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Frank L Brodie,1 David A Ramirez,2,* Sundar Pandian,3,* Kelly Woo,3 Ashwin Balakrishna,3 Eugene De Juan,1 Hyuck Choo,3 Robert H Grubbs3 1Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; 2School of Medicine, University of California San Francisco, San Francisco, CA, USA; 3Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA *These authors contributed equally to this work Introduction: Repair of retinal detachment frequently requires use of intraocular gas. Patients are instructed to position themselves postoperatively to appose the intraocular bubble to the retinal break(s). We developed a novel wearable wireless positioning sensor, which provides real-time audiovisual feedback on the accuracy of positioning.Methods: Eight healthy volunteers wore the wireless sensor for 3 hours while instructed to maintain their head tilted toward the 2 o’clock meridian with no audiovisual feedback. Positioning accuracy was recorded. The subjects repeated the experiment for 3 hours with the audiovisual feedback enabled.Results: With no audiovisual feedback, the percentage of time greater than 10° out of position varied from 8.9% to 93.9%. With audiovisual feedback enabled, these percentages ranged from 9.4% to 65%. Three subjects showed significant improvement in their time out of position (P

Frank L Brodie,1 Kelly Y Woo,2 Ashwin Balakrishna,2 Hyuck Choo,2 Robert H Grubbs2 1Department of Ophthalmology, University of California San Francisco, San Francisco, 2Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA Purpose: Surgical repair of retinal attachment or macular hole frequently requires intraocular gas. This necessitates specific postoperative positioning to improve outcomes and avoid complications. However, patients struggle with correct positioning. We have developed a novel sensor to detect the position of the gas bubble in the eye and provide feedback to patients in real time. In this paper, we determine the specificity and sensitivity of our sensor in vitro using a model eye. Methods: We assessed the reliability of our sensor to detect when a gas bubble has deviated off a model retinal break in a model eye. Various bubble sizes representing the intraocular kinetics of sulfur hexafluoride gas and varying degrees of deviation from the correct position were tested using the sensor attached to a mannequin head with a model eye. Results: We recorded 36 data points. The sensor acted appropriately in 33 (91.7%) of them. The sensor triggered the alarm every time the bubble deviated off the break (n=15, sensitivity =100%). However, it triggered the alarm (falsely) 3/21 times when the bubble was correctly positioned over the retinal break (specificity =86%). Conclusion: Our device shows excellent sensitivity (100%) and specificity (86%) in detecting whether intraocular gas is tamponading a retinal break in a model eye. Keywords: postoperative positioning, intraocular gas, vitrectomy, retinal detachment, macular hole, pneumatic retinopexy

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., (© 2022 Wiley-VCH GmbH.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D 2 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)-β,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., (© 2021 Wiley-VCH GmbH.)

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., (© 2021 Wiley-VCH GmbH.)

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.

Electrochemical CO 2 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 C 2+ 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 CO 2 concentration, increased porosity for gas diffusion, and the local electric field effect together contribute to the increased ethylene and C 2+ product selectivity.

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 ( L 0 ) of the morphologies is found to be thickness dependent, increasing L 0 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 L 0 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 L 0 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 L 0 and morphologies, a property that could be taken advantage of for patterning diverse structures with a single material.

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.

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., Competing Interests: The authors declare the following competing financial interest(s): A provisional patent application has been filed by the technology transfer office of the California Institute of Technology on 3/19/2019., (© 2020 American Chemical Society.)

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.

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.

Complexes with the formula [M(diimine)(CN-BR 3 ) 4 ] 2- , where diimine = bipyridine (bpy), phenanthroline (phen), 3,5-trifluoromethylbipyridine (flpy), R = Ph, C 6 F 5 , and M = Fe II , Ru II , were synthesized and characterized by X-ray crystal structure analysis, UV-visible spectroscopy, IR spectroscopy, and voltammetry. Three highly soluble complexes, [Fe II (bpy)(CN-B(C 6 F 5 ) 3 ) 4 ] 2- , [Ru II (bpy)(CN-B(C 6 F 5 ) 3 ) 4 ] 2- , and [Ru II (flpy)(CN-B(C 6 F 5 ) 3 ) 4 ] 2- , exhibit electrochemically reversible redox reactions, with large potential differences between the bpy 0/- or flpy 0/- and M III/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.

