Affinity,Speciation, and Molecular Features of Copper(II) Complexes with a Prion Tetraoctarepeat Domain in Aqueous Solution: Insights into Old and New Results

Characterization of the copper(II) complexes formed with the tetraoctarepeat peptide at low and high metal‐to‐ligand ratios and in a large pH range, would provide a breakthrough in the interpretation of biological relevance of the different metal complexes of copper(II)‐tetraoctarepeat system. In the present work, the potentiometric, UV/Vis, circular dichroism (CD), and electron paramagnetic resonance (EPR) studies were carried out on copper(II) complexes with a PEG‐ylated derivative of the tetraoctarepeats peptide sequence (Ac‐PEG₂₇‐(PHGGGWGQ)₄‐NH₂) and the peptide Ac‐(PHGGGWGQ)₂‐NH₂. Conjugation of tetraoctarepeat peptide sequence with polyethyleneglycol improved the solubility of the copper(II) complexes. The results enable a straightforward explanation of the conflicting results originated from the underestimation of all metal–ligand equilibria and the ensuing speciation. A complete and reliable speciation is therefore obtained with the released affinity and binding details of the main complexes species formed in aqueous solution. The results contribute to clarify the discrepancies of several studies in which the authors ascribe the redox activity of copper(II)‐tetraoctarepeat system considering only the average effects of several coexisting species with very different stoichiometries and binding modes.     

Multinuclear NMR studies of the interaction of metal ions with adenine-nucleotides

It is well-known that metal ion complexes are essential in various biological systems, including those with adenosine nucleotides which are substrates for a large number of enzymatic processes. The interactions of various metal ions with adenosine nucleotides have been intensively studied by multinuclear NMR spectroscopy. Nucleotides are polydentate ligands with various potential binding sites, including nitrogen atoms on the purine base, hydroxyl groups on the ribose sugar, and negatively charged oxygen atoms in the phosphate group. Depending on the experimental conditions (e.g. pH, concentration range, etc.) and on the size and nature of the metal ions, monodentate, or multidentate coordination to these donor atoms are possible. The review focuses on the applications of different NMR techniques in identifying the stoichiometry and the mode of metal binding in complexes formed with the most important adenosine nucleotides, like adenosine-5′-mono-, di- and triphosphates (AMP, ADP and ATP). Ligand exchange dynamics for some metal ion complexes are also presented.     

Study of noncovalent enzyme—inhibitor complexes and metal binding stoichiometry of matrilysin by electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry (ESI-MS) was used to study the noncovalent metallo-enzyme—inhibitor complexes of matrilysin (a matrix metalloproteinase of mass 18,720 u) under gentle experimental conditions and to determine the metal ion association stoichiometries in both the free enzyme and the complexes. The metal association stoichiometries of the free matrilysin were found to be highly sensitive to solution pH changes. At pH 2.2 the enzyme existed as metal-free apo-matrilysin and was not capable of binding an inhibitor. At pH 4.5–7.0 the enzyme associated specifically with zinc and calcium cations and became active in inhibitor binding. Although the stoichiometries of the metal cofactors varied (zero to two zinc and/or calcium ions) in the free enzyme dependent on solution pH, the predominant form of the enzyme—inhibitor complexes in the pH range of 4.5–7.0, in contrast, always had the metal association stoichiometry of 2Zn + 2Ca, which was the same stoichiometry the most active free metallo-enzyme had at the optimal pH of 7. At the activity onset pH of 4.5 matrilysin existed mostly as apo-enzyme (but in a conformation different from the denatured one at pH 2.2) and bound to an inhibitor slowly (time constant ～ 2.5 min) to form the noncovalent metallo-enzyme—inhibitor complex. Of the two inhibitors studied, the one with the higher solution binding constant also produced larger ion signals for the noncovalent complex in the solvent-free gas phase, which pointed to the feasibility of the use of ESI-MS for inhibitor screening studies.     

