Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase

Organophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid-1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad-spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP-inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non-oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach—that is, until earlier this year. Mannich bases not only serve as reactivators of OP-inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research.     

完全型卤代硼烷的稳定性问题

对完全型硼烷BnHn^2^-(n=4-12)及其全卤代分子BnCln^2^-作了EH系列的计算.通过能级比较,讨论了卤代硼烷以中性价态稳定存在的原因;根据HOMO-LUMO差,排列了稳定性次序,并由重叠布居计算值,对比了B-B键长数据的变化趋势,估计了未知产物的各类B-B键长.     

Ion-interaction chromatography of neutral molecules

Summary The chromatographic behavior of neutral molecules in ion-interaction chromatography (IIC) is investigated theoretically. The physical and chemical modification of the stationary phase in the presence of ion interaction Reagent (IIR) in the eluent, and adsorption competition between test analytes and IIR for inner layer sites are shown theoretically to change the partition coefficient of neutral molecules. The most reliable, literature experimental results, concerming retention behaviour of neutral molecules in IIC, were used to test the new theory. The wide variability among them was elucidated on the basis of the exhaustive retention model developed. Retention equations were compared to those which can be obtained, if the change of the analyte is zero, from the most important retention model in IIC.     

Switchable neutral bistable rotaxanes

Two switchable neutral bistable [2]rotaxanes have been synthesized, and their chemically induced mechanical switching has been studied in solution by 1H NMR spectroscopy. One of the rotaxanes was prepared by a thermodynamically controlled slippage mechanism, while the other rotaxane was obtained by a dynamic covalent chemistry protocol involving the assembly of its dumbbell component by olefin metathesis. The recognition sites present in the rod section of the dumbbell component, namely, naphthodiimide (NpI) and pyromellitic diimide (PmI) residues, were chosen in the knowledge that the ring component, 1,5-dinaphtho[38]crown-10 (1/5DNP38C10), will bind preferentially to the NpI site. However, upon introduction of Li+ ions into the solution, a 1:2 complex is formed between the PmI site, encircled by the 1/5DNP38C10 ring and two Li+ ions. Since this complex is more stable overall than the binding between the 1/5DNP38C10 ring and the NpI site, the ring component moves from the NpI site to the PmI one. This mechanical movement can be reversed by adding an excess of [12]crown-4 to the solution to act as a sequestering agent for the Li+ ions.     

Electrochemical preparation of neutral organocadmium halides

The electrochemical oxidation of cadmium metal in the presence of methyl or ethyl iodide leads to the formation of unstable RCdI. These, and related species, can be stabilised with neutral ligands, and a series of adducts of alkylaryl- and perfluoroaryl-cadmium halides have been prepared. The oxidation apparently involves a free radical mechanism. The results support previous studies of solution equilibria involving R₂Cd and CdX₂ species.     

Photolysis of N-nitrosamines in neutral media

The photolysis of N-nitrosamines in solutions of acetonitrile follows a first-order reaction with respect to the concentration of nitrosamine. Quantum yields are very low (≈ 0.1) and depend on the concentration of nitrosamine, with the observation of a linear correlation between the reciprocal of quantum yield and the reciprocal of nitrosamine concentration. For all the nitrosamines studied, the final product of the photolysis appears to be unique, alkylidenimine, which in the case of nitroso methyl benzyl amine undergoes a relatively rapid hydrolysis, giving rise to benzaldehyde, following second order kinetics. A provisional model consistent with the experimental results obtained in this work is proposed. © 1993 John Wiley & Sons, Inc.     

Electrostatic interaction of neutral semi-permeable membranes

We consider an osmotic equilibrium between bulk solutions of polyelectrolyte bounded by semi-permeable membranes and separated by a thin film of salt-free liquid. Although the membranes are neutral, the counter-ions of the polyelectrolyte molecules permeate into the gap and lead to a steric charge separation. This gives rise to a distance-dependent membrane potential, which translates into a repulsive electrostatic disjoining pressure. From the solution of the nonlinear Poisson-Boltzmann equation, we obtain the distribution of the potential and of ions. We then derive an explicit formula for the pressure exerted on the membranes and show that it deviates from the classical van't Hoff expression for the osmotic pressure. This difference is interpreted in terms of a repulsive electrostatic disjoining pressure originating from the overlap of counterion clouds inside the gap. We also develop a simplified theory based on a linearized Poisson-Boltzmann approach. A comparison with simulation of a primitive model for the electrolyte is provided and does confirm the validity of the theoretical predictions. Beyond the fundamental result that the neutral surfaces can repel, this mechanism not only helps to control the adhesion and long-range interactions of living cells, bacteria, and vesicles, but also allows us to argue that electrostatic interactions should play enormous role in determining behavior and functions of systems bounded by semi-permeable membranes.     

