Ionic Liquid-Functionalized Carbon Quantum Dots Modulate the Structure and Function of Human Serum Albumin: Insights...

Biocompatible carbon quantum dots (CQDs) are widely explored as functional nanomaterials; however, the molecular basis of their interactions with serum proteins still remains unclear. Herein, CQDs functionalized with surface-active ionic liquids (SAILs) bearing imidazolium (IB) and pyridinium (PB) head groups with dodecyl (DD) and tetradecyl (TD) alkyl chains were employed to elucidate their interaction with human serum albumin (HSA). Fluorescence quenching revealed predominantly enthalpy-driven binding, with CQD-TDIB exhibiting the highest apparent affinity toward HSA (∼108 M-1), representing a 9-64-fold increase over the other SAIL-functionalized CQDs. Circular dichroism, FTIR, and MD analyses demonstrated that pristine CQDs partially disrupted the α-helical structure of HSA, whereas SAIL functionalization largely preserved the native secondary structure through localized interfacial interactions. MD simulations further showed stable Trp214-CQD separations within the Förster distance, consistent with the experimentally observed energy transfer. SAIL-functionalized CQDs enhanced the nonenzymatic activity of HSA by 120-227%, while pristine CQDs produced only minor effects. Notably, the results demonstrate that preservation of native-like protein structure, rather than binding strength alone, governs the functional response. These results provide molecular-level insight into how ionic liquid functionalization governs nanoparticle-protein interfacial interactions toward structural stability and protein function.