Large Number Of Bonds Research Articles

Structure and hydrogen bonds of cyclohexapeptide RA-VII by molecular dynamics simulations and quantum chemical calculations

We computationally examined the structure of anti-tumour bicyclic hexapeptide RA-VII. This peptide adopts three conformations (confs.), A, B and C, in dimethyl sulfoxide (DMSO). Although it was experimentally reported that the structure of conf. A is important for anti-tumour activity, the dynamics of confs. A, B and C are not well known. We performed quantum chemical calculations and molecular dynamics (MD) simulations of RA-VII in DMSO. The MD simulations indicated two different local stable structures for conf. C: a structure containing a bent 18-membered ring and another structure containing a rotated peptide bond between Tyr6 and d-Ala1. The root-mean-square fluctuation of the 14-membered ring for conf. A was larger than that for confs. B and C. Ala4 formed intramolecular hydrogen bonds more often in conf. A than in the other conformations. A large number of hydrogen bonds and large structural fluctuations are important for the anti-tumour activity of RA-VII. Our results for the structural change of conf. C and the analysis of the dynamics for confs. A, B and C may contribute to the design of new analogues of cyclic peptides.

Molecular dynamics simulation of the membrane binding and disruption mechanisms by antimicrobial scorpion venom-derived peptides

Pandinin 2 (Pin2) is an alpha-helical polycationic peptide, identified and characterized from venom of the African scorpion Pandinus imperator with high antimicrobial activity against Gram-positive bacteria and less active against Gram-negative bacteria, however it has demonstrated strong hemolytic activity against sheep red blood cells. In the chemically synthesized Pin2GVG analog, the GVG motif grants it low hemolytic activity while keeping its antimicrobial activity. In this work, we performed 12 μs all-atom molecular dynamics simulation of the antimicrobial peptides (AMPs) Pin2 and Pin2GVG to explore their adsorption mechanism and the role of their constituent amino acid residues when interacting with pure POPC and pure POPG membrane bilayers. Starting from an α-helical conformation, both AMPs are attracted at different rates to the POPC and POPG bilayer surfaces due to the electrostatic interaction between the positively charged amino acid residues and the charged moieties of the membranes. Since POPG is an anionic membrane, the PAMs adhesion is stronger to the POPG membrane than to the POPC membrane and they are stabilized more rapidly. This study reveals that, before the insertion begins, Pin2 and Pin2GVG remained partially folded in the POPC surface during the first 300 and 600 ns, respectively, while they are mostly unfolded in the POPG surface during most of the simulation time. The unfolded structures provide for a large number of intermolecular hydrogen bonds and stronger electrostatic interactions with the POPG surface. The results show that the aromatic residues at the N-terminus of Pin2 initiate the insertion process in both POPC and POPG bilayers. As for Pin2GVG in POPC the C-terminus residues seem to initiate the insertion process while in POPG this process seems to be slowed down due to a strong electrostatic attraction. The membrane conformational effects upon PAMs binding are measured in terms of the area per lipid and the contact surface area. Several replicas of the systems lead to the same observations.

Low temperature carrier transport mechanism in high-mobility zinc oxynitride thin-film transistors

The authors investigate the low-temperature carrier transport mechanism in high-mobility zinc oxynitride (ZnON) thin-film transistors (TFTs) over a wide range of operating temperatures below room temperature (90–293 K) by analyzing the temperature-dependent field-effect characteristics. In the subthreshold and transition regions, the variable range hopping and trap-limited band transport are considered as dominant carrier transport mechanisms in the ZnON TFT at temperatures below ∼207 K and above ∼243 K, respectively. In the above-threshold region, the field-effect mobility almost linearly depends on 1/T (T: absolute temperature) at all temperatures, which represents that the trap-limited band transport is the dominant carrier transport mechanism through the entire temperature range of 90 to 293 K in the fabricated ZnON TFT. Approximately 1 order of magnitude higher subgap density of states is extracted from the fabricated ZnON TFT compared with a conventional amorphous indium-gallium-zinc oxide TFT, which is primarily attributed to the large number of defective ZnXNY bonds inside the ZnON.

