Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Structure-activity relationships in halogenated biphenyls: unifying hypothesis for structural specificity.

J D McKinney, P Singh

    Chemico-Biological Interactions
    |January 1, 1981
    PubMed
    Summary

    Structural requirements for halogenated aromatic hydrocarbon toxicity were investigated. Planarity is not essential for receptor binding; instead, molecular polarizability and halogen arrangement are key factors for toxicity induction in guinea pigs.

    Related Concept Videos

    You might also read

    Related Articles

    Articles linked to this work by shared authors, journal, and citation graph.

    Sort by
    Same author

    Metabolism and disposition of inorganic arsenic in laboratory animals and humans.

    Environmental geochemistry and health·2013
    Same author

    Characterization and imaging in optically scattering media by use of laser speckle and a variable-coherence source.

    Optics letters·2007
    Same author

    Millimeter-wave arbitrary waveform generation with a direct space-to-time pulse shaper.

    Optics letters·2007
    Same author

    Cost efficiency in the prospective diagnosis and follow-up of polyomavirus allograft nephropathy.

    Transplantation proceedings·2005
    Same author

    Effects of a mixture of polychlorinated biphenyls (Aroclor 1254) on the transcriptional activity of thyroid hormone receptor.

    Journal of endocrinological investigation·2004
    Same author

    In vivo veritas: the search for TB drug targets goes live.

    Nature medicine·2000

    Area of Science:

    • Environmental Chemistry
    • Toxicology
    • Structural Biology

    Background:

    • Halogenated aromatic hydrocarbons (HAHs) like polychlorinated biphenyls (PCBs) are environmental contaminants.
    • Understanding their structure-activity relationships is crucial for assessing toxicity and biological interactions.
    • Cytochrome P-450 enzymes and associated monooxygenase activities are key targets for HAHs.

    Purpose of the Study:

    • To elucidate the specific structural requirements for the induction of cytochrome P-448, P-450, and related activities.
    • To determine the structural basis for the exquisite toxicity of HAHs in guinea pigs.
    • To investigate the roles of molecular planarity, symmetry, and polarizability in receptor binding and toxicity.

    Main Methods:

    • Single crystal X-ray diffraction techniques were employed to determine the solid-state structure and conformation of PCBs and polybrominated biphenyls (PBBs).

    Related Experiment Videos

  • Crystallographic data were correlated with theoretical and toxicological data to establish structure-activity relationships.
  • Conformational analysis was used to approximate interactions with biological receptors.

    • Main Results:

    • The most stable conformation for biphenyls, even with ortho-substituents, is non-planar.
    • Neither planarity nor symmetry is an inherent requirement for receptor binding.
    • A minimum of three lateral bromines or four lateral chlorines, arranged in a specific triangular or box-like pattern, is required for toxicity.
    • Net molecular polarizability, influenced by halogen arrangement and ortho-substitution, is the primary factor for binding affinity.

    Conclusions:

    • Molecular planarity is only necessary to achieve the required juxtaposition of halogens for binding.
    • Binding affinity is primarily determined by molecular polarizability, while steric fit is influenced by coplanarity.
    • Variations in conformational preferences and their impact on polarizability explain mixed induction patterns observed for certain isomers.
    • A unifying hypothesis for structural specificity in HAH toxicity is proposed, integrating crystallographic, theoretical, and toxicological data.