Scalable and continuous access to pure cyclic polymers enabled by 'quarantined' heterogeneous catalysts.

Cyclic polymers are topologically interesting and envisioned as a lubricant material. However, scalable synthesis of pure cyclic polymers remains elusive. The most straightforward way is to recover a used catalyst after the synthesis of cyclic polymers and reuse it. Unfortunately, this is demanding because of the catalyst's vulnerability and inseparability from polymers, which reduce the practicality of the process. Here we develop a continuous circular process, where polymerization, polymer separation and catalyst recovery happen in situ, to dispense a pure cyclic polymer after bulk ring-expansion metathesis polymerization of cyclopentene. It is enabled by introducing silica-supported ruthenium catalysts and newly designed glassware. Different depolymerization kinetics of the cyclic polymer from its linear analogue are also discussed. This process minimizes manual labour, maximizes the security of vulnerable catalysts and guarantees the purity of cyclic polymers, thereby showcasing a prototype of a scalable access to cyclic polymers with increased turnovers (≥415,000) of precious catalysts.

Cascade Cyclopolymerization of 5-Ethynyl-1,8-Nonadiyne Derivatives to Synthesize Low Band Gap Conjugated Polyacetylenes Containing a Fused Bicyclic Structure.

Cyclopolymerization is a powerful method for synthesizing polyacetylenes containing four- to seven-membered rings. However, the structure of the repeat unit only consists of mono-cycloalkene due to the single cyclization of diyne monomers. Herein, we demonstrate a novel cascade cyclopolymerization to synthesize polyacetylenes containing fused bicyclic rings from triyne monomers containing bulky dendrons via sequential cascade ring-closing metathesis. These dendrons provided solubility and stability to the rigid bicyclic polyacetylene backbone. In addition, we controlled the regioselectivity of the catalyst approach by altering its structure and synthesized polymers containing fused bicyclo[4,3,0] or [4,4,0] rings with high molecular weights of up to 120 kg mol-1 . Interestingly, the resulting polymers showed narrower band gaps (down to 1.6 eV) than polymers with mono-cycloalkene repeat units due to the planarization of the conjugated segment resulting from the fused bicyclic structure.

Bulky Cyclometalated Ruthenium Nitrates for Challenging Z-Selective Metathesis: Efficient One-Step Access to α-Oxygenated Z-Olefins from Acrylates and Allyl Alcohols.

α-Oxygenated Z-olefins are ubiquitous in biologically active molecules and serve as versatile handles for organic synthesis, but their syntheses are often tedious and less selective. Here we report the efficient Z-selective metathesis of various terminal acrylates and allyl alcohols, which enables facile and selective construction of high value-added α-oxygenated Z-olefins from readily available feedstock chemicals. These challenging metathesis transformations are enabled by novel cyclometalated Ru-carbene-nitrate complexes bearing bulky-yet-flexible side arms, whose assembly was unlocked by new organometallic syntheses.

Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester.

A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D2 metabolite (tricyclic-PGDM) methyl ester in racemic form was accomplished in eight steps from a readily available known cyclopentene-diol derivative. The synthesis features a nickel-catalyzed Ueno-Stork-type dicarbofunctionalization to generate two consecutive stereocenters, a palladium-catalyzed carbonylative spirolactonization to build the core oxaspirolactone, and a Z-selective cross-metathesis to introduce the (Z)-3-butenoate side chain, a group challenging to introduce through traditional Wittig protocols and troublesome for the two previous total syntheses. A general Z-selective cross-metathesis protocol to construct (Z)-ß,γ-unsaturated esters was also developed that has broad functional group tolerance and high stereoselectivity. Additionally, our synthesis already accumulated 75 mg of valuable material for an 18 O-tricyclic-PGDM-based assay used in clinical settings for inflammation.

Selective CO2 Electrochemical Reduction Enabled by a Tricomponent Copolymer Modifier on a Copper Surface.

Electrochemical CO2 reduction over Cu could provide value-added multicarbon hydrocarbons and alcohols. Despite recent breakthroughs, it remains a significant challenge to design a catalytic system with high product selectivity. Here we demonstrate that a high selectivity of ethylene (55%) and C2+ products (77%) could be achieved by a highly modular tricomponent copolymer modified Cu electrode, rivaling the best performance using other modified polycrystalline Cu foil catalysts. Such a copolymer can be conveniently prepared by a ring-opening metathesis polymerization, thereby offering a new degree of freedom for tuning the selectivity. Control experiments indicate all three components are essential for the selectivity enhancement. A surface characterization showed that the incorporation of a phenylpyridinium component increased the film robustness against delamination. It was also shown that its superior performance is not due to a morphology change of the Cu underneath. Molecular dynamics (MD) simulations indicate that a combination of increased local CO2 concentration, increased porosity for gas diffusion, and the local electric field effect together contribute to the increased ethylene and C2+ product selectivity.

