Coordination Binding Research Articles

Benchmarking biomolecular force field-based Zn2+ for mono- and bimetallic ligand binding sites.

Zn2+ is one of the most versatile biologically available metal ions, but accurate modeling of Zn2+ -containing metalloproteins at the biomolecular force field level can be challenging. Since most Zn2+ models are parameterized in bulk solvent, in-depth knowledge about their performance in a protein environment is limited. Thus, we systematically investigate here the behavior of non-polarizable Zn2+ models for their ability to reproduce experimentally determined metal coordination and ligand binding in metalloproteins. The benchmarking is performed in challenging environments, including mono- (carbonic anhydrase II) and bimetallic (metallo-β-lactamase VIM-2) ligand binding sites. We identify key differences in the performance between the Zn2+ models with regard to the preferred ligating atoms (charged/non-charged), attraction of water molecules, and the preferred coordination geometry. Based on these results, we suggest suitable simulation conditions for varying Zn2+ site geometries that could guide the further development of biomolecular Zn2+ models.

Tumor immunomodulatory effects of polyphenols.

Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.

Carbon dots derived from peptone as “off-on” fluorescent probes for the detection of oxalic acid

A simple and rapid microwave heating approach was reported for the preparation of water soluble carbon dots (CDs) using peptone as carbon source with the assistance of ethylenediamine. Several characterization techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were employed to analyze CDs. The optical properties of synthesized CDs were examined by UV–vis and fluorescence spectroscopy. The CDs exhibit strong blue emission under 365 nm UV lamp and have the excitation and pH (2.0–12.0) dependent emission behavior. The fluorescence intensity of CDs can be selectively quenched by Co2+ via dynamic mechanism, while the addition of oxalic acid (OA) results in a remarkable recovery of the fluorescence intensity due to the strong coordination binding between oxalic acid and Co2+. Hence, the prepared CDs can conveniently serve as “off-on” fluorescent probes for highly sensitive determination of oxalic acid. The wide linear range is 0.5–70 mg/L with a low detection limit of 0.288 mg/L. Furthermore, the probes were successfully applied to detect oxalic acid in tomato and cherry tomato samples with the recovery of 96.4 %–106.4 % and the relative standard deviation lower than 0.25 %.

Gallium (III) Complexes with 5-Bromosalicylaldehyde Benzoylhydrazones: In Silico Studies and In Vitro Cytotoxic Activity.

Gallium (III) complexes with the ligands 5-bromosalicylaldehyde-4-hydroxybenzoylhydrazone and 5-bromosalicylaldehyde isonicotinoylhydrazone were synthesized to receive compounds with improved antiproliferative action. Compounds were characterized by elemental analysis, IR, and NMR spectroscopy. Density functional theory calculations with Becke’s 3-parameter hybrid functional and 6-31+G(d,p) basis set were carried out to investigate the structural features of the ligands and Ga(III) complexes. Cytotoxic screening by MTT-dye reduction assay was carried out using cisplatin and melphalan as reference cytotoxic agents. A general formula [Ga(HL)2]NO3 for the complexes obtained was suggested. The complexes are mononuclear with the Ga(III) ions being surrounded by two ligands. The ligands acted as monoanionic tridentate (ONO) donor molecules. The analysis revealed coordination binding through deprotonated phenolic-oxygen, azomethine-nitrogen, and amide-oxygen atoms. The bioassay demonstrated that all compounds exhibited concentration-dependent antiproliferative activity at low micromolar concentrations against the acute myeloid leukemia HL-60 and T-cell leukemia SKW-3 cell lines. IC50 values of 5-bromo-derivative ligands and gallium (III) complexes are lower than those of cisplatin and much lower than these of melphalan. The coordination to gallium (III) additionally increased the cytotoxicity compared to the metal-free hydrazones.

