Ab initio Computational Modeling of Glyphosate Analogs: Conformational Perspective

A historical perspective on the application of conformational analysis to structure-based ligand design approach is presented. The application of isodensity molecular electrostatic potential surfaces with the conformational energy surfaces (CES) have allowed us to reach pertinent conclusions for aiding synthetic and biochemical studies. Here we illustrate such an application on the modeling of the potent analogs of an important, environmentally stringent herbicidal compound glyphosate by constructing conformational energy surfaces. The systems were modeled by substituting F, Cl, and NH— OH moiety to the position of pharmacophoric nitrogen center in glyphosate structure. All the calculations were thoroughly performed with ab initio MO theory at Hartree–Fock method using 3-21G(d) basis functions. On the basis of the results, we identified the bioactive conformations for N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate as (−38^∘, 77^∘), (−61^∘, 111^∘), and (−167^∘, −169^∘), respectively. Geometry optimization of certain selected conformations of these compounds using hybrid DFT method with 6–31+G(d) basis functions provides nearly equal values of φ and ψ. Moreover, the results indicate that the global minimum structures of N-fluoro and N-chloro analogs of glyphosate show cyclic conformation whereas the N-hydroxyamino-glyphosate global minimum structure shows spyrocyclic and zig-zag conformation. Also, the predicted bioactive conformation of N-hydroxyamino analog optimally overlaps with glyphosate backbone in EPSPS complex with 0.1 Å RMSD value. However, the other two compounds slightly deviate from the backbone of glyphosate with RMSD of 0.92 Å for N-fluoro-glyphosate and 0.83 Å for N-chloro-glyphosate. The linear N-hydroxyamino-glyphosate exhibits relatively more number of intermolecular hydrogen bond interactions as compared to the other two analogs. Further, comparison of CES of previously studied glyphosate analogs such as N-hydroxy-glyphosate (2.2 μM) and N-amino-glyphosate (0.61 μM) with the present systems reveals the order of activity as: N-hydroxyamino-glyphosate > N-fluoro-glyphosate > N-chloro-glyphosate based on CES flexibility. Also, the calculated heats of formation of N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate are −288, −209, and −288 kcal/mol, respectively, which clearly indicate that the N-hydroxyamino and N-fluoro analogs of glyphosate are thermodynamically more stable than N-amino-glyphosate (−278 kcal/mol).     

Spectrophotometeric determination of someN-substituted phenothiazine derivatives usingN-bromophthalimide

A simple, rapid and sensitive spectrophotometric method is described for the quantitative determination ofN-substituted phenothiazines. The method depends on the formation of a stable phenothiazine free radical cation by the use ofN-bromophthalimide as oxidising agent in a strong acid medium (methanol/ sulphuric acid 1 1 v/v). The produced red or violet color possesses absorption maximum range from 500 to 530 nm. A linear relationship exists between the absorbance at (_max) and concentration in the range 5 to 40 g ml^–1 with apparent molar absorptivities range from 6 × 10³ to 12 × 10³1 mol^–1 cm^–1. The color is developed instantaneously for all the studied phenothiazines except for thioproperazine mesylate, trifluoperazine dihydrochloride and prochlorperazine mesylate that require 25, 15 and 25 min, respectively, for complete reaction. The developed colors are stable over 24 h. The average % recovery is 99.85±0.61 to 100.28±0.95. The method was applied successfully to the microdetermination of chlorpromazine HCl, promethazine HCl, pericyazine, thioproperazine mesylate, perphenazine, prochlorperazine mesylate, trimeprazine tartrate and trifluoperazine 2HCl either in pure form or incorporated in their pharmaceutical preparations. The results of analysis are in good agreement with those of the official B.P. 1988 and USP XXII.     

