The utility of computed superdelocalizability for predicting the LC50 values of epoxides to guppies

Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models

“…The following is a partial list of descriptors that can be calculated: LUMO (lowest unoccupied molecular orbital) energy, HOMO (highest occupied molecular orbital) energy, dipole moment, molecular polarisability, solvent accessible surface area, atomic charge on an atom, nucleophilic and electrophilic superdelocalisabilities of bonds, atoms and molecules, heat of formation, and the change in free energy of reactions. Many of these descriptors are useful in predicting reactivity and since some chemicals are toxic because they react with cellular biochemicals to denature them, the descriptors can be used to predict toxicity (Verhaar et al, 1996;Purdy, 1991;Lewis, 1992). These descriptors have recently started to be commonly used and so there are not yet many QSARs based on them, but the descriptors appear to provide tools to lump chemicals into larger classes than the traditional classes based on substructures.…”

Guidelines for developing and using quantitative structure‐activity relationships

“…The following is a partial list of descriptors that can be calculated: LUMO energy, highest‐occupied molecular orbital (HOMO) energy; hydrogen bonding ability; dipole moment; molecular polarizability; solvent accessible surface area; atomic charge on an atom; nucleophilic and electrophilic superdelocalizabilities of bonds, atoms and molecules; heat of formation; and the change in free energy of reactions. Many of these descriptors are useful in predicting reactivity and because some chemicals are toxic they react with cellular biochemicals to denature them, the descriptors can be used to predict toxicity [96–98] and receptor binding affinities [99]. These descriptors became commonly used only in the last five years, but the descriptors appear to provide tools to group chemicals into larger classes than the traditional classes based on chemical substructures [100].…”

Modeling the nucleophilic reactivity of small organochlorine electrophiles: A mechanistically based quantitative structure‐activity relationship

“…In the past few years attempts have been made to develop aquatic toxicity QSARs for reactive compounds that try to model the excess toxicity of these compounds. To give some examples, Purdy [19] used the nucleophilic delocalizability as originally proposed by Fukui and coworkers [20,21] to model the excess toxicity of epoxides; Schüürmann [22] used semiempirical quantum chemical parameters to account for the excess toxicity of organophosphorus pesticides; and Eriksson et al [23,24] used a set of structural and semiempirical quantum chemical parameters together with partial least squares (PLS) multivariate regression techniques to describe the electrophilic reactivity of an extensive set of epoxides. These approaches are fairly successful in describing the actual aquatic toxicity of the training set that was used to develop the model.…”