatalysts for ring‐opening metathesis polymerization (ROMP) of norbornene implicating PN−Fe=CHR species as possible intermediates. In yet another separate report, we prepared Zn analogues of PN−Fe‐alkyl complexes and herein provide an account for the synthesis, characterization, and reactivity of some new iron complexes with the same tBu substituted PN platform.

Facile Utilization of Renewable Resources Containing Cyclobutene Mechanophores: Preparation and Properties of High-Toughness Materials with One-Step Cross-Linking by Frontal Ring-Opening Metathesis Polymerization

Facile Utilization of Renewable Resources Containing Cyclobutene Mechanophores: Preparation and Properties of High-Toughness Materials with One-Step Cross-Linking by Frontal Ring-Opening Metathesis Polymerization

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.

Dithiophosphoric Acids for Polymer Functionalization.

Dithiophosphoric acids (DTPAs) are an intriguing class of compounds that are sourced from elemental sulfur and white phosphorus and are prepared from the reaction of phosphorus pentasulfide with alcohols. The electrophilic addition of DTPAs to alkenes and unsaturated olefinic substrates is a known reaction, but has not been applied to polymer synthesis and polymer functionalization. We report on the synthesis and application of DTPAs for the functionalization of challenging poly-enes, namely polyisoprene (PI) and polynorbornene (pNB) prepared by ring-opening metathesis polymerization (ROMP). The high heteroatom content within DTPA moieties impart intriguing bulk properties to poly-ene materials after direct electrophilic addition reactions to the polymer backbone introducing DTPAs as side chain groups. The resulting materials possess both enhanced optical and flame retardant properties vs the poly-ene starting materials. Finally, we demonstrate the ability to prepare crosslinked polydiene films with di-functional DTPAs, where the crosslinking density and thermomechanical properties can be directly tuned by DTPA feed ratios.

Dithiophosphoric Acids for Polymer Functionalization

AbstractDithiophosphoric acids (DTPAs) are an intriguing class of compounds that are sourced from elemental sulfur and white phosphorus and are prepared from the reaction of phosphorus pentasulfide with alcohols. The electrophilic addition of DTPAs to alkenes and unsaturated olefinic substrates is a known reaction, but has not been applied to polymer synthesis and polymer functionalization. We report on the synthesis and application of DTPAs for the functionalization of challenging poly‐enes, namely polyisoprene (PI) and polynorbornene (pNB) prepared by ring‐opening metathesis polymerization (ROMP). The high heteroatom content within DTPA moieties impart intriguing bulk properties to poly‐ene materials after direct electrophilic addition reactions to the polymer backbone introducing DTPAs as side chain groups. The resulting materials possess both enhanced optical and flame retardant properties vs the poly‐ene starting materials. Finally, we demonstrate the ability to prepare crosslinked polydiene films with di‐functional DTPAs, where the crosslinking density and thermomechanical properties can be directly tuned by DTPA feed ratios.

Functionalized [2.2]Paracyclophanedienes as Monomers for Poly(p-phenylenevinylene)s.

Poly(p-phenylenevinylene)s (PPVs) featuring complex side-chains, to date, have only been synthesized by nonliving polymerization methods which have no control over PPV molecular weights, dispersities, or end groups. [2.2]Paracyclophane-1,9-diene (pCpd) has gained attention as a monomer for its ability to be ring-opened to PPV in a living fashion. pCpd, an organic cyclic scaffold with planar chirality, has seen minimal structural diversity due to the harsh reaction conditions required to afford the highly strained compound. Herein, we introduce a general method to overcome this by targeting the synthesis of a monohydroxy-pCpd via mono-demethylation of a dialkoxy-pCpd. The monohydroxy-pCpd can then be functionalized easily, which we demonstrate using three distinct side-chains with four moieties commonly incorporated in conjugated polymers: an alkyl bromide, an oligo(ethylene glycol) chain, an enantiomerically pure side-chain, and a Boc-protected amine. These monofunctionalized-pCpds were investigated as monomers in the ring-opening metathesis polymerization (ROMP) to afford functionalized PPVs in a living manner. The functional-group-containing PPVs are synthesized with full control over their end groups, repeat units, and dispersities. The feasibility of post-polymerization modifications to incorporate any desired moiety to PPV fabricated by this method was demonstrated using an azide-alkyne click reaction. All synthesized PPVs were soluble in organic solvents and display the same fluorescent emission, indicating their conjugated backbones are unaltered.

Structural and thermodynamic insights into the coordination preference of norbornadiene with the initiator complex [RuCl2(PPh3)2(piperidine)] in polymerization via olefin metathesis.

