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Metal-Ligand Bonds02:51

Metal-Ligand Bonds

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The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
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Complexation Equilibria: Factors Influencing Stability of Complexes01:09

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In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
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Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Extraction: Advanced Methods00:56

Extraction: Advanced Methods

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Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
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Amyloid Fibrils03:03

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Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
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EDTA: Auxiliary Complexing Reagents01:26

EDTA: Auxiliary Complexing Reagents

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EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
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Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation.

Sara La Manna1, Valentina Roviello2, Fabiana Napolitano3

  • 1Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.

Inorganic Chemistry
|June 20, 2023
PubMed
Summary

Three metal-based carbon monoxide-releasing molecules (CORMs) were tested for their impact on amyloid aggregation. Two CORMs promoted aggregation, while one inhibited it, suggesting potential for developing antiamyloidogenic agents.

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Area of Science:

  • Biochemistry
  • Materials Science
  • Medicinal Chemistry

Background:

  • Neurodegenerative diseases are linked to uncontrolled protein aggregation, specifically amyloid formation.
  • Modulating protein self-recognition is a key strategy for developing treatments.

Purpose of the Study:

  • To investigate the effects of three novel metal-based carbon monoxide-releasing molecules (CORMs) on the aggregation of the amyloidogenic peptide fragment NPM1264-277.
  • To explore the potential of these CORMs as antiamyloidogenic agents.

Main Methods:

  • Synthesis and characterization of three metal complexes: Cym-Ade, Cym-Cipro, and Re-Flavo.
  • Thioflavin T (ThT) assay, UV-vis absorption, fluorescence spectroscopy, scanning electron microscopy (SEM), and electrospray ionization mass spectrometry (ESI-MS) were employed.
  • Analysis of peptide aggregation kinetics and fiber morphology.

Main Results:

  • Cym-Ade and Cym-Cipro acted as aggregating agents, promoting the formation of longer and stiffer/thicker amyloid fibers.
  • Irradiation of Cym-Ade accelerated fiber formation, yielding more flexible and thicker fibers.
  • Re-Flavo demonstrated anti-aggregating properties, inhibiting NPM1264-277 self-assembly.
  • The study revealed distinct aggregation modulation effects based on the CORM's structure.

Conclusions:

  • Metal-based CORMs exhibit diverse effects on amyloid fiber formation, acting as either aggregators or inhibitors.
  • The choice of ligands significantly influences the biological activity of CORMs.
  • These findings highlight the potential for designing metal-based compounds as therapeutic agents against amyloid-related pathologies.