Molecular-to-Atomic Transcription Programs Single-Atom Interfaces for Molecular Recognition

Abstract Molecular recognition is conventionally encoded in multidentate organic or biological receptors whose persistent structures define complementary binding environments. Whether recognition information can instead be written into the spatial organization of individual atoms at a solid interface remains unresolved. Here, we establish molecular-to-atomic transcription, a template-directed strategy that converts molecular donor identity and intramolecular spacing into single-atom sites. Molecular templates preorganize the metal precursors through donor-selective interactions, while frozen-state electrochemical construction restricts precursor redistribution and preserves the template-biased organization. A 3 × 3 library spanning three donor environments and three molecular spacings produces a matched recognition matrix in which molecular response is jointly governed by coordination chemistry and intersite distance. We define this mechanism as single-atom recognition: molecular identity is read by the chemical identity and spatial organization of isolated metal atoms rather than by a retained molecular receptor. This principle enables stringent discrimination between homocysteine and cysteine, which share the same principal donors but differ by one methylene unit. Their corresponding encoded interfaces exhibit reciprocal recognition preferences consistent with geometry-dependent dual-site engagement. Recognition persists in serum and during continuous in vivo measurements, demonstrating that molecular information transcribed into an inorganic atomic interface remains functional in chemically complex environments. Molecular-to-atomic transcription therefore establishes a chemical design principle for programming selective solid interfaces atom by atom.