The effects of 1-hydroxyethane-(1,1-diphosphonic acid) on the adsorptive partitioning of metal ions onto gamma-AlOOH

1-Hydroxyethane-(1,1-diphosphonic acid) (HEDP) is extensively used in many technical applications. This work, as a first stage, examines the adsorption of aqueous HEDP, Cu(II), and Zn(II) onto boehmite (gamma-AlOOH) as single solutes. These processes can be described by the formation of inner-sphere complexes by the surface complexation model with constant capacitance. Uncomplexed HEDP is adsorbed as a mononuclear complex over the entre pH range. Four mononuclear surface complexes with different protonation levels are required to obtain a good fit of the experimental data for the pH range studied. Cu(II)- and Zn(II)-HEDP complexes at equimolar concentrations are studied at high and low surface density. The results indicate that the presence of HEDP significantly promotes metal adsorption at low pH in defects of surface sites. However, metal adsorption exhibits the same trend in the absence and presence of HEDP when the surface sites are in excess. The constant capacitance model successfully describes the experimental data through a ligand-like adsorption complex at low pH. At high pH, the model predicts separate adsorption of divalent metal and HEDP onto different surface sites as the preferred adsorption form.     

New analytical procedure based on a cellulose bag and ionic exchanger with p-aminobenzoic acid groups for differentiation of labile and inert metal species in aquatic systems

A new procedure was developed for the in situ characterization of the lability of metal species in aquatic systems by using a system equipped with a diffusion membrane and cellulose organomodified with p-aminobenzoic acid groups (DM-Cell-PAB). To this end, the DM-Cell-PAB system was prepared by adding cellulose organomodified with p-aminobenzoic acid groups (Cell-PAB) to pre-purified cellulose bags. After the DM-Cell-PAB system was sealed, it was examined in the laboratory to evaluate the influence of complexation time, mass of exchanger, pH, metal ions (Cu, Cd, Fe, Mn, and Ni), and concentration of organic matter on the relative lability of metal species. It was found that the pH and kinetics strongly influence the process of metal complexation by the DM-Cell-PAB system. At all pH levels, Cd, Mn, and Ni showed lower complexation with Cell-PAB resin than Cu and Fe metals. Note that relative lability of metals complexed to aquatic humic substances (AHS) in the presence of Cell-PAB resin showed the following order: Cu≅Fe≫Ni>Mn=Cd. The results presented here also indicate that increasing the AHS concentration decreases the lability of metal species by shifting the equilibrium to AHS–metal complexes. Our results indicate that the system under study offers an interesting alternative that can be applied to in situ experiments for differentiation of labile and inert metal species in aquatic systems.     

稀土离子及其配合物对二棕榈酰磷脂酰乙醇胺相变性质的影响

用差示扫描量热研究了金属离子和稀土配合物对二棕榈酰磷脂酰乙醇胺(DPPE)脂双层由凝胶态向液晶态相转变的影响T~m的影响。发现加入金属离子提高了DPPE脂双层的相转变温度。其中, Na^+＜Ca^2^+＜Ln^3^+。Pr^3^+的影响较La^3^+强。在pH 7.4时, 柠檬酸镧对T~m影响很小, 相反在pH 2.0时, 则降低相变温度T~m。乳酸稀土在pH 2.0和pH 7.4时都显著提高T~m, 在中性条件下, 对T~m影响更大。同时, 乳酸稀土较相同浓度下的稀土离子影响大, 说明乳酸稀土中稀土离子和乳酸根配体存在协同作用。我们初步探讨了金属离子以及稀土配合物对DPPE脂双层相变温度影响的原因。     

