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

The reactions of PbR2(OAc)2 (R = Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H2tspa) 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)]·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 tspa2− ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa2− remains coordinated to PbR22+ in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe2(NO3)2 in D2O. Prior addition of H2tspa protected LLC-PK1 renal proximal tubule cells against PbMe2(NO3)2; thiamine had no statistically significant effect by itself, but greatly potentiated the action of H2tspa. Administration of either H2tspa or thiamine to male albino Sprague−Dawley rats dosed 30 min previously with PbMe2(NO3)2 was associated with reduced inhibition of δ-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H2tspa and thiamine only lowered lead concentration in the kidney.