Basic Ideas of the Electron-Topological Approach

The main shortcomings of the qualitative QSAR methods mentioned above lie in the poor description of the molecular properties determining the biological activity. In particular, while the spatial structure and atomic composition in the above methods (e.g., in the method of DC) are given fully enough, the electronic properties are presented rather poorly, or even completely ignored. This is unjustified because the electronic structure is the most important feature of the molecule as it interacts with the bioreceptor. 

On the other hand, in the quantitative methods discussed above where the electronic parameters are included, the compounds under consideration are strongly limited by the requirement that they be similar in structure over the whole series. The purpose of the electron-topological QSAR method under consideration in this review is to overcome the shortcomings of the previous QSAR methods, which ignore (completely or partly) the role of electronic structure in the description of the molecules or consider only series of compounds with similar structures. 

Given a series of N molecules with known biological activity or inactivity and provided that the conformations and electronic structure of these molecules can be determined, the essence of the ET method is as follows.For each molecule the so-called electron-topological matrix of congruity (ETMC) or, in the more sophisticated versions, a set of ETMC —the three-dimensional ETMC (TDETMC) —is constructed as shown schematically below. 

Each of the ETMC in this set is a square matrix that is symmetric == with respect to the diagonal elements. Therefore only the upper half of it is shown the whole number of independent elements is n[n + l)/2, where n equals the number of atoms in the molecule. The number m of ETMC in the TDETMC depends on our choice of electronic structure parameters. For the diagonal elements i = 2,.. . , n k = 1,2. w, the atomic param- 

Although the geometric parameters for a given conformation of the molecule remain fixed, the electronic ones can be chosen differently and with different combinations of atomic and bond parameters. For instance, one can take atomic charges as atomic characteristics in combination with bond orders as bond characteristics, or atomic polarizabilities with bond energies, or atomic charges with bond polarizabilities, and so on. Each of these combinations produces a certain ETMC. Hence there are m such possibilities, the number m 

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