Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis

Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects.