The electrochemical characterization of brush polymer ion gels containing embedded small-molecule redox-active species is reported. Gels comprising PS-PEO-PS triblock brush polymer, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIm-TFSI), and some combination of ferrocene (Fc), cobaltocenium (CoCp), and Re(bpy)(CO)Cl (1) exhibit diffusion-controlled redox processes with diffusion coefficients approximately one-fifth of those observed in neat BMIm-TFSI. Notably, 1 dissolves homogeneously in the interpenetrating matrix domain of the ion gel and displays electrocatalytic CO reduction to CO in the gel. The catalytic wave exhibits a positive shift versus Fc compared with analogous nonaqueous solvents with a reduction potential 450 mV positive of onset and 90% Faradaic efficiency for CO production. These materials provide a promising and alternative approach to immobilized electrocatalysis, creating numerous opportunities for application in solid-state devices.
McNicholas Brendon J. James Blakemore Chang Alice B. Bates Christopher M. Kramer Robert H.Grubbs Harry Gray
Journal of the American Chemical Society
2016
The microstructures of polymers produced by ring-opening metathesis polymerization (ROMP) with cyclometalated Ru-carbene metathesis catalysts were investigated. A strong bias for a cis,syndiotactic microstructure with minimal head-to-tail bias was observed. In instances where trans errors were introduced, it was determined that these regions were also syndiotactic. Furthermore, hypothetical reaction intermediates and transition structures were analyzed computationally. Combined experimental and computational data support a reaction mechanism in which cis,syndio-selectivity is a result of stereogenic metal control, while microstructural errors are predominantly due to alkylidene isomerization via rotation about the Ru=C double bond.
Rosebrugh Lauren E. Ahmed Tonia Marx Vanessa M. Hartung John Liu López Kendall Houk Robert H.Grubbs
Journal of the American Chemical Society
2016
A tandem olefin metathesis/oxidative cyclization has been developed to synthesize 2,5-disubstituted tetrahydrofuran (THF) diols in a stereocontrolled fashion from simple olefin precursors. The ruthenium metathesis catalyst is converted into an oxidation catalyst in the second step and is thus responsible for both catalytic steps. The stereochemistry of the 1,5-diene intermediate can be controlled through the choice of catalyst and the type of metathesis conducted. This olefin stereochemistry then controls the THF diol stereochemistry through a highly stereospecific oxidative cyclization.
Dornan Peter K. Lee Daniel Robert H.Grubbs
Journal of the American Chemical Society
2016
A tandem S
Koy Maximilian Keary Engle Lawrence Henling Takase Michael K. Robert H.Grubbs
Organic Letters
2015
A three-step procedure has been developed for preparing ortho-alkoxybenzaldehydes from ortho-fluorobenzaldehydes that tolerates the use of sterically hindered sodium alkoxide nucleophiles. The protocol is modular and operationally convenient. The ortho-alkoxybenzaldehyde products can be converted in one additional step to ortho-alkoxystyrenes by a Wittig reaction. These styrenes are precursors to the chelating benzylidene moiety in a proposed series of novel ruthenium complexes for use in olefin metathesis. Chelation with three representative styrenes has been demonstrated.
Keary Engle Luo Shao-Xiong Robert H.Grubbs
Journal of Organic Chemistry
2015
Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine.
Ramaswamy Krishna Marx Vanessa M. Laser Daniel Thomas Kenny Chi Thomas Bailey Michael R. Sorensen Mathew D Robert H.Grubbs Stoller Marshall L.
BJU International
2015
Chemotherapy often involves broad-spectrum cytotoxic agents with many side effects and limited targeting. Corroles are a class of tetrapyrrolic macrocycles that exhibit differential cytostatic and cytotoxic properties in specific cell lines, depending on the identities of the chelated metal and functional groups. The unique behavior of functionalized corroles towards specific cell lines introduces the possibility of targeted chemotherapy. Many anticancer drugs are evaluated by their ability to inhibit RNA transcription. Here we present a step-by-step protocol for RNA transcription in the presence of known and potential inhibitors. The evaluation of the RNA products of the transcription reaction by gel electrophoresis and UVVis spectroscopy provides information on inhibitive properties of potential anticancer drug candidates and, with modifications to the assay, more about their mechanism of action. Little is known about the molecular mechanism of action of corrole cytotoxicity. In this experiment, we consider two corrole compounds: gallium(III) 5,10,15-(tris)pentafluorophenylcorrole (Ga(tpfc)) and freebase analogue 5,10,15-(tris)pentafluorophenylcorrole (tpfc). An RNA transcription assay was used to examine the inhibitive properties of the corroles. Five transcription reactions were prepared: DNA treated with Actinomycin D, triptolide, Ga(tpfc), tpfc at a [complex]:[template DNA base] ratio of 0.01, respectively, and an untreated control. The transcription reactions were analyzed after 4 hr using agarose gel electrophoresis and UV-Vis spectroscopy. There is clear inhibition by Ga(tpfc), Actinomycin D, and triptolide. This RNA transcription assay can be modified to provide more mechanistic detail by varying the concentrations of the anticancer complex, DNA, or polymerase enzyme, or by incubating the DNA or polymerase with the complexes prior to RNA transcription; these modifications would differentiate between an inhibition mechanism involving the DNA or the enzyme. Adding the complex after RNA transcription can be used to test whether the complexes degrade or hydrolyze the RNA. This assay can also be used to study additional anticancer candidates.
