PhotoROMP: The Future Is Bright.

Since the earliest investigations of olefin metathesis catalysis, light has been the choice for controlling the catalyst activity on demand. From the perspective of energy efficiency, temporal and spatial control, and selectivity, photochemistry is not only an attractive alternative to traditional thermal manufacturing techniques but also arguably a superior manifold for advanced applications like additive manufacturing (AM). In the last three decades, pioneering work in the field of ring-opening metathesis polymerization (ROMP) has broadened the scope of material properties achievable through AM, particularly using light as both an activating and deactivating stimulus. In this Perspective, we explore trends in photocontrolled ROMP systems with an emphasis on approaches to photoinduced activation and deactivation of metathesis catalysts. Recent work has yielded a myriad of commercial and synthetically accessible photosensitive catalyst systems, although comparatively little attention has been paid to achieving precise control over polymer morphology using light. Metal-free, photophysical, and living ROMP systems have also been relatively underexplored. To take fuller advantage of both the thermomechanical properties of ROMP polymers and the operational simplicity of photocontrol, clear directions for the field are to improve the reversibility of activation and deactivation strategies as well as to further develop photocontrolled approaches to tuning cross-link density and polymer tacticity.

Additive Manufacturing of Degradable Materials via Ring-Opening Metathesis Polymerization (ROMP).

Thermoset materials comprise a significant proportion of high-performance plastics due to their shape permanence and excellent thermal and mechanical properties. However, these properties come at the expense of degradability. Here, we show for the first time that the industrial thermoset polydicyclopentadiene (PDCPD) can be additively manufactured (AM) with degradable 2,3-dihydrofuran (DHF) linkages using a photochemical approach. Treatment of the manufactured objects with acid results in rapid degradation to soluble byproducts. This work highlights the potential of ring-opening metathesis polymerization (ROMP) chemistry to create degradable materials amenable to advanced manufacturing processes.

Stimuli-responsive and core cross-linked micelles developed by NiCCo-PISA of helical poly(aryl isocyanide)s.

We report the synthesis of redox- and pH-sensitive block copolymer micelles that contain chiral cores composed of helical poly(aryl isocyanide)s. Pentafluorophenyl (PFP) ester-containing micelles synthesised via nickel-catalysed coordination polymerisation-induced self-assembly (NiCCo-PISA) of helical poly(aryl isocyanide) amphiphilic diblock copolymers are modified post-polymerisation with various diamines to introduce cross-links and/or achieve stimulus-sensitive nanostructures. The successful introduction of the diamines is confirmed by Fourier-transform infrared spectroscopy (FT-IR), while the stabilisation effect of the cross-linking is explored by dynamic light scattering (DLS). The retention of the helicity of the core-forming polymer block is verified by circular dichroism (CD) spectroscopy and the stimuli-responsiveness of the nanoparticles towards a reducing agent (l-glutathione, GSH) and pH is evaluated by following the change in the size of the nanoparticles by DLS. These stimuli-responsive nanoparticles could find use in applications such as drug delivery, nanosensors or biological imaging.

Log Poct/SA Predicts the Thermoresponsive Behavior of P(DMA-co-RA) Statistical Copolymers.

Polymers that exhibit a lower critical solution temperature (LCST) have been of great interest for various biological applications such as drug or gene delivery, controlled release systems, and biosensing. Tuning the LCST behavior through control over polymer composition (e.g., upon copolymerization of monomers with different hydrophobicity) is a widely used method, as the phase transition is greatly affected by the hydrophilic/hydrophobic balance of the copolymers. However, the lack of a general method that relates copolymer hydrophobicity to their temperature response leads to exhaustive experiments when seeking to obtain polymers with desired properties. This is particularly challenging when the target copolymers are comprised of monomers that individually form nonresponsive homopolymers, that is, only when copolymerized do they display thermoresponsive behavior. In this study, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temperature (TCP). A series of statistical copolymers were synthesized based on hydrophilic N,N-dimethyl acrylamide (DMA) and hydrophobic alkyl acrylate monomers, and their hydrophobicity was compared using surface area-normalized octanol/water partition coefficients (Log Poct/SA). Interestingly, a correlation between the Log Poct/SA of the copolymers and their TCPs was observed for the P(DMA-co-RA) copolymers, which allowed TCP prediction of a demonstrative copolymer P(DMA-co-MMA). These results highlight the strong potential of this computational tool to improve the rational design of copolymers with desired temperature responses prior to synthesis.

