A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers.

A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-, VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE.

Interplay of Noncovalent Interactions in Ionic Liquid/Sodium Bis(2-ethylhexyl) Sulfosuccinate Mixtures: From Lamellar to Bicontinuous Cubic Liquid Crystalline Phase.

Phase transitions in mixtures of imidazolium based ionic liquid ([C12mim]Br) and anionic double tail surfactant, sodium bis(2-ethylhexyl) sulfosuccinate (AOT), were studied using a multitechnique approach. The system was primarily chosen for its expected ability to form a variety of lamellar and nonlamellar liquid crystalline phases which can transform into each other via different mechanisms. Depending on the bulk composition and total surfactant concentration, mixed micelles, coacervates, and lamellar and inverse bicontinuous cubic liquid crystalline phase were observed. Along with electrostatic attractions and geometric packing constraints, additional noncovalent interactions (hydrogen bonding, π-π stacking) enhanced attractive interactions and stabilized low curvature aggregates. At stoichiometric conditions, coexistence of coacervates and vesicles was found at lower, while bicontinuous cubic phase and vesicles were present at higher total surfactant concentrations. The phase transitions from a dispersed lamellar to inverse cubic bicontinuous phase occur as a consequence of charge shielding and closer packing of oppositely charged headgroups followed by a change in bilayer curvature. Transition is continuous with both phases coexisting over a relatively broad range of concentrations and very likely involves a sponge-like phase as a structural intermediate. To the best of our knowledge, this type of phase transition has not been observed before in surface active ionic liquid/surfactant mixtures.