Journal of the American Chemical Society, Vol.132, No.45, 16134-16145, 2010
Design, Synthesis, and Operation of Small Molecules That Walk along Tracks
The synthesis and system dynamics of a series of small-molecule walker-track conjugates, 3,4-C-n, (n = 2, 3, 4, 5, and 8), based on dynamic covalent linkages between the "feet" of the walkers and the "footholds" of the track, is described. Each walker has one acyl hydrazide and one sulfur-based foot separated by a spacer chain of "n" methylene groups, while the track consists of four footholds of alternating complementary functionalities (aldehydes and masked thiols). Upon repeatedly switching between acid and base, the walker moiety can be exchanged between the footholds on the track, primarily through a "passing-leg gait" mechanism, until a steady state, minimum energy, distribution is reached. The introduction of a kinetically controlled step in the reaction sequence (redox-mediated breaking and reforming of the disulfide linkages) can cause a directional bias in the distribution of the walker on the track. The different length walker molecules exhibit very different walking behaviors: Systems n = 2 and 3 cannot actually "walk" along the track because their stride lengths are too short to bridge the internal footholds. The walkers with longer spacers (n = 4, 5, and 8) do step up and down the track repeatedly, but a directional bias under the acid-redox conditions is only achieved for the C-4 and C-5 systems, interestingly in opposite directions (the C-8 walker has insufficient ring strain with the track). Although they are extremely rudimentary systems, the C-4 and C-5 walker-track conjugates 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.