Acid-base and metal-ion binding properties of the RNA dinucleotide uridylyl-(5'-->3')-[5']uridylate (pUpU3-)

It is well known that Mg2+ and other divalent metal ions bind to the phosphate groups of nucleic acids. Subtle differences in the coordination properties of these metal ions to RNA, especially to ribozymes, determine whether they either promote or inhibit catalytic activity. The ability of metal ions to coordinate simultaneously with two neighboring phosphate groups is important for ribozyme structure and activity. However, such an interaction has not yet been quantified. Here, we have performed potentiometric pH titrations to determine the acidity constants of the protonated dinucleotide H2(pUpU)-, as well as the binding properties of pUpU3- towards Mg2+, Mn2+, Cd2+, Zn2+, and Pb2+. Whereas Mg2+, Mn2+, and Cd2+ only bind to the more basic 5'-terminal phosphate group, Pb2+, and to a certain extent also Zn2+, show a remarkably enhanced stability of the [M(pUpU)]- complex. This can be attributed to the formation of a macrochelate by bridging the two phosphate groups within this dinucleotide by these metal ions. Such a macrochelate is also possible in an oligonucleotide, because the basic structural units are the same, despite the difference in charge. The formation degrees of the macrochelated species of [Zn(pUpU)]- and [Pb(pUpU)]- amount to around 25 and 90 %, respectively. These findings are important in the context of ribozyme and DNAzyme catalysis, and explain, for example, why the leadzyme could be selected in the first place, and why this artificial ribozyme is inhibited by other divalent metal ions, such as Mg2+.     

Water-Soluble Polyacids with Capability to Remove Metal Ions in Homogenous Phase by Using the Liquid Phase Polymer-Based Retention Technique

Water-soluble polymers containing carboxylic acid and sulfonic acid groups were investigated as polychelatogens under different experimental conditions in view to study their metal ion binding properties, using the liquid-phase polymer-based retention technique. The divalent metal ions investigated were: Co²⁺, Cu²⁺, Zn²⁺, and Cd²⁺. When the pH increased above 3, and especially at pH 5, metal ion retention capability increased as the majority of the functional groups are carboxylate, which can form more stable complexes with the metal ions. The retention capability also depended on the structure of the polyacid and the filtration factor, Z.     

ACE applied to the quantitative characterization of benzo‐18‐crown‐6‐ether binding with alkali metal ions in a methanol–water solvent system

ACE was applied to the quantitative evaluation of noncovalent binding interactions between benzo‐18‐crown‐6‐ether (B18C6) and several alkali metal ions, Li⁺, Na⁺, K⁺, Rb⁺ and Cs⁺, in a mixed binary solvent system, methanol–water (50/50 v/v). The apparent binding (stability) constants (K_b) of B18C6–alkali metal ion complexes in the hydro‐organic medium above were determined from the dependence of the effective electrophoretic mobility of B18C6 on the concentration of alkali metal ions in the BGE using a nonlinear regression analysis. Before regression analysis, the mobilities measured by ACE at ambient temperature and variable ionic strength of the BGE were corrected by a new procedure to the reference temperature, 25°C, and the constant ionic strength, 10 mM . In the 50% v/v methanol–water solvent system, like in pure methanol, B18C6 formed the strongest complex with potassium ion (log K_b=2.89±0.17), the weakest complex with cesium ion (log K_b=2.04±0.20), and no complexation was observed between B18C6 and the lithium ion. In the mixed methanol–water solvent system, the binding constants of the complexes above were found to be about two orders lower than in methanol and about one order higher than in water.     

Complexation of divalent metal ions with diols in the presence of anion auxiliary ligands: zinc‐induced oxidation of ethylene glycol to glycolaldehyde by consecutive hydride ion and proton shifts

