Sarin mechanism

The rate of hydrolysis of sarin on Dowex-50 cation exchange resin is insensitive to the stirring rate. However, with a more active catalyst (Amberlite-IRA 400), the rate constant at 20°C was 5.3, 7.5, and 8.5 h at 60,800 and 1000 revolutions/min , respectively, suggesting that film diffusion was the rate-limiting. step. Thus, the mechanism of the rate-limiting step depends on the nature of the catalyst [34]. 

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

A hydroxoaqua copper complex containing N, N, N, A -tetramethyl-1,2-diamino-ethane (250) is an excellent catalyst for the hydrolysis of sarin, O-isopropyl methylphosphonofluoridate (251), and diethyl p-nitrophenyl phosphate (252 R = Et). The mechanism of the reaction probably involves bound hydroxide attacking the phosphoryl group with concomitant electrophilic catalysis by copper. 

During the Second World War, even before the mechanism of toxicity had been established, related compounds including sarin and tabun were developed for use as so-called nerve gases. These compounds possess exceptionally high mam-... 

Warren, R. and Sarin, V.K. (1989). In Application of Fracture Mechanics to Composite Materials. Composite Materials Series, Vol. 6 (K. Friedrich ed.), Elsevier, Amsterdam, pp. 571-614. 

The oxime-induced reactivation of organophosphorus-inhibited AChE has been modeled recently through the Density Functional Theory (DFT) approach. Two possible computed reactivation pathways of Sarin-inhibited AChE adduct by formoximate anion are shown in Scheme The two-step mechanism (Scheme 7B) is favored by the authors. 

Today, everyone is aware of terrorist activity. A well-known terrorist attack involving chemicals occurred in 1995 with the release of the nerve gas sarin in the subway systems of Tokyo, resulting in the death of 12 people and injury of many more. Should chemicals again be used for terrorist activity, forensic pharmacologists and toxicologists may be called upon to analyze bodily samples in order to identify the chemical, determine its mechanism of action, and propose antidotes and preventive measures. 

Acetylcholine is a neurotransmitter that functions in conveying nerve impulses across synaptic clefts within the central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across the synapse by the release of acetylcholine, acetylcholinesterase is released into the synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of the nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation. Organophosphorus and carbamate pesticides (Chapter 5) along with some nerve gases (i.e., sarin) elicit toxicity via this mechanism. 

Also the reaction pathways of Sarin decomposition catalyzed by selected forms of MgO were investigated [38]. In the case of the decomposition on the nonhydroxylated MgO surface, the removal of fluorine from Sarin was modeled. Fluorine was transferred from Sarin into binding distance with the Mg atom of the MgO surface (Fig. 13.9). It was revealed that such a structure provides a reliable model for the reaction mechanism. A two-step reaction mechanism was assumed. In the first step, Sarin creates a stable adsorbed complex with MgO through three chemical bonds with the MgO surface (the Al-GB model). It is expected that the transfer of the fluorine atom to the surface of MgO is accompanied by a change in the conformation of Sarin. In the second step, the bond between P and F is broken (the Al(t)-GB model) the fluorine atom is transferred to the Mg atom of the surface and the remaining part of Sarin adopts the most energetically favorable conformation (the Al(f)-GB model). 

An ONIOM study of the adsorption of Sarin on dickite (a 1 1 dioctahedral clay mineral of the kaolinite group)85 was recently published. For the calculations of the studied systems, the two-layered ONIOM method using combinations of quantum-mechanical methods was applied.43,86,87 The investigated systems of... 

Grigoryan, H., Schopfer, L.M., Thompson, C.M., Terry, A.V., Masson, P., Lockridge, O. (2008). Mass spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin a potential mechanism of long term toxicity by organophos-phoms agents. Chem. Biol. Interact. April 22. (Epub ahead of print)... 

One of the major mechanisms known for sarin-induced toxicity is the irreversible inhibition of the enzyme acetyl-eholinesterase (AChE), resulting in central accumulation of acetylcholine (ACh) and overexcitation of cholinergic neurons in sarin exposure related neurotoxicity. Besides this, a range of noncholinergic effects have been observed... 

DNA polymerase alpha was up-regulated following low-level sarin exposure. Since mammalian DNA replication (and possibly DNA repair) mechanisms utilize DNA... 

---