'Tetol': a stereo-rigid four-strand motif for alkali and alkaline earth metal ion coordination

The tetraalcohol 2,3,5,6-endo,endo,endo,endo-tetrakis(hydroxymethyl]bicyclo[2.2.1]heptane (tetol, 1) has been prepared and crystallises readily as the lithium(I) complex [Li(1)(2)]Cl, forming an oligomeric multi-chain structure in which pairs of alcohols from two crystallographically independent tetol molecules bind lithium ions tetrahedrally. However, formation of monomeric structures in solution is inferred from electrospray mass spectroscopy, which has also shown evidence of exchange of lithium ion in the complexed species by added alkaline earth ions. (C) 2000 Elsevier Science S.A. All rights reserved.

The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome

Purpose:To identify the gene causing rod-cone dystrophy/amelogenesis imperfecta Methods:Homozygosity mapping was performed using the Affymetrix 50K XbaI array in one family and candidate genes in the linked interval were sequenced with ABI Dye Terminator, vers. 1 in the index patient of 3 families. The identified mutations were screened in normal control individuals. Expression analyses were performed on RNA extracted from the brain, various parts of the eye and teeth; immunostaining was done on mouse eyes and jaw and knock-down experiments were carried out in zebrafish embroys. Results:Sequencing the coding regions of ancient conserved domain protein 4 (CNNM4), a metal ions transporter, revealed a 1-base pair duplication (p.L438fs) in family A, a p.R236Q mutation in family B and a p.L324P in family C. All these mutations were homozygous and involved very conserved amino acids in paralogs and orthologs. Immunostaining and RT-PCR confirmed that CNNM4 was strongly expressed in various parts of the eye and in the teeth. Morpholino experiments in zebrafish showed a loss of ganglion cells at 5 days post fertilization. Conclusions:The rod-cone dystrophy/amelogenesis imperfecta syndrome is caused by mutation in CNNM4 and is due to aberrant metal ion homeostasis.

Diffusive transport properties in monovalent and divalent metal-ion halide melts: A computer simulation study

Self- and cross-velocity correlation functions and related transport coefficients of molten salts are studied by molecular-dynamics simulation. Six representative systems are considered, i.e., NaCl and KCl alkali halides, CuCl and CuBr noble-metal halides, and SrCl2 and ZnCl2 divalent metal-ion halides. Computer simulation results are compared with experimental self-diffusion coefficients and electrical conductivities. Special attention is paid to dynamic cross correlations and their dependence on the Coulomb interactions as well as on the size and mass differences between anions and cations.

FM127: Systemic metal ion levels in patients with modular neck total hip arthroplasties: a prospective cohort study

There is increasing evidence that modular neck stems are prone to corrosion-related complications. Recent studies showed elevated metal ions levels and occasional pseudotumor formation in patients with such implants. The purpose of this study was to compare systemic metal-ion levels in patients after primary THA with modular neck stems to those of patients after non-modular implants. To our knowledge, this is the first cohort study including a control group, THA without CoCr heads and dry-assembled neck-stem connections. Methods: 50 patients after THA at a minimum follow-up of 1 year have been selected for the study. Patients with multiple prosthesis or other implants have been deselected. All received a cementless SPS stem from Symbios (Ti6Al4V). 40 patients have the modular neck (CoCr) version and 10 a monobloc version. All bearings were either ceramic-ceramic or ceramic-polyethylene to minimize other sources of CoCr ion release. In the modular group, the neck was chosen pre-operatively based on a 3D planning, allowing for a dry assembly of the stem and neck on the back table before implantation. A plasma system coupled to mass spectrometry was used for a complete elementary quantification in blood and serum separately. Clinical outcome was measured using the Oxford Hip Score. Results : Complete data sets of 29 patients (24 in the modular neck-group (10male, mean age 63y, 35-84y) and 5 in the monobloc-group (3 male, 69 y, 51-83y) are available to date. Mean Co blood levels were .95 ug/L (.14-12.4) in the modular group vs .27 ug/L (.10-.73) in the monobloc group (p=.2). Respective values for Cr were significantly higher in the modular group (.99 g/L; range .75-1.21) compared to those in the monobloc group (.74 g/L ;.62-.86; p=.001). No significant difference was found when comparing serum levels. 5/24 patients had Co levels above 1 g/L (12/24 for Cr), which is by some considered as a relevant elevation. The maximum Co level was measured in an asymptomatic patient. The Oxford Hip Scores were similar in both groups. Conclusion: Cr levels were significantly elevated in the modular neck group compared to those in the monobloc group. 1/24 patients with a modular prosthesis exhibited Co levels, which are beyond the threshold accepted even for metal-on-metal bearing couples. These results have contributed to our decision to abandon the use of modular neck stems. Routine follow-up including annual measurements of systemic CoCr concentrations should be considered.

