Pathways for the Formation of Formamide, a Prebiotic Biomonomer: Metal-Ions in Interstellar Gas-Phase Chemistry.

The chemistry occurring in the interstellar medium (ISM) is an active area of contemporary research. New aspects of interstellar chemistry are getting unraveled regularly. In this context, the role of metal-ions in the chemistry occurring in the ISM is not well-studied so far. Herein, we highlight the role of metal-ions in interstellar chemistry. For this purpose, we choose the problem of gas-phase formamide formation in interstellar molecular clouds. Formamide is a key biomonomer and contains the simplest peptide [-(C═O)-NH-] linkage. With its two electronegative atoms ("O" and "N"), it provides an excellent platform to probe the role of the metal-ions. The metal-ions chosen are Na+, K+, Al+, Mg+, and Mg2+-all of them present in the ISM. The metal-ions are studied in three different forms as bare positively charged ions, as hydrated metal-ions co-ordinated with a molecule of water, and when the metal-ions are part of a neutral covalent molecule. With the aid of electronic structure calculations [CCSD(T) and DFT methods], we study different gas-phase pathways which result in the generation of interstellar formamide. Throughout our study, we find that metal-ions lower the barriers (with Mg+, Mg++, and Al+ offering maximal stabilization of the transition states) and facilitate the reactions. The chemical factors influencing the reactions, how we consider the putative conditions in the ISM, the astrochemical implications of this study, and its connection with terrestrial prebiotic chemistry and refractory astrochemistry are subsequently presented. Based on our results, we also recommend the detection of two new closed-shell molecules, NH2CH2OH (aminomethanol) and CH2NH2+ (iminium ion), and two open-shell molecules, CONH2 (carbamyl radical) and HCONH (an isomer of carbamyl radical), in the ISM.

Application of Group I Metal Adduction to the Separation of Steroids by Traveling Wave Ion Mobility Spectrometry.

Steroids represent an interesting class of small biomolecules due to their use as biomarkers and their status as scheduled drugs. Although the analysis of steroids is complicated by the potential for many isomers, ion mobility spectrometry (IMS) has previously shown promise for the rapid separation of steroid isomers. This work is aimed at the further development of IMS separation for the analysis of steroids. Here, traveling wave ion mobility spectrometry (TWIMS) was applied to the study of group I metal adducted steroids and their corresponding multimers for five sets of isomers. Each set of isomers had a minimum of one dimeric metal ion adduct that exhibited a resolution greater than one (i.e., approaching baseline resolution). Additionally, ion-neutral collision cross sections (CCSs) were measured using polyalanine as a calibrant, which may provide an additional metric contributing to analyte identification. Where possible, measured CCSs were compared to previously reported values. When measuring CCSs of steroid isomers using polyalanine as the calibrant, nitrogen CCS values were within 1.0% error for monomeric sodiated adducts and slightly higher for the dimeric sodiated adducts. Overall, TWIMS was found to successfully separate steroids as dimeric adducts of group I metals. Graphical Abstract ᅟ.

MetalPDB in 2018: a database of metal sites in biological macromolecular structures.

MetalPDB (http://metalweb.cerm.unifi.it/) is a database providing information on metal-binding sites detected in the three-dimensional (3D) structures of biological macromolecules. MetalPDB represents such sites as 3D templates, called Minimal Functional Sites (MFSs), which describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. The 2018 update of MetalPDB includes new contents and tools. A major extension is the inclusion of proteins whose structures do not contain metal ions although their sequences potentially contain a known MFS. In addition, MetalPDB now provides extensive statistical analyses addressing several aspects of general metal usage within the PDB, across protein families and in catalysis. Users can also query MetalPDB to extract statistical information on structural aspects associated with individual metals, such as preferred coordination geometries or aminoacidic environment. A further major improvement is the functional annotation of MFSs; the annotation is manually performed via a password-protected annotator interface. At present, ∼50% of all MFSs have such a functional annotation. Other noteworthy improvements are bulk query functionality, through the upload of a list of PDB identifiers, and ftp access to MetalPDB contents, allowing users to carry out in-depth analyses on their own computational infrastructure.

