Surface Modification of Titania Nanoparticles Using Ultrathin Ceramic Films

Surface modification of titania nanoparticles was achieved by coating them with ultrathin alumina films using atomic layer deposition. The coating process was performed in a fluidized bed reactor at low pressure and under mechanical vibration. Films were deposited using self-limiting, sequential surface reactions of trimethylaluminum and water. The composition of alumina-coated particles was verified using infrared spectroscopy. The deposited films had an average growth rate of 0.2 nm/coating cycle and were highly uniform and conformal as demonstrated by transmission electron microscopy and X-ray spectroscopy. Deposited alumina films were amorphous as verified through X-ray diffraction and high-resolution electron microscopy. The coating process did not promote particle sintering as validated via particle size and surface area analysis.     

Identification, Synthesis, and Field Testing of the Sex Pheromone of the Citrus Leafminer, Phyllocnistis citrella

The citrus leafminer is an important vector of citrus canker in many of the major citrus production areas of the world. (7Z,11Z)-Hexadecadienal was reported as a sex attractant for this insect in the 1980s, based on trap catches during pheromone screening trials in Japan. However, attempts to reproduce this work in other areas of the world have not been successful. We report here that (7Z,11Z)-hexadecadienal is only one component of the pheromone, with the other critical component being the analogous trienal, (7Z,11Z,13E)-hexadecatrienal. Both compounds were identified in the effluvia from live female moths by coupled gas chromatography (GC)-electroantennography using nonpolar and polar GC columns, and the identifications were confirmed by comparisons of mass spectra with those of authentic standards. Stereoisomers of the two compounds, and a number of analogs, were synthesized to confirm the identifications. In field trials, neither compound alone was attractive to male moths, but blends of the two were highly attractive, with thousands of insects being caught per trial. Addition of the isomeric (7Z,11Z,13Z)-hexadecatrienal inhibited attraction to the two-component blend. Electronic Supplementary Material Supplementary material is available for this article at and accessible for authorized users. This paper and the preceding paper (Leal et al.) were submitted within a few days of each other. The editors and the authors agreed that they should be published in tandem.     

Prediction of Experimental Methanol Decomposition Rates on Platinum from First Principles

A microkinetic model for methanol decomposition on platinum is presented. The model incorporates competitive decomposition pathways, beginning with both O–H and C–H bond scission in methanol, and uses results from density functional theory (DFT) calculations [Greeley and Mavrikakis, J. Am. Chem. Soc. 124 (2002) 7193, Greeley and Mavrikakis, J. Am. Chem. Soc. 126 (2004) 3910]. Results from reaction kinetics experiments show that the rate of H₂ production increases with increasing temperature and methanol concentration in the feed and is only nominally affected by the presence of CO or H₂ with methanol. The model, based on the values of binding energies, pre-exponential factors and activation energy barriers derived from first principles calculations, accurately predicts experimental reaction rates and orders. The model also gives insight into the most favorable reaction pathway, the rate-limiting step, the apparent activation energy, coverages, and the effects of pressure. It is found that the pathway beginning with the C–H bond scission (CH₃OH→H₂COH→HCOH→CO) is dominant compared with the path beginning with O–H bond scission. The cleavage of the first C–H bond in methanol is the rate-controlling step. The surface is highly poisoned by CO, whereas COH appears to be a spectator species.     

Rheological study of the curing kinetics of epoxy–phenol novolac resin

The curing reaction of an epoxy–phenolic resin under different conditions was monitored using rheological measurements. The evolution of viscoelastic properties, such as storage modulus, G′, and loss modulus, G″, was recorded. Several experiments were performed to confidently compare the rheological data obtained under varied curing conditions of temperature, catalyst concentration, and reactive ratios. The values of G′ measured at the end of the reactions (at maximum conversion) were independent of the frequency and temperature of the tests in the range of high temperatures investigated. The overall curing process was described by a second‐order phenomenological rheokinetic equation based on the model of Kamal. The effects of the epoxy‐to‐phenolic ratio as well as the curing temperature and the catalyst concentration were also investigated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4430–4439, 2006     

