Ion Binding Properties Research Articles

Metal ion binding to an RNA internal loop

Studying the interaction of metal ions with RNA is challenging because of the fast dynamics of the system and the intricate interplay between structural and functional roles of metal ions. NMR spectroscopy is an exceptional tool to investigate such interactions in solution and allows for a detailed description of both metal ion binding sites and binding modes in complex and dynamic RNA structures. We recently applied heteronuclear NMR to study the metal ion binding properties of a three-way junction RNA (D1κζ) which plays an important role in group II intron splicing, and observed metal ion binding in both κ and ζ regions of the construct. Here we concentrate in more detail on the ζ region (D1ζ) using NMR to investigate the interaction with Mg(II), Cd(II) and cobalt(III)hexammine. Our data confirm Cd(II) induced macrochelate formation at the 5′-end triphosphate, suggest an overall similar behaviour for the two divalent metal ions, but with much clearer changes in chemical shifts upon Cd(II) addition, and reveal only little changes upon cobalt(III)hexammine addition, allowing to discriminate between inner- and outer-sphere binding. Moreover, we observed distinct differences when we titrated the sample with Cd(II) in the presence of either KCl or KClO4 as background monovalent salt.

Studying metal ion binding properties of a three-way junction RNA by heteronuclear NMR.

Self-splicing group II introns are highly structured RNA molecules, containing a characteristic secondary and catalytically active tertiary structure, which is formed only in the presence of Mg(II). Mg(II) initiates the first folding step governed by the κζ element within domain 1 (D1κζ). We recently solved the NMR structure of D1κζ derived from the mitochondrial group II intron ribozyme Sc.ai5γ and demonstrated that Mg(II) is essential for its stabilization. Here, we performed a detailed multinuclear NMR study of metal ion interactions with D1κζ, using Cd(II) and cobalt(III)hexammine to probe inner- and outer-sphere coordination of Mg(II) and thus to better characterize its binding sites. Accordingly, we mapped (1)H, (15)N, (13)C, and (31)P spectral changes upon addition of different amounts of the metal ions. Our NMR data reveal a Cd(II)-assisted macrochelate formation at the 5'-end triphosphate, a preferential Cd(II) binding to guanines in a helical context, an electrostatic interaction in the ζ tetraloop receptor and various metal ion interactions in the GAAA tetraloop and κ element. These results together with our recently published data on Mg(II) interaction provide a much better understanding of Mg(II) binding to D1κζ, and reveal how intricate and complex metal ion interactions can be.

Modeling of stability and properties of anionic and cationic tautomers of the 3-hydroxypyridin-4-one system

DFT, MP2, CBS-APNO, G4 and CCSD(T) calculations were performed for anionic and cationic tautomers of 3-hydroxypyridin-4-one molecule, a parent molecular system for the family of hydroxypyridinones that are known in coordination chemistry as efficient metal ions chelators. Performed calculations show that the 3-hydroxypyridin-4-one’s anion exists in the structure with one hydroxyl group (in the meta position to the nitrogen atom in the ring) and protonated nitrogen atom. Such a “protection” of the OCCO by protonation of one oxygen atom should weaken potentially strong metal ion binding properties of studied system. In the case of 3-hydroxypyridin-4-one’s cation, the most stable is the structure in which all hetero atoms, two oxygens and the nitrogen atoms, are protonated. Properties of anionic and cationic tautomers were studied using several aromaticity indices (HOMA, NICS, PDI, Iring, MCI KMCI) and population analyses (AIM, NBO and GAPT methods). The AIM methodology was also used for determination of hydrogen bond properties and integration of atomic energies. Results served by these methods were used to explain the energetical orders of anionic and cationic tautomers. Changes in atomic charges upon protonation and deprotonation are also discussed.

Correction: Metal ion binding properties of a bimodal triazolyl-functionalized calix[4]arene on a multi-array microcantilever system. Synthesis, fluorescence and DFT computation studies

Correction for ‘Metal ion binding properties of a bimodal triazolyl-functionalized calix[4]arene on a multi-array microcantilever system. Synthesis, fluorescence and DFT computation studies’ by Abdullah N. Alodhayb et al., RSC Adv., 2016, 6, 4387–4396.

