Density Functional Theory Investigation of Polycyclical Peroxide Stability.

Polycyclic peroxide compounds have been of interest for their antimalarial activity. The synthesis of stable peroxide compounds can be challenging, thus making preliminary computational determination of the stability of promising compounds advisable. Density functional theory is used to gauge the st...

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Publicado en:Journal of the Utah Academy of Sciences, Arts & Letters Vol. 93; pp. 293 - 307
Autores principales: Simon, Charles Joseph, Davies, Don R., Berghout, H. Laine
Formato: Artículo
Publicado: Utah Academy of Sciences, Arts & Letters 2016
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2016
      vid: 93
      pid: 59066
      pub: Utah Academy of Sciences, Arts & Letters
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        atl: Density Functional Theory Investigation of Polycyclical Peroxide Stability.
      aug:
        au:
          Simon, Charles Joseph
          Davies, Don R.
          Berghout, H. Laine
        affil: Weber State University
      su:
        Peroxide synthesis
        Antimalarials
        Density functional theory
        Hydrogen bonding
        Biochemical mechanism of action
      sug:
        subj:
          Peroxide synthesis
          Antimalarials
          Density functional theory
          Hydrogen bonding
          Biochemical mechanism of action
      ab: Polycyclic peroxide compounds have been of interest for their antimalarial activity. The synthesis of stable peroxide compounds can be challenging, thus making preliminary computational determination of the stability of promising compounds advisable. Density functional theory is used to gauge the stability of one such peroxide, 2,3,10-trioxabicyclo[5.2.1]decan-4-ol. An intramolecular hydrogen bond between the two rings of this bridged bicyclical compound is anticipated to contribute to the stability of the molecule. Based on coordinate scans of the hydroxyl dihedral bond angle at the B3LYP/6-311+G(2d, p) level of theory, we estimate the strength of this intramolecular hydrogen bonding interaction at 8.6 kcal/mol, considerably above the 5 kcal/mol typical for R-O-H---O=C-R'. The mechanism of action of peroxide antimalarial compounds is likely initiated via homolytic bond cleavage of the O-O bond. The energy of activation (ΔG‡) for this homolysis process is calculated to be approximately 40.6 kcal/mol in the gas phase, similar to the literature bond dissociation value of hydrogen peroxide at 43.7 kcal/mol, which makes it likely that this process is fairly slow with an estimated uncatalyzed first-order rate constant of 1×10 s.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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