MolrMachNN15

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ABENDROTH ET AL VOL 9 rsquo NO 8 rsquo 7746ndash

7768 rsquo 2015

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July 14 2015

C2015 American Chemical Society

Controlling Motion at the NanoscaleRise of the Molecular MachinesJohn M Abendrothdagger^ Oleksandr S BushuyevDagger^ Paul S Weissdaggersect and Christopher J BarrettdaggerDagger

daggerCalifornia NanoSystems Institute and Department of Chemistry amp Biochemistry University of California Los Angeles Los Angeles California 90095 United StatesDaggerDepartment of Chemistry McGill University Montreal QC Canada and sectDepartment of Materials Science amp Engineering University of California Los Angeles

Los Angeles California 90095 United States ^JMA and OSB contributed equally to the work

Inspired by the complexity and hierarchi-

cal organization of biological machinesthe design of arti1047297cial molecular ma-

chines that exhibit controlled mechanicalmotion and perform sophisticated tasks is anultimate pursuitof molecular-scaleengineer-ing17 The design and synthesis of mole-cules that can undergo reversible structuralchanges with various stimuli have receivedconsiderable attention but there remainfar fewer reports of dynamic molecular sys-tems such as cleverly designed motors andpumps where the mechanistic action of

their molecular components has beenexploited to do controlled work on theirenvironment The very de1047297nition of a ma-chine has been a fascinating debate sinceIsaac Asimov began to lay out the early lawsof robotics over 70 years ago8 Inaneff ort toadvance the 1047297eld a stringent language hasbeen sought to diff erentiate simple molec-ular switches from motors that are capableof driving a system away from equilib-rium910 While the working principles of these molecular devices cannot be compared

to macroscopic analogues a practical ac-

ceptance has emerged that a molecularmachine can be a multicomponent systemwith de1047297ned energy input that is capable of performing a measurable and useful sec-ondaryfunction eitherat thenanoscale or if ampli1047297ed through collective action at themacroscale The system should ideally act ina reversible manner with the capacity tocomplete repeated mechanical operationsSpatial control and temporal control overthis motion and work performed are furtherhallmarks of successful machines helping

to diff erentiate deliberate actuated me-chanics that leverage Brownian motionfrom undirected thermal eff ects and ma-chinesfrom simplemolecules that wiggleordiff use randomly1112

In this Review we draw from this rapidlyexpanding and diverse 1047297eld to highlightsome of the most exciting recent reportsof molecules and assemblies that (a) exem-plify practical and advantageous attributesthat can be applied to other systems and(b) show the most promise in successfully

Address correspondence to

pswcnsiuclaedu

christopherbarrettmcgillca

Received for review June 3 2015

and accepted July 14 2015

Published online

101021acsnano5b03367

ABSTRACT As our understanding and control of intra- and intermolecular

interactions evolve ever more complex molecular systems are synthesized and

assembled that are capable of performing work or completing sophisticated

tasks at the molecular scale Commonly referred to as molecular machines these

dynamic systems comprise an astonishingly diverse class of motifs and are

designed to respond to a plethora of actuation stimuli In this Review we outline

the conditions that distinguish simple switches and rotors from machines and

draw from a variety of 1047297elds to highlight some of the most exciting recent

examples of opportunities for driven molecular mechanics Emphasis is placed on

the need for controllable and hierarchical assembly of these molecular components to display measurable e ff ects at the micro- meso- and macroscales As

in Nature this strategy will lead to dramatic ampli1047297cation of the work performed via the collective action of many machines organized in linear chains on

functionalized surfaces or in three-dimensional assemblies

KEYWORDS molecular machines molecular switches rotors and motors hierarchical assembly azobenzene

mechanically interlocked molecules DNA nanotechnology amphidynamic crystals thermophotosalient crystals

photomechanical crystals

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This is an open access article published under an ACS AuthorChoice License which permits copying and redistribution of thearticle or any adaptations for non-commercial purposes



ABENDROTH ET AL VOL 9 rsquo NO 8 rsquo 7746ndash7768 rsquo 2015

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advancing the development of arti1047297cial molecularmachines We 1047297rst summarize some of the key ad-vances in the development of molecular switches androtors ranging from simple hydrazone switches tocomplex deoxyribonucleic acid (DNA)-based nano-mechanical walkers Although these systems in isola-tion are distinct from scaled-up arti1047297cial machines

recent progress in the diversity and complexity of theirdesign has facilitated greater control over mechanicalmotion at the molecular level This control has enabledthe conversion of simple molecular components intofunctional tools that can interact with one another orcouple to their environment to operate as machines atthe nanoscale We highlight some of the most prom-ising examples of the organization of switches androtors into linear assemblies then two-dimensionalarrays on surfaces and 1047297nally polymeric networksand dynamic three-dimensional crystals Ultimatelythe precise and robust integration into higher dimen-sional architectures that take advantage of mechanicalaction by many components is essential to bridge thegap between actuating molecular motion and per-forming microscopic mesoscopic and macroscopicwork Throughout we address fundamental obstaclesyet to beovercometo advance the 1047297eldand to convertthese molecular systems into functioning machinesand off er a glimpse into the untapped potential of these versatile systems in an eff ort to identify some of the most viable directions toward future molecularmachine design and implementation

MOLECULAR SWITCHES ROTORS AND MOTORS

Increasing Sophistication of Molecular Design Numerousclasses of molecules that reversibly isomerize betweenmultiple structuralconfigurations in responseto externalstimuli fall within the realm of molecular switchesCommonexamples of photochromic molecularswitchesaredisplayed in Figure 1 Some of the most extensivelystudied small-molecule motifsinclude (but arefar fromlimited to) azobenzenes whose isomerization be-tween E and Z conformations about a double bondmimics flapping motions1314 diarylethenes and spiro-pyrans in which conformational changes are accom-panied by ring-opening or ring-closing reactions1518

anthracene and coumarin derivatives that reversibly

dimerize with one another1921 and overcrowdedalkenes hydrazones and imines which behave asrotors that can revolve about a rigid internal axis2225

Covalent modification of parent switch and rotormolecules provides near infinite opportunities to de-sign alternate isomerization pathways and to tuneactuation stimuli Additionally noncovalent interac-tions between molecules such as hydrogen bondinghydrophobic effects and π π stacking enable theconstruction of dynamic hostguest systems expand-ing the versatility of switches via supramolecular self-assembly of twoor more components26 Thesedynamic

molecules represent the smallest building blocks avail-able for a bottom-upapproach to synthesize functionalmechanical devices that exhibit motion Increasinglycomplex mechanically interlocked molecules (MIMs)such as catenanes rotaxanes and pseudorotaxanesrepresent another class of switches and rotors andhave regularly been targeted as promising architec-tures in the design of molecular muscles that facilitate

contractile and extensile motions due to theirmechanostereochemistry2729 Catenanes are MIMsconstructed from two or more interlocked macrocyclesin a chain-like architecture that may be designed toadopt distinct and stable conformations with control-lable rotary motions (Figure 2a) Alternatively rotax-anes pseudorotaxanes and their derivatives aremolecules composed of a linear rod-like componentthreaded through a cyclic host the exact position andorientation (station) of the relative components in themechanically interlocked compound can be controlledby external stimuli The macrocycle host may besterically constrained bybulkyend groupson thelinear

species as in rotaxanes or designed to possess suffi-cient free energy to dethread from the rod-like com-ponent as in pseudorotaxanes (Figure 2bc) Finallynanomechanical switches rotors and walkers com-posed of a few to hundreds of DNA biopolymerstrands whose design and synthesis have developedinto a rapidly burgeoning field of its own offer thecapability to extend the dynamic boundaries of indivi-dual molecular components to the submicrometerscale3032

While diverse all of the aforementioned switchand rotor components operate on similar principles33

VOCABULARYMolecular machine - a multicomponent

molecular system with de1047297ned energy input that is cap-

able of performing a measurable and useful secondary

function reversibly either at the nanoscale or if ampli1047297ed

through collective action at larger scales Hierarchical

assembly - the bottom-up arrangement or ordering of

individual components that results in increased overall

size dimensionality complexity andor functionality

Cooperativity - the property of complex action within

coupled molecular systems that yields diff erent results

from isolated or ensemble (collective) switching events

Mechanostereochemistry - the relative spatial arrange-

mentof atoms within mechanically interlocked molecules

Amphidynamic crystal - an ordered solid that has both

rigid ordered lattice constraints and highly mobile com-

ponents simultaneously Thermophotosalient crystal -

an orderedsolidthatexhibits rapid phase transitionsupon

heating or irradiation resulting in jumping of the crystal

which may be accompanied by fracturing Photomecha-

nical crystal - an ordered solid that changes shape(expands bends or twists) under ultraviolet (UV) or visible

light irradiation in the process of crystal-to-crystal chemi-

cal transformation

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The actuation of switching events such as the absorp-tion of a photon electrochemical reduction or oxida-tion reactions binding or unbinding of a ligand orchanges in temperature manipulates the relative en-ergy barrier(s) between two or more possible statesHowever intra- or intermolecular rotational transla-tional or extensile and contractile movements are

ultimately driven by the irrepressible eff ects of thermalnoise This competing driving force highlights the

importance of molecular switch designs to considerthe potential energy landscape to facilitate thermo-dynamically uphill transformations with sufficientlydeep new minima and spatiotemporal control overbiased switching events The most remarkable exam-ples of mechanical control employed to overcome therandomizing eff ect of Brownian motion impart neces-

sary directionality to molecular rotations or trans-lations3435 Typically this control is achieved in avariety of systems by maintaining a judicious balancebetween molecular 1047298exibility and rigidity and utilizingsterically demanding or asymmetric molecular geome-tries Examples include the unidirectional rotationabout double bonds in chiral overcrowded alkenesand imines3637 circumrotation in catenanes38 prefer-ential threading and dethreading of MIMs3940 anddirectedwalkers and nanocars4143 Recently Stoddartand co-workers successfully demonstrated the ener-getically uphill unidirectional threadingof a dumbbell-shaped molecular rod containing a noninteractingoligomethylene chain by tetracationic macrocyclehosts44 This redox-driven molecular pump performswork by 1047297rst con1047297ning one macrocycle on the rod andsubsequently threading a second ring against a localconcentration gradient into an entropically unfavor-able con1047297guration on the oligomethylene chain inclose proximity to the 1047297rst macrocycle The proposed1047298ashing energy ratchet mechanism for the energeti-cally demanding action of the pump can be describedby modulation of the potential energy landscape of the molecule upon redox-switching events

A signi1047297cant yet challenging goal in molecular de-

sign that has received less attention however is thedevelopment of switches whose actuation is engi-neered to trigger cooperative or coordinated actionthus amplifying motion where a switching eventdirectly in1047298uences simultaneous or subsequent con-formational change in another molecule Here theintermolecular coupling of switching events is distinctfrom collective ensemble motion The paradigmaticexample of cooperativity found in Nature is the uptake

Figure 2 Example schematics of switchable mechanically interlocked molecules (MIMs) Functional groups incorporatedwithin the molecular architecture that are in1047298uenced by various stimuli including light pH redox activity and ions programthe switching of stable recognition stations The actuation stimuli thus facilitate movement of the interlocked componentswith respect to one another (a) Catenane composed of interlocked macrocycles that are free to rotate and contain multiplethermodynamically stable con1047297gurations (b) Shuttling motion of a threaded macrocycle (blue) between two stable stateswithin a rotaxane motif in which sterically bulky end groups (green) on the rod-like component prevent dethreading of themacrocycle (c) Unidirectional dethreading and rethreading of a macrocycle host from the rod in a pseudorotaxane

Figure 1 Examples of common small-molecule switchmotifsthat undergo various types of chemical bond rearrange-ments (a) Isomerization of azobenzene between trans andcis conformations upon irradiation or heating (b) Photoin-duced ring-opening and ring-closing reactions of diary-lethene derivatives The closed-ring form is thermally stableand will generally not return to the open-ring con1047297gurationunder ambient conditions when kept in the dark (c) Forma-tion and disassociation of cyclic dimers of anthracene mol-ecules(d) Rotationabouta centraldoublebond in a stericallyovercrowded alkene Numerous structural possibilities existbut the general form consists of a tricyclic stator (bottom)connected to a heterocyclicrotor (top)by a double bond Thereverse reaction most often proceeds via helix inversion of the tricyclic stator upon heating

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of molecular oxygen (O2) by themetalloprotein hemo-globin4546 The binding of O2 by one of four hemegroups induces intramolecular conformational changesin the protein that triggers the favorable uptake of three additional O2 molecules While examples of cooperativity are abundant in Nature there has beenlittle success in the 1047297eld of molecular machine designin synthesizing and operating switchable moietieswhose states are in1047298uenced directly by other mol-ecules An early example of an arti1047297cial multistepswitching cascade was recently reported by Apraha-mian and co-workers in which structurally simple

hydrazone-based switches were shown to facilitatecross-talk between molecules reminiscent of biologi-cal proton-relay processes (Figure 3)47 The input of Zn2thorn initiates EZ isomerization and deprotonation of ahydrazone molecule that contains hydrogen-bond-accepting methylimidazole and quinoline groups tostabilize a metal-ion binding pocket The subsequentproton transfer to a structurally related hydrazoneswitchthat does not interact strongly with Zn2thorn resultsin the isomerization of a second molecule Capitalizingon the leveraging of intermolecular interactions toin1047298uence switching events represents a paradigm shiftin the design of next generation molecular switches as

it exempli1047297es active and dynamic communication be-tween separate components to work in tandem4850