Ion-binding properties of a K+ channel selectivity filter in different conformations

K(+) channels are membrane proteins that selectively conduct K(+) ions across lipid bilayers. Many voltage-gated K(+) (KV) channels contain two gates, one at the bundle crossing on the intracellular side of the membrane and another in the selectivity filter. The gate at the bundle crossing is responsible for channel opening in response to a voltage stimulus, whereas the gate at the selectivity filter is responsible for C-type inactivation. Together, these regions determine when the channel conducts ions. The K(+) channel from Streptomyces lividians (KcsA) undergoes an inactivation process that is functionally similar to KV channels, which has led to its use as a practical system to study inactivation. Crystal structures of KcsA channels with an open intracellular gate revealed a selectivity filter in a constricted conformation similar to the structure observed in closed KcsA containing only Na(+) or low [K(+)]. However, recent work using a semisynthetic channel that is unable to adopt a constricted filter but inactivates like WT channels challenges this idea. In this study, we measured the equilibrium ion-binding properties of channels with conductive, inactivated, and constricted filters using isothermal titration calorimetry (ITC). EPR spectroscopy was used to determine the state of the intracellular gate of the channel, which we found can depend on the presence or absence of a lipid bilayer. Overall, we discovered that K(+) ion binding to channels with an inactivated or conductive selectivity filter is different from K(+) ion binding to channels with a constricted filter, suggesting that the structures of these channels are different.

Calcium ion binding properties and the effect of phosphorylation on the intrinsically disordered Starmaker protein.

Starmaker (Stm) is an intrinsically disordered protein (IDP) involved in otolith biomineralization in Danio rerio. Stm controls calcium carbonate crystal formation in vivo and in vitro. Phosphorylation of Stm affects its biomineralization properties. This study examined the effects of calcium ions and phosphorylation on the structure of Stm. We have shown that CK2 kinase phosphorylates 25 or 26 residues in Stm. Furthermore, we have demonstrated that Stm's affinity for calcium binding is dependent on its phosphorylation state. Phosphorylated Stm (StmP) has an estimated 30 ± 1 calcium binding sites per protein molecule with a dissociation constant (KD) of 61 ± 4 μM, while the unphosphorylated protein has 28 ± 3 sites and a KD of 210 ± 22 μM. Calcium ion binding induces a compaction of the Stm molecule, causing a significant decrease in its hydrodynamic radius and the formation of a secondary structure. The screening effect of Na(+) ions on calcium binding was also observed. Analysis of the hydrodynamic properties of Stm and StmP showed that Stm and StmP molecules adopt the structure of native coil-like proteins.

Scorpion toxins prefer salt solutions.

There is a wide variety of ion channel types with various types of blockers, making research in this field very complicated. To reduce this complexity, it is essential to study ion channels and their blockers independently. Scorpion toxins, a major class of blockers, are charged short peptides with high affinities for potassium channels. Their high selectivity and inhibitory properties make them an important pharmacological tool for treating autoimmune or nervous system disorders. Scorpion toxins typically have highly charged surfaces and-like other proteins-an intrinsic ability to bind ions (Friedman J Phys Chem B 115(29):9213-9223, 1996; Baldwin Biophys J 71(4):2056-2063, 1996; Vrbka et al. Proc Natl Acad Sci USA 103(42):15440-15444, 2006a; Vrbka et al. J Phys Chem B 110(13):7036-43, 2006b). Thus, their effects on potassium channels are usually investigated in various ionic solutions. In this work, computer simulations of protein structures were performed to analyze the structural properties of the key residues (i.e., those that are presumably involved in contact with the surfaces of the ion channels) of 12 scorpion toxins. The presence of the two most physiologically abundant cations, Na(+) and K(+), was considered. The results indicated that the ion-binding properties of the toxin residues vary. Overall, all of the investigated toxins had more stable structures in ionic solutions than in water. We found that both the number and length of elements in the secondary structure varied depending on the ionic solution used (i.e., in the presence of NaCl or KCl). This study revealed that the ionic solution should be chosen carefully before performing experiments on these toxins. Similarly, the influence of these ions should be taken into consideration in the design of toxin-based pharmaceuticals.

