DNA Origami for Silicon Patterning.

Desoxyribonucleic acid (DNA) origami architectures are a promising tool for ultimate lithography because of their ability to generate nanostructures with a minimum feature size down to 2 nm. In this paper, we developed a method for silicon (Si) nanopatterning to face up current limitations for high-resolution patterning with standard microelectronic processes. For the first time, a 2 nm-thick 2D DNA origami mask, with specific design composed of three different square holes (with a size of 10 and 20 nm), is used for positive pattern transfer into a Si substrate using a 15 nm-thick silicon dioxide (SiO2) layer as an intermediate hard mask. First, the origami mask is transferred onto the SiO2 underlayer, by an HF vapor-etching process. Then, the Si underlayer is etched using an HBr/O2 plasma. Each hole is transferred in the SiO2 layer and the 20 nm-sized holes are transferred into the final stack (Si). The resulting patterns exhibited a lateral resolution in the range of 20 nm and a depth of 40 nm. Patterns are fully characterized by atomic force microscopy, scanning electron microscopy, focused ion beam-transmission electron microscopy, and ellipsometry measurements.

Proton-Coupled Redox Switching in an Annulated π-Extended Core-Modified Octaphyrin.

Proton-coupled electron transfer (PCET) is an important chemical and biological phenomenon. It is attractive as an on-off switching mechanism for redox-active synthetic systems but has not been extensively exploited for this purpose. Here we report a core-modified planar weakly antiaromatic/nonaromatic octaphyrin, namely, a [32]octaphyrin(1.0.1.0.1.0.1.0) (1) derived from rigid naphthobipyrrole and dithienothiophene (DTT) precursors, that undergoes proton-coupled two-electron reduction to produce its aromatic congener in the presence of HCl and other hydrogen halides. Evidence for the production of a [4 n + 1] π-electron intermediate radical state is seen in the presence of trifluoroacetic acid. Electrochemical analyses provide support for the notion that protonation causes a dramatic anodic shift in the reduction potentials of octaphyrin 1, thereby facilitating electron transfer from halide anions (viz. I-, Br-, and, Cl-). Electron-rich molecules, such as tetrathiafulvene (TTF), phenothiazine (PTZ), and catechol, were also found to induce PCET in the case of 1. Both the oxidized and two-electron reduced forms of 1 were characterized by X-ray diffraction analyses in the solid state and in solution via spectroscopic means.

Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations.

The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations. Progressing alternative salt forms with improved solubility and dissolution properties can minimise this concern. This manuscript outlines a nonclinical approach comprising multiple biopharmaceutical, in vitro and physiologically based pharmacokinetic model (PBPK) modelling studies to enable selection of an alternative salt form for danirixin (DNX, GSK1325756), a pharmaceutical agent being developed for chronic obstructive pulmonary disease (COPD). The hydrobromide salt of DNX was identified as having superior biopharmaceutical properties compared to the free base (FB) form in clinical development and the impact of switching to the hydrobromide salt (HBr) was predicted by integrating the nonclinical data in a PBPK model (using GastroPlus™) to enable simulation of clinical drug exposure with FB and HBr salts in the absence and presence of a gastric acid reducing comedication (omeprazole, a proton pump inhibitor (PPI)). Subsequent investigation of DNX pharmacokinetics in a Phase 1 clinical study comparing FB with HBr salt forms confirmed that DNX HBr had reduced the variability of drug exposure and that exposure was not affected by PPI co-administration with DNX HBr. This case study therefore adds to the surprisingly few examples of a more soluble salt of a weak base translating to an improvement in human pharmacokinetics and illustrates a clear clinical benefit of salt selection during drug development.

Structures and physicochemical properties of vortioxetine salts.

In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKa being greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl), p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT-IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The acidic proton is transferred to the secondary N atom on the piperazine ring of VT, forming the charge-assisted hydrogen bond N+-H...X- (X = Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were carried out in distilled water (pH = 7.0) to compare the solubilities of the salts with that of VT. The VT-ASP-H2O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT-ASP-H2O (1:1:2) is a high solubility salt that is stable in a slurry experiment at 298 K in 95% ethanol. The experimental data for the VT-ASP-H2O (1:1:2) salt identify it as a promising drug candidate.