Tang Grace Y. Pribisko Melanie A. Henning Ryan K. Lim Punnajit Termini John Harry Gray Robert H.Grubbs
Journal of Visualized Experiments
2015
Chemotherapy often involves broad-spectrum cytotoxic agents with many side effects and limited targeting. Corroles are a class of tetrapyrrolic macrocycles that exhibit differential cytostatic and cytotoxic properties in specific cell lines, depending on the identities of the chelated metal and functional groups. The unique behavior of functionalized corroles towards specific cell lines introduces the possibility of targeted chemotherapy. Many anticancer drugs are evaluated by their ability to inhibit RNA transcription. Here we present a step-by-step protocol for RNA transcription in the presence of known and potential inhibitors. The evaluation of the RNA products of the transcription reaction by gel electrophoresis and UV-Vis spectroscopy provides information on inhibitive properties of potential anticancer drug candidates and, with modifications to the assay, more about their mechanism of action. Little is known about the molecular mechanism of action of corrole cytotoxicity. In this experiment, we consider two corrole compounds: gallium(III) 5,10,15-(tris)pentafluorophenylcorrole (Ga(tpfc)) and freebase analogue 5,10,15-(tris)pentafluorophenylcorrole (tpfc). An RNA transcription assay was used to examine the inhibitive properties of the corroles. Five transcription reactions were prepared: DNA treated with Actinomycin D, triptolide, Ga(tpfc), tpfc at a [complex]:[template DNA base] ratio of 0.01, respectively, and an untreated control. The transcription reactions were analyzed after 4 hr using agarose gel electrophoresis and UV-Vis spectroscopy. There is clear inhibition by Ga(tpfc), Actinomycin D, and triptolide. This RNA transcription assay can be modified to provide more mechanistic detail by varying the concentrations of the anticancer complex, DNA, or polymerase enzyme, or by incubating the DNA or polymerase with the complexes prior to RNA transcription; these modifications would differentiate between an inhibition mechanism involving the DNA or the enzyme. Adding the complex after RNA transcription can be used to test whether the complexes degrade or hydrolyze the RNA. This assay can also be used to study additional anticancer candidates.
Tang Grace Y. Pribisko Melanie A. Henning Ryan K. Lim Punnajit Termini John Harry Gray Robert H.Grubbs
Journal of visualized experiments : JoVE
2015
Abstract: A stereoselective synthesis of anti-1,2-diols has been developed using a multitasking Ru catalyst in an assisted tandem catalysis protocol. A cyclometalated Ru complex catalyzes first a Z-selective cross-metathesis of two terminal olefins, followed by a stereospecific dihydroxylation. Both steps are catalyzed by Ru, as the Ru complex is converted to a dihydroxylation catalyst upon addition of NaIO. A variety of olefins were transformed into valuable, highly functionalized, and stereodefined molecules. Mechanistic experiments were performed to probe the nature of the oxidation step and catalyst inhibition pathways. These experiments point the way to more broadly applicable tandem catalytic transformations. Two steps with one cat.: 1,2-anti-Diols are accessible through a tandem Z-selective cross-metathesis/dihydroxylation using an assisted tandem catalysis protocol. Both steps are catalyzed by the Ru complex, and the stereocontrol of the cross-metathesis is translated through high stereospecificity in the dihydroxylation step to diastereoselectivity for the 1,2-anti-diol.
Dornan Peter K. Wickens Zachary K. Robert H.Grubbs
Angewandte Chemie - International Edition
2015
The synthesis, self-assembly, conductivity, and rheological properties of ABA triblock brush polymers (BBCPs) with grafted polystyrene (A block, N
Bates Christopher M. Chang Alice B. Momčilović Nebojša Jones Simon C. Robert H.Grubbs
Macromolecules
2015