Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking,molecular dynamics and MM/PBSA studies

Recently, ganoderic acids (GAs) give rise to the attractive candidates of novel neuraminidase (NA) inhibitors. However, there is still no evident conclusion about their binding patterns. To this end, docking, molecular dynamics and MM/PBSA methods were combined to study the binding profiles of GAs with the N1 protein and familiar H274Y and N294S mutations (A/Vietnam/1203/04 stain). It was found that the binding affinities of ganoderic acid DM and Z (ΔG_bind, −16.83 and −10.99 kcal mol⁻¹) are comparable to that of current commercial drug oseltamivir (−23.62 kcal mol⁻¹). Electrostatic interaction is the main driving force, and should be one important factor to evaluate the binding quality and rational design of NA inhibitors. The 150-loop residues Asp151 and Arg152 played an important role in the binding processes. Further analysis revealed that ganoderic acid DM is a potential source of anti-influenza ingredient, with novel binding pattern and advantage over oseltamivir. It had steric hindrance on the 150 cavity of N1 protein, and exerted activities across the H274Y and N294S mutations. This work also pointed out how to effectively design dual-site NA inhibitors and reinforce their affinities. These findings should prove valuable for the in-depth understanding of interactions between NA and GAs, and warrant the experimental aspects to design novel anti-influenza drugs.     

Reaction mechanism and free energy profile for acylation of Candida Antarctica lipase B with methylcaprylate and acetylcholine: Density functional theory calculations

Candida Antarctica lipase B (CALB), a specific enzyme to catalyze the hydrolysis of esters, can be a good candidate for acetylcholine (ACh) hydrolysis instead of acetylcholinesterase. The catalytic mechanism of the CALB acylation, as the first stage in the hydrolysis reaction, with ACh and methylcaprylate (MEC) has been examined by using density functional theory technique. The significant emphasis of this article is on the free energy barriers for the acylation step of hydrolysis reactions. Computed free energy barriers of the first step are 9.2 and 15.9 kcal mol⁻¹, but for the second step are 7.9 and 11.6 kcal mol⁻¹ for MEC and ACh respectively. Activation free energies are in the comparable and acceptable range and imply both of two reactions are theoretically possible. The stability role of the adjacent amino acids was examined by using two applied tools. It is exposed that the oxyanion hole residues decrease energy barriers by stabilizing the transition state structures.     

Electrochemical determination of ascorbic acid in fruits on a vanadium oxide polypropylene carbonate modified electrode

A novel vanadium oxide polypropylene carbonate modified glassy carbon electrode was developed and used for the measurement of ascorbic acid (AA). The electrode was prepared by casting a mixture of vanadium tri(isopropoxide) oxide (VO(OC₃H₇)₃) and poly(propylene carbonate) (PPC) onto the surface of a glassy carbon electrode. The electrochemical behavior of the VO(OC₃H₇)₃–PPC film modified glassy carbon electrode was investigated by cyclic voltammetry and amperometry. This modified electrode exhibited electrocatalytic response to the oxidation of ascorbic acid. Compared with a bare glassy carbon electrode, the modified electrode exhibits a 220 mV shift of the oxidation potential of ascorbic acid in the cathodic direction and a marked enhancement of the current response. The response current revealed a good linear relationship with the concentration of ascorbic acid in the range of 4 × 10⁻⁸ and 1 × 10⁻⁴ mol L⁻¹ and the detection limit of 1.5 × 10⁻⁸ mol L⁻¹ (S/N = 3) in the pH 8.06 Britton–Robinson solution. Quantitative recovery of the ascorbic acid in synthetic samples has been obtained and the interferences from different species have been studied. The method has been successfully applied to the determination of ascorbic acid in fruits. The concentrations of ascorbic acid measured by this method are in good agreement with the literature value. It is much promising for the modified films to be used as an electrochemical sensor for the detection of ascorbic acid.     

