Charge Distribution Patterns Research Articles

Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.

The classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator, including immune complexes. Factor H is regarded as the key downregulatory protein of the complement alternative pathway. However, both C1q and factor H bind to target surfaces via charge distribution patterns. For a few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation through such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are known to recognize foreign or altered-self materials, e.g., bacteria, viruses, and apoptotic/necrotic cells. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the complement classical pathway and whether this is regulated by factor H. We show here that both C1q and factor H bind to the fibrin formed in microtiter plates and the fibrin clots formed under in vitro physiological conditions. Both C1q and factor H become covalently bound to fibrin clots, and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the activation of the classical pathway induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences.

Study of structural characteristics and charge distribution in pyranocoumarins: A computational approach

Fourteen pyranocoumarin (PC) molecules having cis and trans conformations are studied for charge distribution patterns with the help of computational study. To understand the structural characteristics of these molecules, global molecular descriptors, TD-DFT, and NLO studies are employed. On the basis of charge symmetry and MEP plots, it was predicted that trans PC would produce better outcomes. From the findings, it is evident that cis PC had less charge symmetry than trans PC. Although the electrophilicity index suggested the opposite pattern, the values for chemical potential, chemical hardness, and hyperhardness were higher for cis conformation than for trans conformation. Based on the data, it can be concluded that PC with a benzimidazole group exhibits higher intramolecular charge transfer in both its cis and trans forms. Compared to other pyranocoumarins, PC with no substituent clearly displayed weak inference.

Charge Distribution Patterns of IA3 Impact Conformational Expansion and Hydration Diffusivity of the Disordered Ensemble.

IA3 is a 68 amino acid natural peptide/protein inhibitor of yeast aspartic proteinase A (YPRA) that is intrinsically disordered in solution with induced N-terminal helicity when in the protein complex with YPRA. Based on the intrinsically disordered protein (IDP) parameters of fractional net charge (FNC), net charge density per residue (NCPR), and charge patterning (κ), the two domains of IA3 are defined to occupy different domains within conformationally based subclasses of IDPs, thus making IA3 a bimodal domain IDP. Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and low-field Overhauser dynamic nuclear polarization (ODNP) spectroscopy results show that these two domains possess different degrees of compaction and hydration diffusivity behavior. This work suggests that SDSL EPR line shapes, analyzed in terms of their local tumbling volume (VL), provide insights into the compaction of the unstructured IDP ensemble in solution and that protein sequence and net charge distribution patterns within a conformational subclass can impact bound water hydration dynamics, thus possibly offering an alternative thermodynamic property that can encode conformational binding and behavior of IDPs and liquid-liquid phase separations.

Chemical reduction of indenocorannulene: A two-electron addition stop

Chemical reduction behavior of the indenyl-fused corannulene bowl, monoindenocorannulene (1), was investigated using two alkali metals with different binding abilities, namely Na and Rb. The sodium-induced reaction in THF in the presence of 18-crown-6 ether afforded a solvent-separated ion product, [Na+(18-crown-6)(THF)2]2[12−]·THF (2·THF), which enabled structural evaluation of the “naked” dianion. The controlled addition of the secondary ligand in rubidium-induced reduction reactions allowed modulation of metal coordination and solid-state packing of the doubly-reduced indenocorannulene. Two products with different topologies and metal ion binding, [Rb+(18-crown-6)]2[12−]·THF (3·THF) and [Rb+(18-crown-6)][Rb+(18-crown-6)0.5][12−]·4THF (4·4THF), were isolated and characterized crystallographically. A direct comparison of 1 and 12− using DFT calculation methods provided insights into consequences of two-fold reduction. The significant change in aromaticity was revealed by NICS calculations, while ACID plots showed a good agreement between the negative charge distribution patterns and the observed metal ion binding sites.

