The active analog approach applied to the pharmacophore identification of benzodiazepine receptor ligands

Summary Applied to seven potent benzodiazepine-receptor ligands belonging to chemically different classes, the active analog approach allowed the stepwise identification of the pharmacophoric pattern associated with the recognition by the benzodiazepine receptor.A unique pharmacophore model was derived which involves six critical zones: (a) a -electron rich aromatic (PAR) zone; (b) two electron-rich zones ₁ and ₂ placed at 5.0 and 4.5 Å respectively from the reference centroid in the PAR zone; (c) a freely rotating aromatic ring (FRA) region; (d) an out-of-plane region (OPR), strongly associated with agonist properties; and (e) an additional hydrophobic region (AHR).The model accommodates all presently known ligands of the benzodiazepine receptor, identifies sensitivity to steric hindrance close to the ₁ zone, accounts forR andS differential affinities and distinguishes requirements for agonist versus non-agonist activity profiles.Abbreviations Pyrazoloquinolines CGS (2-phenyl-2,5-dihydro pyrazolo [4,3-c] quinoline-3 (3H)-one) - Cinnolinones CIN (2-(4-methoxyphenyl)-benzo [h] 3-cinnolinone - Triazolophthalazines TZPH (3-(4-methoxyphenyl)-6 pyrrolidinotriazolo [4,3-a] phthalazine - Cyclopyrrolones RP 27267, CLO ([6-(5-chloro-2-pyridyl)-6,7-dihydro-7 oxo-5H-pyrrolo [3,4-b]pyrazin-5-yl] 4-methyl-l-piperazine carboxylate) - Phenylquinolines PK (phenyl-2 (morpholinocarbonyl methyl oxy)-4 quinoline - -Carbolines BCC (3-carboethoxy--carboline) - Benzodiazepines: Diazepam DZ (7-chloro-1,3-dihydro-1-methyl-5 phenyl-2H-1,4-benzodiazepin-2-one)     

Supramolecular control of charge-transfer dynamics on dye-sensitized nanocrystalline TiO2 films

A [Ru(dcbpy)(2)(NCS)(2)] dye has been chemically modified by the addition of a secondary electron donor moiety, N,N-(di-p-anisylamino)phenoxymethyl. Optical excitation of the modified dye adsorbed to nanocrystalline TiO(2) films shows a remarkably long-lived charge-separated state, with a decay half time of 0.7 s. Semiempirical calculations confirm that the HOMO of the modified dye molecule is localised on the electron donor group. The retardation of the recombination dynamics relative to the unmodified control dye is caused by the increase in the spatial separation of the HOMO orbital from the TiO(2) surface. The magnitude of the retardation is shown to be in agreement with that predicted from the non-adiabatic electron-tunnelling theory.     

Electrospray mass spectrometry of

There has been a substantial growth in the application of mass spectrometry (MS) methods for the analysis of inorganic materials, due to the inherent sensitivity of mass spectrometry ionization to the specific composition and structure of the analyzed materials. To date, few mass spectrometry studies have focused on metal-chalcogenide materials, an important class of semiconductor materials at the nanoscale, that exhibit interesting optical and electronic properties as a function of size. In this study, we report the application of a correlated electrospray mass spectrometry (ESMS) study between negative-ion and positive-ion mode under low-cone voltage to probe size, composition, and stability of metal-chalcogenide materials at the <1 nm scale. This correlation approach provides insight into the ionization behavior and thermodynamic stability of clusters in the <1.0 nm size domain of the form [Zn4(SPh)10][Me4N]2, [Cd4(SPh)10][Me4N]2, [E4Zn10(SPh)16][Me4N]4, [E4Cd10(SPh)16][Me4N]4 (E = S, Se). It is demonstrated that application of low-cone voltage ESMS can be a useful technique for the rapid analysis of intact solid state nanomaterials when both negative and positive ionic modes are analyzed, with a potential for extrapolation to other classes of nanoscale materials.     

High-sensitivity quantitation of cabergoline and pergolide using a triple-quadrupole mass spectrometer with enhanced mass-resolution capabilities

Quantitative analysis of pharmaceuticals with low systemic plasma levels requires the utmost in sensitivity and selectivity from the analytical method used. A recently introduced triple-quadrupole mass spectrometer with unique enhanced mass-resolution capability was evaluated in the analysis of two such drugs, cabergoline and pergolide, in plasma. Liquid chromatographic/electrospray ionization selected reaction monitoring determination of cabergoline in plasma at unit mass-resolution demonstrated improved sensitivity (50 fg on-column), coupled with suitable accuracy and precision over a broad linear dynamic range covering five orders of magnitude (50 fg to 5 ng on-column). Liquid chromatographic/atmospheric pressure chemical ionization selective reaction monitoring determination of pergolide in plasma also attained a high level of sensitivity (500 fg on-column) at unit mass-resolution, with accuracy and precision values well within pharmaceutical industry standards. Again, a linear dynamic range covering five orders of magnitude (500 fg to 50 ng on-column) was achieved for the assay. Utility of the enhanced mass-resolution feature of the triple-quadrupole mass spectrometer in the determination of pergolide resulted in an improvement in analyte sensitivity (250 fg on-column) and linear dynamic range (250 fg to 50 ng on-column).     

Sodium-iron fluorophosphate glasses: Part 2: EPR and mössbauer resonance study

EPR and Mössbauer measurements have been performed on sodium-iron fluorophosphate glasses. Mössbauer spectra show the presence of Fe³⁺ and Fe²⁺ both in octahedral coordination sites. However, for low iron concentration, EPR suggests a small number of Fe³⁺ tetrahedra coexisting with Fe³⁺ octahedra. On the basis of these results, Fe³⁺ tetrahedrally and/or octahedrally coordinated, connected with P(O, F)₄ tetrahedra would behave as a network-former cation, whereas Fe²⁺ would substitute for Na⁺ as a netweork-modifier. Long range magnetic order previously observed by magnetic measurements has been confirmed for iron-rich compositions.     

The effective dielectric constant of plasmas — A mean field theory built from the electromagnetic ionic T-matrix

This work aims to obtain the effective dielectric constant tensor of a warm plasma in the spirit of the derivation of a mixing law. The medium is made of non point-like ions immersed in an electron gas with usual conditions relating the various lengths which define the problem. In this paper the ion dielectric constants are taken from their RPA responses as developed in a previous paper [1]. Furthermore the treatment of the screening effects is made through a mathematical redefinition of the initial problem as proposed in Ref. [1]. Here the complete calculation of the T-matrix describing the scattering of an electromagnetic wave on an isolated ion immersed in an “effective medium” is given. It is used for building , in the spirit of a mixing law, a self-consistent effective medium theory for the plasma dielectric tensor. We then extend the results obtained in Ref. [1] to higher orders in ion or dielectric inclusion densities. The techniques presented are generic and can be used in areas such as elasticity, thermoelasticity, and piezoelectricity.     

Cascaded optical parametric oscillation with a dual-grating periodically poled lithium niobate crystal

We demonstrate continuous-wave cascaded optical parametric oscillation in which the signal field of the primary parametric oscillator internally pumps the secondary parametric oscillator. Wavelength tuning is achieved with temperature tuning and a fan-out grating structure of a dual-grating periodically poled lithium niobate crystal. Above the secondary threshold the primary signal power is clamped, and all the other output powers increase linearly with the input pump power, in accordance with theory. Cascaded parametric oscillation offers a convenient and efficient way to generate multiple tunable outputs.