Copper ion Cu(I) interaction effect on DNA nucleotides: DFT study

In this work we have studied copper ion Cu(I) interaction with separated or adjacent nucleotides: Adenosine A-Cu(I), Thymidine T-Cu(I) and [Adenosine-Thymidine Cu(I)(2)]. The structures and thermodynamic stabilities of these molecules were studied in the gas phase by using the DFT method was used at the B3LYP/6-311 + G(d,p) level. In this manner, both the metal ion affinity (MIA = -Delta H) and the molecular electrostatic potential (MEP) were estimated and compared for all complexes. The molecular energies, which were monitored on performing angular torsions such as the [C4-N9-C12-O12] one for Adenosine and the [O10-C11-N1-C2] one for Thymidine, proved that copper Cu(I) interaction with Adenosine is larger. Then, the NBO charges were calculated for the adjacent nucleotides [A-T] and for their copper adduct [A-TCu(I)(2)]. The results show that hyper-conjugative interaction between a donor group (i.e., the non-bonding n lone pair of the nitrogen atom N33) and the acceptor orbital (i.e., anti-bonding sigma* level of the N3-H13 linkage) is best stabilizing. In other words, the -18.51 kcal mol(-1) energy associated to the D-A couple LP(N33))/sigma*(N3-H13)) is found to be lower that the corresponding LP(O7)/sigma*(N41-H42)) one -11.70 kcal mol(-1). Accordingly, the hyper-conjugative component involving the adjacent nucleotides (LP(N33)/sigma*(N3-H13)) favors the interaction of the nucleotide with the copper ion by about -6 kcal mol(-1). The NBO charges prove that the hydrogen bond formed by [N33 (delta = - 0.627)center dot center dot center dot H13 (delta = 0.457)] has stronger electrostatic character than that formed by [O7(delta = - 0.679) center dot center dot center dot H42(delta = 0.432)].