Beyond switches: ratcheting a particle energetically uphill with a compartmentalized molecular machine.

Here we correlate chemical (covalent), physical (thermodynamic), and statistical (population distribution) descriptions of behavior with the way that two new types of simple molecular machines (the threads of rotaxanes) perform the task of transporting a Brownian substrate (the rotaxane macrocycle) between two distinguishable binding sites. The first machine-substrate ensemble is a [2]rotaxane that operates through a mechanism that intrinsically causes it to change the average position of the macrocycle irreversibly. This contrasts with the behavior of classic stimuli-responsive molecular shuttles that act as reversible molecular switches. The second system is a compartmentalized molecular machine that is able to pump its substrate energetically uphill using the energy provided by a photon by means of an olefin photoisomerization. Resetting this compartmentalized molecular machine does not undo the work it has carried out or the task performed, a significant difference to a simple molecular switch and a characteristic we recognize as "ratcheting" (see Scheme 8). The ratcheting mechanism allows the [2]rotaxane to carry out the transport function envisaged for the historical thought-machines, Smoluchowski's Trapdoor and Maxwell's Pressure Demon, albeit via an unrelated mechanism and using an input of energy. We define and exemplify the terms "ratcheting" and "escapement" in mechanical terms for the molecular level and outline the fundamental phenomenological differences that exist between what constitutes a two-state Brownian switch, a two-state Brownian memory or "flip-flop", and a (two-stroke) Brownian motor. We also suggest that considering the relationship between the parts of a molecular machine and a substrate in terms of "statistical balance" and "linkage" could be useful in the design of more complex systems and in helping to understand the role of individual amino acids and peptide fragments during the directional transport of substrates by biological pumps and motors.