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At least 613 records · Page 34Linked to original sources
PubMed1996

Ferrocene-oligonucleotide conjugates for electrochemical probing of DNA.

Toward the development of a universal, sensitive and convenient method of DNA (or RNA) detection, electrochemically active oligonucleotides were prepared by covalent linkage of a ferrocenyl group to the 5'-aminohexyl-terminated synthetic oligonucleotides. Using these electrochemically active probes, we have been able to demonstrate the detection of DNA and RNA at femtomole levels by HPLC equipped with an ordinary electrochemical detector (ECD) [Takenaka,S., Uto,Y., Kondo,H., Ihara,T. and Takagi,M. (1994) Anal. Biochem., 218, 436-443]. Thermodynamic and electrochemical studies of the interaction between the probes and the targets are presented here. The thermodynamics obtained revealed that the conjugation stabilizes the triple-helix complexes by 2-3 kcal mol-1 (1-2 orders increment in binding constant) at 298 K, which corresponds to the effect of elongation of additional several base triplets. The main cause of this thermodynamic stabilization by the conjugation is likely to be the overall conformational change of whole structure of the conjugate rather than the additional local interaction. The redox potential of the probe was independent of the target structure, which is either single- or double stranded. However, the potential is slightly dependent (with a 10-30 mV negative shift on complexation) on the extra sequence in the target, probably because the individual sequence is capable of contacting or interacting with the ferrocenyl group in a slightly different way from each other. This small potential shift itself, however, does not cause any inconvenience on practical applications in detecting the probes by using ECD. These results lead to the conclusion that the redox-active probes are very useful for the microanalysis of nucleic acids due to the stability of the complexes, high detection sensitivity and wide applicability to the target structures (DNA and RNA; single- and double strands) and the sequences.

DNA↗
PubMed2004

Automated synthesis of new ferrocenyl-modified oligonucleotides: study of their properties in solution.

We have developed new ferrocenyl-modified oligonucleotide (ODN) probes for electrochemical DNA sensors. A monofunctional ferrocene containing phosphoramidite group has been prepared, and a new bisfunctional ferrocene containing phosphoramidite and dimethoxytrityl (DMT) groups has been developed. These ferrocenyl-phosphoramidites have been directly employed in an automated solid-phase DNA synthesizer using phosphoramidite chemistry. The advantages of this method are that it allows a non-specialist in nucleotide chemistry to access labeled ODNs and that it has demonstrated good results. ODNs modified at the 3' and/or 5' extremities have been prepared, with the incorporation of the ferrocenyl group into the chain. The 5' position appears to be more important due to its particular behavior. The thermal stability and electrochemical properties of these new ODN ferrocenes were analyzed before and after hybridization with different ODNs. The feasibility of using these new ferrocenyl-labeled ODNs in DNA sensors has been demonstrated.

Biosensing Techniques↗
PubMed2002

An anthracene derivative carrying ferrocenyl moieties at its 9 and 10 positions as a new electrochemically active threading intercalator.

A ferrocenyl anthracene derivative (FAN) was synthesized by connecting ferrocene moieties to the amino termini of its substitutents at 9 and 10 positions, aiming at an improved hybridization indicator. Spectrophotometric experiments revealed that FAN can bind to double stranded DNA (dsDNA) by threading intercalation. Evaluation of FAN in the dsDNA preference as hybridization indicator revealed that FAN has higher preference for dsDNA than ferrocenyl naphthalene diimdie (FND) reported previously.

Anthracenes↗
PubMed2003

Development of a novel genosensor based on ferrocenyl oligonucleotides.

Two types of ferrocenyl oligonucleotides, Fc1-ODN and Fc2-ODN, carrying a 5'-ATT GCT CAG GGG TAA GGT CAT TAG TTG GAA-3' sequence were allowed to hybridize with the DNA probe carrying a complementary sequence immobilized on the gold electrode to give rise to a redox signal deriving from their ferrocenyl moieties. When a mixture of these oligonucleotides in a proper ratio was used as a model of DNA samples, two redox peaks were observed in one differential pulse voltammogram. The peak currents varied depending on the initial ratio of the two oligonucleotides, suggesting a possibility that this technique may be applied to electrochemical monitoring of gene expression by, for example, the electrochemical differential hybridization, EDH.

