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Structural Isomerism02:34

Structural Isomerism

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Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can...
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Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
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Stereoisomerism02:52

Stereoisomerism

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Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
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Valence Bond Theory02:42

Valence Bond Theory

10.9K
Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...
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Crystal Field Theory - Tetrahedral and Square Planar Complexes02:46

Crystal Field Theory - Tetrahedral and Square Planar Complexes

47.5K
Tetrahedral Complexes
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than the dxy,...
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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
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Structurally Strained Half-Sandwich Iridium(III) Complexes As Highly Potent Anticancer Agents.

Ana C Carrasco1, Vanessa Rodríguez-Fanjul1, Abraha Habtemariam1,2

  • 1IMDEA Nanociencia, Faraday 9, 28049 Madrid, Spain.

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|March 26, 2020
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Researchers developed new iridium-based anticancer drugs. These tether-ring complexes show significantly higher potency against cancer cells compared to non-tethered versions, offering a promising new class of drug candidates.

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Area of Science:

  • Organometallic Chemistry
  • Medicinal Chemistry
  • Cancer Research

Background:

  • Development of novel anticancer agents is crucial for improving cancer therapy.
  • Iridium complexes have shown promise as anticancer drugs, but their potency needs enhancement.
  • Structural modifications can significantly impact the efficacy and mechanism of action of metal-based drugs.

Purpose of the Study:

  • To synthesize and characterize novel iridium complexes with a unique tether-ring structure.
  • To evaluate the in vitro anticancer activity of these complexes against cancer cell lines.
  • To investigate the mechanism of action, including mitochondrial disruption and oxidative stress induction.

Main Methods:

  • Synthesis of six iridium complexes with the formula [Ir(η⁵:κ¹-C₅Me₄CH₂py)(C,N)]PF₆.
  • Structural characterization using X-ray crystallography for key complexes.
  • Anticancer activity evaluation against MCF7 cancer cells, comparison with cisplatin, and assessment of mitochondrial membrane potential and oxidative stress.

Main Results:

  • The synthesized tether-ring iridium complexes (1-6) demonstrated significantly enhanced anticancer potency (1-2 orders of magnitude higher) compared to their non-tethered counterparts.
  • Complexes 1-6 were found to disrupt mitochondrial membrane potential (ΔΨm) and induce oxidative stress in cancer cells.
  • Internalization studies confirmed a strong correlation between intracellular accumulation and observed anticancer activity.

Conclusions:

  • A new class of organo-iridium drug candidates with a tether-ring structural motif has been developed.
  • This structural feature leads to a substantial increase in anticancer potency.
  • These findings highlight the potential of these iridium complexes as next-generation anticancer therapeutics.