If analogous approaches toward amplifying molecularmotion can be applied to other switching motifs withgreater speci1047297city and without the use of sacri1047297cialreagents substantial increases in the operational yieldof isolated or hierarchically assembled systems can beenvisioned and may thereby increase their practicalityin real-world applications

Isolated Small-Molecule Machines The rational designof switches and rotors or even the impressive direc-tional control over walkers and motorized nanocars is

clearly not a final objective (unless of course thedesign is to be entered in a molecular nanocarrace)5152 It is instead necessary to harness and toamplify the mechanical motion of individual compo-nents to drive iterative chemical processes or to com-plete complex tasks in order to qualify these dynamicsystems as functional machines Some of the mostinnovative examples of mechanistic function of isolated molecules are switchable catalysts that arecapable of raising or lowering the energetic barriers tochemical transformations5355 Molecular machines thatcontrol bidirectional enantioselectivity in asymmetric

catalysis are particularly exciting as the preparation of enantiopure catalysts and the separation of racemicmixtures of synthetic products are typically tedious andcumbersome processes Wang and Feringa demon-strated in situ switching with enantiomeric preferenceof the chiral product of a conjugate addition reactionusing a rotary-motor catalyst fueled by light56 Morerecently Leigh and co-workers described a rotaxane-based asymmetric catalyst that can be switched on andoff by revealing and concealing respectively a chiralorgano-catalytically active amine built into a mechani-cally interlocked axle via simple protonation or deproto-nationof the amine group5758Temperature may alsobe

used as a means to control product enantioselectivitywith a single switchable catalyst as reported by StorchandTrapp to direct asymmetric hydrogenationreactionsupon catalystepimerization59The precise spatial controlafforded by these dynamic molecular designs facilitatesthe integration of enzymatic behavior with mechanicalmotion thus exemplifying the potential of small-molecule machines to perform useful tasks at themolecular level for applications ranging from catalysisto photopharmacology60

Another ingenious example of leveraging fueledmolecular motion for performing useful operations at

Figure 3 Cooperativeswitching eventsbetween two distinct molecular switches an imidazole-containing hydrazone switch(QIH-Me) and pyridine-containing hydrazone switch (PPH) Upon addition of Zn2thorn QIH-Me isomerizes to a structure thatcontains an acidic imidazolium ring (Zn(QIH-Me(Z-Hthorn))) The PPH switch subsequently isomerizes to PPH(Z-Hthorn) upon protontransfer from Zn(QIH-Me(Z-Hthorn)) The addition of tetrabutylammonium cyanide (nBu4NCN) to the reaction mixture regener-ates the original switch con1047297gurations The scheme illustrates coupled switching events between two molecules throughproton relay Reproduced with permission from ref 47 Copyright 2012 Nature Publishing Group

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the molecular scale is the sequence-de1047297ned synthesisof oligomer chains In Nature the polyribosome hasbeen shown to have roles in both biosynthesis andprotein assembly61 Utilizing the mechanically inter-locked nature of rotaxanes Leigh and co-workersdesigned a ribosomal mimic that travels along amolecular strand to assemble amino acids iterativelybynativechemicalligation(Figure4)62Onceassembled

the rotaxane-based machine is activated by acidiccleavage of protecting groups on the macrocycleallowing itsmovementalongthe strandbearing aminoacid building blocks A bulky terminal-blocking groupon one end of the strand facilitates unidirectionaldethreading once all amino acids have been sequen-tially added to the macrocycle Although the reactionkinetics remain slow (the formation of each amide

Figure 4 Scheme depicting the proposed mechanism for sequence-speci1047297c oligopeptide synthesis using a rotaxane-basedmolecular machine (a) Machine is activated upon removal of protective groups from the macrocycle (b) Under basicconditions the amino acid moieties that are tethered to the rod-like component are sequentially transferred to the

macrocycle as it unidirectionally dethreads from the rod (c) Macrocycle can then be subsequently hydrolyzed to obtainthe isolated oligopeptide-containing motif The stimulated directed motion facilitates small-molecule synthesis by amolecular machine through the intelligent functionalization of the cyclic host and threading strand Reproduced withpermission from ref 62 Copyright 2013 American Association for the Advancement of Science

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bond takes approximately 12 h) the modular designand new threading protocol in machine preparationoff er the possibility of analogous molecular synthesisfrom other monomer types and the employment of

longer oligo- or polymer tracks63

DNA-Based Machines and Walkers DNA-based nano-mechanical devices such as tweezers and gears havealso shown promise as artificial molecular machines asdemonstrated by the specificity and predictability withwhich these molecules can be modified6465 Boostedby the advent of DNA origami the advances in pro-grammability of these devices have enabled rapidstrides toward the design and operation of DNAmachines66 These devices are engineered for a varietyof applications including catalysis and the capture andrelease of targets ranging from single metal ions tolarge proteins6769 Their motion may be actuated by

the targets themselves sacrificial staple strands oraptamers (synthetically designed DNARNA motifs)or light-utilizing oligonucleotide sequences chemicallymodified with photoswitching molecules such asazobenzene7073 The recognition of targets by DNAor RNA devices that induce sophisticated secondaryfunctions based on Boolean logic-gatedmechanisms isparticularly impressive utilizing conjunction (AND)disjunction (OR) or negation (NOT) operations74 Logic-gate operations performed by DNA were demonstratedby Adleman and Lipton two decades ago but DNA-based computing remains underdeveloped due to

challenges associated with scale-up and slow reactionkinetics7576 Church and co-workers recently designeda DNA nanorobot composed of over 200 uniqueoligonucleotides and capable of delivering payloads

such as antibody fragments or nanoparticles to cells byincorporating an AND gate based on two lockingaptamer-complement duplexes (Figure 5)77 Uponsimultaneous recognitionof theirtargets the duplexesdissociate and the nanorobot undergoes a structuralrearrangement to expose the sequestered payloadsWhile the implementation of such complex proof-of-principle nanorobots in vivo is not likely in the nearfuture analogous logic-gated target discriminationmay be advantageous in the design of moleculardevices for future biomedical applications such as drugdelivery and gene therapy as well as sensing andcomputation737880

Inspired predominately by biological motor pro-teins from the kinesin dynein and myosin familiesclever DNA walkers have been designed to enableprogressive movement along prescripted tracks8184

Numerous strategies have been employed to facilitatedirectional movement including the incorporation of Brownian ratchet and enzymatic ldquoburnt bridgerdquo me-chanisms asymmetric molecular design and the use of chemically modi1047297ed architectures containing azoben-zene that initialize walking upon photoisomeriza-tion8588 These walkers may behave autonomouslyor require external intervention the latter most often

Figure 5 Design of a logic-gated DNA nanorobot (a) Front and (b) perspective view of a DNA nanorobot loaded with aprotein payload (pink) The boxed area denotes one of the two aptamer locks that clasp the front of the nanomechanicaldevice (c) Aptamer-based gate is composed of an aptamer (blue) and a partially complementary DNA strand (orange) Theldquoopenrdquo con1047297guration canbe stabilized byan antigenkey (redcircle) (d)Payloadsincluding gold nanoparticles (gold)or smallproteins (magenta) may be tethered inside the nanorobot The DNA-based nanomechanical device enables the loading andcell-speci1047297c delivery of various cargo that utilizes an AND gate both aptamer-based lock sites must be unlocked with theirantigen keyfor thenanorobot to openReproduced with permission from ref77Copyright 2012 AmericanAssociationfor theAdvancement of Science

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enables greater complexity in programmability Someof the 1047297rst remarkable reports of functional DNA walk-ers utilized stepwise mechanics to design systemscapable of synthesizing organic molecules or donat-ing cargo8990 In a more recent example Choi andco-workers described the fueled autonomous translo-cation of CdS nanocrystal cargo by a single-stranded

RNA-cleaving DNA enzyme over 3 μm along a RNA-decorated carbon nanotube track whiledemonstratingrobust control over stopping and starting the walker(Figure 6)91 These proof-of-principle designs for DNAwalkers show promise for DNA-based circuits nano-robotics and cargo transport supported by quanti-tative control over rates for complementary stranddisplacement reactions9293 Still these complicatedmechanical systems have generally been plagued byslow kinetics and poor overall performanceThe opera-tional yields of complementary strand hybridization ordisplacement reactions that facilitate the progressiveand repetitive movement of many DNA walkers are

generally lower than the elementary reactions thattake place outside the context of complex DNAarchitectures94 Considerable eff ort has been directedtoward improving the operational yieldof DNA walkersto improve reliability motility and control by targetingvarious parameters that in1047298uence theirmechanics9596

For example Nir and co-workers recently demon-strated a two orders of magnitude increase in theoperational yield of a DNA walking device throughmechanistic investigation of oligonucleotide strandfuel removal and fuel addition reactions to preventundesirable trapped states97 Nevertheless further

improvements in walking speed yield and fuel opti-mization may be necessary for efficient and practicaltransport and assembly of molecular and nanoscalecargo Maintaining autonomy with increasingly com-plex programmability in the design of walkers andtracks is a challenging task but will help DNA walkersmove beyond the initial steps that have been taken to

convert these nanomechanical devices into usefulmachines9899

Nanostructure Functionalization The intelligentfunction-alization of larger organic or inorganic nanostructureswith small molecular switch and rotor componentsas well as complex DNA assemblies further expandsthe versatility of these dynamic systems for applica-tions such as drug delivery and to tune the chemicaland physical properties of the hybrid materials100101

Exemplary demonstrations of artificial molecular ma-chinery that employ functionalized nanostructures aremesoporous nanocrystals modified with molecularnanoimpellers valves or gates for the capture and

release of cargo with external control102 Numerousswitchmotifs have been utilized as gatekeepersto con-trol payload release from these versatile materials includ-ing rotaxanes103 pseudorotaxanes104105 DNA mole-cules106107 coumarins108109 and azobenzenes110111

Besides the necessity for biocompatibility tissue spe-cificity and high loading capability to implementthese systems in vivo for biomedical applications suchas controlled drug release noninvasive actuation me-chanisms are also required because some stimuli maybe detrimental to biological environments112 In arecent example a nanoimpeller system developed by

Figure 6 (a) Schematic of a DNA enzyme-based molecular machine that walks autonomously along a RNA-functionalizedcarbon nanotube track (black) carrying a CdS nanoparticle (yellow) The DNA enzyme (E) here is a synthetic oligonucleotidesequence that contains recognition regions (red) and a catalytically active sequence (green) that cleaves an associated RNAmolecule (S1) in the presence of Mg2thorn Upon cleaving S1 the DNA enzyme processes through a series of conformationalchanges to hybridize with another RNA molecule (S2) attached to the carbon nanotube facilitating its movement along the

track as the process is repeated(b) Series of overlaid1047298uorescence microscopy images (to determine CdS position) and near-infrared nanotube imagesover 30 h in the presence of Mg2thorn Scale bar2 μm The DNAmotor is capable of carrying inorganiccargo with a maximum velocity of ca 01 nm s1 The noninvasive optical measurements used here are ideal for monitoringthe real-time in situ motion of cargo-carrying DNA walkers and may be applied to other systems for the characterization of various parameters that in1047298uence walker motility Reproduced with permission from ref 91 Copyright 2014 NaturePublishing Group

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Croissant et al utilizes azobenzene photoisomeriza-tion as a driving force to release the anticancer drugcamptothecin from mesoporous silica nanoparticles(Figure 7)113 Contrary to classic designs in whichazobenzene trans to cis isomerization is triggered byultraviolet (UV) light which is harmful to living cellsthis prototype system is based on two-photon excita-tion (TPE) of a fluorophore with near-infrared (NIR)light The use of NIR light facilitates isomerization of the azobenzene moieties through Foumlrster resonanceenergy transfer (FRET) from a nearby fluorophore

Isomerization of the azobenzene nanoimpellers sub-sequently kicks out thecamptothecin cargo leading tocancer cell death in vitro Using TPE with NIR light totrigger drug release from mesoporous nanoparticleshas not yet been extensively explored but offers thebenefits of deeper tissue penetration in the biologicalspectral window (7001000 nm) and lower scatteringloss114115 The TPE-based designs illustrate how theactuated mechanicsof photoswitches canbe tailored bytheir immediate surroundings by coupling simpleswitches or rotors to their nanostructured environmentprovided that the fluorophores have large two-photon

absorption cross sections and sufficient emission quan-tum yields (gt05) for FRET

The integration of switchable molecular systemswith inorganic nanostructures and nanoparticle as-semblies also enables the manipulation of the hybridmaterials optical properties in situ Two commonmethods to direct the optical properties of nanostruc-

tured materials are the active tuning of refractiveindices at the surface of plasmonic nanoparticles func-tionalized with switchable molecules116118 and phys-ically modulating interparticle distances or orienta-tions119123 Using the latter strategy Willner andco-workers have designed a myriad of hybrid DNA-based tweezers catenanes and rotaxanes functiona-lized with gold nanoparticles or quantum dots whoseinterparticle distances can be directly manipulatedwith stimuli including pH metal ions and oligonucleo-tide strands124 The switchable mechanical controlover these hybrid assemblies is accompanied byunique spectroscopic features as a result of plasmoniccoupling between gold nanoparticles chemilumines-cence resonance energy transfer between quantumdots or the photoluminescent properties of attached1047298uorophores125127 Increasing the modularity anddimensionsof DNA-basednanomechanical assembliesin this manner has enabled exceptional function stillchallenges remain as the increases in size and com-plexity of devices may be accompanied by lowersynthetic yield and product heterogeneity128129

