Definition of a novel atomic index for QSAR: the refractotopological state.

ABSTRACT

PURPOSE: In this work, a novel descriptor of atoms in molecules is introduced. The Refractotopological State Index for atoms (R-state,R), rectifies the atomic refractivity values reported by Crippen et al with the atomic refractivity values of the topological environment of each skeletal atom in the molecule. METHOD: The R-state (R(i)), for atom i is an hybrid index that is defined as the intrinsic refractivity value of the atom i (AR(i)) plus a perturbation term Delta AR(i) in the non-hydrogen depleted graph. RESULTS: The variations of the R values in different molecules are showed. QSAR examples previously reported by other authors are given for benzimidazole inhibition of Lee strain flu virus and receptor binding affinity of beta-carbolines. CONCLUSIONS: The index does not only describe the representation of the atomic dispersive forces related to the molar refractivity but also the influence of bounded and unbounded atoms as a measure of the distance-effect of the other groups in the molecule. The R-state index has proved a good performance, either alone or combined with the electro topological (E)-state index. This implies that in those cases this representation of dispersive forces between the molecule and the active site is a valid approach to the biological problem: