Walking Molecules
Synthetic Strollers | Science & Technology | Chemical & Engineering News http://pubs.acs.org.ezproxy.webfeat.lib.ed.ac.uk/isubscribe/journals/cen...

Lit. Seminar
11.5.31(Tue.)
Katsuya SATO(M1)Royal Society of Chemistry

Resizing Synthetic DNA walkers are about the same size as biological protein walkers. Small-molecule

walkers are about 1,000 times smaller.
Dozens of DNA walkers now exist. Some have more than two legs; others use alternatives to fuel strands tostimulate a step forward. For example, some researchers use protein enzymes that can cleave DNA to cut
connections between trailing legs and the track so that the foot can swing forward. Other researchers have devised
hybrid DNA and RNA walkers that can themselves chemically cleave connections between their own trailing legs andthe track.

2011年6月4日土曜日

Table of Contents
I. Introduction
II.Biological Walker
III.DNA Walker

prof. D. Leigh

IV.Small-molecule Walker
V. Summary

see review : D. Leigh Chem. Soc. Rev. 2011, ASAP (DOI:10.1039/c1cs15005g)
2011年6月4日土曜日

I. Introduction

2011年6月4日土曜日

Introduction• What is “walking” ?
But he walks back.

She walks along the“road” to “forward”.

2011年6月4日土曜日

Why they walk on the “ground”
not on the “wall” or “ceiling”?

Introduction• Walking needs...

2011年6月4日土曜日

a.

Processivity : the ability to remain attached to the trackb.

Directionality : migration preferentially or exclusively towards
one end of the trackc.

Repetitive operation : the ability to repeatedly perform similar
mechanical cyclesd.

Progressive operation : the capability to be reset at the end ofeach mechanical cycle without undoing the physical task thatwas originally performede.

Autonomous operations : the ability to continually function aslong as an energy input is present

Processivity• To achieve processivity

View On

4 Three possible strategies to confer processivity on the migration of a molecular walker: (a) two different feet and two different reaction
ditions/fuels. (b) Two identical feet, but an interaction with the track that breaks their symmetry and makes one foot significantly more
ceptible to the fuel. (c) One-legged walker that relies on secondary (tether) interactions (indicated by dashed lines) with the track.

a) two different feet, two different fuels/conditionsb) two identical feet, the fuel with asymmetric interaction
An energy input: in biological systems this is commonly
Directionality—Brownian ratchet mechanismsc) one-legged walker with secondaryinteractions
suppliedby ATP hydrolysis; however in synthetic systems

biological molecular walkers operate with directional bias
wards one end of their respective tracks, an indication ofimportance that directionality plays in the function ofnslational
molecular motors. In fact, a molecule that
2011年6月4日土曜日

many other forms of energy input are conceivable.
D. Leigh Chem. Soc. Rev. 2011, ASAP
An asymmetric potential of energy or information in the
direction in which the motion occurs.

Directionality

all mannerof hypotheticalconstruc
Maxwellenvisaged
a gas
enclosed
withina container,
to toto describe
to describe
all mannerof hypotheticalcons
Maxwellenvisaged
a gas
enclosed
withina container,
the second
law lawof thermodynamics
andandfromwhich
no heator matter
could
flow.flow.
TheThesecondlaw lawovercome
overcome
the secondof thermodynamb
from
which
no heator matter
could
secondenergyto dotoworkfromfrom
the thermal
of ofthermodynamics
requiresthatthatno nogradientof heator orextracting
extracting
energydo work
the thethermodynamics
requiresgradientof heatpressure
cancanspontaneously
arisearise
in sucha system,as that
notedthat thatthe thedemon
princippressurespontaneously
in sucha system,as that Maxwell
Maxwell
noted
demon
pr
would
constitutea reduction
in entropy.
Maxwellimaginedin ainnumberof different
ways;
would
constitutea reduction
in entropy.
Maxwellimagineddemonstrated
demonstrated
a numberof differentw
the thesystemseparatedintointo
twotwosectionsby bya partition
for example,(Figure2 b) 2could
sort sorpa
systemseparatedsectionsa partitiondemon,
demon,
for example,(Figureb) could(Figure2). Having
justjust
proventhatthat
the themolecules
in aingas
at atmoreend endup in
end endof a ofvesselthanthanthe(Figure2). Having
provenmolecules
a gas
more
upone
in onea vesselrequireddifferent
requireddifferi
operatefromfromtheoperateperaturedemon(thperaturedemo
approachof aofpaa
approach
speed).
speed).

