Simulation of the VUV Absorption Spectra of Oxygenates and Hydrocarbons: A Joint Theoretical-Experimental Study.

Vacuum UV absorption spectroscopy is regularly used to provide unambiguous identification of a target species, insight into the electronic structure of molecules, and quantitative species concentrations. As molecules of interest have become more complex, theoretical spectra have been used in tandem with laboratory spectroscopic analysis or as a replacement when experimental data is unavailable. However, it is difficult to determine which theoretical methodologies can best simulate experiment. This study examined the performance of EOM-CCSD and 10 TD-DFT functionals (B3LYP, BH&HLYP, BMK, CAM-B3LYP, HSE, M06-2X, M11, PBE0, ωB97X-D, and X3LYP) to produce reliable vacuum UV absorption spectra for 19 small oxygenates and hydrocarbons using vertical excitation energies. The simulated spectra were analyzed against experiment using both a qualitative analysis and quantitative metrics, including cosine similarity, relative integral change, mean signed error, and mean absolute error. Based on our ranking system, it was determined that M06-2X was consistently the top performing TD-DFT method with BMK, CAM-B3LYP, and ωB97X-D also producing reliable spectra for these small combustion species.

Solution-Phase Conformational/Vibrational Anharmonicity in Comonomer Incorporation Polyolefin Catalysis.

The prediction of comonomer incorporation statistics in polyolefin catalysis necessitates an accurate calculation of free energies corresponding to monomer binding and insertion, often requiring sub-kcal/mol resolution to resolve experimental free energies. Batch reactor experiments are used to probe incorporation statistics of ethene and larger α-olefins for three constrained geometry complexes which are employed as model systems. Herein, over 6 ns of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics is performed in combination with the zero-temperature string method to characterize the solution-phase insertion barrier and to analyze the contributions from conformational and vibrational anharmonicity arising both in vacuum and in solution. Conformational sampling in the solution-phase results in 0-2 kcal/mol corrections to the insertion barrier which are on the same scale necessary to resolve experimental free energies. Anharmonic contributions from conformational sampling in the solution phase are crucial energy contributions missing from static density functional theory calculations and implicit solvation models, and the accurate calculation of these contributions is a key step toward the quantitative prediction of comonomer incorporation statistics.

Unexpected Precatalyst σ-Ligand Effects in Phenoxyimine Zr-Catalyzed Ethylene/1-Octene Copolymerizations.

Recent decades have witnessed intense research efforts aimed at developing new homogeneous olefin polymerization catalysts, with a primary focus on metal-Cl or metal-hydrocarbyl precursors. Curiously, metal-NR2 precursors have received far less attention. In this contribution, the Zr-amido complex FI2ZrX2 (FI = 2,4-di- tert-butyl-6-((isobutylimino)methyl)phenolate, X = NMe2) is found to exhibit high ethylene polymerization activity and relatively high 1-octene coenchainment selectivity (up to 7.2 mol%) after sequential activation with trimethylaluminum, then Ph3C+B(C6F5)4-. In sharp contrast, catalysts with traditional hydrocarbyl ligands such as benzyl and methyl give low 1-octene incorporation (0-1.0 mol%). This unexpected selectivity persists under scaled/industrial operating conditions and was previously inaccessible with traditional metal-Cl or -hydrocarbyl precursors. NMR, X-ray diffraction, and catalytic control experiments indicate that in this case an FI ligand is abstracted from FI2Zr(NMe2)2 by trimethylaluminum in the activation process to yield a catalytically active cationic mono-FIZr species. Heretofore this process was believed to serve only as a major catalyst deactivation pathway to be avoided. This work demonstrates the importance of investigating diverse precatalyst monodentate σ-ligands in developing new catalyst systems, especially for group 4 olefin polymerization catalysts.

Influence of the Ether Functional Group on Ketohydroperoxide Formation in Cyclic Hydrocarbons: Tetrahydropyran and Cyclohexane.

Photolytically initiated oxidation experiments were conducted on cyclohexane and tetrahydropyran using multiplexed photoionization mass spectrometry to assess the impact of the ether functional group in the latter species on reaction mechanisms relevant to autoignition. Pseudo-first-order conditions, with [O2]0:[R•]0 > 2000, were used to ensure that R• + O2 → products were the dominant reactions. Quasi-continuous, tunable vacuum ultraviolet light from a synchrotron was employed over the range 8.0-11.0 eV to measure photoionization spectra of the products at two pressures (10 and 1520 Torr) and three temperatures (500, 600, and 700 K). Photoionization spectra of ketohydroperoxides were measured in both species and were qualitatively identical, within the limit of experimental noise, to those of analogous species formed in n-butane oxidation. However, differences were noted in the temperature dependence of ketohydroperoxide formation between the two species. Whereas the yield from cyclohexane is evident up to 700 K, ketohydroperoxides in tetrahydropyran were not detected above 650 K. The difference indicates that reaction mechanisms change due to the ether group, likely affecting the requisite •QOOH + O2 addition step. Branching fractions of nine species from tetrahydropyran were quantified with the objective of determining the role of ring-opening reactions in diminishing ketohydroperoxide. The results indicate that products formed from unimolecular decomposition of R• and •QOOH radicals via concerted C-C and C-O ß-scission are pronounced in tetrahydropyran and are insignificant in cyclohexane oxidation. The main conclusion drawn is that, under the conditions herein, ring-opening pathways reduce the already low steady-state concentration of •QOOH, which in the case of tetrahydropyran prevents •QOOH + O2 reactions necessary for ketohydroperoxide formation. Carbon balance calculations reveal that products from ring opening of both R• and •QOOH, at 700 K, account for >70% at 10 Torr and >55% at 1520 Torr. Three pathways are confirmed to contribute to the depletion of •QOOH in tetrahydropyran including (i) γ-•QOOH → pentanedial + •OH, (ii) γ-•QOOH → vinyl formate + ethene + •OH, and (iii) γ-•QOOH → 3-butenal + formaldehyde + •OH. Analogous mechanisms in cyclohexane oxidation leading to similar intermediates are compared and, on the basis of mass spectral results, confirm that no such ring-opening reactions occur. The implication from the comparison to cyclohexane is that the ether group in tetrahydropyran increases the propensity for ring-opening reactions and inhibits the formation of ketohydroperoxide isomers that precede chain-branching. On the contrary, the absence of such reactions in cyclohexane enables ketohydroperoxide formation up to 700 K and perhaps higher temperature.