Dimension-Controlled Assemblies Comprising π-Electronic Systems.

Dimension-Controlled Assemblies Comprising π-Electronic Systems.

Meso-piperidine calix[4]pyrrole: synthesis, structure and ion binding studies

We report the synthesis, structure and preliminary solution phase ion binding properties of the calix[4]pyrrole 3a–c. Calix[4]pyrrole 3a and 3b, the first to be prepared via one-pot reaction, were obtained by reacting the ketone 7 with pyrrole in the presence of an acid catalyst. On the basis of 1H NMR spectroscopic analyses and the titrations of UV spectrophotometry, it was concluded that compound 3a possesses significantly enhanced selectivity for fluoride anion in chloroform, and formes 1:1 (ligand: anion) complexes with fluoride and chloride anions.

Complexation and Adsorption Studies of 27-Membered Dioxadiazapentathia Macrocycles with Some Transition Metals

The metal ion-binding properties of two 27-membered macrocycles with N2S5O2 donor atoms 1 and 2 were investigated using solvent extraction experiments. In order to explain complexation behavior of macrocycles, extraction of ions in the interfacial region of liquid-liquid phase was modeled by Langmuir adsorption isotherm. The macrocycles 1 and 2 extracted Ag+ metal ion up to 95% to the dichloromethane and chloroform phase effectively. The Ag+ ion adsorption capacities of macrocycles 1 and 2 were obtained as 75% and 98% at 20°C, respectively.

Resurfaced fluorescent protein as a sensing platform for label-free detection of copper(II) ion and acetylcholinesterase activity.

Protein engineering by resurfacing is an efficient approach to provide new molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new variant of green fluorescent protein (GFP) containing 39 histidine residues in the primary sequence that was developed by protein resurfacing. Herein, taking H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+) sensing was developed based on the unique multivalent metal ion-binding property of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further applied for the turn-on fluorescence detection of acetylcholinesterase (AChE) activity. The assay was based on the reaction between Cu(2+) and thiocholine, the hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening inhibitors of AChE. Furthermore, the practicability of this method was demonstrated by the detection of pesticide residue (carbaryl) in real food samples. Hence, the successful applications of H39GFP in the detection of metal ion and enzyme activity present the prospect of resurfaced proteins as versatile biosensing platforms.

Introduction of luminescent rhenium(i), ruthenium(ii), iridium(iii) and rhodium(iii) systems into rhodamine-tethered ligands for the construction of bichromophoric chemosensors

Several classes of luminescent transition metal complexes, including rhenium(I) tricarbonyl diimine, ruthenium(II) diimine, cyclometallated iridium(III) and rhodium(III) diimine, as well as ruthenium(II) and iridium(III) terpyridine systems, tethered with rhodamine moieties, have been synthesized and characterized. The X-ray crystal structure of one cyclometallated rhodium(III) diimine (11) with a rhodamine pendant was determined. Most of the complexes were found to exhibit emission in fluid solution at room temperature. Depending on the nature of the transition metal system, the emission origin was mainly assigned to be derived from the triplet excited state of the metal-to-ligand charge transfer ((3)MLCT) or the intraligand ((3)IL) transition. The cation-binding properties of these complexes toward various cations were investigated by electronic absorption and emission spectroscopy. Some of them were found to exhibit new low-energy absorption and emission bands, attributed to the ring opening of the rhodamine moiety, with high selectivity and/or high sensitivity for various cations, in agreement with sensing and spectroscopic behaviours of the rhodamine derivative. Depending on the nature of the transition metal centres, the chelating ligands as well as the linker to the rhodamine derivative, different sensing properties in terms of selectivity, sensitivity and binding stability, could be obtained.

