Interactions of alkyltin salts with biological dithiols: dealkylation and induction of a regular beta-turn structure in peptides

Organotin compounds specifically target vicinal dithiols, thereby inhibiting the function of essential enzymes. Here, we present the NMR binding studies of trimethyltin (TMT) and dimethyltin (DMT) chlorides with a linear peptide (ILGCWCYLR) derived from the membrane protein stannin (SNN). We show that this peptide is able to dealkylate TMT and bind DMT, adopting a stable type-I beta-turn conformation. Both the NMR data and the calculated structures indicate that the two cysteines coordinate the tin atom in a distorted tetrahedral geometry. The molecular geometries and tin coordination state were confirmed using density functional theory (DFT). In addition, NMR spectral parameters back calculated from the DFT minimized structure compared well with experimental data. These results in conjunction with studies on peptide variants (i.e., C4S, C6S, and Y7F) demonstrate unequivocally the key role of biological dithiols in both the dealkylation and binding of organotin compounds. This peptide serves as a model system for alkyltin-protein interactions and gives new insights into the biological fate of alkyltin compounds.     

Microanalytical determination of tin in organotin compounds

Existing procedures for the determination of tin in organotin compounds are reviewed, and a new procedure is described which can be used for the rapid microanalysis of most organotin compounds. Wet oxidation with sulphuric acid and 30% hydrogen peroxide is followed by spectrophotometric determination of the extracted ternary tin(IV)-chloride-oxine complex in chloroform. Time for a single determination is 20 min, and the relative standard deviation is 0.7% for 1-5 mg of tin. On account of their volatility, methyltin compounds must be subjected to a sealed-tube wet oxidation in sulphuric-nitric acid mixture. Addition of sulphamic acid after boiling to remove most of the nitric acid makes this compatible with the solvent extraction step. Tin present as organotin stabilizer in PVC samples can also be determined by this method, after destruction of the organic matter with sulphuric acid and 50% hydrogen peroxide.     

Synthesis of organotin polymers from diallylidenepentaerithritol (DAPE) and organotin monohydrides having an alkenyl substituent

Tri-n-butyltin hydride (Bu₃SnH) and modified organotin monohydrides which had an allylic ether group were employed for polymerizations of diallylidenpentaerithritol (DAPE) to prepare crosslinked polymers containing both organotin and acetal groups. The use of the latter monohydrides having a terminal unsaturated bond was particularly effective for introduction of various contents of the organotin moieties into the polymers, althought they did not undergo homopolymerizations.     

The in vitro antiherpes activity of some selected antitumor organotin compounds

A number of antitumor-active octahedral organotin complexes of the type R₂SnX₂L₂, where R=ethyl or phenyl, X = chloride or bromide, and L₂ = o- phenanthroline or 2-(2-pyridyl)benzimidazole, have been shown to exhibit in vitro antiherpes activity towards both herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). In addition, a series of mono-, di-, and tri-organotin halides (alkyl and phenyl) demonstrated weak antiherpes activity in the same viral assay system. Selectivity indexes for the tin compounds were calculated and compared with those available in the literature for a number of well-characterized and commercially important antivirals, e.g. adenine-9-β-D-arabinofuranoside (ara-A), cytosine-β-D-arabinofuranoside (ara-C), 5-iodo-2′-deoxyuridine (IDU) and 9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACY). Although the organotin complexes are less effective in vitro than either ACY or IDU, as determined by their selectivity indexes, they are comparable in activity with both ara-A and ara-C in this particular assay. With few exceptions, most notably (C₂H₅)₂SnBr₂(o-phen), the organotin compounds examined in this study are more active against HSV-1 (F strain) than HSV-2 (MS strain). The results presented here represent the first study of the potential antiviral properties of organotin compounds.     