A DFT study on the physical adsorption of cyclophosphamide derivatives on the surface of fullerene C60 nanocage

The physical sorption of a series of cyclophosphamide drug derivatives with formula

where x = 2, X = F (2), Cl (3), Br (4); x = 3, X = F (5), Cl (6), Br (7) and x = 4, X = F (8), Cl (9), Br (10) on the surface of fullerene C₆₀ was studied using density functional theory (DFT) at B3LYP and B3PW91 levels. The most negative binding energies obtained using the B3LYP approach and corrected for geometrical BSSE and dispersion energies (gCP-D3-ΔE_binding) were measured for compounds 8 (among isolated drugs) and 13 (among complexes). The dipole moments of isolated drugs were obtained close to those of their complexes with C₆₀ (∼4.0–5.5 Debye) indicating their hydrophililic nature that is an appropriate property appealing for drug delivery in biological media. The adsorption of all drugs on the surface of fullerene was endergonic with all of the ΔG_adsorption > 0. The ΔH_adsorption values at B3PW91 level were only negative for complexes 14–16 indicating their exothermic adsorption nature. The HOMO–LUMO band gaps of complexes 11–19 were about 2.7 eV and are comparable with the gap in C₆₀ but are much smaller than the gaps in isolated drugs 2–10 (6.5–8.0 eV) reflecting the increase in electrical conductivities upon complexation. The QTAIM data supported the covalent character of the C–O, C–N and N–H bonds, the intermediate character of PO, P–O and P–N bonds while the electrostatic nature of PO…C(fullerene) interactions. According to the gCP-D3-ΔE_binding binding energies and ΔH_adsorption values at B3LYP level, it seems that the complexes 12 and 13 can be the most promising prodrug + carrier delivery systems.

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Bounds for the Roots of Lacunary Polynomials

A polynomial P(X)  = X^d + a_d − 1X^d − 1 + ⋯ is called lacunary when a_d − 1 =  0. We give bounds for the roots of such polynomials with complex coefficients. These bounds are much smaller than for general polynomials.     

Simulation of solid thermal explosion and liquid thermal explosion of dicumyl peroxide using calorimetric technique

Dicumyl peroxide (DCPO), is produced by cumene hydroperoxide (CHP) process, is utilized as an initiator for polymerization, a prevailing source of free radicals, a hardener, and a linking agent. DCPO has caused several thermal explosion and runaway reaction accidents in reaction and storage zone in Taiwan because of its unstable reactive property. Differential scanning calorimetry (DSC) was used to determine thermokinetic parameters including 700 J g^–1 of heat of decomposition (ΔH_d), 110 °C of exothermic onset temperature (T₀), 130 kJ mol^–1 of activation energy (E_a), etc., and to analyze the runaway behavior of DCPO in a reaction and storage zone. To evaluate thermal explosion of DCPO with storage equipment, solid thermal explosion (STE) and liquid thermal explosion (LTE) of thermal safety software (TSS) were applied to simulate storage tank under various environmental temperatures (T_e). T_e exceeding the T₀ of DCPO can be discovered as a liquid thermal explosion situation. DCPO was stored under room temperature without sunshine and was prohibited exceeding 67 °C of self-accelerating decomposition temperature (SADT) for a tank (radius = 1 m and height = 2 m). SADT of DCPO in a box (width, length and height = 1 m, respectively) was determined to be 60 °C. The TSS was employed to simulate the fundamental thermal explosion behavior in a large tank or a drum. Results from curve fitting demonstrated that, even at the earlier stage of the reaction in the experiments, ambient temperature could elicit exothermic reactions of DCPO. To curtail the extent of the risk, relevant hazard information is quite significant and must be provided in the manufacturing process.     