Cellulose/silsesquioxane grafted Ti3C2Tx MXene for synergistically enhanced adsorption of uranium

The emerging two-dimensional material MXene is widely used in metal ions adsorption. However, among the various modification strategies of MXene, the study on the synergistically effect of linear natural polymer and nano-sized particles and their interaction mechanism remains unclear. In this work, polyhedral oligomeric silsesquioxane (POSS-OH) and hydroxypropyl cellulose (HPC) were grafted onto Ti3C2Tx MXene, producing chemically stable HPC/Ti3C2Tx/POSS-OH (CHMP) with adjustable interlayer space. Under the synergistic interaction, the CHMP exhibited obviously increased kinetics, high selectivity and good repeatability towards the adsorption of uranium ions (UO22+). The adsorption capacity of CHMP has been increased by 35.08%. In addition, X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscope (HR-TEM) indicated high chemical stability of CHMP. Langmuir isotherm model suggested that the adsorption mechanism of CHMP on UO22+ was the single-layer adsorption coordinated with oxygen-containing functional groups. The maximum adsorption capacity of CHMP was 307.67 mg g−1. Furthermore, XPS and simulation results suggested that the adsorption mechanism of UO22+ was both strong coordination binding with hydroxyl groups and electrostatic interaction.

Coordination behavior and binding properties of 2,6-pyridinedimethanol with Cu(II), Zn(II), and Cd(II) cations

Selective extraction of water-bound metal cations through chelating agents is investigated. Reactions of 2,6-pyridinedimethanol (L1) with Cu(NO3)2·3H2O, Zn(NO3)2·6H2O and Cd(NO3)2·4H2O produced complexes [Cu(L1)2] (1), [Zn(L1)2] (2), and [Cd2(μ-NO3)(L1)2] (3), respectively. The solid-state structures of 1, 2, and 3 confirmed that L1 coordinates in a tridentate fashion. The chelating ligand 2,6-pyridinedimethanol (L1) was also used as a model chelating agent for liquid–liquid extraction of copper(II), zinc(II), cadmium(II), and lead(II) cations from water using dichloromethane as the organic solvent. The relative affinities of these chelating ligands for Cu(II), Zn(II), Cd(II), and Pb(II) by liquid–liquid extraction were found to be in the order Cu(II) > Zn(II) > Pb(II) > Cd(II). Extraction efficiencies of 85% for Cu(II), 80% for Zn(II), 58% for Pb(II), and 45% for Cd(II) were observed.

A Universal Mechanochemistry Allows On-Demand Synthesis of Stable and Processable Liquid Metal Composites.

Gallium-based liquid metal (LM) is regarded as one of the most promising candidates for the new-generation jigsaw of stretchable electronics. Nonetheless, the obstacle for the LM application lies in its high surface tension and easy fluidity which leads to great difficulty in handling and processing. Herein, a cross-mechanochemistry between liquid metal and inorganic solid, mediated via the coordination binding between the empty electronic orbits of the former and the lone electron pair of the latter is reported. The mechanism is validated via density functional theory calculation and electron energy loss spectroscopy, and experimentally proven to be universally applicable for various liquid metals and inorganic solids. With the unique mechanochemistry, simple ball milling allows on-demand transformation of the liquid metal into a low-surface-tension liquid, semi-solid paste, or even solid powder. The overcoming of the intrinsic high surface tension of the liquid metal with this approach unleashes the freedom to easily process the liquid metal composites into polymer composites or as direct molding processable paste and printable electronic ink.

Homogeneous solution assembled Turing structures with near zero strain semi-coherence interface

Turing structures typically emerge in reaction-diffusion processes far from thermodynamic equilibrium, involving at least two chemicals with different diffusion coefficients (inhibitors and activators) in the classic Turing systems. Constructing a Turing structure in homogeneous solutions is a large challenge because of the similar diffusion coefficients of most small molecule weight species. In this work, we show that Turing structure with near zero strain semi-coherence interfaces is constructed in homogeneous solutions subject to the diffusion kinetics. Experimental results combined with molecular dynamics and numerical simulations confirm the Turing structure in the spinel ferrite films. Furthermore, using the hard-soft acid-base theory, the design of coordination binding can improve the diffusion motion of molecules in homogeneous solutions, increasing the library of Turing structure designs, which provides a greater potential to develop advanced materials.

