Coordination Of Calcium Ions Research Articles

Host defence peptide plectasin targets bacterial cell wall precursor lipid II by a calcium-sensitive supramolecular mechanism

Antimicrobial resistance is a leading cause of mortality, calling for the development of new antibiotics. The fungal antibiotic plectasin is a eukaryotic host defence peptide that blocks bacterial cell wall synthesis. Here, using a combination of solid-state nuclear magnetic resonance, atomic force microscopy and activity assays, we show that plectasin uses a calcium-sensitive supramolecular killing mechanism. Efficient and selective binding of the target lipid II, a cell wall precursor with an irreplaceable pyrophosphate, is achieved by the oligomerization of plectasin into dense supra-structures that only form on bacterial membranes that comprise lipid II. Oligomerization and target binding of plectasin are interdependent and are enhanced by the coordination of calcium ions to plectasin’s prominent anionic patch, causing allosteric changes that markedly improve the activity of the antibiotic. Structural knowledge of how host defence peptides impair cell wall synthesis will likely enable the development of superior drug candidates.

Design, One-Step Highly Selective Synthesis and Enhancing Insecticidal Activity and Photo-Self-Degradation of Phenylpyrazole Esterified Derivatives as GABA and nACh Receptor Inhibitors.

In the pursuit of novel insecticides with high activity and a unique mode of action on the GABA receptor, a series of phenylpyrazole esterified derivatives (PEs) were synthesized using an improved Pinner reaction with high selectivity. Lewis acid catalysis was employed in a one-step solvent-thermal method to convert the cyano group of fipronil into an ester unit. FeCl3 was found to exhibit the highest selectivity for PEs synthesis, yielding PEs at 96.4%, with the byproduct being phenylpyrazole amide (PE0) at 2.1%. Initial biological assays indicated superior insecticidal activity of the target compounds against Plutella xylostella and Mythimna separata compared to fipronil. Particularly, the smaller and shorter ester units, PE3, PE5, and PE8, demonstrated 2-2.5 times higher insecticidal activity against P. xylostella than fipronil. The higher activity of ester units compared to amide and acylhydrazone units can be attributed to the enhanced lipid solubility of PEs. Additionally, it may be due to the impact of PEs on the neurotransmitter nACh or the coordination of calcium and chloride ions with the ester's -C═O and -O- bonds, blocking the chloride ion channel. Hydrophobic parameters were confirmed by reversed-phase high-performance liquid chromatography (HPLC), indicating the enhanced lipophilicity conferred by the ester units of PEs. Molecular docking and CoMFA analysis preliminarily validated the strong interactions and structure-activity relationships between PEs and the GABA receptor and nACh receptor in P. xylostella. Furthermore, under simulated natural sunlight, PEs exhibited photodegradation capabilities, transforming back into fipronil parent fragments and enhancing their insecticidal activity. Moreover, PEs displayed excellent fluorescent properties, enabling self-detection of residues. These research findings provide new insights and directions for the development of efficient pesticides, with potential wide applications in the fields of medicine and biosensors.

Morphological, microstructural, and mechanical properties of highly-ordered C–S–H regulated by cellulose nanocrystals (CNCs)

Microstructures of calcium silicate hydrates (C–S–H) are relevant to the mechanical properties and durability of cement-based materials. Random growth of the microstructures of C–S–H largely compromises the mechanical properties and durability. This paper proposes to utilize cellulose nanocrystals (CNCs) to modify the microstructures of C–S–H. This research investigates the effect of CNCs on the morphological, microstructural, and mechanical properties of C–S–H through dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetry analysis (TGA), atomic force microscopy (AFM), and three-point bending tests. The results showed that CNCs effectively mitigated the agglomeration of C–S–H and generated C–S–H/CNC nanocomposites with highly ordered, layered, and dense microstructures. The C–S–H and CNCs in the C–S–H/CNC nanocomposites had strong interactions through hydrogen bonds and calcium ion coordination bonds. The strong interactions and ordered microstructures enable C–S–H/CNCs nanocomposites to achieve high strength and flexibility.

