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Formation of Complex Ions03:45

Formation of Complex Ions

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A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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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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Complexation Equilibria: Factors Influencing Stability of Complexes01:09

Complexation Equilibria: Factors Influencing Stability of Complexes

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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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EDTA: Chemistry and Properties01:22

EDTA: Chemistry and Properties

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Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
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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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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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Related Experiment Video

Updated: Sep 11, 2025

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
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Divalent and Trivalent Metallic Ions Differentially Affect Alpha-Synuclein Aggregation.

Noah J Graves1, Ali K Jaafar1, Yann Gambin1

  • 1EMBL Australia Node for Single Molecule Sciences and School of Biomedical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales 2052, Australia.

ACS Chemical Neuroscience
|August 11, 2025
PubMed
Summary
This summary is machine-generated.

Metal ions influence alpha-synuclein (αSyn) aggregation, a key factor in Parkinson's disease. Zinc accelerates αSyn aggregation, while iron and aluminum show concentration-dependent effects, impacting strain formation and toxicity.

Keywords:
Parkinson’s diseasealpha-synucleinamyloidkineticsmetal ionsstrains

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alpha-synuclein (αSyn) aggregation is central to synucleinopathies like Parkinson's disease.
  • Altered metal ion homeostasis is implicated in αSyn's pathological behavior and disease progression.

Purpose of the Study:

  • To investigate the impact of various metal ions on αSyn aggregation kinetics and strain formation.
  • To characterize the structural properties and cellular toxicity of metal-associated αSyn aggregates.

Main Methods:

  • In vitro aggregation assays of recombinant αSyn with Ca2+, Mg2+, Cu2+, Zn2+, Fe3+, and Al3+.
  • Limited proteolysis, single molecule fingerprinting, and transmission electron microscopy (TEM) were used to analyze aggregate structures.
  • Cellular toxicity assays were performed on metal-associated αSyn strains.

Main Results:

  • Zinc ions accelerated de novo αSyn aggregation in a concentration-dependent manner.
  • Trivalent cations (Fe3+, Al3+) exhibited dual effects: promoting elongation at low concentrations and inhibiting aggregation at high concentrations.
  • Al3+-associated αSyn strains displayed distinct structural properties and enhanced cellular toxicity compared to metal-free and Fe3+-associated fibrils.

Conclusions:

  • Metal ions differentially modulate αSyn aggregation kinetics and lead to the formation of distinct αSyn strains.
  • Metal ion dyshomeostasis contributes to αSyn pathologies through altered strain formation and cellular toxicity, offering new therapeutic targets.