Role of the Residue Q1919 in Increasing Kinase Activity of G2019S LRRK2 Kinase: A Computational Study

Mutations in multi-domain leucine-rich repeat kinase 2 (LRRK2) have been an interest to researchers as these mutations are associated with Parkinson's disease. G2019S mutation in LRRK2 kinase domain leads to the formation of additional hydrogen bonds by S2019 which results in stabilization of the active state of the kinase, thereby increasing kinase activity. Two additional hydrogen bonds of S2019 are reported separately. Here, a mechanistic picture of the formation of additional hydrogen bonds of S2019 with Q1919 (also with E1920) is presented using ‘active’ Roco4 kinase as a homology model and its relationship with the stabilization of the ‘active’ G2019S LRRK2 kinase. A conformational flipping of residue Q1919 was found which helped to form stable hydrogen bond with S2019 and made ‘active’ state more stable in G2019S LRRK2. Two different states were found within the ‘active’ kinase with respect to the conformational change (flipping) in Q1919. Two doubly-mutated systems, G2019S/Q1919A and G2019S/E1920 K, were studied separately to check the effect of Q1919 and E1920. For both cases, the stable S2 state was not formed, leading to a decrease in kinase activity. These results indicate that both the additional hydrogen bonds of S2019 (with Q1919 and E1920) are necessary to stabilize the active G2019S LRRK2.     

Conformational Mobility of 4,4′-Bisdimethyl-Aminobenzophenone in the Excited State

Quantum-chemical calculations on various conformational states of the molecule of Michler’s ketone have been carried out by semi-empirical and non-empirical methods (HyperChem 7.0 suite of programs and Gaussian 98). The influence of solvation on the relative levels of different orbital types and on the spin states of the molecule has been examined. The possibility of the TICT process occurring in polar media, which may have an important effect on the spectral characteristics of Michler’s ketone, has been investigated.__________Translated from Teoreticheskaya i Eksperimental’naya Khimiya, Vol. 41, No. 3, pp. 185–189, May–June, 2005.     

Excess Volume of Mixing of 1:1 Electrolyte Solutions at 298.15 K in the Aquo-1,4-Dioxane Mixed-Solvent System

Excess volumes of mixing for six possible binary combinations of solutions of NaCl, KCl, NaBr and KBr have been determined at constant ionic strengths of 1.000 and 2.000 mol-kg^{− 1} at 298.15 K using a dilatometer in the water + 1,4-dioxane mixed-solvent system. Pitzer’s ion-interaction model has been utilized to obtain binary and triplet interaction parameters, i.e., θ^V and ψ^V. The data were also analyzed by the Friedman Model and it is suggested that interactions between solvated ions are dictated not only by coulombic interactions but also by appreciable asymmetric effects. The data are dependent on the nature of the common ion and do not support Young’s cross-square rule. The deviation from the cross-square rule is considered to arise from preferential solvation of the ions and ion clusters in the mixed-solvent system as reflected by the appreciable contribution of triplet interactions.     

2019年毛细管电泳技术年度回顾

本文归纳了ISI Web of Science中检索的2019年度毛细管电泳（CE）技术的相关论文,从生物分析、药物分析、临床检验及医学诊断、手性拆分、食品检测、其他化合物和离子检测以及毛细管电泳-质谱（CE-MS）的应用等7个方面进行了分类说明;简要介绍了2019年度与CE技术有关的国际会议和国内会议及各会议的重点研究报告。     

Determination of the electric field gradient asymmetry from Berry’s phase in NQR of powder samples

An effect of Berry’s phase on the NQR spectrum of the rotating powder sample is described and applied for the determination of the electric field gradient asymmetry. The proposed method involves the analysis of the frequency singularities in the NQR powder patterns of the rotating samples. The Berry’s phases for the eigenstates, associated with an adiabatically changing quadrupole hamiltonian, are calculated for nuclei with a spin I = 3/2 and I = 1 as a function of the asymmetry parameter.     

Implicit allowance for “specific” hydrogen bonding contributions to hydration energies in quantum chemically based continuum models: a phenomenological perspective

The abilities of some quantum mechanically based continuum models to accurately predict hydration energies, even where “specific” hydrogen bonding interactions to the aqueous solvent are anticipated, suggests that such effects are implicitly allowed for in the electrostatic model. Examples of this phenomenon involving various ’onium ions are presented and discussed in the context of COSMO, SM2, and a revised version of the authors’ previously described PCM method.     

