Search

The controlled radical polymerization of a variety of acrylate monomers is reported using an Ir-catalyzed visible light mediated process leading to well-defined homo-, random, and block copolymers. The polymerizations could be efficiently activated and deactivated using light while maintaining a linear increase in molecular weight with conversion and first order kinetics. The robust nature of the fac-[Ir(ppy)3] catalyst allows carboxylic acids to be directly introduced at the chain ends through functional initiators or along the backbone of random copolymers (controlled process up to 50 mol % acrylic acid incorporation). In contrast to traditional ATRP procedures, low polydispersity block copolymers, poly(acrylate)-b-(acrylate), poly(methacrylate)-b-(acrylate), and poly(acrylate)-b-(methacrylate), could be prepared with no monomer sequence requirements. These results illustrate the increasing generality and utility of light mediated Ir-catalyzed polymerization as a platform for polymer synthesis.

Oxiranes are a class of cyclic ethers formed in abundance during low‐temperature combustion of hydrocarbons and biofuels, either via chain‐propagating steps that occur from unimolecular decomposition of β‐hydroperoxyalkyl radicals (β‐̇QOOH) or from reactions of HOȮ with alkenes. Ethyloxirane is one of four alkyl‐substituted cyclic ether isomers produced as an intermediate from n‐butane oxidation. While rate coefficients for β‐̇QOOH → ethyloxirane + ȮH are reported extensively, subsequent reaction mechanisms of the cyclic ether are not. As a result, chemical kinetics mechanisms commonly adopt simplified chemistry to describe ethyloxirane consumption by convoluting several elementary reactions into a single step, which may introduce mechanism truncation error—uncertainty derived from missing or incomplete chemistry. The present work provides fundamental insight on reaction mechanisms of ethyloxirane in support of ongoing efforts to minimize mechanism truncation error. Reaction mechanisms are inferred from the detection of products during chlorine atom‐initiated oxidation experiments using multiplexed photoionization mass spectrometry conducted at 10 Torr and temperatures of 650 K and 800 K. To complement the experiments, calculations of stationary point energies were conducted using the ccCA‐PS3 composite method on ̇R + O2 potential energy surfaces for the four ethyloxiranyl radical isomers, which produced barrier heights for 24 reaction pathways. In addition to products from ̇QOOH → cyclic ether + ȮH and ̇R + O2 → conjugate alkene + HOȮ, both of which were significant pathways and are prototypical to alkane oxidation, other species were identified from ring‐opening of both ethyloxiranyl and ̇QOOH radicals. The latter occurs when the unpaired electron is localized on the ether group, causing the initial ̇QOOH structure to ring‐open and form a resonance‐stabilized ketohydroperoxide‐type radical. The present work provides the first analysis of ethyloxirane oxidation chemistry, which reveals that consumption pathways are complex and may require an expansion of submechanisms to increase the fidelity of chemical kinetics mechanisms. [ABSTRACT FROM AUTHOR]

Oxiranes are a class of cyclic ethers formed in abundance during low‐temperature combustion of hydrocarbons and biofuels, either via chain‐propagating steps that occur from unimolecular decomposition of β‐hydroperoxyalkyl radicals (β‐̇QOOH) or from reactions of HȮO with alkenes. The cis‐ and trans‐isomers of 2,3‐dimethyloxirane are intermediates of n‐butane oxidation, and while rate coefficients for β‐̇QOOH → 2,3‐dimethyloxirane + ̇OH are reported extensively, subsequent reaction mechanisms of the cyclic ethers are not. As a result, chemical kinetics mechanisms commonly adopt simplified chemistry to describe the consumption of 2,3‐dimethyloxirane by convoluting several elementary reactions into a single step, which may introduce mechanism truncation error—uncertainty derived from missing or incomplete chemistry. The present research examines the isomer dependence of 2,3‐dimethyloxirane reaction mechanisms in support of ongoing efforts to minimize mechanism truncation error. Reaction mechanisms are inferred via the detection of products from Cl‐initiated oxidation of both cis‐2,3‐dimethyloxirane and trans‐2,3‐dimethyloxirane using multiplexed photoionization mass spectrometry (MPIMS). The experiments were conducted at 10 Torr and temperatures of 650 K and 800 K. To complement the experiments, the enthalpies of stationary points on the ̇R + O2 surfaces were computed at the ccCA‐PS3 level of theory. In total, 28 barrier heights were computed on the 2,3‐dimethyloxiranylperoxy surfaces. Two notable aspects are low‐lying pathways that form resonance‐stabilized ketohydroperoxide‐type radicals caused by ̇QOOH ring‐opening when the unpaired electron is localized adjacent to the ether group, and cis‐trans isomerization of ̇R and ̇QOOH radicals, via inversion, which enable reaction pathways otherwise restricted by stereochemistry. Several species were identified in the MPIMS experiments from ring opening of 2,3‐dimethyloxiranyl radicals. Neither of the two conjugate alkene isomers prototypical of ̇R + O2 reactions were detected. Products were also identified from decomposition of ketohydroperoxide‐type radicals. The present work provides the first analysis of 2,3‐dimethyloxirane oxidation chemistry and reveals that consumption pathways are complex and require the expansion of submechanisms in chemical kinetics mechanisms. [ABSTRACT FROM AUTHOR]