• Maxwell’s “Demon”

1.2.1.2.
Szilard’sEng
1.2.1.2.
Szilard’s

BothBoth
MaxwellMaxwappreciatedthat thth
appreciatedthesethesesystemsfosystems
Brownian
particles
Brownianpart
rely relyon thedemon theas anasanim
Figure2. a)2.Maxwell’s“temperaturedemon”
in whicha gasa attemperature
is sorted
into “hot”
gence”
an a
Figurea) Maxwell’s“temperaturedemon”
in whichgasuniform
at uniform
temperature
is sorted
into “hot”gence”
[15]
[15]
and and“cold”
molecules.
Particleswithenergyhigherthanthanthe average
are represented
by reddots
whilewhiledid did
not not
try to“cold”
molecules.
Particleswithenergyhigherthe average
are b)
represented
bydemonred dotsa) temperature
demonpressuretryquatoblueblue
dotsdots
represent
particleswithenergies
lower
than
the
average.
Allmechanicaloperations
carriedout
mademadethe fitrepresent particles with energies lower than the average. All mechanical operations carried outSzilard
Szilardby theinvolveno work—that
is, theis frictionlessand itis opened
and closed
infinitely
by demonthe demon
involveno work—that
is, door
the door
is frictionlessandit is opened
and closed
infinitely mathematicallymathematicallyslowly.
The Thedepictionof theoutsidethe vessel
is arbitrary
and wasspecified
by byslowly.
depictionof demonthe demon
outsidethe vessel
is arbitrary
and not
was explicitly
not explicitly
specifieddemon!sintelligenc
demon!sintellMaxwell.
b)A
Maxwellian“pressuredemon”
inwhich
apressure
gradientisestablished
by
the
door
Maxwell. b) A Maxwellian “pressure demon” in which a pressure gradientisestablished
by
the
door
modynamics
of tho[15c]
modynamics
[15c]
being
openedonly
whenaparticle
in
the
left
compartment
approaches
it.
being opened only when a particle in the left compartment approaches it.
considering
the perconsideringthemachinebasedonmachinebaseddemon”,
namely,Sz
demon”,
name
D. Leigh Angew.
Chem.
Int.
Ed.
2007,
46,
72-191[17][17](Figure3).
a particulartemperature
haveenergies
statistically
distribrealizedthat thatthe operatio(Figure 3).Szilard
a particular temperature have energies statistically distribSzilard
realized
the ope
uted
about
a
mean,
Maxwellpostulatedatiny“being”
able
to
demon
carriesout
canbe
reducedtoasimpleuted about a mean, Maxwell postulated a tiny “being” able todemon carries out can be reduced to a simc
2011年6月4日土曜日

Demon works against the second law of thermodynamics.
( randomness -> direction )•Directionality

Angewandte
ChemieFeynman’s Brownian Ratchet
Whether can the random oscillations produced by gas
molecules bombarding the vanes be rectified by theratchet and pawl so as to get net motion in one direction?

If T1 = T2, the answer is “no”.

However, on the contrary, cooling the ratchet and pawl by external means
makes it possible to rectify the random motion.

moluchowski’s trapdoor: an “automatic” pressure
rectionally discriminating behavior is carried out by anical device, a trapdoor which is intended to open when
direction but not the other).[16] Like the pressure demon
re2011年6月4日土曜日
2 b, Smoluchowski’s trapdoor aims to transport

D. Leigh Angew. Chem. Int. Ed. 2007, 46, 72-191

Figure 6). The result is net directional transport ofparticles across the surface (left to right in Figure 6).
More general than the special case of an on–off ratch
any asymmetric periodic potential may be regularly
stochastically varied to give a ratchet effect (such mechanis
are generally termed “fluctuating potential” ratchets).
with the simple on–off ratchet, most commonly encounte
examples involve switching between two different potent
and are therefore often termed “flashing” ratchets. A cla
example, which has particular relevance for explainin

