We report the synthesis of a new class of strained macrocycle that performs well in ring-opening metathesis polymerization (ROMP). The polymerization displays chain growth characteristics with evidence of secondary metathesis in the form of chain transfer. The unique structure enables access to stilbene-based polymers that are traditionally prepared via uncontrolled polymerizations.
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 to 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.
Block copolymers with unique architectures and those that can self‐assemble into supramolecular structures are used in medicine as biomaterial scaffolds and delivery vehicles for cells, therapeutics, and imaging agents. To date, much of the work relies on controlling polymer behavior by varying the monomer side chains to add functionality and tune hydrophobicity. Although varying the side chains is an efficient strategy to control polymer behavior, changing the polymer backbone can also be a powerful approach to modulate polymer self‐assembly, rigidity, reactivity, and biodegradability for biomedical applications. There are many developments in the syntheses of polymers with segmented backbones, but these developments are not widely adopted as strategies to address the unique constraints and requirements of polymers for biomedical applications. This review highlights dual polymerization strategies for the synthesis of backbone‐segmented block copolymers to facilitate their adoption for biomedical applications.
We used digital light processing additive manufacturing (DLP-AM) to produce mechanochemically responsive test specimens from custom photoresin formulations, wherein designer, flex activated mechanophores enable quantitative assessment of the total mechanophore activation in the specimen. The manufactured object geometries included an octet truss unit cell, a gyroid lattice, and an “8D cubic lattice”. The mechanophore activation in each test specimen was measured as a function of uniaxial compressive strain applied to the structure. Full shape recovery after compression was exhibited in all cases. These proof-of-concept results signify the potential to use flex activated mechanophore for nondestructive, quantitative volumetric assessment of mechanochemistry in test specimens with complex geometries. Additionally, the integration of DLP-AM with flex activated mechanophore build materials enabled the creation of customizable, three-dimensional mechanochemically responsive parts that exhibit small molecule release without undergoing irreversible deformation or fracture.
We report facile synthesis of 3-trifluoromethyl-6-methyl-1,4-dioxane-2,5-dione and ring opening polymerization of the fluoro-lactide monomer to prepare polylactides composed of trifluoromethyl and methyl pendent groups on each repeat unit (FPLA). Molecular weights of the prepared polymers correlated well with the initial molar ratio of monomer to initiator, and were found to range from 6.6 to 22.5 kDa as determined by 1H NMR spectroscopy. GPC analysis revealed an Mn of up to 16.5 kDa. 1H, 13C, and 19F NMR spectroscopy were consistent with the structures of the lactide monomer isomers, and 1H NMR analysis was consistent with polymer backbones of alternating trifluoromethyl- and methyl-substituted lactate constituents. Glass transition temperature (Tg) and decomposition temperature (Td) of the new FPLA were found to be 39 °C and 225 °C by DSC and TGA, respectively. Additionally, we prepared amphiphilic block copolymers of FPLA and polyethylene glycol (PEG). Specifically, FPLA-b-PEG diblocks and FPLA-PEG-FPLA triblocks were synthesized by using PEG monomethyl ether (mPEG) or PEG as alcohol initiators, respectively. We observed the formation of vesicles or worm-like micelles from the particles of FPLA-PEG-FPLA in dilute aqueous solution by transmission electron microscopy (TEM), suggesting potential applications for drug delivery.
We demonstrate concomitant release of HNO and small molecule organics from amphiphilic poly(norbornene)-based copolymers. This key function was achieved by incorporation of thermally-labile oxazine units within random and block copolymer architectures. Upon thermolysis, we observed generation of HNO and release of a small molecule conjugate. Importantly, the release kinetics of HNO and a UV-active small molecule (4-nitroaniline) were found to be 1:1, signifying an ability to monitor HNO production indirectly, or to simultaneously release organic therapeutics (e.g., nonsteroidal anti-inflammatory drugs)) along with HNO. To our knowledge, these are the first reported polymeric materials demonstrating HNO release from covalently attached HNO donors.
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.
The field of polymer mechanochemistry has experienced rapid growth over the past decade, propelled largely by the development of force-activated functional groups (mechanophores) and polymer structure-reactivity principles for mechanochemical transduction. In addition to fundamental guidelines for converting mechanical input into chemical output, there has also been increasing focus toward the application of polymer mechanochemistry for specific functions, materials, and devices. These endeavors are made possible by multidisciplinary approaches involving designer polymer synthesis, computational modeling and design, and different fields of engineering. Described herein are contributions from our group on the development of flex activated mechanophores for small molecule release and star polymer mechanochemistry, as well as collaborative efforts toward mechanochemically triggered depolymerizations and 3D printed mechanochromic materials.
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.
This paper aims to explore and demonstrate the ability to integrate entry-level additive manufacturing (AM) techniques with responsive polymers capable of mechanical to chemical energy transduction. This integration signifies the merger of AM and smart materials.