Identification of unstable metabolites of Lonafarnib using liquid chromatography-quadrupole time-of-flight mass spectrometry, stable isotope incorporation and ion source temperature alteration

Structural characterization of unstable metabolites and other drug-derived entities poses a serious challenge to the analytical chemist using instrumentation such as LC-MS and LC-MS/MS, and may lead to inaccurate identification of metabolite structures. The task of structural elucidation becomes even more difficult when an analyte is unstable in the ion source of the mass spectrometer. However, a judicious selection of the experimental conditions and the advanced features of new generation mass spectrometers can often overcome these difficulties. We describe here the identification of three drug-derived peaks (A, B and C) that were detected from a Schering-Plough developmental compound (Lonafarnib) following incubation with cDNA-expressed human CYP3A4. Definitive characterization was achieved using (1) accurate mass measurement, (2) stable isotope incorporation, (3) reduced ion source temperature, (4) alkali ion attachment and (5) MS/MS fragmentation studies. The protonated ions of compounds A and B fragmented almost completely in the source, yielding ions of the same mass-to-charge ratio (m/z) as that of protonated C (CH+). Fortunately, the presence of Na+ and K+ adducts of A and B provided information crucial to distinguishing AH+ and BH+ from their fragment ions. Metabolite A was shown to be an unstable hydroxylated metabolite of Lonafarnib. The metabolite C was shown to be a dehydrogenated metabolite of Lonafarnib (Lonafarnib-2H), unstable in the presence of protic solvents. Finally, B was artifactually formed most likely from C by the solvolytic addition of methanol during sample preparation. MS/MS fragmentation experiments assisted in identifying the site of metabolism in A and chemical modification in B. A and C readily interconvert through hydration/dehydration, and B and C through addition/elimination of methanol present in the sample-processing solvents. Finally, NMR experiments were performed to confirm the structures of A and C.     

The Modified Ghost Fluid Method Applied to Fluid-Elastic Structure Interaction

In this work, the modified ghost fluid method is developed to deal with 2D compressible fluid interacting with elastic solid in an Euler-Lagrange coupled system. In applying the modified Ghost Fluid Method to treat the fluid-elastic solid coupling, the Navier equations for elastic solid are cast into a system similar to the Euler equations but in Lagrangian coordinates. Furthermore, to take into account the influence of material deformation and nonlinear wave interaction at the interface, an Euler-Lagrange Riemann problem is constructed and solved approximately along the normal direction of the interface to predict the interfacial status and then define the ghost fluid and ghost solid states. Numerical tests are presented to verify the resultant method.     

The radiation shielding offered by the commercial glass installed in Bangladeshi dwellings

One sign of a vibrant Bangladeshi economy has been the move away from the use of more traditional housing materials towards a preference for modern constructional media. Glass, one such example, used both decoratively and in a structural context, offers various advantageous properties and facets including a protective feature against radiation that has not previously been considered. Current interest examines the dosimetric possibilities offered by the commercial glass as a secondary shield and also in retrospective ionising radiation exposure analysis. Four popular brands of window glass are investigated, all available within the local market (PHP-Bangladesh, Usmania-Bangladesh, Nasir-Bangladesh and Rider-China), all with the same thickness and colour, varying in terms of elemental weight fractions as evaluated by energy dispersive X-ray analysis. As potential attenuators of transmitted radiation thereby forming secondary barriers against radiation exposure from penetrating radiations, the four brands of glass have been studied using photon energies from 59 up to 1332 keV, a range of values representative of that potentially encountered in incidents. Use has been made of a well-shielded high-purity germanium γ-ray spectrometer and associated electronics, providing for evaluation of the characteristic barrier parameters of half-value layer, radiation protection efficiency and effective atomic number (Z_eff). Of the four brands investigated, Rider provides superior secondary shielding performance. Concerning potential retrospective dosimetry the effective atomic number of the glass samples are comparable with that of the commercial thermoluminescence (TL) dosimeter TLD-200. At high doses, the TL yields are sufficient to provide for retrospective accident dosimetry.     

Enhanced crosstalk tolerance in RSOA based WDM-PONs by using coded RZ modulation

A centralized seeding source based loopback WDM-PON is fundamentally limited by Rayleigh backscattering (RB) noise. Here a novel modulation format, called as Coded RZ (CoRZ), is proposed to enhance the system performance in the presence of RB for RSOA based reflective access networks. The result shows that the proposed technique can be effectively improved the tolerance of signal-to-crosstalk ratio (SCR) by about 8 dB and 2.5 dB from conventional NRZ and RZ modulation formats respectively to maintain power penalty ≤ 2 dB.     