Processing Effects on the Self-Assembly of Brush Block Polymer Photonic Crystals.

The self-assembly of poly(dimethylsiloxane)-b-poly(trimethylene carbonate) (PDMS-b-PTMC) bottlebrush block polymers was investigated under different processing conditions. Small-angle X-ray scattering (SAXS) and UV/Visible spectroscopy provided insight into the self-assembly and structure in response to heating and applied pressure. In the absence of applied pressure (i.e., before annealing), the PDMS-b-PTMC bottlebrush block polymers are white solids and adopt small, randomly oriented lamellar grains. Heating the materials to 140 °C in the absence of applied pressure appears to "lock in" the isotropic, short-range-ordered state, preventing the formation of the long-range-ordered lamellar structure responsible for photonic properties. Applying modest anisotropic pressure (3 psi) between parallel plates at ambient temperature orients the short-range lamellar grains; however, applied pressure alone does not produce long-range order. Only when the bottlebrush block polymers were heated (>100 °C) under modest pressure (3 psi) were long-range-ordered photonic crystals formed. Analysis of the SAXS data motivated analogies to liquid crystals and revealed the potential self-assembly pathway. These results provide insight into the structure and self-assembly of bottlebrush block polymers with low glass transition temperature side chains in response to different processing conditions.

Addressing the challenges of modeling the scattering from bottlebrush polymers in solution.

Small-angle scattering measurements of complex macromolecules in solution are used to establish relationships between chemical structure and conformational properties. Interpretation of the scattering data requires an inverse approach where a model is chosen and the simulated scattering intensity from that model is iterated to match the experimental scattering intensity. This raises challenges in the case where the model is an imperfect approximation of the underlying structure, or where there are significant correlations between model parameters. We examine three bottlebrush polymers (consisting of polynorbornene backbone and polystyrene side chains) in a good solvent using a model commonly applied to this class of polymers: the flexible cylinder model. Applying a series of constrained Monte-Carlo Markov Chain analyses demonstrates the severity of the correlations between key parameters and the presence of multiple close minima in the goodness of fit space. We demonstrate that a shape-agnostic model can fit the scattering with significantly reduced parameter correlations and less potential for complex, multimodal parameter spaces. We provide recommendations to improve the analysis of complex macromolecules in solution, highlighting the value of Bayesian methods. This approach provides richer information for understanding parameter sensitivity compared to methods which produce a single, best fit.

Efficient Z-Selective Olefin-Acrylamide Cross-Metathesis Enabled by Sterically Demanding Cyclometalated Ruthenium Catalysts.

The efficient Z-selective cross-metathesis between acrylamides and common terminal olefins has been developed by the use of novel cyclometalated ruthenium catalysts with bulky N-heterocyclic carbene (NHC) ligands. Superior reactivity and stereoselectivity are realized for the first time in this challenging transformation, allowing streamlined access to an important class of cis-Michael acceptors from readily available feedstocks. The kinetic preference for cross-metathesis is enabled by a pivalate anionic ligand, and the origin of this effect is elucidated by density functional theory calculations.

Aldehyde-Functionalized Magnetic Particles to Capture Off-Target Chemotherapeutic Agents.

Drug capture is a promising technique to prevent off-target chemotherapeutic agents from reaching systemic circulation and causing severe side effects. The current work examines the viability of using immobilized aldehydes for drug-capture applications via Schiff base formation between doxorubicin (DOX) and aldehydes. Commercially available pyridoxal-5'-phosphate (VB6) was immobilized on iron oxide nanoparticles (IONPs) to capture DOX from human serum. Leaching of VB6 persisted as a primary issue and thus various aldehydes with anchoring groups such as catechol, silatrane, and phosphonate esters have been studied. The phosphonate group-based anchor was the most stable and used for further capture studies. To improve the hydrophilic nature of the aldehydes, sulfonate-containing aldehydes and polyethylene glycols (PEGs) were investigated. Finally, the optimized functionalized iron oxide particles, PEGylated-IONP, were used to demonstrate doxorubicin capture from human serum at biologically relevant temperature (37 °C), time (30 min), and concentrations (µM). The current study sets the stage for the development of potential compact dimension capture device based on surface-anchorable polymers with aldehyde groups.

Confinement and Processing Can Alter the Morphology and Periodicity of Bottlebrush Block Copolymers in Thin Films.