Continuous Additive Manufacturing using Olefin Metathesis.

The development of chemistry is reported to implement selective dual-wavelength olefin metathesis polymerization for continuous additive manufacturing (AM). A resin formulation based on dicyclopentadiene is produced using a latent olefin metathesis catalyst, various photosensitizers (PSs) and photobase generators (PBGs) to achieve efficient initiation at one wavelength (e.g., blue light) and fast catalyst decomposition and polymerization deactivation at a second (e.g., UV-light). This process enables 2D stereolithographic (SLA) printing, either using photomasks or patterned, collimated light. Importantly, the same process is readily adapted for 3D continuous AM, with printing rates of 36 mm h-1 for patterned light and up to 180 mm h-1 using un-patterned, high intensity light.

DNA-polymer conjugates via the graft-through polymerisation of native DNA in water.

The direct, graft-through, ring-opening metathesis polymerisation (ROMP) of unprotected DNA macromonomers is reported. By tuning the polymerisation conditions, good control is achieved, enabling the rapid and efficient synthesis of DNA-containing bottlebrush copolymers, without the need for protection of the DNA bases.

Probing and Tuning the Permeability of Polymersomes.

Polymersomes are a class of synthetic vesicles composed of a polymer membrane surrounding an aqueous inner cavity. In addition to their overall size, the thickness and composition of polymersome membranes determine the range of potential applications in which they can be employed. While synthetic polymer chemists have made great strides in controlling polymersome membrane parameters, measurement of their permeability to various analytes including gases, ions, organic molecules, and macromolecules remains a significant challenge. In this Outlook, we compare the general methods that have been developed to quantify polymersome membrane permeability, focusing in particular on their capability to accurately measure analyte flux. In addition, we briefly highlight strategies to control membrane permeability. Based on these learnings, we propose a set of criteria for designing future methods of quantifying membrane permeability such that the passage of a variety of molecules into and out of their lumens can be better understood.

Tuning Epoxy Thermomechanics via Thermal Isomerization: A Route to Negative Coefficient of Thermal Expansion Materials.

Fine control over the thermal expansion and contraction behavior of polymer materials is challenging. Most polymers have large coefficients of thermal expansion (CTEs), which preclude long performance lifetimes of composite materials. Herein, we report the design and synthesis of epoxy thermosets with low CTE values below their Tg and large contraction behavior above Tg by incorporating thermally contractile dibenzocyclooctane (DBCO) motifs within the thermoset network. This atypical thermomechanical behavior was rationalized in terms of a twist-boat to chair conformational equilibrium of the DBCO linkages. We anticipate these findings to be generally useful in the preparation of materials with designed CTE values.

Strong Variation of Micelle-Unimer Coexistence as a Function of Core Chain Mobility.

Polymeric micelles coexist in solution with unassembled chains (unimers). We have investigated the influence of glass transition temperature (T g) (i.e., chain mobility) of the micelle core-forming blocks on micelle-unimer coexistence. We synthesized a series of seven PEG-b-P(nBA-ran-tBA) amphiphilic block copolymers (PEG = poly(ethylene glycol), nBA = n-butyl acrylate, tBA = tert-butyl acrylate) with similar molecular weights (12 kg/mol). Varying the nBA/tBA molar ratio enabled broad modulation of core block T g with no significant change in core hydrophobicity or micelle size. NMR diffusometry revealed increasing unimer populations from 0% to 54% of total polymer concentration upon decreasing core block T g from 25 to -46 °C. Additionally, unimer population at fixed polymer composition (and thus core T g) increased with temperature. This study demonstrates the strong influence of core-forming block mobility on polymer self-assembly, providing information toward designing drug delivery systems and suggesting the need for new dynamical theory.

100th Anniversary of Macromolecular Science Viewpoint: The Role of Hydrophobicity in Polymer Phenomena.