Preparation of methyl (1R,2S,5S)- and (1S,2R,5R)-2-amino-5-tert-butyl-cyclopentane-1-carboxylates by parallel kinetic resolution of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate

Comparison of the kinetic and parallel kinetic resolutions of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate allows for the efficient synthesis of both (1R,2S,5S)- and (1S,2R,5R)-enantiomers of methyl 2-amino-5-tert-butyl-cyclopentane-1-carboxylate.     

Hygrometric Determination of Water Activities, Osmotic and Activity Coefficients, and Excess Gibbs Energy of the System MgSO4–K2SO4–H2O

Ternary aqueous solutions of MgSO₄ and K₂SO₄ have been studied by the hygrometric method at 25°C. The relative humidity of this system is measured at total molalities from 0.35 mol-kg^–1 to about saturation for three ionic-strength fractions (y = 0.25, 0.50, and 0.80 of MgSO₄. The data allow calculation of water activities and osmotic coefficients. From these measurements, the Pitzer ionic mixing parameters are determined and used to predict the solute activity coefficients in the mixture. The results are used to calculate the excess Gibbs energy at total molalities for ionic-strength fraction y.     

(m‐CH3C6H4NH3)6P6O18

In hexakis(m‐toluidinium) cyclo­hexaphosphate, 6C₇H₁₀N⁺·­P₆O₁₈^6?, the atomic arrangement is typical of a layer structure. Layers including the centrosymmetric P₆O₁₈ ring anions develop around the (100) planes at x = . The hydrogen‐bond distribution is described.     

Rotenoid and isoflavone metabolites from an antioxidant seed extract of Dalbergia lanceolaria subsp. paniculata (roxb.) thoth

Abstract

A new rotenoid named 12-O-methylrotenolol along with five known rotenoid and isoflavone metabolites were isolated from the seeds of Dalbergia lanceolaria subsp. paniculata, collected from Egypt. The structures of these compounds were identified by physical and spectroscopic data measurements ([α]_D, UV, 1D- and 2D-NMR and MS). The methanol extract of the seeds exhibited strong antioxidant activity with IC₅₀ value 0.7?µg/µl against DPPH radical, in respect to quercetin as antioxidant reference (IC₅₀ 1.5?μM), while the tested compounds from this extract showed weak activities with IC₅₀ values ranged from 19.6 to 33.0?µM.     

Quartz crystal microbalance (QCM) in high-pressure carbon dioxide (CO2): experimental aspects of QCM theory and CO2 adsorption

The quartz crystal microbalance (QCM) technique has been developed into a powerful tool for the study of solid-fluid interfaces. This study focuses on the applications of QCM in high-pressure carbon dioxide (CO2) systems. Frequency responses of six QCM crystals with different electrode materials (silver or gold) and roughness values were determined in helium, nitrogen, and carbon dioxide at 35-40 degrees C and at elevated pressures up to 3200 psi. The goal is to experimentally examine the applicability of the traditional QCM theory in high-pressure systems and determine the adsorption of CO2 on the metal surfaces. A new QCM calculation approach was formulated to consider the surface roughness contribution to the frequency shift. It was found that the frequency-roughness correlation factor, Cr, in the new model was critical to the accurate calculation of mass changes on the crystal surface. Experiments and calculations demonstrated that the adsorption (or condensation) of gaseous and supercritical CO2 onto the silver and gold surfaces was as high as 3.6 microg cm(-2) at 40 degrees C when the CO2 densities are lower than 0.85 g cm(-3). The utilization of QCM crystals with different roughness in determining the adsorption of CO2 is also discussed.     

