Unraveling the Stoichiometric Interactions and Synergism between Ligand-Protected Gold Nanoparticles and Proteins

Bihan Zhang; María Francisca Matus; Qiaofeng Yao; Xiaorong Song; Zhennan Wu; Wenping Hu; Hannu Häkkinen; Jianping Xie

doi:10.1021/jacs.4c09879

Unraveling the Stoichiometric Interactions and Synergism between Ligand-Protected Gold Nanoparticles and Proteins

J Am Chem Soc. 2025 Jan 17. doi: 10.1021/jacs.4c09879. Online ahead of print.

Authors

Bihan Zhang^{1

2}, María Francisca Matus³, Qiaofeng Yao^{4

5}, Xiaorong Song⁶, Zhennan Wu⁷, Wenping Hu^{4

5}, Hannu Häkkinen³, Jianping Xie^{1

2}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
² Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, China.
³ Departments of Physics and Chemistry, Nanoscience Center, University of Jyväskylä, FI-40014 Jyväskylä, Finland.
⁴ Key Laboratory of Organic Integrated Circuits, Ministry of Education & Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, China.
⁵ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
⁶ MOE Key Laboratory for Analytical Science of Food Safety and Biology & State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350116, China.
⁷ State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, China.

PMID: 39823220
DOI: 10.1021/jacs.4c09879

Abstract

Nanomaterials that engage in well-defined and tunable interactions with proteins are pivotal for the development of advanced applications. Achieving a precise molecular-level understanding of nano-bio interactions is essential for establishing these interactions. However, such an understanding remains challenging and elusive. Here, we identified stoichiometric interactions of water-soluble gold nanoparticles (Au NPs) with bovine serum albumin (BSA), unraveling their synergism in manipulating emission of nano-bio conjugates in the second near-infrared (NIR-II) regime. Using Au₂₅(p-MBS)₁₈ (p-MBS = para-mercaptobenzenesulfonic acid) as paradigm particles, we achieved precise binding of Au NPs to BSA with definitive molar ratios of 1:1 and 2:1, which is unambiguously evidenced by high-resolution mass spectrometry and transmission electron microscopy. Molecular dynamics simulations identified well-defined binding sites, mediated by electrostatic interactions and hydrogen bonds between the p-MBS moieties on the Au₂₅(p-MBS)₁₈ surface and BSA. Particularly, positively charged residues on BSA were found to be pivotal. By careful control of the molar ratio of Au₂₅(p-MBS)₁₈ to BSA, atomically precise [Au₂₅(p-MBS)₁₈]_x-BSA conjugates (x = 1 or 2) could be formed. Through a comprehensive spectroscopy study, an electron transfer process and synergistic effect were manifested in the Au₂₅(p-MBS)₁₈-BSA conjugates, leading to drastically enhanced emission in the NIR-II window. This work offers insights into the precise engineering of nanomaterial-protein interactions and opens new avenues for the development of next-generation nano-bio conjugates for nanotheranostics.