Comparison on mechanical properties of lignocellulosic flour epoxy composites prepared by using coconut shell, rice husk and teakwood as fillers

The objective of this work was to investigate the feasibility of using lignocellulosic fillers (coconut shell, rice husk and teakwood) as alternative reinforcement for expensive non-renewable fillers used in conventional composites. Various concentrations of epoxy based bio-fillers composites were prepared and the influences of filler size (75–105 and 106–180 μm) and mass concentration (2.5 and 4.5 wt%) on the mechanical properties were investigated. Properties such as deformability, stiffness, elasticity and strain energy absorption ability of each material combination were determined using single indentation load control, single indentation displacement control and multi-cyclic indentation tests. The results showed that parameters such as filler size, volume content, filler type (chemical composition and shape) dispersion influenced these properties. It was revealed that high lignin content increased the stiffness whereas high cellulose content with high impregnation ability favoured deformability. High cellulose content and surface roughness supported better adhesion due to a large number of hydrogen bonds and high mechanical interlocking, respectively.

Radiation of short waves from the resonantly excited capillary–gravity waves

Capillary–gravity waves resonantly excited by an obstacle (Froude number: $Fr=1$) are investigated by the numerical solution of the Euler equations. The radiation of short waves from the long nonlinear waves is observed when the capillary effects are weak (Bond number: $Bo<1/3$). The upstream-advancing solitary wave radiates a short linear wave whose phase velocity is equal to the solitary waves and group velocity is faster than the solitary wave (soliton radiation). Therefore, the short wave is observed upstream of the foremost solitary wave. The downstream cnoidal wave also radiates a short wave which propagates upstream in the depression region between the obstacle and the cnoidal wave. The short wave interacts with the long wave above the obstacle, and generates a second short wave which propagates downstream. These generation processes will be repeated, and the number of wavenumber components in the depression region increases with time to generate a complicated wave pattern. The upstream soliton radiation can be predicted qualitatively by the fifth-order forced Korteweg–de Vries equation, but the equation overestimates the wavelength since it is based on a long-wave approximation. At a large Bond number of $Bo=2/3$, the wave pattern has the rotation symmetry against the pattern at $Bo=0$, and the depression solitary waves propagate downstream.

Synthesis and Characterization of Doxorubicin Loaded pH-Sensitive Magnetic Core–Shell Nanocomposites for Targeted Drug Delivery Applications

In order to improve the effects of medical therapy for cancer, we prepared magnetic nanocomposites (Fe3O4@SiO2–NH–NH[Formula: see text] as doxorubicin (DOX) carriers via two different schemes. Scheme (I): the carriers were synthesized from magnetic silica nanoparticles (Fe3O4@SiO[Formula: see text] via layer by layer modification, scheme (II): the carriers were obtained from amino-modified magnetic silica nanoparticles (Fe3O4@SiO2–NH[Formula: see text] synthesized by one-step, and followed by surface modification. In order to load DOX effectively, the surface of the carriers were further modified to make the surface with a large number of hydrazine bonds which can form a pH-sensitive bond (hydrazone bond) with DOX. The two kinds of carriers both exhibited a size around 80[Formula: see text]nm, high stability and superparamagnetic behavior. However, DOX-loaded carriers (Fe3O4@SiO2–DOX(2)) performed relatively poorer performance in terms of drug loading and releasing (the loading efficiency of DOX decreased from 67.33% to 42.15%, while the releasing efficiency of DOX decreased from 66.16% to 62.23% within 72[Formula: see text]h at pH 4.0). Water-soluble tetrazolium salts (WST-1) assays in cancer cells (Hela) demonstrated that the Fe3O4@SiO2–DOX presented high anti-tumor activity, while the carriers were nearly nontoxic. Thus, the results suggested that the magnetic nanocomposites synthesized by the two different methods both can be employed to deliver DOX, while the carriers obtained via the first method may perform better and would be applied in the field of cancer therapy in the future.

Breakdown of 1D water wires inside charged carbon nanotubes

Using molecular dynamics approach we investigated the structure and dynamics of water confined inside pristine and charged 6,6 carbon nanotubes (CNTs). This study reports the breakdown of 1D water wires and the emergence of triangular faced water on incorporating charges in 6,6 CNTs. Incorporation of charges results in high potential barriers to flipping of water molecules due to the formation of large number of hydrogen bonds. The PMF analyses show the presence of ∼2kcal/mol barrier for the movement of water inside pristine CNT and almost negligible barrier in charged CNTs.

