Hexameric Clusters Research Articles

Roles of glial cells in neuroinflammation and neurodegeneration

AbstractA gap junction is the major intercellular channel that facilitates direct signaling between cytoplasmic compartments of adjacent cells by transferring various small molecules (approximately 1 kDa) and ions. A gap junction consists of a pair of hemichannels, each of which is a hexameric cluster of protein subunits named connexin. Besides the functional gap junction with the coupled hemichannels, the uncoupled “free” hemichannels also facilitate two‐way transfer of molecules between the cytosol and extracellular space. Both gap junctions and hemichannels form the neuron–glia network, and contribute to the maintenance of homeostasis by propagating signals and buffering against toxins in the central nervous system. In contrast, recent evidence has also shown that microglial glutamate from hemichannels induces neuronal damage, and death signals are propagated from damaged cells to neighboring cells through gap junctions, suggesting that gap junctions and hemichannels are involved in the initiation and amplification of neuroinflammation and neurodegeneration in the central nervous system. Understanding the precise pathological roles of gap junctions and .hemichannels might lead to a new therapeutic approach that could slow and halt the progression of various neurological disorders.

Spectra and energy levels of Yb3+ ions in CaF2 transparent ceramics

Abstract Fluoride CaF 2 :Yb 3+ transparent ceramics for high power lasers are obtained by vacuum sintering and hot pressing of nanoparticles synthesized through a soft chemistry route. Comparative investigation of the luminescent properties of CaF 2 :Yb 3+ ceramics with the properties of single crystals counterpart is performed. A detailed spectroscopic analysis of the crystal-field splitting of the energy levels of Yb 3+ in CaF 2 ceramics is reported based on assignments made to the absorption and selective emission spectra observed between 905 nm and 1100 nm obtained at 20 K. The experimental Stark energy levels of the two Yb 3+ manifolds are established for all the present site symmetries in the CaF 2 ceramics host. Furthermore, a crystal field investigation of Yb 3+ doped CaF 2 transparent ceramics is presented. Very satisfactory agreement was obtained between calculated and experimental Stark energy levels of Yb 3+ ion corresponding to isolated and complex sites. Using the calculated Stark energy levels, the majority of the emission lines is attributed to the cubic ( O h ), tetragonal ( C 4v ) and trigonal ( C 3v ) site symmetries of Yb 3+ in CaF 2 ceramics, which are the dominant luminescent centers at low ytterbium concentrations (0.5 at%). For higher dopant concentrations, above the 2.5 at%, these emission lines are related only for one dominant class of Yb 3+ centers which corresponds to some hexameric clusters (Yb 6 F 36 and Yb 6 F 37 ).

APO010, a synthetic hexameric CD95 ligand, induces death of human glioblastoma stem-like cells.

The treatment of glioblastoma remains a major challenge in the field of neuro-oncology. There is emerging evidence that glioblastomas consist of heterogeneous cell populations with a small subset of cells with stem cell-like properties which might be resistant to conventional therapy and are thus crucial for tumor recurrence. These glioma-initiating cells (GICs) are therefore an attractive therapeutic target. Death receptor activation is one promising approach of cancer therapy. The synthetic hexameric cluster of differentiation 95 (CD95) agonist APO010 exhibits strong antiglioma activity towards human glioma cell lines, as well as in cell cultures of primary glioblastoma. Here, we investigated the ability of APO010 to induce cell death in a panel of previously well-defined GIC lines. The GIC lines and their derived differentiated cultures expressed CD95 on the cell surface and were sensitive towards APO010-mediated cell death to a variable extent. Temozolomide enhanced sensitivity of GICs to APO010. APO010 warrants being further evaluated as a tool to target GICs.

Photocatalytic Hydrogen Generation System Using a Nickel-Thiolate Hexameric Cluster

We report the use of a nickel-thiolate hexameric cluster, Ni6(SC2H4Ph)12, for photocatalytic hydrogen production from water. The nickel cluster was synthesized ex-situ and characterized by various techniques. Single crystal X-ray analysis, (1)H NMR, 2D COSY, ESI-MS, UV-visible spectroscopy, and TGA provided insight into the structure and confirmed the purity and stability of the cluster. Cyclic voltammetry helped confirm hydrogen evolution reaction (HER) activity of this catalyst. Photoreactions carried out using an iridium photosensitizer, Ir(F-mppy)2(dtbbpy)[PF6], and TEA as the sacrificial reductant revealed the high activity of the Ni6 cluster as a water reducing catalyst. High TONs (3750) and TOFs (970 h(-1)) were obtained at optimum catalyst concentration (0.025 mM), with low concentrations of catalyst yielding up to 30,000 turnovers. Quenching studies, along with the evidence obtained from the electrochemical analysis, showed that this water reduction system proceeds through a reductive quenching mechanism. Mercury poisoning studies confirmed that no active, metallic colloids were formed during the photocatalytic reaction.