Influence of Monovalent Cation Size on Nanodomain Formation in Anionic-Zwitterionic Mixed Bilayers.

Phosphatidylserine (PS) and phosphatidylcholine (PC) are two of the major anionic and zwitterionic phospholipids in mammalian cell membranes. Ion-PS interaction is hypothesized to play a crucial role in a range of biological events including membrane fusion, lipid phase modulation, membrane protein insertion and translocation. In this study, we characterize lipid nanodomain formation in PC/PS mixed bilayers using coarse-grained simulations. We investigate the role of monovalent cation sizes in modulating lipid-ion binding modes and lipid demixing. Our simulations suggest that certain lipid-ion binding modes lead to growth of ion-mediated PS lipid clusters. The existing literature reveals the polymorphism in binding and partitioning patterns in monovalent cations (Na+, K+, and Li+) with anionic lipids. Our work provides a microscopic view on the ion-size-dependent PS lipid packing pattern observed experimentally. A coupled relationship between lipid curvature and asymmetry is observed in highly demixed PC/PS mixed bilayers.

From Widely Accepted Concepts in Coordination Chemistry to Inverted Ligand Fields.

We begin with a brief historical review of the development of our understanding of the normal ordering of nd orbitals of a transition metal interacting with ligands, the most common cases being three below two in an octahedral environment, two below three in tetrahedral coordination, and four below one in a square-planar environment. From the molecular orbital construction of these ligand field splittings evolves a strategy for inverting the normal order: the obvious way to achieve this is to raise the ligand levels above the metal d's; that is, make the ligands better Lewis bases. However, things are not so simple, for such metal/ligand level placement may lead to redox processes. For 18-electron octahedral complexes one can create the inverted situation, but it manifests itself in the makeup of valence orbitals (are they mainly on metal or ligands?) rather than energy. One can also see the effect, in small ways, in tetrahedral Zn(II) complexes. We construct several examples of inverted ligand field systems with a hypothetical but not unrealistic AlCH3 ligand and sketch the consequences of inversion on reactivity. Special attention is paid to the square-planar case, exemplified by [Cu(CF3)4](-), in which Snyder had the foresight to see a case of an inverted field, with the empty valence orbital being primarily ligand centered, the dx2-y2 orbital heavily occupied, in what would normally be called a Cu(III) complex. For [Cu(CF3)4](-) we provide theoretical evidence from electron distributions, geometry of the ligands, thermochemistry of molecule formation, and the energetics of abstraction of a CF3 ligand by a base, all consistent with oxidation of the ligands in this molecule. In [Cu(CF3)4](-), and perhaps more complexes on the right side of the transition series than one has imagined, some ligands are σ-noninnocent. Exploration of inverted ligand fields helps us see the continuous, borderless transition from transition metal to main group bonding. We also give voice to a friendly disagreement on oxidation states in these remarkable molecules.

Na, K, Ca, Mg, and U-series in fossil bone and the proposal of a radial diffusion-adsorption model of uranium uptake.

Fossil bones are often the only materials available for chronological reconstruction of important archeological sites. However, since bone is an open system for uranium, it cannot be dated directly and therefore it is necessary to develop models for the U uptake. Hence, a radial diffusion-adsorption (RDA) model is described. Unlike the classic diffusion-adsorption (D-A) model, RDA uses a cylindrical geometry to describe the U uptake in fossil bones. The model was applied across a transverse section of a tibia of an extinct megamammal Macrauchenia patachonica from the La Paz Local Fauna, Montevideo State, Uruguay. Measurements of spatial distribution of Na, K, Ca, and Mg were also performed by neutron activation analysis (NAA). Gamma-ray spectrometric U-series dating was applied to determine the age of the bone sample. From U concentration profile, it was possible to observe the occurrence of a relatively slow and continuous uranium uptake under constant conditions that had not yet reached equilibrium, since the uranium distribution is a ∪-shaped closed-system. Predictions of the RDA model were obtained for a specific geochemical scenario, indicating that the effective diffusion coefficient D/R in this fossil bone is (2.4 ± 0.6)10(-12) cm(2)s(-1). Mean values of Na, K, Ca, and Mg contents along the radial line of the fossil tibia are consistent with the expected behavior for spatial distributions of these mineral elements across a modern bone section. This result indicates that the fossil tibia may have its mineral structure preserved.