Ternary complexes of the type AH???M²⁺???L^– (AH = diol, including diethylene and triethylene glycol, M = Ca, Mn, Fe, Co, Ni, Cu and Zn and auxiliary anion ligand L^– = CH₃COO^–, HCOO^– and Cl^–) have been generated in the gas phase by MALDI and ESI, and their dissociation characteristics have been obtained. Use of the auxiliary ligands enables the complexation of AH with the divalent metal ion without AH becoming deprotonated, although A^–???M²⁺ is often also generated in the ion source or after MS/MS. For M = Ca, dissociation occurs to AH + M²⁺???L^– and/or to A^–???M²⁺ + LH, the latter being produced from the H‐shifted isomer A^–???M²⁺???LH. For a given ligand L^–, the intensity ratio of these processes can be interpreted (barring reverse energy barriers) in terms of the quantity PA(A^–) – Ca_aff(A^–), where PA is the proton affinity and Ca_aff is the calcium ion affinity. Deuterium labeling shows that the complex ion HOCH₂CH₂OH???Zn²⁺???^–OOCCH₃, in addition to losing acetic acid (60 Da), also eliminates glycolaldehyde (HOCH₂CH=O, also 60 Da); it is proposed that these reactions commence with a hydride ion shift to produce the ion–dipole complex HOCH₂CHOH⁺??? HZnOOCCH₃, which then undergoes proton transfer and dissociation to HOCH₂CH=O + HZn⁺???O = C(OH)CH₃. In this reaction, ethylene glycol is oxidized by consecutive hydride ion and proton shifts. A minor process leads to loss of the isomeric species HOCH=CHOH. Copyright © 2012 John Wiley & Sons, Ltd.     

Competitive binding exchange between alkali metal ions (K+, Rb+, and Cs+) and Na+ ions bound to the dimeric quadruplex [d(G4T4G4)]2: a 23Na and 1H NMR study

A comparative study of the competitive cation exchange between the alkali metal ions K⁺, Rb⁺, and Cs⁺ and the Na⁺ ions bound to the dimeric quadruplex [d(G₄T₄G₄)]₂ was performed in aqueous solution by a combined use of the ²³Na and ¹H NMR spectroscopy. The titration data confirm the different binding affinities of these ions for the G‐quadruplex and, in particular, major differences in the behavior of Cs⁺ as compared to the other ions were found. Accordingly, Cs⁺ competes with Na⁺ only for the binding sites at the quadruplex surface (primarily phosphate groups), while K⁺ and Rb⁺ are also able to replace sodium ions located inside the quadruplex. Furthermore, the ¹H NMR results relative to the CsCl titration evidence a close approach of Cs⁺ ions to the phosphate groups in the narrow groove of [d(G₄T₄G₄)]₂. Based on a three‐site exchange model, the ²³Na NMR relaxation data lead to an estimate of the relative binding affinity of Cs⁺ versus Na⁺ for the quadruplex surface of 0.5 at 298 K. Comparing this value to those reported in the literature for the surface of the G‐quadruplex formed by 5′‐guanosinemonophosphate and for the surface of double‐helical DNA suggests that topology factors may have an important influence on the cation affinity for the phosphate groups on DNA. Copyright © 2009 John Wiley & Sons, Ltd.     

Structure–Activity Studies on the Fluorescent Indicator in a Displacement Assay for the Screening of Small Molecules Binding to RNA

A series of xanthone and thioxanthone derivatives with aminoalkoxy substituents were synthesized as fluorescent indicators for a displacement assay in the study of small‐molecule–RNA interactions. The RNA‐binding properties of these molecules were investigated in terms of the improved binding selectivity to the loop region in the RNA secondary structure relative to 2,7‐bis(2‐aminoethoxy)xanthone (X2S) by fluorimetric titration and displacement assay. An 11‐mer double‐stranded RNA and a hairpin RNA mimicking the stem loop IIB of Rev response element (RRE) RNA of HIV‐1 mRNA were used. The X2S derivatives with longer aminoalkyl substituents showed a higher affinity to the double‐stranded RNA than the parent molecule. Introduction of a methyl group on the aminoethoxy moiety of X2S effectively modulated the selectivity to the RNA secondary structure. Methyl group substitution at the C1′ position suppressed the binding to the loop regions. Substitution with two methyl groups on the amino nitrogen atom resulted in reducing the affinity to the double‐stranded region by a factor of 40 %. The effect of methyl substitution on the amino nitrogen atom was also observed for a thioxanthone derivative. Titration experiments, however, suggested that thioxanthone derivatives showed a more prominent tendency of multiple binding to RNA than xanthone derivatives. The selectivity index calculated from the affinity to the double‐stranded and loop regions suggested that the N,N‐dimethyl derivative of X2S would be suitable for the screening of small molecules binding to RRE.     