Study of MFL signal identification in pipelines based on non-uniform magnetic charge distribution patterns

Magnetic flux leakage (MFL), a pipeline internal detection, is the mainstream technology for international oil and gas pipeline safety maintenance. To address the problem of large errors in the assessment of defects in pipeline inspection by existing theoretical analysis models, this paper introduces the charge density parameter to establish a mathematical model of non-uniform magnetic charge for pipeline leakage detection and calculates the non-uniform distribution pattern of magnetic charge on the defect side wall. The contour plot method is proposed to visually analyze the size of defects. To compare the error between uniform and non-uniform models, and verify the correctness of the theoretical model, experiments were systematically conducted on the X70 pipeline with internal MFL technology. The results show that: the magnetic charge distribution curve is symmetrically shaped at the center of the defect, with a valley at the center and two peaks at the defect edge. As the defect depth and width increase, the magnetic charge density increases sharply near the surface and edge. The peak-to-valley spacing and peak-to-valley values in the contour map of the MFL signal can directly reflect the location and size of defects. The signal characteristic values follow the trend of a first-order decreasing exponential function as the value of the lift-off increases. The first-order derivative of the signal characteristic value tends to decrease and then increase as the mesh size decreases, and the extreme point of the derivative curve is the best mesh size.

Mercury (II) complex based on quinoxaline–aminoantipyrine: Synthesis, crystal structure, computational studies and anticancer activities evaluation

A new complex of a heterocyclic Schiff base derived from 4-aminoantipyrine and 2-carboxaldehyde quinoxaline ((4E)-4-((quinoxalin-3-yl) methylene amino)-1, 2-dihydro-1, 5-dimethyl-2-phenylpyrazol-3-one) (L) with Hg(II) iodide, [Hg(L)I2], was synthesized and characterized using elemental analysis, FT-IR, 13CNMR and 1H NMR spectra methods. Stoichiometry of the complex was determined as 1: 1. The structure of the ligand and its mercury iodide complex was investigated using single-crystal X-ray diffraction method, which revealed that the complex had a distorted square-pyramidal geometry. In the molecular structure of the complex, the ligand coordinated to the central metal in a tridentate form (one oxygen and two nitrogen atoms as donors). The mercury atom also had a five-coordinate geometry with τ5 of 0.044. The optimization geometry, charge distribution pattern, HOMO and LUMO energy, and quantum chemical parameters for the ligand and its complex were confirmed by Density Functional Theory (DFT) calculations and NBO analysis. The synthesized compounds were tested against MCF-7 and HT-29 cancer cell lines using MTT cell viability assay. A comparative study of the IC50 values indicated that the Hg(II) complex exhibited a higher activity compared to the related free ligand against MCF-7 and HT-29 cell lines after 48 h.

Effects of Charged Polyelectrolytes on Amyloid Fibril Formation of a Tau Fragment.

The microtubule-associated protein tau is involved in more than 20 different neurological disorders characterized by aberrant intracellular aggregation of tau in the brain. Here, we investigated the aggregation of a novel 20-residue model peptide, tau298-317, which is derived from the key microtubule binding domain of the full sequence tau. Our results show that tau298-317 highly mimics the physical and aggregation properties of tau. Under normal physiological conditions, the peptide maintains a disordered random coil without aggregation. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution and the introduction of the negatively charged phosphate group on a serine (Ser305) residue in the sequence, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), were found to effectively inhibit Hep-induced aggregation of tau298-317 in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep-peptide interactions and suppressing peptide aggregation. Our results suggest that positively charged polyelectrolytes with optimized charged groups and charge distribution patterns can serve as effective molecular candidates to block tau-Hep interactions and prevent aggregation of tau induced by Hep and other polyanions.

