The Electrotopological State: An Atom Index for QSAR

Abstract

AbstractA new characterization of atoms in molecules is introduced as the electrotopological state index, which combines both the electronic character and the topological environment of each skeletal atom in a molecule. The electrotopological state (E‐state) of a skeletal atom is formulated as an intrinsic value Ii plus a perturbation term ΔIi, arising from the electronic interaction within the molecular topological environment of each atom in the molecule. The atom intrinsic value, for first row atoms, is expressed as I = (δv + 1)δ, in which δv and δ are the counts of valence and sigma electrons, respectively, for the atom in the molecular skeleton. The E‐state, Si, for atom i is defined as Si = Ij + ΔIj, where the influence of other atoms on atom i, ΔIi, is given as Σ(Ij — Ij)/rij2; rij is the graph separation between atoms i and j, counted as number of atoms, including i and j. Information in the electrotopological state is revealed by examples of various types of organic structures, including skeletal branching and heteroatom variation. The relation of the E‐state value to NMR chemical shift is demonstrated for a series of carbonyl compounds. QSAR examples are given for hydrazide inhibition of MAO and for receptor binding of β‐carbolines. These examples reveal the power of this approach to QSAR using atom level indexes, computed directly from molecule connection tables, in which it is possible to identify atoms and regions in the molecule which are important for activity.