Effect of carboxymethyl substitution position on urea interaction with carboxymethyl chitosan: a density functional...

Among natural polymers, chitosan has gained considerable attention due to its excellent hemocompatibility and ability to enhance urea transport. Modifying chitosan into carboxymethyl chitosan (CMCs) enhances the number of active sites for hydrogen bonding, leading to greater selectivity toward urea molecules. The position of carboxymethyl substitution influences the physicochemical properties of CMCs, including hydrogen-bonding ability and molecular interactions with urea. Theoretical calculations are employed in this study to elucidate the role of carboxymethylation position in governing CMCs…urea interactions and membrane performance. The results indicate that O-substituted carboxymethyl chitosan exhibits the most favorable interaction energies and forms cyclic or multiple hydrogen bonds with urea, whereas N-substituted derivatives show weaker stabilization. Quantum reactivity descriptors reveal enhanced electronic stability for O-substituted complexes and increased reactivity for N-substituted systems. Topological and bond strength analyses consistently confirm stronger and more localized hydrogen bonding in O-containing carboxymethyl chitosan. These findings provide molecular-level insights for optimizing carboxymethyl chitosan-based hemodialysis membranes.

The interactions of O-CMCs, N-CMCs, N,O-CMCs, and N,N-CMCs with urea were investigated using density functional theory (DFT) at the B3LYP-D3/6-31++g(d,p) level of theory in water medium. All of the quantum calculations were performed using ORCA 6.0.0. The semi-empirical dispersion correction (DFT-D), developed by Grimme, in its latest D3 version was applied. The solvent effect was modeled using the solvation model based on density (SMD) implemented through the conductor-like polarizable continuum model (CPCM) framework. Intermolecular interactions were analyzed through frontier molecular orbital analysis, natural bond orbital (NBO), non-covalent interaction-reduced density gradient (NCI-RDG), quantum theory of atoms in molecules (QTAIM), and intrinsic bond strength index (IBSI) approaches.