Exploring the influence of metal cations on individual hydrogen bonds in Watson–Crick guanine–cytosine DNA base pair: An interacting quantum atoms analysis

This study delves into the nature of individual hydrogen bonds and the relationship between metal cations and hydrogen bonding in the Watson–Crick guanine–cytosine (GC) base pair and its alkali and alkaline earth cation-containing complexes (Mⁿ⁺–GC). The findings reveal how metal cations affect the nature and strength of individual hydrogen bonds. The study employs interacting quantum atoms (IQA) analysis to comprehensively understand three individual hydrogen bonds within the GC base pair and its cationic derivatives. These analyses unveil the nature and strength of hydrogen bonds and serve as a valuable reference for exploring the impact of cations (and other factors) on each hydrogen bond. All the H$\cdots$D interactions (H is hydrogen and D is oxygen or nitrogen) in the GC base pair are primarily electrostatic in nature, with the charge transfer component playing a substantial role. Introducing a metal cation perturbs all H$\cdots$D interatomic interactions in the system, weakening the nearest hydrogen bond to the cation (indicated by a) and reinforcing the other (b and c) interactions. Notably, the interaction a, the strongest H$\cdots$D interaction in the GC base pair, becomes the weakest in the Mⁿ⁺–GC complexes. A broader perspective on the stability of GC and Mⁿ⁺–GC complexes is provided through interacting quantum fragments (IQF) analysis. This approach considers all pairwise interactions between fragments and intra-fragment components, offering a complete view of the factors that stabilize and destabilize GC and Mⁿ⁺–GC complexes. The IQF analysis underscores the importance of electron sharing, with the dominant contribution arising from the inter-fragment exchange-correlation term, in shaping and sustaining GC and Mⁿ⁺–GC complexes. From this point of view, alkaline and alkaline earth cations have distinct effects, with alkaline cations generally weakening inter-fragment interactions and alkaline earth cations strengthening them. In addition, IQA and IQF calculations demonstrate that the hydration of cations led to small changes in the hydrogen bonding network. Finally, the IQA interatomic energies associated with the hydrogen bonds and also inter-fragment interaction energies provide robust indicators for characterizing hydrogen bonds and complex stability, showing a strong correlation with total interaction energies.