Synthesis, characterization, and metal extraction studies of a new macrobicyclic ligand

This article describes the synthesis, characterization, and metal ion binding properties of a new macrobicyclic ligand. Solvent extraction experiments were performed in order to determine the extraction behavior of new macrobicyclic ligand towards selected metal cations. Selective extraction of heavy metals and precious metals is highly demanded due to their toxicity and commercial importance. Based on our experimental results, macrobicyclic ligand 3 demonstrated remarkable anity towards the Ag + ion by 96.7% and 96.9% to the dichloromethane and chloroform phases, respectively. The extraction experiments with macrobicyclic ligand 3 for the Ag + ion were repeated at dierent temperatures to calculate thermodynamic parameters. The negative values of thermodynamic parameters indicated that the formation of complex during solvent extraction was an exothermic process.

Synthesis, Characterization with Photophysical and Ion Binding Properties of Ruthenium Complex

Synthesis, Characterization with Photophysical and Ion Binding Properties of Ruthenium Complex

Synthesis of metal-free and metallophthalocyanines containing 18- and 21-membered macrocycles with mixed donor atoms and their metal-ion binding properties

This paper describes the synthesis of a series of metal-free phthalocyanines and metallophthalocyanines peripherally substituted by macrocycles of different ring sizes with the same donor atom sets. The effects of varying ring size of the macrocycle on the spectroscopic and metal ion binding properties of phthalocyanines were examined. For these purposes, electronic absorption properties for metal-free phthalocyanines and metallophthalocyanines were studied in dimethylformamide and tetrahydrofuran. The liquid-liquid extraction of metal picrates such as Ag(I), Hg(II), Cd(II), Zn(II), Cu(II), Ni(II), Pb(II), and Co(II) from the aqueous phase to the organic phase was carried out using metallophthalocyanines. All new compounds were characterized using several spectroscopic techniques.

Physicochemical and ion-binding properties of highly aliphatic humic substances extracted from deep sedimentary groundwater.

Humic substances (HSs) are ubiquitous in various aquatic systems and play important roles in many geochemical processes. There is increasing evidence of the presence of HSs in deep groundwater; nevertheless, their ion binding properties are largely unknown. In this study we investigated the physicochemical and ion-binding properties of humic and fulvic acids extracted from deep sedimentary groundwater. The binding isotherms of protons (H(+)) and copper (Cu(2+)) were measured by potentiometry and fitted to the NICA-Donnan model, and the obtained parameters were compared with the generic parameters of the model, which are the average parameters for HSs from surface environments. The deep groundwater HSs were different from surface HSs, having high aliphaticities, high sulfur contents, and small molecular sizes. Their amounts of acidic functional groups were comparable to or slightly larger than those of surface HSs; however, the magnitude of Cu(2+) binding to the deep groundwater HSs was smaller. The NICA-Donnan model attributed this to the binding of Cu(2+) to chemically homogeneous low affinity sites, which presumably consist of carboxylic groups, via mono-dentate coordination at relatively low pH. The binding mode tended to shift to multi-dentate coordination with carboxylic groups and more heterogeneous alcoholic/phenolic groups at higher pH. X-ray absorption spectroscopy also revealed that Cu(2+) binds to O/N containing functional groups and to a lesser extent S containing functional groups as its divalent from. This study shows the particularity of the deep groundwater HSs in terms of their physicochemical and ion-binding properties, compared with surface HSs.

The conserved potassium channel filter can have distinct ion binding profiles: structural analysis of rubidium, cesium, and barium binding in NaK2K.