Treatment Prices at the Point of Care in a Clinical Oncology Service: Pilot Project.

PURPOSE: Patients with cancer increasingly wish to discuss cancer care costs with clinicians. We aimed to improve clinician access to treatment prices. METHODS: We developed a pilot tool and accompanying workflow for four oncology clinics in an integrated care system. The online tool included 50 printable worksheets for cancer treatment protocols and was accessible directly from the electronic health record. Each sheet included codes and prices for all drugs and services for one treatment cycle in patient-friendly language. The worksheets did not provide patient-level cost-shares. We evaluated the resource's launch, initial use, and acceptability through a convenience survey of initial users. RESULTS: The project was successfully launched. Initial Web traffic to price sheets exceeded the number of treatments ordered during the launch period. One third of survey respondents reported use of the cost sheets at least once a week. The most useful features were improved access to cost information, treatment protocol-based layout, and ability to meet patient needs. The resource was rated as generally high value to patients, staff, and the organization. Suggested improvements included provision of patient-level cost sharing (63%) followed by expansion of the project to include more protocols (33%). These improvements are in progress. CONCLUSION: The pilot was feasible, built capacity to locate price data, and did not adversely affect staff workload. It addressed a clear need and demonstrated high potential overall value, especially with its protocol-based format. The resource's lack of personalized estimates of out-of-pocket charges was the biggest gap reported.

Enhanced Block Copolymer Phase Separation Using Click Chemistry and Ionic Junctions.

In addition to the traditional parameters of chi (χ) and degree of polymerization (N), we demonstrate that the segregation strength of a diblock copolymer can be increased by introduction of an ionic unit at the junction of the two blocks. Compared to neutral linking groups, the electrostatic interactions between counterions of adjacent domain junctions leads to increased enthalpy, segregation strength, and phase separation. As a result, the order disorder transition temperatures of block copolymers with a 1,2,3-triazolium ionic junction were observed to be significantly higher than the corresponding neutral block copolymers. To demonstrate the potential of block copolymers with ionic junctions for nanopatterning, block copolymers were prepared by click coupling of homopolymers and then used to fabricate well-defined sub-10 nm line features. We believe that the concept of improved thin-film assembly through the introduction of ionic junctions is a powerful tool for block copolymer lithography and complements chi (χ) and degree of polymerization (N) in the design of macromolecular systems with enhanced phase separation.

Predictive and prognostic biomarkers with therapeutic targets in breast, colorectal, and non-small cell lung cancers: a systemic review of current development, evidence, and recommendation.

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.

Controlled Radical Polymerization of Acrylates Regulated by Visible Light.

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.

Stopped-flow NMR: determining the kinetics of [rac-(C2H4(1-indenyl)2)ZrMe][MeB(C6F5)3]-catalyzed polymerization of 1-hexene by direct observation.

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(C(6)F(5))(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(C(6)F(5))(3) forms rapidly upon beta-hydride elimination but reacts relatively slowly with alkene to reinitiate chain growth is supported by these data.

Metallocene-catalyzed alkene polymerization and the observation of Zr-allyls.

Single-site polymerization catalysts enable exquisite control over alkene polymerization reactions to produce new materials with unique properties. Knowledge of catalyst speciation and fundamental kinetics are essential for full mechanistic understanding of zirconocene-catalyzed alkene polymerization. Currently the effect of activators on fundamental polymerization steps is not understood. Progress in understanding activator effects requires determination of fundamental kinetics for zirconocene catalysts with noncoordinating anions such as [B(C6F5)4]-. Kinetic NMR studies at low temperature demonstrate a very fast propagation rate for 1-hexene polymerization catalyzed by [(SBI)Zr(CH2SiMe3)][B(C6F5)4] [where SBI is rac-Me2Si(indenyl)2] with complete consumption of 1-hexene before the first NMR spectrum. Surprisingly, the first NMR spectrum reveals, aside from uninitiated catalyst, Zr-allyls as the sole catalyst-containing species. These Zr-allyls, which exist in two diastereomeric forms, have been characterized by physical and chemical methods. The mechanism of Zr-allyl formation was probed with a trapping experiment, leading us to favor a mechanism in which Zr-polymeryl undergoes beta-H transfer to metal without dissociation of coordinated alkene followed by sigma-bond metathesis to form H2 and Zr-allyl. Zr-allyl species undergo slow reactions with alkene but react rapidly with H2 to form hydrogenation products.

Determinants of insulin availability in parenteral nutrition solutions.

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.