Rate constants for the reactions between the simplest Criegee intermediate, CH2OO, with acetone, the α-diketones biacetyl and acetylpropionyl, and the β-diketones acetylacetone and ...3,3-dimethyl-2,4-pentanedione have been measured at 295 K. CH2OO was produced photochemically in a flow reactor by 355 nm laser flash photolysis of diiodomethane in the presence of excess oxygen. Time-dependent concentrations were measured using broadband transient absorption spectroscopy, and the reaction kinetics was characterized under pseudo-first-order conditions. The bimolecular rate constant for the CH2OO + acetone reaction is measured to be (4.1 ± 0.4) × 10–13 cm3 s–1, consistent with previous measurements. The reactions of CH2OO with the β-diketones acetylacetone and 3,3-dimethyl-2,5-pentanedione are found to have broadly similar rate constants of (6.6 ± 0.7) × 10–13 and (3.5 ± 0.8) × 10–13 cm3 s–1, respectively; these values may be cautiously considered as upper limits. In contrast, α-diketones react significantly faster, with rate constants of (1.45 ± 0.18) × 10–11 and (1.29 ± 0.15) × 10–11 cm3 s–1 measured for biacetyl and acetylpropionyl. The potential energy surfaces for these 1,3-dipolar cycloaddition reactions are characterized at the M06-2X/aug-cc-pVTZ and CBS-QB3 levels of theory and provide additional support to the observed experimental trends. The reactivity of carbonyl compounds with CH2OO is also interpreted by application of frontier molecular orbital theory and predicted using Hammett substituent constants. Finally, the results are compared with other kinetic studies of Criegee intermediate reactions with carbonyl compounds and discussed within the context of their atmospheric relevance.
Though there is a growing body of literature on the kinetics of CIs with simple carbonyls, CI reactions with functionalized carbonyls such as hydroxyketones remain unexplored. In this work, the ...temperature-dependent kinetics of the reactions of CH2OO with two hydroxyketones, hydroxyacetone (AcOH) and 4-hydroxy-2-butanone (4H2B), have been studied using a laser flash photolysis transient absorption spectroscopy technique and complementary quantum chemistry calculations. Bimolecular rate constants were determined from CH2OO loss rates observed under pseudo-first-order conditions across the temperature range 275–335 K. Arrhenius plots were linear and yielded T-dependent bimolecular rate constants: k AcOH(T) = (4.3 ± 1.7) × 10–15 exp(1630 ± 120)/T and k 4H2B(T) = (3.5 ± 2.6) × 10–15 exp(1700 ± 200)/T. Both reactions show negative temperature dependences and overall very similar rate constants. Stationary points on the reaction energy surfaces were characterized using the composite CBS-QB3 method. Transition states were identified for both 1,3-dipolar cycloaddition reactions across the carbonyl and 1,2-insertion/addition at the hydroxyl group. The free-energy barriers for the latter reaction pathways are higher by ∼4–5 kcal mol–1, and their contributions are presumed to be negligible for both AcOH and 4H2B. The cycloaddition reactions are highly exothermic and form cyclic secondary ozonides that are the typical primary products of Criegee intermediate reactions with carbonyl compounds. The reactivity of the hydroxyketones toward CH2OO appears to be similar to that of acetaldehyde, which can be rationalized by consideration of the energies of the frontier molecular orbitals involved in the cycloaddition. The CH2OO + hydroxyketone reactions are likely too slow to be of significance in the atmosphere, except at very low temperatures.