Performance of tocopherols as antioxidants in ABS

Mixed tocopherols, γ‐tocopherol, and δ‐tocopherol were evaluated for antioxidant performance in acrylonitrile–butadiene–styrene by using oxidative induction time as the response. Three commonly used phenolic antioxidants and vitamin E (α‐tocopherol) were used as controls. Mixed tocopherols were found to have a greater antioxidant effect than the hindered phenolic antioxidants or vitamin E in acrylonitrile–butadiene–styrene. γ‐tocopherol was found to be primarily responsible for the improved performance of mixed tocopherols. J. VINYL. ADDIT. TECHNOL. 12:66–72, 2006. © 2006 Society of Plastics Engineers     

Antioxidant performance of mixed tocopherols in styrenic block copolymers

Mixed tocopherols (MT) containing a predominance of γ‐tocopherol were evaluated for antioxidant (AO) performance in polybutadiene‐ and polyisoprene‐based styrenic block copolymers (SBS and SIS, respectively) by using oxidative induction time as a measure of AO performance. A conventional hindered phenolic AO and α‐tocopherol (vitamin E) were evaluated in comparison. MT exhibited significantly higher performance than the controls in both SIS and SBS polymers. J. VINYL ADDIT. TECHNOL., 12:73–77, 2006. © 2006 Society of Plastics Engineers     

Automated self seeding of batch crystallizations via plug flow seed generation

In this study, seed slurry from a single addition anti-solvent plug flow crystallization of benzoic acid was used to seed the equivalent batch cooling crystallization. The experimental conditions were carried out to simulate automated self-seeding. This involves withdrawal of solution from a batch crystallizer, which is then mixed with anti-solvent within a plug flow crystallizer, in order to generate a seed slurry which is fed directly back to the batch crystallizer. This seeding strategy allowed the final CSD of the batch crystallization to be controlled by variation of the crystal size from the plug flow seeding device at a constant seed loading. The ability to use unequal feed/anti-solvent inlet flowrates (in the Roughton vortex mixer) proved effective in controlling the batch CSD at 2% seed loading and constant feed composition.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Catalytic Molecular Logic Devices by DNAzyme Displacement

Chemical reactions catalyzed by DNAzymes offer a route to programmable modification of biomolecules for therapeutic purposes. To this end, we have developed a new type of catalytic DNA‐based logic gates in which DNAzyme catalysis is controlled via toehold‐mediated strand displacement reactions. We refer to these as DNAzyme displacement gates. The use of toeholds to guide input binding provides a favorable pathway for input recognition, and the innate catalytic activity of DNAzymes allows amplification of nanomolar input concentrations. We demonstrate detection of arbitrary input sequences by rational introduction of mismatched bases into inhibitor strands. Furthermore, we illustrate the applicability of DNAzyme displacement to compute logic functions involving multiple logic gates. This work will enable sophisticated logical control of a range of biochemical modifications, with applications in pathogen detection and autonomous theranostics.     

Discovery of 5′′‐Chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064): A Selective Orexin 2 Receptor Antagonist (2‐SORA) for the Treatment of Insomnia

The field of small‐molecule orexin antagonist research has evolved rapidly in the last 15 years from the discovery of the orexin peptides to clinical proof‐of‐concept for the treatment of insomnia. Clinical programs have focused on the development of antagonists that reversibly block the action of endogenous peptides at both the orexin 1 and orexin 2 receptors (OX₁R and OX₂R), termed dual orexin receptor antagonists (DORAs), affording late‐stage development candidates including Merck’s suvorexant (new drug application filed 2012). Full characterization of the pharmacology associated with antagonism of either OX₁R or OX₂R alone has been hampered by the dearth of suitable subtype‐selective, orally bioavailable ligands. Herein, we report the development of a selective orexin 2 antagonist (2‐SORA) series to afford a potent, orally bioavailable 2‐SORA ligand. Several challenging medicinal chemistry issues were identified and overcome during the development of these 2,5‐disubstituted nicotinamides, including reversible CYP inhibition, physiochemical properties, P‐glycoprotein efflux and bioactivation. This article highlights structural modifications the team utilized to drive compound design, as well as in vivo characterization of our 2‐SORA clinical candidate, 5′′‐chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064), in mouse, rat, dog, and rhesus sleep models.