C-H Functionalization and Allylic Amination for Post-Polymerization Modification of Polynorbornenes.

Post-polymerization modification (PPM) via direct C-H functionalization is a powerful synthetic strategy to convert polymer feed-stocks into value-added products. We found that a metal-free, Se-catalyzed allylic C-H amination provided an efficient method for PPM of polynorbornenes (PNBs) produced via ring-opening metathesis polymerization. Inherent to the mechanism of the allylic amination, PPM on PNBs preserved the alkene functional groups along the polymer backbone, while also avoiding transposition of the double bonds. Amination using a series of aryl sulfonamides led to good control over the degree of functionalization, access to a range of functionalities, and tunable thermal properties from the resulting polymers.

Metal-Free Ring-Opening Metathesis Polymerization: From Concept to Creation.

Ring-opening metathesis polymerization (ROMP), which is derived from transition-metal-based olefin metathesis, has evolved into one of the most prevalent technologies for making functional polymeric materials in academia and in industry. The initial discovery of and advances in ROMP used ill-defined mixtures of metal salts to initiate polymerization. The initiators most commonly used today, developed with tremendous efforts, are well-defined metal-alkylidene complexes that have enabled a good mechanistic understanding of the polymerization as well as improvement of the initiators' activity, stability, and functional group tolerance.The evolution of ROMP has been decidedly metal-centric, with the path to accolades being paved primarily in ruthenium-, molybdenum-, and tungsten-based systems. Our departure from the ROMP trailhead was inspired in part by recent breakthroughs in radical-mediated polymerizations, whereby their mechanisms were leveraged to develop metal-free reaction conditions. Inventing a metal-free complement to traditional ROMP would essentially involve stepping away from decades of inorganic and organometallic developments, but with the promise of crossing new synthetic capabilities and curiosities.Driven by this motivation, as well as a community-inspired desire to develop "greener" controlled polymerizations, our team pioneered the search for, and discovery of, a wholly organic alternative to traditional metal-mediated ROMP. In this Account, we review our recent efforts to develop metal-free ring-opening metathesis polymerization (MF-ROMP), which is inspired by previous reports in electro- and photo-mediated organic transformations.This work began with an exploration of the direct oxidation of enol ethers and the propensity of the ensuing radical cations to initiate ROMP. To overcome limitations of the electrochemical conditions, a photoredox-mediated method was investigated next, using photoexcited pyrylium salts to oxidize the enol ethers. With this system, we demonstrated the ability to produce ROMP products and temporally control the polymerization.Further investigations into different aspects of the reaction included monomer scope, functional group tolerance, the impact of changing photocatalyst properties, and the ability to control molecular weight. The unique mechanism of MF-ROMP, along with the relative ease of synthesizing enol ether initiators, enabled the preparation of numerous polymeric materials that are hard to access through traditional metal-mediated pathways. At the end of this Account, we provide a perspective on future opportunities in this emerging area.

Mechanochemical Release of N-Heterocyclic Carbenes from Flex-Activated Mechanophores.

We have discovered a new flex-activated mechanophore that releases an N-heterocyclic carbene (NHC) under mechanical load. The mechanophore design is based upon NHC-carbodiimide (NHC-CDI) adducts and demonstrates an important first step toward flex-activated designs capable of further downstream reactivities. Since the flex-activation is non-destructive to the main polymer chains, the material can be subjected to multiple compression cycles to achieve iterative increases in the activation percentage of mechanophores. Two different NHC structures were demonstrated, signifying the potential modularity of the mechanophore design.

An Ion-Pairing Approach to Stereoselective Metal-Free Ring-Opening Metathesis Polymerization.

Stereochemistry can have a profound impact on polymer and materials properties. Unfortunately, straightforward methods for realizing high levels of stereocontrolled polymerizations are often challenging to achieve. In a departure from traditional metal-mediated ring-opening metathesis polymerization (ROMP), we discovered a remarkably simple method for controlling alkene stereochemistry in photoredox mediated metal-free ROMP. Ion-pairing, initiator sterics, and solvation effects each had profound impact on the stereochemistry of polynorbornene (PNB). Simple modifications to the reaction conditions produced PNB with trans alkene content of 25 to >98 %. High cis content was obtained from relatively larger counterions, toluene as solvent, low temperatures (-78 °C), and initiators with low Charton values. Conversely, smaller counterions, dichloromethane as solvent, and enol ethers with higher Charton values enabled production of PNB with high trans content. Data from a combined experimental and computational investigation are consistent with the stereocontrolling step of the radical cationic mechanism proceeding under thermodynamic control.