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[4.2.2.0 2,5 ]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 M n 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 for 'Aqueous electrocatalytic CO 2 reduction using metal complexes dispersed in polymer ion gels' by Shunsuke Sato et al., Chem. Commun., 2020, DOI: .

We use fac-[Re(bpy)(CO) 3 Cl] ([Re-Cl]) dispersed in polymer ion gel (PIG) ([Re]-PIG) to carry out electrocatalytic CO 2 reduction in water. Electrolysis at -0.68 V vs. RHE in a CO 2 -saturated KOH and K 2 CO 3 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.

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.

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.

An enantioselective synthesis of 15-deoxy-Δ 12,14 -prostaglandin J 2 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-Δ 12,14 -prostaglandin J 2 in high enantiopurity.

The mechanism of Ru-catalyzed ring-opening metathesis polymerization (ROMP) is studied in detail using a pair of third generation ruthenium catalysts with varying sterics of the N-heterocyclic carbene (NHC) ligand. Experimental evidence for polymer chelation to the Ru center is presented in support of a monomer-dependent mechanism for polymerization of norbornene monomers using these fast-initiating catalysts. A series of kinetic experiments, including rate measurements for ROMP, rate measurements for initiation, monomer-dependent kinetic isotope effects, and activation parameters were useful for distinguishing chelating and nonchelating monomers and determining the effect of chelation on the polymerization mechanism. The formation of a chelated metallacycle is enforced by both the steric bulk of the NHC and by the geometry of the monomer, leading to a ground-state stabilization that slows the rate of polymerization and also alters the reactivity of the propagating Ru center toward different monomers in copolymerizations. The results presented here add to the body of mechanistic work for olefin metathesis and may inform the continued design of catalysts for ROMP to access new polymer architectures and materials.

Cyclopolymerization (CP) of 1,6-heptadiyne derivatives is a powerful method for synthesizing conjugated polyenes containing five- or six-membered rings via α- or β-addition, respectively. Fifteen years of studies on CP have revealed that user-friendly Ru-based catalysts promoted only α-addition; however, we recently achieved β-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 β-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 1 H 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., (This journal is © The Royal Society of Chemistry 2019.)

Understanding the stability and reactivity of the propagating species is critical in living polymerization. Therefore, most living olefin metathesis polymerizations require the stabilization of the catalyst by coordination of external ligands containing Lewis basic heteroatoms, e.g., phosphines and pyridines. However, in some cases, chemists postulated that the propagating metal carbene could also be stabilized by olefin chelation. Here, we disclose that stable 16-electron olefin-chelated Ru carbenes play a key role in previously reported living/controlled ring-opening metathesis polymerization of endo-tricyclo[4.2.2.0 2,5 ]deca-3,9-diene and cyclopolymerization of 1,8-nonadiynes using Grubbs catalysts. We successfully isolated these propagating species during polymerization and confirmed their olefin-chelated structures using X-ray crystallography and NMR analysis. DFT calculations and van 't Hoff plots from the equilibrium between olefin-chelated Ru carbenes and 3-chloropyridine (Py)-coordinated carbenes revealed that entropically favored olefin chelation overwhelmed enthalpically more stable Py-coordinated Ru carbenes at room temperature. Therefore, olefin chelation stabilized the propagating species and slowed down the propagation relative to initiation, thereby lowering polydispersity. This finding provides a deeper understanding of the olefin metathesis polymerization mechanism using Grubbs catalysts and offers clues for designing new controlled/living polymerizations.

We report the synthesis and characterization of homoleptic borane adducts of hexacyanoferrate(ii). Borane coordination blueshifts d-d transitions and CN IR and Raman frequencies. Control over redox properties is established with respect to borane Lewis acidity, reflected in peak anodic potential shifts per borane of +250 mV for BPh 3 and +350 mV for B(C 6 F 5 ) 3 . Electron transfer from [Fe(CN-B(C 6 F 5 ) 3 ) 6 ] 4- to photogenerated [Ru(2,2'-bipyridine) 3 ] 3+ is very rapid, consistent with voltammetry data. Coordination by Lewis acids provides an avenue for selective modification of the electronic structures and electrochemical properties of cyanometalates.

