Biomimetic Chiral Recognition of Biothiols by Enantiomeric Nanoclusters in Plasma

The biomimetic chiral recognition and detection of biothiols, such as cysteine, homocysteine, and glutathione, in plasma present significant challenges due to the limited understanding of chiral recognition mechanisms beyond the molecular level. Herein, enantiomeric and twisted octahedron silver nanoclusters (D-/L-Ag₆SP₆), featuring bichirality at both the molecular and nanoscopic scales, are designed and synthesized by employing a chiral bidentate ligand of thiazolethione enantiomer (D- or L-4-phenylthiazolidine-2-thione, abbreviated as D-SP or L-SP) in conjunction with silver acetate. The resulting nanoclusters are further modified with PEG₂₀₀₀ to produce water-dispersible D-Ag₆SP₆@PEG and L-Ag₆SP₆@PEG nanoparticles, enabling enantioselective recognition and quantitative determination of various biothiols in plasma through circular dichroism measurements. The study also elucidates the bichiral recognition and determination of biothiols through a ligand-induced disassembly-assembly mechanism. Both D- and L-type Ag₆SP₆@PEG nanoparticles demonstrate excellent anti-interference properties for discriminating biothiols using principal component analysis. The bichirality of nanoclusters shows high enantioselectivity in chiral recognition of biothiols and their corresponding enantiomers. This work not only provides a convenient strategy for bichiral recognition and quantitative determination of biothiols in plasma, but also holds promise for developing hierarchically chiral nanomaterials applicable in biomedical engineering, nanomedicine, and drug screening.