Temperature dependence of the 1H chemical shift of tetramethylsilane in chloroform, methanol, and dimethylsulfoxide

The chemical shift of tetramethylsilane (TMS) is usually taken to be zero. However, it does vary slightly with temperature, having obvious implications for studies of temperature effects on chemical shifts. In this work, we measure the variation in the chemical shift of TMS with temperature in three solvents, CDCl3, CD3OD, and DMSO-d6, relative to the resonant frequency of 3He gas, which can be reasonably assumed to be temperature independent. In all three solvents, the average temperature coefficient over a wide temperature range is about -6 x 10(-4) ppm/degrees C, a factor of five smaller than that previously reported in the literature. Data are included for 3He resonance frequencies over a temperature range of -110 to +180 degrees C, along with new measurements of volume magnetic susceptibilities of the three solvents and estimates of their temperature dependence. A novel method is used to provide temperature measurement via 2H resonances of methanol and ethylene glycol samples, which can concurrently be used for field/frequency locking.     

Novel formulations of vitamins and insulin by nanoengineering of polyelectrolyte multilayers around microcrystals

Microcapsules loaded with vitamin K3 (VK3), biotin, or insulin were prepared by using a novel coating technology based on the layer-by-layer (LbL) deposition of oppositely charged polyelectrolytes onto microcrystal templates. This produced multilayered, polymeric shells of varying thickness around the crystalline cores. Dissolution of the core material (VK3 with ethanol, biotin with basic solution, and insulin with acidic solution), resulted in its release through the shells. Microelectrophoresis was employed to monitor the microcrystal coating process; confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM) were used to verify multilayer coating and the formation of hollow polymer shells following removal of the microcrystal templates. The release rates of both VK3 and insulin decreased as the wall thickness (the number of polyelectrolyte layers deposited onto the microcrystal cores), increased. The release time could be varied by a factor of more than ten, depending on the number of polyelectrolyte layers applied. Following the addition of 70 mass % ethanol, the solubility of VK3 increased by as much as 170-fold, resulting in an increased rate of VK3 release. By selecting appropriate polymer materials for the shells, and by controlling the number of polyelectrolyte layers applied, shells of various thickness, stiffness, aqueous solubility, dispersibility, biocompatibility, and permeability can be constructed.     

Acoustic excitations in a self-assembled block copolymer photonic crystal

High resolution Brillouin light scattering can sensitively detect acoustic phonons in concentrated solutions of a high molecular weight poly(styrene-b-isoprene) symmetric copolymer in toluene. This block copolymer lamellar forming system also possesses a photonic stop band in the visible spectrum. Based on the low but finite contrast in mechanical properties between the styrene and isoprene components and taking into account the geometrical characteristics of the layered microstructure, we calculate the acoustic band structure and represent the observed acousticlike and opticlike phonons.     

Single Machine Scheduling of Unit-time Jobs with Controllable Release Dates

The paper presents a bicriterion approach to solve the single-machine scheduling problem in which the job release dates can be compressed while incurring additional costs. The two criteria are the makespan and the compression cost. For the case of equal job processing times, an O(n⁴) algorithm is developed to construct integer Pareto optimal points. We discuss how the algorithm developed can be modified to construct an -approximation of noninteger Pareto optimal points. The complexity status of the problem with total weighted completion time criterion is also established.     

Synthesis and structural study of 2′‐ and 2′,6′‐positioned methyl‐ and nitro‐substituted 3‐(arylhydrazono)pentane‐2,4‐diones

A systematic series of ortho‐methyl‐ and nitro‐substituted arylhydrazones 2–6 formed by Japp–Klingemann reaction between pentane‐2,4‐dione and the respective aryldiazonium salts have been synthesized and studied by X‐ray crystal structure analysis, with added quantum chemical calculations. The optimized molecular geometries based on DFT calculations, enabling determination of relevant rotational barriers, and the calculated bond and ring critical points, using the method of ‘atoms in molecules’, were found to correspond with the experimental data, involving specific molecular conformations and hydrogen‐bonded ring structure dependent on the ortho‐substitution, thus making possible reliable structural prediction of this compound class. Copyright © 2007 John Wiley & Sons, Ltd.     