Directionality• Energy-ratchet

http://www.s-graphics.co.jp/tankentai/news/molecularmotor2.htm
2011年6月4日土曜日

Figure 6. An example of a pulsating ratchet mechanism—an on–of
ratchet.[39f ] a) The Brownian particles start out in energy minima on
potential-energy surface with the energy barriers @ kBT. b) The potetial is turned off so that free Brownian motion powered diffusion isallowed to occur for a short time period (much less than required t
D. Leigh Angew. Chem. Int. Ed. 2007, 46, 72-191
reach global equilibrium). c) On turning the potential back on again
the asymmetry of the potential means that the particles have a grea

es start out ine energy barriersn equal andmoval of thes to the average
steps (b)–(d)further to the•

Directionality
Angewandte

Information-ratchet
Chemiea) The particle starts in one of the identical-minima energy wells.

b) The position of the particle lowers the kinetic barrier.

c) The particle moves to the adjacent right-hand well by Brownian
motion.

d) The particle can no longer go back to the starting well.

Figure 10. A type of information ratchet mechanism for transport of a
Brownian particle along a potential-energy surface.[39h, 42b, 45] Dottedelectric fieldarrows indicate the transfer of information that signals the position ofan the other),the particle. If the signal is distance-dependent—say, energy transfer
general,thesefrom an excited state which causes lowering of an energy barrier—
2011年6月4日土曜日

D. Leigh Angew. Chem. Int. Ed. 2007, 46, 72-191

Directionality

View Online• To achieve directionality

Fig. 7 Four possible strategies to confer directionality on the migration of a molecular walker: (a) reversible foot exchange coupled toreversible
footconsumption of a)
stoichiometriccomplexfuel Xexchange(an information ratchet mechanism). The driving force for directional transport is provided by thereaction X - Y. The feet can be identical (coordination required) or different (in which case a second fuel, X 0 , may be required). (b) A ‘burntb) a “burnt-bridges” walker
bridges’ walker catalyses the decomposition of the footholds, thus rendering any step in the forward direction essentially irreversible (aninformation ratchet
Feet
can be identical(coordination
required)or different.
(c) Reversible stimulus
migration processes that can be inducedc) mechanism).
migrationrequiringenergyinput
throughswitchingby catalytic reagents, but require energy input through switching stimulus (an energy ratchet mechanism). Feet cannot be identical. (d) One (ord) irreversible, kinetically controlled migrationmore) irreversible, kinetically controlled, migration process (I; an information ratchet mechanism). Feet cannot be identical.

could only be realised in a walker system where the two feetcan be addressed separately.
2011年6月4日土曜日

D. Leigh Chem. Soc. Rev. 2011, ASAP
building blocks have been reported.88 Many of these
DNA-walkers are genuine molecular motors since they exhibit

II.Biological Walker
Synthetic Strollers | Science & Technology | Chemical & Engineering News http://pubs.acs.org.ezproxy.webfeat.lib.ed.ac.uk/isubscribe/journals/cen...

Royal Society of Chemistry

Resizing Synthetic DNA walkers are about the same size as biological protein walkers. Small-molecule

walkers are about 1,000 times smaller.
Dozens of DNA walkers now exist. Some have more than two legs; others use alternatives to fuel strands to2011年6月4日土曜日

Walker in Cell

2011年6月4日土曜日

Daigaku on 29 March 2011n http://pubs.rsc.org | doi:10.1039/C1CS15005G• Motor Proteins

a
b
st
is
1
(s
p
tw
b
a
re
tr
d
F

m
a
st
Fig. 2 Examples of processive motor proteins from the three majorSsuperfamilies: (a) Myosin-V. (b) Cytoplasmic dynein. (c) Kinesin-1.
stRepresentations based on atomic resolution structures.10 Blue: motorddomains; light blue: mechanical amplifiers; purple: cargo attachmentthsite; green: associated motor units. Adapted by permission fromhElsevier: Cell (ref. 10),D.
copyright
Leigh(2003).
Chem. Soc. Rev. 2011, ASAP
coof their two feet, so that at any time during the catalytic cyclewWalker in Cell