Pressurised solvent extraction for organotin speciation in vegetable matrices

Because organotin compounds (OTC) are widely used in many fields of activity, they have become an ubiquitous environmental presence. The presence of organotins in the environment impacts upon food safety, making it important to monitor the levels of organotin pesticides in fruits and vegetables. Nevertheless, only a few studies have been published on organotin speciation in plants. The objective of the present study was to evaluate and optimise a specific procedure based on pressurised solvent extraction (PSE) that is suitable for monitoring organotin content in vegetables. In ASE, solvents are used at elevated temperatures and pressures to increase the rate and efficiency of the extraction process. The results from this procedure were compared to those from the technique usually employed, solid/liquid extraction (SLE) performed in an acidic solvent by mechanical shaking. Three extracting solutions were tested—methanol, ethyl acetate and a mixture of methanol and ethyl acetate—and the mixture was found to give the most quantitative results while preserving the speciation. French bean and lettuce leaves as well as potato tubers were used as the plant materials. These vegetables were considered because they are the vegatables consumed in the most quantities in Europe. The study focuses on trisubstituted OTCs, which are the most toxic tin species. The samples were spiked with four trisubstituted organotins: tributyltin (TBT), triphenyltin (TPhT), tricyclohexyltin (TcHexT) and trioctyltin (TOcT). The influence of the pressure and the temperature of the PSE on the quantitativity of the process and on species preservation was evaluated using the experimental design methodology. The optimised PSE allowed detection limits down to 1–2 ng (Sn) g^–1 to be reached. These are higher than those obtained by SLE (0.1–1 ng (Sn) g^–1). Although the repeatability is similar for both PSE and SLE (2–12% for triorganotin compounds), this appears to be highly time-dependent in the case of SLE. Comparison with SLE confirms that PSE is an interesting tool for vegetable analysis considering the satisfactory OTC preservation and repeatability obtained for a relatively short extraction duration (only 15 min against 2–12 h for SLE).     

Labelling of organotin compounds for fluorimetric detection

A systematic study of the fluorescence of complexes of some flavone derivatives with organotin compounds in hexane and in an aqueous micellar medium on Triton X-100 is reported. Some relationships between fluorescence intensity and the structure of the fluorogenic reagent or that of the organotin compound can be deduced, and the most suitable reagent for each organotin species can be chosen on the basis of sensitivity and selectivity. Results point out that flavone derivatives are appropriate post-column derivatization reagents for organotin compounds in liquid chromatography.     

Pentacoordinate organotin complexes as neutral carriers for salicylate-selective PVC membrane electrodes

Selectivity properties are established for three new electrodes prepared by incorporating three pentacoordinate organotin(IV) complexes, mono(2,4-pentanedionato-o,o') tri(phenylmethyl)tin (DMTBS), mono(benzoylacetonato-o,o') tri(phenylmethyl)tin (MPTBS) and mono(dibenzoylmethanato-o,o') tri(phenylmethyl)tin (DPTBS) into plasticized PVC membranes. These electrodes exhibit linear response to salicylate and an anti-Hofmeister selectivity pattern with high specificity for salicylate over many common anions. The results show that the potentiometric response characteristics are related to the structure of organic ligands. The detection limit and the slope of the electrodes based on these pentacoordinate organotin complexes exhibit a tendency to decrease as the substituent in organic ligands changes from a methyl group to a phenyl group. Electrodes prepared with DMTBS have the best detection limit and the highest degree of selectivity and sensitivity for salicylate. The response mechanism is also investigated by use of a.c. impedance and i.r. spectroscopic techniques.     

Preparation and structural studies on organotin(IV) complexes with flavonoids

Fourteen complexes of di-n-butyltin(IV)²⁺ cations with flavonoid glycosides (rutin, hesperidin, 2′,4′,3-trihydroxy-5′,4-dimetoxychalkone 4-rutinoside) and flavonoid aglycones (quercetin, morin, hesperitin and sorte flavones) were prepared. The composition of the complexes was determined by standard analytical methods. The results showed that complexes containing diorganotin(IV)²⁺ moiety and the ligand in 1∶1, 2∶1 or 3∶1 ratio are formed. The FTIR spectra were consistent with the presence of Sn-O (phenol or carbohydrate) vibration in the compounds. The structure of the complexes was measured by Mössbauer spectroscopy. Comparison of the experimental quadrupole splitting with those calculated on the basis of partial quadrupole splitting concept revealed that the complexes are of four types: with the central tin atoms surrounded by donor atoms in a purely trigonal-bipyramidal, octahedral+trigonal-bipyramidal, trigonal-bipyramidal+tetrahedral and octahedral+tetrahedral arrangement. This procedure also distinguished between the different structural isomers of both trigonal-bipyramidal and octahedral complexes. Conclusions could therefore be drawn on the factors determining which of the isomers are formed in the systems. The Mössbauer parameters obtained for organotin(IV)-flavonoid complexes were compared with those measured for organotin(IV)-carbohydrate complexes.     

