Scientists have made a groundbreaking advancement in atomic-level control of matter, a leap that could transform both fundamental scientific understanding and practical applications, particularly in the realm of pharmaceuticals. This achievement, led by physicists at the University of Bath in collaboration with an international team, could revolutionize the way researchers develop medications, improving both precision and efficiency in chemical processes.
While controlling single-molecule reactions with specific outcomes has become standard in laboratories worldwide, this level of mastery was not always achievable. Over a decade ago, IBM researchers demonstrated the potential of atomic manipulation by creating A Boy and His Atom, the world’s smallest movie, by moving individual molecules—each comprising two bonded atoms—frame by frame. Although this was a landmark achievement, controlling chemical reactions with multiple outcomes remained elusive. This limitation has been a challenge, especially in drug synthesis, where controlling byproducts could improve efficiency.
For example, in drug synthesis, the process of ‘cyclization’ produces the desired therapeutic compound, while ‘polymerization’ leads to unwanted byproducts. Precisely controlling these reactions to favor the desired outcomes and minimize byproducts promises to significantly enhance the sustainability and efficiency of pharmaceutical processes.
The study, published in Nature Communications on November 28, sets a new precedent by demonstrating for the first time that scanning tunneling microscopy (STM) can be used to influence competing chemical reaction outcomes at the atomic level. Conventional microscopes, which use light and lenses to magnify specimens, are unable to reach the scale of atoms and molecules. To explore these minuscule realms, scientists have long relied on STM, a technique that operates similarly to a record player but with unparalleled precision.
STM uses a finely-tipped probe that hovers just a single atom’s width above a material’s surface. When connected to a power source, electrons flow through the tip and make a quantum leap across the tiny gap to the surface. The strength of the current varies based on the tip’s proximity to the surface, enabling scientists to map the atomic landscape with extraordinary detail. This method builds a precise, line-by-line image of molecules, revealing features invisible to conventional light microscopes.
STM’s precision has allowed scientists to not only map molecules but also to reposition individual atoms and influence chemical reactions. This breakthrough marks a significant milestone in controlling reaction outcomes in real-time, an area that had previously remained unpredictable.
Dr. Kristina Rusimova, who led the study at the Department of Physics, explained: “STM technology is typically used to manipulate individual atoms and molecules, enabling targeted chemical interactions. However, controlling reactions with competing outcomes has remained a challenge. These competing outcomes occur with specific probabilities governed by quantum mechanics—like rolling a molecular die.”
The team demonstrated how STM could manipulate chemical reaction probabilities by injecting electrons into toluene molecules. This electron injection prompted the breaking of chemical bonds, leading to either a shift to a nearby site or the desorption of the molecule. Crucially, they discovered that the ratio of these two outcomes could be controlled by adjusting the energy of the electrons injected into the system. The ability to influence these outcomes by targeting specific energy thresholds allows for the precise control of reaction paths.
“We found that the energy dependence of the electron injection allowed us to control the probability of each reaction outcome,” said Dr. Peter Sloan, senior lecturer at the Department of Physics and co-author of the study. “This enables us to ‘heat’ an intermediate molecular state, guiding the reaction towards a desired outcome.”
Pieter Keenan, a Physics PhD student and first author of the study, elaborated: “The key was to maintain identical initial conditions for the reactions—matching the injection site and excitation state—while varying the energy of the injected electrons. By doing so, we could alter the reaction probabilities. It’s like loading the molecular dice to favor one outcome over another.”
This discovery has profound implications for a range of applications, from drug synthesis to molecular manufacturing. The team’s ability to control the specific reaction outcome at such a precise level opens the door to previously unattainable possibilities.
Professor Tillmann Klamroth from Potsdam University in Germany, a collaborator on the study, added, “This study combines advanced theoretical modeling with experimental precision, providing a pioneering understanding of how molecular energy landscapes govern reaction probabilities. This will drive future innovations in nanotechnology.”
Looking ahead, Dr. Rusimova anticipates that this work could be a major step toward fully programmable molecular systems. “This advancement has far-reaching implications for both basic and applied science,” she said. “We expect this technology to pave the way for breakthroughs in fields such as medicine, clean energy, and materials science, with potential applications in everything from drug development to sustainable manufacturing.”
This new research not only advances our fundamental understanding of chemical reactions but also opens the door to practical applications that could lead to more efficient, sustainable, and precisely controlled processes in various industries. As the ability to manipulate matter at the atomic level continues to evolve, it promises to unlock new frontiers in molecular manufacturing and beyond.
By Impact Lab