• Myosin-V

2011年6月4日土曜日

!!
analy
tubule (Fig. out
1B).
Then
added fluorescently probe thus
allowedus to visualize,31!,34!!]. In
on theyeastwemyosins.
tively,due to intramolecularstrainneck[5,6,19motion
this model
myoV moves
processively
longwereas the leadfourlabeled microtubules, hoping that in some myo- and confirm
the expectedbehavior,
butasweheadrebinds
strongly
toactin
before
the
trail
head
releases
Models for processive movements
sin molecules
only one of the two necks would unable toADP
obtainsufficient data to study details of angle
and subsequently binds ATP, resulting in detachSeveral models have been presented for the processive(Figs.
bind a microtubule
points.
An actin
stepping
ment dynamics.
of that head and, thus, the whole molecule. The
movementatofmultiple
myoV. Nearly
all assume
that thethe
twopathway
in Figure
2 wouldbe (a)!(b)!(c)!(d)astructureinis solution
necessary by(for holding
an alternative, seefilament washeaded
suspended
We thustried
a reverse
scheme(Fig. 2A): for prom
single step. Unresolved issues are whether the lead head[41]). The critical issues are the nucleotide state and thetwo polystyrene beads attached to the filament Instead of fixing an actin filament in space, we (Fig.
Figure2ends with dual
opticaltweezers (21). By moving fixed a microtubule carrying myosin V (0.3 to of thethe microscope stage, we manipulated a floating 1 molecule mm−1) on a glass surface and waited micro
microtubule, typically 2 to 3 mm long and binding for a short (~1 mm) actin filament to land on it and tion (at most eight myosin V molecules per mm, onto move. For myosin V on the top surface of a positi
the actin filament. On rare occasions, the microtu- microtubule 25 nm in diameter, movement of the werebule bound to actin, presumably through myosin actin filament in a horizontal plane would not be nm, F
V, and swung to and fro several times, primarily hindered by the glass surface. Note that the werein the image plane (Fig. 1; see also fig. S1 and bound neck of myosin V is not necessarily par- clock
movies S1 and S2). We think the swings reflect allel to the thick microtubule consisting of 13 by a
the myosin neck motion because (i) the two tubulin protofilaments (Fig. 2A). In this reverse (Fig.
Browinanrelativelymotion
stationary angles (blue and red hori- configuration, the actin filament would swing due tzontal bars in Fig. 1D and fig. S1) were separated between two stationary angles where both heads Mostby ~100° (±20° SD for 17 swings), consistent of myosin V bind the filament. In between, the tions

Walker in Cell

• Myosin-V

B

Neck

D

240

Angle (° )

A

Head

2011年6月4日土曜日

120
60
0

-60
Actin filament-120
280
Microtubule
210
72 nm
3 µm
J. R. Sellers Curr. Opin. Cell Biol. 2006, 18, 68; K. Kinoshita Science,140
2007, 316, 208
Models for processive stepping. Two main pathways — (a)!(b)!(c)!(d) or (a)!(e)!(c)!(d) — are indicated as described in70the text. The red
dot represents Pi and the blue dot represents ADP. The faint blue lines in (c) represent a case where the lead head has gone0through its working

lacement (nm)C180

Walker in Cell

039/C1CS15005G• Kinesin-I

2011年6月4日土曜日

ATP-ind
Since bofeet andprocessiv
both feetdimers) a
for a step
The coover theprocess oThis consuch asbeyond 5
biologicaof explo
Fig. 3 The mechanochemical cycle of kinesin-I. Adapted by permission(e.g. for
P.R.Selvin Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 12717
from the National Academy of Sciences of the United States of America:
progress
Proc. Natl. Acad. USA (ref. 56), copyright (2010).

III.DNA Walker

ynthetic Strollers | Science & Technology | Chemical & Engineering News http://pubs.acs.org.ezproxy.webfeat.lib.ed.ac.uk/isubscribe/journals/cen...