Computer simulation of neutral atom traps

In this paper an efficient technique to compute properties of magnetic traps with axially symmetric configurations is presented. The corresponding computer code is available. By way of example we discuss quadrupole and octupole traps of comparable trapping volume and field strength. First the quality of the multipole expansion used to represent the field is tested and then Monte Carlo calculations for the efficiency of the traps are performed. They show the octupole configuration to be slightly more efficient than the quadrupole one.     

Chemiluminescent detection of neutral gaseous radicals

This paper presents a systematic approach to the development of novel solid-state chemical sensors on the basis of heterogeneous chemiluminescence. The method is applicable for the identification and measurements of concentration of H, O, and other gaseous chemical radicals, where utilization of standard techniques is difficult. The luminescence is invoked during Eley-Rideal recombination of the radicals in question on the surface of the sensor core. A technique is discussed to separate the contributions of Eley-Rideal and Langmuir-Hinshelwood mechanisms, and to select appropriate materials for the sensor emitter fabrication. Typical sensor characteristics include sensitivity of 10(5) cm(-3), working gas pressures of 10(-8) - 10(1) Torr, and measurement time approximately 1 s.     

Gas-phase structures of neutral silicon clusters

Vibrational spectra of neutral silicon clusters Si(n), in the size range of n = 6-10 and for n = 15, have been measured in the gas phase by two fundamentally different IR spectroscopic methods. Silicon clusters composed of 8, 9, and 15 atoms have been studied by IR multiple photon dissociation spectroscopy of a cluster-xenon complex, while clusters containing 6, 7, 9, and 10 atoms have been studied by a tunable IR-UV two-color ionization scheme. Comparison of both methods is possible for the Si(9) cluster. By using density functional theory, an identification of the experimentally observed neutral cluster structures is possible, and the effect of charge on the structure of neutrals and cations, which have been previously studied via IR multiple photon dissociation, can be investigated. Whereas the structures of small clusters are based on bipyramidal motifs, a trigonal prism as central unit is found in larger clusters. Bond weakening due to the loss of an electron leads to a major structural change between neutral and cationic Si(8).     

Electrokinetic effects of adsorbed neutral polymers

On the basis of a previously developed hydrodynamic model for adsorbed polymers the charge flow along a charged interface with adsorbed (uncharged) polymer is calculated. An effective electrokinetic layer thickness is defined and its dependence on the characteristics of the adsorbed polymer and the ionic strength is studied. It is found that tails are very important for the hydrodynamic effects considered because they effectively screen the solvent flow from inner parts of the absorbed layer. The electrokinetic layer thickness increases with decreasing ionic strength, and tends to a limit equal to the hydrodynamic thickness at very low ionic strength.     

Transformation of N-chloro-N-methylbenzylamine in neutral medium

Conclusions A study was made of the transformation of N-chloro-N-methylbenzylamine in benzene medium at 80°. The main reaction products (after hydrolysis) are: the N-methylamide of benzoic acid, N-methylbenzylamine and benzaldehyde.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 185–187, January, 1971.     

Efficiency of collision-induced ionization of fast neutrals: Effects of neutral internal energy and neutral translational energy

The ionization efficiencies of fast beams of CO and C₂H₄, with oxygen as target gas were shown to increase with increasing translational energy and to decrease with increase in internal energy. The latter may arise from a greater probability of homolysis in the neutral projectile species; it is not likely to arise from increased ionization of the target. Experimental parameters (and their validity) relating to the measurement of collision-induced dissociative ionization mass spectra and which are also applicable to the reionization step in neutralization—reionization mass spectra were investigated.