DFT Chemical Reactivity Driven by Biological Activity: Applications for the Toxicological Fate of Chlorinated PAHs

摘要

The logistic kinetics model of quantitative reactivity-activity relationships is presented as a modern tool for modeling chemical-biological interactions using catalytic progress curves for the chemical ligand species that bind biological cell receptors. Chemical reactivity principles of electronegativity and chemical hardness, their necessity, the associated scenario of chemical bonding, the critical points in ab initio quantum chemical computations of the molecular structures, and the QSAR-OECD principles are reviewed. Illustrative applications are described for chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) bound to aryl hydrocarbon receptors (AhRs) in human breast cancer MCF-7 cells, Pimephales promelas and rats by recognizing key features of Biological Activity driving Chemical Reactivity (BioAct-ChemReact) interaction mechanisms. The specific feedback behavior of biological sites against chemical attacks unveil the manner in which chemical reactivity indices and principles of electronegativity and chemical hardness act successively or synergistically (in chemical power and electrophilicity) to regulate chemical reactivity hierarchies in ligand-receptor mechanisms that reflect observed (or in silico computed) biological or toxicological effects.