Microbial formation and transformation of organometallic and organometalloid compounds

Abstract: Microbial formation and transformation of organometallic and organometalloid compounds comprise significant components of biogeochemical cycles for the metals mercury, lead and tin and the metalloids arsenic, selenium, tellurium and germanium. Methylated derivatives of such elements can arise as a result of chemical and biological mechanisms and this frequently results in altered volatility, solubility, toxicity and mobility. The major microbial methylating agents are methylcobalamin (CH₃CoB₁₂), involved in the methylation of mercury, tin and lead, and S -adenosylmethionine (SAM), involved in the methylation of arsenic and selenium. Evidence for the methylation of other toxic metal(loid)s is sparse. Biomethylation may result in metal(loid) detoxification since methylated derivatives may be excreted readily from cells, are often volatile and may be less toxic, e.g. organoarsenicals. However, for mercury, low yields of methylated derivatives and the existence of more efficient resistance mechanisms, e.g. reduction of Hg²⁺ to Hg⁰, suggest a lower significance in detoxification. Bioalkylation has only been characterised in detail for arsenic. Microorganisms can accumulate organometal(loid)s, a phenomenon relevant to toxicant transfer to higher organisms. As well as bioaccumulation, many microorganisms are capable of the degradation and detoxification of organometal(loid) compounds by, e.g. demethylation and dealkylation. Several organometal(loid) transformations have potential for environmental bioremediation.     

Unusual metals as carcinogens

A review of the literature on unusual metals as carcinogens was carried out. The metals covered are some of the rare earths, copper, silver, gold, mercury, germanium, tin, antimony, lead, platinum, palladium, aluminum, titanium, niobium, manganese, scandium, yttrium, indium, rhodium, and gallium.     

The microsomal metabolism of the organometallic derivatives of the group-IV elements, germanium, tin and lead.

The NADPH- and oxygen-dependent microsomal metabolism of the di-, tri- and tetra-ethyl-substituted derivatives of germanium, tin and lead was shown to give rise to ethylene as a major product and ethane as a minor product. These reactions were shown to be catalysed by the liver microsomal cytochrome P-450-dependent mono-oxygenase. Since formation of ethane and ethylene was differentially inhibited by anaerobiosis, the results suggest that at least a large portion of the ethane produced may be derived by a reductive mechanism. Triethyltin bromide in both the absence and presence of NADPH was shown to convert cytochrome P-450 into cytochrome P-420 and to affect the function of the mono-oxygenase in vitro. Tetraethyltin caused the NADPH- and time-dependent formation of cytochrome P-420, suggesting that tetraethyltin is converted into triethyltin salts in significant concentrations. The order of potency in formation of cytochrome P-420 was closely paralleled by the ability of the tin derivatives to induce microsomal lipid peroxidation in vitro.     

Criticality of the Geological Zinc,Tin, and Lead Family

Concerns about the future availability and continuity of metal supplies have triggered research efforts to define and assess metal criticality. In this study, we apply a comprehensive methodology to the elements of the geological zinc, tin, and lead family: zinc (Zn); germanium (Ge); cadmium (Cd); indium (In); tin (Sn); and lead (Pb). Zn, Sn, and Pb have played important roles in various technological sectors for centuries, whereas Ge, Cd, and In are by‐product metals that are increasingly utilized in emerging and strategic technologies. Criticality assessments are made on national (i.e., the United States) and global levels for 2008. The results are presented with uncertainty estimates in three‐dimensional “criticality space,” comprised of supply risk (SR), environmental implications, and vulnerability to supply restriction (VSR) axes. SR is the highest for In for both the medium (i.e., five to ten years) and long term (i.e., a few decades). Pb and Zn have the lowest SR for the medium term and Pb the lowest SR for the long term. In and Ge production have the highest environmental burdens, mainly as a result of emissions from Zn smelting and subsequent metals purification and recovery from Zn leaching residues. VSR is highest for Pb at the global and national levels.     