Royal Society of Chemistry

Resizing Synthetic DNA walkers are about the same size as biological protein walkers. Small-molecule

walkers are about 1,000 times smaller.
Dozens of DNA walkers now exist. Some have more than two legs; others use alternatives to fuel strands to2011年6月4日土曜日

DNA Walker

2011
oi:10.1039/C1CS15005G• Non-autonomous DNA Walker

2011年6月4日土曜日

The composit
polyacrylamidegels confirmed twere stable andmixture throughled to the formaof the experimen
From a mec
depicted in Schesince it correspo
leading), not awalker is, howdetachment doe
and scramblingis unlikely at
0.5 mM). The
supplied by the
eight
bases
in th
Scheme 1 Non-autonomous inchworm walker describedbySeeman
ShermanN. C.
Nano Lett.
2004,
4, 1203complementaryand Seeman.89 (a) Self-assembly of the system from three components:
Shin and Pierigid triple-crossover track featuring three protruding single-strandedach the feet to thehe track establishedk after detachment
B attached to footoot A released from. Matching colours; the lines indicatingof bases.

with the backbone of the track consisting of only one linear
double helix and the walker comprising two partially complementary oligonucleotides (see Scheme 2a). The walker–track
conjugate was assembled by the sequential addition of anchor
strand 1A and anchor strand 2B to the walker and the track(Scheme 2b). Foot A could be detached from the track

DNA Walker• Non-autonomous DNA Walker

he walker and theperative base pairnchor strands 1A
e aggregate. The
aving an overhangremain unpaired.
e removal of an
idisation (branchof one zipper atfor example, cannd and completely
oot behind. This
ined through theable duplex waste
B1 kcal mol!1)91
gh
the interaction
2011年6月4日土曜日

Scheme 2 Hand-over-hand DNA-walker described by Shin and
N. A. Pierce J. Am. Chem. Soc. 2004, 126, 10834
Pierce.92 (a) Self-assembly of the system from three components:
rigid, double-stranded track featuring four protruding single-strandedDNA Walker

View Online• Two-dimensional Walker

ation upon addition of a fuelour different anchor and fuele able to control their device
ther direction down the trackg experiments was analysed byfluorescence spectroscopy. The
functionalised with a fluorescentn wavelength while each foot of
onalised with an appropriate
alizing the gels with different
position of the walker on themple, when foot A is attached tothe dye on foothold 1 is almost
fluorescence of the dye on
d. Using multiplexed real-timelking process could be followed

d coworkers93,94 demonstrated
A-based molecular walkers canat the nanometre scale. For a. 300 nm wide) two-dimensionaled from a total of 202 DNA
mi tile featured 18 protruding
three large slots (Fig. 8a). Thea2011年6月4日土曜日
precise pattern on the DNA

93
Fig. 8 Nanoscale assembly line published by Seeman and coworkers.
N. C. Seeman Nature 2010, 465, 202(a) Schematic illustration of the entire assembly, consisting of a large
DNA origami tile (track), three cassettes each including a DNA

cuts the walker from foothold 1 (Scheme 4, 1 W-2). The energy
required for this step, which represents the crucial process
for the emergence of net-directionality, is supplied by ATPhydrolysis of the restriction enzyme. Repetition of the ligationand cleavage processes (with only restriction enzyme BstAP I
recognising a cleavage site) leads to the partial formation ofwalker state W-3 (Scheme 4). The walker migration occurs
with overall net-directionality as there is no mechanism for thewalker to step backwards.

enzyme (Scheme 5a, right hand side). The partial hydrolysis of
the first two footholds of the track provides the energy sourcefor directional walker transport. Turberfield and coworkers
functionalised footholds 2 and 3 with different fluorescencedyes and the walker with a quencher, which allowed theverification of the behaviour of their system as well as theextraction of kinetic data (stepping rate B0.01 s!1).
Mao and coworkers published a conceptually very similarburnt-bridges walker (Scheme 5b),101 however in their case no

DNA Walker• Autonomous DNA Walker

Scheme 4 Autonomous walker transport mediated by three enzymes reported by the groups of Turberfield, Reif and Yan.99 The walker consistsof six DNA bases (displayed in red). In the descriptions of the states, covalent attachment of the walker (W) to a foothold is indicated by a hyphen;lines indicating base pairing do not represent a particular number of bases.

This journal is c The Royal Society of Chemistry 20112011年6月4日土曜日

Chem. Soc. Rev.

