CATALYTIC 'GREEN' APPROACH TOWARDS NEUTRALISATION OF ORGANOPHOSPHATE TOXICANTS

Background: Some organophosphorous derivatives have been widely used for various industrial and household applications, e.g., as pesticides, plasticizers, flame retardants and solvents. Pesticides of this family are highly toxic because of their chemical reactivity, low volatility and environmental persistency. Before WW(II) the German military started developing these substances into neurotoxin warfare agents like sarin and tabun, among others. These compounds are threats to humanity and are still being used by armies and terrorists. Their toxicity stems from potent inhibition of the enzyme acetylcholinesterase (AChE), which is crucial for the regulation of neural activity. Methods: AChE is crucial for the regulation of neural activity. “Green” decontamination strategies are necessary to reduce or eliminate the adverse effects of organophosphorous toxins on human health and our environment. Treatment of the nerve gas stock pile may be carried out by physical methods (e.g., adsorption, flushing) or by chemical decomposition to less toxic products. The latter is often done by hydrolysis, either stoichiometrically (e.g., strong alkaline solutions) or catalytically (e.g., enzymes, transition metal complexes). Recent examples of inorganic catalysts for organophosphate hydrolysis include polyoxoniobates, zirconium-based metal-organic frameworks, and zinc-based complexes. In the past, bioscavanger based on human butyrylcholinesterase was developed for neutralization of nerve gas agents but there are limitations associated with this kind of enzyme due to high stoichiometric requirement even for a single LD₅₀ dose. Results: We have recently begun efforts to develop “Green approach” for the decomposition of organophosphosphorous nerve agents, focusing on hydrolytic cleavage of P-O bonds. A combinatorial approach has been chosen for identification of the catalyst. Phage display libraries will be scanned for P-O hydrolytic activity in the presence and in the absence of various transition metal cations. In our approach, screening and isolation of the lead catalysts will be aided by activity-based probes including responsive fluorescent tags, and attached to magnetic beads. Preliminary results, using a model system, demonstrate that our quinone-methide-based active probes readily form covalent bonds to target nucleophiles upon hydrolysis of their organophosphorous moiety. These results indicate that our designed molecules will be capable of recognizing hydrolytic peptides or metallo-peptides from phage display libraries. Conclusion: In our presentation, we shall outline our general strategy for catalyst development, including results pertaining to the synthesis of organophosphorous active probes which would be novel techniques for betterment of research in the field of defence industries.