Bottlebrush block copolymers (BBCPs) are intriguing architectural variations on linear BCPs with highly tunable structure. Confinement can have a significant impact on polymer assembly, giving rise to changes in morphology, assembly kinetics, and properties like the glass transition. Given that confinement leads to significant changes in the persistence length of bottlebrush homopolymers, it is reasonable to expect that BBCPs will see significant changes in their structure and periodicity relative to the bulk morphology. Understanding how confinement influences assembly will be important for designing BBCPs for thin film applications including membranes, integrated photonic structures, and potentially BCP lithography. In order to study the effects of confinement on BBCP conformation and morphology, a blade coating was used to prepare films with continuous variation in film thickness. Unlike thin films of linear BCPs, islands/holes were not observed, and instead mixtures of parallel and perpendicular morphologies emerge after annealing. The lamellar periodicity (L0) of the morphologies is found to be thickness dependent, increasing L0 with decreasing film thickness for blade coated films. Films coated out of tetrahydrofuran (THF) resulted in a single well-defined lamellar periodicity, verified through atomic force microscopy (AFM) and grazing incidence small-angle X-ray scattering (GISAXS), which increases dramatically from the bulk value (30.6 nm) and continues to increase as the film thickness decreases. The largest observed L0 was 65.5 nm, and this closely approaches the estimated upper limit of 67 nm corresponding to a fully extended backbone in a bilayer arrangement. Films coated out of propylene glycol methyl ether acetate (PGMEA) resulted in a mixture of perpendicular lamellae and a smaller, likely cylindrical morphology. The lamellar portion of the film shows the same thickness dependence as the lamellae observed in the THF coated films. The scaling of the lamellar L0 with respect to film thickness follows predictions for confined semiflexible polymers with weak excluded volume interactions and can be related to models for confinement of DNA. Spin coated films shows the same reduction in periodicity, although at very different film thicknesses. This result suggests that the material has shallow free-energy barriers to transitioning between different L0 and morphologies, a property that could be taken advantage of for patterning diverse structures with a single material.

Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles.

Ovarian cancer survival and the recurrence rate are drastically affected by the amount of tumor that can be surgically removed prior to chemotherapy. Surgeons are currently limited to visual inspection, making smaller tumors difficult to be removed surgically. Enhancing the surgeon's ability to selectively remove cancerous tissue would have a positive effect on a patient's prognosis. One approach to aid in surgical tumor removal involves using targeted fluorescent probes to selectively label cancerous tissue. To date, there has been a trade-off in balancing two requirements for the surgeon: the ability to see maximal tumors and the ability to identify these tumors by eye while performing the surgery. The ability to see maximal tumors has been prioritized and this has led to the use of fluorophores activated by near-infrared (NIR) light as NIR penetrates most deeply in this surgical setting, but the light emitted by traditional NIR fluorophores is invisible to the naked eye. This has necessitated the use of specialty detectors and monitors that the surgeon must consult while performing the surgery. In this study, we develop nanoparticles that selectively label ovarian tumors and are activated by NIR light but emit visible light. This potentially allows for maximal tumor observation and real-time detection by eye during surgery. We designed two generations of up-converting nanoparticles that emit green light when illuminated with NIR light. These particles specifically label ovarian tumors most likely via tumor-associated macrophages, which are prominent in the tumor microenvironment. Our results demonstrate that this approach is a viable means of visualizing tumors during surgery without the need for complicated, expensive, and bulky detection equipment. Continued improvement and experimentation could expand our approach into a much needed surgical technique to aid ovarian tumor removal.

Electronic Structures, Spectroscopy, and Electrochemistry of [M(diimine)(CN-BR3)4]2- (M = Fe, Ru; R = Ph, C6F5) Complexes.

Complexes with the formula [M(diimine)(CN-BR3)4]2-, where diimine = bipyridine (bpy), phenanthroline (phen), 3,5-trifluoromethylbipyridine (flpy), R = Ph, C6F5, and M = FeII, RuII, were synthesized and characterized by X-ray crystal structure analysis, UV-visible spectroscopy, IR spectroscopy, and voltammetry. Three highly soluble complexes, [FeII(bpy)(CN-B(C6F5)3)4]2-, [RuII(bpy)(CN-B(C6F5)3)4]2-, and [RuII(flpy)(CN-B(C6F5)3)4]2-, exhibit electrochemically reversible redox reactions, with large potential differences between the bpy0/- or flpy0/- and MIII/II couples of 3.27, 3.52, and 3.19 V, respectively. CASSCF+NEVPT2 calculations accurately reproduce the effects of borane coordination on the electronic structures and spectra of cyanometallates.

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.