Effective electrostatic forces between two neutral surfaces with surface charge separation: valence asymmetry and dielectric constant heterogeneity

Based on CDFT calculations, we study new features of surface electrostatic force (SEF) between two face-to-face overall neutral surfaces, each of which is comprised of atomic scale strip shape charge distribution and is immersed in +2:−1 electrolyte. Dielectric constant of near surface fluid is lower than that of distant fluid. Ion valence and dielectric constant heterogeneity effects are reflected in the following aspects. (i) For asymmetrical configuration of the strip shape charge distribution, if the coexistence bulk mole concentration is high like , one repulsion peak of the SEF appears at approximately two times the ion diameter and the peak height increases obviously with the ion valence and the strip shape domain width ; however, for low value, like , the ion valence almost does not cause any effect on the SEF shape and strength at small distances except that the higher valence ion causes a higher decaying rate of the SEF with the surface separation. (ii) For the case of the asymmetrical configuration and bivalent ion, strength of the small distance attractive SEF always reduces with the value, and is positively correlated with the value except when the value is high and the domain surface charge strength is low. (iii) The symmetrical strip shape charge distribution is an efficient way in inducing the attractive SEF in presence of bivalence ions even if the value is low down to ; the attraction strength is positively correlated with the value. (iv) The ion adsorption, playing a key role in influencing the SEF for the present overall neutral two-surface system, generally increases with the value, and far higher than that relevant to two similarly charged surfaces with equal value. (v) The lower surface fluid dielectric constant accords both the force and potential curves with new features like alternative mode of attraction and repulsion even in low bulk concentration, big strength in comparison with the average thermal energy, and large insensitivity to the surface charge distribution patterns and ion valence.

The Aggregation of Destabilized Ag Triangular Nanoplates and Its Application in Detection of Thiram Residues.

An aggregation or assembly of Ag triangular nanoplates (Ag TNPs) can cause dramatic changes in their optical properties, which is widely used in applications in the field of sensing. The assembly forms of nanoparticles are crucial for obtaining sensitive sensing signals, but it is unknown what kind of assembly dominates the aggregated Ag TNPs in aqueous solutions. Herein, using thiram-induced Ag TNP aggregation as a model, six different assembly models were established, including three planar (side-by-side, side-to-tip, and tip-to-tip) assemblies and three tridimensional (plane-to-plane, plane-to-tip, and plane-to-side) assemblies. The corresponding optical properties were then investigated. Both theoretical and experimental findings indicate that three-dimensional assemblies, especially plane-to-plane assembly, dominate the Ag TNPs aggregation solution, causing a blue shift of the absorption spectrum. Analysis of charge distribution patterns in Ag TNPs indicates that such a blue shift is caused by the electrostatic repulsive force in plane-to-plane assembly. Thus, we propose a simple colorimetric method for thiram detection using Ag TNPs as an indicator. The method exhibits a selective and sensitive response to thiram with a limit of detection of 0.13 μM in the range of 0.2–0.5 μM, as well as excellent performance in real samples like wheat.

Mononuclear and polymeric zinc(II) β-diketonate complexes with aromatic N-donor ligands: Structural, spectral, thermal, theoretical and docking studies

Four new compounds, {[Zn(μ-DPP)(DBM)2].2MeOH}n (1), {[Zn(μ-Pyrazine)(DBM)2]}n (2), [Zn(PHEN)(DBM)2] (3) and [Zn(2,2′-BPY)(DBM)(CH3COO)] (4) (DPP: 1,3-di(4-pyridyl)propane, HDBM: dibenzoylmethanato, PHEN: 1,10-phenanthrolin, 2,2′-BPY: 2,2′-bipyridine), were prepared and identified by elemental analysis, FT-IR and 1H NMR spectroscopy and single-crystal X-ray diffraction. In addition, the thermal stability of the compounds was evaluated by thermogravimetric analysis (TGA and DTA). The complexes 1 and 2 form 1D coordination polymers whereas 3 and 4 adopt a mononuclear structure. In these structures, the zinc atoms have octahedral (1–3) and square-pyramidal (4) geometries. The charge distribution pattern of the complexes 3 and 4 and their ligands was studied by NBO analysis and their ability to interact with ten biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) is investigated by docking calculations.