Gas-Phase Reaction of Hydroxyl Radical with p-Cymene over an Extended Temperature Range.

The kinetics of the reaction of OH radicals with p-cymene has been studied in the temperature range of 243-898 K using a flow reactor combined with a quadrupole mass spectrometer: OH + p-cymene → products. The reaction rate constant was determined as a result of absolute measurements, from OH decay kinetics in excess of p-cymene and employing the relative rate method with OH reactions with n-pentane, n-heptane,1,3-dioxane, HBr, and Br2 as the reference ones. For the rate coefficient of the H atom abstraction channel, the expression k1b = (3.70 ± 0.42) × 10(-11) exp[-(772 ± 72)/T] was obtained over the temperature range of 381-898 K. The total rate constant (addition + abstraction) determined at T = 243-320 K was k1 = (1.82 ± 0.48) × 10(-12) exp[(607 ± 70)/T] or, in a biexponential form, k1 = k1a + k1b = 3.7 × 10(-11) exp(-772/T) + 6.3 × 10(-13) exp(856/T), independent of the pressure between 1 and 5 Torr of helium. In addition, our results indicate that the reaction pathway involving alkyl radical elimination upon initial addition of OH to p-cymene is most probably unimportant.

Mercury adsorption characteristics of HBr-modified fly ash in an entrained-flow reactor.

In this study, the mercury adsorption characteristics of HBr-modified fly ash in an entrained-flow reactor were investigated through thermal decomposition methods. The results show that the mercury adsorption performance of the HBr-modified fly ash was enhanced significantly. The mercury species adsorbed by unmodified fly ash were HgCl2, HgS and HgO. The mercury adsorbed by HBr-modified fly ash, in the entrained-flow reactor, existed in two forms, HgBr2 and HgO, and the HBr was the dominant factor promoting oxidation of elemental mercury in the entrained-flow reactor. In the current study, the concentration of HgBr2 and HgO in ash from the fine ash vessel was 4.6 times greater than for ash from the coarse ash vessel. The fine ash had better mercury adsorption performance than coarse ash, which is most likely due to the higher specific surface area and longer residence time.

Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization.

An efficient and practical system for inexpensive bromination and iodination of arenes as well as heteroarenes by using readily available dimethyl sulfoxide (DMSO) and HX (X = Br, I) reagents is reported. This mild oxidative system demonstrates a versatile protocol for the synthesis of aryl halides. HX (X = Br, I) are employed as halogenating reagents when combined with DMSO which participates in the present chemistry as a mild and inexpensive oxidant. This oxidative system is amenable to late-stage bromination of natural products. The kilogram-scale experiment (>95% yield) shows great potential for industrial application.

A THz/FTIR fingerprint of the solvated proton: evidence for Eigen structure and Zundel dynamics.

In continuation of earlier work on La(III), Ni(II) and Mn(II) halides, we present low frequency (30-400 cm(-1)) spectra of solvated HCl and HBr as a function of solute concentration. This frequency range provides direct access to water network modes and changes induced by solvated solutes. We were able to dissect the spectra into components associated to solvated ions and ion pairs using a chemical equilibrium model in combination with principal component analysis. While the Cl(-) rattling mode at 190 cm(-1) is found to be unchanged, the Br(-) resonance around 90 cm(-1) is decreased in intensity below the detection threshold when replacing the divalent or trivalent metal ions by a proton. The solvated proton shows two resonances: a solvation water mode around 140 cm(-1) and a high frequency resonance at 325 cm(-1) that we assign to the rattling motion of an Eigen structure H3O(+) in its solvation cage. This assignment is corroborated by isotopic substitution measurements which show a redshift of the high frequency peak when HCl/H2O is replaced by DCl/D2O. The linewidth of the H3O(+) rattling mode corresponds to a relaxation time of the oscillatory process of τ ≈ 60 fs, considerably faster than the relaxation time of τ ≈ 160 fs for Cl(-). In addition, we find a broad background that we attribute to fast non-oscillatory motions of a proton in a Zundel-like complex. Our results are in agreement with an Eigen-Zundel-Eigen (EZE) model of proton transport. Upon ion pairing the broad background is strongly reduced indicating a reduction of fast proton transfer processes. The Cl(-) resonance blueshifts by 20 cm(-1) which indicates a transition from free ions to a solvent shared ion pair. Surprisingly, the center frequency of the Eigen complex does not change upon ion pairing. This can be rationalized in terms of an unchanged local solvation structure.

