Oxime and Non Oxime based Molecules as Detectors for Organophosphorus and Reactivators for Acetylcholinesterase

Abstract

Organophosphorus compounds are used as pesticides to control pests, as chemical newlineweapons in military conflict and unfortunately in terrorist attacks. These compounds are newlineirreversible inhibitors of acetylcholinesterase, resulting in the accumulation of newlineacetylcholine that leads to severe health complications which may be ended with the newlinedeath of the victim. Current antidotes used for reactivation of OP-AChE are not able to newlinecross the BBB efficiently, therefore being incapable to reactivate OP-AChE of the newlinecentral nervous system. Due to limitations with current antidotes, there is an urgent need newlinefor new effective antidotes that could be included in the treatment regimen of OP newlinepoisoning. Also, these OP compounds are directly sprayed on the plants and soil, newlineincreasing the chances of exposure to the civilians. So, there is a need for the newlinedevelopment of a fast, sensitive and stable sensor that can detect the presence of OP newlinecompounds in food and aqueous system. The thesis includes 5 chapters as follows: newlineIn chapter 1st, comprehensive work has been done to improve the permeability newlineof existing antidotes using a variety of strategies that include synthesis of oxime bonded newlineto peripheral site binding moiety via an alkyl, aryl, or heteroatom-containing linker, newlinesynthesis of sugar oximes, and prodrug of 2-PAM, incorporating fluorine and chlorine newlinein the structure of charged oximes. Other classes of compounds such as the mannich newlinebase, N-substituted hydroxyimino acetamide and alkylating agents, have been newlineinvestigated for reactivation of OP-AChE. Also, the rapid and sensitive, selective, real newlinetime detection of OP compounds is very much required in terms for environmental newlineprotection, health and life of living beings. A number of techniques have been newlinedeveloped over a few decades to easily detect them but still, there are numerous newlinechallenges and problems that are still to be solved.