CHROMATOGRAPHIC STUDIES ON ORGANO-TIN COMPOUNDS. I. THE GAS CHROMATOGRAPHY OF ALKYL-TIN COMPOUNDS.
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The influence of organic and inorganic compounds of tin on the dynamic properties of liposome membranes obtained in the process of dipalmitoylphosphatidylcholine (DPPC) sonication in distilled water was investigated. This was carried out by means of the spin ESR probe method. The probes were selected in such a way as to penetrate different areas of the membrane (a TEMPO probe, 5-DOXYL stearic acid, 16-DOXYL stearic acid). Four compounds of tin were chosen: three organic ones, (CH(3))(4)Sn, (C(2)H(5))(4)Sn and (C(3)H(7))(3)SnCl, and one inorganic one, SnCl(2). The investigated compounds were added to a liposome dispersion, which was prepared prior to that. The concentration of the admixture was changed within the values from 0 to 10%-mole in proportion to DPPC. The studies indicated that the chlorides of tin display the highest activity in their interaction with liposome membranes. Since these compounds have ionic form in a water solution, the obtained result can mean that this form of admixture has a considerable influence on its activity. Furthermore, it was found that there is a slightly stronger influence of tin compounds with a longer hydrocarbon chain on changes in the probes' spectroscopic parameters.
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Injection of metallic tin powder causes intense proliferation of plasma cells in draining lymph nodes of Lewis rats. Pretreatment orally with soluble tin salts prevents this response to subsequently injected metallic tin. In the present work, pretreatment with tin salts by parenteral injection was just as effective as addition to the drinking water. This new approach made the following experiments possible. Poorly soluble tin compounds were found to be inhibitory when injected parenterally. Tin salts injected parenterally into one of two rats joined in parabiotic union prevented the plasma cell response to metallic tin in both parabionts. The transfer of the inhibitory effect via the cross-circulating blood represents significant progress toward understanding the mechanisms involved. The evidence suggests the possibility that tin salts elicit an intermediary substance or process that is responsible for inhibition of the plasma cell response to metallic tin.
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Organic tin compounds are primary substances used as heat stabilizers by the polyvinyl chloride (PVC) industry. The use of these compounds in the PVC industry is generally well controlled, usually by automated processes. This study was conducted to provide an overview of worker exposure to organic tin compounds at PVC processing facilities and to verify that these exposures are below the threshold limit value (TLV((R))) set by the American Conference of Governmental Industrial Hygienists for organic tin. The basis of the TLV indicates the principal concern is to minimize adverse effects on immune function and the central nervous system from airborne exposure to organic tin. The TLV has a skin designation based on the potential for percutaneous absorption; the TLVs for inhalation exposures are based on the presumption that there is no concurrent exposure via the skin and oral ingestion routes. Personal exposure monitoring was conducted following the National Institute for Occupational Safety and Health (NIOSH) 5504 sampling method and a modified version of the NIOSH analytical method. The results were reported as"total tin."The data indicated no average exposure levels for individual tasks exceeded the organic tin TLV, and 96%of results the samples were less than 20%of the TLV. Only 1 sample of 102 exceeded the TLV, and the individual was wearing appropriate respiratory protection. Subsequent investigation indicated the highest exposures occurred while the operators were conducting tasks that included manual handling of the organic tin compounds. These data suggest manual operations may have a greater potential for organic tin exposure.
The effect of tripropyl-tin chloride on anion permeability was studied using red cells previously treated with a covalent binding inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) to inhibit completely and irreversibly the natural anion transport system. It was demonstrated that the tin compound can mediate chloride-hydroxide and chloride-chloride exchanges across the "impermeabilised" erythrocyte membrane. In the non hemolytic range, the rate of exchange increased with the concentration of the tin compound in a non linear fashion, and no saturation effect was seen. The temperature profile of the chloride self exchange induced by tripropyl-tin was studied and the apparent activation energy found was 29 Kcal/mol. The tripropyl-tin chloride cannot mediate a chloride-bicarbonate exchange. Because of this discriminatory effect between hydroxide and bicarbonate, the tin compound can be useful in certain experimental conditions as seen for the study of the anion "carrier" of the red cell membrane ("cousin, J.L., Motais, R. and Sola, F. (1975) J. Physiol. Lond. 253, 385-399).