The metathesis reaction has been an important tool in both organic and inorganic synthetic chemistry. More specifically in polymer chemistry, ring opening metathesis polymerization (ROMP), via the formation of an active metal-carbene species (MCHR), has been widely used. The elucidation of the mechanism for ROMP opened the way for the development of well-defined catalysts, suited to local conditions. In the present study, we employed density functional theory (DFT) to investigate three reaction pathways for the formation of a species capable of activating ROMP. The active species is formed from the [RuCl2(PPh3)2(pip)] complex in the presence of norbornadiene (NBD) and the carbene source ethyl diazoacetate (EDA). Formation of a hexacoordinated intermediate [RuCl2(PPh3)2(pip)(NBD)] is favored in the first step, with NBD doubly coordinated to the [RuCl2(PPh3)2(pip)] moiety. Analysis of donation (X → Ru) and back-donation (Ru → X) processes in the [RuCl2(PPh3)2(pip)(NBD)] complex shows that piperidine behaves as a σ donor, while NBD behaves as a π donor and the PPh3 groups act as π acceptors. The intensity of the orbital component is predominant in relation to the steric component in the complex. Thus, we propose that the reaction occurs through the formation of a hexacoordinated complex, followed by the dissociation of a PPh3 group, thus forming a complex where NBD is doubly coordinated to the metal center. Coordination of EDA leads finally to the catalyst capable of forming the metallocyclobutane intermediate required for the ROMP reaction.

An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

Polymer-protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by "graft-through" ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP-protein conjugates (albumin and ERG), setting the stage for a new class of BP-protein conjugates for future therapeutic and imaging applications.

Ring-opening metathesis polymerization with 2–5 orders of rate increment

Re-coordination-suppressed ROMP achieved by a binary mechanism pathway with 2–5 orders of rate increment.

A general synthesis of cyclic bottlebrush polymers with enhanced mechanical properties via graft-through ring expansion metathesis polymerization.

Bottlebrush polymers represent an important class of macromolecular architectures, with applications ranging from drug delivery to organic electronics. While there is an abundance of literature describing the synthesis, structure, and applications of linear bottlebrush polymers using ring-opening metathesis polymerization (ROMP), there are comparatively less reports on their cyclic counterparts. This lack of research is primarily due to the difficulty in synthesizing cyclic bottlebrush polymers, as extensions of typical routes towards linear bottlebrush polymers (i.e., "grafting-through" polymerizations of macromonomers with ROMP) produce only ultrahigh molar mass cyclic bottlebrush polymers with poor molar mass control. Herein, we report a ring-expansion metathesis polymerization (REMP) approach to cyclic bottlebrush polymers via a "grafting-through" approach utilizing the active pyr-CB6 initiator developed in our lab. The resulting polymers, characterized via GPC-MALS-IV, are shown to have superior molar mass control across a range of target backbone lengths. The cyclic materials are also found to have superior mechanical properties when compared to their linear counterparts, as assessed by ball-mill grinding and compression testing experiments.

Synthesis of oxanorbornene-based phosphonium polymeric ionic liquids (PILs) and investigation of their electrical properties

A series of phosphonium polymeric ionic liquids (PILs) was synthesized by ring-opening metathesis polymerization (ROMP). The optimum conductivity obtained was 6 × 10−4 S cm−1.

Study of uricase-polynorbornene conjugates derived from grafting-from ring-opening metathesis polymerization.

PEGylation has been the 'gold standard' in bioconjugation due to its ability to improve the pharmacokinetics and pharmacodynamics of native proteins. However, growing clinical evidence of hypersensitivity reactions to PEG due to pre-existing anti-PEG antibodies in healthy humans have raised concerns. Advancements in controlled polymerization techniques and conjugation chemistries have paved the way for the development of protein-polymer conjugates that can circumvent these adverse reactions while retaining the benefits of such modifications. Herein, we show the development of polynorbornene based bioconjugates of therapeutically relevant urate oxidase (UO) enzymes used in the treatment of gout synthesized by grafting-from ring-opening metathesis polymerization (ROMP). Notably, these conjugates exhibit comparable levels of bioactivity to PEGylated UO and demonstrate increased stability across varying temperatures and pH conditions. Immune recognition of conjugates by anti-UO antibodies reveal low protein immunogenicity following the conjugation process. Additionally, UO conjugates employing zwitterionic polynorbornene successfully avoid recognition by anti-PEG antibodies, further highlighting a potential replacement for PEG.

Janus bottlebrush compatibilizers.

