Characterisation of selected hypnotic drugs and their metabolites using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by liquid chromatography-electrospray ionisation-ion trap mass spectrometry

The electrospray ionisation-ion trap mass spectrometry (ESI-MSⁿ) of selected hypnotic drugs, i.e. zopiclone, zolpidem, flunitrazepam and their metabolites have been investigated. Sequential product ion fragmentation experiments (MSⁿ) have been performed in order to elucidate the degradation pathways for the [M+H]⁺ ions and their predominant fragment ions. These MSⁿ experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as neutral molecules such as H₂O, CO, CO₂, NO₂, amines and HF. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with zopiclone and its N-desmethyl metabolite fragmentation initially occurs at the latter ring with the former being resistant to fragmentation. The structures of fragment ions proposed for ESI-MSⁿ can be supported by electrospray ionisation-quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS).These molecules can be identified and determined in mixtures at low ng/ml concentrations by the application of liquid chromatography (LC)-ESI-MSⁿ which can be used for their analysis in saliva samples.This paper includes a tabulation of mass losses/signals at low m/z values for these hypnotic drugs and many others in recent publications which will be of value in the characterisation of drug metabolites of unknown structure and also natural product pharmaceuticals isolated from plants, etc.     

Estimating reaction parameters in mechanism-enabled population balance models of nanoparticle size distributions: A Bayesian inverse problem approach

In order to quantitatively predict nano- as well as other particle-size distributions, one needs to have both a mathematical model and estimates of the parameters that appear in these models. Here, we show how one can use Bayesian inversion to obtain statistical estimates for the parameters that appear in recently derived mechanism-enabled population balance models (ME-PBM) of nanoparticle growth. The Bayesian approach addresses the question of “how well do we know our parameters, along with their uncertainties?.” The results reveal that Bayesian inversion statistical analysis on an example, prototype nanoparticle formation system allows one to estimate not just the most likely rate constants and other parameter values, but also their SDs, confidence intervals, and other statistical information. Moreover, knowing the reliability of the mechanistic model's parameters in turn helps inform one about the reliability of the proposed mechanism, as well as the reliability of its predictions. The paper can also be seen as a tutorial with the additional goal of achieving a “Gold Standard” Bayesian inversion ME-PBM benchmark that others can use as a control to check their own use of this methodology for other systems of interest throughout nature. Overall, the results provide strong support for the hypothesis that there is substantial value in using a Bayesian inversion methodology for parameter estimation in particle formation systems.     

Chern Character in Twisted K-Theory: Equivariant and Holomorphic Cases

 It was argued in [25, 5] that in the presence of a nontrivial B-field, D-brane charges in type IIB string theories are classified by twisted K-theory. In [4], it was proved that twisted K-theory is canonically isomorphic to bundle gerbe K-theory, whose elements are ordinary Hilbert bundles on a principal projective unitary bundle, with an action of the bundle gerbe determined by the principal projective unitary bundle. The principal projective unitary bundle is in turn determined by the twist. This paper studies in detail the Chern-Weil representative of the Chern character of bundle gerbe K-theory that was introduced in [4], extending the construction to the equivariant and the holomorphic cases. Included is a discussion of interesting examples. Received: 10 January 2002 / Accepted: 9 December 2002 Published online: 25 February 2003 RID="⋆" ID="⋆" The authors acknowledge the support of the Australian Research Council Communicated by R.H. Dijkgraaf     

An annulene-fused cyclopentadienide. A photochromic cyclopentadienodimethyldihydropyrene where the fused cyclopentadienide group resembles benzene in its effect on the dihydropyrene-metacyclophanediene valence isomerization

The synthesis of the green cyclopentadiene-fused dimethyldihydropyrene 12 was achieved in 36% yield in 7 steps from the parent dihydropyrene 3. Reaction of 12 with KH or LiCH(2)SiMe(3) gave the [14]annulene-fused cyclopentadienide anion quantitatively. In the (1)H NMR spectra, the internal methyl protons of 12 at delta -3.9, change dramatically on formation of anion 5, becoming deshielded to delta -1.82. This is caused by the reduction in diatropicity of the [14]annulene ring on fusion to the 6pi-cyclopentadienide ring. The anion is also a photochromic switch. Irradiation of the closed form 5 with visible light opens it to the open form 5', which reverts to the closed form 5 either with UV light or thermally. The switching behavior is between that of the parent 3/3' and the benzannelated system 4/4' and suggests that in its effect on the photoswitching, cyclopentadienide is behaving chemically similar to benzene.     

