New modified β-cyclodextrin derivatives as detoxifying agents of chemical warfare agents (II). In vitro detoxification of cyclosarin (GF): General screening and toxicokinetic aspects of OP scavengers

As standard therapy of intoxication with organophosphorus (OP) compounds is still insufficient, developing new treatment strategies is urgently required. For evaluating potential of OP detoxification of several compounds correctly, different toxicodynamic impact of OP enantiomers has to be considered thoroughly. It has already been demonstrated that β-cyclodextrin (β-CD) derivatives with attached nucleophilic substituent iodosobenzoic acid (IBA) can be regarded as potent OP scavengers due to an accelerating effect on decay of different OP. Herein, six CD derivatives permethylated or not on CD torus as well as differently attached nucleophilic substituent IBA derivative were investigated regarding detoxification of GF as an OP model substance. Acceleration of GF detoxification could be detected for all compounds with highest rate constants for propylene chain linked nucleophilic substituents on CD derivative. In addition, fast initial binding of GF on CD could be observed and is ascribed to formation of CD complexes. Furthermore, terminal plateau phase was detected of about 1% of each enantiomer reflecting the necessity of a quantitative determination at low concentrations. Moreover, this molecular depot formation may represent an additional detoxification pathway for OP.

► Quantitative GF stereoisomer detoxification by new CD derivatives is presented.
► Parameters for toxicokinetic analysis are defined for future investigations.
► Important structural elements of CD derivatives for GF detoxification are defined.
► Binding of GF on CD derivatives was slightly different for stereoisomers.
► For the first time a molecular depot of GF in CD derivative could be detected.