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
Subject(s)
Chemistry, Pharmaceutical , Models, Chemical , Quantitative Structure-Activity Relationship , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Molecular Conformation , Orthomyxoviridae/drug effectsABSTRACT
PURPOSE: Development of a novel semi-empirical descriptor (MR(chi) for molecular modelling. METHOD: The index is based on a molar refractivity partition using Randictype graph-theoretical invariant. RESULTS: This hybrid index describes not only the London dispersive forces in a ligand fragment related to the molar refractivity but also structural features of the molecule It is also applicable in Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) studies. CONCLUSIONS: The method is convenient and can discriminate between isomers.
Subject(s)
Models, Chemical , Molecular Structure , Chemistry, Pharmaceutical , Computer Simulation , Ligands , Models, Statistical , Pharmaceutical Preparations/chemistry , Quantitative Structure-Activity Relationship , Structure-Activity Relationship , ThermodynamicsABSTRACT
PIP: The article discusses the case of a young patient with ruptured benign adenoma of the liver, possibly related to previous treatment with oral contraceptives. The patient, whose adenoma was bleeding into the peritoneal cavity, underwent right hepatectomy by the Lin technique. There were no complications. Complete resection is the only known adequate treatment for these benign tumors, and Lin's technique and surgical instruments have proven to be very helpful.^ieng