Nickel‐Triad Complexes of a Side‐on Coordinating Distannene

NHC adducts of the stannylene Trip₂Sn (Trip=2,4,6‐triisopropylphenyl) were reacted with zero‐valent Ni, Pd, and Pt precursor complexes to cleanly yield the respective metal complexes featuring a three‐membered ring moiety Sn‐Sn‐M along with carbene transfer onto the metal and complete substitution of the starting ligands. Thus the easily accessible NHC adducts to stannylenes are shown to be valuable precursors for transition‐metal complexes with an unexpected Sn? Sn bond. The complexes have been studied by X‐ray diffraction and NMR spectroscopy as well as DFT calculations. The compounds featuring the structural motif of a distannametallacycle comprised of a [(NHC)₂M⁰] fragment and Sn₂Trip₄ represent rare higher congeners of the well‐known olefin complexes. DFT calculations indicate the presence of a π‐type Sn–Sn interaction in these first examples for acyclic distannenes symmetrically coordinating to a zero‐valent transition metal.     

Dendritic chelating agents. 1. Cu(II) binding to ethylene diamine core poly(amidoamine) dendrimers in aqueous solutions

This paper describes an investigation of the uptake of Cu(II) by poly(amidoamine) (PAMAM) dendrimers with an ethylenediamine (EDA) core in aqueous solutions. We use bench scale measurements of proton and metal ion binding to assess the effects of (i) metal ion-dendrimer loading, (ii) dendrimer generation/terminal group chemistry, and (iii) solution pH on the extent of binding of Cu(II) in aqueous solutions of EDA core PAMAM dendrimers with primary amine, succinamic acid, glycidol, and acetamide terminal groups. We employ extended X-ray absorption fine structure (EXAFS) spectroscopy to probe the structures of Cu(II) complexes with Gx-NH2 EDA core PAMAM dendrimers in aqueous solutions at pH 7.0. The overall results of the proton and metal ion binding measurements suggest that the uptake of Cu(II) by EDA core PAMAM dendrimers involves both the dendrimer tertiary amine and terminal groups. However, the extents of protonation of these groups control the ability of the dendrimers to bind Cu(II). Analysis of the EXAFS spectra suggests that Cu(II) forms octahedral complexes involving the tertiary amine groups of Gx-NH2 EDA core PAMAM dendrimers at pH 7.0. The central Cu(II) metal ion of each of these complexes appears to be coordinated to 2-4 dendrimer tertiary amine groups located in the equatorial plane and 2 axial water molecules. Finally, we combine the results of our experiments with literature data to formulate and evaluate a phenomenological model of Cu(II) uptake by Gx-NH2 PAMAM dendrimers in aqueous solutions. At low metal ion-dendrimer loadings, the model provides a good fit of the measured extent of binding of Cu(II) in aqueous solutions of G4-NH2 and G5-NH2 PAMAM dendrimers at pH 7.0.     

Metal uptake by a novel bidentate thiosemicarbazide chelating polymer

1-Cyanoethanoyl-4-acryloyl thiosemicarbazide (CEATS) has been prepared and polymerized by a free radical mechanism. The polymer PCEATS has chelating affinity, and metal-uptake capacities were determined for the chlorides of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) in the pH range 1.04–6.0. The extraction experiments show high capacity for Cu(II), (0.26?mmol/g) at pH 5.34 and lower uptake capacities for the other divalent metal ions around pH 5 in buffered solutions, under noncompetitive conditions. However, competitive experiments, performed with solutions containing a mixture of metal chloride salts and acetate buffer, showed a high selectivity for Cu(II) and Cd(II) over other cations. Distribution coefficients determined for the polymer and the metal ions indicate that the Cu(II) complex is more stable than the Cd(II) are and suggest that the stability of the complex decreases rapidly with decreasing pH. Kinetic experiments have shown that uptake of Cu(II), is slow, with t _0.5?=?10?h. Ligand regeneration experiments for Cu(II)-loaded PCEATS performed with 2.00?M H₂SO₄ have shown that the capacity for Cu(II) stays at the same level after several cycles of consecutive loading and stripping, indicating that the polymer is chemically stable. ESR spectra of Cu(II)–CEATS resin show that there are two different coordination complexes present in the polymer. IR spectra of the Cu(II) complex confirms the bidentate behavior (S, O; N, O) of CEATS and PCEATS (it is supposed that the cations bridge vicinal CEATS ligands through S, O and N, O atoms); the acetate group completes the octahedral coordination. The obtained data suggest that the polymer behaves as a bidentate ligand via the thiocarbonyl, carbonyl and imide groups. PCEATS and its complexes have an inhibitory effect on both the bacterium Azotobacter and the fungus Fusarium oxysporium. The effect on the microorganisms is proportional to the amount of free ligand in the complex.     