Artificial Ribonucleases: Oligonucleotides Conjugated with Metal Ion Chelates of Azacrowns

Ribonucleic acid (RNA) has many biological roles in cells: it takes part in coding, decoding, regulating and expressing of the genes as well as has the capacity to work as a catalyst in numerous biological reactions. These qualities make RNA an interesting object of various studies. Development of useful tools with which to investigate RNA is a prerequisite for more advanced research in the field. One of such tools may be the artificial ribonucleases, which are oligonucleotide conjugates that sequence-selectively cleave complementary RNA targets. This thesis is aimed at developing new efficient metal-ion-based artificial ribonucleases. On one hand, to solve the challenges related to solid-supported synthesis of metal-ion-binding conjugates of oligonucleotides, and on the other hand, to quantify their ability to cleave various oligoribonucleotide targets in a pre-designed sequence selective manner. In this study several artificial ribonucleases based on cleaving capability of metal ion chelated azacrown moiety were designed and synthesized successfully. The most efficient ribonucleases were the ones with two azacrowns close to the 3´- end of the oligonucleotide strand. Different transition metal ions were introduced into the azacrown moiety and among them, the Zn2+ ion was found to be better than Cu2+ and Ni2+ ions.

Metal-Ion-Binding Oligonucleotides: High-Affinity Probes for Nucleic Acid Sequences

Small non-coding RNAs have numerous biological functions in cell and are divided into different classes such as: microRNA, snoRNA, snRNA and siRNA. MicroRNA (miRNA) is the most studied non-coding RNA to date and is found in plants, animals and some viruses. miRNA with short sequences is involved in suppressing translation of target genes by binding to their mRNA post-transcriptionally and silencing it. Their function besides silencing of the viral gene, can be oncogenic and therefore the cause of cancer. Hence, their roles are highlighted in human diseases, which increases the interest in using them as biomarkers and drug targets. One of the major problems to overcome is recognition of miRNA. Owing to a stable hairpin structure, chain invasion by conventional Watson-Crick base-pairing is difficult. One way to enhance the hybridization is exploitation of metal-ion mediated base-pairing, i. e. oligonucleotide probes that tightly bind a metal ions and are able to form a coordinative bonds between modified and natural nucleobases. This kind of metallo basepairs containing short modified oligonucleotides can also be useful for recognition of other RNA sequences containing hairpin-like structural motives, such as the TAR sequence of HIV. In addition, metal-ion-binding oligonucleotides will undoubtedly find applications in DNA-based nanotechnology. In this study, the 3,5-dimethylpyrazol-1-yl substituted purine derivatives were successfully incorporated within oligonucleotides, into either a terminal or non-terminal position. Among all of the modified oligonucleotides studied, a 2-(3,5-dimethylpyrazol-1-yl)-6-oxopurine base containing oligonucleotide was observed to bind most efficiently to their unmodified complementary sequences in the presence of both Cu2+ or Zn2+. The oligonucleotide incorporating 2,6-bis(3,5-dimethylpyrazol-1-yl)purine base also markedly increased the stability of duplexes in the presence of Cu2+ without losing the selectivity.

Recognition of nucleic acids by metal ion complexes

Metal-ion-mediated base-pairing of nucleic acids has attracted considerable attention during the past decade, since it offers means to expand the genetic code by artificial base-pairs, to create predesigned molecular architecture by metal-ion-mediated inter- or intra-strand cross-links, or to convert double stranded DNA to a nano-scale wire. Such applications largely depend on the presence of a modified nucleobase in both strands engaged in the duplex formation. Hybridization of metal-ion-binding oligonucleotide analogs with natural nucleic acid sequences has received much less attention in spite of obvious applications. While the natural oligonucleotides hybridize with high selectivity, their affinity for complementary sequences is inadequate for a number of applications. In the case of DNA, for example, more than 10 consecutive Watson-Crick base pairs are required for a stable duplex at room temperature, making targeting of sequences shorter than this challenging. For example, many types of cancer exhibit distinctive profiles of oncogenic miRNA, the diagnostics of which is, however, difficult owing to the presence of only short single stranded loop structures. Metallo-oligonucleotides, with their superior affinity towards their natural complements, would offer a way to overcome the low stability of short duplexes. In this study a number of metal-ion-binding surrogate nucleosides were prepared and their interaction with nucleoside 5´-monophosphates (NMPs) has been investigated by 1H NMR spectroscopy. To find metal ion complexes that could discriminate between natural nucleobases upon double helix formation, glycol nucleic acid (GNA) sequences carrying a PdII ion with vacant coordination sites at a predetermined position were synthesized and their affinity to complementary as well as mismatched counterparts quantified by UV-melting measurements.