From the Physicochemical Characteristic of Novel Hesperetin Hydrazone to Its In Vitro Antimicrobial Aspects.

Microorganisms are able to give rise to biofilm formation on food matrixes and along food industry infrastructures or medical equipment. This growth may be reduced by the application of molecules preventing bacterial adhesion on these surfaces. A new Schiff base ligand, derivative of hesperetin, HABH (2-amino-N′-(2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene)benzohydrazide), and its copper complex, CuHABH [CuLH2(OAc)], were designed, synthesized and analyzed in terms of their structure and physicochemical properties, and tested as antibacterial agents. Their structures both in a solid state and in solution were established using several methods: FT-IR, 1H NMR, 13C NMR, UV-Vis, FAB MS, EPR, ESI-MS and potentiometry. Coordination binding of the copper(II) complex dominating at the physiological pH region in the solution was found to be the same as that detected in the solid state. Furthermore, the interaction between the HABH and CuHABH with calf-thymus DNA (CT-DNA) were investigated. These interactions were tracked by UV-Vis, CD (circular dichroism) and spectrofluorimetry. The results indicate a stronger interaction of the CuHABH with the CT-DNA than the HABH. It can be assumed that the nature of the interactions is of the intercalating type, but in the high concentration range, the complex can bind to the DNA externally to phosphate residues or to a minor/major groove. The prepared compounds possess antibacterial and antibiofilm activities against Gram-positive and Gram-negative bacteria. Their antagonistic activity depends on the factor-strain test system. The glass was selected as a model surface for the experiments on antibiofilm activity. The adhesion of bacterial cells to the glass surface in the presence of the compounds was traced by luminometry and the best antiadhesive action against both bacterial strains was detected for the CuHABH complex. This molecule may play a crucial role in disrupting exopolymers (DNA/proteins) in biofilm formation and can be used to prevent bacterial adhesion especially on glass equipment.

Distinct Binding Mechanisms for Allosteric Sodium Ion in Cannabinoid Receptors.

The therapeutic potential of cannabinoid receptors is not fully explored due to psychoactive side effects and lack of selectivity associated with orthosteric ligands. Allosteric modulators have the potential to become selective therapeutics for cannabinoid receptors. Biochemical experiments have shown the effects of the allosteric Na+ binding on cannabinoid receptor activity. However, the Na+ coordination site and binding pathway are still unknown. Here, we perform molecular dynamic simulations to explore Na+ binding in the cannabinoid receptors, CB1 and CB2. Simulations reveal that Na+ binds to the primary binding site from different extracellular sites for CB1 and CB2. A distinct secondary Na+ coordination site is identified in CB1 that is not present in CB2. Furthermore, simulations also show that intracellular Na+ could bind to the Na+ binding site in CB1. Constructed Markov state models show that the standard free energy of Na+ binding is similar to the previously calculated free energy for other class A GPCRs.

Coordination Behavior and Binding Properties of 2,6-Pyridinedimethanol with Cu(Ii), Zn(Ii), and Cd(Ii) Cations

Coordination Behavior and Binding Properties of 2,6-Pyridinedimethanol with Cu(Ii), Zn(Ii), and Cd(Ii) Cations

Phenoxy-imino ligands: coordination chemistry and binding properties with copper(II) cations

