Monodisperse Cyclic Polymer Mechanochemistry: Scission Kinetics and the Dynamic Memory Effect with Ultrasonication and Ball-Mill Grinding.

A series of monodisperse cyclic and linear poly(d,l-lactide)s (c-PLA and l-PLA, respectively) were prepared with various degrees of polymerization (DP) using an iterative convergent synthesis approach. The absence of a molecular weight distribution provided us a chance to study their mechanochemical reactivity without obstructions arising from the size distribution. Additionally, we prepared l- and c-PLAs with identical DPs, which enabled us to attribute differences in scission rates to the cyclic polymer architecture alone. The polymers were subjected to ultrasonication (US) and ball-mill grinding (BMG), and their degradation kinetics were explored. Up to 9.0 times larger scission rates were observed for l-PLA (compared to c-PLA) with US, but the difference was less than 1.9 times with BMG. Fragmentation requires two backbone scission events for c-PLA, and we were able to observe linear intermediates (formed after a single scission) for the first time. We also developed a new method of studying the dynamic memory effect in US by characterizing and comparing the daughter fragment molecular weight distributions of l- and c-PLAs. These results provide new insights into the influence of the cyclic polymer architecture on mechanochemical reactions as well as differences in reactivity observed with US and BMG.

Mechanochemical ring-opening metathesis polymerization: development, scope, and mechano-exclusive polymer synthesis.

Ruthenium-alkylidene initiated ring-opening metathesis polymerization has been realized under solid-state conditions by employing a mechanochemical ball milling method. This method promotes greenness and broadens the scope to include mechano-exclusive products. The carbene- and pyridine-based Grubbs 3rd-generation complex outperformed other catalysts and maintained similar mechanistic features of solution-phase reactions. High-speed ball milling provides sufficient mixing and energy to the solid reaction mixture, which is composed of an initiator and monomers, to minimize or eliminate the use of solvents. Therefore, the solubility and miscibility of monomers and Ru-initiators are not limiting factors in solid-state ball milling. A wide variety of solid monomers, including ionomers, fluorous monomers, and macromonomers, were successfully polymerized under ball milling conditions. Importantly, direct copolymerization of immiscible (ionic/hydrophobic) monomers exemplifies the synthesis of mechano-exclusive polymers that are difficult to make using traditional solution procedures. Finally, the addition of a small amount of a liquid additive (i.e., liquid-assisted grinding) minimized chain-degradation, enabling high-molecular-weight polymer synthesis.

Controlled Living Cascade Polymerization of Polycyclic Enyne Monomers: Leveraging Complete Degradability for a Stereochemical and Structural Investigation.

Cascade polymerizations recently gained significant attention due to their use of unique transformations, involving multiple bond making and/or breaking steps, when converting monomers to repeat units. However, designing complex cascade polymerizations which proceed in a controlled manner is very challenging. Various side reactions can hamper polymerization performance and the efficiency of the cascade. In this work, we explore a metathesis-based cascade polymerization of unique polycyclic enyne monomers, which contain a terminal alkyne and two cyclic alkenes. By modifying the monomer's stereochemistry, linkers, and ring types, we were able to modulate the polymerization performance and the extent to which a complete cascade reaction occurs. Upon subjecting the resulting polymers to mild acidic conditions and analyzing the degradation products, we were able to calculate the percentage of repeat units derived from a complete cascade reaction (termed the cascade efficiency). In addition to identifying how various structural parameters in the monomer influence the success of a cascade polymerization, we were able to achieve controlled living cascade polymerizations of multiple monomers with >99% cascade efficiency and produce various block copolymers.

Mechanochemical Reactivity of Bottlebrush and Dendronized Polymers: Solid vs. Solution States.

We explored the mechanochemical degradation of bottlebrush and dendronized polymers in solution (with ultrasonication, US) and solid states (with ball-mill grinding, BMG). Over 50 polymers were prepared with varying backbone length and arm architecture, composition, and size. With US, we found that bottlebrush and dendronized polymers exhibited consistent backbone scission behavior, which was related to their elongated conformations in solution. Considerably different behavior was observed with BMG, as arm architecture and composition had a significant impact on backbone scission rates. Arm scission was also observed for bottlebrush polymers in both solution and solid states, but only in the solid state for dendronized polymers. Motivated by these results, multi-mechanophore polymers with bottlebrush and dendronized polymer architectures were prepared and their reactivity was compared. Although dendronized polymers showed slower arm-scission, the selectivity for mechanophore activation was much higher. Overall, these results have important implications to the development of new mechanoresponsive materials.