A DFT study on the central-ring doped HBC nanographenes

Nanographenes (NGs) are a segment of graphene whose dangling bonds are saturated with hydrogen atoms, introducing different properties and promising applications. Here we investigate the electronic, thermodynamic, optical, and structural properties of four C₃₆X₃Y₃H₁₈ NGs (X = B, and Al; and Y = N, and P) based on the density functional theory calculations. It was mainly found that 1) BN-NG is planar molecule and the others are buckybowl-shaped ones, 2) The bowl-to-bowl inversion Gibbs free energies (ΔG^#) of buckybowl shaped NGs are very huge and the rate constant is very small, hindering the inversion, 3) The relative energetic stability order based on the standard enthalpy of formation (ΔH_f^°) is as BN > AlN > BP > AlP, which the BN, and AlN doped NGs are stable at room temperature but the BP and AlP doped ones are instable, 4) The electrical conductivity order of magnitude is inverse of that of stability, 5) An exciton binding energy is predicted in the range of 0.57–0.75 eV for the NGs which corresponds to Frenkel exciton type, 6) the NGs are not soluble in organic solvent in agreement with the experimental results and is partially soluble in water solvent with Gibbs free energy of solvation (ΔG_solv) in the range of −6.1 to −10.1 kcal/mol.     

Simultaneous determination of epinephrine and ascorbic acid at the electrochemical sensor of triazole SAM modified gold electrode

The electrochemical sensor of triazole (TA) self-assembled monolayer (SAM) modified gold electrode (TA SAM/Au) was fabricated. The electrochemical behaviors of epinephrine (EP) at TA SAM/Au have been studied. The TA SAM/Au shows an excellent electrocatalytic activity for the oxidation of EP and accelerates electron transfer rate. The diffusion coefficient is 1.135 × 10⁻⁶ cm² s⁻¹. Under the optimum experiment conditions (i.e. 0.1 mol L⁻¹, pH 4.4, sodium borate buffer, accumulation time: 180 s, accumulation potential: 0.6 V, scan rate: 0.1 Vs⁻¹), the cathodic peak current of EP versus its concentration has a good linear relation in the ranges of 1.0 × 10⁻⁷ to 1.0 × 10⁻⁵ mol L⁻¹ and 1.0 × 10⁻⁵ to 6.0 × 10⁻⁴ mol L⁻¹ by square wave adsorptive stripping voltammetry (SWASV), with the correlation coefficient of 0.9985 and 0.9996, respectively. Detection limit is down to 1.0 × 10⁻⁸ mol L⁻¹. The TA SAM/Au can be used for the determination of EP in practical injection. Meantime, the oxidative peak potentials of EP and ascorbic acid (AA) are well separated about 200 ± 10 mV at TA SAM/Au, the oxidation peak current increases approximately linearly with increasing concentration of both EP and AA in the concentration range of 2.0 × 10⁻⁵ to 1.6 × 10⁻⁴ mol L⁻¹. It can be used for simultaneous determination of EP and AA.     

Perchlorate-selective polymeric membrane electrode based on a cobaloxime as a suitable carrier

A cobaloxime ([chlorobis(dimethylglyoximeato)(triphenylphosphine)] cobalt (III), [Co(dmgH)₂pph₃Cl]) incorporated in a plasticized poly(vinyl chloride) membrane was used to develop a perchlorate-selective electrode. The influence of membrane composition on the electrode response was studied. The electrode exhibits a Nernstian response over the perchlorate concentration range 1.0 × 10⁻⁶ to 1 × 10⁻¹ mol l⁻¹ with a slope of −56.8 ± 0.7 mV per decade of concentration, a detection limit of 8.3 × 10⁻⁷, a wide working pH range (3–10) and a fast response time (<15 s). The electrode shows excellent selectivity towards perchlorate with respect to many common anions. The electrode was used to determine perchlorate in water and human urine.     