Predictive Engineering of Coating Adhesion on a Molecular Basis

Molecular design of polymer/metal interfaces relies on understanding single molecular interactions and their scaling towards integral interactions at the meso- and macroscopic scale. Here, we will discuss how one can measure the interaction free energy of single interacting functional groups and polymers with electrified and corroding surfaces for predicting the stability of macroscopic polymer/metals bondings. In particular, we will show how single interactions scale with the number density towards the macroscopic level [1, 2], where a large number of single bonds interact simultaneously and in parallel. For this, we developed a synergistic experimental approach combining electrochemical Surface Forces Apparatus (SFA) experiments and single molecule force spectroscopy (SMFS) in an electrochemical Atomic Force Microscope. First, in model experiments we can demonstate how macroscopic measurements scale linearly with the number density of a gold-amine bond at an electrified interface, providing gold-amine interaction energies of ~35 ± 2 kT at OCP. Using Bell-Evans theory together with non-equilibrium thermodynamics, we can show how a set of single molecule interaction forces measured by SMFS similarly converges to an interaction energy of 36 ± 3 kT. This demonstrates excellent predictive power of our newly developed scaling approach. Second, and in addition to gold-amine interactions, we now tested a number of different bonds including hydrophobic, electro-active mussel-peptide/surface and metal/polymer [2] bonds with our model and find that our model is widely applicable, in particular also to electrified and corroding interfaces. In this context, we will discuss in detail how single molecule unbinding energy landscapes can be measured and utilized to predict scenarios where a large number of molecules simultaneously interact, giving rise to adhesive failure and coating delamination under corrosive and wet conditions. Our experimental strategy provides a unique framework for the molecular design of novel functional coatings through predicting of large-scale properties such as adhesion and molecular interactions in electrochemical systems based on experimentally determined single molecule energy landscapes. [1] S. Raman et al. in Nature Communications , 5 (2014), 5539. [2] T. Utzig et al. in Langmuir, 31(9) (2015), 2722.

Asp32 and Asp228 determine the selective inhibition of BACE1 as shown by docking and molecular dynamics simulations

Inhibition of β-site amyloid–β-protein precursor cleaving enzyme 1 (BACE1) represents a promising approach for the treatment of Alzheimer's disease (AD). However, the development of a selective BACE1 inhibitor is difficult due to its highly flexible catalytic site and homology to other aspartic proteases, including BACE2 and Cathepsin D (CTSD). Aiming to better understand the structural factors responsible for selective BACE1 inhibition, we performed alignment studies, molecular dynamics (MD) simulations and docking studies to explore the recognition of four selective BACE1 inhibitors by aspartyl proteases. The results show that selective BACE1 inhibition may be due to the formation of strong electrostatic interactions with Asp32 and Asp228 and a large number of hydrogen bonds, π-π and Van der Waals interactions with the amino acid residues located inside the catalytic cavity, which has different volume and shape compared to BACE2 and CTSD. Hindrance effects avoid the accommodation of ligands in the small catalytic site of BACE2, resulting in a lower affinity and the high cavity of CTSD results in the formation of a small number of interactions with the ligands, although they show a similar binding mode with BACE1. These results might help to rationalize the design of selective BACE1 inhibitors.

Formation mechanism of ovalbumin gel induced by alkali

In this paper, the alkali-induced gelling behavior of ovalbumin, including its microstructure characteristics, intermolecular forces, and molecular structure changes, was investigated. The results showed that ovalbumin formed a three-dimensional gel with an ordered fibrous mesh structure under alkali conditions. The active force between gel molecules was maintained by a large number of ionic bonds (∼85%), a small number of disulfide bonds (∼5%), and very few hydrophobic interactions and hydrogen bonds. SDS-PAGE analysis showed that ovalbumin formed aggregates via ionic and disulfide bonds. ANS fluorescence spectroscopy analysis showed that strong alkali caused rapid denaturation of ovalbumin molecules to expose the hydrophobic core, thus greatly increasing the surface hydrophobicity. However, the hydrophobicity decreased during the gelation stage. FTIR analysis showed that strong alkali induced the secondary-level structure of ovalbumin molecules to interconvert, and most of them existed in a relatively stable α-folding structure. Endogenous fluorescence and UV spectroscopic analyses showed that the amino acid residues of ovalbumin in the gelation stage moved towards the polar environment. It was concluded that the secondary and tertiary structures of ovalbumin changed after treatment with strong alkali and that a crystal gel formed through the action of ionic and disulfide bonds. In addition, the long-term action of strong alkali gradually decreased the gelatinous property.

