Abstract
Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.
Highlights
Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health
A subcategory of the organophosphorus compounds, have been produced and used during wars, and they have been used in terrorist activities. ese compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis
In Iran, Japan, and other terrorist attacks [10] including the assassination of Kim Jong-nam in Malaysia [11], these compounds were used as warfare agents, due to which, many international protocol and treaties have been entrenched. e Organisation for the Prohibition of Chemical Weapons (OPCW) was formed for implementing the Chemical Weapons Convention, which came in force on 29 April 1997. is body with its 193 member states supervises the global venture to permanently or verifiably eliminate chemical weapons [12]
Summary
Organophosphorus compounds (OPCs) are organic chemicals derived from phosphoric acids and its derivatives and contain at least one carbon-phosphorus bond. Ese nerve agents can be classified into four types: (1) the G-series agents which were developed by Germans and include tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF) (Figures 1(a)–1(d)). E fluoride-releasing volatile soman and sarin, cyanidereleasing tabun, and the thiocholine-releasing VX have a stereogenic phosphorus atom All of these OPCs have two enantiomers P(−) and P(+), except for Soman which has two chiral atoms, one being a carbon centre and other being the phosphorus, which has four enantiomeric forms: C (+)P(+), C (+)P(−), C (−)P(+), and C (−)P(−) [24]. P(−) enantiomers are more toxic in nature [27]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.