Preparation and Properties of Epoxy Asphalt Modified by Biomimetic Graphene Oxide Nanocomposites

In order to solve the current problem of insufficient toughness of epoxy asphalt and immiscibility between resin and asphalt binder (not aged) in epoxy asphalt, nanomodifiers (GOs-CS-Ca2+) were prepared by a biomimetic mechanism from chitosan (CS), calcium ions (Ca2+), and graphene oxide nanoplatelets (GOs). In GOs-CS-Ca2+, CS connects GOs through calcium ion coordination bonds and amide bonds. GOs-CS-Ca2+-modified epoxy asphalt was prepared by directly adding different percentages of GOs-CS-Ca2+ to epoxy asphalt. Then, the properties of GOs-CS-Ca2+-modified epoxy asphalt were analyzed through macro and micro tests. The macroscopic tests included tensile, cyclic, and stress relaxation tests. The microscopic tests included fluorescence microscopy (FM) and scanning electron microscopy (SEM) tests. Tensile tests showed that after adding 0.05% GOs-CS-Ca2+ to the total mass of epoxy asphalt, the tensile strength and fracture toughness of epoxy asphalt increased by 29.6% and 20%. Cyclic tensile tests showed that GOs-CS-Ca2+-modified epoxy asphalt had greater consuming work recovery capacity, and stress relaxation tests showed that the addition of GOs-CS-Ca2+ delayed the relaxation modulus decline of epoxy asphalt. The infrared spectrum, scanning electron microscope, X-ray diffraction, and Raman spectra of GOs-CS-Ca2+ in the micro test can show the successful synthesis of GOs-CS-Ca2+. FM and SEM of GOs-CS-Ca2+-modified epoxy asphalt showed that the addition of GOs-CS-Ca2+ could reduce the particle-size distribution of the asphalt phase in epoxy resin and establish a miscible bridge between epoxy resin and asphalt, which led to the improvement of macroscopic mechanical properties of GOs-CS-Ca2+-modified epoxy asphalt. Finally, the modification mechanism of GOs-CS-Ca2+-modified epoxy asphalt was proposed by combining macroscopic and microscopic test results.

Supramolecular Self‐Assembly Modes of Cyclopentanocucurbit[6]uril and Aromatic Amines

AbstractZnCl2 has been used as a structural inducer in hydrochloric acid solution to construct three supramolecular frameworks of action utilizing cyclopentanocucurbit[6]uril (CyP6Q[6]) as the host and (4‐aminophenyl)methanol (G1), 4‐benzylaniline (G2), and 4,4’‐diaminobenzophenone (G3) as guests. The structure was confirmed using X‐ray single crystal diffraction, 1HNMR spectroscopy, and mass spectroscopy (MS). The results showed that G1 entered the molecular cavity of CyP6Q[6], CyP6Q[6] had portal and outer‐surface interactions with G2, and G3 only acted on the outer surface of CyP6Q[6] with calcium ion coordination.

Water-in-Salt Electrolyte-Based Extended Voltage Range, Safe, and Long-Cycle-Life Aqueous Calcium-Ion Cells.

The narrow electrochemical stability window (1.23 V) of an aqueous electrolyte hinders the practical realization of calcium-ion chemistries of high-energy-density and long-cycle-life batteries. Furthermore, developing an aqueous electrolyte that is low cost, is environmentally friendly, and has a wide voltage window is essential to designing safe, high-energy-density, and sustainable calcium-ion batteries. A calcium-based water-in-salt (WISE) aqueous electrolyte surpasses the narrow stability window by offering a 2.12 V wide window by suppressing the hydrogen evolution at the anode and minimizing the overall water activity at the cathode. A comprehensive theoretical study predicts the preferential reduction of salt aggregates over water to form a passivation layer at the electrode-electrolyte interface and enhance the electrolyte stability window. Additionally, Raman spectroscopy reveals that the calcium ion coordination number, which is the number of nitrate ions surrounding the calcium ions in the aqueous electrolyte, gradually increases with an increase in the electrolyte concentration, leading to a gradual decrease in the hydration number of the calcium ions. A full cell in WISE was demonstrated to exhibit an excellent rate capability and cycling stability with negligible capacity loss (0.01 per cycle), maintaining 80% capacity retention over 1800 cycles with ∼99.99% Coulombic efficiency. The full cell provides an energy density of 232 Wh kg-1 at a power density of 69 W kg-1 and a current rate of 0.15 A g-1. Even at a higher current rate of 5 A g-1, the battery delivers an energy density of 182 Wh kg-1 (based on the active mass of the anode). This is one of the best performances to date of all previously reported full-cell aqueous calcium-ion batteries. A fundamental understanding of the storage mechanism and a electrode degradation study was achieved. This work suggests and expands new avenues for the practical realization of low-cost, safe, eco-friendly, and high-performance aqueous calcium-ion batteries for future large storage applications.

