Could 2,6-bis((E)-2-(furan-2-yl)vinyl)-1-methylpyridinium iodide and analog compounds intercalate DNA? A first principle prediction based on structural and electronic properties

DFT calculations were used to investigate the structure and electronic properties of some analogs of 2,6-bis((E)-2-(furan-2-yl)vinyl)-1-methylpyridinium iodide which was considered as a benchmark. We focus our attention over the ability of these molecules to intercalate between the two strands of DNA indicating a potential antitumor activity. DFT optimized structures, compared with experimental biological data, allowed us to suggest that the activity decreases when the molecules deviate from geometric planarity. In this sense it is to note the role played by substituent such as the phenyl group which, giving rise to a rigid steric hindrance, obstructs the DNA intercalation. Further features make favorable the binding with DNA, in particular we underline the presence of hydrogen bond acceptor atoms and a properly disposition of the planar portion of the molecule with respect to the positive charged portion. Finally calculated binding energies between the molecules and a short fragment of DNA well describe experimental results. From these findings one can argue that the biological activity of such compounds can be related to the DNA intercalation