All organic host-guest crystals based on a dumb-bell-shaped conjugated host for light harvesting through resonant energy transfer

Together we glow: Fully organic host-guest crystals with two dyes inserted in their parallel nanochannels display broad emission in the visible range thanks to resonant energy transfer. The conjugated host crystal provides light harvesting in the UV region.     

Electrostatic Potential Field and Nucleophilicity of 3, 5, 8, 10-Tetramethyl-aceheptylene

The electrostatic potential (EP.) for aceheptylene (I) is calculated using ab-initio wavefunctions. In addition, the EP. around I is approximated by a monopole expression, using wavefunctions from various semiempirical procedures as a basis. It is found that the previously noted discrepancy between the thoretical prediction of differential nuclophilicity of the individual unsaturated C-atoms in 3,5,8,10-tetramethyl-aceheptylene(II) and the experimental results of protonation is removed, if instead of local atomic charges, the EP. around II, approximated by that of I is considered.     

High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles

Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics.     

Ethynyl and Propynylpyrene Inhibitors of Cytochrome P450

Abstract  

The single-crystal X-ray structures and in vivo activities of three aryl acetylenic inhibitors of cytochromes P450 1A1, 1A2, 2A6, and 2B1 have been determined and are reported herein. These are 1-ethynylpyrene, 1-propynylpyrene, and 4-propynylpyrene. To investigate electronic influences on the mechanism of enzyme inhibition, the experimental electron density distribution of 1-ethynylpyrene has been determined using low-temperature X-ray diffraction measurements, and the resulting net atomic charges compared with various theoretical calculations. A total of 82,390 reflections were measured with Mo Kα radiation to a (sinθ/λ)_max = 0.985 Å⁻¹. Averaging symmetry equivalent reflections yielded 8,889 unique reflections. A least squares refinement procedure was used in which multipole parameters were added to describe the distortions of the atomic electron distributions from spherical symmetry. A map of the model electron density distribution of 1-ethynylpyrene was obtained. Net atomic charges calculated from refined monopole population parameters yielded charges that showed that the terminal acetylenic carbon atom (C18) is more negative than the internal carbon (C17). Net atomic charges calculated by ab initio, density functional theory, and semi-empirical methods are consistent with this trend suggesting that the terminal acetylenic carbon atom is more likely to be the site of oxidation. This is consistent with the inhibition mechanism pathway that results in the formation of a reactive ketene intermediate. This is also consistent with assay results that determined that 1-ethynylpyrene acts as a mechanism-based inhibitor of P450s 1A1 and 1A2 and as a reversible inhibitor of P450 2B1. Crystallographic data: 1-ethynylpyrene, C₁₈H₁₀, P2₁/c, a = 14.571(2) Å, b = 3.9094(5) Å, c = 20.242(3) Å, β = 105.042(2)°, V = 1,113.5(2) Å³; 1-propynylpyrene, C₁₉H₁₂, P2₁/n, a = 8.970(2) Å, b = 10.136(1) Å, c = 14.080(3) Å, β = 99.77(2)°, V = 1,261.5(4) Å³; 4-propynylpyrene, C₁₉H₁₂, Pbca, a = 9.904(1) Å, b = 13.174(2) Å, c = 19.401(1) Å, V = 2,531.4(5) Å³.     

Metalated aziridines for cross-coupling with aryl and alkenyl halides via palladium catalysis

The palladium-catalyzed coupling of an aziridinylzinc chloride intermediate with alkenyl and aryl halides has been demonstrated. The method provides products with retention of aziridine stereochemistry. The utility of the coupling procedure is illustrated in the synthesis of structures related to l-furanomycin.