Organometallic complexes with biological molecules. X: Dialkyltin(IV) and Trialkyltin(lV) orotates: Spectroscopic and in vivo investigations

Several novel diorgano- and triorgano-tin(IV) derivatives of erotic acid, ( 2,6-dihydroxypyrimidine-4-carboxylic acid; H(3)or) have been synthesized. I n the diorganotin(IV) derivatives, the erotic acid behaved either as a mono anionic or as a dianionic ligand, yielding R2Sn(H(2)or)(2) and R(2)SnHor (R = Me, Bu) species, respectively, while in the triorganotin(IV) orotates on ly monodeprotonation of the erotic acid occurred, giving R(3)SnH(2)or (R=Me , Bu) derivatives. Structural hypotheses are proposed and discussed for the solid state based on Mossbauer and IR spectroscopic data, and for solution on H-1 and C-13 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 th e 2-4-blastomere stage has been studied. The compound which exerts the high est cytotoxic effect is Bu(3)SnH(2)or at 10(-5) M concentration because it blocks embryo development immediately. Me(3)SnH(2)or at 10(-5) M concentrat ion inhibits cell cleavage in the embryos at the 32-blastomere stage, while Bu(2)SnHor at the same concentration gives rise to abnormal embryos. Me2Sn Hor, is less toxic than the trimethyl, dibutyl and tributyl analogues, sinc e 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)SnH(2)or, interfere with polymerization of tubulin during the process of cell division in early embryo development. Copyright (C) 199 9 John Wiley & Sons, Ltd.