Synthetic Small-Molecule Walkers
A R T I C L E S
synthesis and some of the properties of the C5 system were
recently reported in a preliminary communication.6
been described as “biased Brownian movement” or “diffusion
with a drift”.15
Molecules That Walk along Tracks. Spectacular examples
of biological linear molecular motors include the kinesin,
myosin, and dynein bipedal motor proteins, which are direc-
tionally driven along intracellular tracks by adenosine triphos-
phate (ATP) hydrolysis.7 The main features8,9 of biological
linear molecular motor dynamics are processivity, directionality,
and repetitive, progressive, and autonomous operation.
(i) Processivity is the ability of the molecular motor to remain
attached to its track while it is directionally transported, that is,
without detaching or exchanging with other molecules in the
bulk.10 Most wild-type kinesins exhibit a relatively high level
of processivity, falling off their microtubular11 tracks after an
average of ∼100 steps.12
(iii) Repetitive operation is the motor’s ability to repeatedly
perform similar mechanical cycles. Kinesin takes one 8 nm step,
putting one foot in front of the other, and each time an ATP
molecule is hydrolyzed by the protein.8
(iv) Progressive operation is the ability of the molecular motor
to be reset at the end of each mechanical cycle without undoing
the physical task that was originally performed. The two feet
of kinesin are identical, and yet it selectively moves first one
foot and then the other in a passing-leg gait to transport itself
continuously in the same direction along the track.8
(v) Autonomous operation is the ability of the molecular
motor to undergo directional, processive motion as long as a
chemical “fuel” is present, that is, without further external
intervention (such as the application of a sequence of stimuli).
(ii) Directionality is the tendency of a molecular walker to
migrate preferentially toward a particular end of a polymeric
track. Most kinesins show near-perfect directionality,8 moving
toward the plus-end of microtubules as long as the chemical
potential of ATP is greater than that of adenosine diphosphate
(ADP) and inorganic phosphate (Pi).13 However, some kinesins,
such as KIF1A,14 only migrate with modest net directionality;
that is, they take almost as many steps in the backward direction
as they do in the forward direction. This type of dynamics has
Features i-iv are key requirements for most types of
molecular motor.10 Autonomous operation, (v), can be an
additional desirable trait but could also result in reduced control
over a system; for example, it may not be possible to control
the speed or distance traveled by a walker, nor to stop it unless
and until the “fuel” runs out or the system is “clocked”.
Autonomous operation also implies that walker transport is only
possible in one direction with a given fuel, a feature of biological
motors but not necessarily a constraint that synthetic systems
must adhere to. Our initial aim was to learn how to construct
and operate synthetic small molecules that possess some of these
key features of linear molecular motor dynamics. Until recently,6
the only synthetic molecular structures that had been shown to
exhibit most of these features were systems constructed from
DNA.16 Small-molecule walkers that do not utilize building
blocks taken from biology are more fundamental systems that
could offer advantages in terms of size, function, and modes of
operation.
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