A one-dimensional coordination polymer with a three-dimensional supramolecular framework:catena-poly[[[(3,4,7,8-tetramethyl-1,10-phenanthroline)cadmium(II)]-μ3-4,4′-sulfonyldibenzoato] trihydrate

In the title mixed-ligand metal-organic polymeric compound, {[Cd(C14H8O6S)(C16H16N2)]·3H2O}n, the asymmetric unit contains a crystallographically unique Cd(II) atom, one doubly deprotonated 4,4'-sulfonyldibenzoic acid (H2SDBA) ligand, one 3,4,7,8-tetramethyl-1,10-phenanthroline (TMPHEN) molecule and three solvent water molecules. Each Cd(II) centre is six-coordinated by two O atoms from a chelating carboxylate group of a SDBA(2-) ligand, two O atoms from monodentate carboxylate groups of two different SDBA(2-) ligands and two N atoms from a chelating TMPHEN ligand. There are two coordination patterns for the carboxylate groups of the SDBA(2-) ligand, with one in a μ1-η(1):η(1) chelating mode and the other in a μ2-η(1):η(1) bis-monodentate mode. Single-crystal X-ray diffraction analysis revealed that the title compound is a one-dimensional double-chain polymer containing 28-membered rings based on the [Cd2(CO2)2] rhomboid subunit. More interestingly, a chair-shaped water hexamer cluster is observed in the compound.

Supramolecular Ring Structures of 7-Methylguanine: A Computational Study of Its Self-assembly and Anion Binding

The density functional theory calculations of 7-methylguanine clusters revealed that stable ring assemblies can be formed with or without anions in the center position and hexameric clusters are the most stable and most planar ones. The coordination of anions (Cl−, Br−, NO3−) stabilizes and thus favors the formation of planar aggregates. We believe that the predicted planar structures stabilized by anions are good models for self-assembly structures formed at solid-liquid or solid-gas interfaces. Comparing the bonding and average H-bond energy to reference ribbon calculations we pointed out the presence of the previously introduced cooperativity effect in circular supramolecular structures of 7-methylguanine.

Performance of Non-Local and Atom-Pairwise Dispersion Corrections to DFT for Structural Parameters of Molecules with Noncovalent Interactions.

The nonlocal, electron density dependent dispersion correction of Vydrov and Van Voorhis (Vydrov, O. A.; Van Voorhis, T. J. Chem. Phys.2010, 133, 244103), termed VV10 or DFT-NL, has been implemented for structural optimizations of molecules. It is tested in combination with the four (hybrid)GGA density functionals TPSS, TPSS0, B3LYP, and revPBE38 for inter- and intramolecular noncovalent interactions (NCI) and compared to results from atom-pairwise dispersion corrected DFT-D3. The methods are applied to a wide range of different problems, namely the S22 and S66 test sets, large transition metal complexes, water hexamer clusters, hexahelicene, and four other difficult cases of intramolecular NCI. Critical interatomic distances are computed remarkably accurately by both dispersion corrections compared to theoretical or experimental reference data and inter- and intramolecular interactions are treated on equal footing. The methods can be recommended as reliable and robust tools for geometry optimizations of large systems in which long-range dispersion forces are crucial.

Relativistic Density Functional Study on Uranium(IV) and Thorium(IV) Oxide Clusters of Zonohedral Geometry

Free and ligated oxide clusters of thorium(IV) and uranium(IV) were studied with density functional theory using all-electron scalar relativistic method, as well as energy-consistent relativistic f-in-core pseudopotentials. The main driving force for the cluster formation is the sintering of the dioxoactinide moieties, which is more favorable for thorium(IV) than for uranium(IV) because, for the latter, a penalty for bending of the uranyl(IV) is to be paid. We assumed that the rhombic structural motif that exists already in the (AnO(2))(2) dimer could be a guide to explaining the preference for the existing An(6)O(8)-type clusters. On the basis of this, we have theoretically explored the possibility of the existence of similar (zonohedric) polyhedral actinide oxide clusters and found that the next possible cluster would be of An(12)O(20) stoicheometry. We have predicted by our DFT computations that the corresponding zonohedral clusters would be minima on the potential energy surface. The alternating An-O rhombic structural motif also offers a possible explanation of the existence and stoichiometry of the only nonfluorite cluster thus far, the An(12)O(20), which is nonzonohedral, nonconvex, but still a rhombic polyhedron. Our relativistic all electron DFT computations of both free cationic and ligated clusters predict that preparation of the larger clusters is not forbidden thermodynamically. We have also found that for the uranium(IV), oxide dimer and hexamer clusters are antiferromagnetic, broken spin singlet in their ground state, while ligated [U(6)O(8)] clusters prefer an all high-spin electronic configuration.

