C. Mansueto

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

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 Mossbauer and IR spectroscopic data, and for solution on 1 H and 1 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 2-4-blastomere stage has been studied. The compound which exerts the highest 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 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.

Organometallic complexes with biological molecules. XI. Solid state and in vivo investigations of some diorganotin(IV)-chloramphenicol and cycloserine derivatives

Abstract Diorganotin(IV) derivatives of chloramphenicol, {=D-(-)threo-2,2-dichloro-N-[ β -hydroxy- α -(hydroxymethyl)- β -(4-nitrophenyl)ethyl]acetamide (=Hchloramph)}, and D-cycloserine, {=(R)-4-amino-3-isoxazolidone [=Hcyclos]} have been prepared. The stoichiometries of the obtained compounds were R 2 SnClantib and R 2 Snantib 2 (antib −1 =chloramph −1 , R=methyl and phenyl; antib −1 =cyclos −1 , R=methyl). The solid state configuration of the complexes was investigated by I.R. and Mossbauer spectroscopy, from which structural hypotheses were inferred. In particular, the experimental data suggested monomer structures both for R 2 Sn(IV)Clchloramph and R 2 Sn(IV)chloramph 2 , in which chloramphenicolate anion behaved as monoanionic monodentate ligand through the oxygen atom of the deprotonated secondary alcoholic group, with formation of tetrahedral R 2 SnOCl and R 2 SnO 2 environments. In R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 derivatives, Mossbauer spectroscopy, and in particular the narrowness of the full width at half height of the resonant peaks, Γ 1 and Γ 2 , suggested the occurrence of two different absorbing tin sites with different environments around the tin(IV) atoms. According to calculations performed by applying the point charge model formalism, one site was constituted by a tin(IV) tetrahedrically coordinated by monoanionic monodentate cycloserinate groups, through the oxygen atom of the resonance stabilised hydroxamate anion, originating R 2 SnClO and R 2 SnO 2 polyhedrons both in R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 , respectively. The second site would correspond to a tin(IV) in a polymeric octahedral configuration with Me 2 SnCl 2 ON and Me 2 SnO 2 N 2 environments, in Me 2 Sn(IV)Clcyclos and Me 2 Sn(IV)cyclos 2 derivatives, respectively, in which the second donor atoms was the amino nitrogen atom. 1 H and 13 C NMR spectra, of both chloramphenicol and its diorganotin(IV) derivatives were carried in DMSO-d 6 solution, in which R 2 Sn(IV)Clchloramph and R 2 Sn(IV)chloramph 2 underwent total, (R=Me), or partial, (R=Ph), dissociation. As far as the organotin(IV)-D-cycloserine derivatives were concerned, 1 H and 13 C NMR spectra, also carried out for the free D-cycloserine, showed that, owing to the coordinating properties of the solvent, octahedral and trigonal bipyramidal isomers were present in DMSO solution of Me 2 Sn(IV)Clcyclos and Me 2 Sn(IV)cyclos 2 . Finally, the cytotoxic activity of the free chloramphenicol, D-cycloserine and of their dimethyltin(IV) derivatives has been investigated towards Ciona intestinalis and Ascidia malaca fertilised eggs, at different developing stages.

Organometallic complexes with biological molecules : IX. Diorgano- and triorgano-tin(IV)[meso-tetra(4-sulfonatophenyl)porphinate] derivatives : Solid-state and solution-phase structural aspects and in vivo effects

Diorgano- and triorgano-tin(IV) derivatives of meso-tetra(4-sulfonatophenyl)porphine (H4TPPS) with general formula (R2Sn)2TPPS and (R3Sn)4TPPS (TPPS4−=[meso-tetra(4-sulfonatophenyl)porphinate]4−, R=Me, Bu, Ph) have been obtained and their solid-state configuration inferred on the basis of IR and Mossbauer spectroscopy, while solution-phase studies have been carried out by 1H and 13C NMR in DMSO-d6, together with determination of the in vivo cytotoxicity of the new derivatives towards embryonic development of Ciona intestinalis. In particular, octahedral and trigonal-bipyramidal eq-R3Sn polymeric configurations are proposed, in the solid state, respectively for (R2Sn)2TPPS and (R3Sn)4TPPS complexes, with the arylsulfonate groups behaving as monoanionic bidentate bridging ligands. The 1H and 13C NMR data lead to the conclusion that the metal-to-ligand ratio (2:1 or 4:1), binding site (the sulfonato-group oxygens), and the coordination polyhedron around the metal (trans-octahedral or trigonal-bipyramidal) found in the solid state are preserved in solution.