Quantitative chemical imaging of the intracellular spatial distribution of fundamental elements and light metals in single cells.

We report a method that allows a complete quantitative characterization of whole single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and magnesium and providing submicrometer maps of element molar concentration, cell density, mass, and volume. This approach allows quantifying elements down to 10(6) atoms/µm(3). This result was obtained by applying a multimodal fusion approach that combines synchrotron radiation microscopy techniques with off-line atomic force microscopy. The method proposed permits us to find the element concentration in addition to the mass fraction and provides a deeper and more complete knowledge of cell composition. We performed measurements on LoVo human colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg concentration with higher values within the nucleus in LoVo-R and in the perinuclear region in LoVo-S cells. This feature was not so evident for the other elements, suggesting that Mg compartmentalization could be a significant trait of the drug-resistant cells.

Characterization of carbonic anhydrase from Turkish native "Gerze" chicken and influences of metal ions on enzyme activity.

Abstract Carbonic anhydrase was purified and characterized from erythrocytes of the Turkish native chicken, Gerze, for the first time. The enzyme was purified 57.65-fold with a yield of 52%, and a specific activity of 954.08 U/mg proteins having optimum pH at 8.0; optimum temperature at 30 °C; optimum ionic strength at 10 mM and stable pH at 8.0. The purified enzyme had apparent KM and Vmax values of 0.73 mM and 0.236 µmol × min(-1), respectively. Al(+3), Hg(+2), Cu(+2), Pb(+2), and Cd(+2) showed inhibitory effects on the enzyme. Pb(+2) exhibited the strongest inhibitory action. Cd(+2) and Hg(+2) were moderate inhibitor, whereas Al(+3) and Cu(+2) showed weaker actions. All tested metals inhibited the enzyme in competitive manner. Our findings indicate that these metals inhibit the chicken enzyme in a similar manner to other α-CAs from mammals investigated earlier, but susceptibility to various metals differ between the native chicken and other mammalian enzymes.

Behavioral, clinical, and pathological characterization of acid metalliferous water toxicity in mallards.

From September to November 2000, United States Fish and Wildlife Service biologists investigated incidents involving 221 bird deaths at 3 mine sites located in New Mexico and Arizona. These bird deaths primarily involved passerine and waterfowl species and were assumed to be linked to consumption of acid metalliferous water (AMW). Because all of the carcasses were found in or near pregnant leach solution ponds, tailings ponds, and associated lakes or storm water retention basins, an acute-toxicity study was undertaken using a synthetic AMW (SAMW) formulation based on the contaminant profile of a representative pond believed to be responsible for avian mortalities. An acute oral-toxicity trial was performed with a mixed-sex group of mallards (Anas platyrhynchos). After a 24-h pretreatment food and water fast, gorge drinking was evident in both SAMW treatment and control groups, with water consumption rates greatest during the initial drinking periods. Seven of nine treated mallards were killed in extremis within 12 h after the initiation of dose. Total lethal doses of SAMW ranged from 69.8 to 270.1 mL/kg (mean ± SE 127.9 ± 27.1). Lethal doses of SAMW were consumed in as few as 20 to 40 min after first exposure. Clinical signs of SAMW toxicity included increased serum uric acid, aspartate aminotransferase, creatine kinase, potassium, and P levels. PCV values of SAMW-treated birds were also increased compared with control mallards. Histopathological lesions were observed in the esophagus, proventriculus, ventriculus, and duodenum of SAMW-treated mallards, with the most distinctive being erosion and ulceration of the kaolin of the ventriculus, ventricular hemorrhage and/or congestion, and duodenal hemorrhage. Clinical, pathological, and tissue-residue results from this study are consistent with literature documenting acute metal toxicosis, especially copper (Cu), in avian species and provide useful diagnostic profiles for AMW toxicity or mortality events. Blood and kidney Cu concentrations were 23- and 6-fold greater, respectively, in SAMW mortalities compared with controls, whereas Cu concentrations in liver were not nearly as increased, suggesting that blood and kidney concentrations may be more useful than liver concentrations for diagnosing Cu toxicosis in wild birds. Based on these findings and other reports of AMW toxicity events in wild birds, we conclude that AMW bodies pose a significant hazard to wildlife that come in contact with them.

