Metal chelation Research Papers - Academia.edu (original) (raw)

Nutritional iron deficiency represents a relevant health problem mainly in developing countries. Children and
pregnant women represent the main target of this disease, and the low amount of bio-available iron mostly depends on
plant-based diets. Iron deficiency may have serious consequences, with severe impairment of the immune function leading
to infectious diseases. The brain development in embryos and fetuses during gestation can be greatly affected by iron deficiency
of the mother with heavy outcomes on the cognition status of children. A better understanding of molecular
pathways involved in iron absorption and metabolism are the basis for new strategies for developing a therapy for iron deficiency.
Different therapeutic strategies are summarized, and iron fortification appears the best tool.

This work reports the synthesis, characterization and study of complex formation equilibria of the new ligand
6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) with
FeIII, AlIII, CuII and ZnII. On the basis of previous encouraging results with tetradentate bis-kojic acid chelators,
this ligand was designed to improve the pharmacokinetic properties: increase the solubility, neutral at physiological
pH 7.4, and enhancement of membrane crossing ability. FeIII and AlIII complexation gave evidence of high
metal-sequestering capacity of L9. Cellular assays showed that the ligand is capable of crossing cellular
membranes and it does not present toxic effects. Complex formation equilibria with the essential metal
ions CuII and ZnII have been furthermore studied to evaluate disturbances of this chelator on the homeostatic
equilibria of these essential metal ions. A variety of techniques (potentiometry, UV–visible spectrophotometry,
1D and 2D NMR spectroscopy, ESI–MS (electrospray ionization–mass spectrometry), quantum mechanical
calculations and X-ray diffraction) have facilitated the characterization of the ligand, and the corresponding
iron and zinc complexes, together with an exhaustive analysis of the protonation and complex equilibria.

5-Hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one ligand, an iron chelator, was evaluated for its coordination ability toward Al(III), Cu(II) and Zn(II) ions by using potentiometric, NMR, EPR and UV–Vis techniques. The behavior of the ligand with the non-essential Al(III) ion has been examined, as well as its potential influence on the homeostatic equilibria of the essential Cu(II) and Zn(II) ions. Structural information on the complex formation equilibria have been obtained from 1D and 2D NMR study. The donor atoms involved in the coordination of Al(III), Cu(II) and Zn(II) ions are (O, O) the same as for Fe(III) at physiological pH value, even if from the complexation competition study the ligand appears to be more selective toward Fe(III) ions supporting that it can be used as an iron chelating agent. The involvement of N-donor atoms at high pH in Cu(II) coordination has been determined by using EPR and UV–Vis techniques.

- by Massimiliano Peana and +1
- •
- Coordination Chemistry, Modelling Knowledge Coordination, NMR Spectroscopy, EPR Spectroscopy

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe 3+ , studied by combining chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe 3+. The pFe 3+ value 22.0 of P1-iron complexes is noticeable higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al 3+ , Cu 2+ and Zn 2+ has been studied to evaluate the possible use of P1 against a second toxic metal ion (Al 3+), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these last ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelator.

- by Massimiliano Peana and +1
- •
- Coordination Chemistry, Heavy metals, Metal chelation, Heavy metals toxicity

Beer freshness is that what makes a good beer pop. Sadly enough, for both brewers and consumers alike, beer is unresistant to the tooth of time. Noticeable staling can already occur 2-3 months from packaging when stored at room temperature. As beer starts to fade, it loses precious aromas and pleasant (hop) bitterness, all while developing unpalatable or harsh off-flavours.
The question is: does this phenomenon really concern the average home brewer?

- by Tuur Mertens
- •
- Beer (Alcohol Studies), Brewing, Transition metals, Metal chelation

At Eurobic11 in Granada we presented a Keynote Lecture on chelation
therapy, a consolidated medical procedure used primarily to
hinder the effects of toxic metal ions on human tissues [1–2]. Its
application spans a broad spectrum of serious disorders, ranging from
acute metal intoxication to genetic metal-overload. The use of chelating
agents is compromised by a number of serious side effects,
mainly attributable to perturbed equilibrium of essential metal ion
homeostasis and dislocation of complexed metal ions to dangerous
body sites. For this reason, chelation therapy has been limited to
specific critical and otherwise untreatable conditions and it needs to
be monitored within an appropriate clinical context [3–4].
In this meeting we want warn against the widespread fraudulent
use of the term ‘‘chelation therapy’’ to take advantage of and make
profit from people with tragic health problems. We believe that scientists
working in this field have the corollary obligation to deter
these frauds and to inform the scientific community of the possible
side effects and complications of chelation therapy. This duty is all
the more important if we consider the detrimental and even life
threatening consequences that can occur in subjects with no clear
clinical and laboratory evidence of metal intoxication. The aim of this
communication is to present how this ‘‘false chelation therapy’’
developed and in which diseases it is currently applied [5].
This research was supported by the Regione Autonoma Sardegna [CRP-27564].