The influence of polymer architecture in polymer mechanochemistry.

Polymer architecture is an important factor in polymer mechanochemistry. In this Feature Article, we summarize recent developments in utilizing polymer architecture to modulate mechanochemical reactions within polymers, or more specifically, the location and rates of bond scission events that lead to polymer fragmentation or mechanophore activation. Various well-defined architectures have been explored, including those of cyclic, intramolecularly cross-linked, dendritic, star, bottlebrush, and dendronized polymers. We primarily focus on describing the enhancement or suppression of mechanochemical reactivity, with respect to analogous linear polymers, as well as differences in solution- and solid-state behavior.

Sugar-Based Polymers from d-Xylose: Living Cascade Polymerization, Tunable Degradation, and Small Molecule Release.

Enyne monomers derived from D-xylose underwent living cascade polymerizations to prepare new polymers with a ring-opened sugar and degradable linkage incorporated into every repeat unit of the backbone. Polymerizations were well-controlled and had living character, which enabled the preparation of high molecular weight polymers with narrow molecular weight dispersity values and a block copolymer. By tuning the type of acid-sensitive linkage (hemi-aminal ether, acetal, or ether functional groups), we could change the degradation profile of the polymer and the identity of the resulting degradation products. For instance, the large difference in degradation rates between hemi-aminal ether and ether-based polymers enabled the sequential degradation of a block copolymer. Furthermore, we exploited the generation of furan-based degradation products, from an acetal-based polymer, to achieve the release of covalently bound reporter molecules upon degradation.

Ru-Catalyzed, cis-Selective Living Ring-Opening Metathesis Polymerization of Various Monomers, Including a Dendronized Macromonomer, and Implications to Enhanced Shear Stability.

An unsaturated polymer's cis/trans-olefin content has a significant influence on its properties. For polymers obtained by ring-opening metathesis polymerization (ROMP), the cis/trans-olefin content can be tuned by using specific catalysts. However, cis-selective ROMP has suffered from narrow monomer scope and lack of control over the polymerization (giving polymers with broad molecular weight distributions and prohibiting the synthesis of block copolymers). Herein, we report the versatile cis-selective controlled living ROMP of various endo-tricyclo[4.2.2.02,5]deca-3,9-diene and various norbornene derivatives using a fast-initiating dithiolate-chelated Ru catalyst. Polymers with cis-olefin content as high as 99% could be obtained with high molecular weight (up to Mn of 105.1 kDa) and narrow dispersity (<1.4). The living nature of the polymerization was also exploited to prepare block copolymers with high cis-olefin content for the first time. Furthermore, owing to the successful control over the stereochemistry and narrow dispersity, we could compare cis- and trans-rich polynorbornene and found the former to have enhanced resistance to shear degradation.

Cascade polymerizations: recent developments in the formation of polymer repeat units by cascade reactions.

Traditionally, most polymerizations rely on simple reactions such as alkene addition, ring-opening, and condensation because they are robust, highly efficient, and selective. These reactions, however, generally only yield a single new C-C or C-O bond during each propagation step. In recent years, novel macromolecules have been prepared with propagation steps that involve cascade reactions, enabling various combinations of bond making and breaking steps to form more complex repeat units. These polymerizations are often challenging, given the requirements for high conversion and selectivity in controlled polymerizations, yet they provide polymers with unique chemical structures and significantly broaden the scope of how polymers can be made. In this perspective, we summarize the recent developments in cascade polymerizations, primarily focusing on single-component cascades (rather than multi-component polymerizations). Polymerization performance, monomer scope, and mechanisms are discussed for polymerizations utilizing radical, ionic, and metathesis-based mechanisms.

Controlled Living Cascade Polymerization To Make Fully Degradable Sugar-Based Polymers from d-Glucose and d-Galactose.

Monomers derived from glucose and galactose, which contain an endocyclic alkene (in the sugar ring) and a terminal alkyne, underwent a cascade polymerization to prepare new polymers with the ring-opened sugar incorporated into the polymer backbone. Polymerizations were well-controlled, as demonstrated by a linear increase in molecular weight with monomer-to-initiator ratio and generally narrow molecular weight dispersity values. The living nature of the polymerization was supported by the preparation of a block copolymer from two different sugar-based monomers. The resulting polymers were also fully degradable. They underwent fast and complete depolymerization to small molecules under acidic conditions.

Synthesis of Functional Polyacetylenes via Cyclopolymerization of Diyne Monomers with Grubbs-type Catalysts.

