Encapsulation of the Be(II) cation: spectroscopic and computational study.

The structures of a series of tetracoordinate beryllium(II) complexes with ligands derived from tertiary-substituted amines have been computationally modeled and their (9)Be magnetic shielding values determined using the gauge-including atomic orbital (GIAO) method at the 6-311++g(2d,p) level. A good correlation was observed between calculated (9)Be NMR chemical shifts when compared to experimental values in polar protic solvents, less so for the values recorded in polar aprotic solvents. A number of alternative complex structures were modeled, resulting in an improvement in experimental versus computational (9)Be NMR chemical shifts, suggesting that in some cases full encapsulation on the beryllium atom was not occurring. Several of the synthesized complexes gave rise to unexpected fluorescence, and inspection of the calculated molecular orbital diagrams associated with the electronic transitions suggested that the rigidity imparted by the locking of certain conformations upon Be(II) coordination allowed delocalization across adjacent aligned aromatic rings bridged by Be(II).

Beryllium and strong hydrogen bonds.

We compare beryllium to H+ and show that beryllium can displace H+ in many "strong hydrogen bonds" where Be as a "tetrahedral proton" (O-Be-O angle is tetrahedral as opposed to the nearly linear O-H-O angle) is thermodynamically preferred. The strong hydrogen bond provides two advantages. First, the O-X distance in a strong hydrogen bond is in the range 2.4-2.8 A, which brings two oxygen atoms into a predefined chelating binding site for beryllium. Second, the strong hydrogen bond provides a low barrier pathway to displace the proton without breaking a strong covalent O-H bond by shifting the proton to the more acidic site as Be interacts with the basic oxygen. The low barrier to proton transfer associated with a strong hydrogen bond provides a kinetic pathway for Be binding, and the binding strength increases with the increasing basicity of the site as indicated by the pKa. The physiological importance of this type of interaction is demonstrated with the solubility of a variety of Be complexes at pH 7. Based on this concept, new ligands have been designed for Be binding that solubilize Be in phosphate media and can be used as fluorescent imaging agents. Finally, the binding of Be to the iron transport protein transferrin is discussed as it relates to the same type of binding.

Beryllium alters lipopolysaccharide-mediated intracellular phosphorylation and cytokine release in human peripheral blood mononuclear cells.

Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.

Recent advances in understanding the biomolecular basis of chronic beryllium disease: a review.

In this review we summarize the work conducted over the past decade that has advanced our knowledge of pulmonary diseases associated with exposure to beryllium that has provided a molecular-based understanding of the chemistry, immunopathology, and immunogenetics of beryllium toxicity. Beryllium is a strong and lightweight metal that generates and reflects neutrons, resists corrosion, is transparent to X-rays, and conducts electricity. Beryllium is one of the most toxic elements on the periodic table, eliciting in susceptible humans (a) an allergic immune response known as beryllium sensitization (BeS); (b) acute beryllium disease, an acutely toxic, pneumonitis-like lung condition resulting from exposure to high beryllium concentrations that are rarely seen in modern industry; and (c) chronic beryllium disease (CBD) following either high or very low levels of exposure. Because of its exceptional strength, stability, and heat-absorbing capability, beryllium is used in many important technologies in the modern world. In the early 1940s, beryllium was recognized as posing an occupational hazard in manufacturing and production settings. Although acute beryllium disease is now rare, beryllium is an insidious poison with a latent toxicity and the risk of developing CBD persists. Chronic beryllium disease-a systemic granulomatous lung disorder caused by a specific delayed immune response to beryllium within a few months to several decades after exposure-has been called the "unrecognized epidemic". Although not a disease in itself, BeS, the innate immune response to beryllium identified by an abnormal beryllium lymphocyte proliferation test result, is a population-based predictor of CBD. Genetic susceptibility to CBD is associated with alleles of the major histocompatibility gene, human leukocyte antigen DP (HLA-DP) containing glutamic acid at the 69th position of the beta chain (HLA-DPbeta-E69). Other genes are likely to be involved in the disease process, and research on this issue is in progress. The current Occupational Safety & Health Administration permissible exposure limit of 2 microg/m3 has failed to protect workers from BeS/CBD. As a safe exposure limit that will not lead to BeS or CBD has not yet been determined, the realization that the risk of CBD persists has led to a renaissance in research on the effects of the metal on human health. Current data support further reductions in exposure levels to help minimize the incidence of CBD. Steps that would directly impact both the power of epidemiologic studies and the cost of surveillance would be to develop and validate improved screening and diagnostic tests, and to identify more genetic factors that affect either sensitization or disease process. The major focus of this review is the recent research on the cellular and molecular basis of beryllium sensitization and disease, using a multidisciplinary approach of bioinorganic chemistry and immunology. First we present a historical background of beryllium exposure and disease, followed by occurrence of beryllium in the environment, toxicokinetics, biological effects, beryllium lung disease, and other human health effects.

