Multipurpose Iron-Chelating Ligands Inspired by Bioavailable Molecules.

Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents and cleaning solutions as well as in soil remediation, electroplating, waste treatment, and so on. For instance, iron-chelation therapy, which is used to treat iron-overload disorders, involves removing excess iron from the blood through the use of particular molecules, like deferoxamine, that have the ability to chelate the metal. The creation of bioinspired and biodegradable chelating agents is a crucial objective that draws inspiration from natural products.

A family of kojic acid derivatives aimed to remediation of Pb and Cd.

The present work analyzes the complex formation ability towards Pb and Cd of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by H and C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb and Cd was proved: in the case of Pb, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd.

Entropy and Enthalpy Effects on Metal Complex Formation in Non-Aqueous Solvents: The Case of Silver(I) and Monoamines.

Access to the enthalpy and entropy of the formation of metal complexes in solution is essential for understanding the factors determining their thermodynamic stability and speciation. As a case study, in this report we systematically examine the complexation of silver(I) in acetonitrile (AN) with the following monoamines: n-propylamine (), n-butylamine (), hexylamine (), diethylamine (), dipropylamine (), dibutylamine (), triethylamine () and tripropylamine (). The study shows that the complex stabilities are quite independent of the length of the substitution chain on the N atom and demonstrates that, in general, the overall enthalpy terms associated with the complex formation are strongly exothermic, whereas the entropy values oppose the complex formations.

A Multi-Technique Investigation of the Complex Formation Equilibria between Bis-Deferiprone Derivatives and Oxidovanadium (IV).

The increasing biomedical interest in high-stability oxidovanadium(IV) complexes with hydroxypyridinone ligands leads us to investigate the complex formation equilibria of VO ion with a tetradentate ligand, named KC21, which contains two 3-hydroxy-1,2-dimethylpyridin-4(1)-one (deferiprone) moieties, and with the simple bidentate ligand that constitutes the basic unit of KC21, for comparison, named L5. These equilibrium studies were conducted with joined potentiometric-spectrophotometric titrations, and the results were substantiated with EPR measurements at variable pH values. This multi-technique study gave evidence of the formation of an extremely stable 1:1 complex between KC21 and oxidovanadium(IV) at a physiological pH, which could find promising pharmacological applications.

Thermodynamic Study of Oxidovanadium(IV) with Kojic Acid Derivatives: A Multi-Technique Approach.

The good chelating properties of hydroxypyrone (HPO) derivatives towards oxidovanadium(IV) cation, VO, constitute the precondition for the development of new insulin-mimetic and anticancer compounds. In the present work, we examined the VO complex formation equilibria of two kojic acid (KA) derivatives, L4 and L9, structurally constituted by two kojic acid units linked in position 6 through methylene diamine and diethyl-ethylenediamine, respectively. These chemical systems have been characterized in solution by the combined use of various complementary techniques, as UV-vis spectrophotometry, potentiometry, NMR and EPR spectroscopy, ESI-MS spectrometry, and DFT calculations.

A Friendly Complexing Agent for Spectrophotometric Determination of Total Iron.

Iron, one of the most common metals in the environment, plays a fundamental role in many biological as well as biogeochemical processes, which determine its availability in different oxidation states. Its relevance in environmental and industrial chemistry, human physiology, and many other fields has made it necessary to develop and optimize analysis techniques for accurate determination. Spectrophotometric methods are the most frequently applied in the analytical determination of iron in real samples.

Metal Toxicity and Speciation: A Review.

Background: Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned, and any concentration imbalance in the form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes, may eventually causing death. Conversely, non-essential metals are not necessary for life, and only noxious effects could arise after their exposure.

Phosphonate Chelators for Medicinal Metal Ions.

A family of phosphonate-bearing chelators was synthesized to study their potential in metal-based (radio)pharmaceuticals. Three ligands (Hphospa, Hdipedpa, Heppy; structures illustrated in manuscript) were fully characterized, including X-ray crystallographic structures of Hphospa and Hdipedpa. NMR spectroscopy techniques were used to confirm the complexation of each ligand with selected trivalent metal ions.

