Synthesis and Resolution of ATPO,a Potent and Selective Ampa Receptor Antagonist

Abstract

The excitatory amino acid (EAA) receptors mediate one of the major signaling systems in the central nervous system, and they are thought to be implicated in some neurodege-nerative disorders, e.g. Alzheimer's disease and stroke. It is of key importance to design selective ligands for every group of EAA receptors. The AMPA receptors are one such group of EAA receptors. (RS)-ATPO is a potent antagonist at the AMPA receptors, but it has hitherto been pharmacologically characterized only as the racemate.[1, 2]     

The neuroprotective effect of post ischemic brief mild hypothermic treatment correlates with apoptosis, but not with gliosis in endothelin-1 treated rats

ABSTRACT: BACKGROUND: Stroke remains one of the most common diseases with a serious impact on quality of life but few effective treatments exist. Mild hypothermia (33[DEGREE SIGN]C) is a promising neuroprotective therapy in stroke management. This study investigated whether a delayed short mild hypothermic treatment is still beneficial as neuroprotective strategy in the endothelin-1 (Et-1) rat model for a transient focal cerebral ischemia. Two hours of mild hypothermia (33[DEGREE SIGN]C) was induced 20, 60 or 120 minutes after Et-1 infusion. During the experiment the cerebral blood flow (CBF) was measured via Laser Doppler Flowmetry in the striatum, which represents the core of the infarct. Functional outcome and infarct volume were assessed 24 hours after the insult. In this sub-acute phase following stroke induction, the effects of the hypothermic treatment on apoptosis, phagocytosis and astrogliosis were assessed as well. Apoptosis was determined using caspase-3 immunohistochemistry, phagocytic cells were visualized by CD-68 expression and astrogliosis was studied by glial fibrillary acidic protein (GFAP) staining. RESULTS: Cooling could be postponed up to 1 hour after the onset of the insult without losing its positive effects on neurological deficit and infarct volume. These results correlated with the caspase-3 staining. In contrast, the increased CD-68 expression post-stroke was reduced in the core of the insult with all treatment protocols. Hypothermia also reduced the increased levels of GFAP staining, even when it was delayed up to 2 hours after the insult. The study confirmed that the induction of the hypothermia treatment in the Et-1 model does not affect the CBF. CONCLUSIONS: These data indicate that in the Et-1 rat model, a short mild hypothermic treatment delayed for 1 hour is still neuroprotective and correlates with apoptosis. At the same time, hypothermia also establishes a lasting inhibitory effect on the activation of astrogliosis.     

Mass Spectrometry Study of Coumarins: Correlation Between Charges of Atoms and Fragmentation Processes

The mass spectrometry of a number of 6-substituted coumarins was studied in the context of correlating fragmentation pathways and electronic charges of atoms performed by AM₁ semiempirical method. The atomic charges of atoms are found to be good predictors of the fragmentation pathways.     

Effect of pH on the fluorescence and phosphorescence spectra of indolecarboxylic acids. Evidence for the existence of a singlet excited-state indole acid dianion

Room-temperature electronic absorption, fluorescence, and low-temperature (77 K) phosphorescence spectra of a series of indolecarboxylic acids have been measured in predominantly aqueous solutions at pH 1.2, 7.0, 12.5, and in 5 N NaOH. The ¹L_a and ¹L_b π, π ¹ states have been assigned to the electronic transitions for all the compounds under study. The quenching of fluorescence, the appearance of a new fluorescence emission band, red-shifted by 40 nm, in very alkaline media, and the disappearance of the indole carboxylate short-wavelength band have been attributed to the formation of an excited singlet-state indolate carboxylate (dianion) stabilized by hydrogen bonding with the solvent. The existence of two successive excited singlet-state prototropic equilibria is discussed.     

