MS-CASPT2 Study of Hole Transfer in Guanine-Indole Complexes Using the Generalized Mulliken-Hush Method: Effective Two-State Treatment C. Butchosa, † S. Simon, † L. Blancafort,* ,† and A. Voityuk* ,†,‡ † Institut de Química Computacional, Departament de Química, Universitat de Girona, Campus de Montilivi, Girona, 17071 Spain ‡ Institució Catalana de Recerca i Estudis Avanç ats (ICREA), Barcelona, 08010 Spain * S Supporting Information ABSTRACT: Because hole transfer from nucleobases to amino acid residues in DNA-protein complexes can prevent oxidative damage of DNA in living cells, computational modeling of the process is of high interest. We performed MS-CASPT2 calculations of several model structures of π- stacked guanine and indole and derived electron-transfer (ET) parameters for these systems using the generalized Mulliken-Hush (GMH) method. We show that the two-state model commonly applied to treat thermal ET between adjacent donor and acceptor is of limited use for the considered systems because of the small gap between the ground and first excited states in the indole radical cation. The ET parameters obtained within the two- state GMH scheme can deviate significantly from the corresponding matrix elements of the two-state effective Hamiltonian based on the GMH treatment of three adiabatic states. The computed values of diabatic energies and electronic couplings provide benchmarks to assess the performance of less sophisticated computational methods. ■ INTRODUCTION During the past three decades, hole transfer (migration of radical cation states) through DNA and its artificial analogues has been an area of extensive experimental and theoretical studies. 1-5 Attention to this field is motivated by the role played by hole transfer (HT) in several biological processes such as damage and repair of DNA and mediation of signaling in living cells. 6 In particular, special proteins called photolyases can repair damaged DNA in living cells. 7 The underlying mechanism has been analyzed by computational studies (see recent articles 8,9 and references therein). Also, migration of a hole from DNA to a neighboring cofactor or an amino acid residue of the protein environment can protect genomic DNA from the oxidative damage. This implies that HT is faster than irreversible reactions of the radical cation state of a nucleobase with water, oxygen, and other species leading to the formation of DNA lesions. 6,10 The formation of radical cation states in biomolecules is controlled by their oxidation potential. Among natural nucleobases, guanine has the lowest ionization energy and acts as a hole trap in DNA. In proteins, the best hole acceptor is the amino acid tryptophan (Trp), the indole group (Ind) of which can effectively trap an electron hole. In particular, it was experimentally found that the guanine radical cation is able to oxidize tryptophan residues. 11,12 Whereas hole migration through DNA π stacks is well-documented, 1-5 much is still unknown about HT in DNA-protein complexes. Only a few computational studies of HT between nucleobases and amino acid residues have been reported. 13,14 Density functional theory (DFT) calculations of indole complexes with guanine (G) and adenine (A) showed that the HT process can occur not only in π-stacked but also in T-shaped structures, where the aromatic rings of Ind and G or A are perpendicular to each other. It was also found that the driving force and electronic coupling of the HT depend significantly on the mutual orientation of the donor and acceptor sites. 15-17 Distinct from radical cations G + and A + , Ind + has a small energy gap between the ground and first excited states, as shown in Figure 1. Experimental values of the vertical ionization energies were obtained from refs 18 and 19. The excited state in G + lies 1.6 eV higher than the ground state, whereas the energy gap in Ind + is only ∼0.5 eV. This means that the excited state of Ind + can affect the thermal HT process G + + Ind → G + Ind + . To take this effect into account, a three- state scheme rather than the commonly used two-state scheme must be applied to derive the site energies and coupling for thermal HT between G + and Ind. Moreover, because the HT parameters depend on the mutual positions of the redox centers, the contribution of the Ind + excited state is expected to be sensitive to the orientations of the G and Ind molecules. Received: April 17, 2012 Revised: June 5, 2012 Published: June 14, 2012 Article pubs.acs.org/JPCB © 2012 American Chemical Society 7815 dx.doi.org/10.1021/jp303675h | J. Phys. Chem. B 2012, 116, 7815-7820