手性过渡金属(Mn, Co, Ni)-Salen配合物催化NaOCl不对称环氧化苯乙烯的反应研究

本文论述了由手性1, 2-二苯基乙二胺与适当取代的邻羟基苯甲醛生成的希佛碱作为过渡金属Co(II)、Ni(II)、Mn(II)的配体合成的6种过渡金属-Salen配合物在NaOCl下均相催化苯乙烯不对称环氧化反应的效果。对环氧化反应进行控制性研究, 我们发现环氧化反应与中心金属离子的相关性可能主要源于配体结构、金属离子的选择及二者结合形成的配合物的空间构型。好的不对称环氧化反应催化剂要求中心金属离子具有适当的氧化还原电位, 对底物烯烃因其取代基的大小, 催化剂结构的空间构型应有好坏之分, 我们得到的循环伏安数据及实验结果部分说明这一点。同时对手性镍(II)-Salen及手性锰(III)-Salen配合物的催化反应机理配合实验现象分别作出假设, 都经过自由基历程, 但却是截然不同的活性氧化物种, 同时, 由于起主要作用的不对称诱导因素不同, 不对称诱导方向有异。对同一催化剂在不同pH值下起作用的活性氧化物种类别也可能不同。     

甲基取代基对四苯基卟啉与铜显色反应的影响

为探讨甲基取代基对四苯基卟啉(TPPH2)结构和性质的影响,以四苯基卟啉与铜[Ⅱ]显色反应为参照,采用条件实验方法,对比研究了四(间甲苯基)卟啉(TMPPH2)和四(3,4-二甲苯基)卟啉(TDMPPH2)与铜Cu[Ⅱ]的显色反应,采用摩尔比法和连续变化法测定了配合物组成。结果表明:TMPPH2和TDMPPH2与Cu[Ⅱ]的显色配合物最大吸收峰与TPPCu的相同:均在416 nm处;TPPH2、TMPPH2和TDMPPH2与Cu[Ⅱ]进行显色反应的溶液最佳pH值分别是8、9和7,水浴温度100℃,最佳加热时间分别是20、20和25 min;形成配合物的组成分别是1:1、2:1和2:1(n卟啉:n铜);由此可知间甲基和3,4-二甲基取代对四苯基卟啉铜的配合物B吸收带(Soret带)峰位无影响,但对配合物的组成影响明显。     

Chromatographic determination of metal chelates of 2,6-diacetylpyridine bis(N-methylenepyridiniohydrazone)

Metal ions were determined chromatographically as their metal chelates after complexation with 2,6-diacetylpyridine bis(N-methylenepyridiniohydrazone). At a pH of 7 it was possible to separate and determine eight metal complexes, in a single run, under gradient conditions on a polyestyrene-divinylbenzene polymer-based column. Possible separation of rare earth complexes and ion-pairing behavior were also investigated. Linear calibration ranges and detection limits are presented for the metal complexes of Sn(II), Ti(IV), Mn(II), Co(II), Cd(II), Sb(III), Cu(II), Ni(II) and U(VI). Interferences due to the presence of other metal ions in solution were also investigated.     

