Organometallic complexes with biological molecules. X: dialkyltin(IV) and trialkyltin(IV) orotates: spectroscopic and in vivo investigations

✍ Scribed by S. Lencioni; A. Pellerito; T. Fiore; A. M. Giuliani; L. Pellerito; M. T. Cambria; C. Mansueto

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 345 KB
• Volume: 13
• Category: Article
• ISSN: 0268-2605
• DOI: 10.1002/(sici)1099-0739(199903)13:3<145::aid-aoc793>3.0.co;2-6

✦ Synopsis

Several novel diorgano-and triorgano-tin(IV) derivatives of orotic acid, (2,6-dihydroxypyrimidine-4-carboxylic acid; H 3 or) have been synthesized. In the diorganotin(IV) derivatives, the orotic acid behaved either as a monoanionic or as a dianionic ligand, yielding R 2 Sn(H 2 or) 2 and R 2 SnHor (R = Me, Bu) species, respectively, while in the triorganotin(IV) orotates only monodeprotonation of the orotic acid occurred, giving R 3 SnH 2 or (R = Me, Bu) derivatives. Structural hypotheses are proposed and discussed for the solid state based on Mo ¨ssbauer and IR spectroscopic data, and for solution on 1 H and 13 C NMR results. Finally, investigations have been carried out in vivo, showing the inhibitor properties of all of the newly synthesized derivatives towards Ciona intestinalis embryos. In particular, in order to test the cytotoxicity in vivo of Me 2 SnHor, Bu 2 SnHor, Me 3 SnH 2 or and Bu 3 SnH 2 or, exposure to these chemicals of C. intestinalis embryos at the 2-4blastomere stage has been studied. The compound which exerts the highest cytotoxic effect is Bu 3 SnH 2 or at 10 À5 M concentration because it blocks embryo development immediately. Me 3 SnH 2 or at 10 À5 M concentration inhibits cell cleavage in the embryos at the 32-blastomere stage, while Bu 2 SnHor at the same concentration gives rise to abnormal embryos. Me 2 SnHor, is less toxic than the trimethyl, dibutyl and tributyl analogues, since 40% of the total number of treated embryos resulted in normal larvae. The ligand does not affect embryonic development significantly. The results seem to indicate that the chemical species under investigation, especially Bu 3 Sn-H 2 or, interfere with polymerization of tubulin during the process of cell division in early embryo development.