Though there is a growing body of literature on the kinetics of CIs with simple carbonyls, CI reactions with functionalized carbonyls such as hydroxyketones remain unexplored. In this work, the ...temperature-dependent kinetics of the reactions of CH
OO with two hydroxyketones, hydroxyacetone (AcOH) and 4-hydroxy-2-butanone (4H2B), have been studied using a laser flash photolysis transient absorption spectroscopy technique and complementary quantum chemistry calculations. Bimolecular rate constants were determined from CH
OO loss rates observed under pseudo-first-order conditions across the temperature range 275-335 K. Arrhenius plots were linear and yielded
-dependent bimolecular rate constants:
(
) = (4.3 ± 1.7) × 10
exp(1630 ± 120)/
and
(
) = (3.5 ± 2.6) × 10
exp(1700 ± 200)/
. Both reactions show negative temperature dependences and overall very similar rate constants. Stationary points on the reaction energy surfaces were characterized using the composite CBS-QB3 method. Transition states were identified for both 1,3-dipolar cycloaddition reactions across the carbonyl and 1,2-insertion/addition at the hydroxyl group. The free-energy barriers for the latter reaction pathways are higher by ∼4-5 kcal mol
, and their contributions are presumed to be negligible for both AcOH and 4H2B. The cycloaddition reactions are highly exothermic and form cyclic secondary ozonides that are the typical primary products of Criegee intermediate reactions with carbonyl compounds. The reactivity of the hydroxyketones toward CH
OO appears to be similar to that of acetaldehyde, which can be rationalized by consideration of the energies of the frontier molecular orbitals involved in the cycloaddition. The CH
OO + hydroxyketone reactions are likely too slow to be of significance in the atmosphere, except at very low temperatures.
Herein, we describe how video games, TV shows, or movies have been used to provide an innovative framework for students to think about chemistry and chemical engineering. The main objective of this ...paper is to show how science can be linked with pop-culture, to provide educators with recent materials to use in classrooms, and to discuss the benefits and limitations of such tools. The video games Fortnite, Spiderman, and Angry Birds, the TV shows Game of Thrones and Breaking Bad, the Marvel movies, and the animated programs Raving Rabbids and Dragon Ball are used to illustrate different approaches to engage with students and encourage them to learn in a more recreational environment.
The photochemistry of glyoxylic acid (HC(O)C(O)OH) is explored in the near UV in both the singlet (S 1/S 0) and triplet (T 1) manifolds using density functional theory (M06-2X/aug-cc-pVTZ) to ...reach an overall mechanistic picture of the atmospherically relevant photochemistry in the gas phase. The calculated energies and structures are also used in RRKM kinetics calculations to compare the relative reaction rates on each of these electronic states. The major photolysis pathways are two possible photodecarboxylation reactions: direct C–C bond cleavage (Norrish Type I reaction) and β-hydrogen transfer followed by CO2 loss. These results indicate that from λ = 350–380 nm both photodecarboxylation pathways can occur following intersystem crossing to the T 1 surface. However, hydrogen transfer–decarboxylation initiated on S 1 becomes increasingly important at λ < 350 nm. At the lower energy UV wavelengths available in the atmosphere (λ = 380–400 nm), reactions can only occur in S 0 where concerted hydrogen transfer–decarboxylation is the dominant dissociation pathway with some minor contributions from CO loss/decarbonylation reactions.
Temperature‐dependent rate constants for the reactions of CH2OO with acetone (Ac), biacetyl (BiAc), and acetylacetone (AcAc) have been measured over the range 275–335 K using a flash photolysis, ...transient absorption spectroscopy technique. The measurements were performed at a total pressure of ∼80 Torr in N2 bath gas, which corresponds to the high‐pressure limit for these reactions. All three reactions show linear Arrhenius plots with negative temperature dependences. Rate constants increase in the order Ac < AcAc « BiAc across the temperature range; at 295 K the rate constants are kAc = (4.8 ± 0.4) × 10–13 cm3 s–1, kAcAc = (8.0 ± 0.7) × 10–13 cm3 s–1, and kBiAc = (1.10 ± 0.09) × 10–11 cm3 s–1. Sensitivity to temperature, characterized by the magnitude of the negative activation energy, increases in the order AcAc < BiAc < Ac (Ea/R values of –1830 ± 170 K, –1260 ± 170 K, and –460 ± 180 K, respectively). CBS‐QB3 calculations show that the Ac and BiAc reactions proceed via formation of an entrance channel complex followed by 1,3‐dipolar cycloaddition to form secondary ozonide products via a submerged transition state. For the BiAc reaction, the rate limiting step appears to be rearrangement of a long‐range van der Waals complex into the short‐range complex that subsequently leads directly to the cycloaddition transition state with a very low energy barrier. The calculations show that two reaction pathways are competitive for AcAc with nearly identical transition state free energies (ΔG° = +10.1 kcal mol–1 at 298 K) found for cycloaddition at the C=O and at the C=C site of the dominant enolone tautomer. The weak temperature dependence observed is likely due to competition between these pathways.