(Invited) The Regioselectivity of Bingel-Hirsch Cycloadditions on IPR Endohedral Metallofullerenes

Given the large number of possible non-equivalent bonds of Endohedral MetalloFullerenes (EMFs), the elucidation of the preferred addition sites for a target reaction is tremendously challenging.1 The development of a set of simple rules able to rationalize the preferred regioselectivities by solely inspecting the fullerene structure would be extremely appealing for the whole fullerene community. This communication describes a set of predictive criteria called Predictive Aromaticity Criteria (PAC), to a priori identify the most reactive bonds of a given EMF towards the Bingel-Hirsch (BH) cycloaddition based on a simple evaluation of the cage structure, and without need to perform any expensive theoretical calculation or experimental measure.2 We take as starting point the investigation of the BH addition of diethylbromomalonate on all non-equivalent bonds of Sc3N@D3h-C78 using density functional theory calculations. From the Sc3N@D3h-C78 analysis, a set of rules that we called Predictive Aromaticity Criteria (PAC) is derived, which are further applied to predict the most favorable BH adducts for the challenging case of Sc3N@D5h-C80. The predictions based on PAC are afterwards fully confirmed by both the computational and experimental results of the complete study of the regioselectivity of BH reaction to Sc3N@D5h-C80. These results provide conclusive evidence on the reliability of the PAC, indicating that these rules are general and applicable to any BH reaction on IPR EMFs. Moreover, this work provides clear evidence of the key role played by the local aromaticity of the cage in EMF functionalization.2-5

A global stability approach to wake and path instabilities of nearly oblate spheroidal rising bubbles

A global Linear Stability Analysis (LSA) of the three-dimensional flow past a nearly oblate spheroidal gas bubble rising in still liquid is carried out, considering the actual bubble shape and terminal velocity obtained for various sets of Galilei (Ga) and Bond (Bo) numbers in axisymmetric numerical simulations. Hence, this study extends the stability analysis approach of Tchoufag et al. [“Linear stability and sensitivity of the flow past a fixed oblate spheroidal bubble,” Phys. Fluids 25, 054108 (2013) and “Linear instability of the path of a freely rising spheroidal bubble,” J. Fluid Mech. 751, R4 (2014)] (which considered perfectly spheroidal bubbles with an arbitrary aspect ratio) to the case of bubbles with a realistic fore-aft asymmetric shape (i.e., a flatter front and a more rounded rear). The critical curve separating stable and unstable regimes for the straight vertical path is obtained both in the (Ga,Bo) and the (Re,χ) planes, where Re is the bubble Reynolds number and χ its aspect ratio (i.e., the major-to-minor axes length ratio). This provides new insight into the effect of the shape asymmetry on the wake instability of bubbles held fixed in a uniform stream and on the path instability of freely rising bubbles, respectively. For the range of Ga and Bo explored here, we find that the flow past a bubble with a realistic shape is generally more stable than that past a perfectly spheroidal bubble with the same aspect ratio. This study also provides the first critical curve for the onset of path instability that can be compared with experimental observations. The tendencies revealed by this critical curve agree well with those displayed by available data. The quantitative agreement is excellent for O(1) Bond numbers. However, owing to two simplifying assumptions used in the LSA scheme, namely, the steadiness of the base state and the uncoupling between the bubble shape and the flow disturbances, quantitative discrepancies (up to 20%–30%) with experimental threshold values of the Galilei number remain for both small and large Bond numbers.

The glycocalyx promotes cooperative binding and clustering of adhesion receptors.