Base Sequence↗
PubMed2004

Electrochemical gene detection by using adamantyl naphthalene diimide coupled with ferrocenyl-beta-cyclodextrin.

The adamantyl moieties of adamantylnaphthalene diimide (AND) can be incorporated into the cavity of ferrocenyl-beta-cyclodextrin even where they are bound to double stranded DNA by threading intercalation. When this ternary complex is formed on the DNA probe-immobilized electrode, electrochemical DNA detection is feasible: the electrode hybridized with target DNA gave rise to a current peak corresponding to the ferrocene oxidation upon treatment with AND and ferrocenyl-beta-cyclodextrin (Fc-beta-CD).

Adamantane↗
PubMed2004

Properties of ferrocene-polyamide compounds as redox active DNA binding molecules toward the SNPs detection.

Ferrocene-polyamides having not only sequence discrimination ability but also a redox mediator were synthesized. The affinity and selectivity of these compounds for a DNA duplex having a cognate GCG sequence were investigated by CD spectroscopy. Furthermore, the binding of the ferrocene-polyamides to DNA duplexes immobilized to a gold electrode was detected by cyclic voltammetry (CV) experiments. The electrochemical studies revealed that the fully matched DNA duplex having a GCG sequence showed the largest electric current, and the introduction of a mismatch site decreased the current significantly. These results suggested the potential of the ferrocene-polyamide compounds as new electrochemical ligands for electrochemical SNPs detection.

Circular Dichroism↗
PubMed2004

Synthesis of ferrocenyl carbodiimide as a novel ferrocenyl reagent of single stranded DNA.

Ferrocenyl carbodiimide (FcCDI) was newly synthesized as a ferrocenylation reagent for single stranded DNA. FcCDI could attach to oligodeoxyribonucleotides (ODN) through a covalent bond with thymine and guanine bases. The reactivity of thymine with FcCDI was higher than that of guanine, but independent of their location on the DNA sequence. After a single stranded DNA was treated with FcCDI, resulting ODN could be detected electrochemically by a redox signal deriving from the ferrocenyl moiety with a DNA probe-immobilized electrode. These results suggest that the labeling of DNA with FcCDI can be applied to rapid analysis of electrochemical genosensors.

Carbodiimides↗
PubMed2003

Ferrocene-induced lymphocyte activation and anti-tumor activity is mediated by redox-sensitive signaling.

Ferrocene, a stable, synthetic, iron-containing compound induces in vitro and in vivo activation of mouse lymphocytes and macrophages. Ferrocene also has a marked antitumor effect in mice, upon its administration intraperitoneally and in drinking water. Ferrocene's antitumor activity is attributed to its immune-stimulatory property. This conclusion is supported by adoptive transfer experiments demonstrating that immune cells from ferrocene-treated tumor-bearing mice elicit an antitumor effect in mice not treated with ferrocene. We postulate that the immune stimulatory effect of ferrocene is mediated by redox-sensitive signaling such as activation of p21ras. This postulation is supported by the following findings: Ferrocene generates H2O2 by autooxidation; N-acetylcysteine, a free-radical scavenger, reduces its antitumor effect; and it stimulates GTPase activity catalyzed by pure recombinant p21ras and activates ERK 1/2 in wild Jurkat T cells but fails to do so in the Jurkat T cells expressing p21ras in which cysteine 118 was replaced by serine. Lastly, ferrocene activates and translocates NF-kappaB in human PBM, a pathway which is mediated by ras. It is most plausible that additional redox-sensitive signaling proteins mediate the biological effects of ferrocene.

Animals↗
PubMed1989

Enantiotopic differentiation in horse-liver alcohol-dehydrogenase-catalyzed oxidoreduction studied with novel substrates having organometallic moieties.

