Characterization of complexes formed between [Me2Sn(IV)]2+ and carboxymethylcelluloses.

Complexes formed between carboxymethylcellulose (CMC) and the [Me(2)Sn(IV)]2+ cation have been prepared in the solid state and characterized by FTIR and Mössbauer spectroscopy. The complexes contained CMC with varying molar weight and degree of carboxylation, and the complexes were isolated both from acidic and from neutral solutions at varying metal-to-ligand ratios. The characteristic vibration bands of the ligands were identified from their pH-dependent FTIR spectra. In the organotin(IV) complexes obtained at pH approximately 2, the -COO- moieties were found to be coordinated in a monodentate manner, and the band characteristic of the protonated (unbound) -COO- group(s) was also identified. The broad -OH band can be interpreted as the sum of the contributions of the alcoholic -OH groups of the anhydroglucose units and the mixed organotin aqua complexes. In complexes obtained at pH approximately 7, the broad -OH band significantly sharpens, which is probably due to the metal-ion induced deprotonation and subsequent coordination of the alcoholic -OH groups. At the same time, -COO- groups are also involved in the coordination of the metal ions, resulting in a complicated network that forms through inter- and intramolecular bridges. Quadrupole splitting (/Delta(exp)/) values observed by Mössbauer spectroscopy revealed that the valence state of tin is four in all of the complexes. The /Delta(exp)/ values were compared with the calculated ones, obtained from the pqs theory. From these data, trigonal bipyramidal (Tbp) and octahedral (Oh) geometries have been suggested for the complexes obtained. It has also been concluded that the structure of the complexes prepared depends mainly on the pH of the solution, and it is relatively insensitive to the other parameters, like molar mass or degree of carboxylation of the ligand, or the metal-to-ligand ratio in the reaction mixture.

Coordination properties of adenosine-5'-monophosphate and related ligands towards Me2Sn(IV)2+ in aqueous solution.

The coordination of Me2Sn(IV)2+ to adenosine-5'-monophosphate (AMP) and the related compounds D-ribose-5-phosphate (R5P), D-glucose-1-phosphate (G1P) and D-glucose-6-phosphate (G6P) in aqueous solution was investigated by means of potentiometric titration, and 1H-, 31P-NMR and Mössbauer spectroscopic methods in the pH range 2-11 (I=0.1 M NaClO4, 298 K). The complex of AMP and Me2Sn(IV)2+ precipitated at low pH was characterised by elemental analysis, FT-IR and Mössbauer spectroscopic methods. From a comparison of the pK values obtained in the presence and absence of metal ion and the stability constants for the different systems, the coordination of [N] is excluded, while bidentate coordination of the phosphate group is presumed. Mössbauer spectroscopic measurements recorded in the glassy state confirmed bidentate coordination of the phosphate and the formation of mixed hydroxo complexes in the weakly acidic, neutral and strongly basic pH range. With increasing pH, the phosphate groups were replaced by the deprotonated alcoholic [O] atoms of the sugar moiety. The solid complex proved to be tbp structure with bidentate phosphate coordination.

Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations.

Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-(d-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O (Alk=Me, n-Bu), while structural information has been gained by FT-IR, (119)Sn Mössbauer and (1)H, (13)C, (119)Sn NMR data. In particular, IR results suggested polymeric structures both for Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through beta-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk(2)SnOHceph(.)H(2)O complexes. On the basis of (119)Sn Mössbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration. As far as Alk(3)Sn(IV)ceph(.)H(2)O derivatives are concerned, cephalexin coordinated the Alk(3)Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, (119)Sn Mössbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R(3)Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using (1)H, (13)C and (119)Sn NMR spectroscopy. Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA(3), towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia). Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals. Moreover, structural damages such as "chromosome achromatic lesions", "chromosome breakages" and "chromosome fragments" have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.

Organometallic complexes with biological molecules. XVII. Triorganotin(IV) complexes with amoxicillin and ampicillin.