Bio‐inspired iron/sulfur/graphene nanocomposite and its use in the catalysis of the oxygen reduction reaction at room temperature in alkaline media on a glassy carbon electrode

This work demonstrates the performance of a bio‐inspired iron/sulfur/graphene nanocomposite as a non‐platinum electrocatalyst for the oxygen reduction reaction (ORR) in an alkaline medium. The catalyst shows the most positive ORR onset potential (1.1 V vs. RHE) according to its unique structure in the alkaline medium (KOH solution, pH = 13) at low temperature (T = 298 K). The catalyst is evaluated by the rotating‐disk electrode (RDE) method under various rotating speeds (0–2,000 rpm) in the potential range ?0.02–1.18 V vs. a rechargeable hydrogen electrode (RHE). The number of transferred electrons, as one of the most important parameters, is almost constant over a wide range of potentials (0.1–0.8 V), which indicates a more efficient four‐electron pathway from O₂ to H₂O on the FePc‐S‐Gr surface. The mean size of catalyst centers are in the nanoscale (<10 nm). The estimated Tafel slope in the appropriate range is about ?110 mV per decade at low current density, and E_1/2 of FePc‐S‐Gr displays a negative shift of only 7.1 mV after 10,000 cycles.     

Comparison of the capacity of nitrogen, oxygen, sulfur, and selenium atoms to exist in onium states. quantum-chemical investigation of isomeric model systems with two heteroatoms

HF, B3LYP, and MP2 calculations with the 6-31+G(d) basis set with correction to the energy of zero-point vibrations were carried out to determine the energy characteristics of model molecules containing two heteroatoms in the sp ³- and sp ²-hybrid states; different combinations of N, O, S, and Se atoms were studied. The stability of the onium states of the nitrogen atom was found to be greater than for its chalcogen analogs and the relative stability of onium states of the chalcogen analogs was found to depend on the hybridization of these atoms. Analysis of these results permitted us to construct a stability series of onium derivatives and to interpret the positional selectivity in electrophilic substitution reactions of five-membered heterocyclic compounds with one heteroatom. To J. Stradins, an outstanding and tireless scientist, with our deep respect and sincere affection. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1801–1808, December, 2008.     

Selective reduction of aqueous protons to hydrogen with a synthetic cobaloxime catalyst in the presence of atmospheric oxygen

Protons preferred: A cobalt catalyst is reported that evolves H(2) electro- and photocatalytically at room temperature, in pH-neutral water, and in the presence of atmospheric O(2) . The catalyst shows respectable Faradaic efficiencies under N(2) and 21?% O(2) in N(2) , and can be used under both homogeneous and heterogeneous conditions.     

Limiting current to a rotating disk electrode modified with an electroactive polymeric film in the presence of a redox pair in the adjacent solution volume

Expressions for the limiting current to a rotating disk electrode modified by a conductive polymeric film are obtained for different localization of a redox process that involves redox species in the bulk of the adjacent solution. For an electrode reaction on the modifying film surface, it is shown that the dependence of the limiting current on the bulk concentration of reacting species is described by a curve with saturation. Such a limitation does not arise for a reaction on the electrode substrate. This can serve as a criterion in location of the reaction zone. In addition, other possible prospects of the use of a rotating disk in studying the charge transfer in electroactive polymeric films are discussed.     

An aqueous thermodynamic model for a high valence 4∶2 electrolyte Th4+−SO 4 2− in the system Na+−K+−Li+−NH 4 + −Th4+−SO 4 2− −HSO 4 − −H2O to high concentration

An aqueous thermodynamic model that is valid from zero to high concentration is proposed for the Na⁺–K⁺–Li⁺–NH ₄ ⁺ –Th⁴⁺–SO ₄ ^2– –HSO ₄ ^– –H₂O system. The model is based on the aqueous ion-interaction model of Pitzer and coworkers. The thorium sulfate complex species Th(SO₄)₂(aq) and Th(SO₄) ₃ ^2– are also included in the model. The final thermodynamic model presented here accurately predicts all reliable thermodynamic data, including solvent extraction and solubility data, for the Na⁺–K⁺–Li⁺–NH ₄ ⁺ –Th⁴⁺–SO ₄ ^2– –HSO ₄ ^– –H₂O system to high concentration. The aqueous thermodynamics of high-valence (3:2, 4:2), electrolytes are complicated by very strong specific ion interactions or ion pairing in dilute solution and by an effective redissociation of aqueous complex species at high concentration. Methods of treating these complications, in terms of valid aqueous thermodynamic models, are discussed in detail for the high-valence Th⁴⁺–SO ₄ ^2– –H₂O system.     

