ORIGINAL PAPER DFT investigation of the mismatched base pairs (T-Hg-T) 3 , (U-Hg-U) 3 , d(T-Hg-T) 2 , and d(U-Hg-U) 2 Tiziana Marino Received: 31 January 2014 /Accepted: 12 May 2014 # European Union 2014 Abstract Mismatched T:T and U:U base pairs in DNA and RNA duplexes represent the preferred target for mercury(II) cations. In this work, the structural, energetic, and electronic properties of the metallo base pairs T-Hg-T and U-Hg-U were investigated using density functional theory. In order to eval- uate the geometric and energetic effects on the stacking inter- action, the systems (T-Hg-T) 3 and (U-Hg-U) 3 systems as well as the dinucleotide systems d(T-Hg-T) 2 and d(U-Hg-U) 2 were examined. Results show that the exchange–correlation func- tionals B3LYP-D3 and M06-L yield reasonable information on these systems that is in agreement with the available experimental data. Keywords Nucleic acids . DFT . Mismatched base pair . Mercury ion Introduction Metal-mediated base pairs of nucleic acids (NA) have attracted considerable interest due to their potential applica- tions in nanotechnology [1–5]. The metal–NA interactions and the metallophilic attractions in these systems can affect their thermodynamic properties when compared to the corre- sponding nonmetalated systems. In the pyrimidine–pyrimi- dine T:T and U:U mismatched base pairs, the structural inclu- sion of an Hg(II) cation gives rise to a stable system with a melting point that is higher by about 4 °C (6 °C) for the DNA and RNA duplexes, respectively, than the melting points of the corresponding metal-free duplexes [6–8]. Mercury is well known for its polluting and toxic properties as well as its capacity to affect physiological processes involv- ing important biological molecules such as nucleic acids [9–11]. In particular, although the binding of mercury ions to large DNA and RNA fragments causes denaturation and structural destabilization in principle, the Hg(II) metalation process occurs on the A-T base pair, generating mismatched T-Hg-T base pairs. This mechanism is believed to account for the cytotoxicity of mercury [1, 12]. The preferred binding sites of the metal ions are the nitrogen atoms of the nucleic acid bases [13]. In pyrimidine bases, the Hg 2+ ion binds directly to N3 of thymidine, replacing the imino proton and linking two thymine residues T:T (or U:U), giving rise to a T-Hg-T (or U-Hg-U) monomer characterized by a neutral charge, as evidenced by previous works [1, 2, 5, 14]. The formation of these kinds of complexes has been demonstrated by different experimental techniques (e.g., CD, NMR, and UV) [1, 2, 5, 15]. A further peculiarity of such T:T base pairs is that the metal links form reversibly after temperature denaturation [2, 15, 16]. The ionic size of mercury (1.44 Å) combined with the natural spacing present in the DNA duplex (~3.4 Å) makes it possible to incorporate the ion without inducing significant alterations to the structure of the double helix. Furthermore, the presence of other monomers (T-Hg-T or U-Hg-U) in- creases the hole transfer efficiency of the DNA (RNA) chain [17] due to the dominance of the dispersion interaction over the electrostatic one [18, 19]. The possibility of using novel DNA structure-based sen- sors that are capable of selectively detecting Hg 2+ ion in aqueous solutions and designing new (nano) materials con- taining metals [1, 20–23] has recently drawn the attentions of many experimentalists and theoreticians, as confirmed by the This paper belongs to Topical Collection QUITEL 2013 Electronic supplementary material The online version of this article (doi:10.1007/s00894-014-2303-8) contains supplementary material, which is available to authorized users. T. Marino (*) Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87030 Arcavacata di Rende, CS, Italy e-mail: tmarino@unical.it J Mol Model (2014) 20:2303 DOI 10.1007/s00894-014-2303-8