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•Phase imaging technique used to identify areas on surfaces where water accumulates.•Water accumulation was confirmed by direct force measurements with AFM.•Adhesion forces were ...quantified as a function of RH.•The effect of RH on adhesion force was attributed to hydrogen bonding.
Atomic force microscopy (AFM) was used to investigate the effect of relative humidity (RH) on the adhesion forces between silicon nitride AFM probes, hydrophilic stainless steel, and hydrophobic Perspex® (polymethylmethacrylate, PMMA). In addition, AFM-based phase contrast imaging was used to quantify the amount and location of adsorbed water present on these substrates at RH levels ranging from 15% to 65% at 22°C. Both the adhesion forces and the quantities of adsorbed moisture were seen to vary with RH, and the nature of this variation depended on the hydrophobicity of the substrate. For the Perspex®, both the adhesion force and the amount of adsorbed moisture were essentially independent of RH. For the stainless steel substrate, adsorbed moisture increased continuously with increasing RH, while the adhesion force rose from a minimum at 15% RH to a broad maximum between 25% and 35% RH. From 35% to 55% RH, the adhesion force dropped continuously to an intermediate level before rising again as 65% RH was approached. The changes in adhesion force with increasing relative humidity in the case of the stainless steel substrate were attributed to a balance of effects associated with adsorbed, sub-continuum water on the cantilever and steel. Hydrogen bonding interactions between these adsorbed water molecules were thought to increase the adhesion force. However, when significant quantities of molecular water adsorbed, these molecules were expect to decrease adhesion by screening the van der Waals interactions between the steel and the cantilever tip, and by increasing the separation distance between these solid surfaces when they were 'in contact'. Finally, the slight increase in adhesion between 55% and 65% RH was attributed to true capillary forces exerted by continuum water on the two solid surfaces.
Rapid advances in immunotherapy have identified adoptive cell transfer as one of the most promising approaches for the treatment of cancers. Large numbers of cancer reactive T lymphocytes can be ...generated ex vivo from patient blood by genetic modification to express chimeric antigen receptors (CAR) specific for tumor-associated antigens. CAR T cells can respond strongly against cancer cells, and adoptive transferred CAR T cells can induce dramatic responses against certain types of cancers. The ability of T cells to respond against disease depends on their ability to localize to sites, persist and exert functions, often in an immunosuppressive microenvironment, and these abilities are reflected in their phenotypes. There is currently intense interest in generating CAR T cells possessing the ideal phenotypes to confer optimal antitumor activity. In this article, we review T cell phenotypes for trafficking, persistence and function, and discuss how culture conditions and genetic makeups can be manipulated to achieve the ideal phenotypes for antitumor activities.
To study thermal desulfurization of pyrite (FeS2), we conducted in situ neutron diffraction experiments in the temperature range 298–1073 K. On heating, pyrite remained stable up to 773 K, at which ...it started to decompose into pyrrhotite (Fe1−xS) and S2 gas. Rietveld analysis of the neutron data from 298 to 773 K allowed determination of the thermal expansion coefficient of pyrite (space group Pa$\bar 3$) to be αV = 3.7456 × 10−5 K−1, which largely results from the expansion of the Fe–S bond. With further increase in temperature to 1073 K, all the pyrite transformed to pyrrhotite (Fe1−xS) at 873 K. Unit-cell parameters of Fe1−xS (space group P63/mmc) increase on heating and decrease on cooling. However, the rates in cell expansion are larger than those in contraction. This hysteresis behavior can be attributed to continuous desulfurization of pyrrhotite (i.e., x in Fe1−xS decreases) with increasing temperature until the stoichiometric troilite (FeS) was formed at 1073 K. On cooling, troilite underwent a magnetic transition to an orthorhombic structure (space group Pnma) between 473 and 573 K. In addition, using differential thermal analysis (DTA) and thermogravimetric analysis (TGA) implemented with a differential scanning calorimeter, we performed kinetic measurements of pyrite decomposition. Detailed peak profile and Arrhenius (k = A exp(−Ea/RT)) analyses yielded an activation energy Ea of 302.3 ± 28.6 kJ/mol (based on DTA data) or 302.5 ± 26.4 kJ/mol (based on TGA data) and a ln(A) of 35.3 ± 0.1.
In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human ...pancreatic cancer xenograft model.
We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano).
The combination treatment enabled significant suppression of Her2
pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice.
We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano.
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