title: Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis.
abstract: 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.
authors: Molecular Biophysics Group, IBMC-Institute for Molecular and Cell Biology, Porto, Portugal; Institute for Research and Innovation in Health (I3S), University of Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal.
authors: Luís
authors: L
authors: Gales
authors: Center of Medical Chemistry (CEQUIMED-UP), Faculty of Pharmacy, University of Porto, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR/CIMAR), Porto, Portugal.
authors: Ricardo
authors: R
authors: Amorim
authors: Center of Medical Chemistry (CEQUIMED-UP), Faculty of Pharmacy, University of Porto, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR/CIMAR), Porto, Portugal.
authors: Carlos Manuel M
authors: CM
authors: Afonso
authors: UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors: Félix
authors: F
authors: Carvalho
authors: UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal; IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal. Electronic address: ricardinis@med.up.pt.
authors: Ricardo Jorge
authors: RJ
authors: Dinis-Oliveira
mesh_terms: D003461:Crystallography; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity; D012980:Sodium Salicylate / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006540:Herbicides; D010269:Paraquat; D012980:Sodium Salicylate
keywords: Complexation; Crystallography; Paraquat; Salicylates