The seemingly simple notion of the hydrophobic effect can be viewed from multiple angles involving theory, simulation, and experiments. This viewpoint examines five attributes of predictive models to enhance synthetic efforts as well as experimental methods to quantify hydrophobicity. In addition, we compare existing predictive models against experimental data for polymer surface tension, lower critical solution temperature, solution self-assembly morphology, and degradation behavior. Key conclusions suggest that both the Hildebrand solubility parameters (HSPs) and surface area-normalized Log P (Log P SA-1) values provide unique and complementary insights into polymer phenomena. In particular, HSPs appear to better describe bulk polymer phenomena for thermoplastics such as surface tension, while Log P SA-1 values are well-suited for describing and predicting the behavior of polymers in solution.

Tuning small molecule release from polymer micelles: Varying H2S release through cross linking in the micelle core.

Polymer micelles, used extensively as vehicles in the delivery of active pharmaceutical ingredients, represent a versatile polymer architecture in drug delivery systems. We hypothesized that degree of crosslinking in the hydrophobic core of amphiphilic block copolymer micelles could be used to tune the rate of release of the biological signaling gas (gasotransmitter) hydrogen sulfide (H2S), a potential therapeutic. To test this hypothesis, we first synthesized amphiphilic block copolymers of the structure PEG-b-P(FBEA) (PEG = poly(ethylene glycol), FBEA = 2-(4-formylbenzoyloxy)ethyl acrylate). Using a modified arm-first approach, we then varied the crosslinking percentage in the core-forming block via addition of a 'O,O'-alkanediyl bis(hydroxylamine) crosslinking agent. We followed incorporation of the crosslinker by 1H NMR spectroscopy, monitoring the appearance of the oxime signal resulting from reaction of pendant aryl aldehydes on the block copolymer with hydroxylamines on the crosslinker, which revealed crosslinking percentages of 5, 10, and 15%. We then installed H2S-releasing S-aroylthiooxime (SATO) groups on the crosslinked polymers, yielding micelles with SATO units in their hydrophobic cores after self-assembly in water. H2S release studies in water, using cysteine (Cys) as a trigger to induce H2S release from the SATO groups in the micelle core, revealed increasing half-lives of H2S release, from 117 ± 6 min to 210 ± 30 min, with increasing crosslinking density in the micelle core. This result was consistent with our hypothesis, and we speculate that core crosslinking limits the rate of Cys diffusion into the micelle core, decreasing the release rate. This method for tuning the release of covalently linked small molecules through modulation of micelle core crosslinking density may extend beyond H2S to other drug delivery systems where precise control of release rate is needed.

Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical Copolymers.

Thermoresponsive copolymers that exhibit a lower critical solution temperature (LCST) have been exploited to prepare stimuli-responsive materials for a broad range of applications. It is well understood that the LCST of such copolymers can be controlled by tuning molecular weight or through copolymerization of two known thermoresponsive monomers. However, no general methodology has been established to relate polymer properties to their temperature response in solution. Herein, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temperature (T CP). A series of statistical copolymers were synthesized based on hydrophilic oligoethylene glycol monomethyl ether methacrylate (OEGMA) and hydrophobic alkyl methacrylate monomers and their hydrophobicity was compared using surface area-normalized partition coefficients (log P oct/SA). However, while some insight was gained by comparing T CP and hydrophobicity values, further statistical analysis on both experimental and literature data showed that the molar percentage of comonomer (i.e., grafting density) was the strongest influencer of T CP, regardless of the comonomer used. The lack of dependence of T CP on comonomer chemistry implies that a broad range of functional, thermoresponsive materials can be prepared based on OEGMA by simply tuning grafting density.

It is Better with Salt: Aqueous Ring-Opening Metathesis Polymerization at Neutral pH.