The complex [Ru(bpy)2(ttma)]+ (bpy = 2,2’-
bipyridine; ttma = 3-hydroxy-2-methylthiopyran-
4-thionate, 1, has previously been
shown to undergo an unusual C-H activation of
the dithiomaltolato ligand upon outer-sphere
oxidation. The reaction generated alcohol and
aldehyde products 2 and 3 from C-H oxidation
of the pendant methyl group. In this report, we
demonstrate that the same products are formed
upon photolysis of 1 in presence of mild
oxidants such as methyl viologen,
[Ru(NH3)6]3+ and [Co(NH3)5Cl]2+, which do
not oxidize 1 in the dark.
This reactivity is engendered only upon
excitation into an absorption band attributed
to the ttma ligand. Analogous experiments
with the homoleptic Zn(ttma)2, 4, also result
in reduction of electron acceptors upon
excitation of the ttma absorbance band.
Complexes 1 and 4 exhibit short-lived
visible fluorescence and long-lived nearinfrared
phosphorescence bands. Singlet
oxygen is both generated and quenched
during aerobic excitation of 1 or 4, but is not
involved in the C-H activation process.

- by Md. Shiblur Rahaman and +2
- •
- Water quality, Arsenic, Metal chelation, Intoxication

Highly sensitive and simple method was developed for preconcentration and determination of trace amounts of cobalt in natural waters and soils using diffuse reflectance spectroscopy was developed. Method is based on the application of the new sorbent-silica gel sequentially modified with polyhexamethylene guanidine and 2-nitroso-1-naphthol-4-sulfonic acid sodium salt (nitroso-N-salt). Optimal conditions of solid-phase extraction of cobalt (II) such as stirring time, pH and volume of the solution, surface concentration of the reagent were determined. During sorption, intensively colored complex of cobalt (III) with nitroso-N-salt, that have a stripe in diffuse reflectance spectrum with maximum at 530 nm, was formed. Sorption-photometric method of cobalt determination directly in the sorbent phase by the color of its complex with nitroso-N-salt using diffuse reflectance spectroscopy was developed. The linearty of calibration curve depended on the surface concentration of nitroso-N-salt. For the surface concentration of nitroso-N-salt of 2.8 µmol g-1 the linearty was maintained in the concentration range of 0.05-5.0 µg Co per 0.100 g of the sorbent, or 0.005-0.50 µg mL-1 if the sorption was carried out from 10 mL of the solution. As the surface concentration of the reagent decreased, the range of linearty of the calibration curve narrowed. The detection limit was calculated as 0.01 μg per 0.100 g of the sorbent (or 1 ng mL-1 if the sorption was carried out from 10 mL of the solution) and didn't depend on the surface concentration of the reagent. Method was applied to the determination of cobalt in natural waters and soils. The accuracy of the results was confirmed by inductively coupled plasma optical emission spectroscopy and recovery test of spiked samples.

- by Pavel Nesterenko
- •
- Solid Phase Extraction, Metal chelation, Cobalt, Preconcentration

Cadmium is not an essential element for humans, but instead its compounds are known for their toxicity. In addition to the risks for workers in industries that use cadmium, this metal can enter the food chain at different levels to be absorbed by the body, where it replaces other metals with similar chemical activity. This also applies to the cadmium inhaled via cigarette smoking. Thus, understanding the interactions between cadmium and biologically relevant molecules, such as amino acids, peptides, and proteins, is important, but it is also useful to study the chelating methods that can cure or alleviate acute or chronic cadmium poisoning cases. 111/113 Cd isotopes are used as NMR probes to determine the complex formation sites and geometry of metals in metalloproteins and metalloenzymes. This review provides a general introduction to the general properties of cadmium as well as the main uses of this metal, its compounds, and artifacts. The toxicity of cadmium in humans is also discussed and the most significant results regarding the interactions between cadmium and other potentially competing divalent metal ions with biological relevance, i.e. Fe(II), Zn(II), Mn(II), Ni(II), and Cu(II), and amino acids and peptides, particularly those containing histidine and/or thiolic groups, are collected. To the best of our knowledge, this is the most comprehensive summary reported for the speciation models of these systems. Distribution and competition diagrams were constructed to facilitate comparisons of the binding abilities of different metals with the same ligand (or vice versa) over a wide pH range and with different reagent concentrations and/or concentration ratios, thereby providing insights into the in vivo behavior both inside and outside cells where the pH and concentration can be very different. The vast topic of complexes with phy-tochelatins and metallothioneins is left for a more focused study. Finally, cadmium chelators with potential pharmacological applications are thoroughly reviewed.