Density functional theory study of defective silicenes as anode materials for lithium ion batteries

In this contribution, we explore Li adsorption and diffusion on defective silicenes using first principles calculations. Defect formation energy (E_f) values showed that silicenes with 5105 and 5559 vacancy defects (Si-5559 and Si-5105) are likely to form during the fabrication process and E_f values are about one-third of graphenes. Calculation of Li adsorption energy indicated that Si-5559 and Si-5105 are better than pristine silicene for Li dispersion in the half-lithiated state. The diffusion barrier of Li on the surface of Si-5559 and Si-5105 and in the proximity of defected zone were obtained to be 0.24 eV and 0.29 eV, respectively. Diffusion barrier values show the easy motion of Li on these silicenes in comparison with defective graphenes. Ab-initio molecular dynamic (AIMD) simulations revealed that fully lithiated Si-5559 is not stable and can not accommodate lithium atoms. On the contrary, Si-5105 is stable and could store a certain amount of lithium atoms. The theoretical capacity of Si-5105 was calculated to be 664 mA h g⁻¹.     

Curves of Genus 2 with (N,N) Decomposable Jacobians

Let C be a curve of genus 2 and ψ₁: C  −  → E ₁  a map of degree n, from C to an elliptic curveE₁ , both curves defined over C. This map induces a degree n map φ₁:P¹  −  → P ¹  which we call a Frey–Kani covering. We determine all possible ramifications for φ₁. If ψ₁:C  −  → E ₁  is maximal then there exists a maximal map ψ₂: C  −  → E ₂  , of degree n, to some elliptic curveE₂ such that there is an isogeny of degree n²from the JacobianJ_C to E₁ × E₂. We say thatJ_C is (n, n)-decomposable. If the degree n is odd the pair (ψ₂, E₂) is canonically determined. For n =  3, 5, and 7, we give arithmetic examples of curves whose Jacobians are (n, n)-decomposable.     

Flow-injection determination of iron(III) in soil by biamperometry using two independent redox couples

A flow-injection biamperometric method for the determination of iron(III) has been described. The detector consists of two chambers separated by a salt bridge, and one platinum wire working electrode is embedded in each chamber, respectively. When iron(III) solution and hydrogen peroxide solution simultaneously flow through two chambers, the reduction of iron(III) at one platinum electrode is associated with the oxidation of hydrogen peroxide at the other platinum electrode, forming such a system as similar to a reversible couple one. The biamperometric system can perform the determination of iron(III) without any external potential difference. The linear relationship is obtained from 1.0 × 10⁻⁶ to 1.0 × 10⁻⁴ mol l⁻¹ with a detection limit of 6.0 × 10⁻⁷ mol l⁻¹. The proposed method exhibits the satisfactory reproducibility with a relative standard derivation (R.S.D.) of 1.4% for 17 successive determinations of 2.0 × 10⁻⁵ mol l⁻¹ iron(III) and is applied to the determination of iron(III) in soil.     

Evaluation of response characteristics of resistive oxygen sensors based on porous cerium oxide thick film using pressure modulation method

In order to reduce the response time of resistive oxygen sensors using porous cerium oxide thick film, it is important to ascertain the factors controlling response. Pressure modulation method (PMM) was used to find the rate-limiting step of sensor response. This useful method measures the amplitude of sensor output (H(f)) for the sine wave modulation of oxygen partial pressure at constant frequency (f). In PMM, “break” response time, which is minimum period in which the sensor responds precisely, can be measured. Three points were examined: (1) simulated calculations of PMM were carried out using a model of porous thick film in which spherical particles are connected in a three-dimensional network; (2) sensor response speed was experimentally measured using PMM; and (3) the diffusion coefficient and surface reaction coefficient were estimated by comparison between experiment and calculation. The plot of log f versus log H(f) in the high f region was found to have a slope of approximately −0.5 for both porous thick film and non-porous thin film, when the rate-limiting step was diffusion. Calculations showed the response time of porous thick film was 1/20 that of non-porous thin film when the grain diameter of the porous thick film was the same as the thickness of non-porous thin film. At 973 K, “break” response time (t_b) of the resistive oxygen sensor was found by experiment to be 109 ms. It was concluded that the response of the resistive oxygen sensor prepared in this study was strongly controlled by diffusion at 923–1023 K, since the experiment revealed that the slope of plot of log f versus log H(f) in the high f region was approximately −0.5. At 923–1023 K, the diffusion coefficient of oxygen vacancy in porous ceria (D_V) was expressed as follows: D_V (m²s⁻¹) = 5.78 × 10⁻⁴ exp(−1.94 eV/kT). At 1023 K, the surface reaction coefficient (K) was found to exceed 10⁻⁴ m/s.     

