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-C₃N₄) 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-C₃N₄. 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-C₃N₄. 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-C₃N₄ 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.     

Supramolecular Barrel-Rosette Ion Channel Based on 3,5-Diaminobenzoic Acid for Cation-Anion Symport

The structural tropology and functions of natural cation-anion symporting channels have been continuously investigated due to their crucial role in regulating various physiological functions. To understand the physiological functions of the natural symporter channels, it is vital to develop small-molecule-based biomimicking systems that can provide mechanistic insights into the ion-binding sites and the ion-translocation pathways. Herein, we report a series of bis((R)-(−)-mandelic acid)-linked 3,5-diaminobenzoic acid based self-assembled ion channels with distinctive ion transport ability. Ion transport experiment across the lipid bilayer membrane revealed that compound 1 b exhibits the highest transport activity among the series, and it has interesting selective co-transporting functions, i.e., facilitates K⁺/ClO₄⁻ symport. Electrophysiology experiments confirmed the formation of supramolecular ion channels with an average diameter of 6.2±1 Å and single channel conductance of 57.3±1.9 pS. Selectivity studies of channel 1 b in a bilayer lipid membrane demonstrated a permeability ratio of , , and indicating the higher selectivity of the channel towards KClO₄ over KCl salt. A hexameric assembly of a trimeric rosette of 1 b was subjected to molecular dynamics simulations with different salts to understand the supramolecular channel formation and ion selectivity pattern.