Δ 12 -Prostaglandin J family is recently discovered and has potent anticancer activity. Concise syntheses of four Δ 12 -prostaglandin J natural products (7-8 steps in the longest linear sequences) are reported, enabled by convergent stereoretentive cross-metathesis. Exceptional control of alkene geometry was achieved through stereoretention.

Nitrile hydration provides access to amides that are indispensable to researchers in chemical and pharmaceutical industries. Prohibiting the use of this venerable reaction, however, are (1) the dearth of biphasic catalysts that can effectively hydrate nitriles at ambient temperatures with high turnover numbers and (2) the unsolved challenge of hydrating cyanohydrins. Herein, we report the design of new " donor-acceptor"-type platinum catalysts by precisely arranging electron-rich and electron-deficient ligands trans to one other, thereby enhancing both the nucleophilicity of the hydroxyl group and the electrophilicity of the nitrile group. Leveraging a high-throughput, automated workflow and evaluating a library of bidentate ligands, we have discovered that commercially available, inexpensive DPPF [1,1'-ferrocenendiyl-bis(diphenylphosphine)] provides superior reactivity. The corresponding " donor-acceptor"-type catalyst 2a is readily prepared from (DPPF)PtCl 2 , PMe 2 OH, and AgOTf. The enhanced activity of 2a permits the hydration of a wide range of nitriles and cyanohydrins to proceed at 40 °C with excellent turnover numbers. Rational reevaluation of the ligand structure has led to the discovery of modified catalyst 2c, harboring the more electron-rich 1,1'-bis[bis(5-methyl-2-furanyl)phosphino] ferrocene ligand, which demonstrates the highest activity toward hydration of nitriles and cyanohydrins at room temperature. Finally, the correlation between the electron-donating ability of the phosphine ligands with catalyst efficiencies of 2a, 2c, 2d, and 2e in the hydration of nitrile 7 are examined, and the results support the " donor-acceptor" hypothesis.

Fluoride ion batteries are potential "next-generation" electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion-conducting electrolytes are known only in the solid state. We report a liquid fluoride ion-conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper-lanthanum trifluoride (Cu@LaF 3 ) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion-mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Chemotherapy agents are notorious for producing severe side-effects. One approach to mitigating this off-target damage is to deliver the chemotherapy directly to a tumor via transarterial infusion, or similar procedures, and then sequestering any chemotherapeutic in the veins draining the target organ before it enters the systemic circulation. Materials capable of such drug capture are yet to be fully realized. Here, we report the covalent attachment of genomic DNA to iron-oxide nanoparticles. With these magnetic materials, we captured three common chemotherapy agents-doxorubicin, cisplatin, and epirubicin-from biological solutions. We achieved 98% capture of doxorubicin from human serum in 10 min. We further demonstrate that DNA-coated particles can rescue cultured cardiac myoblasts from lethal levels of doxorubicin. Finally, the in vivo efficacy of these materials was demonstrated in a porcine model. The efficacy of these materials demonstrates the viability of genomic DNA-coated materials as substrates for drug capture applications.

Ruthenium-based olefin metathesis catalysts, known for their functional group tolerance and broad applicability in organic synthesis and polymer science, continue to evolve as an enabling technology in these areas. A discussion of recent mechanistic investigations is followed by an overview of selected applications.

The linear viscoelastic behavior of poly(norbornene)- graft -poly(±-lactide) was investigated as a function of grafting density and overall molar mass. Eight sets of polymers with grafting densities ranging from 0 to 100% were synthesized by living ring-opening metathesis copolymerization. Within each set, the graft chain molar mass and spacing between grafts were fixed, while the total backbone length was varied. Dynamic master curves reveal that these polymers display Rouse and reptation dynamics with a sharp transition in the zero-shear viscosity data, demonstrating that grafting density strongly impacts the entanglement molar mass. The entanglement modulus ( G e ) scales with inverse grafting density ( n g ) as G e ∼ n g 1.2 and G e ∼ n g 0 in accordance with scaling theory in the high and low grafting density limits, respectively. However, a sharp transition between these limiting behaviors occurs, which does not conform to existing theoretical models for graft polymers. A molecular interpretation based on thin flexible chains at low grafting density and thick semiflexible chains at high grafting density anticipates the sharp transition between the limiting dynamical regimes.