INCREASING DIMENSIONALITY AND HIERARCHICAL

ORGANIZATION

Linear Assemblies The actuated inter- or intramole-cular motion of small individual switch and rotorcomponents occurs on the Aringngstroumlm to nanometerscales In order to perform macroscopic work it wouldbe useful to harness the synchronized mechanics of ordered ensembles of molecules in which the collec-tive action translates into motion orders of magnitudelarger than that of individuals This hierarchical orga-nization is exemplified by skeletal muscle tissue Sar-comeres the basic repeating units throughout musclecells are composed of interdigitated myosin and actinfilaments The sliding of actin along myosin is facili-tated by the walking of globular motor proteins at-

tached to cross-bridges between the filaments Thismotion generates tension and is responsible for thelinear contraction and expansion of each sarcomereAnalogously MIMs exhibit practical architectures forthebuilding blocksof synthetic molecular muscles dueto their mechanostereochemistry130 In particular bi-stable daisy-chain rotaxanes which are composed of two interlocked cyclic dimers display muscle-like con-traction and expansion upon switching (Figure 8a)Many stimuli may be used to actuate motion in theseefficient and versatile switches including pH redoxreactions light solvent and ions131135 Efforts have

Figure 7 Two-photon excitation (TPE) of a 1047298uorophore tofacilitateFoumlrster resonance energytransfer (FRET)to photo-izomerize azobenzene nanoimpellers on mesoporous silicananocrystals and subsequent cargo release (a) Overlap of the emission spectrum of the 1047298uorophore and absorptionspectrum of the azobenzene nanoimpeller enables FRET(b) Structure of the azobenzene moiety (c) Structure of thetwo-photon1047298uorophore (d) Photoisomerization of azoben-zene using two-photon (760 nm) excitation of the 1047298uoro-phore (e) Schematic of the mesoporous silica nanocrystal(f) Transmission electron microscopy image of a singlenanocrystal Light-activated nanovalves that utilize near-infrared irradiationsuch as this TPE-basedmechanismshowpromise for targeted drug delivery applications and shouldbe further explored to extend their scopeReproduced with

permission from ref 113 Copyright 2013 Wiley

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been made to polymerize daisy-chain rotaxanes intolinear assemblies with varying success136137 In one of the most remarkable examples Giuseppone Buhlerand co-workersdemonstrateda metallo-supramolecularpolymerization process to combine thousands of pH-switchable daisy-chain rotaxanes138 The polymersdemonstrated global changes of contour length of approximately 6 μm (Figure 8b) This contraction ison the same order of magnitude as that observed insarcomeres Subsequently assembling these chainsinto ordered fibersand bundles similar to thehierarchi-cal assembly of sarcomeres in myofibrils and theirattachment to surfaces will be a significant accomplish-ment toward enhanced engineering of artificial mus-cles from small switch components

Another molecular switch motif that holds promisefor arti1047297cial muscles through linear polymerization isthe azobenzene chromophore By incorporating azo-benzenewithinthemainchainofalinearassemblythe

culmination of modest dimensional changes of merelya few Aringngstroumlms for each chromophore can result indramatic changes in thecontourlength of thepolymerUtilizing this strategy Gaub and co-workers demon-strated the capability of individual polyazobenzenepeptides to perform mechanical work by tetheringone end of the chain to a substrate and the other toa 1047298exible cantilever to measure the force exerted bythe contracting polymer upon photoisomerization139

The extent of polymer deformation and thus theusefulness of the molecules for optomechanical appli-cations depends on both the conformational rigidityof the backbone and minimization of electronic cou-

pling between azobenzene moieties140 The synthesisof rigid-rod polymers that include azobenzene withina poly( para-phenylene) backbone is one strategy tomaximize photodeformation enabling accordion-likecompression and extension of chains upon cyclingwith UV andvisible light (Figure9a)141Lee etal demon-strated that these single-chain polymeric assembliesmay even exhibitcrawlingmovements when depositedonto an octadecylamine-modi1047297ed graphite surface andimaged with scanning force microscopy (Figure 9b)142

Chemically or physically cross-linked supramolecularassemblies of these linear photomechanical polymers

may be envisioned to behave as actuators to liftweights and to perform other types of work withgreater resistance to deformation fatigue than indivi-dual strands143 For example Fang et al reported usinga simple melt spinning method to fabricate hydrogen-bonded cross-linked 1047297bers of azobenzene-containingmain-chain polymers that were prepared via a Michaeladdition reaction (Figure 10)144 The authors also in-vestigated the photoinduced mechanical propertiesof the 1047297bers reporting a maximum stressgenerated bya single 1047297ber of 240 kPa upon UV irradiation at 35 CThis force is similar to the maximal tension forces of

Figure 8 (a) Bistable daisy-chain rotaxane (b) Metallo-supramolecular polymer of multiple pH-switchable daisy-chainrotaxanes The culmination of contraction or extension by individual monomers results in global changes in large contourlength of the polymer on the order of microns Reproduced with permission from ref 138 Copyright 2012 Wiley

Figure 9 (a) Schematic of a main-chain azobenzene-containing polymer (P1 R = C12H25) with a poly( para-phenylene) backbone Irradiation with UV or visible lightfacilitates photoisomerization of azobenzene and conver-sion to the compressed and extended conformations re-spectively Reproduced with permission from ref 141Copyright 2011 Wiley (b) Scanning force microscopyimages of P1 deposited on a modi1047297ed graphite surfaceThe polymer crawls along the surface as it contracts uponUV irradiation Demonstrating control over movementdirection and the functionalization or tethering of thepolymer strands to scaff olds may enable the macromole-cules to perform work by lifting weights or transportingcargo Reproduced from ref 142 Copyright 2014 AmericanChemical Society

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some chemically cross-linked azobenzene-containingpolymer 1047297bers and even human striated muscles(ca 300 kPa)145

Two-Dimensional Assemblies and Surface Functionalization

The aforementioned systems describe molecularswitches rotors and motors in relative isolation How-ever without a suitable frame of reference even thecontraction and extension over dramatic micronlength scales by polymerized chains of functionalrotaxanes is difficult to utilize for practical applicationsComplicating matters to leverage the mechanicalmotion of ensembles of molecules some director ismandatory to overcome the chaotic application of force Similar to Archimedes need for a place to standto move the Earth a surface may be utilized to instill

directionality to harness thepowerof large numbers of molecular machines Two-dimensional coverage bymolecular switches and rotors on planar surfacesprovides advantages over isolated molecules or func-tionalized nanoparticles by facilitating the manipula-tion of physical andchemicalproperties of a material atthe micro- meso- and macroscales For examplethrough the amplification of collective molecular me-chanical motion the integration of small-moleculeswitches and rotors into ordered arrays has resultedin dynamic control overwork function refractive indexand surface wettability146150 In more obvious de-monstrations of performing work the cumulative

nanoscale movements of stimuli-responsive rotaxanesassembled on metal surfaces have been harnessed tomove liquid droplets uphill or to bend flexible micro-cantilever beams151155 Micropumps that are capableof establishing a steady flow of liquid or small particlesmay also take advantage of surface functionalizationby molecular machines for microfluidics or drugdelivery156 Molecular pumps based on hostguestinteractions composed of cyclodextrin and azoben-zene designed by Sen and co-workers perform such afunction by external stimulation with light157 Thesehybrid systems are organized within gels or adsorbed

directly on glass substrates (Figure 11ab) Upon UV light absorption azobenzene molecules isomerize andleave their cyclodextrin hosts The created cavity is thenpromptlyfilled withwater molecules The amplified and

Figure 10 (a) Synthetic route and chemical structures of acrylate-type azobenzene monomers (b) Supramolecularhydrogen-bonding interactions between main-chain polymers to facilitate physical cross-linking (c) Photographs of apolymeric 1047297berfabricated by simplemelt spinning The1047297ber reversibly bends upon irradiation with UV and visible light The1047297bers demonstrate robust photodeformation fatigue resistanceand high thermalstabilityand show promise for applicationsas photomechanical actuators Reproduced from ref 144 Copyright 2013 American Chemical Society

Figure 11 (a) Schematic of a dual-responsive micropumpon a glass surface Light or chemical stimuli may be used toinduce 1047298uid 1047298ow by a β-cyclodextrinpolyethylene glycol( β-CD-PEG) gel upon isomerization of the azobenzene moi-ety (b) Schematic of the direct functionalization of glasssurfaces by covalently tethering azobenzene-containing

molecules Reversible formation or disassociation of thehostguest complex with R-cyclodextrin results in 1047298uidpumping (c) Optical microscopy image of tracer particlesin solution above a β-CD-PEG gel on a glass surface beforeirradiation (d) Optical microscopy image of tracer particlesaccumulatingat the edge of a β-CD-PEG gel afterirradiationwith UV light for 1 h Scale bars 50 μm The reversibility of the hostguest interaction makes the design particularlyappealing for rechargeable microdevices Reproduced fromref 157 Copyright 2013 American Chemical Society

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collective actions of the multitude of neighboringpumps creates a steadyflow of fluid aroundthe surfaceat the rate of ca 2 μms (Figure 11cd) The pump canalso be activated by chemical stimuli and rechargedby visible light irradiation Despite these impressiveexamples there exist few reports of integration of molecular switches and rotors in planar assemblies

because of the challenging design rules that accom-pany surface functionalization as described below

Self-assembled monolayers (SAMs) LangmuirBlodget (LB) 1047297lms and layer-by-layer (LbL) assembliesare all well-understood organic thin-1047297lm technologiesthat can be utilized to fabricate nanoscale functionalsurfaces158160Within SAMs intermoleculardistancesmolecular orientation and substratemolecule in-teractions strongly in1047298uence whether assembledswitches and rotors retain their functionality due tothe varied chemistries of their interfaces161162 Physi-cally and electronically decoupling these functionalmoieties from surfaces or from neighboring moleculesis often necessary to avoidsteric constraints or quench-ing of excited states163168 For example molecularrotors can be tethered such that the axis of rotation isaligned parallel or perpendicular to the surface ineither altitudinal or azimuthal orientations respec-tively Feringa and co-workers reported the tunableand reversible wettability of gold surfaces modi1047297edwith SAMs of altitudinal rotors based on light-drivenovercrowded alkenes bearing per1047298uorinated alkylchains (Figure 12a)169 Taking advantage of unhin-dered rotation enabled by the superior altitudinalorientation of the rotor units dramatically modi1047297ed

the surface energy with resulting water contact anglechanges of as much as 822 owing to diff erences inthe orientation of the hydrophobic per1047298uorobutylgroup (Figure 12b) The photoconversion efficiencyand rotation speed of these surface-bound rotors arestill generally lower than for free molecules in solutionhighlighting how proper spatial arrangement andsufficient room to rotate are necessary parameters tooptimize for these dynamic molecular motifs to retaintheir large-scale functionality170

The design rules to retain functionality and tounderstand substratemolecule and intermolecularinteractions of MIMs that self-assemble on surfaces

are not as well understood Rotaxanes may be cova-lently modi1047297ed with thiol or disul1047297de tethers to enablebinding to noble metal surfaces providing a platformfor potential applications in diverse areas includingmolecular-scale electronics and nanoelectromechani-cal systems152154155171 However many rotaxane andpseudorotaxane motifs have poorly de1047297ned orienta-tions or conformations when tethered to surfaces dueto their 1047298exibility making it difficult to predict condi-tions for reproducible self-assembly168 Heinrich et al

recently demonstrated that tight packing may beadvantageous for the efficient switching of many

rotaxane molecules on the surface (Figure 13a)172

The authors used angle-resolved near-edge X-ray ab-sorption 1047297ne structure (NEXAFS) spectroscopy to studycooperative eff ects in chemically switchable rotaxanesdeposited on gold surfaces by LbL self-assembly Lin-ear dichroism eff ects in NEXAFS spectra re1047298ect pre-ferred ensemble molecular orientation and thereforethe disappearance or enhancement of linear dichroismmay be used to monitor conformational changes onsurfaces Densely packed monolayers of rotaxanesexhibited a pronounced increase in linear dichroismupon switching indicating conversion of one orderedsurface structure into another (Figure 13b) On the

other hand dilute monolayers in which the rotaxanesmotifs were less densely packed displayed negligiblelinear dichroism eff ects both before and after applica-tion of chemical stimuli (Figure 13c) These resultssuggest that in this system properly designed denselypacked rotaxanes can switch in a coupled manner incontrast to previous reports of interference of proximalrandomlyassembledsurface-boundrotaxanes168Whileinducing conformational changein a single rotaxane isunfavorable in the densely packed array once a smallnumber of molecules have converted to their iso-meric forms it becomes less sterically demanding for

Figure 12 (a) Molecular rotors based on overcrowdedalkenes attached to a gold surface in azimuthal (left) andaltitudinal (right) orientations (b) Water droplet on a goldsurface functionalized with self-assembled monolayers of overcrowded alkenes in the cis conformation bearing per-1047298uorinated alkyl chains The hydrophobic per1047298uorobutylgroup on the rotor is hidden from the interface resulting ina contactangle of60 ( 1 (c) Inthe trans conformation thehydrophobic group is exposed to the interface resulting ina water contactangle of 82( 1 The altitudinal orientationof the rotor and the tripod tethering unit are advantageousmolecular structures that may be applied to other func-tional surfaces based on self-assembled monolayers of molecular machines Reproduced from ref 169 Copyright2014 American Chemical Society

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neighboring molecules to switch resulting in rapidgrowth of newly ordered domains This cooperativeswitching scenario is analogous to that observed indensely packed SAMs of molecules containing azoben-zene headgroups173174 Applying similar design prin-ciplesto other assemblies of switchand rotor motifsonsurfaces to facilitate cooperative switching mechan-

isms would be advantageous for faster more robustand more energy-efficient molecular machines