Synthesis, Characterization, Luminescence, and Electrochemistry of New Tetranuclear Gold(I) Amidinate Clusters: Au4[PhNC(Ph)NPh]4, Au4[PhNC(CH3)NPh]4, and Au4[ArNC(H)NAr]4

The syntheses and the X-ray structures of the tetranuclear gold(I) benzamidinate, Au₄[PhNC(Ph)NPh]₄, and the tetranuclear gold(I) acetamidinate, Au₄[PhNC(CH₃)NPh]₄, clusters are reported. The clusters are produced by the reaction of the sodium salt of an amidine ligand with the gold precursor Au(THT)Cl in a (1:1) stoichiometry. The average Au...Au distance between adjacent Au(I) atoms is ∼2.9 ?, typical of compounds having an aurophilic interaction. The four gold atoms are arranged in a square (Au...Au...Au... = 88–91°) in the acetamidinate and in a distorted square (Au...Au...Au... = 82–97°) in the benzamidinate derivative. Electrochemical oxidation of the tetranuclear complex Au₄[PhNC(Ph)NPh]₄ show three reversible waves at 0.87, 1.19, 1.42 V vs. Ag/AgCl at a scan rate of 100 mV/s in CH₂Cl₂ similar to the three reversible waves seen before from the tetranuclear complexes Au₄[ArNC(H)NAr]₄, Ar = C₆H₄-4-OMe, Ar = C₆H₄-4-Me, and Ar = C₆H₃-3,5-Cl. A summary of the chemistry of the tetranuclear Au(I) amidinate complexes Au₄[ArNC(H)NAr]₄, Ar = C₆H₄-4-OMe, C₆H₃-3,5-Cl, C₆H₄-4-Me, C₆H₄-3-CF₃, C₆F₅, C₁₀H₇ also is presented. The tetranuclear clusters Au₄[ArNC(H)NAr]₄, Ar = C₆H₄-4-OMe, Ar = C₆H₄-3-CF₃, Ar = C₆H₄-4-Me and Ar = C₆H₄-3,5-Cl are the first tetranuclear gold(I) cluster species from group 11 elements to show fluorescence at room temperature. The lifetimes of the naphthyl and trifluoromethylphenyl complexes are in the millisecond range indicating phosphorescent processes. Recently it has been shown that Au₄[ArNC(H)NAr]₄ are very effective catalysts upon calcination for room temperature CO oxidation. Congratulations to Dieter Fenske, a superb synthetic chemist with exceptional talents in cluster chemistry, on the occasion of his 65th birthday.     

Spectrophotometric determination of aluminum and copper ions using spadns

Aluminum and copper ions are selectively estimated spectrophotometrically. These ions form colored complexes with spadns which have a maximum absorbance at 580 nm. The complexes formed with both cations are stable and pH dependant; aluminum is favorably complexed at pH 5, while copper is complexed at pH 7.The percentage recoveries were found to be 99.69 ± 0.75 and 99.32 ± 0.6 with a minimum detection limit of 0.08 and 0.23 g ml^–1 for aluminum and copper ions respectively. There is insignificant interference from the 10-fold concentrations of other metal ions under the proposed reaction conditions.     

Three-stage sequential extraction procedure for metal partitioning in polluted soils and sediments

The sequential extraction procedure proposed by the Standard, Measurements and Testing program "SM&T" of the European Union has been applied to evaluate the amounts of Cr, Cu, Mn, Ni, Pb and Zn, extracted at each stage and indirectly their mobility and bioavailability in soil and sediment samples from a polluted area. Analysis of the extracts was carried out by flame atomic absorption spectrometry (FAAS). No significant matrix interferences were found except for Cr in the acetic acid and hydroxylammonium chloride extracts, which required determination by the standard additions method. Both of soils and sediments studied show similar partitioning of Mn, Ni, Cu and Cr. Mn and Ni can be considered to have significant component bound to the acido-soluble fraction, whereas, Cr and Cu occur largely in the organic and residual phases. The partitioning of Pb and Zn was different between soil and sediment. In terms of mobility and bioavailability, in soils, Ni and Mn can be regarded as moderately available followed by a lower availability of Pb while Cu, Zn and Cr have a very limited availability. In sediments, a higher availability (short-medium term) of Mn and Zn was presumed followed by a lower availability of Ni and Pb, whereas, Cu and Cr, occurring largely in the organic and residual phases, were of very limited availability.