The phosphodiester dissociative hydrolysis of a DNA model promoted by metal dications

Phosphodiester bonds, which form the backbone of DNA, are highly stable in the absence of catalysts. This stability is crucial for maintaining the integrity of genetic information. However, when exposed to catalytic agents, these bonds become susceptible to cleavage. In this study, we investigated the role of different metal dications (Ca²⁺, Mg²⁺, Zn²⁺, Mn²⁺, and Cu²⁺) in promoting the hydrolysis of phosphodiester bonds. A minimal DNA model was constructed using two pyrimidine nucleobases (cytosine and thymine), two deoxyribose units, one phosphate group, and one metallic dication coordinated by six water molecules. The results highlight that Cu²⁺ is the most efficient in lowering the energy barrier for bond cleavage, with an energy barrier of 183 kJ/mol, compared to higher barriers for metals like Zn²⁺ (202 kJ/mol), Mn²⁺ (202 kJ/mol), Mg²⁺ (210 kJ/mol), and Ca²⁺ (223 kJ/mol). Understanding the interaction between these metal ions and phosphodiester bonds offers insight into DNA stability and organic data storage systems.

DFT calculations were employed using Gaussian 16 software, applying the B3LYP hybrid functional with def2-SVP basis sets and GD3BJ dispersion corrections. Full geometry optimizations were performed for the initial and transition states, followed by identifying energy barriers associated with phosphodiester bond cleavage. The optimization criteria included maximum force, root-mean-square force, displacement, and energy convergence thresholds.