Several stopped-flow NMR measurements are conducted to explain the mechanisms involved in the [rac-([C.sub.2][H.sub.4][(1-indenyl).sub.2])ZrMe][MeB[([C.sub.6][F.sub.5]).sub.3]]-catalyzed polymerization of 1-hexene. The different initiation, propagation and termination rate constants exhibited during the process are also determined.

Appropriate evidence-based roles of prognostic and predictive biomarkers of known therapeutic targets in breast, colorectal, and non-small cell lung cancers in adults are reviewed, with summary of evidence for use and recommendation. Current development in biomarker studies is also discussed. Computerized literature searches of PubMed (National Library of Medicine), the Cochrane Collaboration Library, and commonly accepted US and international guidelines (American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network) were performed from 2001 to 2012. Literature published before 2001 was noted for historical interest but not evaluated. Literature review was focused on available systematic reviews and meta-analyses of published predictive (associated with treatment response and/or efficacy) and prognostic (associated with disease outcome) biomarkers of known therapeutic targets in colorectal, breast, and non-small cell lung cancers. In general, significant health outcomes (e.g. predicted response to therapy, overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Four breast cancer biomarkers were evaluated, two of which (2D6 genotyping, Oncotype Dx) were considered emerging with insufficient evidence. Seven colorectal cancer biomarkers were evaluated, five of which (EGFR gene expression, K-ras G13D gene mutation, B-raf V600E gene mutation, dihydropyrimidine dehydrogenase deficiency, and UGT1A1 genotyping) were considered emerging. Seven non-small cell lung cancer biomarkers were evaluated, five of which were emerging (EGFR gene expression, ERCC gene expression, RRM1 gene expression, K-ras gene mutation, and TS gene expression). Of all 18 biomarkers evaluated, the following showed evidence of clinical utility and were recommended for routine use in practice: ER/PR and HER2 for breast cancer; K-ras gene mutation (except G13D gene mutation) for colorectal cancer; mismatch repair deficiency or microsatellite instability for colorectal cancer; and EGFR and EML4-ALK gene mutations for non-small cell lung. Not all recommendations for these biomarkers were uniformly supported by all guidelines. [ABSTRACT FROM PUBLISHER]

Stopped-flow NMR measurements suitable for determination of reaction kinetics on time scales of 100 ms or longer have been achieved by adaptation of a commercial NMR flow probe with a high-efficiency mixer and drive system. Studies of metallocene-catalyzed alkene polymerization at room temperature have been complicated by high rates, imprecise knowledge of the distribution of different catalyst species with time, and the high sensitivity of the catalysts to low concentrations of impurities. Application of the stopped-flow NMR method to the study of the kinetics of 1-hexene polymerization in the presence of (EBI)ZrMe[MeB(C6F5)3] demonstrates that NMR spectroscopy provides an efficient method for direct and simultaneous measurement of substrate consumption and catalyst speciation as a function of time. Kinetic modeling of the catalyst and substrate concentration time courses reveal efficient determination of initiation, propagation, and termination rate constants. As first suggested by Collins and co-workers (Polyhedron 2005, 24, 1234-1249), a kinetic model in which Zr-HB(C6F5)3 forms rapidly upon β-hydride elimination but reacts relatively slowly with alkene to reinitiate chain growth is supported by these data. [ABSTRACT FROM AUTHOR]

Background: Management of hyperglycemia in patients receiving parenteral nutrition (PN) often includes the addition of regular insulin to the PN solution. A literature review has shown insulin availability in such solutions to range from 10% to 95%. This discrepancy in availability may be due to differences in the composition of the PN solution, the final concentration of insulin, or the assay method used to determine insulin concentrations. The purpose of this study was to evaluate insulin recovery from a standard PN solution used at our medical center., Methods: Solutions were manually prepared in our pharmacy according to standard practice. Multivitamins and trace elements were added to 1 of 2 L of solution each day. Each of 3 simulated patients received 2 L of solution per day for 3 consecutive days. Samples from each bottle were drawn at baseline, 1 hour after the start of infusion, and 1 hour before the end of infusion and were subsequently analyzed for immunoreactive insulin levels by radioimmunoassay., Results: Recovery of insulin from solutions containing multivitamins and trace elements was much greater (95%) than from those without (5%)., Conclusions: The presence of multivitamins and trace elements is a major determinant of insulin availability in PN solutions. Additional research is necessary to determine the mechanism mediating this effect and to assess its clinical significance.