As described above the design and fabrication of organic thin 1047297lms of molecular switches or rotors onsurfaces that retain switching yields comparable tothose of free molecules in solution remain challengingtasks Complicating matters the favored molecularorientations steric considerations and intermolecularelectronic coupling strengths are diff erent for eachsystem whether the molecules are chemically ad-sorbed directly on surfaces or within polymeric assem-blies Nevertheless the successful demonstrations of predictable surface attachment of molecular machines

that give rise to directed andde1047297ned stimulus-inducedfunction provide promising examples for applicabilityin the future New directions may take advantage of combining bottom-up molecular assembly techniqueswith top-down patterning methods to design novelmaterials with controllable features from sub-100 nmto thecentimeter scale175179Patterningdiverseswitchandor rotor components side-by-side withprecise two-dimensional control may give rise to new surface func-tionality with molecular packing density gradients ormultiplexed domains with various available actuationmechanisms

Three-Dimensional Assemblies and Crystals The integra-tion of dynamic molecular switches and rotors intothree-dimensional architectures is a natural and desir-able extension of supramolecular assemblies yieldingdynamic materials with controllable properties in alldirections Some of the first three-dimensional molecu-lar machines were fashioned from polymeric mate-

rials or photomobile crystalline arrays such as light-powered walkers rollers and beltpulley motors byYamada etal180181Theseexamplesutilized azobenzenemoieties within liquid-crystalline elastomers in whichmechanical strain is strongly correlated with thecharacteristic orientational order of the mesogensThe incorporation of photoswitching molecules intoliquid-crystalline polymer networks enables the ampli-fication of and greater control over the reversiblephotodeformation of actuators Notable advances inthe field of photomechanical polymers include thedevelopment of more complex movement patternsdesigns that respond to a broader range of stimuli

and better addressability and spatial precision182184

Katsonis and co-workers recently described impressivecontroloverthe helicalmotion of azobenzene-containingliquid-crystalline polymer springs mimicking the exten-sile function of plant tendrils185 Unlike previous reportsof twisting motion within photomechanical crystallinesystems in which the helical deformations are dictatedby the facets that are irradiated with UV or visible lightthe handedness and modes of coiling motion can bepreprogrammed by including chiral dopants and con-trolling the relative orientation of the aligned liquidcrystals within each spring respectively186

Figure 13 Molecular structure and angle-resolved near-edge X-rayabsorption1047297ne structure (NEXAFS) spectroscopy of layer-by-layer assembled chloride switchable rotaxanes on gold surfaces (a) Rotaxane molecule under investigation containingtritylphenyl stopper groups on the rod and terpyridine side chains attached to a functionalized tetralactam macrocycleAngle-resolved NEXAFS spectra of (b) a densely packed rotaxane monolayer on a rigidpyridine-functionalizedself-assembledmonolayer (SAM) of (E )-4-(pyridin-4-yl)stilbenethiol (PST) and (c) a dilute rotaxane monolayer on a terpyridine-terminated

dodecanethioldecanethiol mixed SAM The NEXAFS results are depicted from top to bottom before chloride addition afterchloride addition and after chloride removal NEXAFS spectra were obtained for the incident synchrotron light beam at30and 90 angles (red andblacklines) The diff erence between the two spectra is shown in green Linear dichroismeff ects in(b) suggest the coupled motion of densely packed rotaxane monolayers underscoring the advantage of lateral order andmolecular alignment for functional surfaces based on large mechanically interlocked molecules Reproduced from ref 172Copyright 2015 American Chemical Society

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While polymeric materials off er ease of processingand fabrication crystalline motifs off er a path to near-perfect three-dimensional arrangements of dynamicmolecular building blocks as well as a facile meansto monitor the motion of the crystals using nuclearmagnetic resonance (NMR) and X-ray diff raction Fur-thermore energy transduction in crystals is faster andactuating motion is generally of larger magnitudecompared to polymeric assemblies because rigidlypacked molecules have to work as an assembly tofunction whereas in a less-ordered medium motion of the same molecular switches may be less directionallybiased and ultimately less efficient Often derided asa ldquochemical cemeteryrdquo after Leopold Ruzickas famousremark crystal machines have witnessed a remark-able resurgence in recent years with discoveries of

controlled or spontaneous actuation reversible orirreversible movements and reactivity187189 Re-search eff orts toward molecular machines fashionedfrom crystals can be subdivided into two broad classesone in which movable elements are present in thecrystal lattice and the other where the entire crystalbecomes a machine

The former class of crystalline machines is com-posed of amphidynamic crystals that most often in-corporate rotors into a lattice thereby maintainingmacroscopic order If enough free volume is presentthe molecules retain their rotational degrees of free-dom and can spin with varying frequencies within the

range of hertz to gigahertz Such rotation demon-strates promise as a new class of mechanical switchescompasses and gyroscopes190194 When the rotorunits contain an electric dipole amphidynamic crystalsmay also provide an avenue for tunable dielec-trics195197 Solid-state NMR techniques are usefulcharacterization methods to determine molecular or-der and the gyroscopic dynamics within amphidy-namic crystals when rotors contain atoms thatoccupy multiple magnetically nonequivalent sites Asa molecule rotates atoms may exchange positionsbetween these sites the rate of which is determined

by the rotational potential energy barrier and sampletemperature198 Features in the NMR spectra at diff er-ent temperatures provide information aboutensembleexchange rates and therefore rates of rotation of rotors within the crystalline lattice Spontaneous rota-tion is common in crystalline rotors with rotationalactivation energy barriers greater than k BT (the avail-able thermal energy) Notable studies in this 1047297eldhave reported on engineering coupling betweenrotors199201 and controlling the rate of motion bylight or chemical input similar to the design of syn-thetic brakes for noncrystalline rotors202 RecentlyCommins and Garcia-Garibay developed a moleculargyroscope that utilized a photoactive azobenzene unittethered on either side of a rotatable phenylenecenterblock (Figure 14)203 The conformation of the azoben-

zene switch was shown to exhibit robust control overthe rates of phenylene rotation When the azobenzenebrake was in the trans conformation the crystallineassembly rotated 10 timesfaster thansamples contain-ing the cis isomer Sozzani and co-workers demon-strated another sophisticated approach to engineerand to control crystalline rotors using porous molecu-lar crystals204 The authors demonstrated that perma-nently porous crystals that incorporate p-phenylenerotors were accessible to small-molecule guests suchas CO2 and I2 in the vapor phase In particular theuptake of I2 altered the molecular environment of the rotors dramatically the exchange rate decreased

by four orders of magnitude from 108 to 104 Hz(Figure 15) The same group also proposed usingporous organic frameworks as hosts for molecularrotors due to their large surface areas and porecapacities205 Comparable to the molecular cocrystalsdiff usion of I2 into the pores resulted in decreasedrotation rates by three orders of magnitude at roomtemperature Sensing or actuating applications maybe envisioned that utilize the resulting in1047298uence of small-molecule guests on the rotation rates for theuptake and release of small-molecule guests by theseamphidynamic crystals and organic frameworks

Figure 14 (a) Molecular gyroscope that contains benzophenone motifs (green) that bridge the structure from one stator totheother(b) Azobenzene-bridgedmolecular gyroscope In (a)and (b) therotation of thecentral phenylenemay be hinderedby collapse of the bridge toward the rotor The use of an azobenzene motif as a bridge enables control over the rate of rotation using UV or visible light to convert the switch or brake between trans and cis conformations Reproduced fromref 203 Copyright 2014 American Chemical Society

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While the previously described amphidynamiccrystals possess sufficient free volume for rotation of essential structural elements translational motionwithin a crystal is much less common By incorporat-ing rotaxane molecules as organic linkers withina metalorganic framework (MOF) Loeb and co-workers recently succeeded in facilitating the reversi-ble translation of a molecular shuttle inside a solid-state material between two stable states206 The

system contains Zn4O clusters as the nodes of theMOF and carboxylate struts as structural elementsIndividual [24]crown-8 ether macrocycle shuttlescould translate between degenerate benzimidazolestations on cross-bar linkers between struts at a rate of 283 Hz at room temperature Future work to incorpo-rate MIMs within highly dense crystalline arrays withgreater control over theactuation andspeed of switch-ing events will provide new potential applicationsfor mechanically bonded hostguest systems withcontrollable physical and chemical properties in thesolid state

The second approach to fabricate crystalline mo-

lecular machines utilizes the entire crystal as an actua-tor and transfers the external stimulus such as lightor heat into mechanical energy categorized as (a)thermo- and photosalient or (b) photomechanicalcrystals188184207 Thermo- and photosalient crystalsmost often exhibit spontaneous actuation (jumping)upon heating or irradiation Thermosalient crystalsdeveloped by Naumov and co-workers harness theenergy of polymorphic transformations that occurupon heating in crystals The eff ect is driven by ex-tremely rapidanisotropic expansion and contraction of the unit cell axes upon a phase transition that was

found to be 104 times faster than in regular crystal-to-crystal phase transformations208 This class of crystal-line compounds comprises a diverse range of materialsincluding brominated organic molecules terephthalicacid and organometallic complexes209210 Althoughthere exists little directional control or foresight intowhich compounds will exhibit the eff ect the explosive

ldquopopcornrdquo crystals nonetheless exhibit impressivecentimeter-scale jumping movements that greatly ex-ceed the crystal dimensions Light-activated chemicalprocesses within crystals such as changes in the co-ordination sites of small ligands or [2thorn 2] cycloadditionreactions have also been shown to result in ldquopoppingrdquo

under ultraviolet irradiation211212 Similar to thermo-salient materials little control is possible over ldquopop-pingrdquo crystals and thus their utilization as functionalmolecular machines is difficult to envisage To circum-vent this problem Sahoo et al developed smart hybridmaterials that incorporate thermosalient microcrystal-lites on 1047298exible sodium caseinate 1047297lms to impartdirectionality to the crystals movements213 The ma-terial represents a successful marriage of crystals withbiocompatible polymeric 1047297lms in one system combin-ing the bene1047297ts of the plasticity of soft polymers andthe efficient fast actuation of leaping crystalline solids

Alternatively photomechanical materials movebend twist or curl when exposed to light Some of the most promising photomechanical crystalline sys-tems for converting light into mechanical work havebeen proposed by Irie and co-workers and are basedon diarylethene photoswitches214 Light absorptiontriggers pericyclic ring-opening and ring-closing reac-

tions of this photoswitch throughout the crystal and isresponsible for expansion and contraction respec-tively of the unit cell that consequently leads tophotomechanical bending of the crystal Structuralstudies on crystals of diarylethene derivatives link the initial speed of curvature change to crystalthickness215 The bending behavior is also dependenton the crystallographic face that is irradiated which isbe attributed to diff erences in molecular packingWhile the geometric change that occurs during theisomerization of a single diarylethene photoswitch ismodest the collective action of arrays of molecules inthe crystal lattice can produce macroscopic motion

Cleverly engineered such actuating crystals can per-form work by pushing or lifting objects many timestheir weight214216 rotating gears217 or acting as anelectrical circuit switch (Figure 16)218

Other commonly studied photomechanical crystal-line architectures are composed of anthracenes orsalicylidenephenylethylamine molecules Bardeenand co-workers investigated the [4 thorn 4] dimerizationreaction of anthracenes where the photoreaction re-sults in reversible or irreversible twisting of crystallinemicroribbons219220 The curling and twisting motionmay be attributed to strain between spatially distinct

Figure 15 (a) Chemical structures of the components of aporouscocrystal (left)440-bis(sulfophenylethynyl)benzene(SPEB) dianion and (right) n-pentylammonium (PA) cation(b) Deuterium nuclear magnetic resonance (2H NMR) spec-tra of porous cocrystals in the absence of molecular iodineI2 after exposure to I2 in the gas phase and followingremoval of I2 from the crystals Experimental and calculatedspectra are displayed in black or violet and gray respec-tively The exchange rate reversibly decreased by fourorders of magnitude upon uptake of the small-molecule

guest suggesting the use of such crystals for gas phasesensing applications Reproduced from ref 204 Copyright2014 American Chemical Society

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reactant and product domains as a result of diff erentialabsorption by diff erent regions of the crystal or intrin-sic solid-state reaction kinetics221 Another crystalline

molecular machine was proposed by Koshima et albased on photomechanical action in platelike crystalsof salicylidenephenylethylamine (Figure 17)222 Theseactuators are capable of lifting weights up to 300 timesthe crystal weight The motion is linked to geometricchanges in the molecules produced upon tautomerictransformation triggered by light absorption and con-sequent proton migration Collective reorganization of the molecules within the lattice leads to small uniaxialcell expansion which in turn results in bending of thecrystal

While the workhorse of many photomechanicalstudies the azobenzene chromophore has been ex-

tensively probed as isolated molecules on surfaces inpolymers and within liquid crystals it has been far lessstudied by the crystalline photomechanical commu-nity223227 This is due in part to the sterically de-manding trans to cis isomerization process which maybe impeded in a crystal Surprisingly Koshima et al

demonstrated reversible photomechanical bending of thin trans-4-(dimethylamino)azobenzene plates uponultraviolet irradiation concluding that isomerizationcan still occur inside the crystal228 That report was fol-lowed by a study of thin crystalline plates and needles of pseudostilbenes(azobenzeneswith short-lived cisstates)

which were capable of submillisecond bending andrelaxation upon irradiation with visible light229 Pseu-dostilbene bending crystals off er the fastest speed of

bendingrelaxation cyclesas thewholeevent cantakeless than a second and is the only system that com-pletely circumvents the need for ultraviolet lightto induce isomerization More recent reports havefocused on elucidating the mechanistic aspects of azobenzene isomerization in crystals focusing onin situ X-ray diff raction studies of irreversible cistrans

isomerization in crystals230 and cocrystals231 of themolecule (Figure 18) These reports demonstrated thatcis to trans isomerization in crystals is mediated by atransient amorphous state While the sterically de-manding azobenzene isomerization reaction requiresconsiderable free volume to occur and is rarely possi-

ble in a single-crystalsingle-crystal fashion an amor-phization mechanism enables the photochemicalreaction to proceed despite the constraints of thecrystal lattice Amorphous intermediates in the crystalwere corroboratedby theloss of diff raction spots uponirradiation with visible light at low temperature Re-markably isomerization within the crystals of azoben-zene represents a topotactic process in which theorientation of the resultant trans-crystal phase is de-pendent on the initial crystal orientation and eff ec-tively represents template crystal growth directedby light

