A theoretical study on interaction of bispidine analogue of cisplatin [(C7H14N2)PtCl2] with guanine;DFT, EDA-NOCV and NBO analysis

Since discovery of cisplatin, many efforts have been devoted to understand the mechanisms associated with its antitumor activity, which are nowadays quite well established [1]. The primary target of cisplatin is genomic DNA, and more especially the N7 position of guanine bases. Although there is no doubt that a Pt−N7 bond forms during initial attack, the exact structure of the monofunctional adduct is not well known [2]. A better understanding at the molecular level of the interactions between the Pt and DNAbuilding blocks can be helpful in establishing a new strategy to design cisplatin analogues. In this work we report a theoretical study on the interaction of bispidine analogue of cisplatin [(C7H14N2)PtCl2] (1; see Figure 1) with guanine, at BP86/def2- TZVP level of theory. Since the guanine has three possible binding sites with the transition metal, all isomers and conformers of 1-guanine complexes were optimized. The calculated relative free energies and interaction energies between 1 and guanine showed that the preferred binding site of guanine to complex 1 (similar to cisplatin) is N7. To investigate the nature of interaction between 1 and guanine, the EDA-NOCV and NBO analyses were also performed on 1-guanine complex. The results of energy decomposition analysis, at BP86-D3/TZ2P level of theory, for all complexes show that the electrostatic nature of interaction between 1 and guanine is more than the covalent (~60% versus ~35%) and contribution of dispersion forces is ~5%.