Interfacial microenvironments enable abiotic ribonucleoside formation in micro- and nanoscale compartments

The abiotic emergence of ribonucleosides remains a central challenge in origin-of-life research because ribonucleosides form inefficiently and are often unstable under prebiotically plausible conditions. Here we show that interfacial microenvironments within aqueous micro- and nanoscale compartments containing D-ribose, phosphoric acid, and nucleobases promote ribonucleoside formation by creating reaction-permissive physicochemical conditions independent of the specific compartment type. Across a diverse range of compartmentalized systems, including gas–oil–water micro/nanobubbles, gas–water micro/nanobubbles, microscale lipid-bilayer vesicles, and oil–water emulsion systems, ribonucleosides form abiotically in the absence of enzymatic catalysis. Under selected interfacial conditions, multiple ribonucleosides, including cytidine, are generated without added catalysts. Comparison among these systems reveals that interfacial architecture and coupled physicochemical properties strongly influence both reaction efficiency and product stability. CO 2 -based micro/nanobubbles support sustained cytidine accumulation, highlighting the importance of coupled gas–liquid and liquid–liquid interfaces. Ribonucleoside synthesis also depends on compartment size, whereas variations in oil content within micro/nanobubbles selectively modulate inosine formation, underscoring the sensitivity of nucleoside chemistry to interfacial properties. These findings identify interfacial microenvironments within micro- and nanoscale compartments as a general physical framework for ribonucleoside emergence and suggest that ubiquitous compartmentalized interfaces on early Earth could have provided robust settings for prebiotic ribonucleoside chemistry.