Bottlebrush random copolymers (BRCPs), consisting of a random distribution of two homopolymer chains along a backbone, can segregate to the interface between two immiscible homopolymers. BRCPs undergo a reconfiguration, where each block segregates to one of the homopolymer phases, adopting a Janus-type structure, reducing the interfacial tension and promoting adhesion between the two homopolymers, thereby serving as a Janus bottlebrush copolymer (JBCP) compatibilizer. We synthesized a series of JBCPs by copolymerizing deuterated or hydrogenated polystyrene (DPS/PS) and poly(tert-butyl acrylate) (PtBA) macromonomers using ruthenium benzylidene-initiated ring-opening metathesis polymerization (ROMP). Subsequent acid-catalyzed hydrolysis converted the PtBA brushes to poly(acrylic acid) (PAA). The JBCPs were then placed at the interface between DPS/PS homopolymers and poly(2-vinyl pyridine) (P2VP) homopolymers, where the degree of polymerization of the backbone (NBB) and the grafting density (GD) of the JBCPs were varied. Neutron reflectivity (NR) was used to determine the interfacial width and segmental density distributions (including PS homopolymer, PS block, PAA block and P2VP homopolymer) across the polymer-polymer interface. Our findings indicate that the star-like JBCP with NBB = 6 produces the largest interfacial broadening. Increasing NBB to 100 (rod-like shape) and 250 (worm-like shape) reduced the interfacial broadening due to a decrease in the interactions between blocks and homopolymers by stretching of blocks. Decreasing the GD from 100% to 80% at NBB = 100 caused an increase the interfacial width, yet further decreasing the GD to 50% and 20% reduced the interfacial width, as 80% of GD may efficiently increase the flexibility of blocks and promote interactions between homopolymers, while maintaining relatively high number of blocks attached to one molecule. The interfacial conformation of JBCPs was further translated into compatibilization efficiency. Thin film morphology studies showed that only the lower NBB values (NBB = 6 and NBB = 24) and the 80% GD of NBB = 100 had bicontinuous morphologies, due to a sufficient binding energy that arrested phase separation, supported by mechanical testing using asymmetric double cantilever beam (ADCB) tests. These provide fundamental insights into the assembly behavior of JBCPs compatibilizers at homopolymer interfaces, opening strategies for the design of new BCP compatibilizers.

Grafting photochromic spiropyran polymer brushes on graphene oxide surfaces via surface-initiated ring-opening metathesis polymerization.

A practical "grafting-from" strategy is described to grow photochromic polymer brushes bearing spiropyran (SP) functional groups on graphene oxide (GO) surfaces via surface-initiated ring-opening metathesis polymerization (SI-ROMP). The Grubbs II catalyst was fixed on the GO surface, and the norbornene derivatives functionalized using spiropyran were synthesized from this active site via the ROMP method. The results indicated that the spiropyran-modified polymer brushes were obtained on the GO surface in the form of thin films. The solubility of GO modified by spiropyran polymers (GO-SPs) in organic solvents was significantly improved. The GO-SPs exhibited excellent photochromic properties, including fast coloration/decoloration. The modified GO with an isomeric structure was colored in 90 s under ultraviolet irradiation and decolored in 360 s under white light. The fading kinetic rate in the dark was slow and the kinetic attenuation curve followed bi-exponential decay. The GO-SP composite materials took more than 2 h to return to thermodynamically stable forms. The reversible change in the water contact angle reached 8° after continuous cycling with ultraviolet and visible light. GO-SP maintained its photochromic performance and possessed excellent fatigue resistance after more than six successive UV/light cycles. This work describes a practical strategy for the preparation of photochromic polymer brush modified GO composite materials and extends the applications of GO in photochromic materials.

Multimechanophore Polymers for Mechanically Triggered Small Molecule Release with Ultrahigh Payload Capacity.

Polymers that release small molecules in response to mechanical force are promising for a variety of applications including drug delivery, catalysis, and sensing. While a number of mechanophores have been developed for the release of covalently bound payloads, existing strategies are either limited in cargo scope or, in the case of more general mechanophore designs, are restricted to the release of one or two cargo molecules per polymer chain. Herein, we introduce a nonscissile mechanophore based on a masked 2-furylcarbinol derivative that enables the preparation of multimechanophore polymers with ultrahigh payload capacity. We demonstrate that polymers prepared via ring-opening metathesis polymerization are capable of releasing hundreds of small-molecule payloads per polymer chain upon ultrasound-induced mechanochemical activation. This nonscissile masked 2-furylcarbinol mechanophore overcomes a major challenge in cargo loading capacity associated with previous 2-furylcarbinol mechanophore designs, enabling applications that benefit from much higher concentrations of delivered cargo.

Latency for All: Enabling Latency of Hoveyda-Grubbs Second-Generation Catalysts by Adding Phosphite Ligands.