Metathesis cyclopolymerization (CP) of α,ω-diynes is a powerful method to prepare functional polyacetylenes (PAs). PAs have long been studied due to their interesting electrical, optical, photonic, and magnetic properties which make them candidates for use in various advanced applications. Grubbs catalysts are widely used throughout synthetic chemistry, largely due to their accessibility, high reactivity, and tolerance to air, moisture, and many functional groups. Prior to our entrance into this field, only a few examples of CP using modified Grubbs catalysts existed. Inspired by these works, we saw an opportunity to expand the accessibility and utility of Grubbs-catalyzed CPs. We began by exploring CP with popular and commercially available Grubbs catalysts. We found Grubbs third-generation catalyst (G3) to be an excellent catalyst when we used strategies to stabilize the propagating Ru carbene, such as decreasing the polymerization temperature or using weakly coordinating solvent or ligands. Controlled living polymerizations were demonstrated using various 1,6-heptadiyne monomers and yielded polymers with exclusively 5-membered rings (via α-addition) in the polymer backbone. The strategy of stabilizing the Ru carbene was also critical to successful CP with Hoveyda-Grubbs second-generation (HG2) and Grubbs first-generation (G1) catalysts. We found that decomposed Ru species were catalyzing side reactions which could be completely shut down by decreasing the reaction temperature or using weakly coordinating ligands. While HG2 generally led to uncontrolled polymerizations, we found it to be an effective catalyst for monomers with very large side chains. G1 displayed broader functional group tolerance and thus broader monomer scope than G3. We next looked at our ability to change the regioselectivity of the polymerization by using Z-selective catalysts which favor ß-addition and the formation of 6-membered rings in the polymer backbone. While modest ß-selectivity could be obtained using Grubbs Z-selective catalyst at low temperatures, we found that by using one of Hoveyda and co-workers' catalysts with decreased carbene electrophilicity, we could achieve exclusive formation of 6-membered rings. We also pursued alternative routes to achieve 6+-membered rings in the polymer backbone by using diyne monomers with increased distance between alkynes. We found that optimizing the monomer structure for CP was an effective strategy to achieve controlled polymerizations. By using bulky substituents (maximizing the Thorpe-Ingold effect) and/or using heteroatoms (shorter bonds) to bring the alkynes closer together, controlled living CP could be achieved with various 1,7-octadiyne and 1,8-nonadiyne monomers. Finally, we took advantage of several inherent properties of controlled CP techniques to prepare polymers with advanced architectures and nanostructures. For instance, the living nature of the polymerization enabled production of block copolymers, the tolerance of very large substituents enabled production of dendronized and brush polymers, and the insolubility or crystallinity of some monomers was utilized for the spontaneous self-assembly of polymers into various one- and two-dimensional nanostructures. Overall, the strategies of stabilizing the propagating Ru carbene, modulating the selectivity and reactivity of the Ru carbene, and enhancing the inherent reactivity of monomers were key to improving the utility and performance of CP with Grubbs-type catalysts. The insight provided by these studies will be important for future developments of CP and other metathesis polymerizations utilizing ring-closing steps.

Mechanochemical Degradation of Denpols: Synthesis and Ultrasound-Induced Chain Scission of Polyphenylene-Based Dendronized Polymers.

New polyphenylene-based dendronized polymers (denpols), exhibiting extended and rigid conformations, were prepared using ring-opening metathesis polymerization (ROMP). Their mechanochemical degradation was explored in ultrasound-induced elongational flow fields. Degradation rate constants were obtained for polyphenylene-based denpols, of varying generation, across a degree of polymerization (DP) range of ∼100-600. In general, it was found that larger side chains led to increased degradation rates and that the rate enhancement was proportional to the natural log of persistence length (Ln( lp)) or the square root of monomer molecular weight ( Mmon0.5). These relationships led to the generation of "master curves" in which the rate constant trends for each polymer series converged, enabling accurate prediction of degradation rate constants for related polymers bearing long alkyl chains or ester-type dendrons. Furthermore, we observed evidence for, and used computational modeling to support, polymer chains undergoing multiple scissions during a single elongation event, leading to faster degradation of daughter fragments that come from parent polymers with large side chains.

Biodegradable Shape Memory Polymers in Medicine.

Shape memory materials have emerged as an important class of materials in medicine due to their ability to change shape in response to a specific stimulus, enabling the simplification of medical procedures, use of minimally invasive techniques, and access to new treatment modalities. Shape memory polymers, in particular, are well suited for such applications given their excellent shape memory performance, tunable materials properties, minimal toxicity, and potential for biodegradation and resorption. This review provides an overview of biodegradable shape memory polymers that have been used in medical applications. The majority of biodegradable shape memory polymers are based on thermally responsive polyesters or polymers that contain hydrolyzable ester linkages. These materials have been targeted for use in applications pertaining to embolization, drug delivery, stents, tissue engineering, and wound closure. The development of biodegradable shape memory polymers with unique properties or responsiveness to novel stimuli has the potential to facilitate the optimization and development of new medical applications.

