Role of backbones on the interaction of metal ions with deoxyribonucleic acid and peptide nucleic acid: A DFT study.

Metal ion interaction with deoxyribonucleic acid and peptide nucleic acid were studied using B3LYP-D3/6-311++g(d,p)//B3LYP/6-31 + G(d) level of theory in aqueous phase employing polarized continuum (PCM) model. This study reports the role of backbones on deoxyribonucleic acid and peptide nucleic acid for complexation with different metal ions. The systematic study performed with DFT calculations reveals that central binding (Type-4) shows the strongest binding compared to the other binding modes because of the involvement of the backbone as well as the nitrogenous bases. The charged backbone of DNA nucleotides contributes significantly towards binding with the metal ions. The deoxyguanosine monophosphate (dGMP) clearly indicates the strongest binding upon complexation with Mg (-49.6 kcal/mol), Zn (-45.3 kcal/mol) and Cu (-148.4 kcal/mol), respectively. The neutral backbone of PNA also assists to complex the metal ions with PNA nucleotides. The Mg and Cu prefer to bind with the PNA-Cytosine (-32.9 kcal/mol & -132.9 kcal/mol) in central binding mode (type-4). PNA-Adenine-Zn (-29.1 kcal/mol) is the preferred binding mode (type-4) compared to other modes of interaction for this metal ion with PNA-Adenine nucleotide. The Cu ion showed the superior complexation ability with deoxyribonucleic acid and peptide nucleic acid compared to Mg and Zn ions. The cation-π complexation with the bases of nucleotides was also obtained with Cu ion. The AIM (atoms in molecule) theory has been applied to examine the nature of the interaction of Mg, Zn, and Cu ion to the deoxyribonucleic acid and peptide nucleic acid. The alkaline earth metal, Mg ion shows electrostatic nature while interaction with deoxyribonucleic acid and peptide nucleic acid, however, the transition metal ions (Zn, Cu) showed partly covalent nature as well with deoxyribonucleic acid and peptide nucleic acid. The optical properties calculated for the binding of metal ions with deoxyribonucleic acid and peptide nucleic acid showed a diagnostic signature to ascertain the interaction of metal ions with such nucleotides. Cu ion showed larger red shifts in the absorption spectrum values upon complexation with the DNAs and PNAs. The calculated results suggest that such metal ions would prefer to bind with the DNA compared to PNA in DNA-PNA duplexes. The preference for the binding of metal ions with DNA nucleotides is largely attributed to the contribution of charged backbones compared to the neutral PNA backbones.