The stringent base-pairing rules of DNA make it an exceptionally powerful bottom-up nanoscale material for dynamic nanotechnologies. However, current nanomachines are based on rearrangements between DNA duplexes, which limits structural versatility and introduces detrimental background activity. Specifically, to make the reactions unidirectional, product duplexes are designed to be thermodynamically more favorable than their respective substrate duplexes. As a result, the reactions are thermodynamically driven, which represents the main source for the background activity. Here we test an alternative approach based on a structural transformation (ST) between a monomolecular DNA substrate and a quadruplex product. The quadruplex sequence is incorporated into a hairpin substrate. ST reaction is initiated by an addition of a target molecule, which through toehold-mediated strand displacement releases the quadruplex-forming sequence. The liberated sequence folds into a stable quadruplex and stays folded after dissociation of the target molecule. This Article analyzes the thermodynamic principles of ST reactions and demonstrates that the unidirectional nonenzymatic reaction can be run without thermodynamic favorability by transforming thermodynamically stable substrates into metastable products. In other words, ST is capable to drive nanomachines using thermodynamically uphill reactions. This allows for (i) running nanodevices without detrimental background activity and (ii) charging the product molecules with potential energy, which could be used in downstream endergonic activities.