Electronic key-lock matching underpins exclusive recognition of hydrogen sulfide by fluorescent-nanozyme carbon dots.

Achieving selective discrimination of hydrogen sulfide (H2S) from structurally similar biothiols remains challenging due to their comparable nucleophilicity and redox properties. Herein, we report iron-doped carbon dot nanozymes (Fe-CDNEs) that enable highly selective dual-mode H2S sensing based on an electronic key-lock matching mechanism. Fe-CDNEs were synthesized via a one-pot hydrothermal approach using hemin, polyethyleneimine (PEI), and citric acid (CA), integrating peroxidase-like catalytic sites with amino-rich recognition domains. H2S uniquely interacts with the Fe-centered "lock" through favorable electrostatic and orbital matching, leading to catalytic inhibition and coupled fluorescence‒colorimetric responses for ratiometric detection. The platform achieves low detection limits of 0.11 μM (fluorescence), 0.31 μM (colorimetric), and 1.46 μM (smartphone-assisted), while showing negligible interference from excess biothiols. Density functional theory (DFT) calculations reveal distinct electronic features governing selectivity, and principal component analysis (PCA) confirms robust discrimination across a wide concentration range. The method exhibits excellent recoveries (93.0-113.5%) in water samples, serum, and cell lysates, demonstrating strong practical applicability. This work provides mechanistic insight into electronic-structure‒driven molecular recognition and offers a general strategy for designing highly selective nanozyme-based sensors.