Evaluation of oxygen pressurized microwave-assisted digestion of botanical materials using diluted nitric acid.

The feasibility of diluted nitric acid solutions for microwave-assisted decomposition of botanical samples in closed vessels was evaluated. Oxygen pressurized atmosphere was used to improve the digestion efficiency and Al, Ca, K, Fe, Mg and Na were determined in digests by inductively coupled plasma optical emission spectrometry (ICP OES). Efficiency of digestion was evaluated taking into account the residual carbon content (RCC) and residual acidity in digests. Samples were digested using nitric acid solutions (2, 3, 7, and 14 mol L(-1) HNO(3)) and the effect of gas phase composition inside the reaction vessels by purging the vessel with Ar (inert atmosphere, 1 bar), air (20% of oxygen, 1 bar) and pure O(2) (100% of oxygen, 1 bar) was evaluated. The influence of oxygen pressure was studied using pressures of 5, 10, 15 and 20 bar. It was demonstrated that a diluted nitric acid solution as low as 3 mol L(-1) was suitable for an efficient digestion of sample masses up to 500 mg of botanical samples using 5 bar of oxygen pressure. The residual acidities in final digests were lower than 45% in relation to the initial amount of acid used for digestion (equivalent to 1.3 mol L(-1) HNO(3)). The accuracy of the proposed procedure was evaluated using certified reference materials of olive leaves, apple leaves, peach leaves and pine needles. Using the optimized conditions for sample digestion, the results obtained were in agreement with certified values. The limit of quantification was improved up to a factor of 14.5 times for the analytes evaluated. In addition, the proposed procedure was in agreement with the recommendations of the green chemistry once it was possible to obtain relatively high digestion efficiency (RCC<5%) using only diluted HNO(3), which is important to minimize the generation of laboratory residues.

Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms.

Mechanisms of carcinogenicity are discussed for metals and their compounds, classified as carcinogenic to humans or considered to be carcinogenic to humans: arsenic, antimony, beryllium, cadmium, chromium, cobalt, lead, nickel and vanadium. Physicochemical properties govern uptake, intracellular distribution and binding of metal compounds. Interactions with proteins (e.g., with zinc finger structures) appear to be more relevant for metal carcinogenicity than binding to DNA. In general, metal genotoxicity is caused by indirect mechanisms. In spite of diverse physicochemical properties of metal compounds, three predominant mechanisms emerge: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatases.

On the experimental use of light metal salts for negative staining.

All common negative stains are salts of heavy metals. To remedy several technical defects inherent in the use of heavy metal compounds, this study investigates whether salts of the light metals sodium, magnesium, and aluminum can function as negative stains. Screening criteria require aqueous solubility at pH 7.0, formation of a smooth amorphous layer upon drying, and transmission electron microscope imaging of the 87-A (8.7-nm) lattice periodicity in thin catalase crystals. Six of 23 salts evaluated pass all three screens; detection of the protein shell in ferritin macromolecules indicates that light metal salts also provide negative staining of single particle specimens. Appositional contrast is less than that given by heavy metal negative stains; image density can be raised by increasing electron phase contrast and by selecting salts with phosphate or sulfate anions, thereby adding strong scattering from P or S atoms. Low-dose electron diffraction of catalase crystals negatively stained with 200 mM magnesium sulfate shows Bragg spots extending out to 4.4 A. Future experimental use of sodium phosphate buffer and magnesium sulfate for negative staining is anticipated, particularly in designing new cocktail (multicomponent) negative stains able to support and protect protein structure to higher resolution levels than are currently achieved.