Reactions of 2-[{(2-hydroxyethyl)imino}methyl]phenol (L1) and 2-[1-{2-(diethylamino)ethylimino}ethyl]phenol (L3) with copper(II) nitrate yielded monometallic complexes [CuNO3(L1)] (1) and [CuNO3(L3)] (2), respectively. The solid-state structures of 1 and 2 confirmed the κ3-O,N,O’ and κ3-O,N,N’ tridentate binding mode of L1 and L3, respectively. The phenoxy-imino ligands 2-[{(2-hydroxyethyl)imino}methyl]phenol (L1), 2-[{(2-(diethylamino)ethylimino}-methyl]phenol (L2), 2-[1-{2-(diethylamino)ethylimino}ethyl]phenol (L3) and 2-[(2-mercaptoethylimino)methyl]phenol (L4) were also used as model chelating agents for liquid-liquid extraction of copper(II), zinc(II), cadmium(II) and lead(II) cations from water using dichloromethane as the organic solvent. The relative affinities of these chelating ligands for copper(II), zinc(II), cadmium(II) and lead(II) by liquid-liquid extraction were found to be in the order copper(II) > zinc(II) > cadmium(II) > lead(II) in line with the hard-soft acid-base interaction. The ligands L1-L4 showed extraction efficiencies ranging from 75% to 99% for copper(II), 72% to 97% for zinc(II), 64% to 87% for cadmium(II) and 51% to 74% for lead(II). The extraction protocol was successfully applied to sewage effluent.

Stoichiometry between Humate Unit Molecules and Metal Ions in Supramolecular Assembly Induced by Cu2+ and Tb3+ Measured by Gel Electrophoresis Techniques.

Humic acid (HA), a fraction of humic substances, can strongly complex with metal ions to form a supramolecular assembly via coordination binding and other intermolecular forces. However, determining the supramolecular size distribution and stoichiometry between small HA unit molecules constituting HA supramolecules and metal ions has proven to be challenging. Here, we investigated the changes in the size distributions of HAs induced by Cu2+ and Tb3+ ions using unique PAGE for the separation and quantification of HA complexes and metal ions bound, followed by UV-vis spectroscopy and excitation-emission matrix-parallel factor analysis. By determining the concentrations of HA and metal ions, it was possible to estimate the stoichiometry of the HA unit molecule to metal ions in supramolecular complexes. It was found that the supramolecular behaviors of Cu2+ and Tb3+ complexes with HA collected from peat (PAHA) and deep groundwater (HHA) differed. For example, two HHA unit molecules form a supramolecule via cross-linking by a Cu2+ ion in the case of Cu2+-HHA. Our results suggest that this supramolecular stoichiometry is related to the abundance of sulfur atoms in the elemental composition of HHA. Our experimental results and analysis provide new insights into HA supramolecules formed via metal complexation.

Suppression of Eu2+ Luminescence Loss

AbstractOwing to the intriguing luminescence properties, Eu2+ is one of the most desirable activators for next‐generation lighting devices. Yet the application of Eu2+‐doped phosphors is limited because of the drawback of inferior luminescence efficiency. Understanding of this issue is generally from perspectives of frame structural rigidity and electronic band structure, while the lack of persuasiveness of this paradigm is frequently noticed. Herein, the analysis is conducted from a fresh view to investigate the outstanding luminescence properties of Eu2+‐doped SrMgP2O7 owning the narrow‐band emission and near‐unity quantum yield. The structural rigidity of materials is elaborately evaluated, and the influence of ionization on the luminescence efficiency of material is carefully discussed. Efforts are also made to assess the effect of vibronic coupling on 4f−5d transition of Eu2+ and clarify the excitation energy transfer route by using X‐ray spectroscopy. Based on these discussions, the synergy of weak electron−vibration interaction and inactive ionization causes the suppression of Eu2+ luminescence loss, which is associated with highly rigid local coordination and strong binding of Eu2+ to its valence electrons in the system, respectively. This work provides insight into the luminescence mechanism of Eu2+, which benefits the exploration of novel phosphors with superior luminescence features.

NaFSI and NaTFSI Solutions in Ether Solvents from Monoglyme to Poly(ethylene oxide)-A Molecular Dynamics Study.