Stereoelectronic interaction effects on the conformational properties of hydrogen peroxide and its analogues containing S and Se atoms: An ab initio,hybrid-DFT study and NBO analysis

Ab initio molecular orbital (MP2/6-311+G**//MP2/6-31G+G**) and hybrid-density functional theory (B3LYP/6-311+G**//MP2/6-311+G**) methods and NBO analysis were used to study the stereoelectronic interaction effects on the conformational properties of hydrogen peroxide (1), hydrogen disulfide (2) and hydrogen diselenide (3). The results showed that the Gibbs free energy difference (G_T − G_S) values at 298.15 K and 1 atm between the skew (S) and trans (T) conformations (ΔG_T–S) increase from compound 1 to compound 2 but decrease from compound 2 to compound 3. The C conformations of compounds 1–3 are less stable than their S and T conformations. Based on these results, the racemization processes of the axial symmetrical (C₂ symmetry) conformations of compounds 1–3 take place via their T conformations. Based on the optimized ground state geometries using the MP2/6-311+G** level of theory, the NBO analysis of donor–acceptor (bond–antibond) interactions revealed that the stabilization (resonance) energy associated with LP₂M2 → σ*_M3-H4 electronic delocalization for the S conformations of compounds 1–3 are 1.35, 5.94 and 4.68 kcal mol⁻¹, respectively. There is excellent agreement between the variations of the calculated ΔG_T–S and stabilization (resonance) energies associated with LP₂M2→σ*_M3-H4 electronic delocalization for the S conformations of compounds 1–3. The correlations between resonance energies, orbital integrals, dipole moments, bond orders, structural parameters and conformational behaviors of compounds 1–3 have been investigated. Test were made of complete basis set methods (CBS-QB3, CBS-4 and CBS-Q), the first two gave results essentially indistinguishable from those we used, but the CBS-Q results were in disagreement with experimental and other theoretical results.     

On reliability of the folded hypercubes

In this paper, we explore the 2-extra connectivity and 2-extra-edge-connectivity of the folded hypercube FQ_n. We show that κ₂(FQ_n) = 3n − 2 for n ⩾ 8; and λ₂(FQ_n) = 3n − 1 for n ⩾ 5. That is, for n ⩾ 8 (resp. n ⩾ 5), at least 3n − 2 vertices (resp. 3n − 1 edges) of FQ_n are removed to get a disconnected graph that contains no isolated vertices (resp. edges). When the folded hypercube is used to model the topological structure of a large-scale parallel processing system, these results can provide more accurate measurements for reliability and fault tolerance of the system.     

Evolution of structure,stability, and nonlinear optical properties of the heterodinuclear CNLin (n = 1–10) clusters

The lowest-energy structures and stabilities of the heterodinuclear clusters, CNLi_n (n = 1–10) and relevant CNLi_n⁺ (n = 1–10) cations, are studied using the density functional theory with the 6-311 + G(3df) basis set. The CNLi₆ and CNLi₅⁺ clusters are the first three-dimensional ones in the CNLi_n^0/+ series, respectively, and the CN group always caps the Li_n^0/+ moiety in the CNLi_n^0/+ (n = 1–9) configurations. The CN triple bond is found to be completely cleaved in the CNLi₁₀^0/+ clusters where the C and N atoms are bridged by two Li atoms. The CNLi_n (n = 2–10) clusters are hyperlithiated molecules with delocalized valence electrons and consequently possess low VIP values of 3.780–5.674 eV. Especially, the CNLi₈ and CNLi₁₀ molecules exhibit lower VIPs than that of Cs atom and can be regarded as heterobinuclear superalkali species. Furthermore, these two superalkali clusters show extraordinarily large first hyperpolarizabilities of 19,423 and 42,658 au, respectively. For the CNLi_n⁺ cationic species, the evolution of the energetic and electronic properties with the cluster size shows a special stability for CNLi₂⁺.     

