Structural, Chemical Topological, Electrotopological and Electronic Structure Hypotheses

The first important hypothesis in the prediction of properties of synthesized molecules is the structural hypothesis. In the study of drug–receptor interactions, the case where the three-dimensional structure of the receptor is known allows the application of molecular simulation and energy calculations to estimate the binding affinity for a proposed series of compounds. The chemical topological hypothesis permits the description of molecular structures without using concepts such as force or energy. These notions would not be as dominant as supposed since they should be able to be deduced from topology. Although topological descriptors are able to describe specific physicochemical properties, there is no any mechanistic interpretation for topological descriptors, but they can be considered as essential magnitudes, able to describe molecular structure as an alternative and independent approach, since they allow an algebraic description of the structure itself. The hypothesis is based on the ability of topological descriptors for the prediction of virtually any kind of structure-related macroscopic property, and to design directly new compounds showing predetermined properties. It is possible to design new lead drugs ignoring the explicit mechanism of action, but only by topological similarity with other active compounds. This is a basic difference with all the conventional methods based on the use of physical variables, which need to know the specific drug–receptor interaction. The electrotopological hypothesis may be considered a synthesis of both previous hypotheses. Finally, the electronic structure hypothesis is formulated.