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Metabotropic glutamate receptors (mGluRs) are important as candidate therapeutic targets for many neurological disorders. In the present work, the focus has been on the mGluR1 subtype, where agonists have a proconvulsant profile while antagonists exert anticonvulsant activity. Identification of molecular determinants for the inhibition of mGluR1 provides a new avenue for the discovery and development of novel anticonvulsant drugs. Spatial configuration of key groups alone cannot explain activation selectivity at this specific receptor subtype. In fact, all known agonists and antagonists acting at mGluR1 can accommodate the same critical moieties in a similar geometric arrangement that corresponds to the extended conformation of glutamate. Therefore, other factors must account for the differences in activation. This study presents the results of an analysis of a large suite of steric, topological, electrostatic, and thermodynamic molecular properties calculated for a representative set of potent mGluR1 agonists and antagonists. Global steric parameters and the total nonpolar area provide discrimination between the mGluR1 agonists and antagonists considered in the present work. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 2018–2027, 2001  相似文献   

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CL-20 is a polycyclic energetic nitramine, which may soon replace the monocyclic nitramines RDX and HMX, because of its superior explosive performance. Therefore, to predict its environmental fate, analytical and physico-chemical data must be made available. An HPLC technique was thus developed to measure CL-20 in soil samples based on the US Environmental Protection Agency method 8330. We found that the soil water content and aging (21 days) had no effect on the recoveries (>92%) of CL-20, provided that the extracts were kept acidic (pH 3). The aqueous solubility of CL-20 was poor (3.6 mg l(-1) at 25 degrees C) and increased with temperature to reach 18.5 mg l(-1) at 60 degrees C. The octanol-water partition coefficient of CL-20 (log KOW = 1.92) was higher than that of RDX (log KOW = 0.90) and HMX (log KOW = 0.16), indicating its higher affinity to organic matter. Finally, CL-20 was found to decompose in non-acidified water upon contact with glass containers to give NO2- (2 equiv.), N2O (2 equiv.), and HCOO- (2 equiv.). The experimental findings suggest that CL-20 should be less persistent in the environment than RDX and HMX.  相似文献   

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Microstructures of poly (ethylene-co-vinyl acetate) (EVA) are dependent on the distribution of VA units as well as the VA content. Simple analytical method to determine microstructure of EVA was established using melting points of EVA and correlationship with those of wax and its ester. EVAs with the VA contents of 9.5–40 wt% (3.3–17.8 mol%) were used. The melting points were analyzed using differential scanning calorimetry (DSC). EVAs had two melting points of Tm1 and Tm2 at 96–44 and 56 - 36 °C, respectively. The melting points were found to be closely related to the minimum carbon number participating in the crystal formation (CNmin). The crystalline size could be estimated by equation of CNmin = - ln [(106.7 - Tm)/214.8]/0.055 + 15. The CNmin1 and CNmin2 were 68–38 and 41–35, respectively. The CNmin1 decreased by about 4.5/mol% until 6.7 mol% of the VA content, while the CNmin2 slightly decreased by about 0.4/mol%. It was found that EVA would be generally composed of three ethylene block sizes of ~VA-(CH2CH2)c1>20-VA-(CH2CH2)15<c2<20-VA-(CH2CH2)a<15-VÃ (c1 and c2: crystalline regions, a: amorphous region). Size of the amorphous region became smaller by increasing the CNmins. EVAs deviated from the average trends could be explained by difference in the microstructures such as the ethylene block sizes and branched structures. It was possible to explain difference in the microstructures of EVAs with the same VA content by difference in the CNmins obtained using the Tms.  相似文献   

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Chemical graph theory facilitates different tools that have significant applications in drug design and development. Recently Gutman et al., introduced a novel vertex-degree-based topological index called elliptic Sombor index and its application through geometric approach. This article focuses on chemical applicability of elliptic Sombor index through regression models using 22 benzenoid hydrocarbons. In this process, the chemical applicability of elliptic Sombor index with various physicochemical properties of benzenoid hydrocarbons through curvilinear regression models is carried out. The data of the statistical analysis shows that elliptic Sombor index is potential predictive index for the property polarizability.  相似文献   

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The solubilities of solid hexane and cyclohexane in liquid argon at 87.3 K have been measured by the filtration method. The hexane and cyclohexane content in solution was determined using gas chromatography. The solubilities of the C6 hydrocarbons in liquid argon at 87.3 K are (0.56 ± 0.11) × 10-7 mole fraction for hexane and (1.04 ± 0.30) × 10-7 mole fraction for cyclohexane. The Preston–Prausnitz method was used for calculation of the solubilities of solid hexane and cyclohexane in liquid argon in the temperature range 84–110 K. The values of the solvent–solute interaction constant l12 were also calculated.  相似文献   

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The solubilities of pentane, 2-methylbutane (isopentane) and cyclopentane were measured in liquid nitrogen at 77.4 K by the filtration method. The solubilities of the C5 hydrocarbons in liquid nitrogen at 77.4 K vary from 1.8×10–8 mole fraction for cyclopentane, to 3.0×10–8 mole fraction for pentane and 3.2×10–7 mole fraction for 2-metylbutane. Correlations between the solubilities of alkanes, alkenes and cyclic hydrocarbons in liquid nitrogen, and some properties of solutes [normal boiling point T b , enthalpy of vaporization at normal boiling point H b and the mean of the enthalpy of vaporization and the enthalpy of melting [(H b +H m )/2] are presented.  相似文献   

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The melting properties and the heat capacity of the solid state and the melt state 4’-bromomethyl-2-cyanobiphenyl (OTBNBr) were determined. The enthalpy, entropy and Gibbs free energy of fusion were also calculated. The solubility of OTBNBr in eight organic solvents was experimentally measured at temperatures from (283.15 to 323.15) K by using a static method. The reasons for the differences of the solubility of OTBNBr in various solvents are discussed by using the intermolecular interaction. Furthermore, the experimental solubility values were well correlated by the modified Apelblat equation, the λh equation, the Wilson model and the van’t Hoff equation. Finally, the temperature dependence of the activity coefficient and the van’t Hoff enthalpy in the tested solutions was investigated and is discussed.  相似文献   

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The solubilities of 1-pentene ice in liquid nitrogen at a temperature of 77.4 K and in liquid argon at 87.3 K have been measured by the filtration method. The 1-pentene content in solution was determined using gas chromatography. The experimental value of the mole fraction solubility of 1-pentene ice in liquid nitrogen at 77.4 K is: (1.28±0.25)×10–7 and (4.11±0.44)×10–7 in liquid argon at 87.3 K. The Preston–Prausnitz method was used for calculation of the solubilities of 1-pentene ice in liquid nitrogen in the temperature range 64.0–90.0 K and in liquid argon in the temperature range 84.0–90.0 K. The parameters l 12 were also calculated. At 90.0 K liquid argon is the better solvent for 1-pentene ice than is liquid nitrogen.  相似文献   

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