Highly fault-tolerant cycle embeddings of hypercubes

The hypercube Q_n is one of the most popular networks. In this paper, we first prove that the n-dimensional hypercube is 2n − 5 conditional fault-bipancyclic. That is, an injured hypercube with up to 2n − 5 faulty links has a cycle of length l for every even 4 ⩽ l ⩽ 2ⁿ when each node of the hypercube is incident with at least two healthy links. In addition, if a certain node is incident with less than two healthy links, we show that an injured hypercube contains cycles of all even lengths except hamiltonian cycles with up to 2n − 3 faulty links. Furthermore, the above two results are optimal. In conclusion, we find cycles of all possible lengths in injured hypercubes with up to 2n − 5 faulty links under all possible fault distributions.     

Doping effect of Ir(ppy)3 on white-light electrophosphorescent devices based on platinum(II) [1,3-difluoro-4,6-di(2-pyridinyl)benzene] chloride

Phosphorescent white organic light-emitting diodes (WOLEDs) based on single doped platinum(II) [1,3-difluoro-4,6-di(2-pyridinyl)benzene] chloride (Pt-4) emission layers were investigated in this paper. The devices exhibited electroluminescence spectra composed of bluish (λ_max = 480 nm) and reddish (λ_max = 660 nm) emission bands, which corresponding to monomer and excimer emission originated from Pt-4 dopants. With optimized device structures, a maximum current efficiency of 11.5 cd/A was obtained and remained above 10 cd/A even the brightness was over 6000 cd/m². Furthermore, by integrating the fac-tris(2-phenylpyridine) iridium(III) as a complementary emitter and an additional 2,2′,2″-(1,3,5-phenylene)-tris(1-phenyl-1H-benzimidazole) space layer, the device efficiency was further improved, which exhibited a maximum current efficiency of 20.4 cd/A at the luminance of 100 cd/m², and maintained the mild efficiency roll-off that similar to its single Pt-4 doped counterpart.     

Evaluation of a non-point source pollution model,AnnAGNPS, in a tropical watershed

Impaired water quality caused by human activity and the spread of invasive plant and animal species has been identified as a major factor of degradation of coastal ecosystems in the tropics. The main goal of this study was to evaluate the performance of AnnAGNPS (Annualized Non-Point Source Pollution Model), in simulating runoff and soil erosion in a 48 km² watershed located on the Island of Kauai, Hawaii. The model was calibrated and validated using 2 years of observed stream flow and sediment load data. Alternative scenarios of spatial rainfall distribution and canopy interception were evaluated. Monthly runoff volumes predicted by AnnAGNPS compared well with the measured data (R² = 0.90, P < 0.05); however, up to 60% difference between the actual and simulated runoff were observed during the driest months (May and July). Prediction of daily runoff was less accurate (R² = 0.55, P < 0.05). Predicted and observed sediment yield on a daily basis was poorly correlated (R² = 0.5, P < 0.05). For the events of small magnitude, the model generally overestimated sediment yield, while the opposite was true for larger events. Total monthly sediment yield varied within 50% of the observed values, except for May 2004. Among the input parameters the model was most sensitive to the values of ground residue cover and canopy cover. It was found that approximately one third of the watershed area had low sediment yield (0–1 t ha⁻¹ y⁻¹), and presented limited erosion threat. However, 5% of the area had sediment yields in excess of 5 t ha⁻¹ y⁻¹. Overall, the model performed reasonably well, and it can be used as a management tool on tropical watersheds to estimate and compare sediment loads, and identify “hot spots” on the landscape.