A. J. Turberfield Angew. Chem. Int. Ed. 2004, 43, 4906

DNA Walker• Autonomous DNA Walker

View

cheme 6 Turberfield’s autonomous bipedal DNA walker, powered by two DNA hairpin fuels (H1 and H2).108 (a) Equilibrium between tw
arting states results from competition of the two walker feet for the binding site indicated with an arrow. (b) The left foot can partially lom the track and expose a toehold, which is complementary to the toehold in fuel H1. (c) Branch migration leads to detachment of the left foo) Fuel H2 can displace H1 from the left foot; intermediate 2 (shown for reasons of clarity) or an intermediate of the previous branch migratio
ocess can either rebind at site 1 or site 3, which occurs with statistical product distribution (50 : 50). (e) Starting from the 2,3 state, steric reaso
eclude the mechanism shown in steps i–iv; process 2,3 - 2 is therefore 100 times slower
than 1,2 - Phys.
2; complementary
nucleotide
A. J. Turberfield
Rev. Lett. 2008,
101,sequences238101 a
dicated by the use of light and dark colour tones (e.g. a dark red region is complementary to a light red region); lines indicating base pairing dot2011年6月4日土曜日
represent a particular number of bases.

IV.Small-molecule
WalkerSynthetic Strollers | Science & Technology | Chemical & Engineering News http://pubs.acs.org.ezproxy.webfeat.lib.ed.ac.uk/isubscribe/journals/cen...

Royal Society of Chemistry

Resizing Synthetic DNA walkers are about the same size as biological protein walkers. Small-molecule

walkers are about 1,000 times smaller.
Dozens of DNA walkers now exist. Some have more than two legs; others use alternatives to fuel strands to2011年6月4日土曜日

Walking Small Molecule

2011年6月4日土曜日

Downloaded by Tokyo Daigaku on 29 March 2011
Published on 17 March 2011 on http://pubs.rsc.org | doi:10.1039/C1CS15005G

p://pubs.rsc.org | doi:10.1039/C1CS15005G• Migration of small molecule fragments

View Oa large number of constitutional isomers of derivatised
bullvalones119,120 with base (Fig. 10c).
In haptotropic rearrangements, metal complexes migratealong extended p-systems (see Fig. 10d and f for two
examples),121,122 but these are not generally directional in asense that can be repetitively propagated.
In other reactions, for example the exchange of acetals
between the hydroxyl groups of carbohydrates123 (Fig. 10e)the migration of the carbonyl fragments is intrinsicallynon-directional and non-processive (intramolecular exchange
competes with exchange with the bulk).
There are, however, some reports of small molecular units
that move processively (i.e. without detaching) along molecular
frameworks. Lawton and coworkers have described a series oreagents for the cross-linking of biomolecules under thermo
dynamic control.124–127 These molecules are transferred between
accessible nucleophilic (amine and thiol) sites on proteins suchas ribonuclease.124 The transport proceeds intramolecularly
Fig. 10 Selected examples of the migration of small molecular(i.e. processively) due to the clever construction of the crossfragments. (a) In the Payne rearrangement no atoms, only bonds
linking
116 moiety: only one or two—never zero—of the nucleophilic
migrate.
(b) The Claisen rearrangement occurs processively and infootholds
attached117
to (c)
the Base-induced
cross-linkinginterconversion
molecule at any
someinstancesare
repetitively.
of one118 to anothertime asisomers
it is passed
from onesite
bullvalone
via successive
Copenucleophilic
rearrangements.
Shown
3 D. Leigh Chem. Soc. Rev. 2011, ASAP
are intramolecularly
only three of >10 bullvalone
isomers. (d) minimum
Metal
towards constitutional
the thermodynamic
atoms
can10g).
migrateLoss
processively
along somein
molecular
scaffolds.121(e) stil(Fig.
of processivity
these systems
may
Reversible,
non-processive
migrationof acetonebridges,
along athethreitoloccur, however,throughintermolecularpresenceWalking Small Moleculevon Delius et al.

