Regul ar Ar t icl e PHYSICAL CHEMISTRY RESEARCH Published by the Iranian Chemical Society www.physchemres.org info@physchemres.org Phys. Chem. Res., Vol. 2, No. 2, 229-243, December 2014. Nature of Lithium Interactions with DNA Nucleobases: Theoretical Study M. Farrokhnia a,b and A.H. Pakiari a, * a Chemistry Department, College of Science, Shiraz University b The Persian Gulf Marine Biotechnology Research Center, Bushehr University of Medical Sciences, Bushehr, Iran (Received 2 March 2014, Accepted 4 August 2014) In the present study, the interactions of three different lithium species Li + , Li 3 + and CH 3 Li with several different sites of the most stable tautomers of DNA nucleo-bases are presented. This investigation is based on the results of thermochemical properties, Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) analysis, obtained at B3LYP/6-311++G(d,p) level of theory. The calculated results showed that guanine and cytosine have more tendencies for interaction with lithium in all above three lithium species. Also, it was shown that for each tautomer of the same nucleobase, coordination mode of lithium highly affects the value of Metal Ion Affinity (MIA). Bidentate base has more lithium affinity and the carbonyl oxygen is generally preferred over amino nitrogen. Furthermore, the analysis revealed the electrostatic nature of interactions. Li + -DNA-Base has the most MIA value and CH 3 Li-DNA-Base has the least one. Keywords: Lithium cation, DNA nucleobase, Thermochemistry, Metal interaction INTRODUCTION The information stored in deoxyribonucleic acid (DNA) indicates that each step required for the organism to construct a replica of itself. DNA contains three important sites including phosphate groups and the sugar part as well as the DNA-bases. This is well-known that the coordinated metal ions play a significant role in the biological action of nucleic acids, and directly impact on oxidation-reduction reactions or induce conformational changes indirectly [1]. For instance, alkali metal cations interact with DNA-bases and destroy the hydrogen bonded network between the base pairs. Consequently, the structure of DNA will be changed [2-4]. Although metal cations are vital for essential processes and their presence may stabilize the special form of DNA, the improper metal cations or wrong concentration of vital ions may cause undesired effects [5]. As a result of DNA significance in biological environments, knowledge of the thermodynamic, structural, and electronic features *Corresponding author. E-mail: pakiariah@gmail.com which manage the interaction between alkali metal cations and nucleic acid bases, can give useful indication of their interactions with more complex nucleic acid polymers. The H + and Li + interactions with DNA-bases have been investigated by a diversity of experimental and theoretical methods in recent years [6-16]. Experimental gas phase studies on interaction of alkali metal cations including Li + with DNA-bases have been performed by using different mass spectroscopy methods [9,17-24]. Rodgers and Armentrant have studied the lithium affinities for uracil, thymine and adenine by threshold collision-induced dissociation in Xenon using guided ion beam mass spectrometry and the MP2 computational method [12]. NMR studies of Li + interaction with nucleosides have been also reported in literatures [25,26]. Cerda and Wesdemiotis have reported the interaction of Li + , Na + and K + with DNA- bases by modified version of kinetic methods; however, they did not show the information on the coordination site of metal [16] . Del Bene [27] has published the results of a study for the Li + complex of the DNA-bases by ab initio calculations