Synthesis and Characterization of Anionic Poly(cyclopentadienylene vinylene) and Its Use in Conductive Hydrogels.

The use of π-conjugated polymers (CPs) in conductive hydrogels remains challenging due to the water-insoluble nature of most CPs. Conjugated polyelectrolytes (CPEs) are promising alternatives because they have tunable electronic properties and high water-solubility, but they are often difficult to synthesize and thus have not been widely adopted. Herein, we report the synthesis of an anionic poly(cyclopentadienylene vinylene) (aPCPV) from an insulating precursor under mild conditions and in high yield. Functionalized aPCPV is a highly water-soluble CPE that exhibits low cytotoxicity, and we found that doping hydrogels with aPCPV imparts conductivity. We also anticipate that this synthetic strategy, due to its ease and high efficiency, will be widely used to create families of not-yet-explored π-conjugated vinylene polymers.

Molecular Weight Control via Cross Metathesis in Photo-Redox Mediated Ring-Opening Metathesis Polymerization.

Photo-redox mediated ring-opening metathesis polymerization (photo-ROMP) is an emerging ROMP technique that uses an organic redox mediator and a vinyl ether initiator, in contrast to metal-based initiators traditionally used in ROMP. The reversibility of the redox-mediated initiation and propagation steps enable spatiotemporal control over the polymerization. Herein, we explore a simple, inexpensive means of controlling molecular weight, using alpha olefins as chain transfer agents. This method enables access to low molecular weight oligomers, and molecular weights between 1 and 30 kDa can be targeted simply by altering the stoichiometry of the reaction. This method of molecular weight control was then used to synthesize a functionalized norbornene copolymer in a range of molecular weights for specific materials applications.

Hybrid Photo-induced Copolymerization of Ring-Strained and Vinyl Monomers Utilizing Metal-Free Ring-Opening Metathesis Polymerization Conditions.

We introduce the hybrid copolymerization of two disparate monomer classes (vinyl monomers and ring-strained cyclic olefins) via living photopolymerization. The living character of the polymerization technique (metal-free photo-ROMP) is demonstrated by consecutive chain-extensions. Further, we propose a mechanism for the copolymerization and analyze the copolymer structure in detail by high-resolution mass spectrometry.

The Intrinsic Mechanochemical Reactivity of Vinyl-Addition Polynorbornene.

Herein we report the discovery of the intrinsic mechanochemical reactivity of vinyl-addition polynorbornene (VA-PNB), which has strained bicyclic ring repeat units along the polymer backbone. VA-PNBs with three different side chains were found to undergo ring-opening olefination upon sonication in dilute solutions. The sonicated polymers exhibited spectroscopic signatures consistent with conversion of the bicyclic norbornane repeat units into the ring-open isomer typical of polynorbornene made by ring-opening metathesis polymerization (ROMP-PNB). Thermal analysis and evaluation of chain-scission kinetics suggest that sonication of VA-PNB results in chain segments containing a statistical mixture of vinyl-added and ROMP-type repeat units.

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.

Sunflower Polymers for Folate-Mediated Drug Delivery.

Polymeric delivery vehicles can improve the safety and efficacy of chemotherapy drugs by facilitating preferential tumor delivery. Polymer-drug conjugates are especially attractive carriers because additional formulation steps are not required during manufacturing, and drug release profiles can be altered based on linker choice. For clinical translation, these vehicles should also be reproducibly and controllably synthesized. Recently, we reported the development of a class of materials called "sunflower polymers," synthesized by controlled radical polymerization of hydrophilic "petals" from a cyclic multimacroinitiator "core". This synthesis strategy afforded control over the size of the polymer nanostructures based on their petal polymerization time. In this work, we demonstrate that particle size can be further tuned by varying the degree of polymerization of the cyclic core in addition to that of the petals. Additionally, we investigate the application of these materials for tumor-targeted drug delivery. We demonstrate that folate-targeted, doxorubicin-conjugated sunflower polymers undergo receptor-mediated uptake into cancer cells and pH-triggered drug release leading to cytotoxicity. These materials are attractive as drug carriers due to their discrete and small size, shielded drug cargo that can be triggered for release, and relative ease of synthesis.

Investigation of the dynamic nature of 1,2-oxazines derived from peralkylcyclopentadiene and nitrosocarbonyl species.