- by Massimiliano Peana
- •
- Coordination Chemistry, Metal Complexes, Poisoning, Metal chelation
- by Maud Benoit
- •
- Biochemistry, NO, Antioxidant, Metal chelation

Flavor stability remains one of the most challenging quality aspects in brewing. Big instigators of beer staling and oxidation are the so-called transition metals (iron, copper, and manganese), as they catalyze and accelerate the Fenton and Haber-Weiss reactions in the formation of reactive oxygen species (ROS). Chelating these metals whilst brewing could potentially reduce deterioration of beer freshness during storage and ultimately prolong shelf-life. In this study, ten compounds were selected to be screened for their complexing capacities with eight metal ions (and an all-including mix) in both a wort- and beer-simulating model solution, using acetate buffer. Measurements were done by UV/VIS and ICP-OES spectroscopy, respectively, to assess changes in absorption; and monitor reductions in metal concentration after incubation and filtration. Ideal chelators should bind iron, copper, and manganese in a way that they can no longer participate in the generation of ROS, but without removing metals that are vital for the yeast and the brewing process (e.g. zinc, calcium, magnesium). At the time of writing, the results (partial and ongoing) suggest gallotannin, gallic acid, and tannic acid to be selective chelators for iron and copper. Manganese, unfortunately, is not readily complexed.

- by Tuur Mertens
- •
- Beer (Alcohol Studies), Brewing, Metal chelation, Reactive Oxygen Species (ROS)
- by Halyna Antonyak
- •
- Water quality, Arsenic, Metal chelation, Intoxication
- by Joanna Lachowicz
- •
- Coordination Chemistry, Metal chelation, Iron Complexation, Chelation Therapy
- by M Jake Pushie and +2
- •
- Inorganic Chemistry, X ray absorption spectroscopy, Neurodegeneration, Humans

Anthracenylamine and naphthylamine were reacted with 1, 3-cyclohexadienone and 1, 4-benzoquinone in order to prepare four (1, 2, 3 &
4) conjugated Schiff bases for the evaluation of their antibacterial as well as antifungal activities. The results of their activities were
compared with standard drugs against three strains of bacteria as well as three strains of fungi and they showed that the Schiff base 4
(C34H22N2O) exhibited good inhibition zones against all the strains of bacteria (10.74 ± 0.65, 10 ± 0.675, 10.65 ± 0.75 mm) as well as
fungi (9.15 ± 0.815, 10.25 ± 0.55, 10.5 ± 0.575 mm) as compared to others (1, 2 & 3). The Schiff base 3 (C26H24N4) showed better
potential for S. aureus (10 ± 0.856 mm) strain of bacteria and A. alternate (10.5 ± 2.150 mm) strain of fungi. Its activity against other two
strains of bacteria and fungi was also better than other two Schiff bases (1 & 2). The Schiff base 2 (C26H22N2) exhibited reasonable activity
against B. subtilus (10 ± 0.715 mm) and A. alternate (8.55 ± 0.015 mm). The compound (1) showed least antibacterial (4.5 ± 0.815, 5 ±
0.716, 4.75 ± 0.950 mm) as well as antifungal (4 ± 0.575, 4.15 ± 0.570, 6.5 ± 1.725 mm) activity. From the results it is concluded that
delocalization of p electrons has the positive influence on the antimicrobial potential of the titled Schiff bases. Thus these Schiff bases
may serve as a basis for the chemical modifications directed towards the development of a new class of antibacterial agents.
Keywords: Conjugated Schiff base, Bacterial strains, Fungal strains, Activity

- by aliirfan rai
- •
- Pharmacology, Organic Chemistry, Natural Products Chemistry, Medicinal Plants

