Published: June 02, 2011 r2011 American Chemical Society 8032 dx.doi.org/10.1021/jp202839u | J. Phys. Chem. A 2011, 115, 8032–8040 ARTICLE pubs.acs.org/JPCA Use of the Dual Potential to Rationalize the Occurrence of Some DNA Lesions (Pyrimidic Dimers) Christophe Morell,* ,† Vanessa Labet, † Paul W. Ayers, ‡ Luigi Genovese, § Andr  e Grand, † and Henry Chermette || † INAC/SCIB/LAN (UMR-E n°3 CEA-UJF  FRE3200 CNRS), CEA-Grenoble, 17, rue des Martyrs, F-38054 Grenoble Cedex 9, France ‡ Department of Chemistry and Chemical Biology, McMaster University Hamilton, Ontario, L8S 4M1, Canada § SP2M, UMR-E CEA/UJF-Grenoble 1, INAC, Grenoble, F-38054, France ) Sciences Analytiques Chimie Physique Th eorique, Universit  e de Lyon, Universit  e Lyon 1 (UCBL) et UMR CNRS 5180, bat Dirac, 43 bd du 11 novembre 1918, F-69622 Villeurbanne Cedex, France 1. INTRODUCTION Conceptual Density Functional Theory (DFT) is a mathe- matical framework in which qualitative theories are developed to understand chemical reactivity and selectivity. 1,6 Basically, the overall chemical reactivity is assessed by several global descriptors 79 that stem from derivatives of the energy with respect to the number of electrons. Local reactivity parameters, of paramount importance for the understanding of chemical selectivity, arise from the response of the energy as the external potential experienced by the electronic system changes. Within Conceptual DFT, numerous organic and inorganic rules have been rationalized as purely electronic effects. 10 Moreover, differ- ent chemical reactivity principles have arisen from a better understanding of the nature of DFT descriptors. Nevertheless, in spite of three decades of great success, 11,12 two kinds of chemical reactions are still difficult to apprehend within this framework. Specifically, the way radical and excited state species evolve during a chemical process is not yet totally understood. For the former, a whole new mathematical framework 1317 has been set up but so far the results obtained are not totally convincing. For the latter, the issue is inherent in the mathema- tical foundation of DFT. Indeed, the two foundational theorems of DFT, namely, the first and the second HohenbergKohn theorems, 18 are only valid for the ground state of an electronic system. Thus, for excited states, the physical and mathematical equations are still to be developed, even though different tentative studies have already been undertaken. 1924 Very recently, the present authors have proposed an alter- native way to rationalize the chemical selectivity of an excited state species. 25 That analysis starts by hypothesizing that relaxa- tion of the electronic density of the excited state species toward the ground state can be facilitated by a chemical reagent. This is merely an update of the Fukui’s idea 2628 that for the first excited state the highest occupied molecular orbital (HOMO) becomes the lowest unoccupied molecular orbital (LUMO) and vice versa. Indeed a crude model for the first excited state consists to show the promotion of an electron from the HOMO to the LUMO. Thus, the new HOMO is the former LUMO, while the new LUMO is the former HOMO. This approach was successful and the regio-selectivity of different chemical reactions, mainly Received: March 27, 2011 Revised: May 31, 2011 ABSTRACT: Exploiting the locality of the chemical potential of an excited state when it is evaluated using the ground state Density Functional Theory (DFT), a new local descriptor for excited states has been proposed (J. Chem. Theory Comput. 2009, 5, 2274). This index is based on the assumption that the relaxation of the electronic density toward that of the ground state drives the chemical reactivity of excited states. The sign of the descriptor characterizes the electrophilic or nucleophilic behavior of atomic regions. Through an exact excited state DFT formalism provided by Gross, Oliveira, and Kohn, a mathematical argument is given for this descriptor only for the first excited state. It is afterward used to rationalize the occurrence and the regioselectivity of some DNA lesions based on the [2 þ 2] cycloaddition between two adjacent bases.