Cell adhesion plays a pivotal role in various biological processes, e.g., immune responses, cancer metastasis, and stem cell differentiation. The adhesion behaviors depend subtly on the binding kinetics of receptors and ligands restricted at the cell-substrate interfaces. Although much effort has been directed toward investigating the kinetics of adhesion molecules, the role of the glycocalyx, anchored on cell surfaces as an exterior layer, is still unclear. In this paper, we propose a theoretical approach to study the collective binding kinetics of a few and a large number of binders in the presence of the glycocalyx, representing the cases of initial and mature adhesions of cells, respectively. The analytical results are validated by finding good agreement with our Monte Carlo simulations. In the force loading case, the on-rate and affinity increase as more bonds form, whereas this cooperative effect is not observed in the displacement loading case. The increased thickness and stiffness of the glycocalyx tend to decrease the affinity for a few bonds, while they have less influence on the affinity for a large number of bonds. Moreover, for a flexible membrane with thermally-excited shape fluctuations, the glycocalyx is exhibited to promote the formation of bond clusters, mainly due to the cooperative binding of binders. This study helps to understand the cooperative kinetics of adhesion receptors under physiologically relevant loading conditions and sheds light on the novel role of the glycocalyx in cell adhesion.

Carbohydrates in Supramolecular Chemistry.

Carbohydrates are involved in a variety of biological processes. The ability of sugars to form a large number of hydrogen bonds has made them important components for supramolecular chemistry. We discuss recent advances in the use of carbohydrates in supramolecular chemistry and reveal that carbohydrates are useful building blocks for the stabilization of complex architectures. Systems are presented according to the scaffold that supports the glyco-conjugate: organic macrocycles, dendrimers, nanomaterials, and polymers are considered. Glyco-conjugates can form host-guest complexes, and can self-assemble by using carbohydrate-carbohydrate interactions and other weak interactions such as π-π interactions. Finally, complex supramolecular architectures based on carbohydrate-protein interactions are discussed.

What is the Shape of an Air Bubble on a Liquid Surface?

We have calculated the equilibrium shape of the axially symmetric meniscus along which a spherical bubble contacts a flat liquid surface by analytically integrating the Young-Laplace equation in the presence of gravity, in the limit of large Bond numbers. This method has the advantage that it provides semianalytical expressions for key geometrical properties of the bubble in terms of the Bond number. Results are in good overall agreement with experimental data and are consistent with fully numerical (Surface Evolver) calculations. In particular, we are able to describe how the bubble shape changes from hemispherical, with a flat, shallow bottom, to lenticular, with a deeper, curved bottom, as the Bond number is decreased.

Effect of crystallization water on the structural and electrical properties of CuWO4 under high pressure

The effect of crystallization water on the structural and electrical properties of CuWO4 under high pressure has been investigated by in situ X-ray diffraction and alternating current impedance spectra measurements. The crystallization water was found to be a key role in modulating the structural stability of CuWO4 at high pressures. The anhydrous CuWO4 undergoes two pressure-induced structural transitions at 8.8 and 18.5 GPa, respectively, while CuWO4·2H2O keeps its original structure up to 40.5 GPa. Besides, the crystallization water makes the electrical transport behavior of anhydrous CuWO4 and CuWO4·2H2O quite different. The charge carrier transportation is always isotropic in CuWO4·2H2O, but anisotropic in the triclinic and the third phase of anhydrous CuWO4. The grain resistance of CuWO4·2H2O is always larger than that of anhydrous CuWO4 in the entire pressure range. By analyzing the relaxation response, we found that the large number of hydrogen bonds can soften the grain characteristic frequency of CuWO4·2H2O over CuWO4 by one order of magnitude.

Stability of a compound sessile drop at the axisymmetric configuration

The equilibrium configuration of compound sessile drops has been calculated previously in the absence of gravity. Using the Laplace equations, we establish seven dimensionless parameters describing the axisymmetric configuration in the presence of gravity. The equilibrium axisymmetric configuration can be either stable or unstable depending on the fluid properties. A stability criterion is established by calculating forces on a perturbed Laplacian shape. In the zero Bond number limit, the stability criterion depends on the density ratio, two ratios of interfacial tensions, the volume ratio of the two drops, and the contact angle. We use Surface Evolver to examine the stability of compound sessile drops at small and large Bond numbers and compare with the zero Bond number approximation. Experimentally, we realize a stable axisymmetric compound sessile drop in air, where the buoyancy force exerted by the air is negligible. Finally, using a pair of fluids in which the density ratio can be tuned nearly independently of the interfacial tensions, the stability transition is verified for the axisymmetric configuration. Even though the perturbations are different for the theory, simulations and experiments, both simulations and experiments agree closely with the zero Bond number approximation, exhibiting a small discrepancy at large Bond number.