Horse-liver alcohol-dehydrogenase-catalyzed oxidation of 1,2-bis(hydroxymethyl)ferrocene (1) gave (1R)-(+)-1-formyl-2-hydroxymethylferrocene (3) (86 +/- 2% enantiomeric excess, e.e.), while the reduction of the corresponding dialdehyde 1,2-diformylferrocene (2) gave the antipode (1S)-(-)-3 (94 +/- 2% e.e.). This fact indicates that the pro-R group in both 1 and 2 was preferentially converted by the enzyme. When one of two substituents on the substrate was replaced by a methyl group or moved to the beta-site, the stereoselectivity in the reaction decreased as evidenced by the enantiomeric purity of the products (5-64% e.e.). Treatment of racemic 1-hydroxyethylferrocene (14) with horse-liver alcohol dehydrogenase (HLADH) gave optically pure (R)-(-)-14 together with acetylferrocene. The reduction of 2 with HLADH, NAD and (2H6)ethanol gave (-)-(1S,2R)-1-formyl-2-[(R)-hydroxy(2H1)methyl]ferrocene and that of 1,2-di[(2H)formyl]ferrocene with HLADH, NAD and ethanol gave (-)-(1S,2R)-1-(2H)formyl-2-[(S)-hydroxy(2H1)methyl]ferrocene. These configurations indicate that the enzymic reduction occurred on the re-face of pro-R formyl group. The re-face selectivity was also found in the enzymic reduction of (eta 6-benzaldehyde)tricarbonylchromium and its (2H)formyl analogue. Docking of 2 into the active site of HLADH was examined using computer graphics. It has been suggested that the enantioselectivity to the pro-R side in the oxidoreduction of 1 and 2 by HLADH is a natural consequence of the re-face selectivity, which is caused by a steric interaction between the ligand and the side chain of Phe-93 or the Zn complex and strengthened by an interaction between the unreactive polar alpha-substituent and the protein, probably by hydrogen bond formation.

Alcohol Dehydrogenase↗
PubMed1991

Biochemical and biophysical investigations of the ferrocene-iron-loaded rat. An animal model of primary haemochromatosis.

Male Wistar rats fed with ferrocene had high hepatic iron loading (7.24 +/- 1.97 mg Fe/g tissue) after 6 weeks, principally located in lysosomes, which was comparable to the levels and distribution determined in human haemochromatosis. The two iron-storage proteins, ferritin and haemosiderin were isolated from the livers of the ferrocene-loaded rats and their iron cores were investigated by Mössbauer spectroscopy and inductively coupled plasma-emission spectrometry. Ferrihydrite was the predominant form of iron present in both ferritin and haemosiderin, while haemosiderin contained higher amounts of phosphorus, magnesium, calcium and barium, then either normal or ferrocene-loaded ferritin. Free-radical-mediated damage in the iron-loaded livers was inferred by the significant depletion of alpha-tocopherol in both the livers and subcellular hepatic lysosomal fraction, which inversely correlated with the increasing iron content (r = -0.61; P less than 0.05) and was associated with increased fragility of the lysosomal membranes.

Animals↗
PubMed1994

Further characterisation of forms of haemosiderin in iron-overloaded tissues.

The biochemical and biophysical properties of isolated haemosiderins have been compared to that of another iron-containing protein, termed prehaemosiderin, which sediments through chaotropic potassium iodide only after 20 h of ultracentrifugation, in contrast to that of haemosiderin which is recovered after 2 h of ultracentrifugation. The iron/protein ratio and iron/phosphate ratio were less that that of the corresponding haemosiderin, while the elemental composition was also reduced in many of the prehaemosiderin samples. Mossbauer spectroscopy and electron diffraction identified the predominant presence of ferrihydrite in prehaemosiderin species even though the secondary haemochromatosis haemosiderin iron cores were essentially goethite-like. The majority of the prehaemosiderins isolated showed the presence of an additional peptide band at 17 kDa in addition to that at 21 kDa. Further Mossbauer studies of haemosiderin isolated from untreated secondary haemochromatosis patients showed that goethite was the predominant form of iron present, thereby indicating that the presence of this form of ferrihydrite was not wholly attributable to chelation therapy.

Animals↗
PubMed1994

Control of cellular iron homeostasis by iron-responsive elements in vivo.