Selective fluorescence quenching of biologically important acidic and non-acidic indoles by trivalent lanthanide ions and analysis of mixtures by a fluorimetric quenching method

The effects of several lanthanide(II)(Ln³⁺)ions(Dy³⁺,Er³⁺,Eu³⁺,Nd³⁺,Yb³⁺) on the room-temperature fluorescence spectra of 2-indolecarboxylic acid, 5-indolecarboxylic acid, 5-methoxy-2-indolecarboxylic acid and 3-indoleacetic acid were investigated. It was found that the fluorescence quenching by Ln³⁺ ions is much more efficient for the acidic compounds than for non-acidic indoles. Stern-Volmer relationships were obtained for most acidic indoles in the Ln³⁺ concentration range 10^?7–10^?4 M, with quenching constants ranging between 3 × 10³ and 4.6 × 10⁵ l mol^?1. A fluorimetric quenching method was developed for the quantitative analysis of binary mixtures of acidic and non-acidic indoles.     

Photochemically-Induced Fluorescence Dosage of Non-Fluorescent Pyrethroid (Etofenprox) in Natural Water Using a Cationic Micellar Medium

An analytical method based on the use of UV-irradiation to produce fluorescent derivatives from Etofenprox a non-fluorescent pyrethroid insecticide is described. The impact of cetyltrimethylammonium chloride (CTAC) micellar medium on the Etofenprox photochemically-induced fluorescence (PIF) is reported. Parameters influencing the sensitivity and repeatability of the PIF method have been optimized. The alkaline medium (NaOH 6 × 10⁻² M) + CTAC surfactant molecules (3.84 mg/ml) in acetonitrile is found to be very suitable for this pyrethroid insecticide analysis in environment matrices. Linear dynamic range is established over more than two orders of magnitude. The limit of detection is lower than 5 ng/ml. The method seems to be suitable for environmental matrices quality control. Application to the analysis of spiked natural waters gave recoveries rate ranged from 94 to 104% and 107 to 115% respectively for river and pound water.     

Revisiting the photophysical properties and excited singlet-state dipole moments of several coumarin derivatives

The solvent effects on the electronic absorption and fluorescence emission spectra of several coumarins derivatives, containing amino, N,N-dimethyl-amino, N,N-diethyl-amino, hydroxyl, methyl, carboxyl, or halogen substituents at the positions 7, 4, or 3, were investigated in eight solvents with various polarities. The first excited singlet-state dipole moments of these coumarins were determined by various solvatochromic methods, using the theoretical ground-state dipole moments which were calculated by the AM1 method. The first excited singlet-state dipole moment values were obtained by the Bakhshiev, Kawski-Chamma-Viallet, Lippert-Mataga, and Reichardt-Dimroth equations, and were compared to the ground-state dipole moments. In all cases, the dipole moments were found to be higher in the excited singlet-state than in the ground state because of the different electron densities in both states. The red-shifts of the absorption and fluorescence emission bands, observed for most compounds upon increasing the solvent polarity, indicated that the electronic transitions were of π-π* nature.     

1B2(1Sigma(u)+) excited state decay dynamics in CS2

The authors report time resolved photoelectron spectra of the (1)B(2)((1)Sigma(u) (+)) state of CS(2) at pump wavelengths in the region of 200 nm. In contrast to previous studies, the authors find that the predissociation dynamics is not well described by a single exponential decay. Biexponential modeling of the authors' data reveals a rapid decay pathway (tau<50 fs), in addition to a longer lived channel (tau approximately 350-650 fs) that displays a marked change in apparent lifetime when the polarization of the pump laser is rotated with respect to that of the probe. Since the initially populated (1)B(2)((1)Sigma(u) (+)) state may decay to form either S((1)D) or S((3)P) products (the latter produced via a spin-orbit induced crossing from a singlet to a triplet electronic surface), this lifetime observation may be rationalized in terms of changes in the relative ionization cross section of these singlet and triplet states of CS(2) as a function of laser polarization geometry. The experimentally observed lifetime of the longer lived channel is therefore a superposition of these two pathways, both of which decay on very similar time scales.