Gradient expansion of the atomic kinetic energy functional

It is demonstrated that the ground-state atomic kinetic energy functional T[?], where ? is the electron density, can be computed to surprising accuracy from the truncated gradient expansion: T[?] = + T₂[?] + T₄[?], with T_o[?] = $\text{3}\text{10}$(3π²)$\text{2}\text{3}$ ∫ ?$\text{5}\text{3}$ d_τ, T₂ [?] = $\text{1}\text{72}$ ∫ (??)²?^?1 d_τ, and T₄ [?] given by the formula of Hodges. Calculations of T₀, T₂ and T₄ are reported for He with ? both the Hartree—Fock and a very accurate density, and for Ne, Ar and Kr with ? the Hartree—Fock density. For Kr, T₀ + T₂ + T₄ is within 0.3% of the exact Hartree—Fock T, with T₂/T₀ = 0.05, T₄/T₂ = 0.17.     

Oxoneptunium(v) as part of the framework of a polyoxometalate

(NH4)14Na4[(Np3W4O15)(H2O)3(BiW9O33)3].62H2O (1) and (NH4)14.5Na3.5[(Np3W4O15)(H2O)3(SbW9O33)3].40.5H2O (2) each contain three neptunyl(v) moieties encapsulated within heteropolyoxotungstate frameworks in which axial {NpO2}+ oxygens form one face of a WO6 octahedron.     

Alkali Metal Triphenyl- and Trihydridosilanides Stabilized by a Macrocyclic Polyamine Ligand

Potassium silanide [KSiH₃]_∞ contains 4.2 wt % of hydrogen and has been intensely studied as hydrogen storage material. The macrocyclic ligand Me₄TACD (1,4,7,10-tetramethyl-1,4,7,10-tetraaminocyclododecane, L ) stabilizes the full range of triphenylsilyl complexes [( L )MSiPh₃]_n (M=Li–Cs), which react with H₂ or PhSiH₃ to form molecular [( L )MSiH₃]_n that can be isolated in soluble form and fully characterized.     

Interaction of the general volatile anesthetic Enflurane with bacteriorhodopsin-DPPC proteoliposomes

Thermal decomposition of dried crystalline powder obtained from titanium(IV) bis(acetylacetonate) diisopropoxide (75% solution in 2-propanol) (1) was monitored by simultaneous TG/DTA, EGA-FTIR and EGA-MS measurements and the results were compared with those of amorphous powder obtained by gelling of acetylacetonate-modified titanium(IV) tetra-isopropoxide at molar ratio of 1:2 in boiling 2-methoxyethanol (2). Thermal degradation of 1 in the temperature range of 25–700°C consists of 5 steps with a total mass loss of 62.5%. EGA by FTIR and MS revealed the release of H₂O below 120°C; followed by an intensive evolution of acetylacetone around 245°C. The release of acetone and acetic acid occurs up to 270°C and that of CO and CO₂ up to 530°C.     

Microstructure and Defect Characterization of Nanostructured Ni3Al

 Nanostructured Ni₃Al was produced by the inert gas condensation and in situ compaction technique and characterized by means of high-resolution transmission electron microscopy (HRTEM), X-ray diffraction, and density measurements. The defect structure was investigated using positron annihilation lifetime spectroscopy (PALS). It is shown that in some samples besides the cubic also the martensitic phase can be present. The defect structure can be divided into three major components: vacancy-like defects in the grain boundaries and nano-voids with a size of 1 nm as seen with PALS, and large pores with sizes up to 8 nm as seen with HRTEM. Furthermore, it is shown that an increasing compaction temperature leads to significantly smaller nano-voids.     

Influence of Solution Volume on the Dissolution Rate of Silicon Dioxide in Hydrofluoric Acid

Experimental data and modeling of the dissolution of various Si/SiO₂ thermal coatings in different volumes of hydrofluoric acid (HF) are reported. The rates of SiO₂‐film dissolution, measured by means of various electrochemical techniques, and alteration in HF activity depend on the thickness of the film coating. Despite the small volumes (0.6–1.2 mL) of the HF solution, an effect of SiO₂‐coating thickness on the dissolution rate was detected. To explain alterations detected in HF activity after SiO₂ dissolution, spectroscopic analyses (NMR and FTIR) of the chemical composition of the solutions were conducted. This is associated with a modification in the chemical composition of the HF solution, which results in either the formation of an oxidized species in solution or the precipitation of dissolution products. HF₂^? accumulation in the HF solution, owing to SiO₂ dissolution was identified as the source of the chemical alteration.