Figure 16 Photomechanical systems based on diarylethene crystals that convert light into mechanical work (a) Rod-likecrystal pushes a gold microparticle that is 90 times heavier than the crystal when irradiated with UV light Bending of thecrystal pushes the microparticle up to 30 μm Reproduced with permission from ref 214 Copyright 2007 Nature PublishingGroup (b) Rotation of gears facilitated by the reversible bending of a crystalline actuator upon UV and visible irradiationReproduced with permission from ref 217 Copyright 2012 Wiley (c) Irradiation of gold-coated diarylethene crystals with UV and visible light enables the ONOFF photoreversible current switching of an electric circuit Reproduced with permissionfrom ref 218 Copyright 2015 Royal Society of Chemistry (d) Superimposed photographs of a crystal cantilever lifting a leadball with a mass 275 times larger than the crystal upon irradiation with UV light from the underside of the actuatorReproduced from ref 216 Copyright 2010 American Chemical Society

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The growing number of investigations on dynamicmolecular crystals that can perform as actuators de-mands new theoretical models Various models have

been reported in the context of polymer 1047297lms rods orplates such as the analysis by Warner and Mahadevanon photodeformation of nematic elastomers232 How-ever careful structural and kinetic considerationsbased on the spatial density and uniform orientationsof photoactive molecules must be taken into accountfor these models to be fully applicable to crystallinesystems While the molecular motifs responsible forcrystal motions are diverse an attempt to unify photo-mechanical processes was done by Nath et al whoproposed a mathematical treatment of photomecha-nical crystal bending by accounting for the gradualpro1047297le of the product in the crystal irradiation time

direction and power using the azobenzene dye Dis-perse Red 1 as a model compound233 The model isapplicable for any photomechanicalcrystal system andallows an easier comparison between the diff erentplatforms for efficiency modulus stress and otherparameters critical for optimization of the process forpractical use Ultimately with the help of theoreticalframeworks and empirical data the goal of futuredevelopment of photomechanical systems needs tobe directed toward robust and fatigue-resistant de-signs capable for even faster and reliable actuationover thousands of cycles

CONCLUSIONS AND OUTLOOK

In the quest to synthesize and to assemble genuinemolecular machines the eff orts of the scienti1047297c com-munity have evolved from mere observation anddesign of dynamic molecular building blocks to under-standing the mechanisms of their function A neces-sary advance is the intelligent combination of theavailable building blocks to prepare useful and func-tional molecular-driven machines Thus far a widevariety of systems have been proposed that performsome kind of action on their environment and theinitial demonstrations of the applicationare promisingWhile their size and scope are dramatically diff erentthe underlying mechanisms of action are remarkably

similar Whether linear motion rotation bending ortwisting is involved they are all powered by stimulus-driven reversible chemical reactions In somecases likephotoactive catalysis the work is performed at thesingle-molecule level However controllable and mea-surable macroscopic eff ects such as changes in surfaceenergy or the bending of crystalline 1047297lms can beachieved through the collective ampli1047297ed motion of many molecules It should be kept in mind that it is nota simple act of preparing a binary switch or a bendingexpanding or contracting material that constitutes amachine the eff orts should rather be directed towardthe reversible execution of a deliberate function

In combination with the continued eff orts in thedesign synthesis and assembly of novel moleculararchitectures the characterization and analysis of stimulus-drivenmotion by new systemsshould includean assessment of the efficiency and reproducibilityand thus the viability of a molecular machine as aninvention234235 Molecular machine designs must behighly resistant to degradation over long periods of time andor numerous actuation cycles and objec-tively addressing these requirements is critical foranalyzing performance This robustness is importantfor example for in vivo application of DNA-based

Figure 18 Amorphousphase-mediated azobenzene isomer-ization and photomechanical bending in a cocrystal (12 mm 90 μm 20 μm) The cocrystal contains a 11 ratio of ahalogen-bond acceptor (cis-12-bis(4-pyridyl)ethylene) andhalogen-bond donor species Bromine or iodine atoms onper1047298uorinated azobenzenes act as halogen-bond donorsforming a linear interaction with the pyridinenitrogen atomson the halogen-bond acceptor Irradiation of the cocrystalswitha 532nm laser facilitatescis to trans isomerization of thehalogen-bond donors via amorphous intermediates deter-mined by X-ray diff raction Reproduced with permissionfrom ref 231 Copyright 2014 Royal Society of Chemistry

Figure 17 (a) Photoinduced proton transfer in the S en-antiomers of chiral salicylidenephenylethylamines uponketoenol tautomerism (b) Superimposed photographsof a chiral enol-(S)-1 crystal before and after irradiating thetop of the crystal actuator with UV light The crystallinecantileverachieved 26nJ ofworkby lifting a 400mg metalring a height δ of 065 mm Various photomechanicallifting work was achieved with diff erent enantiomericcompositions within the crystal the racemic crystalenol-(rac )-1 achieved 59 nJ of work by lifting a weightwith mass 300 times larger than the crystal (not shown)Reproduced from ref 222 Copyright 2013 American Che-mical Society

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assemblies that are susceptible to biodegradation bynucleases or repetitive UV irradiation cycles of crystalactuators Measuring the efficiency at each step of energy transformation from that of elementaryswitches and rotors to the entire assemblies wouldalso be highly bene1047297cial and results should be dis-seminated as a normal part of reported research 1047297nd-

ings In photoinduced processes this can be easilydetermined by calculating quantum yield or photo-isomerization cross sections Quantitative assessmentof the forces generated by stimulus-induced motion byindividual molecules or hierarchically more complexassemblies is also desirable where applicable

The most glaring question that remains in the 1047297eldis in what environments or at what length scalesmolecular machines will 1047297nd truly impactful applica-tions While the hierarchical assembly of small switchand rotor components may provide more opportu-nities for externallycontrolled motionat greater lengthscales will they be able to compete with other materi-als For example the impressive performance of elec-trochemically or thermally driven shape-memorypolymer 1047297bers and hybrid carbon nanotube bundlesmay make those materials more viable alternatives forcommercial arti1047297cial muscles than linear chains of molecular switches236237 Likewise the combinationof mechanical actuators or sensors with integratedcircuits based on microelectromechanical systems(MEMS) off ers advantages over crystalline molecularmachines due to the compatibility of microfabricationprocesses with complementary metaloxide semicon-ductor (CMOS) technology on the scale of 1 μm to

millimeters To 1047297nd their niche in similar applicationsmolecular machine designs must take advantage of alternative actuation mechanisms and off er more effi-cient energy transduction Ultimately the candid as-sessment of the potential applicability for leveragingthe stimulated motions of molecules is more importantthan ascribing the label of a ldquomachinerdquo With thisadmission in mind the necessity to demonstrate ap-plications that harness the power of molecular ma-chines to perform work on their environment presentsan exciting and unique opportunity for researchersUnderstanding the chemistry and physics that governthis motion will be a continuous challenge as designs

become increasingly complex Nevertheless the futureof this 1047297eld will bene1047297t from the impressive diversityand creativity of individual molecular and assemblymotifs that may be used to direct motion from thenano- to the macroscale

Conflict of Interest The authors declare no competing1047297nancial interest

Acknowledgment We acknowledge support from the USDepartment of Energy Grant SC-1037004OSB acknowledges1047297nancial support from a Vanier Canada Graduate Scholarshipand CJB is grateful for a CNSI Fulbright Canada VisitingResearch Chair that enabled a sabbatical stay in the WeissLaboratories and CNSI at UCLA in 2014

REFERENCES AND NOTES

1 Duncan T M Bulygin V V Zhou Y Hutcheon M LCross R L Rotation of Subunits during Catalysis byEscherichia Coli F1-ATPase Proc Natl Acad Sci U S A1995 92 10964ndash10968

2 Yasuda R Noji H Kinosita K Yoshida M F1-ATPase isa Highly Efficient Molecular Motor that Rotates withDiscrete 120 Steps Cell 1998 93 1117ndash1124

3 Berg H C Anderson R A Bacteria Swim by Rotating

Their Flagellar Filaments Nature 1973 245 380ndash3824 Mahadevan L Matsudaira P Motility Powered by

Supramolecular Springs and Ratchets Science 2000288 95ndash99

5 Kinbara K Aida T Toward Intelligent Molecular Ma-chines Directed Motions of Biological and Arti1047297cialMolecules and Assemblies Chem Rev 2005 1051377ndash1400

6 Li D Paxton W F Baughman R H Huang T JStoddart J F Weiss P S Molecular Supramolecularand Macromolecular Motors and Arti1047297cial Muscles MRSBull 2009 34 671ndash681

7 Wang J Can Man-Made Nanomachines Compete withNature Biomotors ACS Nano 2009 3 4ndash9

8 AsimovI Runaroundin AstoundingScienceFiction Streetamp Smith Publications Inc New York 1942 Vol 1 p 94

9 Kay E R Leigh D A Zerbetto F Synthetic MolecularMotors and Mechanical Machines Angew Chem Int Ed2007 46 72ndash191

10 Coskun A Banaszak M Astumian R D Stoddart J FGrzybowski B A Great Expectations Can Arti1047297cialMolecular Machines Deliver on their Promise ChemSoc Rev 2012 41 19ndash30

11 Serreli V Lee C F Kay E R Leigh D A A MolecularInformation Ratchet Nature 2007 445 523ndash527

12 Browne W R Feringa B L Making Molecular MachinesWork Nat Nanotechnol 2006 1 25ndash35

13 Mahimwalla Z Yager K G Mamiya J Shishido APriimagi A Barrett C J Azobenzene PhotomechanicsProspects and Potential Applications Polym Bull 201269 967ndash1006

14 Bandara H M D Burdette S C Photoisomerization inDiff erent Classes of Azobenzene Chem Soc Rev 201241 1809ndash1825

15 Wirth J Hatter N Drost R Umbach T R Barja SZastrow M Ruumlck-Braun K Pascual J I Saalfrank PFranke K J Diarylethene Molecules on a Ag(111) Sur-face Stability and Electron-Induced Switching J PhysChem C 2015 119 4874ndash4883

16 Irie M Fukaminato T Matsuda K Kobatake S Photo-chromismof Diarylethene Molecules and Crystals Mem-ories Switches and Actuators Chem Rev 2014 11412174ndash12277

17 Berkovic G Krongauz V Weiss V Spiropyrans andSpirooxazines for Memories and Switches Chem Rev2000 100 1741ndash1753

18 Whalley A C Steigerwald M L Guo X Nuckolls CReversible Switching in Molecular Electronic Devices

J Am Chem Soc 2007 129 12590ndash1259119 Kim M Hohman J N Cao Y Houk K N Ma H Jen

A K Y Weiss P S Creating Favorable Geometries forDirecting Organic Photoreactions in AlkanethiolateMonolayers Science 2011 331 1312ndash1315

20 Zheng Y B Payton J L Song T B Pathem B K ZhaoY X Ma H Yang Y Jensen L Jen A K Y Weiss P SSurface-Enhanced Raman SpectroscopyTo Probe Photo-reaction Pathways and Kinetics of Isolated Reactants onSurfaces Flat versus Curved Substrates Nano Lett 201212 5362ndash5368

21 Trenor S RShultz A RLoveB JLongT E Coumarinsin Polymers From Light Harvesting to Photo-Cross-Linkable Tissue Scaff olds Chem Rev 2004 104 3059ndash

307722 Bauer J Hou L L Kistemaker J C M Feringa B L

Tuning the Rotation Rate of Light-Driven MolecularMotors J Org Chem 2014 79 4446ndash4455

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23 Su X Voskian S Hughes R P Aprahamian I Manip-ulating Liquid-Crystal Properties Using a pH ActivatedHydrazone Switch Angew Chem Int Ed 2013 5210734ndash10739

24 Belowich M E Stoddart J F Dynamic Imine ChemistryChem Soc Rev 2012 41 2003ndash2024

25 Tatum L A Su X Aprahamian I Simple HydrazoneBuilding Blocks for Complicated Functional Materials

Acc Chem Res 2014 47 2141ndash2149

26 Qu D-H Wang Q-C Zhang Q-W Ma X Tian HPhotoresponsive Host-Guest Functional Systems ChemRev 2015 101021cr5006342

27 Grunder S McGrier P L Whalley A C Boyle M MStern C Stoddart J F A Water-Soluble pH-TriggeredMolecular Switch J Am Chem Soc 2013 135 17691ndash

1769428 Bruns C J Li J N Frasconi M Schneebeli S T Iehl J

de Rouville H P J Stupp S I Voth G A Stoddart J FAn Electrochemically and Thermally Switchable Donor-Acceptor [c2]Daisy Chain Rotaxane Angew Chem IntEd 2014 53 1953ndash1958

29 Xue M Yang Y Chi X Yan X Huang F Developmentof Pseudorotaxanes and Rotaxanes From Synthesis toStimuli-Responsive Motions to Applications Chem Rev2015 101021cr5005869

