Defense against chemical warfare agents and toxic industrial chemicals

Abstract

Research on mitigation of toxic threats is critical to national defense, but is often hazardous. Toxicity generally arises at the molecular level via reactions between toxins and host biomolecules. This lends itself well to simulations from which one may safely derive the insight required for effective preventative or therapeutic response strategies. Thus, in this paper we have applied quantum chemical methods to address toxicity arising from both hostile (i.e., nerve agents) and inadvertent (e.g., toxic industrial chemicals) sources. Neurotoxic reactions involving inhibition of the acetylcholinesterase enzyme have been structurally and energetically characterized with mind to mitigating the process. In a complementary effort, interactions between toxins and various catalytic and filtering media have been reported with an aim of improving chemical protection devices.

Infrared Spectroscopic Study of the Adsorption of HCN by γ-Al2O3: Competition with Triethylenediamine for Adsorption Sites

“…For HCN adsorption, Cu 2+ functionalization of TEDA-treated surfaces has been shown to be important . Theoretical studies suggest the existence of significant interactions between the Cu 2+ center and HCN, with binding energies for the HCN···Cu 2+ complex as high as ∼112 kcal mol -1 , whereas the HCN···TEDA complex exhibits a much smaller binding energy of only ∼7 kcal mol -1 …”

Acetylcholinesterase: Molecular Modeling with the Whole Toolkit

“…Experimental NMR data and previous molecular dynamics work [52,81] had suggested a shortening of the hydrogen bonding within the active site upon binding. It was demonstrated in the work of Hurley et al that this in fact will only occur in quantum models containing the Glu202 residue [87,88]. It must be noted that this is the case even in configurations where His447-Glu334 is the primary hydrogen bond (rather than His447-Glu202).…”

“…This was furthered by subsequent proton NMR data [86]. Later quantum work [87,88] made an initial attempt to address some of these issues. The model used was expanded from earlier work to include the full catalytic triad residues (rather than sidechain models), the full oxyanion hole residues, Glu202, and an aged DEFP (organophosphorus compound).…”