SP154 The role of pharmacogenetics and pharmacogenomics in cancer therapy

Abstract

A brief survey of modern concepts and principles of the electronic structure and chemical reactivity is presented with an emphasis on the importance of chemical concepts for understanding the molecular behavior. The specificity of the chemical interpretation of molecular processes, in terms of AIM, chemical bonds, functional groups, reactants, etc., is commented upon. The classical structural and reactivity rules are reviewed. The quadratic Taylor expansion of the electronic energy of molecular systems in powers of displacements (perturbations) of the system state-parameters is introduced. It is defined by the generalized response quantities: “potentials”, the first partials of the energy, and charge sensitivities, the second partials of the energy with respect to the system parameters of state. This series constitutes an adequate framework for describing reactant subsystems in a bimolecular reactive system. The role of the electronic density as the source and carrier of the complete information about the system ground-state equilibrium and all its physical and chemical properties is stressed. Basic elements of the electron wave-function and density-functional theories of electronic structure are summarized and the conceptual advantages of DFT over the standard wave-function approach are emphasized. The Euler equation for the ground-state density, the DFT equivalent of the Schrödinger equation of the wave-function theory, is discussed in some detail. It embodies the crucial ground-state relation between the equilibrium distribution of electrons and the external potential due to the system nuclei. This equation is shown to imply the chemical potential (electronegativity) equalization throughout the physical space. A distinction is made between transitions from one ground-state density to another, called here the “horizontal” displacements of the system electronic structure, and those corresponding to flows of electrons between molecular subsystems, for the fixed density of the molecule as a whole, called the “vertical” displacements.