30 Lohmann F Ackermann D Famulok M Reversible

Light Switch for Macrocycle Mobility in a DNA Rotaxane J Am Chem Soc 2012 134 11884ndash11887

31 Rajendran A Endo M Hidaka K Sugiyama H Directand Real-Time Observation of Rotary Movement of aDNA Nanomechanical Device J Am Chem Soc 2013135 1117ndash1123

32 Lund K Manzo A J Dabby N Michelotti N Johnson-Buck A Nangreave J Taylor S Pei R J StojanovicM N Walter N G Winfree E Yan H Molecular RobotsGuided by Prescriptive Landscapes Nature 2010 465206ndash210

33 Astumian R D Microscopic Reversibility as the Organiz-ing Principle of Molecular Machines Nat Nanotechnol2012 7 684ndash688

34 Hutchison J A Uji-i H Deres A Vosch T Rocha SMuumlller S Bastian A A Enderlein J Nourouzi H Li CHerrmann A Muumlllen K De Schryver F Hofkens JA Surface-BoundMoleculethatUndergoes Optically BiasedBrownian Rotation Nat Nanotechnol 2014 9 131ndash136

35 Perera U G E Ample F Kersell H Zhang Y Vives GEcheverria J Grisolia M Rapenne G Joachim C HlaS W Controlled Clockwise and Anticlockwise RotationalSwitching of a MolecularMotor Nat Nanotechnol 20138 46ndash51

36 Chen JW Kistemaker J C MRobertus J Feringa BLMolecular Stirrers in Action J Am Chem Soc 2014 13614924ndash14932

37 Greb L Lehn J M Light-Driven Molecular Motorslmines as Four-Step or Two-Step Unidirectional Rotors

J Am Chem Soc 2014 136 13114ndash1311738 Lu C H Cecconello A Elbaz J Credi A Willner I A

Three-Station DNA Catenane Rotary Motor with Con-trolled Directionality Nano Lett 2013 13 2303ndash2308

39 Arduini A Bussolati R Credi A Secchi A Silvi SSemeraro M Venturi M Toward Directionally Con-trolled Molecular Motions and Kinetic Intra- and Inter-molecular Self-Sorting Threading Processes of Non-symmetric Wheel and Axle Components J Am ChemSoc 2013 135 9924ndash9930

40 Li H Cheng C Y McGonigal P R Fahrenbach A CFrasconi M Liu W G Zhu Z X Zhao Y L Ke C F LeiJY YoungR M Dyar S M Co DT Yang YW BotrosY Y Goddard W A Wasielewski M R Astumian R DStoddart J F Relative Unidirectional Translation in anArti1047297cial Molecular Assembly Fueled by Light J AmChem Soc 2013 135 18609ndash18620

41 Yin P Yan H Daniell X G Turber1047297eld A J Reif J H AUnidirectional DNA Walker that Moves AutonomouslyAlongaTrack Angew ChemInt Ed2004 43 4906ndash4911

42 You M X Huang F J Chen Z Wang R W Tan W HBuilding a Nanostructure with Reversible Motions UsingPhotonic Energy ACS Nano 2012 6 7935ndash7941

43 Kudernac T Ruangsupapichat N Parschau M MaciaacuteB Katsonis N Harutyunyan S R Ernst K H FeringaB L Electrically Driven Directional Motion of a Four-Wheeled Molecule on a Metal Surface Nature 2011 479208ndash211

44 Cheng C McGonigal P R Schneebeli S T Li H

Vermeulen N A Ke C Stoddart J F An Arti1047297cialMolecular Pump Nat Nanotechnol 2015 10 547ndash553

45 Perutz M F Stereochemistry of Cooperative Eff ects inHaemoglobin Nature 1970 228 726ndash734

46 Changeux J P Edelstein S J Allosteric Mechanisms of Signal Transduction Science 2005 308 1424ndash1428

47 Ray DFoyJ THughes R PAprahamian I A SwitchingCascade of Hydrazone-Based Rotary Switches throughCoordination-Coupled Proton Relays Nat Chem 2012 4757ndash762

48 Foy J T Ray D Aprahamian I Regulating SignalEnhancement with Coordination-Coupled Deprotona-tion of a Hydrazone Switch Chem Sci 2015 6 209ndash213

49 Pramanik S De S M Schmittel M Bidirectional Che-mical Communication between NanomechanicalSwitches Angew Chem Int Ed 2014 53 4709ndash4713

50 Pramanik S De S Schmittel M A Trio of Nanoswitches

in Redox-Potential Controlled Communication ChemCommun 2014 50 13254ndash13257

51 Joachim C Rapenne G Molecule Concept NanocarsChassis Wheels and Motors ACS Nano 2013 7 11ndash14

52 Weiss P S Nano Races Prizes and Awards ACS Nano2014 8 1ndash1

53 Yoon H J Kuwabara J Kim J H Mirkin C A AllostericSupramolecular Triple-Layer Catalysts Science 2010330 66ndash69

54 Stoll R S Peters M V Kuhn A Heiles S Goddard RBuumlhl M Thiele C MHechtS PhotoswitchableCatalystsCorrelating Structure and Conformational Dynamics withReactivity by a Combined Experimental and Computa-tional Approach J Am Chem Soc 2009 131 357ndash367

55 Goumlstl R Senf A Hecht S Remote-Controlling ChemicalReactions by Light Towards Chemistry with High Spatio-TemporalResolutionChemSoc Rev2014 43 1982ndash1996

56 Wang J BFeringa BL Dynamic Control ofChiral Spacein a Catalytic Asymmetric Reaction Using a MolecularMotor Science 2011 331 1429ndash1432

57 Blanco V Carlone A Haumlnni K D Leigh D ALewandowski B A Rotaxane-Based Switchable Organo-catalyst Angew Chem Int Ed 2012 51 5166ndash5169

58 Blanco V Leigh D A Marcos V Morales-Serna J ANussbaumer A L A Switchable[2]Rotaxane AsymmetricOrganocatalyst That Utilizes an Acyclic Chiral SecondaryAmine J Am Chem Soc 2014 136 4905ndash4908

59 Storch G Trapp O Temperature-Controlled Bidirec-tional Enantioselectivity in a Dynamic Catalyst for Asym-metric Hydrogenation Angew Chem Int Ed 2015 543580ndash3586

60 Velema W A Szymanski W Feringa B L Photophar-macology Beyond Proof of Principle J Am Chem Soc

2014 136 2178ndash

219161 Mrazek J Toso D Ryazantsev S Zhang X Zhou Z HFernandez B C Kickhoefer V A Rome L H Polyribo-somes are Molecular 3D Nanoprinters That Orchestratethe Assembly of Vault Particles ACS Nano 2014 811552ndash11559

62 Lewandowski B De Bo G Ward J W Papmeyer MKuschel S Aldegunde M J Gramlich P M EHeckmann D Goldup S M DSouza D M FernandesA E LeighD A Sequence-Speci1047297c Peptide Synthesisbyan Arti1047297cial Small-Molecule Machine Science 2013 339189ndash193

63 De Bo G Kuschel S Leigh D A Lewandowski BPapmeyerM WardJ W EfficientAssembly of ThreadedMolecular Machines for Sequence-Speci1047297c Synthesis

J Am Chem Soc 2014 136 5811ndash5814

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W




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64 Kuzuya A Ohya Y Nanomechanical Molecular DevicesMade ofDNAOrigami AccChemRes2014 47 1742ndash1749

65 Jester S S Famulok M Mechanically Interlocked DNANanostructures for Functional Devices Acc Chem Res2014 47 1700ndash1709

66 Rothemund P W K Folding DNA to Create NanoscaleShapes and Patterns Nature 2006 440 297ndash302

67 Yurke B Turber1047297eld A J Mills A P Simmel F CNeumann J L A DNA-Fuelled Molecular Machine Made

of DNA Nature 2000 406 605ndash60868 Hu L Z Lu C H Willner I Switchable Catalytic DNA

Catenanes Nano Lett 2015 15 2099ndash210369 Idili A Plaxco K W Valleacutee-Beacutelishe A Ricci F Thermo-

dynamic Basis for Engineering High-Affinity High-Speci1047297city Binding-Induced DNA Clamp Nanoswitches

ACS Nano 2013 7 10863ndash1086970 Nishioka H Liang X G Kato T Asanuma H A Photon-

Fueled DNA Nanodevice that Contains Two Diff erentPhotoswitches Angew Chem Int Ed 2012 51 1165ndash

116871 Endo M Miyazaki R Emura T Hidaka K Sugiyama H

Transcription Regulation System Mediated by Mechan-ical Operation of a DNA Nanostructure J Am Chem Soc2012 134 2852ndash2855

72 Zadegan R M Jepsen M D E Thomsen K E OkholmAHSchaff ert D HAndersen E S BirkedalV Kjems J

Construction of a 4 Zeptoliters Switchable 3D DNA BoxOrigami ACS Nano 2012 6 10050ndash10053

73 Andersen E S Dong M Nielsen M M Jahn KSubramani R Mamdouh W Golas M M Sander BStark H Oliveira C L P Pedersen J S Birkedal VBesenbacher F Gothelf K V Kjems J Self-Assembly of a Nanoscale DNA Box with a Controllable Lid Nature2009 459 73ndash76

74 Janssen B M G van Rosmalen M van Beek L MerkxM Antibody Activation using DNA-Based Logic Gates

Angew Chem Int Ed 2015 54 2530ndash253375 Adleman L M Molecular Computation of Solutions to

Combinatorial Problems Science 1994 266 1021ndash102476 Lipton R J DNA Solution of Hard Computational Pro-

blems Science 1995 268 542ndash54577 Douglas S M Bachelet I Church G M A Logic-Gated

Nanorobot for Targeted Transport of Molecular Pay-loads Science 2012 335 831ndash834

78 Li T Lohmann F Famulok M Interlocked DNA Nano-structures Controlled by a Reversible Logic Circuit NatCommun 2014 5 4940

79 You M X Zhu G Z Chen T Donovan M J Tan W HProgrammable and Multiparameter DNA-Based LogicPlatform For Cancer Recognition and Targeted Therapy

J Am Chem Soc 2015 137 667ndash67480 Chirieleison S M Allen P B Simpson Z B Ellington

A D Chen X Pattern Transformation with DNA CircuitsNat Chem 2013 5 1000ndash1005

81 Vale R D The Molecular Motor Toolbox for IntracellularTransport Cell 2003 112 467ndash480

82 Yildiz A Forkey J N McKinney S A Ha T GoldmanY ESelvin P R MyosinV Walks Hand-Over-Hand SingleFluorophore Imaging with 15-nm Localization Science2003

300 2061ndash

206583 Yildiz A Tomishige M Vale R D Selvin P R KinesinWalks Hand-over-Hand Science 2004 303 676ndash678

84 Karagiannis P Ishii Y Yanagida T Molecular MachinesLike Myosin Use Randomness to Behave PredictablyChem Rev 2014 114 3318ndash3334

85 Omabegho T Sha R Seeman N C A Bipedal DNABrownian Motor with Coordinated Legs Science 2009324 67ndash71

86 Shin J S Pierce N A A Synthetic DNA Walker forMolecular Transport J Am Chem Soc 2004 12610834ndash10835

87 You M X Chen Y Zhang X B Liu H P Wang R WWang K L Williams K R Tan W H An Autonomousand Controllable Light-Driven DNA Walking Device

Angew Chem Int Ed 2012 51 2457ndash2460

88 Cheng J Sreelatha S Loh I Y Liu M H Wang Z SA Bioinspired Design Principle for DNA NanomotorsMechanics-Mediated Symmetry Breaking and Experi-mental Demonstration Methods 2014 67 227ndash233

89 HeY LiuD R AutonomousMultistep Organic Synthesisin a Single Isothermal Solution Mediated by a DNAWalker Nat Nanotechnol 2010 5 778ndash782

90 Gu H Z Chao J Xiao S J Seeman N C A Proximity-Based Programmable DNA Nanoscale Assembly Line

Nature 2010 465 202ndashU8691 Cha T G Pan J Chen H R Salgado J Li X Mao C D

Choi J H A Synthetic DNA Motor that TransportsNanoparticles along Carbon Nanotubes Nat Nanotech-nol 2014 9 39ndash43

92 Zhang D Y Seelig G Dynamic DNA NanotechnologyUsing Strand-Displacement Reactions Nat Chem 20113 103ndash113

93 Zhang D Y Winfree E Control of DNA Strand Displace-mentKinetics UsingToeholdExchange J Am Chem Soc2009 131 17303ndash17314

94 Gao Y Wolf L K Georgiadis R M Secondary StructureEff ects on DNA Hybridization Kinetics A Solution versusSurface Comparison Nucleic Acids Res 2006 34 3370ndash

337795 Wang C Y Tao Y Song G T Ren J S Qu X G

Speeding Up a Bidirectional DNA Walking Device Lang-

muir 2012 28 14829ndash1483796 Loh IY ChengJ Tee S REfremovA WangZ S From

Bistate Molecular Switches to Self-Directed Track-Walking Nanomotors ACS Nano 2014 8 10293ndash10304

97 Tomov T E Tsukanov R Liber M Masoud R PlavnerN Nir E Rational Design of DNA Motors Fuel Optimiza-tion throughSingle-MoleculeFluorescence J Am ChemSoc 2013 135 11935ndash11941

98 Green S J Bath J Turber1047297eld A J Coordinated Che-momechanical Cycles A Mechanism for AutonomousMolecular Motion Phys Rev Lett 2008 101 238101

99 LiuM H HouR Z ChengJ LohL Y SreelathaS TeyJ N WeiJ Wang Z S Autonomous Synergic Control of Nanomotors ACS Nano 2014 8 1792ndash1803