Density functional theory study of nitrogen-14 nuclear quadrupole coupling parameters of L-histidine: hydrogen-bonded system

The calculations of nitrogen-14 nuclear quadrupole parameters, nuclear quadrupole coupling constant, χ, and asymmetry parameter, η, of L-His were done in two distinct environments: one as a free fully optimized molecule, an isolated molecule with the geometrical parameters taken from X-ray, and the other in the orthorhombic and monoclinic solid states. The most probable interacting molecules with the central molecule in the crystalline phase were considered in the hexameric clusters to include hydrogen-bonding effects in the calculations. The computations were performed with PW91P86/6-31++G** and B3LYP6-31++G** methods using the Gaussian 98 program. The good agreement between the nitrogen-14 quadrupole parameters of the free His and imidazole molecules with their microwave available data demonstrates that the applied level of theory and the 6-31++G** basis set are suitable to obtain reliable electric field gradient values. In the solid state, the shifts of quadrupole coupling parameters from the monomer to the solid phase are reasonably well reproduced for the amino and imino sites of imidazole ring in a hexameric cluster. That implies the fact that the hexameric cluster worked effectively to generate the results which are compatible with the experiment. The quadrupole coupling constant values of -N(+) H(3) group are in fair agreement with the experiment. This discrepancy is due to the absences of vibrational effects and the rotation of -N(+) H(3) group around N-C(α) bond.

Implementation of Dynamical Nucleation Theory Effective Fragment Potentials Method for Modeling Aerosol Chemistry

In this work, the dynamical nucleation theory (DNT) model using the ab initio based effective fragment potential (EFP) is implemented for evaluating the evaporation rate constant and molecular properties of molecular clusters. Predicting the nucleation rates of aerosol particles in different chemical environments is a key step toward understanding the dynamics of complex aerosol chemistry. Therefore, molecular scale models of nanoclusters are required to understand the macroscopic nucleation process. On the basis of variational transition state theory, DNT provides an efficient approach to predict nucleation kinetics. While most DNT Monte Carlo simulations use analytic potentials to model critical sized clusters, or use ab initio potentials to model very small clusters, the DNTEFP Monte Carlo method presented here can treat up to critical sized clusters using the effective fragment potential (EFP), a rigorous nonempirical intermolecular model potential based on ab initio electronic structure theory calculations, improvable in a systematic manner. The DNTEFP method is applied to study the evaporation rates, energetics, and structure factors of multicomponent clusters containing water and isoprene. The most probable topology of the transition state characterizing the evaporation of one water molecule from a water hexamer at 243 K is predicted to be a conformer that contains six hydrogen bonds, with a topology that corresponds to two water molecules stacked on top of a quadrangular (H(2)O)(4) cluster. For the water hexamer in the presence of isoprene, an increase in the cluster size and a 3-fold increase in the evaporation rate are predicted relative to the reaction in which one water molecule evaporates from a water hexamer cluster.

Tapes of water hexamer clusters in the interlayer space of a 2D MOF: Structural, spectroscopic and computational insight of the confined water

The synthesis, crystal structure and characterization of [Er 2(C 4H 4O 4) 3(H 2O) 4]·6H 2O, with particular emphasis on the structural details and the vibrational behavior of the highly organized sub-net of water are reported. X-ray structural analysis reveals that the hybrid framework, which can be classified as belonging to the I 0O 2 type, acts as a host of an infinite tape of six-membered water rings with distorted chair conformation. The water network extends between the hybrid layers helping the close packing and the stabilization of the structure through H-bond interactions, with further development of the supramolecular tridimensional structure. The self-assembly of the hydration water molecules is conditioned by the hybrid host, forcing them to adopt a less stable conformation when compared with hexagonal ice. The vibrational spectra of partially and completely dehydrated samples as well as of partially isotopic diluted ones have been obtained and analyzed. In order to guide the assignment of the vibrational spectra a theoretical calculation was performed at the B3LYP/6-31G ∗∗ level for a model consisting of three water clusters.

