Following the approach adopted in earlier studies in the series, this work undertakes a QSAR investigation of the in vivo interaction of 2- and 6-substituted purine derivatives with murine solid tumour adenocarcinoma CA 755. The interaction is analyzed in terms of hydrophobic, electronic (orbital and electrostatic), and geometric (topological and steric) contributions. Exhaustive correlations with the bioactivity of a large number of different types of indices representing these various contributions have been made. It was concluded that the significant indices here are the electronic superdelocalizality indices S(E)6, S(E)10 and S(N)10, and the hydrophobic index pi (6). Appropriate regression equations are presented, and these support the contention that our methodology is able to satisfactorily model biological interactions produced by sets of structurally related molecules.

Following the approach adopted in earlier studies in the series, this work undertakes a QSAR investigation of the in vivo interaction of 2- and 6-substituted purine derivatives with murine solid tumour adenocarcinoma CA 755. The interaction is analyzed in terms of hydrophobic, electronic (orbital and electrostatic), and geometric (topological and steric) contributions. Exhaustive correlations with the bioactivity of a large number of different types of indices representing these various contributions have been made. It was concluded that the significant indices here are the electronic superdelocalizallity indices SE6, SE10 and SN10, and the hydrophobic index π (6). Appropriate regression equations are presented, and these support the contention that our methodology is able to satisfactorily model biological interactions produced by sets of structurally related molecules.

An approach is presented for modelling the biological activity of organic molecules. This approach requires a consideration of the influence of all factors (topological, steric, hydrophobic, electronic) which determine the bioactivity. In this work, the interaction between substituted pyridines and antibodies generated by anti-3-azapyridine is studied. The stereoelectronic interactions are responsible for the reaction. Meta-positions to nitrogen are found to be the most probable positions for attack. The most likely reaction products are pi-complexes with charges transfer from the biomolecule to the pyridine derivatives followed by the formation of covalent-type bonds.

In the first part of this series it was shown that, for interactions between substituted pyridines and anti-3-azopyridine antibody, the maximum biological activity is observed for an optimum electronic correspondence between the reactants. This particular result, together with data in the literature which points to the necessity for geometrical and lipophilic correspondence, supports a generalization for the nature of the biological action of chemical compounds. Accordingly in this paper it is proposed that the affinity towards a given biomacromolecule will be maximum only for those chemicals within a series of compounds which are characterized by optimum values of basic factors which condition the biological activity: geometric, electronic, and/or lipophilic. The practical aspects of the hypothesis should be valuable in molecular pharmacology, drug design, and theory of chemical reactivity.

A novel approach for modelling the biological activity of organic molecules, which requires simultaneous consideration of the influence of all factors (topological, steric, hydrophobic, and electronic) that determine the bioactivity, is used to study the interaction of a series of benzoates with anti-p-(p'-azophenylazo)benzoate antibody. The results obtained suggest that this biological interaction proceeds by a two-step stereospecific mechanism. The first step requires a geometrical correspondence between the benzoates and the cavity in the biomacromolecule, which enables the pharmacophore to come into close contact with the receptor. The second step is the orbitally controlled electronic interaction between the active parts of the benzoates and the antibody. The electronic interaction results from pi-charge transfer from the pharmacophore to the biomacromolecule and from the formation of pi-complexes. A proposed mathematical model for this biological interaction exhibits some statistical advantages over existing models.