An investigation of the relationships between the inactivation rate constant of the BoNT/A LC neurotoxin by several 1,4-benzoquinone and 1,4-naphthoquinone derivatives was carried out. A statistically significant relationship was found (n=21, R= 0.97, F(7,13)=25.63 (p<0.000001), SD=0.20) involving local atomic reactivity indices of two oxygen atoms and a carbon one. The conditions for a high rate are presented and discussed. The suggestion that these molecules form a covalent bond with Cys-165 after the formation of the reversible ligand-site complex was tested through a docking study of all the molecules with the B monomer of the Clostridium botulinum neurotoxin serotype A light chain. It is found that Cys-165 is very far for the site of the reversible ligand-site interaction. It is suggested that His-223 is a better candidate for a covalent bond formation.