Highly conductive films of layered ternary transition-metal nitrides.

Film studies: Epitaxial films of BaZrN(2) (see TEM image) and BaHfN(2) are grown by polymer-assisted deposition on SrTiO(3) (STO) substrates. The films are phase-pure, allowing the intrinsic physical properties of the ternary nitrides to be studied. From 5 to 300 K, the films exhibit metallic-like resistivity-temperature behavior, with large residual resistivity ratios.

Ultrathin epitaxial superconducting niobium nitride films grown by a chemical solution technique.

Ultrathin epitaxial superconducting NbN (18 nm) films, exhibiting a superconducting transition temperature of 14 K and a critical current density as high as 5.2 MA cm(-2) at 5 K under zero magnetic field, were grown on SrTiO(3) (STO) by a chemical solution technique, polymer assisted deposition (PAD).

Epitaxial ternary nitride thin films prepared by a chemical solution method.

It is indispensable to use thin films for many technological applications. This is the first report of epitaxial growth of ternary nitride AMN2 films. Epitaxial tetragonal SrTiN2 films have been successfully prepared by a chemical solution approach, polymer-assisted deposition. The structural, electrical, and optical properties of the films are also investigated.

Upregulation of I-CAM1 in response to beryllium exposure in small airway epithelial cells.

Chronic Beryllium Disease (CBD) is a delayed-type hypersensitivity immune reaction that leads to granuloma formation in the lungs and potentially severe loss of pulmonary function. Although the molecular mechanisms that mediate beryllium (Be)-stimulated granuloma formation are not well understood, cell adhesion molecules are likely to play a key role in the migration of immune cells to sites of inflammation. In this study, we examined the role of the cell adhesion molecule I-CAM1 in Be-stimulated small airway epithelial cells (SAECs). These epithelial cells line the airway and represent the first point of contact for inhaled foreign substances. We find that Be exposure specifically induced I-CAM1 expression on the cell surface of SAEC and release of soluble I-CAM1 into the extracellular medium. Furthermore, anti-I-CAM1 antibodies inhibited Be-stimulated adhesion of SAEC to the macrophage cell-line THP1, indicating that the Be-induced adhesive properties of SAEC are at least partly due to I-CAM1 expression. These studies support a model in which I-CAM1 cell adhesion functions may play a role in directing immune cells to the lung and activating a Be-specific immune response in Be hypersensitivity disease.

The bioinorganic chemistry and associated immunology of chronic beryllium disease.

Chronic beryllium disease (CBD) is a debilitating, incurable, and often fatal disease that is caused by the inhalation of beryllium particulates. The growing use of beryllium in the modern world, in products ranging from computers to dental prosthetics (390 tons of beryllium in the US in the year 2000) necessitates a molecular based understanding of the disease in order to prevent and cure CBD. We have investigated the molecular basis of CBD at Los Alamos National Laboratory during the past six years, employing a multidisciplinary approach of bioinorganic chemistry and immunology. The results of this work, including speciation, inhalation and dissolution, and immunology will be discussed.

Extraction and optical fluorescence method for the measurement of trace beryllium in soils.

Beryllium metal and beryllium oxide are important industrial materials used in a variety of applications in the electronics, nuclear energy, and aerospace industries. These materials are highly toxic, they must be disposed of with care, and exposed workers need to be protected. Recently, a new analytical method was developed that uses dilute ammonium bifluoride for extraction of beryllium and a high quantum yield optical fluorescence reagent to determine trace amounts of beryllium in airborne and surface samples. The sample preparation and analysis procedure was published by both ASTM International and the National Institute for Occupational Safety and Health (NIOSH). The main advantages of this method are its sensitivity, simplicity, use of lower toxicity materials, and low capital costs. Use of the technique for analyzing soils has been initiated to help meet a need at several of the U.S. Department of Energy legacy sites. So far this work has mainly concentrated on developing a dissolution protocol for effectively extracting beryllium from a variety of soils and sediments so that these can be analyzed by optical fluorescence. Certified reference materials (CRM) of crushed rock and soils were analyzed for beryllium content using fluorescence, and results agree quantitatively with reference values.

Perturbation of local solvent structure by a small dication: a theoretical study on structural, vibrational, and reactive properties of beryllium ion in water.