Polymerization of N-carboxy anhydrides by organotin catalysts

Organotin compounds were found to lead to polymerization of N-carboxy anhydrides. The polymerization was studied in detail using γ-benzyl N-carboxyl-t-glutamate anhydride (BGA). Compounds such as tributyltin methoxide, bis(tributyltin)oxide, and N-tributyltin imidazole polymerized BGA while others like dibutyltin dichloride, which are Lewis acids, failed. Polymerization of BGA in dioxane at various monomer to dibutyltin dimethoxide ratios showed a first order reaction to monomer. The plot of In M₀/M₁ vs time showed two stage kinetics, the second one being faster. The pseudo first order rate constants were smaller than those for primary amine initiated polymerizations and much smaller than that for polymerization initiated by sodium methoxide. The molecular weights were independent of the monomer to initiator ratio both in dioxane and in DMF. In the reaction of an equimolar amount of tributyltin methoxide with NCA, the methyl ester of the amino acid was formed.The mechanism suggested is that of addition of the organotin compound to the NCA forming an organotin carbamate which decarboxylates, leaving an active -N-Sn-group which adds to another NCA molecule. This process is repeated in every step of the propagation.     

HPTLC analysis of organotin compounds in preservative solutions and preservative-treated wood

A high-performance thin-layer chromatographic (HPTLC) method is described for the determination of tributyltin compounds (bis(tri-n-butyltin) oxide, TBTO, and tri-n-butyltin naphthenate, TBTN) and their degradation products (dibutyltin and monobutyltin compounds). The organotin compounds are extracted from wood with ethanol containing 0.5% (v/v) of hydrochloric acid and the separation of the defferent kinds of organotin compounds is achieved by thin-layer chromatography. The sample spots are measured using a scanning densitometer after decomposing the organotin compounds to inorganic tin by ultraviolet irradiation and visualization of the spots with pyrocatechol violet. Applications of the method to detection and quantification of organotin compounds in preservative solutions, in recently impregnated wood, and in wood samples from five-year-old window frames are described.     

Speciation of organotin in environmental sediment samples

An optimized sample preparation procedure for organotin speciation in sediment samples has been applied to the analysis of sediments collected in the environment. The method is based on tropolone complexation of the ionic organotins, followed by extraction into a hexane-ethylacetate mixture and derivatization by NaBEt(4). The method was applied to the determination of organotin in various harbour, shipyard and dry-dock sediments in Belgium. Butyltin compounds were detected in all samples analyzed, often at high mg kg(-1) levels. A limited number of samples showed the presence of phenyltin compounds. Further, the method was adapted to the analysis of river sediments sampled from the vicinity of shipyards. Butyltin concentrations were detected at the microg kg(-1) level in the majority of samples.     

The structure of organotin mercaptoesters

This paper describes the structural differences existing among various organotin mercaptoesters of the general formula R_nSn[S(CH₂)_1–2COOR′]_4–n. Infrared and Mössbauer spectroscopies were the methods of choice to investigate such differences and they have revealed that thioglycolate and 3-mercaptopropionate esters adopt cyclic cis- or trans-trigonal bipyramidal as well as trans-octahedral configurations, according to the composition of the organotin compounds and their mode of preparation. Structural relationship among organotin mercaptides and thioacetates are also discussed.     

Effect of organotin compounds on trout AMP‐deaminases

The comparative toxicity of the organotin compounds tributyltin chloride (TBTC), dibutylin dichloride (DBTC) and monobutyltin trichloride (MBTC) was investigated on 5′ adenylic acid deaminase (AMP‐deaminase) purified from trout skeletal muscle and heart. Treatment with TBTC of both enzymatic forms of AMP‐deaminase rapidly decreases the enzyme activity, and the organotin derivatives DBTC and MBTC have a significant minor inhibitory effect. Differences were observed in TBTC inhibition rate between trout muscle and heart purified enzymes that could be related to the different cellular localization of the two AMP‐deaminases. Copyright © 2001 John Wiley & Sons, Ltd.     

Self-assembly and characterization of a novel 2D network polymer containing a 60-membered organotin macrocycle

The reaction of 1-(4-carboxyphenyl)-5-mercapto-1 H-tetrazole with trimethyltin chloride in the presence of sodium ethoxide in benzene affords a novel 2D organotin network structure complex 1, which is an unusual organotin network containing a hexanuclear 60-membered organotin macrocycle. The complex has been characterized by elemental analysis, IR, and (1)H, (13)C, and (119)Sn NMR spectroscopy. Furthermore, we have also characterized the complex by X-ray crystallography.     

