Delicate Balance of Non‐Covalent Forces Govern the Biocompatibility of Graphitic Carbon Nitride towards Genetic Materials

Despite a plethora of suggested technological and biomedical applications, the nanotoxicity of two-dimensional (2D) graphitic carbon nitride (g-C3 N4 ) towards biomolecules remains elusive. To address this issue, we employ all-atom classical molecular dynamics simulations and investigate the interactions between nucleic acids and g-C3 N4 . It is revealed that, toxicity is modulated through a subtle balance between electrostatic and van der Waals interactions. When the exposed nucleobases interact through predominantly short-ranged van der Waals and π-π stacking interactions, they get deviated from their native disposition and adsorb on the surface, leading to loss of self-stacking and intra-quartet H-bonding along with partial disruption of the native structure. In contrast, for the interaction with double-stranded structures of both DNA and RNA, long-range electrostatics govern the adsorption phenomena since the constituent nucleobases are relatively concealed and wrapped, thereby resulting in almost complete preservation of the nucleic acid structures. Construction of free energy landscapes for lateral translation of adsorbed nucleic acids suggests decent targeting specificity owing to their restricted movement on g-C3 N4 . The release times of nucleic acids adsorbed through predominant electrostatics are significantly less than those adsorbed through stacking with the surface. It is therefore proposed that g-C3 N4 would induce toxicity towards any biomolecule having bare residues available for strong van der Waals and π-π stacking interactions relative to those predominantly interacting through electrostatics.