Reactivity of paraquat with sodium salicylate: formation of stable complexes.
Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ.
REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. ricardinis@sapo.pt
Ricardo Jorge
RJ
Dinis-Oliveira
Paula Guedes
PG
de Pinho
António César Silva
AC
Ferreira
Artur M S
AM
Silva
Carlos
C
Afonso
Maria de Lourdes
Mde L
Bastos
Fernando
F
Remião
José Alberto
JA
Duarte
Félix
F
Carvalho
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D008401:Gas Chromatography-Mass Spectrometry; D006540:Herbicides / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D010269:Paraquat / Q000737:chemistry*; D012980:Sodium Salicylate / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006540:Herbicides; D007202:Indicators and Reagents; D017665:Hydroxyl Radical; D010269:Paraquat; D012980:Sodium Salicylate