Rational design of second-generation ruthenium olefin metathesis catalysts with desired initiation rates can be enabled by a computational model that depends on a single thermodynamic parameter. Using a computational model with no assumption about the specific initiation mechanism, the initiation kinetics of a spectrum of second-generation ruthenium olefin metathesis catalysts bearing modified chelating ortho -alkoxy benzylidenes were predicted in this work. Experimental tests of the validity of the computational model were achieved by the synthesis of a series of ruthenium olefin metathesis catalysts and investigation of initiation rates by UV/Vis kinetics, NMR spectroscopy, and structural characterization by X-ray crystallography. Included in this series of catalysts were thirteen catalysts bearing alkoxy groups with varied steric bulk on the chelating benzylidene, ranging from ethoxy to dicyclohexylmethoxy groups. The experimentally observed initiation kinetics of the synthesized catalysts were in good accordance with computational predictions. Notably, the fast initiation rate of the dicyclohexylmethoxy catalyst was successfully predicted by the model, and this complex is believed to be among the fastest initiating Hoveyda-Grubbs-type catalysts reported to date. The compatibility of the predictive model with other catalyst families, including those bearing alternative NHC ligands or disubstituted alkoxy benzylidenes, was also examined., Competing Interests: The authors declare no competing financial interest.

Second-generation ruthenium olefin metathesis catalysts bearing aminophosphine ligands were investigated with systematic variation of the ligand structure. The rates of phosphine dissociation ( k 1 ; initiation rate) and relative phosphine reassociation ( k -1 ) were determined for two series of catalysts bearing cyclohexyl(morpholino)phosphine and cyclohexyl(piperidino)phosphine ligands. In both cases, incorporating P-N bonds into the architecture of the dissociating phosphine accelerates catalyst initiation relative to the parent [Ru]-PCy 3 complex; however, this effect is muted for the tris(amino)phosphine-ligated complexes, which exhibit higher ligand binding constants in comparison to those with phosphines containing one or two cyclohexyl substituents. These results, along with X-ray crystallographic data and DFT calculations, were used to understand the influence of ligand structure on catalyst activity. Especially noteworthy is the application of phosphines containing incongruent substituents (PR 1 R' 2 ); detailed analyses of factors affecting ligand dissociation, including steric effects, inductive effects, and ligand conformation, are presented. Computational studies of the reaction coordinate for ligand dissociation reveal that ligand conformational changes contribute to the rapid dissociation for the fastest-initiating catalyst of these series, which bears a cyclohexyl-bis(morpholino)phosphine ligand. Furthermore, the effect of amine incorporation was examined in the context of ring-opening metathesis polymerization, and reaction rates were found to correlate well with catalyst initiation rates. The combined experimental and computational studies presented in this report reveal important considerations for designing efficient ruthenium olefin metathesis catalysts.

The synthesis of E -macrocycles is achieved using stereoretentive, Ru-based olefin metathesis catalysts supported by dithiolate ligands. Kinetic studies elucidate marked differences in activity among the catalysts tested, with catalyst 4 providing meaningful yields of products in much shorter reaction times than stereoretentive catalysts 2 and 3 . Macrocycles were generated with excellent selectivity (>99% E ) and in moderate to high yields (47-80% yield) from diene starting materials bearing two E -configured olefins. A variety of rings were constructed, ranging from 12- to 18-membered macrocycles, including the antibiotic recifeiolide.

Ronald Breslow, Samuel Latham Mitchill Professor of Chemistry at Columbia University, passed away on October 25, 2017, at the age of 86. Breslow made remarkable contributions to the fields of physical-organic and bioorganic chemistry, including biological and biomimetic transformations, and the use of molecular recognition to control reaction selectivity., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bottlebrush block copolymers offer rich opportunities for the design of complex hierarchical materials. As consequences of the densely grafted molecular architecture, bottlebrush polymers can adopt highly extended backbone conformations and exhibit unique physical properties. A recent report has described the unusual phase behavior of ABC bottlebrush triblock terpolymers bearing grafted poly( D,L -lactide) (PLA), polystyrene (PS), and poly(ethylene oxide) (PEO) blocks (LSO). In this work, a combination of resonant soft X-ray reflectivity (RSoXR), near edge X-ray absorption fine structure spectroscopy (NEXAFS), and self-consistent field theory (SCFT) was used to provide insight into the phase behavior of LSO and underlying backbone chain conformations. Consistent with SCFT calculations, RSoXR measurements confirm a unique mesoscopic ACBC domain connectivity and decreasing lamellar periods ( d 0 ) with increasing backbone length of the PEO block. RSoXR and NEXAFS demonstrate an additional unusual feature of brush LSO thin films: when the overall film thickness is ~3.25 d 0 , the film-air interface is majority PS (>80%). Since PS is the midblock, the triblocks must adopt looping configurations at the surface, despite the preference for the backbone to be extended. This result is supported by backbone concentrations calculated through SCFT, which suggest that looping midblocks are present throughout the film. Collectively, this work provides evidence for the flexibility of the bottlebrush backbone and the consequences of low- χ block copolymer design. We propose that PEO blocks localize at the PS/PLA domain interfaces in order to screen the highest- χ contacts in the system, driving the formation of loops. These insights introduce a potential route to overcome the intrinsic penalties to interfacial curvature imposed by the bottlebrush architecture, enabling the design of unique self-assembled materials.

Grafting density and graft distribution impact the chain dimensions and physical properties of polymers. However, achieving precise control over these structural parameters presents long-standing synthetic challenges. In this report, we introduce a versatile strategy to synthesize polymers with tailored architectures via grafting-through ring-opening metathesis polymerization (ROMP). One-pot copolymerization of an ω-norbornenyl macromonomer and a discrete norbornenyl comonomer (diluent) provides opportunities to control the backbone sequence and therefore the side chain distribution. Toward sequence control, the homopolymerization kinetics of 23 diluents were studied, representing diverse variations in the stereochemistry, anchor groups, and substituents. These modifications tuned the homopolymerization rate constants over 2 orders of magnitude (0.36 M -1 s -1 < k homo < 82 M -1 s -1 ). Rate trends were identified and elucidated by complementary mechanistic and density functional theory (DFT) studies. Building on this foundation, complex architectures were achieved through copolymerizations of selected diluents with a poly(d,l-lactide) (PLA), polydimethylsiloxane (PDMS), or polystyrene (PS) macromonomer. The cross-propagation rate constants were obtained by nonlinear least-squares fitting of the instantaneous comonomer concentrations according to the Mayo-Lewis terminal model. In-depth kinetic analyses indicate a wide range of accessible macromonomer/diluent reactivity ratios (0.08 < r 1 /r 2 < 20), corresponding to blocky, gradient, or random backbone sequences. We further demonstrated the versatility of this copolymerization approach by synthesizing AB graft diblock polymers with tapered, uniform, and inverse-tapered molecular "shapes." Small-angle X-ray scattering analysis of the self-assembled structures illustrates effects of the graft distribution on the domain spacing and backbone conformation. Collectively, the insights provided herein into the ROMP mechanism, monomer design, and homo- and copolymerization rate trends offer a general strategy for the design and synthesis of graft polymers with arbitrary architectures. Controlled copolymerization therefore expands the parameter space for molecular and materials design.

Grafting density is an important structural parameter that exerts significant influences over the physical properties of architecturally complex polymers. In this report, the physical consequences of varying the grafting density (z) were studied in the context of block polymer self-assembly. Well-defined block polymers spanning the linear, comb, and bottlebrush regimes (0 ≤ z ≤ 1) were prepared via grafting-through ring-opening-metathesis polymerization. ω-Norbornenyl poly(d,l-lactide) and polystyrene macromonomers were copolymerized with discrete comonomers in different feed ratios, enabling precise control over both the grafting density and molecular weight. Small-angle X-ray scattering experiments demonstrate that these graft block polymers self-assemble into long-range-ordered lamellar structures. For 17 series of block polymers with variable z, the scaling of the lamellar period with the total backbone degree of polymerization (d* ∼ N bb α ) was studied. The scaling exponent α monotonically decreases with decreasing z and exhibits an apparent transition at z ≈ 0.2, suggesting significant changes in the chain conformations. Comparison of two block polymer systems, one that is strongly segregated for all z (System I) and one that experiences weak segregation at low z (System II), indicates that the observed trends are primarily caused by the polymer architectures, not segregation effects. A model is proposed in which the characteristic ratio (C ∞ ), a proxy for the backbone stiffness, scales with N bb as a function of the grafting density: C ∞ ∼ N bb f(z) . The scaling behavior disclosed herein provides valuable insights into conformational changes with grafting density, thus introducing opportunities for block polymer and material design.

Milstein's complex, (PNN)RuHCl(CO), catalyzes the efficient reduction of aryl and alkyl halides under relatively mild conditions by using propan-2-ol and a base. Sterically hindered tertiary and neopentyl substrates are reduced efficiently, as well as more functionalized aryl and alkyl bromides. The reduction process is proposed to occur by radical abstraction/hydrodehalogenation steps at ruthenium. Our research represents a safer and more sustainable alternative to typical silane, lithium aluminium hydride, and tin-based conditions for these reductions., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A comprehensive computational study of stereoretentive olefin metathesis with Ru-dithiolate catalysts has been performed. We have determined how the dithiolate ligand enforces a side-bound mechanism and how the side-bound mechanism allows for stereochemical control over the forming olefin. We have used density functional theory (DFT) and ligand steric contour maps to elucidate the origins of stereoretentive metathesis with the goal of understanding how to design a new class of E-selective metathesis catalysts.

A highly efficient, Z-selective ring-closing metathesis system for the formation of macrocycles using a stereoretentive, ruthenium-based catalyst supported by a dithiolate ligand is reported. The catalyst is remarkably active as observed in initiation experiments showing complete catalyst initiation at -20 °C within 10 minutes. Macrocyclization reactions generated Z-products from easily accessible diene starting materials bearing a Z-olefin moiety. This approach provides a more efficient and selective route to Z-macrocycles relative to previously reported systems. Reactions were completed within shorter reaction times, and turnover numbers of up to 100 could be achieved. Macrocyclic lactones ranging in size from twelve- to seventeen-membered rings were synthesized in moderate to high yields (67-79 %) with excellent Z-selectivity (95-99 %)., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Olefin metathesis is an incredibly valuable transformation that has gained widespread use in both academic and industrial settings. Lately, stereoretentive olefin metathesis has garnered much attention as a method for the selective generation of both E- and Z-olefins. Early studies employing ill-defined catalysts showed evidence for retention of the stereochemistry of the starting olefins at low conversion. However, thermodynamic ratios E/Z were reached as the reaction proceeded to equilibrium. Recent studies in olefin metathesis have focused on the synthesis of catalysts that can overcome the inherent thermodynamic preference of an olefin, providing synthetically useful quantities of a kinetically favored olefin isomer. These reports have led to the development of stereoretentive catalysts that not only generate Z-olefins selectively, but also kinetically produce E-olefins, a previously unmet challenge in olefin metathesis. Advancements in stereoretentive olefin metathesis using tungsten, ruthenium, and molybdenum catalysts are presented., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Brush block copolymers are a class of comb polymers that feature polymeric side chains densely grafted to a linear backbone. These polymers display interesting properties due to their dense functionality, low entanglement, and ability to rapidly self-assemble to highly ordered nanostructures. The ability to prepare brush polymers with precise structures has been enabled by advancements in controlled polymerization techniques. This Feature Article highlights the development of brush block copolymers as photonic crystals that can reflect visible to near-infrared wavelengths of light. Fabrication of these materials relies on polymer self-assembly processes to achieve nanoscale ordering, which allows for the rapid preparation of photonic crystals from common organic chemical feedstocks. The characteristic physical properties of brush block copolymers are discussed, along with methods for their preparation. Strategies to induce self-assembly at ambient temperatures and the use of blending techniques to tune photonic properties are emphasized., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Block polymer self-assembly typically translates molecular chain connectivity into mesoscale structure by exploiting incompatible blocks with large interaction parameters (χ ij ). In this article, we demonstrate that the converse approach, encoding low-χ interactions in ABC bottlebrush triblock terpolymers (χ AC [Formula: see text] 0), promotes organization into a unique mixed-domain lamellar morphology, which we designate LAM P Transmission electron microscopy indicates that LAM P exhibits ACBC domain connectivity, in contrast to conventional three-domain lamellae (LAM 3 ) with ABCB periods. Complementary small-angle X-ray scattering experiments reveal a strongly decreasing domain spacing with increasing total molar mass. Self-consistent field theory reinforces these observations and predicts that LAM P is thermodynamically stable below a critical χ AC , above which LAM 3 emerges. Both experiments and theory expose close analogies to ABA' triblock copolymer phase behavior, collectively suggesting that low-χ interactions between chemically similar or distinct blocks intimately influence self-assembly. These conclusions provide fresh opportunities for block polymer design with potential consequences spanning all self-assembling soft materials., Competing Interests: The authors declare no conflict of interest.

