A programmable modular robot for the synthesis of molecular machines

The assembly of molecular nanomachines using atomically precise manipulations promises to enable nanotechnology with unprecedented architectural features and exquisite functional properties. However, this future is critically limited by the ability to autonomously manufacture nanomachines, with current efforts being heavily labor intensive. A system is needed to program and assemble matter under digital control, unifying molecular nanotechnology and macroscale chemical processes. Herein, we present a universal chemical robotic synthesis platform (Chemputer) that produces functional molecular machines. By integrating autonomous feedback through on-line NMR and liquid chromatography, a divergent four-step synthesis and purification of molecular rotaxane architectures are achieved. The synthetic sequence averaged 800 base steps over 60 h, affording products on an analytical scale for feasibility studies. While standardizing rotaxane synthesis enhances reliability and reproducibility, our workflow addresses two bottlenecks in autonomous synthesis: yield determination (via on-line ¹H NMR) and product purification via multiple column chromatography techniques (silica gel and size exclusion).