Monte Carlo investigation of breast intraoperative radiation therapy with metal attenuator plates.

In intraoperative electron radiation therapy for breast cancer, attenuation plates are commonly used to protect organs at risk. These plates can be made of different materials, and the correct material (or combination of materials) has to be chosen in order to achieve the desired attenuation, while avoiding excessive backscattered radiation. The Monte Carlo method (BEAMnrcMP and DOSXYZnrcMP) has been used to characterize the electron beam generated by the setup (composed of a nondedicated linac and an applicator), and to simulate the percent depth dose (PDD) for plates of different materials. The beam has been characterized for nominal energies of 9 and 12 MeV. Several differently composed plates have been investigated: it was found, as expected, that the use of a plate presenting to the electron beam a high-Z material (i.e., lead) has to be avoided because of excessive backscatter (up to 52% compared to the PDD without plate). On the other hand, the use of a single low-Z material (i.e., aluminum) in the plate can lead to an insufficient attenuation of the beam. The two-layer plate (6 mm of Al plus 3 mm of Cu) used in S. Chiara Hospital has been found to attenuate the beam almost completely for both considered energies, causing negligible backscatter radiation. The spectrum at various depth and at the tissue-plate interface has also been investigated.

A method of test for residual isophorone diisocyanate trimer in new polyester-polyurethane coatings on light metal packaging using liquid chromatography with tandem mass spectrometric detection.

A method of test for residual isophorone diisocyanate (IPDI) trimer in experimental formulation polyester-polyurethane (PEPU) thermoset coatings on metal food packaging is described. The method involves extraction of coated panels using acetonitrile containing dibutylamine for concurrent derivatisation, and then high performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection (LC-MS/MS). Single laboratory validation was carried out using three different experimental PEPU-based coatings. The calibrations were linear, the analytical recovery was good, no interferences were seen, and substance identification criteria were met. The detection limit of the method is around 0.02 micro g/100 cm(2) of coating, which for a typical sized can and assuming complete migration of any residual IPDI trimer, corresponds to about 0.2 micro g/kg food or beverage. Separate studies indicated that, even if migration occurred at such low levels, the IPDI trimer would not be expected to persist in canned aqueous or fatty foodstuffs as it would hydrolyse to the corresponding aliphatic amine or react with food components to destroy the isocyanate moiety. The method of test developed here for residual IPDI trimer in thermoset polyester-polyurethane coatings should prove to be a valuable tool for investigating the cure kinetics of these novel coatings and help to guide the development of enhanced formulations.

Release of toxic metals from button batteries retained in the stomach: An in vitro study.

BACKGROUND: Ingestion of button batteries by children is a rapidly growing problem, and opinions differ on how button batteries distal to the gastroesophageal junction should be managed. The authors therefore performed an experimental study to determine the cumulative load of various toxic elements released from retained button cells in simulated gastric juice. METHODS: Eight different groups of button cells were immersed in simulated gastric juice. Analyzed elements included Al, Ba, Cd, Cr, Cu, Fe, Hg, Li, Mg, Mn, Ni, Pb, Sb, Sn, Sr, Te, TI, V, W; and Zn. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the residual amounts of elements after 4, 24, 72, and 120 hours. RESULTS: At 4 hours, leakage was seen with almost all batteries, with the levels increasing in a time-dependent manner. The highest detected levels at 4 hours were 1.20 microgram for Cd, 280.51 ng for Hg, and 2.63 microgram for Pb. Dissolution, holes, and defragmentation were seen within 24 to 72 hours. Battery weight loss varied between 22 and 104 mg over the course of the study. CONCLUSIONS: Toxic elements contained in button cells are released quickly in gastric juice. This finding might change the current policy of watchful waiting or conservative management of batteries lodged in the stomach.