Quantum dynamics study of H + DBr and D + HBr reaction.

Time-dependent quantum wave packet calculations have been performed for the H + DBr and D + HBr reaction using the recent diabatic potential energy surfaces. Reaction probabilities, integral cross sections, and rate constants are obtained. The results show that the isotopic effects have an influence on the nonadiabatic effect which is generally inversely proportional to the atom mass. The calculated rate constants are in good overall agreement with experimental values, indicating that the ab initio surfaces are accurate to describe the isotopic effects.

Study on simultaneous recycling of EAF dust and plastic waste containing TBBPA.

In the present work we investigated the fates of zinc, lead, and iron present in electric arc furnace dust during thermal treatment of the dust with tetrabromobisphenol A (TBBPA) and tetrabromobisphenol A diglycidyl ether (TBBPADGE). Mixtures of these materials were compressed into pellets and heated in a laboratory-scale furnace at 550 °C for 80 min, under oxidizing and inert conditions. The solid, condensed, and gaseous-phase products were characterized using an array of analytical methods: scanning electron microscopy, X-ray diffraction, electron probe microscopy, inductively coupled plasma, ion chromatography, and gas chromatography. The results indicated that heating the mixtures under specific conditions enabled high separation of zinc and lead from iron-rich residues, by a bromination-evaporation process. In the case of TBBPADGE, a maximum of 85% of zinc and 81% of lead were effectively separated under the above conditions. The process is based on the reaction between the highly reactive HBr gas evolved during thermal degradation of the flame-retarded materials with zinc (ZnO and ZnFe2O4) and lead in the dust, followed by complete evaporation of the formed metallic bromides from the solid residue.

Pulse train induced rotational excitation and orientation of a polar molecule.

We investigate theoretically the rotational excitation and field free molecular orientation of polar HBr molecule, interacting with train of ultrashort laser pulses. By adjusting the number of pulses, pulse period and the intensity of the pulse, one can suppress a population while simultaneously enhancing the desired population in particular rotational state. We have used train of laser pulses of different shaped pulse envelopes. The dynamics and orientation of molecules in the presence of pulse train of different shapes is studied and explained.

Highly stable photoelectrochemical water splitting and hydrogen generation using a double-band InGaN/GaN core/shell nanowire photoanode.

We report on the first demonstration of stable photoelectrochemical water splitting and hydrogen generation on a double-band photoanode in acidic solution (hydrogen bromide), which is achieved by InGaN/GaN core/shell nanowire arrays grown on Si substrate using catalyst-free molecular beam epitaxy. The nanowires are doped n-type using Si to reduce the surface depletion region and increase current conduction. Relatively high incident-photon-to-current-conversion efficiency (up to ~27%) is measured under ultraviolet and visible light irradiation. Under simulated sunlight illumination, steady evolution of molecular hydrogen is further demonstrated.

Fate of lead oxide during thermal treatment with tetrabromobisphenol A.

