Soman characteristics

Branching of the O-alkyl ester chain of organo-phosphorus compounds may introduce an asymmetric center, which together with an asymmetric substituted phosphorus atom creates a number of stereoisomers. Diastereoisomers may even be separated on a conventional capillary GC column. This is, for instance, the case with the nerve gas soman, which usually produces two peaks in a gas chromatogram. Although this is characteristic for identifying soman, it also increases the GC/MS detection limit by a factor of two. 

Interaction of CarbE with nerve agents follows a kinetic of first order characterized by inhibition of CarbE at the active site serine residue described by a bimolecular rate constant, ki (Maxwell and Brecht, 2001). For noncharged nerve agents (e.g. sarin and soman) the ki of rat serum CarbE was found to be >10 M min whereas cationic substrates (e.g. VX) are converted with poor reactivity (ki < 10" M min ). This specificity is explained by the electrostatic characteristics of the large active site containing only a few cation-II bonding and anionic residues (Maxwell and Brecht, 2001 Satoh and Hosokawa, 2006). 

Characteristic Activity mw1 Soman/ DFP Ratio Mn2+ Stimulation Mipafox Inhibition... 

S-200 and S-300 molecular sizing column with a fraction volume of approximately half of that used in previous studies in order to increase resolution. Three repeatable peaks capable of the hydrolysis of DFP immediately became apparent. Upon the addition of Mn2+, a fourth peak appeared. The activities were identified as Tt DFPase-1, Tt DFPase-2,... Tt DFPase-5, and their characteristics can be found in Table 10.2. Molecular weights of the Tetrahymena OPA anhydrases range from 67,000 Da to 96,000 Da. The activity of DFPase-4 is stimulated 17- to 30-fold with Mn2+. Tt DFPase-1, Tt DFPase-2, and Tt DFPase-3 are only stimulated two- to fourfold, and part of this increase may be due to contamination by the higher molecular weight Tt DFPase-4. Soman to DFP ratios are approximately 1 1 for the Tetrahymena OPA anhydrases. 

Nervous tissue of a variety of invertebrates has been screened for OPA anhydrase activity. Other mollusks have been reported to contain OPA anhydrases, notably Octopus, Anisodoris (sea-lemon), Aplysia (sea-hare), and Sepia (cuttlefish) (Hoskin and Long 1972). Sepia and Octopus hydrolyze DFP faster than tabun, a squid-type OPA anhydrase characteristic employed at that time, and now by the DFP/soman ratio. Conversely, Aplysia, Spisula, andHomarus (lobster) hydrolyze tabun faster than DFP (Hoskin and Brande 1973), a typically Mazur characteristic. Soman to DFP ratios and Mn2+ stimulation for several species are shown... 

The multiple activities in T. thermophila share some of the characteristics of both the squid-type OPA anhydrase and classical Mazur-type OPA anhydrase found in hog kidney. In crude preparations, the OPA anhydrase activity has the characteristics of the hog kidney OPA anhydrase in that it hydrolyzes soman faster than DFP, is stimulated by Mn2+, and is inhibited by mipafox. Further purification has revealed that the hydrolysis of soman and the stimulation of this hydrolysis by Mn2+ is principally due to the Tt DFPase-4. The Tt DFPase-1, Tt DFPase-2, and Tt DFPase-3 hydrolyze soman and DFP at approximately the same rates and demonstrate only moderate stimulation of soman hydrolysis by Mn2+ and yet are inhibited by mipafox. The Tetrahymena OPA anhydrases fall within a narrow range from 96,000 Da to 67,000 Da. However, this range of molecular weights is larger than that typically ascribed to the Mazur-type enzymes. The Tetrahymena OPA anhydrases can be purified by ammonium sulfate precipitation, like the squid-type OPA anhydrase. 

Subsequent to the acute cholinergic manifestations of OP toxicity in humans, and approximately 24-96 hours after exposure, the onset of an "intermediate syndrome" which includes ocular effects has been recognised more recently for some OPs (Senanayake and Karalliedde, 1987 Karademir et aL, 1990). The associated clinical signs, which are characteristically different from those seen in OP-induced delayed pol)meuropathy, are paralysis and weakness of proximal limbs, respiratory, neck and cranial muscles, including those innervated by the oculomotor nerve. The occurrence of myopathy in rats exposed to diisopropylfluorophosphate, paraoxon or soman (Wecker et aL, 1978 Vanneste and Lison, 1993) resembled the features of the "intermediate syndrome". The severity and duration of the myopathy in rats appeared directly related to the degree of inhibition of AChE. 

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