A pseudoreceptor docking study of 4,5-α-epoxymorphinans with a range of dielectric constants

Summary Thirteen 4,5-epoxymorphinan agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer -isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted -isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydroco-deinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.     

Dielectric Studies of Glycine–Ethylene Glycol–Water Solutions Using Time Domain Reflectometry

Time domain reflectometry (TDR) has been used for dielectric relaxation measurements on the glycine–ethylene glycol–water ternary system (TDR) at 25, 30, 35, and 40°C in the frequency range from 10 MHz to 10 GHz. Glycine–ethylene glycol–water solutions are prepared with different concentrations of ethylene glycol (0, 5, 10, 15, 20, and 30%) and also for different glycine molar concentrations (0, 0.2, 0.4, 0.6, 0.8, and 1 M). The dielectric relaxation parameters are measured for aqueous glycine solutions also to compare the results with those for the glycine–ethylene glycol–water ternary system. For all the solutions considered, only one relaxation peak was observed in this frequency range. The complex permittivity spectra for the aqueous glycine solutions can be well described by the Cole–Davidson expression, whereas that for the ternary system can be well described by the Havriliak–Negami expression. The logarithm of the relaxation time log() shows a nonlinear relation with the glycine molar concentration that implies a change in the relaxation mechanism with glycine concentration. The dielectric strength increases with an increase in glycine molar concentration, whereas it decreases with an increase in ethylene glycol concentration.     

Comparison of linear-scaling semiempirical methods and combined quantum mechanical/molecular mechanical methods for enzymic reactions. II. An energy decomposition analysis

QM/MM methods have been developed as a computationally feasible solution to QM simulation of chemical processes, such as enzyme-catalyzed reactions, within a more approximate MM representation of the condensed-phase environment. However, there has been no independent method for checking the quality of this representation, especially for highly nonisotropic protein environments such as those surrounding enzyme active sites. Hence, the validity of QM/MM methods is largely untested. Here we use the possibility of performing all-QM calculations at the semiempirical PM3 level with a linear-scaling method (MOZYME) to assess the performance of a QM/MM method (PM3/AMBER94 force field). Using two model pathways for the hydride-ion transfer reaction of the enzyme dihydrofolate reductase studied previously (Titmuss et al., Chem Phys Lett 2000, 320, 169-176), we have analyzed the reaction energy contributions (QM, QM/MM, and MM) from the QM/MM results and compared them with analogous-region components calculated via an energy partitioning scheme implemented into MOZYME. This analysis further divided the MOZYME components into Coulomb, resonance and exchange energy terms. For the model in which the MM coordinates are kept fixed during the reaction, we find that the MOZYME and QM/MM total energy profiles agree very well, but that there are significant differences in the energy components. Most significantly there is a large change (approximately 16 kcal/mol) in the MOZYME MM component due to polarization of the MM region surrounding the active site, and which arises mostly from MM atoms close to (<10 A) the active-site QM region, which is not modelled explicitly by our QM/MM method. However, for the model where the MM coordinates are allowed to vary during the reaction, we find large differences in the MOZYME and QM/MM total energy profiles, with a discrepancy of 52 kcal/mol between the relative reaction (product-reactant) energies. This is largely due to a difference in the MM energies of 58 kcal/mol, of which we can attribute approximately 40 kcal/mol to geometry effects in the MM region and the remainder, as before, to MM region polarization. Contrary to the fixed-geometry model, there is no correlation of the MM energy changes with distance from the QM region, nor are they contributed by only a few residues. Overall, the results suggest that merely extending the size of the QM region in the QM/MM calculation is not a universal solution to the MOZYME- and QM/MM-method differences. They also suggest that attaching physical significance to MOZYME Coulomb, resonance and exchange components is problematic. Although we conclude that it would be possible to reparameterize the QM/MM force field to reproduce MOZYME energies, a better way to account for both the effects of the protein environment and known deficiencies in semiempirical methods would be to parameterize the force field based on data from DFT or ab initio QM linear-scaling calculations. Such a force field could be used efficiently in MD simulations to calculate free energies.     

Recent progress in nanomaterial-enhanced fluorescence polarization/anisotropy sensors

In this review, we summarize the number of scientific publications in the field of FP/FA sensor in recent five years, and introduce the recent progress of FP/FA sensor based on nanomaterial. The various analytical applications of FP/FA sensor based on nanomaterial are discussed. We also provide perspectives on the current challenges and future prospects in the promising field.     

Conventional and unconventional infrared spectrometry and their quantitative interpretation

In condensed matter, optical properties can be described by a dielectric function (DF), and the structures observed in spectra are then related to the poles and zeros of the DF. As an example, model functions are calculated by a fit to measured spectroscopic data for polystyrene and silica. The first material shows weak, narrow bands and the latter strong, broad bands and a negative real part of the DF.Based on these model DFs, spectra are simulated which are expected to be obtained by “conventional” methods such as transmittance or reflectance measurements, or by “unconventional” methods such as reflectance at oblique incidence, diffuse reflectance, photoacoustic spectroscopy and attenuated total reflectance. A variety of simulated, typical spectra are plotted as a small “atlas”. Conditions are discussed that allow a straightforward procedure for interpreting the spectra quantitatively, i.e., the evaluation of the resonance frequency and the concentration of the oscillators under consideration.It is shown that for systems characterized by weak, narrow oscillator lines, mostly an intuitive interpretation is possible, looking only at the position and strength of “lines” in the spectra. Materials showing strong polar vibrations, however, require more sophisticated procedures for interpreting the spectra.     