This article reviews the literature related to the bioavailability of tin, inorganic tin compounds, and organotin compounds. On the one hand, the toxicity of metallic tin and inorganic tin compounds is low. In aqueous systems, the potential bioavailability of tin seems to depend on the concentration of the truly dissolved ion species. Some studies suggest that tin is an essential trace element for humans. However, organotin compounds have been proven to be of toxicological relevance. Triorganotin compounds are particularly toxic explaining their wide use as biocides (e.g., in antifouling paints or pesticides). Persistence of organotin compounds is governed by moderate to fast aerobic biotic degradation processes, slow anaerobic biotic degradation, slow abiotic degradation by photolysis, and fast, but reversible, adsorption/desorption processes. Organotin compounds are ubiquitously distributed in aquatic organisms. Bioconcentration in organisms and ecotoxicity are dependent on the bioavailable fraction. The bioavailability is highest at neutral and slightly alkaline pH and is reduced in the presence of dissolved organic carbon. The biomagnification of organotin compounds via the food chain is of minor importance compared with the bioconcentration from the water phase.
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The occurrence of tin in plants, animals and humans is discussed, in relation to its abundance in the lithosphere and hydrosphere and the range of the different tin(II) and tin(IV) complexes formed. A reasoned consideration of its essentiality for living species is provided. It is concluded that tin is beneficial, even if not yet proved to be an essential element. After reference to the chemistry of tin compounds, there is a detailed discussion of their toxicity in animals and humans. Feasible routes for tin intake and uptake into humans are described. The past and current use of tin pharmaceuticals is reviewed and the areas for which they are currently permitted for use in humans as dentifrices and mouth washes, as radio-pharmaceuticals and for the treatment of jaundiced newborns are described. A detailed review of tin-containing antitumour agents as representative tin pharmaceuticals is also given. Finally, a list of tin-containing drugs and drug candidates is also shown.
Resistance to organic tin compounds of P. aeruginosa and E. coli carrying antibiotic resistance plasmids and to P. putida containing biodegradation plasmids was studied. It was shown that 5 resistance plasmids and the biodegradation CAM plasmid of Pseudomonas increased 3-4 times the strain resistance to triethylstannylsuccinylimide and triethylstannylmaleinimide. All these plasmids belong to the P-2 incompatibility group and also determine the bacterial resistance to potassium tellurite. Isolation and investigation of the mutant plasmids loosing simultaneously the capacity for determination of resistance to potassium tellurite and organic tin compounds suggest that resistance to these compounds in the investigated plasmids is determined by the same genetic system.
We have investigated the patterns of in vitro cytotoxicity, induced by six newly synthesized gold and tin compounds, in three human ovarian cancer cell lines (SW 626, IGROV 1 and OVCAR-3). Four gold compounds, i.e. gold(I)lupinylsulfide hydrochloride [1] (containing a naked gold atom), triethylphosphinogold(I)lupinylsulfide hydrochloride [2], triphenyl-phosphinogold(I)lupinylsulfide hydrochloride [3] and 1 ,2-bis(diphenylphosphino)ethane bis[gold(I)lupinylsulfide] dihydrochloride [4] (all containing a gold atom coordinated with different phosphines), were prepared. Moreover, the triethylphosphinogold(I)(2-diethylamino)ethylsulfide hydrochloride [5] in which the simple diethylaminoethylthiol replaced the bulky lupinylthiol was synthesized. The tin compound, triethyltin(IV)lupinylsulfide hydrochlorlde [6], was also studied. Comparative tests with cisplatin, the most widely used antitumor agent in ovarian cancer, were carried out in biological Investigations. In vitro cytotoxicity, by MTT assay, showed that compound [4] and compound [6] exhibited interesting antiproliferative activity in all the three cell lines (mean IC50=1.3 and 0.7 microM, respectively) compared to cisplatin (mean IC50=4.8 microM). In addition, the PA-1 cell line, more sensitive to cisplatin (IC50=0.6 microM), was included as a comparison in the study. Cell count assays confirmed the cytotoxic properties of compounds [4] and [6] against the four cell lines, reporting higher growth Inhibition potency than cisplatin, with IC50 values in the sub-micromolar range.
The objective of the present work was to investigate the effect of selected organic tin compounds and potassium chloride (used as a reference substance) on the trans-membrane electric voltage and electric resistance of model membranes, the latter being nitrocellulose filters impregnated with butylene ester of lauric acid. The increasing KCl concentration (in the measurement chambers) caused a rapid rise of the negative trans-membrane voltage, whose value stabilized afterwards. In the case of (C3H7)3SnCl an abrupt maximum of the negative voltage was observed followed by a monotonic drop to zero. In the case of highest concentrations of this compound the voltages, after having reached zero, changed their polarization to the opposite. Within the range of small concentrations two slight voltage maxima were observed. Non-ionic tin compounds like (CH3)4Sn and (C2H5)4Sn had an insignificant influence on the electric properties of the studied membranes.