Quantum topological molecular similarity. Part 5. Further development with an application to the toxicity of polychlorinated dibenzo-p-dioxins(PCDDs)

A new method called quantum topological molecular similarity (QTMS), which was previously introduced, is further developed and applied. An excellent and statistically validated QSAR is obtained for the Hammett acidity constants of a set of 68 carboxylic acids including p- and m-benzoic acids, p-phenylacetic acid, 4-X-bicyclo[2.2.2]octane-1-carboxylic acids and poly-substituted benzoic acids. This investigation shows that the previously imposed condition for a minimal and restricted common molecular skeleton can be relaxed. The O–H and the C–O bonds are recovered as the active center as expected. The first time use of atomic properties instead of bond properties leads to valid QSARs. Finally QTMS is applied to predict three different activities (pEC₅₀) of the ecologically relevant polychlorinated dibenzo-p-dioxins (PCDDs). We find that the active center is concentrated near the lateral C–Cl bonds.