Comparative study of three immunoassays based on monoclonal antibodies for detection of the pesticide parathion-methyl in real samples

Three immunoassay systems: indirect, direct competitive enzyme-linked immunosorbent assay (IC-ELISA and DC-ELISA), fluorescence polarization immunoassay (FPIA) based on monoclonal antibodies for the detection of parathion-methyl (PM) were developed and optimized. Several PM derivatives (haptens) were conjugated to proteins and fluoresceinthiocarbamyl ethylenediamine (EDF) to obtain immunogens and competitors. The influence of immunogen and competitor structures on the assay performance was investigated. IC-ELISA was the most sensitive of all techniques developed, with a detection limit of 0.08 ng ml⁻¹, but assay time was the longest (3.5 h per 96-well microtitre plate). DC-ELISA was easier to perform and quicker (1.5 h per 96-well microtitre plate) but less sensitive than IC-ELISA (detection limit was 0.5 ng ml⁻¹). FPIA was the fastest and simplest (7 min per 10 samples) but the least sensitive (detection limit was 15 ng ml⁻¹) technique. The methods were characterized by high specificity and reproducibility. The cross-reactivity for parathion-ethyl was around 30-40% for IC-ELISA and FPIA, but significantly higher (125%) for DC-ELISA. The immunoassays were applied to the analysis of PM residues in different food and environmental matrices. Methanol extracts of vegetable, fruit and soil samples were used for the analysis. Recoveries for most spiked samples averaged between 85 and 110%. The methods developed can be used for screening of food and environmental samples for PM residues without complicated clean-up.     

Neue Kupferkomplexe mit Phosphaalkenliganden. Molekülstruktur von [Cu{P(Mes*)C(NMe2)2}2]BF4 (Mes* = 2,4,6‐tBu3C6H2)

New Copper Complexes Containing Phosphaalkene Ligands. Molecular Structure of [Cu{P(Mes*)C(NMe₂)₂}₂]BF₄ (Mes* = 2,4,6‐tBu₃C₆H₂) Reaction of equimolar amounts of the inversely polarized phosphaalkene tBuP=C(NMe₂)₂ ( 1a ) and copper(I) bromide or copper(I) iodide, respectively, affords complexes [Cu₃X₃{μ‐P(tBu)C(NMe₂)₂}₃] ( 2 ) (X =Br) and ( 3 ) (X = I) as the formal result of the cyclotrimerization of a 1:1‐adduct. Treatment of 1a with [Cu(L)Cl] (L = PiPr₃; SbiPr₃) leads to the formation of compounds [CuCl(L){P(tBu)C(NMe₂)₂}] ( 4a ) (L = PiPr₃) and ( 4b ) (L = SbiPr₃), respectively. Reaction of [(MeCN)₄Cu]BF₄ with two equivalents of PhP=C(NMe₂)₂ ( 1b ) yields complex [Cu{P(Ph)C(NMe₂)₂}₂]BF₄ ( 5b ). Similarly, compounds [Cu{P(Aryl)C(NMe₂)₂}₂]BF₄ ( 5c (Aryl = Mes and 5d (Aryl = Mes*)) are obtained from ArylP=C(NMe₂)₂ ( 1c : Aryl = Mes; 1d : Mes*) and [(MeCN)₄Cu]BF₄ in the presence of SbiPr₃. Complexes 2 , 3 , 4a , 4b , and 5b‐5d are characterized by means of elemental analyses and spectroscopy (¹H‐, ¹³C{¹H}‐, ³¹P{¹H}‐NMR). The molecular structure of 5d is determined by X‐ray diffraction analysis.     

Effect of the Electrode Potential on the Oxygen Reaction Rate in the Electrode System O2, Au/La0.88Sr0.12Ga0.82Mg0.18O2.85

The polarization dependences of a porous gold electrode in contact with a solid electrolyte of the composition La_0.88Sr_0.12Ga_0.82Mg_0.18O_2.85 are studied at 600–800°C and oxygen pressures of 2 × 10⁻²-1 atm. It is shown that the rate of cathodic reduction of oxygen out of the gas phase depends on the preliminary treatment of the sample. The activation energy is equal to 110–135 kJ mol⁻¹ at a low polarization. After increasing the polarization, the activation energy for the cathodic reduction of oxygen equals 75–85 kJ mol⁻¹ and depends on the oxygen pressure as a power function with a power index of 1/4. The rate of the anodic evolution of oxygen is dependent neither on the preliminary treatment of the sample nor on the oxygen pressure in the gas phase and the polarization curve has a characteristic segment, which corresponds to a limiting overvoltage.__________Translated from Elektrokhimiya, Vol. 41, No. 8, 2005, pp. 954–962.Original Russian Text Copyright © 2005 by Shkerin, Sokolova, Beresnev.