Effect of Yb3+ concentration on optical properties of Yb:CaF2 transparent ceramics

In Yb:CaF2, the coordination of Yb3+ in the CaF2 lattice determines the spectroscopic properties that make Yb:CaF2 a good candidate for high power laser applications. In this work, we measure the optical absorption, emission, and fluorescence lifetime of 0.1, 1, 5, and 10at% Yb:CaF2 ceramics to determine whether Yb3+ substitutes as hexamer clusters giving rise to the tenability and long fluorescent lifetime observed in Yb:CaF2 single crystals. Absorption and emission spectra show that the concentration of Yb3+ present in hexamer clusters, as opposed to isolated ions, increases with increasing Yb3+ content. Fluorescence lifetime also increases with increasing Yb3+ content. Laser testing on a 1at% Yb:CaF2 transparent ceramic demonstrates that these materials are viable laser gain media.

A tight binding model for water

We demonstrate for the first time a tight binding model for water incorporating polarizable oxygen atoms. A novel aspect is that we adopt a "ground up" approach in that properties of the monomer and dimer only are fitted. Subsequently we make predictions of the structure and properties of hexamer clusters, ice-XI and liquid water. A particular feature, missing in current tight binding and semiempirical hamiltonians, is that we reproduce the almost two-fold increase in molecular dipole moment as clusters are built up toward the limit of bulk liquid. We concentrate on properties of liquid water, particularly dielectric constant and self diffusion coefficient, which are very well rendered in comparison with experiment. Finally we comment on the question of the contrasting densities of water and ice which is central to an understanding of the subtleties of the hydrogen bond.

A new triol host framework and the remarkable crystal structure of its DMSO inclusion complex

A new trigonal host molecule 1 featuring three 4-(9-hydroxy-9-fluorenyl)phenyl units symmetrically attached to a benzene core was synthesized and is shown to yield a 1:3 (host:guest) crystalline inclusion compound with DMSO (1a). The crystal structure of 1a is distinguished by a rare case of piedfort arrangement of host molecules and a unique hexameric cluster formation of DMSO.

A Conformational Switch Involved in Maturation of Staphylococcus aureus Bacteriophage 80α Capsids

Bacteriophages are involved in many aspects of the spread and establishment of virulence factors in Staphylococcus aureus, including the mobilization of genetic elements known as S. aureus pathogenicity islands (SaPIs), which carry genes for superantigen toxins and other virulence factors. SaPIs are packaged into phage-like transducing particles using proteins supplied by the helper phage. We have used cryo-electron microscopy and icosahedral reconstruction to determine the structures of the procapsid and the mature capsid of 80α, a bacteriophage that can mobilize several different SaPIs. The 80α capsid has T=7 icosahedral symmetry with the capsid protein organized into pentameric and hexameric clusters that interact via prominent trimeric densities. The 80α capsid protein was modeled based on the capsid protein fold of bacteriophage HK97 and fitted into the 80α reconstructions. The models show that the trivalent interactions are mediated primarily by a 22-residue β hairpin structure called the P loop that is not found in HK97. Capsid expansion is associated with a conformational switch in the spine helix that is propagated throughout the subunit, unlike the domain rotation mechanism in phage HK97 or P22.

Excess Electron and Lithium Atom Solvation in Water Clusters at Finite Temperature: An ab Initio Molecular Dynamics Study of the Structural, Spectral, and Dynamical Behavior of (H2O)6− and Li(H2O)6

The roles of hydrogen bonds in the solvation of an excess electron and a lithium atom in water hexamer cluster at 150 K have been studied by means of ab initio molecular dynamics simulations. It is found that the hydrogen bonded structures of (H(2)O)(6)(-) and Li(H(2)O)(6) clusters are very different from each other and they dynamically evolve from one conformer to other along their simulation trajectories. The populations of the single acceptor, double acceptor, and free type water molecules are found to be significantly high unlike that in pure water clusters. Free hydrogens of these type of water molecules primarily capture the unbound electron density in these clusters. It is found that the binding motifs of the free electron evolve with time and the vertical detachment energy of (H(2)O)(6)(-) and vertical ionization energy of Li(H(2)O)(6) also change with time. Assignments of the observed peaks in vibrational power spectra are done, and we found direct correlations between the time-averaged population of water molecules in different hydrogen bonding states and the spectral features. The dynamical aspects of these clusters have also been studied through calculations of time correlations of instantaneous stretch frequencies of OH modes which are obtained from the simulation trajectories through a time series analysis.