Trypsin-induced cell surface changes in ascidian embryonic cells: Regulation of differentiation of a tissue-specific protein

Abstract Developing animal quartets removed surgically from 8-cell stage of Ascidia malaca and Phallusia mamillata have been treated for a short time with a low concentration of trypsin. The result is a differentiation of some neural structures, of pigment spots and of a tissue-specific enzyme, brain pigment cell tyrosinase. Tyrosinase activity, as detected histochemically, appeared in the pigment cells some hours before the normal time independently of any inductive interactions with related embryonic tissues. A study with the electron microscope has given evidence of the presence of presumed nervous cells and melanin granules related to them. An autoradiographic study using [3H]uridine has demonstrated presumed RNA synthesis which suggests gene activation. The results are discussed in relation to the possible role of the plasma membrane during embryonic development.

Effects of Tributyltin(IV) Chloride Exposure on Larvae of Ciona intestinalis (Urochordata): An Ultrastructural Study

The effects of tributyltin(IV) chloride (TBT chloride) have been tested on embryos of the ascidian Ciona intestinalis, at two different stages of development: (1) before hatching (coiled larval stage) and (2) 2 h after hatching (swimming larval stage). In vivo observations carried out with a light microscope showed that embryos at the coiled larval stage did not hatch following exposure to TBT chloride. Severe anomalies in the swimming larva, mainly concerning the morphology of the tail, which appeared twisted and squatter than in the controls, were observed. Such anomalies were also found at a functional level, i.e. contractile movements were poor so that the larvae appeared motionless. Ultrastructural investigations carried out using a transmission electron microscope (TEM) evidenced that the muscle cells of the tail were damaged. Modifications mainly occurred in mitochondria and myofibrils, i.e. the energetic and enzymic centres. This fact is probably the main cause of the loss of mobility of the larvae.

Spectroscopic characterization and biological activity of L-methionyl-L histidinato complexes of R2Sn(IV) ions (R = Me, nBu, Ph) and X-ray structure of Me2SnMetHis ˙ 0.5MeOH

Complexes of L-methionyl-L-histidine (H2MetHis) with R2Sn(IV) ions (R = Me, nBu, Ph) have been synthesized. The crystal and molecular structures of Me2SnMetHis·0.5MeOH have been determined by X-ray diffraction. The title compound contains two crystallographically independent molecular units possessing the same trigonal-bipyramidal geometry at tin, each dimethyltin(IV) moiety being coordinated by the terminal amino nitrogen, deprotonated peptide nitrogen and terminal carboxylate group, neither the imidazole nor thioether groups being involved in bonding. IR spectroscopy was used to probe the structure of the complexes in the solid state, and the structure in solution (CD3OD) was assessed by 1H and 13C NMR. Me2Sn(IV)dipeptide complexes appear to be undissociated and to retain a pentacoordinated structure. Rotamer population of C-terminal histidine was determined by analysis of vicinal coupling constants and side-chain orientations have been interpreted with a view to potential applications of the compounds as recognition agents. Biological activity was tested on Ascidian embryos of Ciona intestinalis at different stages of development. Copyright

Organometallic Complexes with Biological Molecules. XIV. Biological Activity of Dialkyl and Trialkyltin(IV) (Meso-tetra(4-carboxy- phenyl)porphinate) Derivatives

Molecules. XIV. Biological Activity of Dialkyl and Trialkyltin(IV) [Meso-tetra(4-carboxyphenyl)porphinate] Derivatives C. Mansueto, E. Puccia, F. Maggio, R. Di Stefano, T. Fiore, C. Pellerito, F. Triolo and L. Pellerito* Dipartimento di Biologia Animale, Universita di Palermo, Via Archirafi 18, 90123 Palermo, Italy Dipartimento di Chimica Inorganica, Universita di Palermo, Viale delle Scienze, Parco d’Orleans, 90128 Palermo, Italy