Correction: Aqueous electrocatalytic CO2 reduction using metal complexes dispersed in polymer ion gels.

Correction for 'Aqueous electrocatalytic CO2 reduction using metal complexes dispersed in polymer ion gels' by Shunsuke Sato et al., Chem. Commun., 2020, DOI: .

Aqueous electrocatalytic CO2 reduction using metal complexes dispersed in polymer ion gels.

We use fac-[Re(bpy)(CO)3Cl] ([Re-Cl]) dispersed in polymer ion gel (PIG) ([Re]-PIG) to carry out electrocatalytic CO2 reduction in water. Electrolysis at -0.68 V vs. RHE in a CO2-saturated KOH and K2CO3 solution produces CO with over 90% Faradaic efficiency. The PIG electrode is readily combined with water oxidation catalysts to generate a full electrochemical cell. Additionally, we provide evidence that the PIG electrode can be implemented with other molecular catalysts.

The Concentration Dependence of the Size and Symmetry of a Bottlebrush Polymer in a Good Solvent.

Bottlebrush polymers consist of a linear backbone with densely grafted side chains which impact the rigidity of the molecule. The persistence length of the bottlebrush backbone in solution is influenced by both the intrinsic structure of the polymer and by the local environment, such as the solvent quality and concentration. Increasing the concentration reduces the overall size of the molecule due to the reduction in backbone stiffness. In this study we map out the size of a bottlebrush polymer as a function of concentration for a single backbone length. Small-angle neutron scattering (SANS) measurements are conducted on a polynorbornene-based bottlebrush with polystyrene side chains in a good solvent. The data are fit using a model which provides both the long and short axis radius of gyration (R g,2 and R g,1, respectively), providing a measure for how the conformation changes as a function of concentration. At low concentrations a highly anisotropic structure is observed (R g,2/R g,1 ≈ 4), becoming more isotropic at higher concentrations (R g,2/R g,1 ≈ 1.5). The concentration scaling for both R g,2 and the overall R g are evaluated and compared with predictions in the literature. Coarse-grained molecular dynamics simulations were also conducted to probe the impact of concentration on bottlebrush conformation showing qualitative agreement with the experimental results.

An Efficient Synthesis of Geminal-Dialkyl Dienes for Olefin Metathesis Polymerization.

A robust synthesis of gem-dialkyl acyclic diene monomers has been developed. This route is scalable, flexible, and biorenewable, allowing for the production of a wide range of diene monomers of different lengths and different gem-dialkyl substitution starting from unsaturated esters derived from seed oils. The metathesis polymerization of these monomers and the hydrogenation of the resulting polyolefins leads to telechelic gem-dialkyl polyethylenes, which can be used as elastomers in the synthesis of polyurethanes and other block polymers.

Enantioselective Synthesis of 15-Deoxy-Δ12,14-Prostaglandin J2.

An enantioselective synthesis of 15-deoxy-Δ12,14-prostaglandin J2 is reported. The synthesis begins with the preparation of enantiopure 3-oxodicyclopentadiene by a lipase-mediated kinetic resolution. A three-component coupling followed by a retro-Diels-Alder reaction provides the C8 stereochemistry of the prostaglandin skeleton with high enantioselectivity. Stereoretentive olefin metathesis followed by a Pinnick oxidation affords 15-deoxy-Δ12,14-prostaglandin J2 in high enantiopurity.

Living ß-selective cyclopolymerization using Ru dithiolate catalysts.

Cyclopolymerization (CP) of 1,6-heptadiyne derivatives is a powerful method for synthesizing conjugated polyenes containing five- or six-membered rings via α- or ß-addition, respectively. Fifteen years of studies on CP have revealed that user-friendly Ru-based catalysts promoted only α-addition; however, we recently achieved ß-selective regiocontrol to produce polyenes containing six-membered-rings, using a dithiolate-chelated Ru-based catalyst. Unfortunately, slow initiation and relatively low catalyst stability inevitably led to uncontrolled polymerization. Nevertheless, this investigation gave us some clues to how successful living polymerization could be achieved. Herein, we report living ß-selective CP by rational engineering of the steric factor on monomer or catalyst structures. As a result, the molecular weight of the conjugated polymers from various monomers could be controlled with narrow dispersities, according to the catalyst loading. A mechanistic investigation by in situ kinetic studies using 1H NMR spectroscopy revealed that with appropriate pyridine additives, imposing a steric demand on either the monomer or the catalyst significantly improved the stability of the propagating carbene as well as the relative rates of initiation over propagation, thereby achieving living polymerization. Furthermore, we successfully prepared diblock and even triblock copolymers with a broad monomer scope.