A molecular based understanding of beryllium chemistry in the context of biomolecules is necessary for gaining progress in prevention and treatment of chronic beryllium disease. One aspect that has hindered the theoretical progress has been the lack of a simple classical two-body potential for the aqueous beryllium ion (Be2+) to be used with biomolecular simulations. We provide new parameters for Be2+ that capture the structural and reactive properties of this small dication. Using classical molecular dynamics simulations, we show that these parameters reproduce the correct radial distribution function and coordination numbers for this cation in explicit aqueous solution when compared to published diffraction and NMR measurements. The geometrical parameters obtained using classical simulations are also in agreement with ab initio calculations. We successfully predict the vibrational modes of the tetra aqua Be2+ dication from ab initio calculations on solvated structures obtained from the simulations. The calculated vibrational modes show better agreement with experiments compared to any published work. This new potential also produces a well-established hydrogen bonding between the first and second solvation shells. More importantly, when the molecular dynamics (MD) and ab initio results are interpreted in concert, the dynamics and nature of interactions between the first and second shells capture the pivotal role they play on the reactivity of aqua-Be complexes.

Structure and magnetic behavior of transition metal based ionic liquids.

A series of ionic liquids containing different paramagnetic anions have been prepared and all show paramagnetic behavior with potential applications for magnetic and electrochromic switching as well as novel magnetic transport; also, the tetraalkylphosphonium-based ionic liquids reveal anomalous magnetic behavior.

Ultra-trace determination of beryllium in occupational hygiene samples by ammonium bifluoride extraction and fluorescence detection using hydroxybenzoquinoline sulfonate.

A highly sensitive molecular fluorescence method for measuring ultra-trace levels of beryllium has been previously described. The method entails extraction of beryllium workplace samples by 1% ammonium bifluoride (NH(4)HF(2), aqueous), followed by fluorescence detection using hydroxybenzoquinoline sulfonate (HBQS). In this work, modification of the existing procedure resulted in a significant improvement in detection power, thereby enabling ultra-trace determination of beryllium in air filter and surface wipe samples. Such low detection limits may be necessary in view of expected decreases in applicable occupational exposure limits (OELs) for beryllium. Attributes of the modified NH(4)HF(2) extraction/HBQS fluorescence method include method detection limits (MDLs) of <0.8 ng to approximately 2 ng Be per sample (depending on the fluorometer used), quantitative recoveries from beryllium oxide, a dynamic range of several orders of magnitude, and freedom from interferences. Other key advantages of the technique are field portability, relatively low cost, and high sample throughput. The method performance compares favorably with that of inductively coupled plasma-mass spectrometry (ICP-MS).

Isostructural neo-pentoxide derivatives of group 3 and the lanthanide series metals for the production of Ln2O3 nanoparticles.

The synthesis and characterization of a series of neo-pentoxide (OCH2C(CH3)3 or ONep) derivatives of group 3 and the lanthanide (Ln) series' metals were undertaken via an amide/alcohol exchange route. Surprisingly, the products isolated and characterized by single-crystal X-ray diffraction yielded isostructural species for every trivalent cation studied: [Ln(mu-ONep)2(ONep)]4 [Ln=Sc (1), Y (2), La (3), Ce (4), Pr (5), Nd (6), Sm (7), Eu (8), Gd (9), Tb (10), Dy (11), Ho (12), Er (13), Tm (14), Yb (15), Lu (16)]. Compounds 3, 4, 6, and 11 have been previously reported. Within this series of complexes, the Ln metal centers are oriented in a square with each Ln-Ln edge interconnected via two mu-ONep ligands; each metal center also binds one terminal ONep ligand. NMR data of 1-3 indicate that the solid-state structure is retained in solution. FTIR spectroscopy (KBr pellet) revealed the presence of significant Ln---H-C interactions within one set of the bridging ONep ligands in all cases; the stretching frequencies of these C-H bonds appear to increase in magnitude with decrease in metal ion radius. These complexes were used to generate nanoparticles through solution hydrolysis routes, resulting in the formation of lanthanide oxide nanoparticles and rods. The emission properties of these ceramics were preliminarily investigated using UV-vis and PL measurements.

Fluorescence quenching immunoassay performed in an ionic liquid.

We describe the first example of immunoanalysis performed within an ionic liquid with minimal deleterious effect; our results bode well for the development of second-generation biosensors, particularly in applications involving poorly water soluble analytes including pesticides, phospholipids, and illicit drugs.

Conformal coating of nanoscale features of microporous Anodisc membranes with zirconium and titanium oxides.

We have successfully coated a nanofeatured material with ZrO2 and TiO2 using a polymer assisted deposition technique.