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).

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Formation of an unusual charge-transfer network from an ionic liquid.

An intriguing and novel charge-transfer complex between dimethyldihydrophenazine and diethylviologen has been crystallized from an ionic liquid at room temperature, resulting in an interesting stacking motif of interrupted D***A***D type triads: efficient formation of the complex is seen within an ionic liquid and acetone, with the complex absorbing strongly across nearly the entire visible-NIR spectral region.

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.

Beryllium binding at neutral pH: the importance of the Be-O-Be motif.

Beryllium speciation at physiological conditions is critical to understanding chronic beryllium disease (CBD). The MHC-class II receptor alleles that have been linked to CBD have more than six carboxylates in a short 20 amino acid segment of the binding pocket and it has been suggested that beryllium may bind within the MHC-class II receptor via the carboxylates. Previous reports also show that citric acid binds beryllium significantly stronger than similar carboxylate ligands such as tartaric acid and is one of the few ligands that can compete with hydrolysis to solubilize beryllium across the entire pH range at molar concentrations. We have characterized the binding of Be to citric acid and shown using a combination of NMR, mass spectrometry and ligand competition studies that Be2L and Be4L2 species dominate. A Be-O-Be linkage with the bridging oxygen coming from the aliphatic alcohol is critical to the stability of the complex. We show through competition experiments that the most stable Be-O-Be arrangement has one Be in a five-member ring and the other Be in a six-member ring. The unusual deprotonation of an aliphatic alcohol (pK(a) = 18) at neutral pH has significant ramifications on the potential interactions of Be with biological ligands such as carbohydrates and Ser and Thr residues.

Noncontact two-color luminescence thermometry based on intramolecular luminophore cyclization within an ionic liquid.

A self-referencing optical thermometer based on a reversible, temperature-dependent monomer-excimer interconversion of 1,3-bis(1-pyrenyl)propane dissolved in an ionic liquid and operating in the 25 to 140 degrees C range is reported.

Fluorescence studies of protein thermostability in ionic liquids.

Using the single tryptophan residue in the sweet protein monellin as a spectroscopic handle, we show the extreme thermodynamic stabilization offered by an ionic liquid; T(un) approximately 105 degrees C in [C4mpy][Tf2N] compared to 40 degrees C in bulk water.