Adhesion of Blood Plasma Proteins and Platelet-rich Plasma on l-Valine-Based Poly(ester urea).

The competitive absorption of blood plasma components including fibrinogen (FG), bovine serum albumin (BSA), and platelet-rich plasma (PRP) on l-valine-based poly(ester urea) (PEU) surfaces were investigated. Using four different PEU polymers, possessing compositionally dependent trends in thermal, mechanical, and critical surface tension measurements, water uptake studies were carried out to determine in vitro behavior of the materials. Quartz crystal microbalance (QCM) measurements were used to quantify the adsorption characteristics of PRP onto PEU thin films by coating the surfaces initially with FG or BSA. Pretreatment of the PEU surfaces with FG inhibited the adsorption of PRP and BSA decreased the absorption 4-fold. In vitro studies demonstrated that cells cultured on l-valine-based PEU thin films allowed attachment and spreading of rat aortic cells. These measurements will be critical toward efforts to use this new class of materials in blood-contacting biomaterials applications.

Production of Materials with Spatially-Controlled Cross-Link Density via Vat Photopolymerization.

We describe an efficient method to produce objects comprising spatially controlled and graded cross-link densities using vat photopolymerization additive manufacturing (AM). Using a commercially available diacrylate-based photoresin, 3D printer, and digital light processing (DLP) projector, we projected grayscale images to print objects in which the varied light intensity was correlated to controlled cross-link densities and associated mechanical properties. Cylinder and bar test specimens were used to establish correlations between light intensities used for printing and cross-link density in the resulting specimens. Mechanical testing of octet truss unit cells in which the properties of the crossbars and vertices were independently modified revealed unique mechanical responses from the different compositions. From the various test geometries, we measured changes in mechanical properties such as increased strain-to-break in inhomogeneous structures in comparison with homogeneous variants.

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.

α-Amino Acid-Based Poly(Ester urea)s as Multishape Memory Polymers for Biomedical Applications.

The thermal shape memory behavior of a series of α-amino acid-based poly(ester urea)s has been explored. We demonstrate that these materials exhibit excellent shape memory performance in dual- and triple-shape thermomechanical testing. Significant activation of chain mobility above the Tg as well as a hydrogen bonding network provide the basis for shape transformations and recovery. Additionally, we tuned the shape memory properties of these materials with polymer blending, enabling the demonstration of quadruple-shape memory cycles.

3D-printed mechanochromic materials.

We describe the preparation and characterization of photo- and mechanochromic 3D-printed structures using a commercial fused filament fabrication printer. Three spiropyran-containing poly(ε-caprolactone) (PCL) polymers were each filamentized and used to print single- and multicomponent tensile testing specimens that would be difficult, if not impossible, to prepare using traditional manufacturing techniques. It was determined that the filament production and printing process did not degrade the spiropyran units or polymer chains and that the mechanical properties of the specimens prepared with the custom filament were in good agreement with those from commercial PCL filament. In addition to printing photochromic and dual photo- and mechanochromic PCL materials, we also prepare PCL containing a spiropyran unit that is selectively activated by mechanical impetus. Multicomponent specimens containing two different responsive spiropyrans enabled selective activation of different regions within the specimen depending on the stimulus applied to the material. By taking advantage of the unique capabilities of 3D printing, we also demonstrate rapid modification of a prototype force sensor that enables the assessment of peak load by simple visual assessment of mechanochromism.

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.

Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer.

Biological systems rely on recyclable materials resources such as amino acids, carbohydrates and nucleic acids. When biomaterials are damaged as a result of aging or stress, tissues undergo repair by a depolymerization-repolymerization sequence of remodelling. Integration of this concept into synthetic materials systems may lead to devices with extended lifetimes. Here, we show that a metastable polymer, end-capped poly(o-phthalaldehyde), undergoes mechanically initiated depolymerization to revert the material to monomers. Trapping experiments and steered molecular dynamics simulations are consistent with a heterolytic scission mechanism. The obtained monomer was repolymerized by a chemical initiator, effectively completing a depolymerization-repolymerization cycle. By emulating remodelling of biomaterials, this model system suggests the possibility of smart materials where aging or mechanical damage triggers depolymerization, and orthogonal conditions regenerate the polymer when and where necessary.