In this paper, the bromination reaction between lead oxide and hydrogen bromide originating from the thermal decomposition of tetrabromobisphenol A (TBBPA), under inert and oxidizing atmospheres, was investigated, using a laboratory-scale furnace. The results obtained under inert conditions indicated that bromination of PbO proceeded simultaneously with debromination of TBBPA, with an average effectiveness of 69% (max. 80%). Volatilization of the formed PbBr2 began at 315°C, intensified at 750°C, and reached 98% at 850°C. The formed organic char served as a source of carbon for reduction of the unreacted lead oxide to metallic lead in the range 315-750°C. Additional experiments conducted at selected temperatures under slightly oxidizing (5 vol% O2) and quasi-atmospheric (20 vol% O2) conditions showed no significant effects on bromination-evaporation of lead in the studied mixture. However, in isothermal treatment under quasi-atmospheric oxygen levels, complete vaporization of the formed lead bromide was obtained at a temperature of only 650°C.

Controlling rotational dynamics and alignment of molecule by infrared laser pulse.

We investigate the effects of delayed infrared laser (IRL) pulse shape on the non-adiabatic rotational excitation and alignment of a polar molecule. We suggest a control scheme for choosing populations of molecular rotational states by wave packet interference. The rotational wave packets of polar molecule (here HBr) excited non-adiabatically by orienting pulse is controlled actually using the second delayed IRL pulse. By adjusting the time delay between the two laser pulses and the shape of delayed IRL pulse, constructive or destructive interference among these wave packets enables the population to be enhanced or repressed for the specific rotational state. We have used fourth order Runge-Kutta method to study the non-adiabatic rotational excitation (NAREX) dynamics.

Fluorescence photoactivation by intermolecular proton transfer.

We designed a strategy to activate fluorescence under the influence of optical stimulations based on the intermolecular transfer of protons. Specifically, the illumination of a 2-nitrobenzyl derivative at an activating wavelength is accompanied by the release of hydrogen bromide. In turn, the photogenerated acid encourages the opening of an oxazine ring embedded within a halochromic compound. This structural transformation extends the conjugation of an adjacent coumarin fluorophore and enables its absorption at an appropriate excitation wavelength. Indeed, this bimolecular system offers the opportunity to activate fluorescence in liquid solutions, within rigid matrixes and inside micellar assemblies, relying on the interplay of activating and exciting beams. Furthermore, this strategy permits the permanent imprinting of fluorescent patterns on polymer films, the monitoring of proton diffusion within such materials in real time on a millisecond time scale, and the acquisition of images with spatial resolution at the nanometer level. Thus, our operating principles for fluorescence activation can eventually lead to the development of valuable photoswitchable probes for imaging applications and versatile mechanisms for the investigation of proton transport.

An electronic structure theory investigation of the physical chemistry of the intermolecular complexes of cyclopropenylidene with hydrogen halides.

The proton accepting and donating abilities of cyclopropenylidene (c-C(3)H(2)) on its complexation with hydrogen halides H-X (X = F, Cl, Br) are analyzed using density-functional theory with three functionals (PBE0, B3LYP, and B3LYP-D) and benchmarked against second-order Møller-Plesset (MP2) theory. Standard signatures including, inter alia, dipole moment enhancement, charge transfer from the carbenic lone pair to the antibonding σ*(H-X) orbital, and H-X bond elongation are examined to ascertain the presence of hydrogen bonding in these complexes. The latter property is found to be accompanied with a pronounced red shift in the bond stretching frequency and with a substantial increase in the infrared intensity of the band on complex formation. The MP2/aug-cc-pVTZ c-C(3)H(2)···H-F complex potential energy surface turns out to be an asymmetric deep single well, while asymmetric double wells are found for the c-C(3)H(2)···H-Cl and c-C(3)H(2)···H-Br complexes, with an energy barrier of 4.1 kcal mol(-1) for proton transfer along the hydrogen bond in the latter complex. Hydrogen-bond energy decomposition, with the reduced variational space self-consistent field approach, indicates that there are large polarization and charge-transfer interactions between the interacting partners in c-C(3)H(2)···H-Br compared to the other two complexes. The C···H bonds are found to be predominantly ionic with partial covalent character, unveiled by the quantum theory of atoms in molecules. The present results reveal that the c-C(3)H(2) carbene divalent carbon can act as a proton acceptor and is responsible for the formation of hydrogen bonds in the complexes investigated.