Hyperuniform electron distributions controlled by electron interactions in quasicrystals

We study how the electron-electron interactions influence the charge distributions in the metallic state of quasicrystals. As a simple theoretical model, we introduce an extended Hubbard model on the Penrose lattice, and numerically solve the model (up to $\ensuremath{\sim}1.4$ million sites) within the Hartree-Fock approximation. Because each site on the quasiperiodic lattice has a different local geometry, the Coulomb interaction, in particular the intersite one, works in a site-dependent way, leading to a nontrivial redistribution of the charge. The resultant charge distribution patterns are not multifractal but characterized by hyperuniformity, which offers a measure to distinguish various inhomogeneous but ordered distributions. We clarify how the electron interactions alter the order metric of the hyperuniformity, revealing that the intersite interaction considerably affects the hyperuniformity in particular on the electron-rich side.

Coordination of an amino alcoholic Schiff base ligand toward the zinc(II) ion: spectral, structural, theoretical, and docking studies

A new zinc(II) complex of 2-(((2-((2-hydroxyethyl)amino)ethyl)imino)methyl)phenol (L), [Zn(Lz)Br2] (1), is prepared and identified by elemental analysis, FTIR and 1H NMR spectroscopy, and single crystal X-ray diffraction. The X-ray structure analysis of 1 reveals a tetrahedrally coordinated zinc(II) complex containing the NO-donor amino alcoholic Schiff base ligand and two bromo ligands. After complexation, the ligand (L) converts to its zwitterionc form (Lz) of phenol → phenolate; amine → ammonium. In this structure, hydrogen bonds between amine and alcohol units form different types of hydrogen bond motifs, including R21(7), R22(7), R22(10), R44(24), R44(30), R66(38), and R66(44). In addition to the hydrogen bonds in this crystal network, there are π—π stacking interactions between the phenyl ring and the imine group. The ability of the ligand and its isostructural complexes [Zn(Lz)Br2] (1), [Zn(Lz)Cl2] (2), and [Zn(Lz)I2] (3) to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II, and B-DNA) is investigated by docking studies. The results show that in some cases, the studied compound can interact with proteins and DNA better than doxorubicin. The charge distribution pattern of the ligand and complex 1 is studied by the NBO analysis.

De novo sequence redesign of a functional Ras-binding domain globally inverted the surface charge distribution and led to extreme thermostability.

To acquire extremely thermostable proteins of given functions is challenging for conventional protein engineering. Here we applied ABACUS, a statistical energy function we developed for de novo amino acid sequence design, to globally redesign a Ras-binding domain (RBD), and obtained an extremely thermostable RBD that unfolds reversibly at above 110°C, the redesigned RBD experimentally confirmed to have expected structure and Ras-binding interface. Directed evolution of the redesigned RBD improved its Ras-binding affinity to the native protein level without excessive loss of thermostability. The designed amino acid substitutions were mostly at the protein surface. For many substitutions, strong epistasis or significantly differentiated effects on thermostability in the native sequence context relative to the redesigned sequence context were observed, suggesting the globally redesigned sequence to be unreachable through combining beneficial mutations of the native sequence. Further analyses revealed that by replacing 38 of a total of 48 non-interfacial surface residues at once, ABACUS redesign was able to globally "invert" the protein's charge distribution pattern in an optimized way. Our study demonstrates that computational protein design provides powerful new tools to solve challenging protein engineering problems.

Effect of Electron-Electron Interactions on Metallic State in Quasicrystals

We theoretically study the effect of electron-electron interactions on the metallic state of quasicrystals. To address the problem, we introduce the extended Hubbard model on the Ammann-Beenker tiling as a simple theoretical model. The model is numerically solved within an inhomogeneous mean-field theory. Because of the lack of periodicity, the metallic state is nonuniform in the electron density even in the noninteracting limit. We clarify how this charge distribution pattern changes with electron-electron interactions. We find that the intersite interactions change the distribution substantially and in an electron-hole asymmetric way. We clarify the origin of these changes through the analyses in the real and perpendicular spaces. Our results offer a fundamental basis to understand the electronic states in quasicrystalline metals.

Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design.

COVID-19, caused by SARS-CoV-2, has resulted in severe and unprecedented economic and social disruptions in the world. Nucleocapsid (N) protein, which is the major structural component of the virion and is involved in viral replication, assembly and immune regulation, plays key roles in the viral life cycle. Here, we solved the crystal structures of the N- and C-terminal domains (N-NTD and N-CTD) of SARS-CoV-2 N protein, at 1.8 and 1.5Å resolution, respectively. Both structures show conserved features from other CoV N proteins. The binding sites targeted by small molecules against HCoV-OC43 and MERS-CoV, which inhibit viral infection by blocking the RNA-binding activity or normal oligomerization of N protein, are relatively conserved in our structure, indicating N protein is a promising drug target. In addition, certain areas of N-NTD and N-CTD display distinct charge distribution patterns in SARS-CoV-2, which may alter the RNA-binding modes. The specific antigenic characteristics are critical for developing specific immune-based rapid diagnostic tests. Our structural information can aid in the discovery and development of antiviral inhibitors against SARS-CoV-2 in the future.

Electronic structure of 30∘ twisted double bilayer graphene

In this paper, the electronic properties of 30{\deg} twisted double bilayer graphene, which loses the translational symmetry due to the incommensurate twist angle, are studied by means of the tight-binding approximation. We demonstrate the interlayer decoupling in the low-energy region from various electronic properties, such as the density of states, effective band structure, optical conductivity and Landau level spectrum. However, at Q points, the interlayer coupling results in the appearance of new Van Hove singularities in the density of states, new peaks in the optical conductivity and importantly the 12-fold-symmetry-like electronic states. The k-space tight-binding method is adopted to explain this phenomenon. The electronic states at Q points show the charge distribution patterns more complex than the 30{\deg} twisted bilayer graphene due to the symmetry decrease. These phenomena appear also in the 30{\deg} twisted interface between graphene monolayer and AB stacked bilayer.

Enhancing flashover performance of alumina/epoxy spacers by adaptive surface charge regulation using graded conductivity coating

Surface flashover properties of alumina/epoxy spacers, involving a surface charge accumulation process, are critical for the safe and reliable operation of a high-voltage direct-current (HVDC) gas-insulated transmission line (GIL). This study reports surface charging behavior and flashover performance of alumina/epoxy spacers with different surface conductivity graded coating (SCGC) schemes in SF6/N2 mixtures under DC stress. Four kinds of SCGC schemes, i.e. localized coating near high voltage (HV-coating), near grounded electrode (GND-coating), at the middle of spacer surface (SPM-coating) and near both high voltage and grounded electrode (HV-GND-coating), are designed by partially spraying SiC/epoxy composites on the spacer surface. Surface charge distribution patterns exhibit varied features with different SCGC schemes. The HV-coating and GND-coating schemes lead to aggravated homo-charge and hetero-charge accumulation respectively, whereas in the SPM-coating scheme surface charge shows a multi-tier distribution pattern with alternating polarity. A transition of the dominant surface charge mechanism from bulk conductivity to surface conductivity with increasing conductivity on the coated area is found. Flashover performance differs a lot with different SCGC schemes: the HV-coating and HV-GND-coating schemes increase the flashover voltage while the SPM-coating and GND-coating schemes degrade it. The optimal surface insulation strength is achieved in the HV-coating scheme with a coating width of about 10 mm. The impact of different SCGC schemes on flashover performance is revealed based on the electric field analysis by considering the effect of surface charges.

