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Radical Reactivity: Nucleophilic Radicals01:16

Radical Reactivity: Nucleophilic Radicals

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Radicals adjacent to electron-donating groups are called nucleophilic radicals. These radicals readily react with electrophilic alkenes. The SOMO–LUMO interactions are the driving force for the reaction, where the high-energy SOMO of the electron-rich, nucleophilic radicals interacts with the low-energy LUMO of the electron-deficient, electrophilic alkenes. Such SOMO–LUMO interactions are the basis of reactive radical traps, affecting the selectivity in radical reactions. For...
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Radical Reactivity: Electrophilic Radicals01:02

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Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...
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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
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A bond can be broken either by heterolytic bond cleavage to form ions or homolytic bond cleavage to yield radicals. A fishhook arrow is used to represent the motion of a single electron in homolytic bond cleavage. There are two main sources from which radicals can be formed:
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Radical Formation: Homolysis00:54

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A bond is formed between two atoms by sharing two electrons. When this bond is broken by supplying sufficient energy, either two electrons can be taken up by one atom forming ions by the cleavage called heterolysis, or the two electrons are shared by two atoms, with one each creating radicals by the cleavage called homolysis.
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Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
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A RaDiCAL gene hunt.

Mihaela Pupavac1, Ma'n H Zawati2, David S Rosenblatt1

  • 1Department of Human Genetics, McGill University, Montreal, Québec, Canada.

Journal of Taibah University Medical Sciences
|August 23, 2019
PubMed
Summary

Rare disease research using next-generation sequencing has identified many genes, but challenges remain for single-proband studies. The RaDiCAL consortium addresses informed consent and the right not to know for international participants in rare genetic disease research.

Keywords:
GenesMendelian diseasesProbandRaDiCALRight not to know

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Area of Science:

  • Genetics
  • Bioethics
  • Rare Diseases

Background:

  • Next-generation sequencing has advanced rare Mendelian disease gene discovery.
  • Many rare diseases still lack identified genetic causes, particularly those with single affected individuals.

Purpose of the Study:

  • To review the Rare Disease Collaboration for Autosomal Loci (RaDiCAL) approach to identifying disease-causing genes in extremely rare conditions.
  • To discuss challenges in obtaining informed consent from international participants for rare disease genetic studies.
  • To consider the ethical implications of the 'right not to know' in study design.

Main Methods:

  • Review of the RaDiCAL consortium's methodologies for rare disease gene discovery.
  • Analysis of informed consent procedures for international collaborations.
  • Exploration of ethical considerations in genetic research, including participant autonomy.

Main Results:

  • RaDiCAL focuses on the rarest diseases, often involving single probands.
  • The study highlights difficulties in creating effective informed consent documents for diverse international populations.
  • The concept of the 'right not to know' is presented as a key ethical consideration in rare disease research design.

Conclusions:

  • Identifying disease-causing genes for ultra-rare conditions requires innovative approaches.
  • International collaboration in rare disease research necessitates careful attention to informed consent.
  • Ethical frameworks must evolve to incorporate concepts like the 'right not to know' to protect participants in genetic studies.