-Track Conjugate 1,2-C5,a (b) General Structure of Walker-Track Conjugates 3,4-Cn, and (c) 3,4-C5-d4,
m-Labeled on Both the Walker and the Track Units• Synthetic Walker

Synthetic Small-Molecule Walkers

Synthesized small molecule walker

ARTICLES

Scheme 2. Reversible Reactions That Connect Various Pairs of the Four Positional Isomers 1,2-Cn, 2,3-Cn, 3,4-Cn, and 1,4-Cn under

Conditions I or IIa

MF), room temperature, 16 h, 88%; (ii) methanesulfonyl chloride (MsCl), Et3N, CH2Cl2, 0 °C, 30 min; (iii) KSAc,
er two steps); (iv) 6-mercaptohexanoic acid hydrazide, AcOH (cat.), MeOH, room temperature, 2 h, 78%; (v) NaOMe,
KI, CH2Cl2, room temperature, 5 min, 32% (over two steps); (vii) NaH, DMF, 0 °C to room temperature, 16 h, 65%;
erature, 16 h; (ix) KSAc, DMF, room temperature, 3 h, 66% (over two steps); (x) HC(OMe)3, p-toluenesulfonic acid0 min; (xi) NaOMe, MeOH, room temperature, 30 min; (xii) 3-mercaptopropionic acid, I2, KI, CH2Cl2, room temperature,a, CH2Cl2, room temperature,
30 min, hydrazone
58% (overfour steps);
(xiv)
H2SO
room6-96
temperature,
16byh;HPLC(xv) until the distribution no longer
temperature,h (monitored
Condition I (reversible
exchange):
0.1 mM,
TFA,
CHCl
4 (cat.),3, roomMeOH,
Condition(reversible disulfide
exchange): 0.1 mM, DTT (10 equiv), DBU (40 equiv), (TBTA),
dimethyl 3,3′-disulfanediyldipropanoate(20 equiv),
min, 40% (overchanged).
two steps);(xvi) IICu(MeCN)
CH2Cl2/
4PF6, tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine
12-48 h (monitoredby HPLC
untilconnect
the distribution
no longerchanged).
Reversible
reactionsthatvariouspairsof the positional isomers
3, room temperature,emperature, 16CHClh, 79%.

D. Leigh J. Am. Chem. Soc. 2010, 132, 16134

disulfide exchange (Scheme 2, conditions II). In both cases,“double step” route from 1,2-Cn to 3,4-Cn (Scheme 2). It is28
2011年6月4日土曜日
starting
positionof thewalker
3,4-C3, to
3,4-C
, and
3,4-C8statisticalwalker-track
conjugates
3,4-C2,interesting
mixturesof thestarting material
together withpositionalnote 4thatoccasional“errors” to the major

Walking Small Molecule• Distribution of the walker

oaded by Tokyo Daigaku on 29 March 2011
7 March 2011 on http://pubs.rsc.org | doi:10.1039/C1CS15005G

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von Delius et al.