Mixed metal hydroxycarboxylic acid complexes. Spectrophotometric study of complexes of U(VI) with In(III), Cu(II), Zn(II) and Cd(II)

The formation of mixed metal complexes between uranium (VI), as the central metal ion, and aluminium (III), indium (III), copper (II), zinc (II) and cadmium (II), as the additional metal ions, with a hydroxycarboxylic acid chosen between citric, tartaric or malic, has been studied using spectrophotometric methods.The effect of pH has been examined, and the results show that at pH=4 stable complexes are formed for most of the systems. At this pH the method of mole ratio and Job's method of continuous variations, were employed to determine the stoichiometry of the mixed metal complexes. Al(III), In(III) and Cu(II) showed a high tendency to form mixed metal complexes with U(VI), while the formation of complexes is uncertain for Cd(II) and Zn(II). The ratio of the ligand to the total metal ion has been found to be 21 and metal:metal ratios of 11 and 12 have been observed.Represents part of the Ph.D. thesis submitted by Emanuel Manzurola to Ben Gurion University of the Negev.     

胆红素有序分子膜的行为研究

研究了不同亚相表面胆红素(BR)单分子膜和LB膜的性质,讨论了胆红素分子在有序分子膜中的堆积密度、分子伸展和金属离子配位。在气-水界面,BR与金属离子的配位导致BR单分子截面积、崩溃压和可见紫外光谱的变化。原子力显微镜表明BR-Cu单分子膜的厚渡为1.23 nm。     

Metal-complex formation in continuous-flow ligand-exchange reactors studied by electrospray mass spectrometry

Electrospray ionization mass spectrometry was used to investigate complex formation of different metal complexes in a continuous-flow ligand-exchange reactor. A computer program was developed based on normal equilibrium calculations to predict the formation of various metal-ligand complexes. Corresponding to these calculations, infusion electrospray mass spectrometric experiments were performed to investigate the actual complex formation in solution. The data clearly show good correlation between the theoretically calculated formation of metal-ligand complexes and the experimental mass spectrometric data. Moreover, the approach demonstrates that the influence of the pH can be investigated using a similar approach. Indirectly, these infusion experiments provide information on relative binding constants of different ligands towards a metal-ion. To demonstrate this, a continuous-flow ligand-exchange detection system with mass spectrometric detection was developed. Injection of ligands, with different affinity for the metal-ion, into the reactor shows good correlation between binding constants and the response in the ligand-exchange detection system. Additional information on the introduced ligand, and the complexes formed after introduction of the ligand, can be obtained from interpretation of the mass spectra.     

过渡金属与华法灵配合物的合成和抗凝血作用研究

用过渡金属硝酸盐与华法灵钠在不同介质制备了金属配合物, 所试验的各种制备方法均可获得恒定组成的配合物NanML3•2H2O (L＝华法灵离子, n＝0, 1). 通过元素分析、红外光谱、摩尔电导、紫外光谱、热重和溶解性试验对配合物进行了表征. 抗凝血试验表明过渡金属华法灵配合物具有一定的抗凝血性质. 并对过渡金属华法灵、过渡金属水杨酸、稀土金属华法灵、稀土金属华法灵水杨酸配合物的抗凝血性质进行了比较.     

Solid-phase extraction and subsequent capillary zone electrophoresis of trace metal ions as soluble dithiocarbamate complexes

Summary Modest detectability in capillary electrophoresis is often a challenge for the determination of trace-level metal ions. This limitation has been addressed by the development of an enrichment procedure combining the formation of metal bis(carboxymethyl)dithiocarbamate complexes, water soluble at basic pH and sparingly soluble in an acidic environment, and solidphase extraction. Appropriate conditions were developed for a solid-phase extraction step well compatible with subsequent capillary electrophoretic separation in terms of the composition of electrophoresis and eluting buffers. At pH below 4 when the ligand carboxyl groups are non-ionized, metal ion complexes have no apparent charge and are efficiently retained on a conventional C₁₆ cartridge. Application of a basic eluent, a borate buffer at pH9, causes the complexes to be ionized and eluted rapidly and quantitatively. Parameters affecting the retention/recovery behavior, such as the pH and ligand concentration of the loading solution, flow-rate, eluting buffer pH and concentration, etc, were examined to attain the best possible enrichment factors for trace metal ions. As a result, an increase in sensitivity over two orders of magnitude was gained that permitted lowering the detection limits for copper(II), lead(II), cadmium(II), nickel(II), and mercury(II) down to a low-μg L⁻¹ level.     