Chelating Agents in Soil Remediation: A New Method for a Pragmatic Choice of the Right Chelator.

Soil pollution by metal ions constitutes one of the most significant environmental problems in the world, being the ecosystems of extended areas wholly compromised. The remediation of soils is an impelling necessity, and different methodologies are used and studied for reaching this goal. Among them, the application of chelating agents is one of the most promising since it could allow the removal of metal ions while preserving the most meaningful properties of the original soils.

The Potential Clinical Properties of Magnesium.

A significant percentage of costs in pharmaceutical markets is devoted to supplements due to the confidence of consumers in the beneficial effects of these products. Magnesium is one of the supplements with enduring and increasing popularity. According to what is reported online, this metal ion can cure or prevent almost all kinds of diseases.

Gold Nanoparticles: A New Golden Era in Oncology?

In recent years, the spectrum of possible applications of gold in diagnostics and therapeutic approaches in clinical practice has changed significantly, becoming surprisingly broad. Nowadays, gold-based therapeutic agents are used in the therapy of multiple human diseases, ranging from degenerative to infectious diseases and, in particular, to cancer. At the basis of these performances of gold, there is the development of new gold-based nanoparticles, characterized by a promising risk/benefit ratio that favors their introduction in clinical trials.

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson's Disease.

Wilson's disease is a congenital disorder of copper metabolism whose pathogenesis remains, at least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, has encouraged many authors to look for epigenetic factors interacting with the genetic changes.

Metal self-assembly mimosine peptides with enhanced antimicrobial activity: towards a new generation of multitasking chelating agents.

Mimosine is a non-protein amino acid with various properties, such as antibacterial, anti-inflammatory, anti-cancer and anti-virus among others. Due to its structural similarity with deferiprone (DFP), mimosine is a potential excellent metal chelator. In the present work, we combine experimental and theoretical (DFT) approaches in order to investigate the properties of mimosine peptides.

Oxovanadium(IV) Coordination Compounds with Kojic Acid Derivatives in Aqueous Solution.

Hydroxypyrone derivatives have a good bioavailability in rats and mice and have been used in drug development. Moreover, they show chelating properties towards vanadyl cation that could be used in insulin-mimetic compound development. In this work, the formation of coordination compounds of oxovanadium(IV) with four kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone) derivatives was studied.

New strong extrafunctionalizable tris(3,4-HP) and bis(3,4-HP) metal sequestering agents: synthesis, solution and in vivo metal chelation.

Finding new multifunctional metal binders to be potentially used in diagnosis or therapy has been a subject of major challenge. Hydroxypyridinones have long been recognized as privileged chelating structures for the design of metal chelating drugs, especially towards hard metal ions, in view of their decorporation in metal overload disorders. Thus, pursuing our strategy of engineering new polydentate 3-hydroxy-4-pyridinones (3,4-HP) with extrafunctionalization capacity for sensing or targeting purposes, we report herein the synthesis and full characterization of a hexadentate (tris-3,4-HP) and a tetradentate (bis-3,4-HP) ligand, possessing three and two 3,4-HP arms N-attached to an aminomethanetrispropionic acid backbone, respectively.

A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead.

The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg.

A new tripodal kojic acid derivative for iron sequestration: Synthesis, protonation, complex formation studies with Fe, Al, Cu and Zn, and in vivo bioassays.

This work presents the simple and low cost synthesis of a new tripodal ligand, in which three units of kojic acid are coupled to a tris(2-aminoethyl)amine (tren) backbone molecule. The protonation equilibria, together with the complex formation equilibria of this ligand with Fe, Al, Cu and Zn ions were studied. The complementary use of potentiometric, spectrophotometric and NMR techniques, and of Density Functional Theory (DFT) calculations, has allowed a thorough characterization of the different species involved in equilibrium.