The influence of tin compounds on the dynamic properties of liposome membranes: A study using the ESR method

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, (CH₃)₄Sn, (C₂H₅)₄Sn and (C₃H₇)₃SnCl, and one inorganic one, SnCl₂. 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.     

Gas chromatographic determination of inorganic tin in rat urine after a single oral administration of stannous chloride and mono-, di-, and triphenyltin chloride

A method is described for the determination of inorganic tin by gas chromatography with flame photometric detection. The inorganic tins, stannous and stannic, were extracted with hydrochloric acid and n-hexane—benzene in the presence of 0.05% tropolone, and both inorganic tins were pentylated to tetrapentyltin with a Grignard reagent prior to gas chromatography. The absolute limit of detection for tetrapentyltin was 3 pg as tin. The recovery of stannous chloride added to rat urine samples was 80.2 ± 2.4% (mean ± S.D., n = 8). The application of this method to the study of urinary excretion of inorganic tin and organotin compounds in rats following oral administration of tin compounds is presented. The urinary excretion of tin compounds was observed over a period of 96 h following administration of stannous chloride or phenyltin compounds. Most of the inorganic tin was excreted into urine within 24 h after administration of stannous chloride. In the experiments on organotin administration, the level of the excretion as total tin for monophenyltin reached a maximum ca. 0–24 h after administration, whereas the maxima for di- and triphenyltin were found after 24–48 h and 48–72 h, respectively. The predominant excretion product of these tin compounds found in urine was monophenyltin.     

Molecular Dynamics simulations of Inhibitor of Apoptosis Proteins and identification of potential small molecule inhibitors

Chemotherapeutic resistance due to over expression of Inhibitor of Apoptosis Proteins (IAPs) XIAP, survivin and livin has been observed in various cancers. In the current study, Molecular Dynamics (MD) simulations were carried out for all three IAPs and a common ligand binding scaffold was identified. Further, a novel sequence based motif specific to these IAPs was designed. SMAC is an endogenous inhibitor of IAPs. Screening of ChemBank for compounds similar to lead SMAC-non-peptidomimetics yielded a cemadotin related compound NCIMech_000654. Cemadotin is a derivative of natural anti-tumor peptide dolastatin-15; hence these compounds were docked against all three IAPs. Based on our analysis, we propose that NCIMech_000654/dolastatin-15/cemadotin derivatives may be investigated for their potential in inhibiting XIAP, survivin and livin.     

Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity.     

Interactions between selenium and tin,selenium and lead,and their effects on alad activity in blood

Interactions of tin and selenium, as well as of lead and selenium, were investigated in male ICR mice. The toxic effects of selenium on mortality and body weight loss were reduced by simultaneous injection with tin or lead; among mice that were injected ip with selenium at 100 μmol/kg, the 24 h survival rate was 20%, whereas among mice that were administered selenium and tin or selenium and lead at the dose of 100 μmol/kg each, the rates were 100% and 90%, respectively. As for δ-aminolevulinic acid dehydratase (ALAD, EC 4.2.1.24), lead and tin were strong inhibitors, which is well known; selenium showed no effect. When more than an equimolar dose of sodium selenite was injected ip simultaneously with stannous chloride, the ALAD activity was completely retained. On the other hand, in the simultaneous injection with sodium selenite and lead acetate of differing ratios (Se/Pb), 1, 2.5, 5, and 7.5, selenium did not exhibit an obvious protective effect against the inhibition of ALAD activity caused by lead. It is suggested that selenium protects essential thiol groups in ALAD that are otherwise blocked by invading tin; in contrast, selenium, under similar conditions, does not prevent interactions of lead with enzyme thiol groups.     

