Differences between some biological properties of enantiomers of alkyl S-alkyl methylphosphonothioates

Oxidative biodegradation of phosphorothiolates by fungal laccase

“…We have shown here that oxidative biodegradation of both optical enantiomers of VX and RVX by laccase/ABTS was verified by the enzymatic AChE assay, GC/MS and 31 P‐NMR analysis. It was previously noted by Hall et al [21]that the P(−) enantiomer of VX is 6.4‐fold more toxic than its P(+) antipode. However, in contrast to other chiral OP compounds where the P(+) enantiomer is far less toxic than its P(−) counterpart, the P(+) isomer of VX is still very toxic (LD 50 =0.21 μmol/kg, subcutaneous in rats) and the apparent bimolecular rate constants of AChE inhibition in vitro by these isomers are similar (4.5×10 7 and 2.8×10 6 M −1 min −1 , respectively) [21].…”

“…It was previously noted by Hall et al [21]that the P(−) enantiomer of VX is 6.4‐fold more toxic than its P(+) antipode. However, in contrast to other chiral OP compounds where the P(+) enantiomer is far less toxic than its P(−) counterpart, the P(+) isomer of VX is still very toxic (LD 50 =0.21 μmol/kg, subcutaneous in rats) and the apparent bimolecular rate constants of AChE inhibition in vitro by these isomers are similar (4.5×10 7 and 2.8×10 6 M −1 min −1 , respectively) [21]. Therefore, oxidative biodegradation of both optical enantiomers of VX and RVX by laccase/ABTS is important, since it leads to complete detoxification of these toxic nerve agents.…”

Chromatographic resolution, characterisation and quantification of VX enantiomers in hemolysed swine blood samples

“…For comparison, literature data of the specific optical rotation are as follows: −12 for (−)-VX (0 • C, from [7]), −30.2 for (−)-VX and +31.0 for (+)-VX (20 • C, from [15]). …”

“…In previous studies (cf. Table 2) the purity was examined exper- imentally with two methods: NMR with chiral shift reagents (semi-quantitative method [17]) and stereospecific synthesis [7]. The precise quantitative determination of the enantiomeric excess was not possible.…”

“…The first synthesis and determination of the absolute configuration and toxicological characterisation of VX enantiomers were carried out by scientists at the Chemical Defence Establishment in Porton Down [7].…”