Water Microdroplets Transform Reducing Sugars into a Platform Chemical 5-Hydroxymethylfurfural

Sprayed water microdroplets act as open-air microreactors, unlocking reaction pathways that are often inaccessible in bulk solution. Here, we present that aerosolizing aqueous solutions of reducing sugars (d-glucose and l-fructose) spontaneously yield 5-hydroxymethylfurfural (HMF), a versatile platform chemical for biofuels, bioplastics, and pharmaceuticals. Mechanistic studies reveal that the super acidic and "water-starved microenvironment" at the microdroplet interface intrinsically activates sugars, driving the sequential loss of three water molecules via cyclic or acyclic pathways to form HMF. The reaction proceeds without the need for external reagents, catalysts, heat, or harsh conditions, unlike bulk-phase processes required for HMF production. The facile formation of HMF from glucose in water microdroplets under ambient conditions not only offers a sustainable route to a renewable chemical building block but also provides prebiotic insight, highlighting how such interfacial chemistry could have contributed to the molecular diversity essential for the origin of life.