The Hoveyda-Grubbs catalyst (HG2, M720 Umicore) is among the most widely used catalysts in olefin metathesis reactions. Given the usefulness of HG2 and the great interest in developing latent olefin metathesis catalysts for numerous applications, we developed a method to introduce phosphite molecules as ancillary ligands into the precatalyst framework. This modification alters the geometry of the complex from an active trans-dichloro form to a latent cis-dichloro species. Most unusually, the ligands coordinate to HG2 only in solidified solutions (most likely due to entropic factors), providing latent catalysts that can be activated on demand by heat or light by regenerating the original HG2 catalyst. Of particular interest is the use of these latent catalysts in ring-opening metathesis polymerization (ROMP) reactions and 3D printing methods. Indeed, the novel complexes displayed the required latency toward ROMP monomers, even the most reactive dicyclopentadiene. Irradiation with 405 nm light readily results in the expedited formation of the desired polymers. This novel approach provides a general and straightforward way to access efficient and well-defined latent olefin metathesis catalysts.

Alcohol-containing protein transduction domain mimics

The application and design of protein transduction domains (PTDs) and protein transduction domain mimics (PTDMs) have revolutionized the field of biomacromolecule delivery. Our group has previously synthesized block copolymer PTDMs with well-defined hydrophobic and cationic blocks via ring-opening metathesis polymerization (ROMP). We have optimized the balance of hydrophobicity and cationic density to intracellularly deliver model proteins, active proteins, and antibodies. Despite the presence of serine, threonine, and tyrosine in naturally occurring PTDs, synthetic analogs have yet to be studied in PTDMs. In our present work, we introduce different alcohol groups to our PTDM structures as a new design parameter. A library of nine novel PTDMs were synthesized to incorporate alcohol groups of varying structures and evaluated based on their ability to intracellularly deliver fluorescently labeled antibodies. One PTDM in this novel library, named PTDM4, incorporates alcohol groups in both the hydrophobic and cationic blocks and was found to be the best performing PTDM with almost twice the median fluorescence intensity of the delivered antibody and half the cationic density compared to our positive control, a PTDM thoroughly studied by our group. PTDM4 was further studied by intracellularly delivering the active enzyme, TAT-Cre Recombinase. The activity of TAT-Cre Recombinase delivered by PTDM4 was comparable to that of the positive control, again with half the cationic density. This study is one of the first to examine the effects of alcohol groups on intracellular antibody and active enzyme delivery.

Preparation of poly(oxanorbornene) based single and double-folding polymers via nucleophilic aromatic substitution reaction

A facile approach is introduced to prepare single-chain nanoparticles (SCNPs) utilizing intramolecular crosslinking based on nucleophilic aromatic substitution reaction. The linear polymeric precursor comprising dichlorotriazine (DCT) moiety as a reactive pendant group is synthesized via ring-opening metathesis polymerization (ROMP). The reactive chlorine atoms on DCT motifs are substituted with a dithiol nucleophile in varying degrees to yield individually intramolecularly crosslinked polymer nanoparticles. In addition, double-collapse and modification reactions are exploited through the substitution reaction from the remaining unreacted chlorine atoms. A significant reduction in hydrodynamic volumes of the corresponding SCNPs is observed compared to their linear analogues. The obtained nanoparticles are characterized by size exclusion chromatography (SEC), proton nuclear magnetic resonance spectroscopy (1H NMR), diffusion-ordered spectroscopy (DOSY), dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques.

Evaluating Catalyst Performance in Synthesizing Hydroxyl-Terminated Polybutadiene by Ring-Opening-Metathesis Polymerization

AbstractHydroxyl-terminated polybutadiene (HTPB) can be synthesized by ring-opening metathesis polymerization (ROMP) in a one-step process using cyclooctadiene in the presence of a hydroxyl-functionalized chain-transfer agent (CTA). However, previous studies have shown that the presence of primary alcohols can lead to the degradation of some ruthenium catalysts and that the hydroxyl end groups may be converted into aldehydes. Here we compare the performance of five ruthenium-based catalysts — Grubbs first-, second-, and third-generation catalysts (G1, G2, and G3, respectively), Hoveyda–Grubbs Z-selective catalyst (HGZ), and Hoveyda–Grubbs second-generation catalyst (HG2) — in ROMP with a CTA containing primary alcohols. We found that HTPB can be rapidly synthesized in a single step using G3 while avoiding end-group isomerization (2.2% aldehyde formation after full conversion is reached in 5 min). This result suggests that G3 may enable a more effective approach to synthesizing HTPB that avoids protecting groups but still maintains high end-group fidelity.