Classical molecular dynamics simulations have been performed for a series of electrolytes based on sodium bis(fluorosulfonyl)imide or sodium bis(trifluoromethylsulfonyl)imide salts and monoglyme, tetraglyme, and poly(ethylene oxide) as solvents. Structural properties have been assessed through the analysis of coordination numbers and binding patterns. Residence times for Na–O interactions have been used to investigate the stability of solvation shells. Diffusion coefficients of ions and electrical conductivity of the electrolytes have been estimated from molecular dynamics trajectories. Contributions to the total conductivity have been analyzed in order to investigate the role of ion–ion correlations. It has been found that the anion–cation interactions are more probable in the systems with NaTFSI salts. Accordingly, the degree of correlations between ion motions is larger in NaTFSI-based electrolytes.

Selective Binding and Redox-Activity on Parallel G-Quadruplexes by Pegylated Naphthalene Diimide-Copper Complexes.

G-quadruplexes (G4s) are higher-order supramolecular structures, biologically important in the regulation of many key processes. Among all, the recent discoveries relating to RNA-G4s, including their potential involvement as antiviral targets against COVID-19, have triggered the ever-increasing need to develop selective molecules able to interact with parallel G4s. Naphthalene diimides (NDIs) are widely exploited as G4 ligands, being able to induce and strongly stabilize these structures. Sometimes, a reversible NDI-G4 interaction is also associated with an irreversible one, due to the cleavage and/or modification of G4s by functional-NDIs. This is the case of NDI-Cu-DETA, a copper(II) complex able to cleave G4s in the closest proximity to the target binding site. Herein, we present two original Cu(II)-NDI complexes, inspired by NDI-Cu-DETA, differently functionalized with 2-(2-aminoethoxy)ethanol side-chains, to selectively drive redox-catalyzed activity towards parallel G4s. The selective interaction toward parallel G4 topology, controlled by the presence of 2-(2-aminoethoxy)ethanol side chains, was already firmly demonstrated by us using core-extended NDIs. In the present study, the presence of protonable moieties and the copper(II) cavity, increases the binding affinity and specificity of these two NDIs for a telomeric RNA-G4. Once defined the copper coordination relationship and binding constants by competition titrations, ability in G4 stabilization, and ROS-induced cleavage were analyzed. The propensity in the stabilization of parallel topology was highlighted for both of the new compounds HP2Cu and PE2Cu. The results obtained are particularly promising, paving the way for the development of new selective functional ligands for binding and destructuring parallel G4s.

Toward Food Freshness Monitoring: Coordination Binding-Based Colorimetric Sensor Array for Sulfur-Containing Amino Acids.

Herein, a self-assembled colorimetric chemosensor array composed of off-the-shelf catechol dyes and a metal ion (i.e., Zn2+) has been used for the sulfur-containing amino acids (SCAAs; i.e., glutathione, glutathione disulfide, L–cysteine, DL–homocysteine, and L–cystine). The coordination binding–based chemosensor array (CBSA) fabricated by a competitive assay among SCAAs, Zn2+ ions, and catechol dyes [i.e., pyrocatechol violet (PV), bromopyrogallol red (BPR), pyrogallol red (PR), and alizarin red S (ARS)] yielded fingerprint-like colorimetric changes. We succeeded in the qualification of SCAAs based on pattern recognition [i.e., a linear discrimination analysis (LDA)] with 100% correct classification accuracy. The semiquantification of reduced/oxidized forms of SCAAs was also performed based on LDA. Furthermore, we carried out a spike test of glutathione in food samples using the proposed chemosensor array with regression analysis. It is worth mentioning that we achieved a 91–110% recovery rate in real sample tests, which confirmed the accuracy of the constructed model. Thus, this study represents a step forward in assessing food freshness based on supramolecular analytical methods.

A Printed Paper-Based Anion Sensor Array for Multi-Analyte Classification: On-Site Quantification of Glyphosate.

