Materials Science and Engineering B 165 (2009) 266–269 Contents lists available at ScienceDirect Materials Science and Engineering B journal homepage: www.elsevier.com/locate/mseb The –* molecular structure of flavin of FADH - enzymatic cofactor using the LCAO method L.G.D. Hawke a , C. Simserides b,∗ , G. Kalosakas a a University of Patras, Materials Science Department, GR-26504, Rio, Greece b Institute of Materials Science, NCSR Demokritos, GR-15310, Athens, Greece article info Article history: Received 28 August 2008 Received in revised form 26 January 2009 Accepted 18 February 2009 Keywords: Organic substances Atoms and molecules Electron states abstract The –* molecular structure (eigenenergies and eigenfunctions) of flavin tricyclic ring is calculated, using the linear combination of atomic orbitals (LCAO) method containing only p z atomic orbitals. In respect to FADH - position opposite to DNA lesion in photolyase, flavin’s HOMO is found to be distributed in the central and distal side, while LUMO is localized in the distal side of flavin (the side that is closer to the adenine part of FADH - and farther than the DNA dimer lesion). LUMO1 as well as LUMO2 are mainly distributed in the proximal side of flavin (the side that is closer to the DNA dimer). Our findings are com- pared with previous theoretical results as well as with experimental values of known –* transitions. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Pyrimidine dimerization is one of the most common damages caused by UV radiation in DNA. Photolyase is an enzyme that binds to the defected DNA sequence and repairs the damage, through an electron-transfer reaction, when exposed to UV–vis light. A main cofactor of photolyase is a two-electron reduced flavin adenine din- ucleotide (FADH - ). In the electron-transfer repair mechanism, an electron is transferred from an excited * singlet state of flavin of FADH - to the damaged DNA segment. When the dimer is split, the electron is transferred back to the oxidized flavin and then photolyase dissociates from the repaired DNA segment. This mech- anism of light-induced repair of DNA is summarized in several articles [1–4]. It seems that the enzyme binds specifically to UV- irradiated DNA, independent of the DNA conformation or any distortion of the helix [5]. Previous works suggested that the electron-transfer mechanism between flavin adenine dinucleotide and the damaged DNA dimer can be direct [6] or indirect [7]. In both cases the active group of FADH - is the tricyclic ring of flavin. Prytkova et al. proposed a direct mechanism for the electron transfer [6]. In particular using ab ini- tio (time-dependent density functional theory and time-dependent Hartree–Fock) and semiempirical (INDO/S configuration) methods, they computed the lower excited states of FADH - and found that the shorter electron-transfer pathway consists of a direct jump in ∗ Corresponding author. Tel.: +30 210 6503313; fax: +30 210 6519430. E-mail address: simserides@ims.demokritos.gr (C. Simserides). space, from the flavin of FADH - to the dimer lesion of DNA. The main reason that led them to this suggestion was the localization of the donor state (LUMO of flavin) in the proximal side (the side that is closer to the DNA dimer) of flavin tricyclic ring. On the contrary, the indirect mechanism, proposed by Antony et al., suggests that the primary electron transfer from donor (LUMO state of flavin) to acceptor (DNA dimer lesion) occurs via the adenine moiety, which acts as an intermediate [7]. In this case the donor state is found to be localized in the distal side of flavin tricyclic ring (the side that is closer to the adenine part of FADH - and farther than the DNA dimer lesion). Note that, although the planar illustration of FADH - (cf. Fig. 1) indicates that the electron transfer from flavin to adenine is not very likely, the actual FADH - structure is folded up in such a way that the adenine moiety lies above flavin. Flavin is a planar tricyclic ring formed by carbon, nitrogen, and oxygen atoms, connected with sp 2 hybridization bonds. The p z atomic orbitals, perpendicular to the plane of the atoms, are delocalized forming  molecular orbitals. The simplest way to approximately calculate these  molecular orbitals, is by using the LCAO method. Thus, one can obtain the excited * orbitals, including LUMO, which is the donor state of flavin. The squared coefficients of the LCAO expansion of each molecular wavefunc- tion in terms of atomic p z orbitals, provide the probabilities for finding the corresponding electron at the atoms forming flavin. Therefore, addition of these probabilities over certain molecular regions reveals the “localization” of the molecular orbital in vari- ous sides of flavin (distal, central, or proximal side, with reference to the location of the DNA dimer). The donor (LUMO) state is of particular interest in this respect. 0921-5107/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.mseb.2009.02.012