The Multiplicity, Strength, and Nature of the Interaction of Nucleobases with Alkaline and Alkaline Earth Metal Cations:  A Density Functional Theory Investigation

Abstract

Density functional theory (DFT) calculations were performed at the B3LYP/6-311++G(d,p) level to systematically explore the geometrical multiplicity and binding strength for the complexes formed by alkaline and alkaline earth metal cations, viz. Li + , Na + , K + , Be 2+ , Mg 2+ , and Ca 2+ (M n+ , hereinafter), with nucleobases, namely, adenine, cytosine, guanine, thymine, and uracil. Morokuma decomposition and orbital analysis were used to analyze the binding components. A total of 150 initial structures were designed and optimized, of which 93 optimized structures were found, which could be divided into two different types: cation-π complex and cation-heteroatom complex. In the former, a M n+ is located above the nucleobase ring, while in the latter a M n+ directly interacts in flank with the heteroatom(s) of a nucleobase. The strongest binding of -319.2 kcal/mol was found in the Be 2+ -guanine complex. Furthermore, the planar ring structures of the nucleobases in some cation-π complexes were deformed, destroying more or less the aromaticity of the corresponding nucleobases. In the cation-heteroatom complex, bidentate binding is generally stronger than unidentate binding, and of which the bidentate binding with five-membered ring structure has the strongest interaction. Moreover, the calculated Mulliken charges showed that the transferred charge is linearly proportional to the binding strength. Molecular orbital coefficient analysis indicated a significant orbital interaction in cation-π complex, but not in cation-heteroatom interaction. In addition, Morokuma decomposition revealed that electrostatic interaction is more important for cation-heteroatom binding. The majority of the calculated ∆H values are in good agreement with the experimental results. In those cases with significant differences, the experimental results are proximate to an average of the ∆H values of two isomers formed by the same nucleobase and cation.

Unimolecular Reactivity of Uracil–Cu2+ Complexes in the Gas Phase

“…Conventional p complexes, that is, forms c and d are found [10] to be local minima on the potential energy surface. These conventional p complexes are also formed [43] on the interaction with alkali and alkaline earth metal cations, although they are less stable than complexes in which the cation interacts with the heteroatom. Similarly, for Cu + these structures were also found to be much higher in energy (about 176 kJ mol À1 ) than the previously mentioned structures a and b, but they play an important role in the gasphase reactivity of [CuA C H T U N G T R E N N U N G (uracilÀH)] + complexes.…”

Research progress in cation-π interactions

“…All results from these studies not only accorded with the reported data in the literature, but characterized the binding nature of cation-π interactions. For example, the calculated results showed that the binding of alkali and alkaline-earth ions with nucleobases could be divided into two different types: one is cation-heteroatom binding similar to hydrogen bonds; another is cation-π interactions [38] . Cation-π binding evidently distorts the planar ring structure of nucleobases because the binding strength is very strong (up to several hundred kcal·mol −1 ), suggesting cation-π interactions are of sufficient strength to play important roles in maintaining the structure and function of nucleic acids.…”

“…Different cation-π systems possess different proportions of binding components. Since 1997, Zhu and Jiang et al [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] have performed systematic investigations on cation-π interactions by quantum chemical methods. The investigated cations included alkali metal, alkaline-earth metal, NH 4 + , CH 3 NH 3 + , and tetramethylammonium (TMA); the aromatic systems included benzene, substituted benzene, 5-membered and 6-membered aromatic heterocyclic rings, 8-membered aromatic rings, all kinds of aromatic residues and nucleobases.…”

Gas-phase interactions between lead(II) ions and thiouracil nucleobases: A combined experimental and theoretical study

“…We studied mono-and bi-coordination modes and we considered that deprotonation could occur on several sites: nitrogens, C(5), and oxygens or sulfurs for tautomeric forms. We decided not to investigate in detail -interactions because of the resulting distortion of the ring from planarity, which destroys the resonance delocalization and leads to high-energy species [33,41]. Relevant bond lengths of the most stables structures obtained are given in Figure 3.…”