AI Article Synopsis

  • - The study used density functional theory to analyze the structural and electronic properties of 25 phosphonate derivatives, employing the PBEPBE functional with a 6-311++G
  • basis set to assess their chemical reactivity through quantum descriptors like HOMO, LUMO, and Hirshfeld charges.
  • - A multiple linear regression model was developed to predict the toxicity of phosphonates based on factors such as molecular volume, electronegative atom charge, and HOMO eigenvalue, showing strong internal validation results.
  • - The findings suggest that the oxygen atom in the O=P group significantly influences the interaction of phosphonates with the acetylcholinesterase enzyme, contributing to their inhibitory effect and potential toxicity.

Article Abstract

Structural and electronic properties of a series of 25 phosphonate derivatives were analyzed applying density functional theory, with the exchange-correlation functional PBEPBE in combination with the 6-311++G** basis set for all atoms. The chemical reactivity of these derivatives has been interpreted using quantum descriptors such as frontier molecular orbitals (HOMO, LUMO), Hirshfeld charges, molecular electrostatic potential, and the dual descriptor [[Formula: see text]]. These descriptors are directly related to experimental median lethal dose ([Formula: see text], expressed as its decimal logarithm [[Formula: see text]([Formula: see text]] through a multiple linear regression equation. The proposed model predicts the toxicity of phosphonates in function of the volume (V), the load of the most electronegative atom of the molecule (q), and the eigenvalue of the molecular orbital HOMO ([Formula: see text]. The obtained values in the internal validation of the model are: [Formula: see text]%, [Formula: see text]%, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]%. The toxicity of nine phosphonate derivatives used as test molecules was adequately predicted by the model. The theoretical results indicate that the oxygen atom of the O=P group plays an important role in the interaction mechanism between the phosphonate and the acetylcholinesterase enzyme, inhibiting the removal of the proton of the ser-200 residue by the his-440 residue.

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Source
http://dx.doi.org/10.1007/s11030-018-9819-2DOI Listing

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