Waste streams generated by electroless copper plating in the printed circuit boards manufacturing industry often contain copper complexed by strong chelating agents such as EDTA. The consequence of metal complexation by chelating agents... more

The use of chelating agents for iron overload diseases has found ever increasing attention [1- 2]. The different drawbacks presented by the chelating agents nowadays in use ask for research on new chelating drugs. In the frame of our research on FeIII and AlIII chelators, a number of ligands containing two kojic acid units joined by different linkers were designed, synthesized, characterized by solid state X-ray diffraction and quantum chemical calculation, and their protonation and FeIII and AlIII complex formation equilibria, using a variety of techniques such as potentiometry, spectrophotometry, ESI-MS, NMR, were exhaustively studied [3-7]. The ligands bearing in the linker a vanillin/ortho-vanillin residue were found promising as iron chelators. Here we will present four similar molecules in which the vanillin/orthovanillin residue has been substituted by an aromatic ring containing a carboxylic or a phenolic substituent. Being a phenolic group characterized by a pK  9 and a ca...

- by Massimiliano Peana
- •
- Coordination Chemistry, Spectroscopy, NMR Spectroscopy, Metal chelation

Here we report about the complex formation among an amine-bearing bis-kojic acid, 6,6′-(2-
(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) and two
metal ions, the trivalent hard and not essential metal ion AlIII and the borderline and essential divalent metal
ion ZnII. We carried out a thorough NMR study in order to reach the indispensable structural information on
the behavior of these complexes in solution. A combination of 1D, 2D total correlation spectroscopy,
heteronuclear single quantum coherence spectroscopy, nuclear Overhauser enhancement spectroscopy and
rotating-frame Overhauser effect spectroscopy experiments was used to assign the signals of both free and
metal-bound ligand at different pH values. Our results highlighted the different coordination behaviors of the
ligand towards the different metal ions, depending on their hard or borderline character. The trivalent metal
ion, AlIII, mainly forms dinuclear helicate complexes of M2L3 stoichiometry, and the coordination only involves
both hydroxypyrone (O,O)-donor atoms. NMR data are in agreementwith the presence of a rigid and symmetric
structure of L9–AlIII complexes up to physiological pH. On the contrary, with the divalent metal ion, NMR data
showed the coexistence of several species in solution though ZnII forms complexes of ML stoichiometry at
physiological pH, where the metal coordination involves the nitrogen atoms of both the linker and the sidechain
amine groups togetherwith the oxygen atoms of phenolate groups. The in solution study will be of interest
for providing an insight on the ligand bioavailability and on its behavior in the chelation treatments.

Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson's syndrome, in neurological and neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

- by Gabriele Toietta
- •
- Alzheimer's Disease, Parkinson's Disease, Diabetes, Cancer

Discussion: This trial was designed to find the best natural compound that can be safely used for chelating men working in environments that are toxic with heavy metals. If successful, this researched natural compound may play a significant role in the treatment, prevention and general well-being of people working in toxic environments such as metal foundries and other industries with toxic by-products in the environment.

- by George Georgiou
- •
- Toxicology, Heavy metals, Mercury toxicity, Metal chelation

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivati...

- by Elma Veljović
- •
- Cancer, Metal chelation, Pharmacology and toxicology, Applied Sciences

Two medical issues emerge from the above 1. We have a case where the "Exjade induces a decrease in Serum Copper" is not applicable 2. If Exjade continuous to elevate the Serum Copper of Constantine Adraktas and takes it much above 170, then we have a case of an Exjade dangerous side effect Constantine Adraktas has communicated via email with several Hematologists around the world on the above medical issues. Their reactions include silence, annoyance and even "Copper is not part of Hematology", the latter being far from the truth.

- by Constantine Adraktas
- •
- Pharmacology, Biochemistry, Medical Sciences, Pharmacy