100 Klajn R Stoddart J F Grzybowski B A NanoparticlesFunctionalised with Reversible Molecular and Supramo-lecular Switches Chem Soc Rev 2010 39 2203ndash2237

101 Swaminathan S Garcia-Amoroacutes J Fraix A Kandoth NSortino S Raymo F M Photoresponsive Polymer Nano-carrierswith Multifunctional Cargo Chem SocRev 201443 4167ndash4178

102 Song N Yang Y-W Molecular and SupramolecularSwitches on Mesoporous Silica Nanoparticles ChemSoc Rev 2015 44 3474ndash3504

103 Nguyen T D Tseng H R Celestre P C Flood A H LiuY Stoddart J F Zink J I A Reversible Molecular ValveProc Natl Acad Sci U S A 2005 102 10029ndash10034

104 Sun Y L Yang Y W Chen D X Wang G Zhou YWang C Y Stoddart J F Mechanized Silica Nanoparti-cles Based on Pillar[5]arenes for On-Command CargoRelease Small 2013 9 3224ndash3229

105 Chen T Yang N W Fu J J Controlled Release of CargoMolecules from Hollow Mesoporous Silica Nanoparticles

Based on Acid and Base Dual-Responsive Cucurbit[7]urilPseudorotaxanes Chem Commun 2013 49 6555ndash6557106 Zhang Z X Balogh D Wang F A Willner I Smart

Mesoporous SiO2 Nanoparticles for the DNAzyme-Induced Multiplexed Release of Substrates J Am ChemSoc 2013 135 1934ndash1940

107 Zhang G L Yang M L Cai D Q Zheng K Zhang XWu L F Wu Z Y Composite of Functional MesoporousSilica and DNA An Enzyme-Responsive Controlled Re-lease Drug Carrier System ACS Appl Mater Interfaces2014 6 8042ndash8047

108 Mal N K Fujiwara M Tanaka Y Photocontrolled Re-versible Release of Guest Molecules from Coumarin-Modi1047297ed Mesoporous Silica Nature 2003 421 350ndash353

109 Guardado-Alvarez T M Devi L S Russell M MSchwartz B J Zink J I Activation of Snap-Top Capped

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W




wwwacsnanoorg

7765

MesoporousSilica NanocontainersUsingTwo Near-InfraredPhotons J Am Chem Soc 2013 135 14000ndash14003

110 Mei X Yang S Chen DYLi NJ Li H Xu QFGeJ FLu J M Light-Triggered Reversible Assemblies of Azobenzene-Containing Amphiphilic Copolymer with β-Cyclodextrin-Modi1047297ed Hollow Mesoporous Silica Nano-particles for Controlled Drug Release Chem Commun2012 48 10010ndash10012

111 LiQ L Wang L QiuX L SunY L Wang PXLiuYLi

F Qi A D Gao H Yang Y W Stimuli-ResponsiveBiocompatible NanovalvesBasedon β-CyclodextrinModi-1047297ed Poly(glycidyl methacrylate) Polym Chem 2014 53389ndash3395

112 YangY W Towards Biocompatible Nanovalves Based onMesoporous Silica Nanoparticles MedChemComm 20112 1033ndash1049

113 Croissant J Maynadier M Gallud A NDongo H PNyalosaso J L Derrien G Charnay C Durand J ORaehm L Serein-Spirau F Cheminet N Jarrosson TMongin O Blanchard-Desce M Gary-Bobo M GarciaM Lu J Tamanoi F Tarn D Guardado-Alvarez T MZink J I Two-Photon-Triggered Drug Delivery in CancerCells Using Nanoimpellers Angew Chem Int Ed 201352 13813ndash13817

114 Croissant J Chaix A Mongin O Wang M Cleacutement SRaehm L Durand J O Hugues V Blanchard-Desce M

Maynadier M Gallud A Gary-Bobo M Garcia M Lu JTamanoi F Ferris D P Tarn D Zink J I Two-Photon-Triggered Drug Delivery via Fluorescent NanovalvesSmall 2014 10 1752ndash1755

115 Gary-Bobo M Mir Y Rouxel C Brevet D Basile IMaynadier M Vaillant O Mongin O Blanchard-DesceM Moregravere A Garcia M Durand J O Raehm LMannose-Functionalized Mesoporous Silica Nanoparti-cles for Efficient Two-Photon Photodynamic Therapy of Solid Tumors Angew Chem Int Ed 2011 50 11425ndash

11429116 Baudrion A L Perron A Veltri A Bouhelier A Adam

P M Bachelot R Reversible Strong Coupling in SilverNanoparticle Arrays Using Photochromic MoleculesNano Lett 2013 13 282ndash286

117 Zheng Y B Kiraly B Cheunkar S Huang T J WeissP S Incident-Angle-Modulated Molecular PlasmonicSwitches A Case of Weak Exciton-Plasmon CouplingNano Lett 2011 11 2061ndash2065

118 Joshi G K Blodgett K N Muhoberac B B JohnsonM A Smith K A Sardar R Ultrasensitive Photorever-sible Molecular Sensors of Azobenzene-FunctionalizedPlasmonic Nanoantennas Nano Lett 2014 14 532ndash540

119 Mirkin C A Letsinger R L Mucic R C Storhoff J J ADNA-Based Method for Rationally Assembling Nano-particles into Macroscopic Materials Nature 1996 382607ndash609

120 Li H Chen D X Sun Y L Zheng Y B Tan L L WeissP S Yang Y W Viologen-Mediated Assembly of andSensing with Carboxylatopillar[5]arene-Modi1047297ed GoldNanoparticles J Am Chem Soc 2013 135 1570ndash1576

121 Kuzyk ASchreiber RZhang HGovorov A O LiedlTLiu N Recon1047297gurable 3D PlasmonicMetamolecules Nat

Mater 2014 13 862ndash

866122 Liu D B Chen W W Sun K Deng K Zhang W WangZ Jiang X Y Resettable Multi-Readout Logic GatesBased on Controllably Reversible Aggregation of GoldNanoparticles AngewChem Int Ed2011 504103ndash4107

123 Lee J-W Klajn R Dual-Responsive Nanoparticles thatAggregate Under the Simultaneous Action of Light andCO2 Chem Commun 2015 51 2036ndash2039

124 Lu C H Willner B Willner I DNA NanotechnologyFrom Sensing and DNA Machines to Drug-Delivery Sys-tems ACS Nano 2013 7 8320ndash8332

125 Hu L Z Liu X Q Cecconello A Willner I Dual Switch-ableCRET-Induced Luminescence of CdSeZnS QuantumDots (QDs) by the HeminG-Quadruplex-Bridged Aggre-gation and Deaggregation of Two-Sized QDs Nano Lett2014 14 6030ndash6035

126 Cecconello A LuC H ElbazJ Willner I Au Nanoparticle DNA Rotaxane Hybrid Nanostructures Exhibiting Switch-able Fluorescence Properties Nano Lett 2013 13 6275ndash

6280127 Shimron S Cecconello A Lu C H Willner I Metal

Nanoparticle-Functionalized DNA Tweezers From Me-chanically Programmed Nanostructures to SwitchableFluorescencePropertiesNanoLett 2013 133791ndash3795

128 ElbazJ CecconelloA Fan ZY GovorovA OWillnerI

Powering the Programmed Nanostructure and Functionof Gold Nanoparticles with Catenated DNA MachinesNat Commun 2013 4 2000

129 HildebrandtL L Preus S ZhangZ VoigtN V GothelfK V Birkedal V Single Molecule FRET Analysis of the 11Discrete Stepsof a DNAActuator J Am Chem Soc 2014136 8957ndash8962

130 Bruns C J Stoddart J F Rotaxane-Based MolecularMuscles Acc Chem Res 2014 47 2186ndash2199

131 Wu J S Leung KC F Beniacutetez D HanJ Y CantrillS JFang L Stoddart J F An Acid-Base-Controllable[c2]Daisy Chain Angew Chem Int Ed 2008 47 7470ndash

7474132 Bruns C J Frasconi M Iehl J Hartlieb K J Schneebeli

S T Cheng C Y Stupp S I Stoddart J F RedoxSwitchable Daisy Chain Rotaxanes Driven by Radical-Radical Interactions J Am Chem Soc 2014 136 4714ndash

4723133 Tsuda S Aso Y Kaneda T Linear Oligomers Composed

of a PhotochromicallyContractibleand Extendable Janus[2] Rotaxane Chem Commun 2006 3072ndash3074

134 Zhang Z B Han C Y Yu G C Huang F H A Solvent-Driven Molecular Spring Chem Sci 2012 3 3026ndash3031

135 Jimenez-Molero M C Dietrich-Buchecker C SauvageJ P Towards Arti1047297cial Muscles at the Nanometric LevelChem Commun 2003 1613ndash1616

136 Clark P G Day M W Grubbs R H Switching andExtension of a [c2]Daisy-Chain Dimer Polymer J AmChem Soc 2009 131 13631ndash13633

137 Hmadeh M Fang L Trabolsi A Elhabiri M Albrecht-Gary A M Stoddart J F On the Thermodynamicand Kinetic Investigations of a [c2]Daisy Chain Polymer

J Mater Chem 2010 20 3422ndash3430138 Du G YMoulin E Jouault N Buhler E Giuseppone N

Muscle-like Supramolecular Polymers IntegratedMotionfrom Thousands of Molecular Machines Angew ChemInt Ed 2012 51 12504ndash12508

139 Hugel T Holland N B Cattani A Moroder L Seitz MGaub H E Single-Molecule Optomechanical CycleScience 2002 296 1103ndash1106

140 Bleacuteger D Dokic J Peters M V Grubert L Saalfrank PHecht S Electronic Decoupling Approach to Quantita-tive Photoswitching in Linear Multiazobenzene Architec-tures J Phys Chem B 2011 115 9930ndash9940

141 Bleacuteger DLiebig TThiermann RMaskos MRabeJ PHecht S Light-Orchestrated Macromolecular ldquoAccor-dionsrdquo Reversible Photoinduced Shrinking of Rigid-RodPolymers Angew Chem Int Ed 2011 50 12559ndash12563

142 Lee C L Liebig T Hecht S Bleacuteger D Rabe J P Light-Induced Contraction and Extension of Single Macromo-

lecules on a Modi1047297ed Graphite Surface ACS Nano 20148 11987ndash11993143 Wie J J Chatterjee S Wang D H Tan L-S Ravi

Shankar M White T J Azobenzene-FunctionalizedPolyimides as Wireless Actuators Polymer 2014 555915ndash5923

144 Fang L J Zhang H T Li Z D Zhang Y Zhang Y YZhang H Q Synthesis of Reactive Azobenzene Main-Chain Liquid Crystalline Polymers via Michael AdditionPolymerization and Photomechanical Eff ects of TheirSupramolecular Hydrogen-Bonded Fibers Macromole-cules 2013 46 7650ndash7660

145 Yoshino T Kondo M Mamiya J Kinoshita M Yu Y LIkeda T Three-Dimensional Photomobility of Cross-linked Azobenzene Liquid-Crystalline Polymer Fibers

Adv Mater 2010 22 1361ndash1363

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146 Crivillers N Osella S Van Dyck C Lazzerini G MCornil D Liscio A Di Stasio F Mian S Fenwick OReinders F Neuburger M Treossi E Mayor MPalermo V Cacialli F Cornil J Samorigrave P Large Work Function Shift of Gold Induced by a Novel Per1047298uorinatedAzobenzene-Based Self-Assembled Monolayer AdvMater 2013 25 432ndash436

147 Zheng Y B Yang Y W Jensen L Fang L Juluri B KFlood A H Weiss P S Stoddart J F Huang T J Active

Molecular Plasmonics Controlling Plasmon Resonanceswith Molecular Switches Nano Lett 2009 9 819ndash825

148 Chen M Besenbacher F Light-Driven WettabilityChanges on a Photoresponsive Electrospun Mat ACSNano 2011 5 1549ndash1555

149 Ahmad N M Lu X Y Barrett C J Stable Photo-Reversible Surface Energy Switching with AzobenzenePolyelectrolyte Multilayers J Mater Chem 2010 20244ndash247

150 Feng CLZhangY J Jin J Song YLXie LYQuG RJiang L Zhu D B Reversible Wettability of Photorespon-sive Fluorine-Containing Azobenzene Polymer in Langmuir-Blodgett Films Langmuir 2001 17 4593ndash4597

151 Ichimura K Oh S K Nakagawa M Light-Driven Motionof Liquids on a Photoresponsive Surface Science 2000288 1624ndash1626

152 Bernaacute J Leigh D A Lubomska M Mendoza S M

Peacuterez E M Rudolf P Teobaldi G Zerbetto F Macro-scopic Transport by Synthetic Molecular Machines NatMater 2005 4 704ndash710

153 Shu W M Liu D S Watari M Riener C K Strunz TWelland M E Balasubramanian S McKendry R A DNAMolecular Motor Driven Micromechanical CantileverArrays J Am Chem Soc 2005 127 17054ndash17060

154 Liu YFlood AH Bonvallet PA Vignon S ANorthropB H Tseng H R Jeppesen J O Huang T J Brough BBaller M Magonov S Solares S D Goddard W A HoC M Stoddart J F Linear Arti1047297cial Molecular Muscles

J Am Chem Soc 2005 127 9745ndash9759155 Juluri B K Kumar A S Liu Y Ye T Yang Y W Flood

A H Fang L Stoddart J F Weiss P S Huang T J AMechanical Actuator Driven Electrochemically by Arti1047297-cial Molecular Muscles ACS Nano 2009 3 291ndash300

