Molecular architecture of surface-active ionic liquids governs protein structural integrity and drug recognition at engineered carbon quantum dot nano–bio interfaces
Abstract
IntroductionProtein–nanomaterial interfaces are increasingly exploited in biomedicine, yet the influence of ionic liquid (IL) molecular architecture on protein structure and ligand recognition remains poorly understood. Here, we investigate the interactions of lysozyme (LYZ) with surface-active ionic liquids (SAILs), SAIL functionalized carbon quantum dots (CQD-ILs), and the subsequent binding of donepezil (DON) to native LYZ and LYZ–CQD/CQD-IL conjugates.MethodsSAILs bearing imidazolium (IB) or pyridinium (PB) headgroups with dodecyl (DD) or tetradecyl (TD) alkyl chains were systematically examined using steady-state and time-resolved fluorescence spectroscopy, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, small angle neutron scattering (SANS), dynamic light scattering (DLS), and molecular dynamics (MD) simulations.Results and DiscussionDON binding proceeded predominantly through a static and spontaneous mechanism, while CQD association enhanced the binding affinity by approximately 1.3-fold. Functionalization with tetradecyl pyridinium (TDPB) produced a further ∼4.7-fold increase relative to native LYZ. Notably, the enhanced ligand recognition did not correlate directly with the strength of LYZ–CQD/SAIL association, indicating that the local physicochemical organization of the IL-modified nano–bio interface, rather than binding strength alone, governs molecular recognition. CD and FTIR analyses showed that SAIL functionalization substantially preserved the secondary structure of LYZ during ligand binding, with the LYZ–CQD–TDPB conjugate retaining 43.5% α-helical content after DON binding compared with only 12.2% for pristine LYZ–CQD. Consistent with these observations, MD simulations revealed localized interfacial rearrangements consistent with enhanced ligand recognition without compromising the overall structural stability of the protein. Collectively, these findings demonstrate that rational tuning of SAIL molecular architecture enables controlled modulation of protein–ligand recognition at engineered nano-bio interfaces while preserving protein integrity, that may provide molecular-level design principles for biofunctional nanomaterials and protein-based nanotherapeutic platforms.
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BibTeX
@article{nonglamin2026molecular,
title = {{Molecular architecture of surface-active ionic liquids governs protein structural integrity and drug recognition at engineered carbon quantum dot nano–bio interfaces}},
author = {Iaimanda Nonglamin and Sugam Kumar and Sivaprasad Mitra},
journal = {Frontiers in Molecular Biosciences},
year = {2026},
month = nov,
doi = {10.3389/fmolb.2026.1971794},
url = {https://www.frontiersin.org/articles/10.3389/fmolb.2026.1971794},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular architecture of surface-active ionic liquids governs protein structural integrity and drug recognition at engineered carbon quantum dot nano–bio interfaces
AU - Iaimanda Nonglamin
AU - Sugam Kumar
AU - Sivaprasad Mitra
PY - 2026
DA - 2026/11/09
JO - Frontiers in Molecular Biosciences
DO - 10.3389/fmolb.2026.1971794
UR - https://www.frontiersin.org/articles/10.3389/fmolb.2026.1971794
AB - IntroductionProtein–nanomaterial interfaces are increasingly exploited in biomedicine, yet the influence of ionic liquid (IL) molecular architecture on protein structure and ligand recognition remains poorly understood. Here, we investigate the interactions of lysozyme (LYZ) with surface-active ionic liquids (SAILs), SAIL functionalized carbon quantum dots (CQD-ILs), and the subsequent binding of donepezil (DON) to native LYZ and LYZ–CQD/CQD-IL conjugates.MethodsSAILs bearing imidazolium (IB) or pyridinium (PB) headgroups with dodecyl (DD) or tetradecyl (TD) alkyl chains were systematically examined using steady-state and time-resolved fluorescence spectroscopy, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, small angle neutron scattering (SANS), dynamic light scattering (DLS), and molecular dynamics (MD) simulations.Results and DiscussionDON binding proceeded predominantly through a static and spontaneous mechanism, while CQD association enhanced the binding affinity by approximately 1.3-fold. Functionalization with tetradecyl pyridinium (TDPB) produced a further ∼4.7-fold increase relative to native LYZ. Notably, the enhanced ligand recognition did not correlate directly with the strength of LYZ–CQD/SAIL association, indicating that the local physicochemical organization of the IL-modified nano–bio interface, rather than binding strength alone, governs molecular recognition. CD and FTIR analyses showed that SAIL functionalization substantially preserved the secondary structure of LYZ during ligand binding, with the LYZ–CQD–TDPB conjugate retaining 43.5% α-helical content after DON binding compared with only 12.2% for pristine LYZ–CQD. Consistent with these observations, MD simulations revealed localized interfacial rearrangements consistent with enhanced ligand recognition without compromising the overall structural stability of the protein. Collectively, these findings demonstrate that rational tuning of SAIL molecular architecture enables controlled modulation of protein–ligand recognition at engineered nano-bio interfaces while preserving protein integrity, that may provide molecular-level design principles for biofunctional nanomaterials and protein-based nanotherapeutic platforms.
SN - 2296-889X
ER -