Induction of synthesis and activation of Penicillium commune alpha-L-rhamnosidase

For the first time the influence of a number of synthetic porfirin and fluoren derivatives, coordinative germanium substances and surfactants on the biosynthesis and activity of Penicillium commune 266 alpha-L-rhamnosidase has been studied. It is shown that some of porfirin derivatives and coordinative germanium substances may be used as inducers of biosynthesis (143-430%) and also as stimulators of alpha-L-rhamnosidase activity (15-44%). It is more expedient to use biscitratgermanium acid in a complex with asparaginic acid (430%) or threonine (370%) as inducers of biosynthesis of enzyme. At the same time the use of porfirin derivatives, in particular meso-tetra(N-methyl-6-chinoline)porfirin tosilate or its manganese complex, is more efficient as stimulators (40%) of alpha-L-rhamnosidase activity. The utilization of such surfactants as tregaloso-, peptido- and rhamnolipids is not expedient. These compounds either do not influence or inhibit biosynthesis and activity of P. commune alpha-L-rhamnosidase. Only in concentration of 0.01% rhamnolipid increased the activity of enzyme by 7.5%.     

Theoretical investigations on the hydrolysis pathway of tin verdoheme complexes: elucidation of tin’s ring opening inhibition role

In order to obtain a better molecular understanding of inhibitory role of tin metal in the verdoheme ring opening process, hydrolysis of three possibly six, five, and four coordinate verdoheme complexes of tin(IV) and (II) have been studied using DFT method. The results of calculations indicate that, in excellent accord with experimental reports, hydrolysis of different possibly coordinated tin(IV) and (II) verdohemes does not lead to the opening of the macrocycle. Contrary to iron and zinc verdohemes, in five and four coordinate verdoheme complexes of tin(IV) and (II), formation of open ring helical complexes of tin are unfavorable both thermodynamically and kinetically. In these pathways, coordination of hydroxide nucleophile to tin metal due to the highly charged, exclusive oxophilicity nature of the Sn center, and high affinity of Sn to increase coordination state are proposed responsible as inhibiting roles of tin via the ring opening. While, in saturated six coordinate tin(IV) and (II) verdoheme complexes the ring opening of tin verdohemes is possible thermodynamically, but it is not predicted to occur from a kinetics point of view. In the six coordinate pathway, tin plays no coordination role and direct addition of hydroxide nucleophile to the positive oxo-carbon centers and formation of closed ring hydroxy compounds is proposed for preventing the verdoheme ring opening. These key points and findings have been corroborated by the results obtained from atomic charge analysis, geometrical parameters, and molecular orbital calculations. In addition, the results of inhibiting ring opening reaction of tin verdoheme complexes could support the great interest of tin porphyrin analogues as pharmacologic means of chemoprevention of neonatal jaundice by the competitive inhibitory action of tin porphyrins on heme oxygenase.     

Separation of metal chelates and organometallic compounds by SFC and SFE/GC

Supercritical fluid chromatography (SFC) combines the high diffusion coefficients of gas chromatography (GC) and the solubility properties of liquid chromatography (LC). SFC generally requires lower temperatures for chromatographic separations and thus is more suitable for analyzing thermally labile compounds including a number of metal chelates and organometallic compounds. SFC also allows interfacing between supercritical fluid extraction (SFE) and chromatographic analysis of metal-containing compounds. A large number of metal chelates and organometallic compounds can be separated by SFC. This article summarizes SFC separation of various chelates of transition metals, heavy metals, lanthanides and actinides as well as organometallic compounds of lead, mercury, and tin reported in the recent literature. This article also discusses SFC detection systems and the determination of solubility of organometallic compounds by SFC.     

Design,synthesis, docking studies and biological evaluation of novel chalcone derivatives as potential histone deacetylase inhibitors

A group of novel chalcone derivatives comprising hydroxamic acid or 2-aminobenzamide group as zinc binding groups (ZBG) were synthesized. The structure of the prepared compounds was fully characterized by IR, NMR and elemental microanalyses. Most of the tested compounds displayed strong to moderate HDAC inhibitory activity. Some of these compounds showed potent anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines. In particular, compounds 4a and 4b exhibited significant anti-proliferative activity against the three cell lines compared to SAHA as reference drug and displayed promising profile as anti-tumor candidates. The results indicated that these chalcone derivatives could serve as a promising lead compounds for further optimization as antitumor agents.     

