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 PbR(2)(OAc)(2) (R = Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H(2)tspa) in methanol or ethanol afforded complexes [PbR(2)(tspa)] that electrospray ionization-mass spectrometry (ESI-MS) and IR data suggest are polymeric. X-ray studies showed that [PbPh(2)(tspa)(dmso)] x dmso, crystallized from a solution of [PbPh(2)(tspa)] in dmso, is dimeric, and that [HQ](2)[PbPh(2)(tspa)(2)] (Q = diisopropylamine), obtained after removal of [PbPh(2)(tspa)] from a reaction including Q, contains the monomeric anion [PbPh(2)(tspa)(2)](2-). In the solid state the lead atoms are O,S-chelated by the tspa(2-) ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa(2-) remains coordinated to PbR(2)(2+) in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe(2)(NO(3))(2) in D(2)O. Prior addition of H(2)tspa protected LLC-PK1 renal proximal tubule cells against PbMe(2)(NO(3))(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 PbMe(2)(NO(3))(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.
Casas
José S
JS
Departamento de Química Inorgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Galicia, Spain. sergio.casas@usc.es
Castaño
M Victoria
MV
Sánchez
Agustín
A
Sordo
José
J
Torres
M Dolores
MD
Couce
María D
MD
Gato
Angeles
A
Alvarez-Lorenzo
Carmen
C
Camiña
M Félix
MF
Castellano
Eduardo E
EE
D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D011756:Diphosphates / Q000737:chemistry; D007854:Lead / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000097:blood; D011437:Propylamines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013831:Thiamine / Q000737:chemistry*
C549497:3-(2-thienyl)-2-sulfanylpropenoic acid; D000179:Acrylates; D011756:Diphosphates; D009942:Organometallic Compounds; D011437:Propylamines; D013438:Sulfhydryl Compounds; D007854:Lead; C007442:diisopropylamine; D000623:Porphobilinogen Synthase; D013831:Thiamine