J. Mol. Model. 2000, 6, 433 – 437 © Springer-Verlag 2000 F ULL P APER Correspondence to: M. N. Moreno-Carretero Introduction Pteridine derivatives are very interesting molecules because they play important roles in many biological systems, [1,2] especially those related to several metalloenzymes [3,4] and molybdopterins. [5-7] Since their biological significance is often associated with their coordinative properties, we are currently studying the molecular structure of several coor- dination compounds of lumazine (pteridine-2,4(1H,3H)- dione) derivatives. Despite their having two oxygen and four nitrogen at- oms, which may act as potential donor sites, both infrared and X-ray diffraction studies have shown that lumazine de- rivatives act as either neutral [8-14] or monodeprotonated [15,16] bidentate chelating ligands, but always through the N5 and O4 atoms. This paper is focused on justifying this non-versatile behaviour. The prediction and/or explanation of the coordination modes of a ligand from calculations of partial charges has been widely used, [17] but it has also been demonstrated in several papers that this method may be unsuccessful, [18-21] the present paper being a new ex- ample of this fact. Therefore, we have also tried to justify this coordination behaviour from molecular orbital calcula- Theoretical Investigations (PM3) on the Coordinative Properties of Lumazine (Pteridine-2,4(10,30)-dione) and its Methylated Derivatives Esther R. Acuña-Cueva, Francisco Hueso-Ureña, Sonia B. Jiménez-Pulido, and Miguel N. Moreno-Carretero Departamento de Química Inorgánica y Orgánica, Campus Universitario ”Las Lagunillas” (B-3), Universidad de Jaén, E-23071 Jaén, España. Fax: +34-53-212186; E-mail: mmoreno@ujaen.es Received: 12 November 1999/ Accepted: 20 January 2000/ Published: 5 May 2000 Abstract In order to study from a theoretical point of view the coordinative properties and explain the reported N5,O4-chelating behaviour in several oxopteridine derivatives, semiempirical molecular or- bital calculations were carried out on lumazine (pteridine-2,4(1H,3H)-dione), its N- and C-methylated derivatives, as well as their deprotonated and protonated forms using the PM3 hamiltonian as imple- mented in the HYPERCHEM 4.0 package. The study of the partial charges over donor atoms does not allow us to justify the reported N5,O4-coordinating scheme, because some positive charge has been found on the N5 atom. Therefore, a more detailed analysis has been carried out taking into account the contribu- tions of the AOs of each atom to the LCAO that defines each frontier MO. These calculations have confirmed the N5-O4 coordination mode of the neutral lumazine derivatives. The anionic forms could act as ligands in several ways, including the formation of either four- (N1-N8, N3-O4, N3-O2) or five- membered chelate rings (N5,O4). The experimental occurrence of only the latter coordination mode must be related to the higher stability of the five-membered chelate rings if it is compared with those of four and the possibility to establish π-M–N5 back-bonding. Keywords Lumazine, Pteridine, PM3