information ratchet

Fig. 11 (a) Oscillation of pH induces the migration of a synthetic small-molecule walker (shown in red) along a four-foothold molecular track(footholds shown in green and blue; linker groups shown in black).136,137 Replacing the reversible base-induced disulfide exchange reaction with anirreversible two-step redox process transports the walker predominantly to the right hand side of the track (away from the minimum energy
Fig. 11 (a) Oscillation of pH induces the migration of a synthetic small-molecule
walker (shown in red) along a four-footho
distribution). (b) Product distribution during three cycles of directionally-non-biased acid–base operation
starting from pristine 1,2-C5. Note: the136,137(footholds
shown
incyclesgreen
linkergroups during
shown1.5
in cycles
black).
Replacing thereversible
base-induced disulfide exchan
Figure2. isomer
Product
distribution
duringthreeofofand
directionallynonbi1,4-C
folding
thetrack.
(c)blue;
Product
distributionof directionally-biased
acid-redox
operation
5 results fromconditions ased,: (i)minor
0.1mM,
TFA,
CHCl
3, rt (ii) 0.1mM, DTT(10eq), DBU(40eq), dimethyl 3,3’-disulfanediyldipropionate(20eq),
acid-basestartingfrompristine redox
1,2-C5 process(left-handside) and the walker predominantly to the right hand side of the track (away from th
two-steptransports
startingfrom operation
pristine irreversible
1,2-C
5.
CHCl3, rt (iii)
1.0mM,DBU(3eq),
CDCl,
reflux;0.1mM,
methyl 3-mercaptopropionate(8eq),
I2 pristin
froma.
pristine
3,4-C5DTT(6eq),(right-handside).
Under
each
set
of
conditions(I b.
andthree3
distribution). (b) Product distribution
duringcyclesEtof3N(xs),
directionally-non-biased
acid–base operation starting fromII), two different pairs ofminor
positional
isomers
are inequilibrium
Schemeisomer
1,4-C
from (seefoldingof the track.
(12eq),CDClrt (c) Product distribution during 1.5 cycles of directionally-biased ac
3/MeOH,
5 results2). Values
based
integration
and arethat
corrected
joins theareotherfootonto HPLCthe trackis labile allowing
foot to for thestarting
pristine
1,2-C5.Information).
absorbanceat290
nmfrom(seeandthe Supporting
sample coefficients
two different(‘forward’‘backward’)footholds
through hydrazone exchange (left hand side in Fig. 11). Under
basic conditions
relativestabilities
the foot–track
significant
amounttheof
thesekinetic
walkers
to oftraverse
the central
joins
the
other
foot
to
the
track
is labile
tointeractions
theonedisulfidesamples
D. Leigh
J. Am. Chem. Soc. 2010, 132, 16134
footholds
and arethusreversed
move andfromend footof thetrackforward
to theother.allowing that footand backward bindingsites onthe different
track while (‘forward’
the hydrazoneand ‘backward’) footholds
sampletwo(ii)
Thevariation
inspacerlength
of
the
unit
has a
2011年6月4日土曜日
foot is locked in place(righthydrazone
hand side inexchange
Fig.walker
11).141The
through(left
hand side in Fig. 11). Underwhich the walker unit bridges the stilbene linkage (E-2,3-1 in
Fig. 13a). E - Z isomerisation provides a driving force for thewalker to step onto the central stilbene unit, while subsequentZ - E isomerisation results in a majority of the walkers beingtransported away from the stilbene group in a direction
determined by which foot–track interaction is labilised next.
The overall direction in which walker transport occurs is thus
dependant on the sequence of the four applied stimuli: acid orbase for mutually-exclusive ‘foot’ dissociation; UV light or

and repetitively, the incorporation of ratchet mechanisms into
chemical structures is required.15 Molecular bipeds, with their
two distinct sites of interaction with a track, offer a logical andeffective means of achieving this.
Remarkable progress has been made in a relatively shortperiod in the development of synthetic molecules that canwalk along tracks.142 Some of the recently developed DNA
systems, particularly those that move autonomously or can
carry out sophisticated tasks (Fig. 8 and Schemes 4–8), are

Walking Small Molecule• Light-driven small-molecule walker

Fig. 13 A light-driven small-molecule walker.139 (a) Operating mechanism of light-driven walker–track system based on selectively labile feet andenergy ratchetadjustable ring strain between the walker (red) and track in one positional isomer. The reaction sequence shown transports the walker from leftto-right; switching steps (ii) and (iv) would cause the walker to be transported preferentially from right-to-left. Stimuli: (i) UV light; (ii) base; (iii)
visible light, iodine; (iv) acid. (b) Composition of the positional isomer mixture during one cycle of operation applying stimuli sequence: i–ii–iii–iv(leads to bias towards the right end of the track).
D. Leigh Angew. Chem. Int. Ed. 2011, 50, 285

Chem. Soc. Rev.
2011年6月4日土曜日

This journal is c The Royal Society of Chemistry 2011

V. Summary

2011年6月4日土曜日

Walking Molecules• Difference between respective walkers
Biological- efficient- need ATP as fuel- only in aqueous environment- modest stabilityDNA- automated synthesize- designed by a computer- complex tracks(DNA origami)- need DNA as fuelSmall-molecule- small size
- low efficient- more stable- in various environments- not need ATP
2011年6月4日土曜日

Walking Molecules• What is a role of “walker”?

Walker is employed for driving
chemical systems away fromequilibrium.
Life is or isn’t a complex system of equilibrium.

a new chemical system mimicking life
2011年6月4日土曜日