Potassium channels are highly selective for K(+) over the smaller Na(+). Intriguingly, they are permeable to larger monovalent cations such as Rb(+) and Cs(+) but are specifically blocked by the similarly sized Ba(2+). In this study, we used structural analysis to determine the binding profiles for these permeant and blocking ions in the selectivity filter of the potassium-selective NaK channel mutant NaK2K and also performed permeation experiments using single-channel recordings. Our data revealed that some ion binding properties of NaK2K are distinct from those of the canonical K(+) channels KcsA and MthK. Rb(+) bound at sites 1, 3, and 4 in NaK2K, as it does in KcsA. Cs(+), however, bound predominantly at sites 1 and 3 in NaK2K, whereas it binds at sites 1, 3, and 4 in KcsA. Moreover, Ba(2+) binding in NaK2K was distinct from that which has been observed in KcsA and MthK, even though all of these channels show similar Ba(2+) block. In the presence of K(+), Ba(2+) bound to the NaK2K channel at site 3 in conjunction with a K(+) at site 1; this led to a prolonged block of the channel (the external K(+)-dependent Ba(2+) lock-in state). In the absence of K(+), however, Ba(2+) acts as a permeating blocker. We found that, under these conditions, Ba(2+) bound at sites 1 or 0 as well as site 3, allowing it to enter the filter from the intracellular side and exit from the extracellular side. The difference in the Ba(2+) binding profile in the presence and absence of K(+) thus provides a structural explanation for the short and prolonged Ba(2+) block observed in NaK2K.

Bichromophoric rhodamine-rhenium(I) and -iridium(III) sensory system: Synthesis, characterizations, photophysical and selective metal ions binding studies

A new class of rhenium(I) tricarbonyl diimine complexes containing rhodamine derivative as a sensory moiety, have been synthesized and characterized. Their photophysical and selective ion-binding properties have also been investigated, with the comparison of the previously reported cyclometalated iridium(III) system. One of the complex was found to exhibit selective binding toward Hg(II) ion with electronic absorption and emission spectral changes. On the other hand, the iridium(III) complexes were found to give similar electronic absorption response but different emission spectral changes upon addition of Hg(II) ion. Interestingly, efficient intramolecular energy transfer from rhodamine 6G to the cyclometalated iridium(III) moiety was suggested in one of the complexes, which could be modulated by selective ion-binding process upon ring-opening of rhodamine 6G. This report shows that the modification of rhodamine derivatives and the choice of transition metal ion could be important to influence the selective binding properties for development of colorimetric and/or luminescent probe.

Ion Binding Energies Determining Functional Transport of ClC Proteins

The ClC-type proteins, a large family of chloride transport proteins ubiquitously expressed in biological organisms, have been extensively studied for decades. Biological function of ClC proteins can be reflected by analyzing the binding situation of Cl− ions. We investigate ion binding properties of ClC-ec1 protein with the atomic molecular dynamics simulation approach. The calculated electrostatic binding energy results indicate that Cl− at the central binding site Scen has more binding stability than the internal binding site Sint. Quantitative comparison between the latest experimental heat release data isothermal titration calorimetry (ITC) and our calculated results demonstrates that chloride ions prefer to bind at Scen than Sint in the wild-type ClC-ec1 structure and prefer to bind at Sext and Scen than Sint in mutant E148A/E148Q structures. Even though the chloride ions make less contribution to heat release when binding to Sint and are relatively unstable in the Cl− pathway, they are still part contributors for the Cl− functional transport. This work provides a guide rule to estimate the importance of Cl− at the binding sites and how chloride ions have influences on the function of ClC proteins.

Synthesis, characterization, and ion-complexing properties of polymers displaying densely packed arrays of crown-ethers as lateral substituents

We report the synthesis and ion-binding properties of four poly(crown-ethers) displaying either one or two crown-ethers (15-crown-5 or 18-crown-6) on every third carbon alongside the backbone. The polymers were synthesized by living anionic ring-opening polymerization of disubstituted cyclopropane-1,1-dicarboxylates monomers. Cation binding of the polychelating polymers and corresponding monomers to Na+ and K+ was evaluated by picrate extraction and isothermal calorimetry titration. This novel family of poly(crown-ethers) demonstrated excellent initial binding of the alkali ions to the polymers, with a higher selectivity for potassium. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2337–2345