One-step biomimetic conversion of a furanoheliangolide into an eremantholide using Stryker’s reagent

The conversion of a furanoheliangolide structure (15-deoxygoyazensolide) into an eremantholide one (eremantholide C) was achieved by tandem hydride conjugate addition–intramolecular carbanion addition using Stryker’s reagent.     

Polyelectrolyte-mediated non-micellar synthesis of monodispersed ‘aggregates’ of gold nanoparticles using a microwave approach

‘Aggregates’ of monodispersed gold nanoparticles were synthesized for the first time in large quantities. Those particles were made in presence or in absence of gold seed in a polyelectrolyte solution using microwave heating for about 30–60 s. The average diameters of the particles calculated from TEM and SEM analysis were 22 ± 2 nm. Our analysis found that the polyelectrolyte acted as a reducing as well as a stabilizing agent. It controlled the growth of particles by aligning them on the polymeric chain and the nanoparticles were subsequently self-assembled to form an ‘aggregate’ structure. The synthetic procedure is very fast and the particles are stable for at least 6 months under ambient conditions.     

Electron Transport Properties of Ions in Aqueous Solutions of Sodium Selenite

Ion diffusion kinetics has been studied using the data of conductivity measurements for aqueous solutions of sodium selenite with different concentrations and at different temperatures. Molecular and ionic self-diffusion coefficients have been determined for infinitely dilute solutions in the temperature range 288 K-313 K. The limiting values of ion mobility and changes in the energies of translation of water molecules from ions’ hydration shell have been found. At elevated temperatures, ΔE _tr ⁰ increases for both ions in direct proportion to the crystallographic radius of the latter. Ion hydration numbers at 298 K have been calculated. The results of this study are interpreted in the light of Samoilov’s theory on positive and negative hydration of ions.Original Russian Text Copyright © 2004 by L. T. Vlaev and S. D. Genieva__________Translated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 5, pp. 870–876, September–October, 2004.     

Modeling Young’s modulus of rubber–clay nanocomposites using composite theories

The modulus reinforcement of rubber–clay nanocomposites was examined using Guth, Halpin–Tsai and the modified Halpin–Tsai equations, which are universally used for composites reinforced by fiber-like or rod-like fillers. Taking account of the lower contribution of the platelet-like filler to Young’s modulus than that of the fiber-like filler, the modulus reduction factor (MRF) for the platelet-like fillers of 0.66, determined by fitting experimental data, is introduced into the above three equations. The aspect ratios of clay platelets in rubber–clay nanocomposites were determined by statistically analyzing TEM micrographs. The predicting ability of the above three equations for polymer–clay nanocomposites is improved by introducing MRF.     

Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi

Background: Currently, only two drugs are recommended for treatment of infection with Trypanosoma cruzi, the etiologic agent of Chagas’ disease. These compounds kill the trypomastigote forms of the parasite circulating in the bloodstream, but are relatively ineffective against the intracellular stage of the parasite life cycle. Neither drug is approved by the FDA for use in the US. The hypoxanthine phosphoribosyltransferase (HPRT) from T. cruzi is a possible new target for antiparasite chemotherapy. The crystal structure of the HPRT in a conformation approximating the transition state reveals a closed active site that provides a well-defined target for computational structure-based drug discovery.Results: A flexible ligand docking program incorporating a desolvation correction was used to screen the Available Chemicals Directory for inhibitors targeted to the closed conformation of the trypanosomal HPRT. Of 22 potential inhibitors identified, acquired and tested, 16 yielded K_i’s between 0.5 and 17 μM versus the substrate phosphoribosylpyrophosphate. Surprisingly, three of eight compounds tested were effective in inhibiting the growth of parasites in infected mammalian cells.Conclusions: This structure-based docking method provided a remarkably efficient path for the identification of inhibitors targeting the closed conformation of the trypanosomal HPRT. The inhibition constants of the lead inhibitors identified are unusually favorable, and the trypanostatic activity of three of the compounds in cell culture suggests that they may provide useful starting points for drug design for the treatment of Chagas’ disease.     