Synthesis and Study of Photophysical and Metal Ion Binding Properties of a Few Novel Semisquaraine and Croconaine Dyes

Photosciences & Photonics, Chemical Sciences & Technology Division, National Institute for Interdisciplinary Science & Technology

Influence of residual cations (Na+, K+ and Mg2+) in the alkylation activity of benzene with 1-octene over rare earth metal ion exchanged FAU–Y zeolite

The effect of residual cations in rare earth metal modified faujasite–Y zeolite has been monitored using magic angle spinning NMR spectral analysis and catalytic activity studies. The second metal ions being used are Na+, K+ and Mg+. From a comparison of the spectra of different samples, it is concluded that potassium and magnesium exchange causes a greater downfield shift in the 29Si NMR peaks. Also, lanthanum exchanged samples show migration behavior from large cages to small cages, which causes the redistribution of second counter cations. It is also observed that Mg2+ causes the most effective migration of lanthanum ions due to its greater charge. The prepared systems were effectively employed for the alkylation of benzene with 1-octene in the vapor phase. From the deactivation studies it is observed that the as-exchanged zeolites possess better stability towards reaction condition over the pure HFAU zeolite.

A new metal ion doped panchromatic photopolymer for holographic applications

This thesis has discussed the development of a new metal ion doped panchromatic photopolymer for various holographic applications. High-quality panchromatic holographic recording material with high diffraction efficiency, high photosensitivity and high spatial resolution is one of the key factors for the successful recording of true colour holograms. The capability of the developed material for multicolour holography can be investigated.In the present work, multiplexing studies were carried out using He-Ne laser (632.8 nm). Multiplexing can be done using low wavelength lasers like Ar+ ion (488 nm) and frequency doubled Nd: YAG (532 nm) lasers, so as to increase the storage capacity. The photopolymer film studied had a thickness of only 130 Cm. Films with high thickness (~500 Cm) is highly essential for competitive holographic memories . Hence films with high thickness can be fabricated and efforts can be made to record more holograms or gratings in the material.In the present study, attempts were made to record data page in silver doped MBPVA/AA photopolymer film. Image of a checkerboard pattern was recorded in the film, which could be reconstructed with good image fidelity. Efforts can be made to determine the bit error rate (BER) which provides a quantitative measure of the image quality of the reconstructed image . Multiple holographic data pages can also be recorded in the material making use of different multiplexing techniques.Holographic optical elements (HOEs) are widely used in optical sensors, optical information processing, fibre optics, optical scanners and solar concentrators . The suitability of the developed film for recording holographic optical elements like lenses, beam splitters and filters can be studied.The suitability of a reflection hologram recorded in acrylamide based photopolymer for visual indication of environmental humidity is reported . Studies can be done to optimize the film composition for recording of reflection holograms.An improvement in the spatial resolution of PVA/acrylamide based photopolymer by using a low molecular-weight poly (vinyl alcohol) binder was recently reported . Effect of the molecular weight of the binder matrix on the holographic properties of the developed photopolymer system can be investigated.Incorporation of nanoparticles into photopolymer system is reported to enhance the resolution and improve the dimensional stability of the system . Hence efforts can be made to incorporate silver nanoparticles into the photopolymer and its influence on the holographic properties can be studied.This thesis was a small venture towards the realization of a big goal, a competent holographic recording material with excellent properties for practical holographic applications. As a result of the present research, we could successfully develop an efficient panchromatic photopolymer system and could demonstrate its suitability for recording transmission holograms and holographic data page. The developed photopolymer system is expected to have significant applications in the fields of true-color display holography, wavelength multiplexing holographic storage, and holographic optical elements. Highly concentrated and determined effort has yet to be put forth for this expectation to become a reality.

Diffusive transport properties in monovalent and divalent metal-ion halide melts: A computer simulation study

Self- and cross-velocity correlation functions and related transport coefficients of molten salts are studied by molecular-dynamics simulation. Six representative systems are considered, i.e., NaCl and KCl alkali halides, CuCl and CuBr noble-metal halides, and SrCl2 and ZnCl2 divalent metal-ion halides. Computer simulation results are compared with experimental self-diffusion coefficients and electrical conductivities. Special attention is paid to dynamic cross correlations and their dependence on the Coulomb interactions as well as on the size and mass differences between anions and cations.