Aqueous ring-opening metathesis polymerization (ROMP) is a powerful tool for polymer synthesis under environmentally friendly conditions, functionalization of biomacromolecules, and preparation of polymeric nanoparticles via ROMP-induced self-assembly (ROMPISA). Although new water-soluble Ru-based metathesis catalysts have been developed and evaluated for their efficiency in mediating cross metathesis (CM) and ring-closing metathesis (RCM) reactions, little is known with regards to their catalytic activity and stability during aqueous ROMP. Here, we investigate the influence of solution pH, the presence of salt additives, and catalyst loading on ROMP monomer conversion and catalyst lifetime. We find that ROMP in aqueous media is particularly sensitive to chloride ion concentration and propose that this sensitivity originates from chloride ligand displacement by hydroxide or H2O at the Ru center, which reversibly generates an unstable and metathesis inactive complex. The formation of this Ru-(OH)n complex not only reduces monomer conversion and catalyst lifetime but also influences polymer microstructure. However, we find that the addition of chloride salts dramatically improves ROMP conversion and control. By carrying out aqueous ROMP in the presence of various chloride sources such as NaCl, KCl, or tetrabutylammonium chloride, we show that diblock copolymers can be readily synthesized via ROMPISA in solutions with high concentrations of neutral H2O (i.e., 90 v/v%) and relatively low concentrations of catalyst (i.e., 1 mol %). The capability to conduct aqueous ROMP at neutral pH is anticipated to enable new research avenues, particularly for applications in biological media, where the unique characteristics of ROMP provide distinct advantages over other polymerization strategies.

The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer Micelles.

Understanding, predicting, and controlling the self-assembly behavior of stimuli-responsive block copolymers remains a pertinent challenge. As such, the copolymer blending protocol provides an accessible methodology for obtaining a range of intermediate polymeric nanostructures simply by blending two or more block copolymers in the desired molar ratio to target specific stimuli-responsiveness. Herein, thermoresponsive diblock copolymers are blended in various combinations to investigate whether the resultant cloud point temperature can be modulated by simple manipulation of the molar ratio. Thermoresponsive amphiphilic diblock copolymers composed of statistical poly(n-butyl acrylate-co-N,N-dimethylacrylamide) core-forming blocks and four different thermoresponsive corona-forming blocks, namely poly(diethylene glycol monomethyl ether methacrylate) (p(DEGMA)), poly(N-isopropylacrylamide), poly(N,N-diethylacrylamide), and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (p(OEGMA)) are selected for evaluation. Using variable temperature turbidimetry, the thermoresponsive behavior of blended diblock copolymer self-assemblies is assessed and compared to the thermoresponsive behavior of the constituent pure diblock copolymer micelles to determine whether comicellization is achieved and more significantly, whether the two blended corona-forming thermoresponsive blocks exhibit cooperative behavior. Interestingly, blended diblock copolymer micelles composed of p(DEGMA)/p(OEGMA) mixed coronae display cooperative behavior, highlighting the potential of copolymer blending for the preparation of stimuli-responsive nanomaterials in applications such as oil recovery, drug delivery, biosensing, and catalysis.

Nickel-Catalyzed Coordination Polymerization-Induced Self-Assembly of Helical Poly(aryl isocyanide)s.

The interest in helix-containing nanostructures is currently growing as a consequence of their potential applications in areas such as nanomedicine, nanomaterial design, chiral recognition, and asymmetric catalysis. Herein, we present a facile and tunable one-pot methodology to achieve chiral nano-objects. The nickel-catalyzed coordination polymerization-induced self-assembly (NiCCo-PISA) of helical poly(aryl isocyanide) amphiphilic diblock copolymers was realized and allowed access to various nano-object morphologies (spheres, worm-like micelles, and polymersomes). The helicity of the core block was confirmed via circular dichroism (CD) spectroscopy for all morphologies, proving their chiral nature. Small-molecule uptake by the spherical nanoparticles was investigated by encapsulating Nile Red into the core of the spheres and subsequent transfer into aqueous media. The presence of a CD signal for the otherwise CD-inactive dye proved the chiral induction effect of the nano-objects' helical core. This demonstrates the potential of NiCCo-PISA to prepare nanoparticles for applications in nanomaterials, catalysis, and recognition.

Correction to "Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical Copolymers".

[This corrects the article DOI: 10.1021/acsmacrolett.0c00461.].

Polymerization-Induced Polymersome Fusion.