Novel triorganotin(IV) complexes of two beta-lactamic antibiotics, 6-[D-(-)-beta-amino-p-hydroxyphenyl-acetamido]penicillin (=amoxicillin) and 6-[D-(-)-alpha-aminobenzyl]penicillin (=ampicillin), have been synthesized and investigated both in solid and solution states. The complexes corresponded to the general formula R(3)Sn(IV)antib*H(2)O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or amp=ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn Mössbauer data. In particular, IR results suggested polymeric structures both for R(3)Sn(IV)amox.H(2)O and R(3)Sn(IV)amp*H(2)O. Moreover, both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin(IV) atom through ester-type carboxylate, as well as through the beta-lactamic carbonyl. Evidence that in none of these compounds water molecules were involved in coordination, was provided by thermogravimetric investigations. On the basis of 119Sn Mössbauer spectroscopy it can be inferred that tin(IV) was pentacoordinate in all of the complexes in the solid state, showing an equatorial R(3)Sn(IV) trigonal bipyramidal (tbp) configuration. The nature of the complexes in solution state was investigated by using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, while an 119Sn spectrum was obtained for n-Bu(3)Sn(IV)amp*H(2)O. Although 1H- and 13C-NMR measurements suggested that in dimethyl sulfoxide (DMSO)-d(6) solution the polymeric structure collapsed, due to a solvolysis process of the beta-lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same trigonal bipyramidal configuration at tin(IV) atom by the coordination of a DMSO molecule. Cytotoxic activity of these novel semisynthetic antibiotic derivatives has been tested towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) using two different chromosome-staining techniques such as Giemsa and CMA(3). The occurrence of typical colchicinized-like (c-like) mitoses on slides obtained from animals exposed to organotin compounds, directly confirmed the high mitotic spindle-inhibiting potency of these chemicals. In addition, by comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the triorganotin(IV) complexes, structural damages such as 'achromatic lesions' and 'chromosome breakages' have been identified.

Tributyltin affects phagocytic activity of Ciona intestinalis hemocytes.

Organotin compounds have been used in marine anti-fouling paints as biocides. Because tunicates are vulnerable to these compounds in their natural habitats, we used Ciona intestinalis to establish an assay for phagocytosis in vitro of yeast by hemocytes after exposure to different concentrations (0.0015, 0.015, 0.15 and 1.5 microM) of four organotin compounds: tributyltin (TBT), triphenyltin (TPT), dibutyltin (DBT) and diphenyltin (DPT). To evaluate the phagocytic activity, we used a method based on fluorescence excitation of yeast pre-treated with eosin-Y. The percentage of phagocytosis decreased from 45.1 +/- 3.49 to 22.4 +/- 5.14 at 1.5 microM of TBT (P < 0.001); it was significantly reduced in presence of the ionophore A23187. TPT, DPT and DBT did not show significant effects on phagocytosis. Because the effect of TBT was irreversible, differences between the inhibitory mechanisms of ionophore and TBT are suggested. These results indicate that for future analyses, tunicates should become excellent models for dissecting events such as phagocytosis that are associated with immunosuppression after exposure to xenobiotics.

Organic derivatives of mercury and tin as promoters of membrane lipid peroxidation.

The toxicity mechanisms of mercury and tin organic derivatives are still under debate. Generally the presence of organic moieties in their molecules makes these compounds lipophilic and membrane active species. The recent results suggest that Hg and Sn compounds deplete HS-groups in proteins, glutathione and glutathione-dependent enzymatic systems; this process also results in the production of reactive oxygen species (ROS), the enhancement of membrane lipids peroxidation and damage of the antioxidative defence system. The goal of this review is to present recent results in the studies oriented towards the role of organomercury and organotin compounds in the xenobiotic-mediated enhancement of radical production and hence in the promotion of cell damage as a result of enhanced lipids peroxidation. Moreover the conception of the carbon to metal bond cleavage that leads to the generation of reactive organic radicals is discussed as one of the mechanisms of mercury and tin organic derivatives toxicity. The possible use of natural and synthetic antioxidants as detoxification agents is described. The data collected recently and presented here are fundamentally important to recognizing the difference between the role of metal center and of organic fragments in the biochemical behavior of organomercury and organotin compounds in their interaction with primary biological targets when entering a living organism.