Cellulose nanofibril/mineral composites induced by H-bond/ionic coordination in co-refining system

Mineral fillers hinder cellulosic fiber bonding and thus limit the increase of filler content in paper. Herein, precipitated calcium carbonate (PCC)/cellulose nanofibrils (CNF) composites were fabricated by a facile and efficient strategy, i.e., co-refining process (CRP). During this process, CNF and PCC were activated by mechanochemical effect and formed encapsulation structure by calcium ion coordination and hydrogen bonding. The encapsulation structure and H-bond/ionic coordination interactions not only endowed the composite with excellent size stability but also enhanced interfacial interaction between composite fillers and cellulosic fibers. Compare with the paper filled with only PCC, PCC + CNF mixture, the tensile index of the cellulosic paper containing PCC/CNF composite was increased by 44.48% and 12.14%, respectively. These results not only provide a facile and scalable approach to increase interaction between cellulosic fiber and mineral filler but also create more possibilities for special paper-based materials with requiring high content of inorganic materials.

Cloning, sequence analysis, and tissue expression of marmoset paraoxonase 1

Paraoxonase (PON) plays roles in the metabolism of organophosphate xenobiotics and drugs. Despite the importance of marmosets for research into drug metabolism and pharmacokinetics, marmoset paraoxonase has not yet been fully characterized. Consequently, we identified the PON1 gene in the marmoset genome by sequence homology analysis. Marmoset PON1 cDNA containing an open reading frame (1065 bp) was successfully cloned from marmoset liver by reverse transcription-polymerase chain reaction. The deduced amino acid sequence (355 amino acids) has approximately 93% identity with the human ortholog and contains important amino acid residues for substrate binding and calcium ion coordination. According to a phylogenetic tree of PON1 amino acid sequences constructed using data from seven animal species, marmoset PON1 is closer to human PON1 than it is to the PON1 orthologs of experimental animals such as pigs, rabbits, rats, and mice. Marmoset PON1 mRNA was predominantly expressed in liver among the five tissues examined. Marmoset PON1 protein secreted into plasma was detected by immunoblotting. The paraoxon-hydrolyzing activity in plasma was higher in marmosets than in humans. Based on these data, we concluded that marmoset and human PON1 have similar characteristics with regard to genomic structure, amino acid sequences, and tissue distribution.

Visible light-controlled reversible self-assembly of nanorod supramolecular structures

In this article, a nanorod suprastructure constructed by coordination of calcium ions (Ca2+) with complex β-cyclodextrin-4,4′-dipyridyl (B-44) in the presence of the photo-acid merocyanine (MEH). The suprastructure (B-44-Ca) possesses reversible photoswitching with high on/off contrast based on the self-assembly process in aqueous solution. In which, the supramolecular can be activated by visible-light instead of acid or base. The system not only can be carried by remote control, but also by the introduction of additional chemicals, which will facilitate the reversibility of light-controlled supramolecular smart materials.

