Interactions of Diorganolead(IV) with 3-(2-Thienyl)-2-sulfanylpropenoic Acid and/or Thiamine: Chemical and in Vitro and in Vivo Toxicological Results

摘要

The reactions of PbR2(OAc)(2) (R=Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H(2)tSpa) in methanol or ethanol afforded complexes [PbR2(tspa)] that electrospray ionization-mass spectrometry (ESI-MS) and IR data suggest are polymeric. X-ray studies showed that [PbPh2(tspa)(dmso)] center dot dmso, crystallized from a solution of [PbPh2(tspa)] in dmso, is dimeric, and that [HQ](2)[PbPh2(tspa)(2)] (Q=diisopropylamine), obtained after removal of [PbPh2(tspa)] from a reaction including Q, contains the monomeric anion [PbPh2(tSpa)(2)](2-). In the solid state the lead atoms are O,S-chelated by the tspa ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa(2-) remains coordinated to PbR22+ in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe2(NO3)(2) in D2O. Prior addition of H(2)tSpa protected LLC center dot PK1 renal proximal tubule cells against PbMe2(NO3)(2); thiamine had no statistically significant effect by itself, but greatly potentiated the action of H(2)tSpa. Administration of either H(2)tspa or thiamine to male albino Sprague-Dawley rats dosed 30 min previously with PbMe2(NO3)(2) was associated with reduced inhibition of delta-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H(2)tspa and thiamine only lowered lead concentration in the kidney.