AZAPSORALENS-DNA INTERACTIONS - CRYSTAL-STRUCTURE CHARACTERIZATION OFFURAN-SIDE MONOADDUCT AND COMPUTER-AIDED STUDIES

In this paper a theoretical study, concerning molecular mechanics opti mised structures, obtained by quantum mechanics as well as molecular m echanics calculations was carried out with the aim of correlating the theoretical model of the interactions between azapsoralens and DNA wit h the data experimentally obtained. The theoretical model suggests tha t both furan-side and pyrone-side double bonds may be involved in the cycloaddition with pyrimidines (although the cycloaddition at the leve l of furan is preferred), and is in line with the capacity of these co mpounds to form inter-strand cross-links. Moreover, concerning the the oretical intercalation model calculations on 3,4,4',5'-tetramethylazap soralen intercalated inside a polynucleotide, they suggest a cis-syn a rrangement between furan-side of the intercalated ligand and the above situated thymine, with which, under light activation, a cycloadduct m ay take place, having a cis-syn steric arrangement. Also this datum is in agreement with the cis-syn regio and stereochemistry of the isolat ed 4,4',5'-trimethylazapsoralen-thymine cycloadduct. Finally, from the oretical data, the role of nitrogen seems not important: in fact only small differences were found with the corresponding methylpsoralens so that the small differences observed may be mainly attributed to steri c rather than to electronic effects. In general a good correlation bet ween the theoretical model and the experimental data was observed.