Counterparty Credit Risk in the Municipal Bond Market

A large number of municipal bonds are guaranteed by monoline insurers who are at the center of the subprime crisis. This article investigates the effect of insurer-related counterparty risk on municipal bond pricing using a comprehensive dataset. The authors estimate both insurer-specific and systemic components of a counterparty risk effect. Results show that the magnitude of the counterparty risk effect is of economic significance even in normal times and is magnified during the crisis. The findings also indicate that this effect is much larger than that documented for the credit default swap and repo markets. The counterparty risk premium is higher for speculative-grade and illiquid bonds and for bonds issued by troubled states.

Structures of CoII and ZnII complexes of the proton-transfer compound derived from pyrazine-2,3-dicarboxylic acid and piperazine.

The reaction of the proton-transfer compound piperazine-1,4-diium pyrazine-2,3-dicarboxylate 4.5-hydrate, C4H12N2(2+)·C6H2N2O4(2-)·4.5H2O or (pipzH2)(pyzdc)·4.5H2O (pyzdcH2 is pyrazine-2,3-dicarboxylic acid and pipz is piperazine), (I), with Zn(NO3)2·6H2O and CoCl2·6H2O results in the formation of bis(piperazine-1,4-diium) bis(μ-pyrazine-2,3-dicarboxylato)-κ(3)N(1),O(2):O(3);κ(3)O(3):N(1),O(2)-bis[aqua(pyrazine-2,3-dicarboxylato-κ(2)N(1),O(2))zinc(II)] decahydrate, (C4H12N2)2[Zn2(C6H2N2O4)4(H2O)2]·10H2O or (pipzH2)2[Zn(pyzdc)2(H2O)]2·10H2O, (II), and catena-poly[piperazine-1,4-diium [cobalt(II)-bis(μ-pyrazine-2,3-dicarboxylato)-κ(3)N(1),O(2):O(3);κ(3)O(3):N(1),O(2)] hexahydrate], {(C4H12N2)[Co(C6H2N2O4)2]·6H2O}n or {(pipzH2)[Co(pyzdc)2]·6H2O}n, (III), respectively. In (I), pyzdcH2 is doubly deprotonated on reaction with piperazine as a base. Compound (II) crystallizes as a dimer, whereas compound (III) exists as a one-dimensional coordination polymer. In (II), two pyzdc(2-) groups chelate to each of the two Zn(II) atoms through a ring N atom and an O atom of the 2-carboxylate group. In one ligand, the adjacent 3-carboxylate group bridges to a neighbouring metal atom. A water molecule ligates in the sixth coordination site. The structure of (II) can be described as a commensurate superlattice due to an ordering in the hydrogen-bonded network. In (III), no water is coordinated to the metal atom and the coordination sphere is comprised of two N,O-chelates plus two bridging O atoms. A large number of hydrogen bonds are observed in all three compounds. These interactions, as well as π-π and C=O...π stacking interactions, play important structural roles.

Vertical upward intermediate scale Taylor flow: Experiments and kinematic closure

The vertical upward Taylor flow regime has been extensively studied at the capillary and large channel scale limits. However, flow behavior at the intermediate scale (5≲Bo≲40, or 6mm≲D≲17mm for ambient gas–water flows) is comparatively poorly characterized. This regime is fundamentally different because classes of forces conventionally associated with either small or large Bond number flows are all relevant. In this investigation, air–water Taylor-flow experiments are conducted in 6.0, 8.0, and 9.5mm diameter tubes. High-speed video data are collected, and automated image analysis algorithms are developed to measure flow parameters including: bubble rise velocity, liquid film thickness, void fraction, and Taylor bubble and liquid slug lengths. New correlations and flow models are developed to predict these parameters at the intermediate scale. Results from this study enable kinematic closure of intermediate scale Taylor flows.