Coordination of a (Npy)2NimineNamine-Donor Oxazolidine Ligand Toward CdX2 (X = Cl, Br, I) with 1:1 and 2:1 M:L Molar Ratios Along with Spectral, Theoretical, and Structural Studies

A series of reactions between an oxazolidine ligand 2-(2-(pyridin-2-yl)oxazolidin-3-yl)-N-(pyridin-2-ylmethylene)ethanamine (POPME) and CdX2 (X = Cl, Br, I) salts with different M:L molar ratios (1:1 and 2:1) is experimentally studied to determine the most stable product of these reactions. All products are characterized by the elemental analysis, FTIR, Raman, and 1H NMR spectroscopy, and single crystal X-ray diffraction. Examinations reveal that only one product is formed from 1:1 and 2:1 M:L reactions between each cadmium(II) halide with POPME. The thermodynamic stability and charge distribution patterns of the compound containing bromide are analyzed by DFT and NBO.

Spectral, structural, biological and molecular docking studies of a new mixed-valence V(IV)/V(V) ofloxacin complex

In this study, a biologically active mixed-valence V(IV)/V(V) complex [VO(Hofloz)2(H2O)][V4O12]0.5.6H2O (1) (Hofloz = zwitterionic isomer of ofloxacin) was synthesized by the reaction of VOSO4 with ofloxacin (Hofloz) in presence of KOH with 1:1:1 ratio. The complex was characterized through the usage of elemental analysis, FT-IR, molar conductivity and single-crystal X-ray diffraction and thermogravimetric analysis (TGA). The results of single crystal X-ray structure determination revealed an ionic structure consisting of [VO(Hofloz)2(H2O)]2+ and [V4O12]4− units with 1:0.5 stoichiometry. The V+4 ion in the cationic unit has octahedral geometry while each V+5 ion of the eight-member cyclic tetravanadate anion is tetrahedrally coordinated. In regards to the crystal structure of 1, the bidentate ofloxacin ligand is coordinated to the V+4 ion in its zwitterionic form (+HN–···–COO-) through the oxygen atoms of the pyridone and carboxylato groups. The thermodynamic stability of two isomeric forms of Hoflo and 1 along with their charge distribution patterns was studied by DFT and NBO analysis. Also, the ability of the ligand to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) was investigated by docking calculations. These studies revealed that this ligand can bind to the proteins and DNA molecule and could be consider as biologically active compound. Finally, the antibacterial activities of the free Hoflo ligand and its vanadium complex have been evaluated against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains through the utilization of broth microdilution and well diffusion methods. The complex showed antibacterial effect similar to the free Hoflo ligand on the selected bacterial strains and these compounds were more active against Gram-negative bacteria.

A binuclear Cd(II) complex containing bridging pyrimidine-based ligands

AbstractIn this work, a pyrimidine-based ligand,N′-(amino(pyrimidin-2-yl)methylene)pyrimidine-2-carbohydrazonamide hydrate (APPH · H2O), and its binuclear complex of cadmium, [Cd(μ-APPH)Br]2,1, were prepared and identified by elemental analysis, FT-IR,1H NMR spectroscopy as well as single-crystal X-ray diffraction. X-ray structure analysis of1revealed octahedrally coordinated cadmium centers with a CdN4Br2environment containing two bridging APPH ligands; each APPH ligand acts as an N4-donor (N2-donor toward each cadmium atom) and forms two five-membered chelate rings that are approximately perpendicular to each other. In the network of1, the N–H · · · Br hydrogen bonds form motifs such asR22(12, 14), R66(24, 26, …, 46).${\rm{R}}_{\rm{2}}^{\rm{2}}(12,{\rm{ }}14),{\rm{ R}}_{\rm{6}}^{\rm{6}}(24,{\rm{ }}26,{\rm{ }} \ldots ,{\rm{ }}46).$The crystal network is further stabilized by π-π stacking interactions between pyrimidine rings. The optimized structures of the ligand and complex were investigated along with their charge distribution patterns by density functional theory and natural bond orbital analysis, respectively.