We report a paper-based chemosensor array device (PCSAD) for the quantitative detection of oxyanions including the herbicide glyphosate (GlyP) in aqueous media. The mechanism of the oxyanion detection relies on a coordination-binding-based sensor array. In this study, the competitive coordination binding among Zn2+ , four catechol dyes, and seven oxyanions caused noticeable colour changes. The colour changes were employed for qualitative and quantitative analyses using an in-house automated image-processing algorithm with pattern recognition for digital images. A linear discrimination analysis discerned similarly structured oxyanions with 100 % accuracy. The regression analysis allowed the accurate quantification of GlyP in the herbicide products with a limit of detection of 16 mg/L, which is lower than the health advisory value for children (20 mg/L) stipulated by the environmental protection agency (EPA). PCSAD is a powerful sensor device for the on-site quantification of aqueous anions for environmental assessment.

Combination of Coordination and Releasable Covalent Binding for the Delivery of Antisense Therapeutics by Bisphosphonate-Hyaluronan-Oligonucleotide Conjugates

To address the current problems of delivery of antisense oligonucleotide (ON) therapeutics, a macromolecular platform was proposed based on the combination of metal-ion coordination and releasable covalent conjugation. Two kinds of therapeutic molecules, bisphosphonate (BP) and antisense ON, were conjugated to a natural polysaccharide hyaluronic acid (HA). The use of two linkers with a set of terminal chemoselective groups including N-hydroxysuccinimide carbonate, 2-dithiopyridyl, and aromatic aldehyde allowed orthogonal conjugation of the two therapeutics with subsequent detachment under potentially different conditions. In this work, disulfide linkages of varied steric accessibility were utilized in the linkers allowing the release of the linked therapeutics with different kinetics upon incubation in a reducing buffer. The therapeutics were conjugated to HA via their amino groups, and the self-immolative feature of the linkers permitted traceless release of both drugs as free amines. The obtained dual macromolecular prodrug was converted into either nanogels or macroscopic hydrogels upon coordination with calcium ions via Ca2+-mediated bridging of BP groups. Macroscopic hydrogels demonstrated self-healing properties which are useful for the noninvasive administration of ONs as biodegradable implants. Moreover, transformation of the macromolecular prodrug into a nanogel under dilute conditions is a useful property to prolong the circulation of the prodrug and protect antisense ON therapeutics against degradation in vivo.

Mechanisms of Cd (II) binding to GMP and UMP: a combined conductometry, isothermal titration calorimetry and NMR study

In this research, conductometry was applied as a rapid method to screen functional ligands of cadmium ion-imprinted polymers for the first time. To better understand the binding mechanisms of Cd(II) to nucleoside monophosphates (NMPs), isothermal titration calorimetry (ITC) and nuclear magnetic resonance spectroscopy (NMR) experiments were carried out. First, the magnitude of conductivity change, Δσ, was found to be proportional to the ligand’s binding capacity to cadmium, and the ΔσGMP ≈ ΔσdGMP = 103.5 μs $$\cdot $$ cm−1. Second, the ITC experiments indicated that the coordination binding of Cd(II) and guanosine monophosphate (GMP) in 4-(2-hydroxyerhyl)piperazine-1-erhanesulfonic acid (HEPES)/boric acid buffers were demonstrated as different thermodynamic process: an exothermic process (ΔH = -1.446 kcal $$\cdot $$ mol−1) in HEPES, and an exothermic process (ΔH = − 1.495 kcal $$\cdot $$ mol−1) followed by an endothermic one (ΔH = 1.383 kcal mol−1) in boric acid. In contrast, the formation of the Cd(II)–uridine monophosphate (UMP) system was an endothermic process in both buffers. NMR experiments indicated that the shift Δδ of the GMP’s proton signals were different, especially for H1: 0.37 ppm in HEPES, and 0.03 ppm in boric acid. Referring to the results of ITC experiments, the major Cd(II) binding sites of GMP in HEPES buffer was the guanosine group, and phosphate group was another site in the boric acid buffer. By contrast, the major Cd(II) binding site of UMP was the phosphate group in both buffers. In general, investigating the functional ligand–cadmium binding mechanism has provided important theoretical and experimental guidance for the subsequent preparation of cadmium ion-imprinted materials.