The Hematologist who will diagnose somebody with a Myeloblastic Syndrome like mine (see below) will automatically prescribe Blood Transfusions, as the first step From that point onwards the patient starts accumulating Iron in the body and sooner or later the patient will require Iron Chelation, as Iron-Serum Ferritin has the following effects : Inhibits Erythropoiesis For every Ferritin levels above 1000, the death risk increases by a factor of 1.36 for every 500 points So for Ferritin levels like mine the death risk has increased by a factor of 9 Low Risk Myeloblastic Syndrome patients, like me, with Ferritin under 500 survive for 10 years For Ferritin under 500, the Leukemia free survival is much longer The Hematologist who will diagnose somebody with a Myeloblastic Syndrome must :-Run an IPSS-R for the patient including the IPSS-RA category for Ferritin (the latter for survival purposes) and inform the patient upfront that :-EPO + G CSF injections (the second step of a Hematologist), whenever beneficial, will work, on the average, for only 25 months the patient becomes EPO refractory and starts relying of frequent Blood Transfusions. Iron Chelation must be initiated long before it comes to that, long before the ensuing frequent Blood Transfusions pour frequently Iron into the patients body.-He must be under the care of a Nephrologist, as his Ferritin will go up through Blood Transfusions and Kidneys can be affected by the currently available drugs for Iron Chelation-He should have MRIs for Iron in the Liver, as the Iron in the Liver measurement is a better measure of Iron in the body than the Serum Ferritin measurement. MRIs for Iron in the Heart are also advisable. When it comes down to my case, as it can be seen below, my saving grace is now restricted to Luspatercept, if I survive until it appears sometime in 2018 Luspatercept, on its final clinical trials focusing on side effects, appears to be reducing the frequency of Blood Transfusions post the EPO refractory stage, thus reducing indirectly the Iron intake In addition Luspatercept, appears to be a direct Iron Chelator

The slides will make it clear

- by Constantine Adraktas
- •
- Medical Sciences, Hematology, Molecular hematology, Medical Education

Monoclinic single crystals of Ba2(H2O)[μ10-C6H2(COO)4] (1) and Pb2(H2O)[μ10-C6H2(COO)4] (2) were obtained using the silica gel method [space group C2/c (no. 15), Z = 4; 1: a = 780.89(4), b = 1756.19(8), c = 914.80(5) pm, β = 114.512(5)°; 2: a = 756.70(10), b = 1772.8(2), c = 890.2(2) pm, β = 113.590(10)°]. There are two crystallographically independent M2+ ions (M = Ba, Pb). M(1) is surrounded by eight carboxylate oxygen atoms and one water molecule forming a tricapped trigonal prism. M(2) is coordinated by ten carboxylate oxygen atoms in the shape of a tetracapped octahedron. The connection between the M(1) and M(2) polyhedra leads to infinite layers parallel to (010), which are linked by [C6H2(COO)4]4– anions to form a three-dimensional framework. The [C6H2(COO)4]4– anion adopts a μ10 coordination mode. Compound 1 reveals short Ba–Ba contacts of 426.46(2) pm, whereas the Pb–Pb distance of 411.01(6) pm in 2 is larger than twice the van der Waals radius.

- by elma veljovic
- •
- Chemistry, Cancer, Metal chelation, Pharmacology and toxicology

Unusual light induced C–H oxidation initiated by excitation into Ru-bound dithiomaltol ligand absorption.

- by Patrick Farmer
- •
- Chemistry, Inorganic Chemistry, Coordination Chemistry, Electrochemistry
- by Massimiliano Peana
- •
- Coordination Chemistry, Pregnancy, Humans, Female
- by Roman Lysiuk and +1
- •
- Water quality, Arsenic, Metal chelation, Intoxication

- by Akash S Mali and +1
- •
- Cancer, Metal chelation, Pharmacology and toxicology

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human
diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and
the induction of oxidative damage in the cell. One efective strategy in reducing the toxic efects of As is the usage of chelating agents, which provide the formation of inert chelator–metal complexes with their further excretion from the body. This
review discusses diferent aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic efect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium
2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent
agents against As toxicity. The review also considers the possible role of favonoids, trace elements, and herbal drugs as
promising natural chelating and detoxifying agents

- by Massimiliano Peana
- •
- Water quality, Arsenic, Metal chelation, Intoxication
- by Evan Burns
- •
- Nutrition, Food and Nutrition, Heavy metals, Toxicity

The ionization equilibria of a set of ortho, meta, and para substituted benzoic acids have been studied by spectrophotometric and potentiometric methods. A dual substituent analysis of the obtained ionization constants is presented, according to the Swain and Lupton procedure. This analysis allows to assign the weight of field and resonance contributions to equilibrium constants and, furthermore, it greatly contributes to forecast the effect of substituents on other correlated properties.

- by Massimiliano Peana
- •
- Coordination Chemistry, Potentiometry, Metal chelation, Spectrophotometry
- by M Jake Pushie and +1
- •
- Neurodegeneration, Copper, EXAFS, Metal chelation