Autonomous migration of a phosphate group along glycerol and inositol scaffolds driven by a phosphodiester reaction cycle

Artificial molecular machines that autonomously convert chemical fuel into directed motion are rare because designing systems that sustain non-equilibrium steady states without relying on nature's toolbox remains challenging. In particular, a small-molecule walker that combines autonomy with kinetic asymmetry has so far proven elusive. Here we show that simple phosphoric acid esters enable a non-enzymatic reaction cycle that drives the migration of a phosphate group along molecular tracks bearing hydroxy footholds. Carbodiimide fuel transiently generates cyclic phosphodiesters, which undergo selective hydrolytic ring opening to advance the walker. On a glycerol track, the walker reaches a non-equilibrium steady state sustained for several hours, while an extended inositol scaffold supports autonomous migration across five alcohol sites. Modelling reveals the ability of the walker to differentiate the centre of the track from its ends. By introducing migratory endergonic synthesis on biologically relevant phosphate scaffolds, this work expands the scope of synthetic molecular machinery.