'Two-legged' molecular walker takes a stroll

UK chemists have designed a two-legged molecule that can walk up and down a straight molecular track. The system could form the basis for artificial linear molecular motors that can transport cargoes in a way similar to molecular machines used in nature. 

Max von Delius, Edzard Geertsema and David Leigh at the University of Edinburgh constructed the motor from two principal components: a 21 atom ’walker’ which has two chemically distinct ’feet’, and a four-step oligomeric track which has footholds specific for each foot. 

The first foot has a hydrazide moiety, the second a sulfur-based group. The track consists of alternating aldehyde and disulfide groups. Under acidic conditions the hydrazide foot reversibly forms a covalent hydrazone bond with either of the aldehyde footholds on either side of it, while the disulfide foot remains locked in place. Under basic conditions the reverse happens: the sulfur-based foot moves between two disulfide bridges on the track, while the hydrazone foot acts as the fixed pivot. 

By oscillating the environment between acidic and basic, the walker lifts and replaces alternate feet, finding new footholds and moving up and down the track. However, under these conditions the walker will move either up or down the track more or less at random. To make it walk in one direction only - much more useful for carrying out work - a bias needs to be introduced so that at least one foot is more likely to move in one direction than the other. 

This was achieved by replacing the reversible acid-base disulfide reaction with an irreversible redox reaction sequence. ’Under reducing conditions the disulfide bond breaks, while under oxidising conditions the bond rapidly reforms,’ explains Leigh. ’This is a fundamentally different reaction which is under kinetic control rather than thermodynamic control of the acid-base reactions. The bias in the directionality of one of the steps is sufficient to move the walker with net directionaility.’ 

Significantly, the walker can take almost 40 steps before detaching - compared with between 75 and 175 steps taken by biological molecular machines, such as kinesin which transports proteins in the cell. ’That is not a huge difference and so is not bad for a first generation synthetic system,’ Leigh says. Having demonstrated that the system works on four footholds, the Edinburgh team is looking to extend the track, develop more efficient walkers, and aim to start carrying cargo. 

Jonathan Nitschke, who researches complex molecular structures at the University of Cambridge in the UK, says, ’This study puts a new tool in the toolkit of the community of chemists who are interested in getting systems of molecules to do complex and useful things.’ 

Simon Hadlington