We have investigated the reversible hetero-Diels-Alder reaction of 1,2-oxazines derived from a peralkylcyclopentadiene and a series of nitrosocarbonyl dienophiles. The nature of the dienophile was found to impart broad tunability to the dynamic character of the oxazine adducts. The reversibility was also observed in polymeric systems. The fidelity of the reaction and tunable sensitivity toward elevated temperature and water signify potential applications in the development of dynamic covalent materials or delivery systems for small molecule payloads.

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.

Metal-free ring-opening metathesis polymerization.

We have developed a method to achieve ring-opening metathesis polymerization (ROMP) mediated by oxidation of organic initiators in the absence of any transition metals. Radical cations, generated via one-electron oxidation of vinyl ethers, were found to react with norbornene to give polymeric species with microstructures essentially identical to those traditionally obtained via metal-mediated ROMP. We found that vinyl ether oxidation could be accomplished under mild conditions using an organic photoredox mediator. This led to high yields of polymer and generally good correlation between M(n) values and initial monomer to catalyst loadings. Moreover, temporal control over reinitiation of polymer growth was achieved during on/off cycles of light exposure. This method demonstrates the first metal-free method for controlled ROMP.

Successive mechanochemical activation and small molecule release in an elastomeric material.

We have developed a mechanochemically responsive material capable of successively releasing small organic molecules from a cross-linked network upon repeated compressions. The use of a flex activated mechanophore that does not lead to main chain scission and an elastomeric polyurethane enabled consecutive compressions with incremental increases in the % mechanophore activation. Additionally, we examined the effect of multiple applications of compressive stress on both mechanophore activity and the mechanical behavior of the elastomeric matrix in which the mechanophore is embedded.

Kinetic analysis of mechanochemical chain scission of linear poly(phthalaldehyde).

The kinetics of mechanochemical chain scission of poly(phthalaldehyde) (PPA) are investigated. Ultrasound-induced cavitation is capable of causing chain scission in the PPA backbone that ultimately leads to rapid depolymerization of each resulting polymer fragment when above the polymer's ceiling temperature (Tc ). An interesting feature of the mechanochemical breakdown of PPA is that "half-chain" daughter fragments are not observed, since the depolymerization is rapid following chain scission. These features facilitate the determination of rate constants of activation for multiple molecular weights from a single sonication experiment. Additionally, the degradation kinetics are modified with chain-end trapping agents through variation of the nature and amount of small molecule nucleophile or electrophile.

Multi-color dual wavelength vat photopolymerization 3D printing via spatially controlled acidity.

Dual wavelength vat photopolymerization (DW-VP) has emerged as a powerful approach to create multimaterial objects. However, only a limited range of properties have been showcased. In this work, we report the 3D printing (3DP) of multi-color objects from a single resin vat using DW-VP. This was accomplished by concurrently curing resin with visible light and modulating local resin color with 365-nm ultraviolet (UV) light. The key advance was to use a photoacid generator (PAG) in combination with pH responsive dyes in the 3DP resins. The specific color is dictated by the extent of reaction, or local acidity in our case, and controlled by the light dosage and pattern of UV light applied. Multi-color object formation was implemented in two-step processes involving first 3DP to set the object structure, followed by UV exposure, as well as single processes that leveraged DW-VP to create a broad range of vibrant colors and patterns.

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.

"Flex-activated" mechanophores: using polymer mechanochemistry to direct bond bending activation.

We describe studies in mechanochemical transduction that probe the activation of bonds orthogonal to an elongated polymer main chain. Compression of mechanophore-cross-linked materials resulted in the release of small molecules via cleavage of covalent bonds that were not integral components of the elongated polymer segments. The reactivity is proposed to arise from the distribution of force through the cross-linking units of the polymer network and subsequent bond bending motions that are consistent with the geometric changes in the overall reaction. This departure from contemporary polymer mechanochemistry, in which activation is achieved primarily by force-induced bond elongation, is a first step toward mechanophores capable of releasing side-chain functionalities without inherently compromising the overall macromolecular architecture.

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.

Additive Manufacturing by Heating at a Patterned Photothermal Interface.

Direct additive manufacturing (AM) of commercial silicones is an unmet need with high demand. We report a new technology, heating at a patterned photothermal interface (HAPPI), which achieves AM of commercial thermoset resins without any chemical modifications. HAPPI integrates desirable aspects of stereolithography with the thermally driven chemical modalities of commercial silicone formulations. In this way, HAPPI combines the geometric advantages of vat photopolymerization with the materials properties of, for example, injection molded silicones. We describe the realization of the new technology, HAPPI printing using a commercial Sylgard 184 polydimethylsiloxane resin, comparative analyses of material properties, and demonstration of HAPPI in targeted applications.