Localized Hartree product treatment of multiple protons in the nuclear-electronic orbital framework

An approximation for treating multiple quantum nuclei within the nuclear-electronic orbital (NEO) framework for molecular systems is presented. In the approximation to NEO-Hartree-Fock, the nuclear wave function is represented by a Hartree product rather than a Slater determinant, corresponding to the neglect of the nuclear exchange interactions. In the approximation to NEO-density functional theory, the nuclear exchange-correlation functional is chosen to be the diagonal nuclear exchange interaction terms, thereby eliminating the nuclear self-interaction terms. To further enhance the simplicity and computational efficiency, the nuclear molecular orbitals or Kohn-Sham orbitals are expanded in terms of localized nuclear basis sets. These approximations are valid because of the inherent localization of the nuclear orbitals and the numerical insignificance of the nuclear exchange interactions in molecular systems. Moreover, these approximations lead to substantial computational savings due to the reduction in both the number of integrals that must be calculated and the size of the matrices that must be diagonalized. These nuclear Hartree product approximation (HPA) methods scale linearly with the number of quantum protons and are highly parallelizable. Applications to a water hexamer, glycine dimer, and 32-water cluster, where all hydrogen nuclei are treated quantum mechanically, illustrate the accuracy and computational efficiency of the nuclear HPA methods. These strategies will facilitate the implementation of explicitly correlated NEO methods for molecular systems with multiple quantum protons.

Structures of Water Molecules Adsorbed on a Gold Electrode under Negative Potentials

Two stable conformations of water hexamer clusters on gold electrode under negative potentials have been identified by density functional theory calculations. Both form a ring structure but with different orientations of free OH bonds. In one of the structures, labeled as F-Type, four free OH bonds of the water molecules point toward the gold surface and remain stable over a wide range of the negative potential. The other structure, labeled as S-Type, starts with five such free OH bonds pointing toward the gold surface at the low negative potential and ends up with six of them at higher negative potential. From the energetic point of view, the S-Type structure is more stable than the F-Type under the same potential. By comparing the calculated Raman spectra with the experiment, it is found that S-Type structures are the most possible surface adsorption state of water molecules at the electrochemical interface under very negative electrode potentials. It is believed that such a novel water structure could ...

Co-operation of π⋯π, Cu(II)⋯π, carbonyl⋯π and hydrogen-bonding forces leading to the formation of water cluster mimics observed in the reassessed crystal structure of [Cu(mal)(phen)(H 2O)]2·3H 2O (H 2mal = malonic acid, phen = 1,10-phenanthroline)

A copper(II) malonate complex with formula [Cu(mal)(phen)(H 2O)] 2·3H 2O ( 1) [H 2mal = malonic acid, phen = 1,10-phenanthroline] has been synthesized and its crystal structure has been re-determined with an improved R value (the compound 1 was originally synthesized and crystallographically characterized by Kwik et al. with R = 0.047, see: J. Chem. Soc. Dalton Trans. (1986) 2529) with the water hydrogen atom positions located. This has led to the revelation that the water molecules organize around the carboxylate group of the malonate ligand forming tetramer, hexamer and octameric water cluster mimics. These cooperative hydrogen-bonding forces and various π-forces (π⋯π, Cu(II)⋯π, carbonyl⋯π) involving 1,10-phenanthroline aromatic rings determine the overall packing of the molecular units in the unit cell. There exists two identical monomers in the asymmetric unit with Z // = 2. TG measurements reveal the loss of water molecules that are all released at 120 °C. The water sorption/desorption process is reversible as supported by FTIR spectroscopic and XRPD studies.

Nuclear Magnetic Resonance Parameters of Water Hexamers

Nuclear magnetic resonance (1)H, (16)O, and (17)O chemical shifts, as well as (17)O quadrupolar parameters in several isomers of water hexamer clusters, are studied using density functional theory calculations and the gauge including projector augmented wave (GIPAW) pseudopotential method. The prism, cage, book, bag, chain, and two cyclic isomers are investigated, and structures with (16)O and (17)O nuclei are examined. It is found that the hydrogen and oxygen chemical shifts show a substantial variation. In six more stable hexamers, all quadrupole coupling constants decrease and asymmetry parameters increase in a comparison with bulk water, whereas a chain isomer shows an opposite behavior. The values of NMR parameters are in reasonable agreement with existing results obtained by more computationally demanding methods.