Vanillin–Schiff’s bases as organic thermal stabilizers and co-stabilizers for rigid poly(vinyl chloride)

Vanillin–Schiff’s bases (VSB) were examined as thermal stabilizers and co-stabilizers for rigid poly(vinyl chloride) (PVC) in air at 180 °C. Their high stabilizing efficiency were shown by their high thermal stability value (Ts), which is the time elapsed for the detection of HCl gas, if compared with dibasic lead carbonate and cadmium–zinc soap reference stabilizers used industrially, with better extent of discoloration. Blending these derivatives with reference stabilizers in different ratios greatly lengthens the thermal stability and the extent of discoloration of the PVC.Condensation products of Vanillin with amines are very active biologically, besides having good complexation ability with metal ions. The Ni²⁺ and Co²⁺ complexes of VSB derivatives gave better thermal stability and less discoloration than the parent organic stabilizer. Also, blending these complexes with either of the used reference stabilizers in different ratios gave better thermal stability and lower extent of discoloration. Thermogravimetric analysis confirmed the improved stability of PVC in the presence of the VSB derivatives, compared to blank PVC, PVC stabilized with reference stabilizers and PVC stabilized with binary mixture of VSB derivatives with reference stabilizer.The stabilizing efficiency of Vanillin–Schiff’s base (VSB) derivatives is attributed to the replacement of the labile chlorine atoms on the PVC chains by a relatively more stable moiety of the organic stabilizer.     

Synthesis of chiral α-amino acids

A novel method for the synthesis of chiral α-amino acids has been developed where the acid functionality was constructed by oxidizing a hydroxymethyl group introduced by Evans’ method in the α-position of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.     

双子表面活性剂及其抗菌性能

Gemini surfactants contain two hydrophilic and two hydrophobic groups connected by a linkage close to the hydrophilic groups. Gemini surfactants have lower critical micelle concentration, higher surface activity, greater efficiency in decreasing the surface tension of water and the interfacial tension between water and oil, and better water solubility than conventional surfactants. Gemini surfactants are widely used as sterilizing, bacteriostatic, anti-foaming, and drug release agents in various enterprises including food production and industrial cleaning. They, therefore, play a very important social, economic, and industrial role. This paper briefly summarizes gemini surfactant development, structure, self-assembly, activity, classification, and characteristics, as well as focuses on the antibacterial mechanisms of these compounds. It is expected that the antibacterial properties of gemini surfactants may help slow the spread of the novel coronavirus (2019-nCoV).     

Memory formalism in the passive diffusion across highly heterogeneous systems

In this note, we present an extension of the Fick’s second law by introducing a memory formalism based on derivatives of fractional order to take into account the passive diffusion process across two different membranous systems, i.e., a biological membrane, where its structural complexity suggests the introduction of a space-dependent diffusion constant, and a heterogeneous highly porous system at a macroscopic level, composed of an impenetrant matrix and pores across which the solute diffuse. This approach has been employed to describe some recent experimental results concerning the transdermal diffusion of drugs through human stratum corneum and the flux of water observed across a sand layer under a constant hydrostatic pressure difference. Despite the two examples we report concern with deeply different heterogeneous systems at a different scale length, a reasonable good agreement is obtained in both the two cases.     

Flow-through fluorescence immunosensor for atrazine determination

A new flow-through fluoroimmunosensor for atrazine determination based on the use of protein A immobilized on controlled pore glass as immunoreactor is reported. The support, placed in the optical path of the flow cell, allows the ‘in situ’ quantification of atrazine by on-line antigen–antibody binding upon successive injections of both substances. The immunosensor has a detection limit of 2.1 μg l⁻¹, a sample speed of about 10 samples per hour, and provides high reproducibility both within-day (3.2% for 5 μg l⁻¹ and 2.2% for 30 μg l⁻¹) and between days. The optimum working concentration range was 2.1–50 μg l⁻¹. Possible interferences of other triazines like simazine, desethylatrazine (DEA) and desisopropylatrazine (DIA) were evaluated. Simazine and DIA were not cross-reactive; however, the cross-reactivity for DEA was CR=7.7%. The proposed immunosensor was successfully applied to the determination of atrazine in drinking water and citrus fruits.     

Ab initio and DFT computer studies of complexes of trimethylphosphine and products of substituted phosphonium cations with hydroxide, chloride and fluoride anions: Phosphorus analogues of choline and acetylcholine