Complete filling of zeolite frameworks with polyalkynes formed in situ by transition-metal ion catalysts

We report the use of transition-metal-exchanged zeolites as media for the catalytic formation and encapsulation of both polyethyne and polypropyne, and computer modeling studies on the composites so formed. Alkyne gas was absorbed into the pores of zeolite Y (Faujasite) exchanged with transition-metal cations [Fe(II), Co(II), Cu(II), Ni(II), and Zn(II)]. Ni(II) and Zn(II) were found to be the most efficient for the production of poly-ynes. These cations were also found to be effective in polymer generation when exchanged in zeolites mordenite and beta. The resulting powdered samples were characterized by FTIR, Raman, diffuse reflectance electronic spectroscopy, TEM, and elemental analysis, revealing, nearly complete loading of the zeolite channels for the majority of the samples. Based on the experimental carbon content, we have derived the percentage of channel filling, and the proportion of the channels containing a single polymer chain for mordenite. Experimentally, the channels for Y are close to complete filling for polyethyne (PE) and polypropyne (PP), and this is also true for polyethyne in mordenite. Computer modeling studies using Cerius2 show that the channels of mordenite can only accept a single polymer chain of PP, in which case these channels are also completely filled.

An unprecedented mononuclear double helicate with a square planar metal ion

Reactions of the 1:2 condensate (L) of benzil dihydrazone and 1-methyl-2-imidazole carboxaldehyde with Cd(ClO4)(2)center dot xH(2)O and CdI2 yield [CdL2]( ClO4)(2) (1) and LCdI2 (2), respectively. The yellow ligand L, and its yellow complexes 1 and 2 are characterized by NMR and single crystal X-ray diffraction. Though L contains four N-donor centers, 1 is found to be a four-coordinate double helicate with a square planar Cd(II)N-4 core and 2 a spiral coordination polymer with tetrahedral Cd(II)N2I2 moieties. The bidentate nature of L and the occurrence of the square planar coordination of Cd( II) is explained by DFT calculations. (c) 2007 Elsevier B. V. All rights reserved.

Automated two-dimensional separation flow system with electrochemical preconcentration, stripping, capillary electrophoresis and contactless conductivity detection for trace metal ion analysis

This paper describes the automation of a fully electrochemical system for preconcentration, cleanup, separation and detection, comprising the hyphenation of a thin layer electrochemical flow cell with CE coupled with contactless conductivity detection (CE-C(4)D). Traces of heavy metal ions were extracted from the pulsed-flowing sample and accumulated on a glassy carbon working electrode by electroreduction for some minutes. Anodic stripping of the accumulated metals was synchronized with hydrodynamic injection into the capillary. The effect of the angle of the slant polished tip of the CE capillary and its orientation against the working electrode in the electrochemical preconcentration (EPC) flow cell and of the accumulation time were studied, aiming at maximum CE-C(4)D signal enhancement. After 6 min of EPC, enhancement factors close to 50 times were obtained for thallium, lead, cadmium and copper ions, and about 16 for zinc ions. Limits of detection below 25 nmol/L were estimated for all target analytes but zinc. A second separation dimension was added to the CE separation capabilities by staircase scanning of the potentiostatic deposition and/or stripping potentials of metal ions, as implemented with the EPC-CE-C(4)D flow system. A matrix exchange between the deposition and stripping steps, highly valuable for sample cleanup, can be straightforwardly programmed with the multi-pumping flow management system. The automated simultaneous determination of the traces of five accumulable heavy metals together with four non-accumulated alkaline and alkaline earth metals in a single run was demonstrated, to highlight the potentiality of the system.

Insights into metal ion binding in phospholipases A(2): ultra high-resolution crystal structures of an acidic phospholipase A(2) in the Ca2+ free and bound states

The electrophile Ca2+ is an essential multifunctional co-factor in the phospholipase A(2) mediated hydrolysis of phospholipids. Crystal structures of an acidic phospholipase A(2) from the venom of Bothrops jararacussu have been determined both in the Ca2+ free and bound states at 0.97 and 1.60 angstrom resolutions, respectively. In the Ca2+ bound state, the Ca2+ ion is penta-coordinated by a distorted pyramidal cage of oxygen and nitrogen atoms that is significantly different to that observed in structures of other Group I/II phospholipases A(2). In the absence of Ca2+, a water molecule occupies the position of the Ca2+ ion and the side chain of Asp49 and the calcium-binding loop adopts a different conformation. (c) 2005 Elsevier SAS. All rights reserved.