Analysis of organotin compounds by grignard derivatization and gas chromatography-ion trap tandem mass spectrometry

The determination of organotin compounds in water using gas chromatography-tandem mass spectrometry (GC-MS-MS) is described. Several organotin derivatives were synthesized by the reaction of organotin chlorides with Grignard reagents such as methyl-, propyl- and pentylmagnesium halides. After the optimization of the GC-MS-MS conditions, several derivatizations with the Grignard reagents were compared by evaluating the molar responses and volatilities of the derivatives and derivatization yields. As a result, the derivatizing reagent of choice is pentylmagnesium bromide. Calibration curves for the mono-, di- and tributyltins and mono-, di- and triphenyltins with pentylmagnesium bromide were linear in the range of 0.5-100 pg of Sn. The instrumental detection limits of six organotins ranged from 0.20 to 0.35 pg of Sn. The recovery tests from water samples (500 ml) were performed by using sodium diethyldithiocarbamate (DDTC) as a complexing reagent. Except for monophenyltin, the absolute recoveries of organotins from pure water at 200 ng of Sn/l were satisfactory. The recoveries calibrated by surrogate compounds (perdeuterated organotin chlorides) ranged from 71 to 109%. The method detection limits ranged from 0.26 to 0.84 pg of Sn (500-ml sample). This method was applied to the recovery of organotins from river water and seawater. The calibrated recoveries were between 90 and 122%.     

Fine-tuned characterization at the solid/solution interface of organotin compounds grafted onto cross-linked polystyrene by using high-resolution MAS NMR spectroscopy

The structural characterization of organotin compounds that are grafted onto insoluble cross-linked polymers has necessarily been limited to elemental analysis, infrared spectroscopy, and in a few instances, solid-state NMR spectroscopy. This important bottleneck in the development of such grafted systems has been addressed by using high-resolution magic angle spinning (hr-MAS) NMR spectroscopy. The great potential of this technique is demonstrated through the structural characterization of diphenylbutyl-(3,4) and dichlorobutylstannanes (5,6), grafted onto divinylbenzene cross-linked polystyrene by means of a suitable linker (1, 2). First, conditions suitable for the application of hr-MAS NMR spectroscopy were identified by characterizing the (1)H resonance line widths of the grafted organotin moiety following swelling of the functionalized beads in eight representative solvents. The presence of clearly identifiable tin coupling patterns in both the 1D (13)C and 2D (1)H-(13)C HSQC spectra, and the incorporation of (119)Sn chemical shift and connectivity information from hr-MAS 1D (119)Sn and 2D (1)H-(119)Sn HMQC spectra, provide an unprecedented level of characterization of grafted organotins directly at the solid/liquid interface. In addition, the use of hr-MAS (119)Sn NMR for reaction monitoring, impurity detection, and quantification and assessment of the extent of coordination reveals its promise as a novel tool for the investigation of polymer-grafted organotin compounds. The approach described here should be sufficiently general for extension to a variety of other nuclei of interest in polymer-supported organometallic chemistry.     

Radiohalogenation of terguride via organotin intermediate

New (radio)halogen derivatives of 1-allylterguride have been prepared by method of destannylation-halogenation. 1-Alylterguride shows relatively high binding affinity, which can be used in the case of its radiolabeled derivatives with imaging methods like PET or SPET in studies of properties of receptor's binding places and ligand affinity. The (radio)halogenation was performed via organotin precursors: 1-tributylstannyl-3-chlorprop-1-ene and 2-tributylstannyl-3-chloroprop-1-ene, which were prepared from appropriate alcohols. Linkers of the tin group were used for alkylation of N1 of terguride both under microwave irradiation and under conventional heating. In the last step (destannylation-halogenation), fluoro-, bromo- and iododerivatives as well as ¹²⁵I iodo- and ⁸²Br bromoderivatives of 1-allylterguride were obtained.This revised version was published online in November 2005 with corrections to the Cover Date.     

Towards non-polluting organotin reagents for synthesis

New polymer-supported organotin reagents have been prepared. The reducing ability of a polystyrene-supported organotin hydride was evaluated by reaction with haloalkanes. The level of organotin pollution was monitored in comparison with that generated by Bu₃SnH, using ICP–MS analysis.     

超临界流体萃取法对有机锡化合物的选择性萃取

 研究了用超临界流体萃取法直接从脂肪基质的固体样品（大豆粉）中选择性地萃取有机锡化合物的方法。模拟试样萃取结果表明：用较低压力和较高温度的超临界态ＣＯ２作流动相时，有机锡达到最大萃取率，而脂肪类物质仅被少量萃取，从而消除了脂肪类物质对超临界流体色谱法测定有机锡的干扰。