Catalytic Oxidation of Alcohols to Corresponding Aldehydes or Ketones with TEMPO-Mediated Iodosobenzene in Water in the Presence of a Surfactant

An efficient, facile, and rapid oxidation of alcohols to the corresponding aldehydes or ketones with a stoichiometric amount of iodosobenzene (PhIO) in the presence of catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxyl free radical (TEMPO), KBr, and a surfactant, such as SDS (sodium dodecylsulfate), was reported. The oxidation proceeded in water at room temperature to afford aldehydes or ketones in excellent yields and high selectivity without overoxidation to carboxylic acids. Selective oxidation of primary alcohols in the presence of secondary alcohols was also achieved with the catalytic system of PhIO/TEMPO/KBr/SDS. A possible mechanism for the oxidation was supposed.     

Highly selective fenuron-imprinted polymer with a homogeneous binding site distribution prepared by precipitation polymerisation and its application to the clean-up of fenuron in plant samples

In the present study, two different imprinted polymers were synthesised by precipitation polymerisation using methacrylic acid (MAA) or 4-vinylpyridine (VP) as monomer and fenuron (FEN, a phenylurea herbicide) as template. After template removal, their ability to recognise fenuron was evaluated and the optimum loading, washing and elution conditions were established. From this study, it was concluded that imprinted binding sites were not formed in the vinylpyridine-based polymer. However, methacrylic acid-based polymer was able to recognise fenuron with high affinity and to selectively retain it from a mixture of several phenylurea herbicides. In addition, different rebinding experiments were carried out and the experimental binding isotherms were fitted to the Langmuir-Freundlich (LF) isotherm in order to assess the binding site distribution. It was concluded that the methacrylic acid-based polymer possesses a homogeneous binding site distribution and permits to achieve quantitative recoveries in a wide concentration range in molecularly imprinted solid-phase extraction (MISPE) processes. The developed MISPE procedure using methacrylic acid-based polymeric micro-spheres was evaluated for the trace-enrichment and clean-up of fenuron from plant sample extracts.     

Synthesis of tri- or tetrasubstituted pyrimidine derivatives through the [5+1] annulation of enamidines with either N,N-dimethylformamide dialkyl acetals or orthoesters and their application in a ring transformation of pyrimidines to pyrido[2,3-d]pyrimidin-5-one derivatives

The [5+1] annulation of enamidines, which were prepared from functionalized silanes, organolithium compounds and two nitriles, with N,N-dimethylformamide dialkyl acetals as the C1 unit is described, leading to the synthesis of tri- and tetrasubstituted pyrimidine derivatives under catalyst- and solvent-free reaction conditions. Furthermore, the [5+1] annulation of enamidines by using orthoesters as the C1 unit is described, in which catalytic amounts of ZnBr(2) catalyze the annulation to produce polysubstituted pyrimidines under toluene or xylene reflux conditions. Moreover, the combination of a reductive ring-opening reaction with [Mo(CO)(6)] and a subsequent intramolecular cyclization with tBuOK effectively causes a skeletal transformation from the pyrimidines containing an isoxazolyl and an ethoxy substituent to form pyrido[2,3-d]pyrimidin-5-one frameworks in excellent yield.     

Influence of alkali and alkaline earth ions on the O -alkylation of the lower rim phenolic-OH groups of p-tert -butyl-calix[4]arene to result in amide-pendants: Template action of K+ and the structure of K+ bound tetra-amide derivative crystallized with a p-tert -butyl-calix[4]arene anion

Role of alkali and alkaline earth ions on the formation of calix[4]arene-amide derivatives through O-alkylation of the lower rim phenolic-OH groups in general and template action of K⁺ in particular have been explored. Na⁺ and K⁺ ions among alkali, and Ca²⁺ and Sr²⁺ ions among alkaline earth have shown tetra-amide derivatives bound to metal ion species. Among all these, potassium salts act as template and yields a K⁺ bound tetra-amide derivative where the charge is counter balanced by a calix[4] arene-monoanion and the product is crystallographically characterized. Change in the amide precursor used in these O-alkylation reactions has no effect on the type of the amide derivative formed. Also demonstrated is a direct one-step reaction for the preparation of 1,3-di-amide derivative in high yield and low reaction period using CsHCO₃.