Final Report Summary - WALKINGMOLS (Synthetic Molecules that Walk Down Tracks: The First Small-Molecule Linear Motors) Movement is intrinsic to life. Biologists have established that most forms of directed nanoscopic, microscopic and, ultimately, macroscopic movements are powered by molecular motors from the dynein, myosin and kinesin superfamilies. These motor proteins literally walk, step by step, along polymeric filaments, carrying out essential tasks such as organelle transport. Nature’s use of such ‘mechanical’ molecular-level structures has inspired chemists to synthesize molecular analogues of some of the fundamental components of machinery from the macroscopic world. The ultimate objective of such studies is to create relatively simple synthetic devices or materials that can, like their far more complex biological counterparts, carry out tasks by controlled molecular-level mechanical motion. However, the synthetic molecular machines prepared thus far fall well short of the control over motion exhibited by biological systems. The goal of the WalkingMols project is to address this challenge - by making mechanically processive chemical structures from first principles; i.e. to design, synthesize, operate and characterize wholly synthetic molecular structures that progressively advance directionally along a molecular ‘track’ in response to stimuli. The project has made significant progress towards its stated objective. The main scientific achievements include the construction and operation of the first small-molecules which are able to operate in a processive, directional, repetitive and progressive manner. We have succeeded in designing, constructing and operating the first small-molecule walker in the form of a 21-atom two-legged molecular unit that is able to walk up and down a four-foothold molecular track. This breakthrough was followed by the design and synthesis of more progressive molecular “walkers” such as (i) a light-driven molecular walker, (ii) a small molecule that walks along a track without external intervention and, (iii) a molecular walker that can migrate along longer tracks of up to nine footholds long. More importantly, we have been able to gain some understanding of the walking behaviour of our walker systems, giving us valuable insight into the essential requirements that are needed to develop more sophisticated and ultimately, functional molecular walkers. Although these early walker-track conjugates are extremely rudimentary systems, crucially, they exhibit four of the essential characteristics of linear molecular motor dynamics: processive, directional, repetitive, and progressive migration of a molecular unit up and down a molecular track. Until now, no artificial chemical systems have yet been created that display the key mechanical property of sequential processivity (progressive movement of one component directionally across, or through the cavity, of another), a key feature of the linear motor proteins (which utilize processive mechanical movement to transport cargo or generate mechanical force). Sequential processive movement is unprecedented for wholly synthetic molecular structures. Its successful demonstration is a landmark accomplishment for supramolecular chemistry and marks a major new direction for synthetic molecular nanotechnology.