The dynamic interactions of membranes, particularly their fusion and fission, are critical for the transmission of chemical information between cells. Fusion is primarily driven by membrane tension built up through membrane deformation. For artificial polymersomes, fusion is commonly induced via the external application of a force field. Herein, fusion-promoted development of anisotropic tubular polymersomes (tubesomes) was achieved in the absence of an external force by exploiting the unique features of aqueous ring-opening metathesis polymerization-induced self-assembly (ROMPISA). The out-of-equilibrium tubesome morphology was found to arise spontaneously during polymerization, and the composition of each tubesome sample (purity and length distribution) could be manipulated simply by targeting different core-block degrees of polymerization (DPs). The evolution of tubesomes was shown to occur via fusion of "monomeric" spherical polymersomes, evidenced most notably by a step-growth-like relationship between the fraction of tubular to spherical nano-objects and the average number of fused particles per tubesome (analogous to monomer conversion and DP, respectively). Fusion was also confirmed by Förster resonance energy transfer (FRET) studies to show membrane blending and confocal microscopy imaging to show mixing of the polymersome lumens. We term this unique phenomenon polymerization-induced polymersome fusion, which operates via the buildup of membrane tension exerted by the growing polymer chains. Given the growing body of evidence demonstrating the importance of nanoparticle shape on biological activity, our methodology provides a facile route to reproducibly obtain samples containing mixtures of spherical and tubular polymersomes, or pure samples of tubesomes, of programmed length. Moreover, the capability to mix the interior aqueous compartments of polymersomes during polymerization-induced fusion also presents opportunities for its application in catalysis, small molecule trafficking, and drug delivery.

Self-Amplified Depolymerization of Oligo(thiourethanes) for the Release of COS/H2S.

Herein we report the self-amplified depolymerization of an aryl oligo(thiourethane) (OTU) for the release of COS/H2S. The OTU was synthesized via polyaddition of 4-isothiocyanatobenzyl alcohol and end-capped with an aryl azide. The aryl azide chain-end was reduced by tris(2-carboxyethyl)phosphine or H2S to the corresponding aniline, resulting in depolymerization (i.e., self-immolation) and the release of COS/H2S. Depolymerization was monitored by 1H NMR and UV-Vis spectroscopy, and the released COS was converted into H2S by the ubiquitous enzyme carbonic anhydrase in aqueous media.

Ring-opening metathesis polymerization-induced self-assembly (ROMPISA).

Polymerization-induced self-assembly (PISA) has simplified the preparation of polymeric nanoparticles, expanding their commercial importance. Recently, PISA mediated via ring-opening metathesis polymerization (ROMPISA) has emerged as a powerful alternative to existing PISA methodologies. ROMPISA can be conducted under air in minutes, producing nano-object morphologies with unique characteristics. Herein, we highlight recent advances in this field.

Tuning H2S Release by Controlling Mobility in a Micelle Core.

Drug delivery from polymer micelles has been widely studied, but methods to precisely tune rates of drug release from micelles are limited. Here, the mobility of hydrophobic micelle cores was varied to tune the rate at which a covalently bound drug was released. This concept was applied to cysteine-triggered release of hydrogen sulfide (H2S), a signaling gas with therapeutic potential. In this system, thiol-triggered H2S donor molecules were covalently linked to the hydrophobic blocks of self-assembled polymer amphiphiles. Because release of H2S is triggered by cysteine, diffusion of cysteine into the hydrophobic micelle core was hypothesized to control the rate of release. We confirmed this hypothesis by carrying out release experiments from H2S-releasing micelles in varying compositions of EtOH/H2O. Higher EtOH concentrations caused the micelles to swell, facilitating diffusion in and out of their hydrophobic cores and leading to faster H2S release from the micelles. To achieve a similar effect without addition of organic solvent, we prepared micelles with varying core mobility via incorporation of a plasticizing co-monomer in the core-forming block. The glass transition temperature (Tg) of the core block could therefore be precisely varied by changing the amount of the plasticizing co-monomer in the polymer. In aqueous solution under identical conditions, the release rate of H2S varied over 20-fold (t½ = 0.18 - 4.2 h), with the lowest Tg hydrophobic block resulting in the fastest H2S release. This method of modulating release kinetics from polymer micelles by tuning core mobility may be applicable to many types of physically encapsulated and covalently linked small molecules in a variety of drug delivery systems.