Effects of calcium ions on crystal structure and luminescence properties of six rare earth metal complexes

Six heterometallic complexes {[Ln2(pydc)6Ca3(H2O)12]·mH2O}n (Ln = Tb (1), m = 16; Eu (2), m = 14; Sm (3), m = 16; H2pydc = pyridine-2,6-dicarboxylic acid) and [Ln2(pydc)6Ca2(H2O)10]·2Him·xH2O (Ln = Tb (4), x = 8; Eu (5), x = 6; Sm(6), x = 8; im = imidazole) have been hydrothermally synthesized and characterized by elemental analysis, IR, TG, XRD as well as single-crystal X-ray diffraction. Complexes 1–3 display three-dimensional network structure and can be simplified to a new topology, with the point symbol of {4·84·12}2{42.82.102}{8}2. Complexes 4–6 exhibit tetranuclear structures. The luminescence properties for the six complexes were determined using solid samples. They show characteristic emission spectra of lanthanide ions. The complexes 1–6 were compared in terms of emission intensity, fluorescence decay lifetime and quantum yield. The quantum yields Фtotal are 90.02 ± 10%, 81.05 ± 10%, 37.65 ± 10%, and 70.84 ± 10% for complexes 1 (Ca–Tb), 4 (Ca–Tb), 2 (Ca–Eu), and 5 (Ca–Eu), respectively. The effects of the structure of the complexes and the coordination of calcium ions on the luminescent properties of lanthanide complexes were also investigated.

Investigation of the calcium-induced activation of the bacteriophage T5 peptidoglycan hydrolase promoting host cell lysis.

Peptidoglycan hydrolase of bacteriophage T5 (EndoT5) is a Ca2+-dependent l-alanyl-d-glutamate peptidase, although the mode of Ca2+ binding and its physiological significance remain obscure. Site-directed mutagenesis was used to elucidate the role of the polar amino acids of the mobile loop of EndoT5 (111-130) in Ca2+ binding. The mutant proteins were purified to electrophoretic homogeneity, the overall structures were characterized by circular dichroism, and the calcium dissociation constants were determined via NMR spectroscopy. The data suggest that polar amino acids D113, N115, and S117 of EndoT5 are involved in the coordination of calcium ions by forming the core of the EF-like Ca2+-binding loop while the charged residues D122 and E123 of EndoT5 contribute to maintaining the loop net charge density. The results suggest that Ca2+ binding to the EndoT5 molecule could be essential for the stabilization of the long mobile loop in the catalytically active "open" conformation. The possible mechanism of Ca2+ regulation of EndoT5 activity during bacteriophage T5's life cycle through the Ca2+ concentration difference between the cytoplasm and the periplasm of the host bacteria cell has been discussed. The study reveals valuable insight into the role of calcium in the regulation of phage-induced bacterial lysis.

Calcium ion cross-linking alginate/dexamethasone sodium phosphate hybrid hydrogel for extended drug release.

Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH (e.g., its low mechanical property) and is associated with the enhancement of materials performance, which is useful in a variety of biomedical applications. In the present work, a hybrid hydrogel that combines dexamethasone sodium phosphate (Dexp) and a polysaccharide (alginate) was explored via a calcium ion coordination strategy. With the addition of Ca2+ to an aqueous solution of Dexp/alginate, the Ca2+/Dexp/alginate hybrid hydrogel formed spontaneously. The formed Ca2+/Dexp/alginate hybrid hydrogels were thoroughly characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). An in vitro drug release study indicated that the formed Ca2+/Dexp/alginate hybrid hydrogel provided a slower drug release rate than did the Ca2+/Dexp hydrogel, and the drug release behaviour could be finely tailored by the change of Ca2+ concentration. More importantly, the subcutaneous injection of the Ca2+/Dexp/alginate hybrid hydrogel significantly extended the in vivo retention of the hydrogel in situ compared to that of the Ca2+/Dexp hydrogel. The in vivo pharmacokinetic analysis indicated that the Ca2+/Dexp/alginate hybrid hydrogel could greatly extend drug release in vivo and significantly improve drug bioavailability compared to the Ca2+/Dexp hydrogel. As such, the formed Ca2+/Dexp/alginate hybrid hydrogel combined the greater resilience of an alginate network with the long in vivo duration of a low-molecular-weight hydrogel (Ca2+/Dexp hydrogel) and remarkably enhanced drug bioavailability, which might open an avenue for the design of self-assembling steroidal drug-polysaccharide hybrid hydrogels for drug delivery applications.

Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator.

The dissipative quartz crystal microbalance technique is a simple and label-free approach to measure simultaneously the mass uptake and viscoelastic properties of the absorbed/immobilized mass on sensor surfaces, allowing the measurements of the interaction of proteins with solid-supported surfaces, such as lipid bilayers, in real-time and with a high sensitivity. Annexins are a highly conserved group of phospholipid-binding proteins that interact reversibly with the negatively charged headgroups via the coordination of calcium ions. Here, we describe a protocol that was employed to quantitatively analyze the binding of annexin A2 (AnxA2) to planar lipid bilayers prepared on the surface of a quartz sensor. This protocol is optimized to obtain robust and reproducible data and includes a detailed step-by-step description. The method can be applied to other membrane-binding proteins and bilayer compositions.

Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator

The dissipative quartz crystal microbalance technique is a simple and label-free approach to measure simultaneously the mass uptake and viscoelastic properties of the absorbed/immobilized mass on sensor surfaces, allowing the measurements of the interaction of proteins with solid-supported surfaces, such as lipid bilayers, in real-time and with a high sensitivity. Annexins are a highly conserved group of phospholipid-binding proteins that interact reversibly with the negatively charged headgroups via the coordination of calcium ions. Here, we describe a protocol that was employed to quantitatively analyze the binding of annexin A2 (AnxA2) to planar lipid bilayers prepared on the surface of a quartz sensor. This protocol is optimized to obtain robust and reproducible data and includes a detailed step-by-step description. The method can be applied to other membrane-binding proteins and bilayer compositions.

Unusually high mechanical stability of bacterial adhesin extender domains having calcium clamps.

To gain insight into the relationship between protein structure and mechanical stability, single molecule force spectroscopy experiments on proteins with diverse structure and topology are needed. Here, we measured the mechanical stability of extender domains of two bacterial adhesins MpAFP and MhLap, in an atomic force microscope. We find that both proteins are remarkably stable to pulling forces between their N- and C- terminal ends. At a pulling speed of 1 μm/s, the MpAFP extender domain fails at an unfolding force Fu = 348 ± 37 pN and MhLap at Fu = 306 ± 51 pN in buffer with 10 mM Ca2+. These forces place both extender domains well above the mechanical stability of many other β-sandwich domains in mechanostable proteins. We propose that the increased stability of MpAFP and MhLap is due to a combination of both hydrogen bonding between parallel terminal strands and intra-molecular coordination of calcium ions.

Molecular Dynamics Simulations of Hydroxyapatite Nanopores in Contact with Electrolyte Solutions: The Effect of Nanoconfinement and Solvated Ions on the Surface Reactivity and the Structural, Dynamical, and Vibrational Properties of Water

Hydroxyapatite, the main mineral phase of mammalian tooth enamel and bone, grows within nanoconfined environments and in contact with aqueous solutions that are rich in ions. Hydroxyapatite nanopores of different pore sizes (20 Å ≤ H ≤ 110 Å, where H is the size of the nanopore) in contact with liquid water and aqueous electrolyte solutions (CaCl2 (aq) and CaF2 (aq)) were investigated using molecular dynamics simulations to quantify the effect of nanoconfinement and solvated ions on the surface reactivity and the structural and dynamical properties of water. The combined effect of solution composition and nanoconfinement significantly slows the self-diffusion coefficient of water molecules compared with bulk liquid. Analysis of the pair and angular distribution functions, distribution of hydrogen bonds, velocity autocorrelation functions, and power spectra of water shows that solution composition and nanoconfinement in particular enhance the rigidity of the water hydrogen bonding network. Calculation of the water exchange events in the coordination of calcium ions reveals that the dynamics of water molecules at the HAP–solution interface decreases substantially with the degree of confinement. Ions in solution also reduce the water dynamics at the surface calcium sites. Together, these changes in the properties of water impart an overall rigidifying effect on the solvent network and reduce the reactivity at the hydroxyapatite-solution interface. Since the process of surface-cation-dehydration governs the kinetics of the reactions occurring at mineral surfaces, such as adsorption and crystal growth, this work shows how nanoconfinement and solvation environment influence the molecular-level events surrounding the crystallization of hydroxyapatite.

Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells

Tumor metastasis with resistance to anticancer therapies is the main cause of death in cancer patients. It is necessary to develop reliable tumor metastasis models that can closely recapitulate the pathophysiological features of the native tumor tissue. In this study, chondroitin sulfate (CS)-modified alginate hydrogel beads (ALG-CS) are developed to mimic the in vivo tumor microenvironment with an abnormally increased expression of CS for the promotion of tumor cell metastasis. The modification mechanism of CS on alginate hydrogel is due to the cross-linking between CS and alginate molecules via coordination of calcium ions, which enables ALG-CS to possess significantly different physical characteristics than the traditional alginate beads (ALG). And quantum chemistry calculations show that in addition to the traditional egg-box structure, novel asymmetric egg-box-like structures based on the interaction between these two kinds of polymers are also formed within ALG-CS. Moreover, tumor cell metastasis is significantly enhanced in ALG-CS compared with that in ALG, as confirmed by the increased expression of MMP genes and proteins and greater in vitro invasion ability. Therefore, ALG-CS could be a convenient and effective 3D biomimetic scaffold that would be used to construct standardized tumor metastasis models for tumor research and anticancer drug screening.

Homology modeling and molecular dynamics study on Schwanniomyces occidentalis alpha-amylase

With consumers growing increasingly aware of environmental issues, industries find enzymes as a reasonable alternative over physical conditions and chemical catalysts. Amylases are important hydrolase enzymes, which have been widely used in variety of industrial process such as pharmaceutical, food, and fermentation industries. Among amylases α-Amylase is in maximum demand due to its wide range of applications. The homology modeling study on Schwanniomyces occidentalis amylase (AMY1, UniProt identifier number: P19269) was performed by Modeller using Aspergillus oryzae (6TAA) as the template. The resulting structure was analyzed for validity and subjected to 14 ns of molecular dynamics (MD) simulation trough GROMACS. The validity of obtained model may represent that utilized OPLS force field is suitable for calcium-containing enzymes. DSSP secondary structure and contact map analysis represent the conservation of domain A TIM barrel feature together with calcium ion coordination sphere. Investigating the covariance matrix followed by principle component analyses for the first five eigenvectors of both trajectories indicate a little more flexibility for AMY1 structure. The electrostatic calculation for the final structures shows similar isoelectric point and superimposed buffering zone in the 5–8 pH range.

Quantum chemical studies on the role of residues in calcium ion binding to Calmodulin

We perform density functional theory (DFT) based quantum chemical calculations on calcium ion coordination to an isolated loop of Calmodulin. We show that the coordination molecular orbitals in the ground state, having contributions from the valence orbitals of the metal ion and the loop atoms, bring out the roles of the coordinating and the non-coordinating residues to stabilize the coordination geometry in agreement to the mutational studies. The coordinating molecular orbitals are observed to be robust under various truncations of the binding loop and capping at the terminal residues.

Toward Green and Sustainable Chemical Glycosylation: Enhanced Lewis Acidity of Recyclable Solid Super Acid Catalyst, SO4/ZrO2 by CaCl2 Doping

The simple doping of calcium chloride allowed highly improved yields in the glycosylation promoted by sulfated zirconia (SZ) without calcination. It was revealed by means of per-O-benzylated galactose trichloroacetimidate as a model glycosyl donor that this effect depends greatly on the cationic ion radius of used metal chlorides. Temperature-programmed desorption of ammonia (NH3 TPD) and the pyridine IR method showed clearly that coordination of calcium ion provides the SZ surface with newly formed Lewis acidic sites while the Brønsted acid site disappeared, indicating that the enhanced catalytic potency of SZ is due to the increased Lewis acid sites by doping the optimal calcium ions. The present findings might give insight into the relationship between a catalytic mechanism and superacidity of SZ, which is crucial for the design of novel superacid–based catalysts and environmentally benign glycosylation processes.