TITAN: an ion trap for accurate mass measurements of ms-half-life nuclides

The introduction of Paul traps, in particular linear radio-frequency quadrupoles in the early 2000s, has revolutionized the use of ion traps for probing the properties of radioactive nuclides. It opened the path to trapping all available nuclides, independent of their chemical properties. We present an overview of direct mass measurements of short-lived nuclides using TITAN, a Penning trap mass spectrometer facility particularly suitable for precision measurements of ms-half-life nuclides.     

Gate‐Induced Modification of Water Adsorption on Dielectrics Probed by EFM and Carbon Nanotube FETs

Humidity plays an important role in molecular electronics. It facilitates charge movement on top of dielectric layers and modifies the device transfer characteristics. Using two different methods to probe temporal charge redistribution on the surface of dielectrics, we were able to extract the surface humidity for the first time. The first method is based on the relaxation time constants of the current through carbon nanotube field‐effect transistors (CNTFETs), and the second is based on electric force microscopy (EFM) measurements. Moreover, we found that applying external gate biases modifies the surface humidity. A theoretical model based on dielectrophoretic attraction between the water molecules and the substrate is introduced to explain this observation, and the results support our hypothesis. Furthermore, it is found that upon the adsorption of two to three layers of water the surface conductivity saturates.     

Selective recognition of fluoride and acetate by a newly designed ruthenium framework: experimental and theoretical investigations

An effective anion sensor, [Ru(II)(bpy)(2)(H(2)L(-))](+) (1(+)), based on a redox and photoactive {Ru(II)(bpy)(2)} moiety and a new ligand (H(3)L = 5-(1H-benzo[d]imidazol-2-yl)-1H-imidazole-4-carboxylic acid), has been developed for selective recognition of fluoride (F(-)) and acetate (OAc(-)) ions. Crystal structures of the free ligand, H(3)L and [1](ClO(4)) reveal the existence of strong intramolecular and intermolecular hydrogen bonding interactions. The structure of [1](ClO(4)) shows that the benzimidazole N-H of H(2)L(-) is hydrogen bonded with the pendant carboxylate oxygen while the imidazole N-H remains free for possible hydrogen bonding interaction with the anions. The potential anion sensing features of 1(+) have been studied by different experimental and theoretical (DFT) investigations using a wide variety of anions, such as F(-), Cl(-), Br(-), I(-), HSO(4)(-), H(2)PO(4)(-), OAc(-) and SCN(-). Cyclic voltammetry and differential pulse voltammetry established that 1(+) is an excellent electrochemical sensor for the selective recognition of F(-) and OAc(-) anions. 1(+) is also found to be a selective colorimetric sensor for F(-) or OAc(-) anions where the MLCT band of the receptor at 498 nm is red shifted to 538 nm in the presence of one equivalent of F(-) or OAc(-) with a distinct change in colour from reddish-orange to pink. The binding constant between 1(+) and F(-) or OAc(-) has been determined to be logK = 7.61 or 7.88, respectively, based on spectrophotometric titration in CH(3)CN. The quenching of the emission band of 1(+) at 716 nm (λ(ex) = 440 nm, Φ = 0.01 at 298 K in CH(3)CN) in the presence of one equivalent of F(-) or OAc(-), as well as two distinct lifetimes of the quenched and unquenched forms of the receptor 1(+), makes it also a suitable fluorescence-based sensor. All the above experiments, in combination with (1)H NMR, suggest the formation of a 1:1 adduct between the receptor (1(+)) and the anion (F(-) or OAc(-)). The formation of 1:1 adduct {[1(+)·F(-)] or [1(+)·OAc(-)]} has been further evidenced by in situ ESI-MS(+) in CH(3)CN. Though the receptor, 1(+), is comprised of two N-H protons associated with the coordinated H(2)L(-) ligand, only the free imidazole N-H proton participates in the hydrogen bonding interactions with the incoming anions, while the intramolecularly hydrogen bonded benzimidazole N-H proton remains intact as evidenced by the crystal structure of the final product (1). The hydrogen bond mediated anion sensing mechanism, over the direct deprotonation pathway, in 1(+) has been further justified by a DFT study and subsequent NBO analysis.     

Experimental demonstration of terahertz metamaterial absorbers with a broad and flat high absorption band

We present the design, numerical simulations and experimental measurements of terahertz metamaterial absorbers with a broad and flat absorption top over a wide incidence angle range for either transverse electric or transverse magnetic polarization depending on the incident direction. The metamaterial absorber unit cell consists of two sets of structures resonating at different but close frequencies. The overall absorption spectrum is the superposition of individual components and becomes flat at the top over a significant bandwidth. The experimental results are in excellent agreement with numerical simulations.