Chemistry:Isomalathion
Isomalathion is an impurity and a toxic degradation product found in some batches of malathion.[1] It arises from the thermal or photochemical isomerization of malathion.[2] Whereas the structure of malation is, generically, RSP(S)(OCH3)2, the connectivity of isomalathion is RSPO(SCH3)(OCH3). It also has four stereoisomers due to two chiral centers, containing asymmetric phosphorus and carbon atoms placed at positions 1 and 3.[2] Being significantly more toxic to humans than malathion, it has resulted in human poisonings.[3]
History/Discovery
Isomalathion's presence and recognition as a toxic compound, especially in commercial formulations, was revealed in 1976, during Pakistan's malaria epidemic. Out of the 7500 field workers assigned to contain malaria during Pakistan's malaria control program, 2800 spraymen suffered from malathion poisoning, including 5 deaths. The spraymen who exhibited the greatest levels of toxicity were contained the highest levels of isomalathion, highlighting it's significance as a toxic compound.[4]
Properties
Isomalathion's toxicity lies in its ability to act as an inhibitor of carboxyesterase and acetylcholinesterase (AChE). The stereoisomers denoted and ordered in potency of inhibiting AChE are (1R,3R) > (1R,3S) > (1S,3R) > (1S,3S).[2] Isomalathion is considered to be an organophosphorous compound (OP) which, like malathion, is commonly found in insecticides, pesticides and chemical warfare agents. Compounds like isomalathion get their toxicity by the inhibition of enzymes such as AChE, like previously mentioned, and butyrylcholinesterase (BChE). This mechanism of inhibition is primarily through the OP phosphorylating the Ser active site of the enzyme, leading to the formation of a stable conjugate. [1]
References
- ↑ 1.0 1.1 Li, He; Schopfer, Lawrence M.; Nachon, Florian; Froment, Marie-Thérèse; Masson, Patrick; Lockridge, Oksana (2007). "Aging Pathways for Organophosphate-Inhibited Human Butyrylcholinesterase, Including Novel Pathways for Isomalathion, Resolved by Mass Spectrometry" (in en). Toxicological Sciences 100 (1): 136–145. doi:10.1093/toxsci/kfm215. ISSN 1096-6080. https://academic.oup.com/toxsci/article/1626418/Aging.
- ↑ 2.0 2.1 2.2 Doorn, Jonathan A.; Thompson, Charles M.; Christner, Robert B.; Richardson, Rudy J. (2003-08-01). "Stereoselective Inactivation of Torpedo californica Acetylcholinesterase by Isomalathion: Inhibitory Reactions with (1 R )- and (1 S )-Isomers Proceed by Different Mechanisms" (in en). Chemical Research in Toxicology 16 (8): 958–965. doi:10.1021/tx030026e. ISSN 0893-228X. https://pubs.acs.org/doi/10.1021/tx030026e.
- ↑ Rengasamy, S.; Parmer, Balraj S. (1988). "Investigation of some factors influencing isomalathion formation in malathion products". Journal of Agricultural and Food Chemistry 36 (5): 1025–1030. doi:10.1021/jf00083a030.
- ↑ Josse, Rozenn; Sharanek, Ahmad; Savary, Camille C.; Guillouzo, Andre (2014). "Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG cells" (in en). Chemico-Biological Interactions 209: 68–76. doi:10.1016/j.cbi.2013.12.002. https://linkinghub.elsevier.com/retrieve/pii/S0009279713003232.
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