Theoretical calculations (DFT, MP2) are reported for up to four sets of reaction products of trimethylphosphine, (CH₃)₃P, each with H₂O, HCl and HF together with DFT calculations on up to three sets of reaction products of substituted phosphonium cations, (CH₃)₃P–R⁺. These products comprise (a) P(III) normal complexes (CH₃)₃PHY, (b) P(IV) ‘reverse’ complexes Y(H–CH₂)₃P–R, (c) P(IV) ylidic complexes YHCH₂(CH₃)₂P–R and (d) P(V) covalent compounds Y–P(CH₃)₃–R for Y=HO, Cl and F and R=H, CH₃, C₂H₅, C₂H₄OH and C₂H₄OC:OCH₃. Calculations are carried out at the B3LYP/6-31+G(d,p) level in all cases and also at the MP2/6-31+G(d,p) level for systems in which R=H. Minimum energy structures are determined for predicted complexes or structures and geometrical properties, harmonic vibrations and BSSE corrected binding energies are reported and compared with the limited experimental information available. Potential energy scans predict equilibria between covalent trigonal bipyramidal P(V) forms and reverse complexes comprising hydrogen bonded or ion pair, tetrahedral P(IV) forms separated by low potential energy barriers. Similar scans are also reported for equilibria between reverse complexes and ylidic complexes for Y=OH and R=CH₃, C₂H₅, C₂H₄OH and C₂H₄OC:OCH₃. Corrected binding energies, structures and values of harmonic modes are discussed in relation to bonding The names ‘pholine’ and ‘acetylpholine’ are suggested for phosphorus analogues to choline and acetylcholine.     

Coordination geometry of tetradentate Schiff’s base nickel complexes: the effects of donors, backbone length and hydrogenation

The X-ray crystal structures of (N,N′-bis-(o-amidobenzilidene)-1,3-diaminopropane)nickel (Niambpr), (N,N′-bis-(o-amidobenzilidene)-1,4-diaminobutane)nickel (Niambut), (N,N′-bis-(o-thiobenzilidene)-1,4-diaminobutane)nickel(II) (Nitsalbut), bis-acetonitrile-(N,N′-bis-(o-aminobenzyl)-1,2-diaminoethane) nickel(II) tetrafluoroborate [Ni(H₄amben)(MeCN)₂] [BF₄]₂, bis-O-acetato-(N,N′-bis-(o-aminobenzyl)-1,2-diaminoethane) nickel(II) [Ni(H₄amben)(OAc)₂ · H₂O] and bis-O-acetato-(N,N′-bis-(o-aminobenzyl)-1,3-diaminopropane) nickel(II) [Ni(H₄ambpr)(OAc)₂] are presented. These structures complete the structural characterisation of the simple unsubstituted Schiff’s base complexes with N₄ and N₂S₂ donor sets and allow us to assess the effects of donor groups and polymethylene chain length on the coordination geometries of nickel(II). The hydrogenated N₄ complexes offer an insight into the effects of increased flexibility and character of the internal nitrogen donors. Unlike the parent N₄ imine species the hydrogenated amine species do not deprotonate at the peripheral nitrogen donors and do not seem to be restricted to the meridial plane of the nickel.     

STM-theory: Image potential, chemistry and surface relaxation

A critical review of the different methods used nowadays for calculating tunneling currents and STM-images is presented with a special emphasis on the role played by the interface image potential and the interaction between the tip and the sample at short distances. After presenting the most commonly used approaches to this problem, we discuss in full detail how the image potential modifies critically the interface tip–sample barrier and how neglecting this effect underestimates the tunneling currents by several orders of magnitude. Although interface non-local image potential effects are difficult to introduce in a plane-wave Density Functional approach, we show how a Green’s function Density Functional formalism based on a local-orbital basis set allows us to introduce those image effects with a good accuracy. The effect of the interaction between the tip and the sample is illustrated for an Al-tip approaching an Al surface; and the role of the electronegative atoms adsorbed on the tip is discussed considering the O/Pd(1 1 1) interface and the effect of having an O-atom adsorbed on the tip apex. Finally, by analyzing the Si(1 1 2)–Ga interface we also show how the Green’s function Density Functional approach based on a local orbital basis can also be reliably used to analyze surface steochiometries.     

Calorimetric study of cesium hexafluoroarsenate CsAsF<Subscript>6</Subscript> at elevated temperatures

Summary Cobalt(II), nickel(II) and copper(II) complexes of some aroylhydrazone Schiff’s bases derived from isoniazide (hydrazide of isonicotinic acid) with p-hydroxybenzaldehyde; 2,4-dihydroxybenzaldehyde or 2-hydroxy-1-naphthaldehyde are prepared and characterized. The study reveals that the ligands coordinate in the keto form. That transformed to the enol through the loss of HCl upon heating the solid complexes. The copper(II) complexes are thermochromic in the solid-state while the cobalt(II) complex, 3 of 2,4-dihydroxybenzaldehyde moiety is solvatochromic in hot DMF. The chromisms obtained were discussed in terms of change in the ligand field strength and/or coordination geometry.