Germanium: environmental occurrence, importance and speciation

This review discusses the various aspects of the bio-geochemistry of germanium, and of its technological, economical and environmental importance. Despite the relatively low annual production and consumption of this semi-metal (ca. 80 metric tons/a) there are important technological applications of this element in the semiconductor, infrared optics and fibre optics/telecommunication industries. A small, but not insignificant fraction of this element is used for the production of pharmaceuticals and nutritional supplements, although its actual merits have not been fully demonstrated yet, while they are opposed to chronic toxicity of the element when being administrated at relatively high doses for an extended period of time. Neither the exact mechanism of action in the case of cancer treatment or the treatment of infectious diseases is known, nor the reason for the toxicity of inorganic species of this element. In plants, Ge can partially substitute for B in the case of boron deficiency, although deficiency symptoms are still seen with a lag period of ca. one to three weeks. In biogeochemical respect, germanium and silicon react very similar, as if Ge were a very heavy isotope of Si. Their molar ratio is typically in the order of 0.6 × 10⁻⁶, with significant deviations only where germanium is complexed and transported, e.g., by humic-rich waters. Germanium is a very conservative element in biogeochemical terms: It hardly shows involvement in any biogeochemical reaction cycles and is mainly present in the form of complexes or hydroxo-compounds of the tetravalent germanium. The only naturally occurring organogermanium compounds are mono- and dimethylgermanium which are believed to be formed by microbiological activity in continental zones containing Ge-rich minerals, and then are leached into rivers, and finally into the open sea. It becomes evident that, although very sophisticated technological uses of germanium exist, a better understanding of its biogeochemical importance, cycling and reactivity must still be developed.     

Association of Periodontitis with the Concentration Levels of Germanium and Tin in Hair

The purpose of this study was to investigate whether or not the concentration levels of certain kinds of trace elements in hair are associated with periodontitis. We studied a total of 109 participants, which are composed of 25 participants with periodontitis and 84 participants without periodontitis. Periodontal conditions were assessed by measuring the periodontal clinical attachment loss and pocket depth, which were determined at six sites of all teeth. Periodontitis was defined according to the criteria of periodontitis proposed by CDC-AAP. The hair samples were washed with acetone, water, and extran (1%v/v), and then aliquots of hair samples were wet-ashed. This sample solution was analyzed by Perkin-Elmer Mass Spectrometer. The odds ratios and 95% confidence intervals of the concentration levels of trace elements for periodontitis were calculated by multivariate logistic regression analysis. After adjusting all confounders, it was found that the higher concentration level of germanium in hair was significantly and positively associated with periodontitis (odds ratio [OR] 7.12; 95% confidential interval [CI] 2.03–25.00). The higher concentration level of tin in hair was significantly and negatively associated with periodontitis (OR 0.27; 95% CI 0.08–0.94). It was concluded that there was a significant relationship between periodontitis and the concentration level of germanium and tin in hair.     

Design and synthesis of small chemical inhibitors containing different scaffolds for lck SH2 domain

On the basis of the structure of (R)-rosmarinic acid, a series of small chemical compounds with a different scaffold was synthesized as inhibitors for lck SH2 domain. From ELISA results, most of all chemical compounds showed a similar or a little lower binding activity for lck SH2 domain compared to the lead compound, (R)-rosmarinic acid. It was characterized that the backbone rigidity between two catechol substructures was required for the full activity and acid substructure of the lead compound was important for the activity. We successfully identified novel lead compounds that did not contain phosphotyrosine moiety and might have an improved bioavailability as inhibitor for lck SH2 domain.     