A simple scheme for magnetic balance in four-component relativistic Kohn-Sham calculations of nuclear magnetic resonance shielding constants in a Gaussian basis.

We report the implementation of nuclear magnetic resonance (NMR) shielding tensors within the four-component relativistic Kohn-Sham density functional theory including non-collinear spin magnetization and employing London atomic orbitals to ensure gauge origin independent results, together with a new and efficient scheme for assuring correct balance between the large and small components of a molecular four-component spinor in the presence of an external magnetic field (simple magnetic balance). To test our formalism we have carried out calculations of NMR shielding tensors for the HX series (X = F, Cl, Br, I, At), the Xe atom, and the Xe dimer. The advantage of simple magnetic balance scheme combined with the use of London atomic orbitals is the fast convergence of results (when compared with restricted kinetic balance) and elimination of linear dependencies in the basis set (when compared to unrestricted kinetic balance). The effect of including spin magnetization in the description of NMR shielding tensor has been found important for hydrogen atoms in heavy HX molecules, causing an increase of isotropic values of 10%, but negligible for heavy atoms.

Direct perturbation theory in terms of energy derivatives: scalar-relativistic treatment up to sixth order.

A formulation of sixth-order direct perturbation theory (DPT) to treat relativistic effects in quantum-chemical calculations is presented in the framework of derivative theory. Detailed expressions for DPT6 are given at the Hartree-Fock level in terms of the third derivative of the energy with respect to the relativistic perturbation parameter defined as λ(rel)=c(-2). They were implemented for the computation of scalar-relativistic energy corrections. The convergence of the scalar-relativistic DPT expansion is studied for energies and first-order properties such as dipole moment and electric-field gradient within the series of the hydrogen halides (HX, X = F, Cl, Br, I, and At). Comparison with spin-free Dirac-Coulomb calculations indicates that the DPT series exhibits a smooth and monotonic convergence. The rate of convergence, however, depends on the charge of the involved nuclei and significantly slows down for heavy-element compounds.

QTAIM analysis of the HF, HCl, HBr, and HOH elimination reactions of halohydrocarbons and halohydroalcohols.

The 1,2-HX elimination reaction (where X = F, Cl, Br, OH) has been established as an important reaction in the degradation of compounds introduced into the upper atmosphere, including common CFC replacement compounds. By analyzing the electron densities of the transition state geometries of these reactions using QTAIM, we see that we can divide these reactions into two types. For HF and HOH elimination, the transition state is a complete ring of bonds, and neither the C-H nor the C-X bonds have been broken at the maximum of energy. There is very little accumulation of electron density on the X atom, with the majority of charge being lost by the hydrogen atom undergoing elimination, being transferred on to the two carbon atoms. In HCl and HBr elimination, a similar loss of electron density of the hydrogen atom is accompanied by significant accumulation of electron density on the X atom and a smaller change in electron density on the carbon atoms. The C-X bond is broken in the transition state geometry, with no ring critical point being present. This may explain the relative stabilities of halohydrocarbons and haloalcohols with respect to loss of H-X.

Simultaneous identification of tyrosine phosphorylation and sulfation sites utilizing tyrosine-specific bromination.

Tyrosine phosphorylation and sulfation play many key roles in the cell. Isobaric phosphotyrosine and sulfotyrosine residues in peptides were determined by mass spectrometry using phosphatase or sulfatase to remove the phosphate or the sulfate group. Unique Br signature was introduced to the resulting tyrosine residues by incubation with 32% HBr at -20 °C for 20 min. MS/MS analysis of the brominated peptide enabled unambiguous determination of the phosphotyrosine and the sulfotyrosine sites. When phosphotyrosine and sulfotyrosine as well as free tyrosine were present in the same peptide, they could be determined simultaneously using either phosphatase or sulfatase following acetylation of the free tyrosine.