We recently reported a new method for the direct dehydrogenative C-H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si-H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with [KOt-Bu] 4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C-Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H 2 gas. In situ NMR experiments with deuterated substrates show that H 2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a 2 H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.

Exploiting C-H bond activation is difficult, although some success has been achieved using precious metal catalysts. Recently, it was reported that C-H bonds in aromatic heterocycles were converted to C-Si bonds by reaction with hydrosilanes under the catalytic action of potassium tert-butoxide alone. The use of Earth-abundant potassium cation as a catalyst for C-H bond functionalization seems to be without precedent, and no mechanism for the process was established. Using ambient ionization mass spectrometry, we are able to identify crucial ionic intermediates present during the C-H silylation reaction. We propose a plausible catalytic cycle, which involves a pentacoordinate silicon intermediate consisting of silane reagent, substrate, and the tert-butoxide catalyst. Heterolysis of the Si-H bond, deprotonation of the heteroarene, addition of the heteroarene carbanion to the silyl ether, and dissociation of tert-butoxide from silicon lead to the silylated heteroarene product. The steps of the silylation mechanism may follow either an ionic route involving K + and t BuO - ions or a neutral heterolytic route involving the [KO t Bu] 4 tetramer. Both mechanisms are consistent with the ionic intermediates detected experimentally. We also present reasons why KO t Bu is an active catalyst whereas sodium tert-butoxide and lithium tert-butoxide are not, and we explain the relative reactivities of different (hetero)arenes in the silylation reaction. The unique role of KO t Bu is traced, in part, to the stabilization of crucial intermediates through cation-π interactions.

Fabrication of functionalized 3D architected materials is achieved by a facile method using functionalized acrylates synthesized via thiol-Michael addition, which are then polymerized using two-photon lithography. A wide variety of functional groups can be attached, from Boc-protected amines to fluoroalkanes. Modification of surface wetting properties and conjugation with fluorescent tags are demonstrated to highlight the potential applications of this technique., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Control over polymer sequence and architecture is crucial to both understanding structure-property relationships and designing functional materials. In pursuit of these goals, we developed a new synthetic approach that enables facile manipulation of the density and distribution of grafts in polymers via living ring-opening metathesis polymerization (ROMP). Discrete endo,exo-norbornenyl dialkylesters (dimethyl DME, diethyl DEE, di-n-butyl DBE) were strategically designed to copolymerize with a norbornene-functionalized polystyrene (PS), polylactide (PLA), or polydimethylsiloxane (PDMS) macromonomer mediated by the third-generation metathesis catalyst (G3). The small-molecule diesters act as diluents that increase the average distance between grafted side chains, generating polymers with variable grafting density. The grafting density (number of side chains/number of norbornene backbone repeats) could be straightforwardly controlled by the macromonomer/diluent feed ratio. To gain insight into the copolymer sequence and architecture, self-propagation and cross-propagation rate constants were determined according to a terminal copolymerization model. These kinetic analyses suggest that copolymerizing a macromonomer/diluent pair with evenly matched self-propagation rate constants favors randomly distributed side chains. As the disparity between macromonomer and diluent homopolymerization rates increases, the reactivity ratios depart from unity, leading to an increase in gradient tendency. To demonstrate the effectiveness of our method, an array of monodisperse polymers (PLA x -ran-DME 1-x ) n bearing variable grafting densities (x = 1.0, 0.75, 0.5, 0.25) and total backbone degrees of polymerization (n = 167, 133, 100, 67, 33) were synthesized. The approach disclosed in this work therefore constitutes a powerful strategy for the synthesis of polymers spanning the linear-to-bottlebrush regimes with controlled grafting density and side chain distribution, molecular attributes that dictate micro- and macroscopic properties.