Reconnoitring the current characteristics of the double C<Subscript>20</Subscript> fullerene molecular device in two probe configuration

It is worth remarking that the C₂₀ cage like isomer has been the topic of concentrated theoretical research. C₂₀ single fullerene molecular devices gained a lot of popularity in the field of nano research due to their superlative doping dependent conductive properties. In this work, the double fullerene device has been considered. Here double fullerene molecular junction is created when two C₂₀ fullerene molecules, one in pristine form and other in doped form, are positioned between gold electrodes. Doping was done firstly by second period elements, boron, nitrogen, oxygen, and fluorine and then by group 14 tetragens, silicon, germanium, tin, and lead. For both the cases current characteristics were investigated. Superior conductivity was observed in the boron doped double C₂₀ molecular device while the fluorine doped device was the least conducting. Further for group 14 doping, the silicon doped double C₂₀ device showed maximum current carrying feature, whereas, least value of current was noted in tin doped C₂₀ device.     

Isolation and properties of lead-resistant variants of rat glioma cells

Glial cells are thought to protect neurons from heavy-metal toxicity. To gain a better understanding of mechanisms of protection against lead compounds, a number of lead-resistant C6 rat glioma cell sublines have been isolated. After 8 mo of growth in the absence of lead nitrate, three sublines still maintain their lead-resistant phenotype. None of the lead-resistant sublines are cross-resistant to Cd(II) or Ni(II), but all are cross-resistant (in varying degrees) to Hg(II), As(III), Sb(III), and Sn(II), and one is resistant to trimethyl tin. No inducible lead resistance is seen in any glioma line. One subline has been used to create cell-cell hybrids with wild-type cells. The hybrids exhibit dominance of the lead-resistant phenotype. To identify and analyze altered gene expression at the mRNA level in the lead-resistant sublines, the differential display technique was used. Numerous differences are seen between amplified fragments from wild-type and lead-resistant cells. Candidate clones are now being analyzed to confirm the differential expression and to isolate cDNAs that confer lead resistance.     

云锡矿粉诱发大鼠骨髓细胞染色体畸变的研究

云南锡业公司矿工的肺癌发病率高,矿尘中的砷,铁,铅等金属的潜在致癌性已引起了重视(张辅铭等,1985;云南锡业公司劳动防护研究所,华北辐射防护研究所,1982;云锡劳研所流行病室,1982;孙来华等,1986)。鉴于物质的致癌性与致突变性之间有一定的相关性,我们选用5种云锡矿粉,4种金属化合物,研究它们对大鼠骨髓细胞的遗     

Tin compounds interaction with membranes of egg lecithin liposomes

This work is a continuation of earlier research concerning the influence of tin compounds on the dynamic properties of liposome membranes produced with lecithin hen egg yolks (EYL). The experiments were carried out at room temperature (about 25 degrees C). Four tin compounds were chosen, including three organic ones, (CH3)4Sn, (C2H5)4Sn and (C3H7)3SnCl, and one inorganic, SnCl2. The investigated compounds were admixed to water dispersions of liposomes. The content of the admixture changed within the range 0 mol-% to 11mol-% in proportion to EYL. Two spin probes were used in the experiment: 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 2-ethyl-2-(15-methoxy-15-oxopentadecyl)-4,4-dimethyl-3-oxazolidinyloxyl (16-DOXYL-stearic acid), which penetrated through different areas of the membrane. It was found that tin compounds containing chlorine were the most active in interaction with liposome membranes. In the case of (C3H7)3SnCl, after exceeding 4% admixture content, an additional line appeared in the spectrum of the TEMPO probe which can be a result of formation of domain structures in the membranes of the studied liposomes. Compounds containing chlorine are of ionized form in water solution. The obtained results can thus mean that the activity of admixtures can be seriously influenced by their ionic character. In case of an admixture of non-ionic compounds the compound with a longer hydrocarbon chain displayed a slightly stronger effect on the spectroscopic parameters of the probes.