Electronic spectroscopy study and molecular docking simulation of the interaction of terthiophene with DNA

We have performed a study by electronic spectroscopy and molecular docking simulation of the interaction of terthiophene with DNA, modelled as short oligonucleotide sequences containing either the guanine–cytosine or the adenine–thymine motif. We demonstrated that the presence of TT gives rise to a non-vanished increase of the melting temperature of highly polymerized DNA. From this result, we investigated the interaction of TT with the 16-mer oligonucleotides ds(dC–dG)8 and ds(dA–dT)8 using UV–visible and fluorescence emission spectroscopy. UV–visible titrations suggested intercalation of TT into ds(dA–dT)8 and possibility of both intercalation and groove binding in the case of ds(dC–dG)8. The fluorescence spectra demonstrated that TT cannot remove ethidium from both oligonucleotides, while the analysis of the fluorescence emission of TT evidenced sequence selectivity. Thus, the obtained results in the case of ds(dA–dT)8 were compatible with intercalation, while the results for ds(dG–dC)8 suggested the existence of charge-transfer processes between the nucleic bases and the ligand. These processes are favoured by an intercalative binding, although interaction by the grooves is not discarded. In any case, our results suggested a different intercalation mode for these sequences, which was also supported by the docked structures. We built two modified 12-mer oligonucleotides having a hole suitable to host an aromatic planar system as TT. In the model obtained with ds(dA–dT)6 the longest axis of TT was perpendicular to the direction of the hydrogen bonds between the strands. However, in the docked structure with ds(dG–dC)6 the TT axis was parallel to the hydrogen bonds, which could favour the π–π charge-transfer processes.