Abstract

<h2>Summary</h2> The natural selection of ribose as the exclusive sugar for RNA has been one of the greatest puzzles in the origins of life. Here, we present a plausible solution to this problem that circumvents the limitations of previous hypotheses, inspired by the unique retention properties of ribose in ligand-exchange chromatography. It is discovered that metal cations and clay minerals have a synergistic effect to selectively bind to ribose against other monosaccharides. Excitingly, ribose can be continuously and highly selectively enriched on metal-doped-clays (MDCs) from a complex Formose mixture, which could be the origin of its rise to prominence. Prebiotic scenarios of the dynamic isolation of ribose from sugar mixture are simulated with microflow technology. The MDC-retained ribose exhibits long-term stability for the upcoming nucleosidation reactions. Computational studies help elucidate the unique stability of the ribose-MDC complex. MDC also promotes the 5′-phosphorylation of nucleosides with greater yield and selectivity than reported.

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