金属与喹诺酮类药物构筑的配合物的研究进展

本文综述了喹诺酮类药物的发展过程,以及各种金属离子与该类药物构筑形成配合物晶体结构方面的研究进展,展望了此类研究的发展趋势。     

手性过渡金属(Mn,Co,Ni)-Salen配合物催化NaOCl不对称环氧化苯乙烯的反应研究

本文论述了由手性1,2-二苯基乙二胺与适当取代的邻羟基苯甲醛生成的希佛碱作为过渡金属Co(Ⅱ)、Ni(Ⅲ)、Mn(Ⅲ)的配体合成的6种过渡金属-Salen配合物在NaOCl下均相催化苯乙烯不对称环氧化反应的效果。对环氧化反应进行控制性研究,我们发现环氧化反应与中心金属离子的相关性可能主要源于配体结构、金属离子的选择及二者结合而形成的配合物的空间构型。好的不对称环氧化反应催化剂要求中心金属离子具有适当的氧化还原电位,对底物烯烃因其取代基的大小,催化剂结构的空间构型应有好坏之分,我们得到的循环伏安数据及实验结果部分说明这一点。同时对手性镍(Ⅱ)-Salen及手性锰(Ⅲ)-Salen配合物的催化反应机理配合实验现象分别作出假设,都经过自由基历程,但却是截然不同的活性氧化物种,同时,由于起主要作用的不对称诱导因素不同,不对称诱导方向有异。对同一催化剂在不同pH值下起作用的活性氧化物种类别也可能不同。     

Stability and kinetics of the acid-promoted decomposition of Cu(II) complexes with hexaazacyclophanes: kinetic studies as a probe to detect changes in the coordination mode of the macrocycles

The synthesis, protonation and Cu(II) coordination features of the novel azacyclophane type receptors 2,6,10,13,17,21-hexaza[22]-(2,6)-pyridinophane (L2), 2,6,9,12,15,19-hexaza[20]-(2,6)-pyridinophane (L5) and 2,6,9,12,15,19-hexaza[20]metacyclophane (L6) are presented. The protonation and Cu(II) constants are analysed and compared with the previously reported open-chain polyamines 4,8,11,15-tetrazaoctadecane-1,18-diamine (L1) and 4,7,10,13-tetraazahexadecane-1,16-diamine (L4) and of the cyclophane 2,6,10,13,17,21-hexaaza[22]paracyclophane (L3). All the systems form mono- and dinuclear complexes whose stability and pH range of existence depend on the type of hydrocarbon chains and molecular topology. The effects of the cyclic or open-chain nature and of the presence of the pyridine rings on the protonation and formation of mono- and dinuclear complexes are discussed. Stopped-flow kinetic measurements on the acid-promoted decomposition of the Cu(II) complexes have been carried out for the different systems. With respect to the decomposition of the dinuclear complexes, because the size of the macrocycles forces both metal ions to be close to each other, the release of the first ion occurs within the mixing time of the stopped-flow except for the dinuclear complexes of L2. However, the most interesting kinetic result is the observation of different kinetics of decomposition for the different mononuclear complexes formed by a given ligand. This effect is especially evident for L3 and L6 and indicates a change in the coordination mode of the ligand for the different mononuclear species. Therefore the Cu(II) ion performs a slippage motion through the macrocyclic cavity driven by pH changes. The stopped-flow experiments are an excellent tool to detect these slippage processes that may be present for the complexes with other macrocycles.