It has recently been proposed that cellular iron homeostasis in mammalian cells is regulated at the post-transcriptional level by the reciprocal control of transferrin receptor and ferritin mRNA expression via an iron-regulatory factor. This iron-regulatory factor has been shown to be a cytoplasmic aconitase which can bind to iron-responsive elements in the corresponding mRNAs with greater or lesser affinity as a function of the iron status of the cell. In the present study, we show that in vivo the affinity of iron-regulatory factor for iron-responsive elements in liver reflects the long-term iron status of the tissue in animal models for iron overloading and iron deficiency, when combined with altered transferrin saturation and serum iron levels. In contrast hepatic iron overload achieved without altering such haematopoeitic indices, had a less pronounced effect. In both spleen and heart, the affinities of iron-regulatory factor changed in parallel with both altered iron status and haematological markers. In brain and duodenum, there were no consistent changes in iron-regulatory-factor activity with iron loading or depletion. Iron-regulatory-factor activity in kidney responded in an as yet unexplained manner.

Animals↗
PubMed1997

Dopamine and iron induce apoptosis in PC12 cells.

Recent studies have shown that Fe2+ increases the oxidation of monoamines such as serotonin, dopamine and related toxins and that the formed oxidation products can undergo co-valent binding to free sulphydryl groups of proteins such as actin and "serotonin binding proteins" which are present in soluble brain extracts. Here we have tested the ability of ferrous iron to induce [3H]dopamine association to cytoplasmic proteins and we have established that a similar oxidation mechanism evidenced in vitro studies could be applied in cell culture. When PC12 cells were incubated with ferrous iron (ferrocene), the binding of [3H]dopamine to proteins was found to be two fold increased with respect to control. The iron is likely to accelerate the oxidation of dopamine to produce quinones which covalently bind to proteins and induce high-molecular protein aggregates. We evidenced that dopamine/iron combination induced cell death in undifferentiated PC12 cells via an active cellular process evaluated in terms of morphological and biochemical changes indicative of apoptosis. We also demonstrated induction of lipid peroxidation when dopamine and ferrocene were present in high concentrations. Moreover, ascorbic acid diminished apoptosis but not the lipid peroxidation process. It might indicate that ferrocene and dopamine could produce oxidative stress of a different nature. These results show that the actions of dopamine and iron are essential in the induction of apoptosis and lipid peroxidation. However, there is no necessary casual link between lipid peroxidation and apoptosis. Our data also suggest that iron is capable of increasing the cytotoxicity of dopamine merely by increasing its rate of oxidation and without intervention of the monoamine oxidase B enzyme and, hence, both phenomenons may occur independently from each other in rat pheochromocytoma PC12. These observations may have relevance to the understanding of the mechanism by which dopaminergic neurones are destroyed in some neurodegenerative disorders.

Animals↗
PubMed2006

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.

Aminoquinolines↗
PubMed2001

Rapid electron tunneling through oligophenylenevinylene bridges.

We measured rate constants of thermal, interfacial electron transfer through oligophenylenevinylene bridges between a gold electrode and a tethered redox species in contact with an aqueous electrolyte using the indirect laser-induced temperature jump technique. Analysis of the distance dependence indicates that, unlike other bridges studied to date, the rate constants are not limited by electronic coupling for bridges up to 28 angstroms long. The energy levels of the bridges relative to those of the redox species rule out hopping through the bridge. We conclude that, out to 28 angstroms, the transfer is limited by structural reorganization and that electron tunneling occurs in less than 20 picoseconds, suggesting that oligophenylenevinylene bridges could be useful for wiring molecular electronic elements.

Electrochemistry↗
PubMed1995

Autoencapsulation through intermolecular forces: a synthetic self-assembling spherical complex.

The synthesis and characterization of a system for the study of molecular recognition phenomena are described. The system involves a tetraurea molecule that is capable of assembly into various associated states through hydrogen bonding. In organic solvents, the dynamic transition between a low-ordered (aggregate) state and a highly ordered dimeric assembly can be induced by the introduction of smaller molecules of appropriate size and shape. These smaller molecules, such as benzene, adamantanes, and ferrocenes, act as guests that occupy the pseudospherical capsule formed by the dimeric host. Among various guests, those that best fill the cavity and offer chemical complementarity to the host are preferentially encapsulated.

Adamantane↗