156 SenguptaS SpieringM MDey K K DuanW T PatraDButler P J Astumian R DBenkovic S J Sen A DNAPolymerase as a Molecular Motor and Pump ACS Nano2014 8 2410ndash2418

157 Patra D Zhang H Sengupta S Sen A Dual Stimuli-Responsive Rechargeable Micropumps via ldquoHost-GuestrdquoInteractions ACS Nano 2013 7 7674ndash7679

158 Love J C Estroff L A Kriebel J K Nuzzo R G White-sides G M Self-Assembled Monolayers of Thiolates onMetals as a Form of Nanotechnology Chem Rev 2005105 1103ndash1169

159 Zasadzinski J A Viswanathan R Madsen L Garnaes JSchwartz D K Langmuir-Blodgett-Films Science 1994263 1726ndash1733

160 Rubinstein I Vaskevich A Self-Assembly of Nanostruc-tures on Surfaces Using Metal-Organic Coordination Isr

J Chem 2010 50 333ndash346

161 Pathem B K Claridge S A Zheng Y B Weiss P SMolecular Switches and Motors on Surfaces Annu RevPhys Chem 2013 64 605ndash630

162 Bellisario D O Baber A E Tierney H L Sykes E C HEngineering Dislocation Networks for the DirectedAssembly of Two-Dimensional Rotor Arrays J PhysChem C 2009 113 5895ndash5898

163 Mielke J Leyssner F Koch M Meyer S Luo YSelvanathan S Haag R Tegeder P Grill L ImineDerivatives on Au(111) Evidence for 00 Inverted00 ThermalIsomerization ACS Nano 2011 5 2090ndash2097

164 Tegeder P Optically and Thermally Induced MolecularSwitching Processes at Metal Surfaces J Phys CondensMatter 2012 24 394001

165 Pathem B K Zheng Y B Payton J L Song T B YuB C Tour J M Yang Y Jensen L Weiss P S Eff ect of

Tether Conductivity on the Efficiency of Photoisomeriza-tion of Azobenzene-Functionalized Molecules on Au-111 J Phys Chem Lett 2012 3 2388ndash2394

166 Benassi E Granucci G Persico M Corni S Can Azo-benzene Photoisomerize When Chemisorbed on a GoldSurface An Analysis of Steric Eff ects Based on Nonadia-batic Dynamics Simulations J Phys Chem C 2015 1195962ndash5974

167 Klajn R Immobilized Azobenzenes for the Construction

of Photoresponsive Materials Pure Appl Chem 2010 822247ndash2279

168 Ye T Kumar A S Saha S Takami T Huang T JStoddart J F Weiss P S Changing Stations in SingleBistable RotaxaneMolecules under Electrochemical Con-trol ACS Nano 2010 4 3697ndash3701

169 Chen K Y Ivashenko O Carroll G T Robertus JKistemaker J C M London G Browne W R RudolfP Feringa B L Control of Surface Wettability UsingTripodal Light-Activated Molecular Motors J Am ChemSoc 2014 136 3219ndash3224

170 London GChenK YCarrollG TFeringaB L TowardsDynamic Control of Wettability by Using FunctionalizedAltitudinal Molecular Motors on Solid Surfaces Chem -Eur J 2013 19 10690ndash10697

171 Lussis P Svaldo-Lanero T Bertocco A Fustin C ALeigh D A Duwez A S A Single Synthetic Small

Molecule that Generates Force Against a Load NatNanotechnol 2011 6 553ndash557

172 Heinrich T Traulsen C H-H Holzweber M Richter SKunz V Kastner S K Krabbenborg S O Huskens JUnger W E S Schalley C A Coupled Molecular Switch-ing Processes in Ordered Mono- and Multilayers of Stimulus-Responsive Rotaxanes on Gold Surfaces J

Am Chem Soc 2015 137 4382ndash4390173 Pace G Ferri V Grave C Elbing M von Haumlnisch C

Zharnikov M Mayor M Rampi M A Samorigrave P Co-operativeLight-Induced MolecularMovements of HighlyOrdered Azobenzene Self-Assembled Monolayers ProcNatl Acad Sci U S A 2007 104 9937ndash9942

174 Moldt T Brete D Przyrembel D Das S Goldman J RKundu P K Gahl C Klajn R Weinelt M Tailoring theProperties of Surface-Immobilized Azobenzenes byMonolayer Dilution and Surface Curvature Langmuir 2015 31 1048ndash1057

175 Qin D Xia Y N Whitesides G M Soft Lithography forMicro- and Nanoscale Patterning Nat Protoc 2010 5 491ndash502

176 Eichelsdoerfer D J Liao X Cabezas M D Morris WRadha B Brown K A Giam L R Braunschweig A BMirkin C A Large-Area Molecular Patterning with Poly-mer Pen Lithography Nat Protoc 2013 8 2548ndash2560

177 Liao W S Cheunkar S Cao H H Bednar H R WeissP S Andrews A M Subtractive Patterning via ChemicalLift-Off Lithography Science 2012 337 1517ndash1521

178 Claridge S A Liao W S Thomas J C Zhao Y X CaoH H Cheunkar S Serino A C Andrews A M WeissP S From the Bottom Up Dimensional Control andCharacterization in Molecular Monolayers Chem SocRev 2013 42 2725ndash2745

179 Saavedra H Mullen T J Zhang P Dewey D CClaridge S A Weiss P S Hybrid Strategies in Nanolitho-graphy Rep Prog Phys 2010 73 036501

180 Yamada M Kondo M Mamiya J I Yu Y L KinoshitaM Barrett C J Ikeda T Photomobile Polymer MaterialsTowards Light-Driven Plastic Motors Angew Chem IntEd 2008 47 4986ndash4988

181 Yamada M Kondo M Miyasato R Naka Y Mamiya JKinoshita M Shishido A Yu Y L Barrett C J Ikeda TPhotomobile PolymerMaterials-VariousThree-DimensionalMovements J Mater Chem 2009 19 60ndash62

182 Ionov L Polymeric Actuators Langmuir 2015 31 5015ndash

5024183 Ware T H McConney M E Wie J J Tondiglia V P

White T J Voxelated Liquid Crystal Elastomers Science2015 347 982ndash984

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184 Ikeda T Mamiya J-i Yu Y Photomechanics of Liquid-Crystalline Elastomers and Other Polymers AngewChem Int Ed 2007 46 506ndash528

185 Iamsaard S Aszlighoff S J Matt B Kudernac TCornelissen J J L M Fletcher S P Katsonis N Conver-sion of Lightinto Macroscopic Helical Motion Nat Chem2014 6 229ndash235

186 Kitagawa D Nishi H Kobatake S Photoinduced Twist-ing of a Photochromic Diarylethene Crystal Angew

Chem Int Ed 2013 52 9320ndash9322187 Dunitz J D Schomaker V Trueblood K N Interpreta-

tionof Atomic Displacement Parameters fromDiff ractionStudies of Crystals J Phys Chem 1988 92 856ndash867

188 Nath N K Panda M K Sahoo S C Naumov PThermallyInducedand PhotoinducedMechanical Eff ectsin Molecular Single Crystals-A Revival CrystEngComm2014 16 1850ndash1858

189 Lange C W Foldeaki M Nevodchikov V I CherkasovK Abakumov G A Pierpont C G PhotomechanicalProperties of Rhodium(I)-Semiquinone Complexes TheStructure Spectroscopy and Magnetism of (36-di-tert-butyl-12-semiquinonato)dicarbonylrhodium(I) J AmChem Soc 1992 114 4220ndash4222

190 Jiang X Rodriacuteguez-Molina B Nazarian N Garcia-Garibay M A Rotation of a Bulky Triptycene in the SolidState Toward Engineered Nanoscale Arti1047297cial Molecular

Machines J Am Chem Soc 2014 136 8871ndash8874191 Lemouchi C Meacuteziegravere C Zorina L Simonov S

Rodriacuteguez-Fortea A Canadell E Wzietek P Auban-Senzier P Pasquier C Giamarchi T Garcia-GaribayM A Batail P Design and Evaluation of a CrystallineHybrid of Molecular Conductors and Molecular Rotors

J Am Chem Soc 2012 134 7880ndash7891192 Setaka W Yamaguchi K Thermal Modulation of Bire-

fringence Observed in a Crystalline Molecular GyrotopProc Natl Acad Sci U S A 2012 109 9271ndash9275

193 Setaka W Yamaguchi K A Molecular Balloon Expansionof a Molecular Gyrotop Cage Due to Rotation of thePhenylene Rotor J Am Chem Soc 2012 134 12458ndash

12461194 Setaka W Yamaguchi K Order-Disorder Transition of

Dipolar Rotor in a Crystalline Molecular Gyrotop and ItsOptical Change J Am ChemSoc 2013 135 14560ndash14563

195 Kobr L Zhao K Shen Y Q Poliacutevkovaacute K ShoemakerR KClark N APrice J CRogers C TMichl J InclusionCompound Based Approachto Arrays of Arti1047297cial DipolarMolecular Rotors Bulk Inclusions J Org Chem 2013 781768ndash1777

196 Kobr L Zhao K Shen Y Q Shoemaker R K RogersC TMichl J Tris-o-phenylenedioxycyclotriphosphazene(TPP) Inclusion Compounds Containing a Dipolar Molec-ular Rotor Cryst Growth Des 2014 14 559ndash568

197 Zhang W Ye H Y Graf R Spiess H W Yao Y F ZhuR Q Xiong R G Tunable and Switchable DielectricConstant in an Amphidynamic Crystal J Am ChemSoc 2013 135 5230ndash5233

198 Karlen S D Garcia-Garibay M A Amphidynamic Crys-tals Structural Blueprints for Molecular Machines TopCurr Chem 2005 37 179ndash227

199 Rodriacuteguez-Molina B Farfaacuten N Romero M Meacutendez-Stivalet J M Santillan R Garcia-Garibay M A Aniso-chronous Dynamics in a Crystalline Array of SteroidalMolecular Rotors Evidence of Correlated Motion within1D Helical Domains J Am Chem Soc 2011 133 7280ndash

7283200 Sylvester S O Cole J M Solar-Powered Nanomechani-

cal Transduction from Crystalline Molecular Rotors AdvMater 2013 25 3324ndash3328

201 Lemouchi C Iliopoulos K Zorina L Simonov SWzietek P Cauchy T Rodriacuteguez-Fortea A CanadellE Kaleta J Michl J Gindre D Chrysos M Batail PCrystalline Arrays of Pairs of Molecular Rotors CorrelatedMotion Rotational Barriersand Space-Inversion Symme-try Breaking Due to Conformational Mutations J AmChem Soc 2013 135 9366ndash9376

202 Kelly T R Bowyer M C Bhaskar K V Bebbington DGarcia A Lang F R Kim M H Jette M P A MolecularBrake J Am Chem Soc 1994 116 3657ndash3658

203 Commins P Garcia-Garibay M A Photochromic Molec-ular Gyroscope with Solid State Rotational States Deter-mined by an Azobenzene Bridge J Org Chem 2014 791611ndash1619

204 Comotti A Bracco S Yamamoto A Beretta MHirukawa T Tohnai N Miyata M Sozzani P Engineer-

ing Switchable Rotors in Molecular Crystals with OpenPorosity J Am Chem Soc 2014 136 618ndash621

205 Comotti A Bracco S Ben T Qiu S L Sozzani PMolecular Rotors in Porous Organic Frameworks AngewChem Int Ed 2014 53 1043ndash1047

206 Zhu K OKeefe C A Vukotic V N Schurko R W LoebS J A Molecular Shuttle that Operates Inside a MetalOrganic Framework Nat Chem 2015 7 514ndash519

207 Kim T Zhu L Al-Kaysi R O Bardeen C J OrganicPhotomechanical Materials ChemPhysChem 2014 15400ndash414

208 Panda M K Runcevsk T Sahoo S C Belik A A NathN K Dinnebier R E Naumov P Colossal Positive andNegative Thermal Expansion and Thermosalient Eff ect ina Pentamorphic Organometallic Martensite Nat Com-mun 2014 5 4811

209 Sahoo S C Panda M K Nath N K Naumov P

Biomimetic Crystalline Actuators Structure-KinematicAspects of the Self-Actuation and Motility of Thermo-salient Crystals J Am Chem Soc 2013 135 12241ndash

12251210 Sahoo S C Sinha S B Kiran M S R N Ramamurty U

Dericioglu A F Reddy C M Naumov P Kinematic andMechanical Pro1047297le of the Self-Actuationof ThermosalientCrystal Twinsof 1245-Tetrabromobenzene A MolecularCrystalline Analogue of a Bimetallic Strip J Am ChemSoc 2013 135 13843ndash13850

211 Naumov P Sahoo S C Zakharov B A Boldyreva E VDynamic Single Crystals Kinematic Analysis of Photo-induced Crystal Jumping (The Photosalient Eff ect)

Angew Chem Int Ed 2013 52 9990ndash9995212 Medishetty R Husain A Bai Z Z Runcevsk T

Dinnebier R E Naumov P Vittal J J Single CrystalsPopping Under UV Light A Photosalient Eff ect Triggeredbya[2thorn2] CycloadditionReaction Angew Chem Int Ed2014 53 5907ndash5911

213 Sahoo S C Nath N K Zhang L D Semreen M HAl-Tel T H Naumov P Actuation Based on Thermo Photosalient Eff ect A Biogenic Smart Hybrid Driven byLight and Heat RSC Adv 2014 4 7640ndash7647

214 Kobatake S Takami S Muto H Ishikawa T Irie MRapid and Reversible Shape Changes of Molecular Crys-tals on Photoirradiation Nature 2007 446 778ndash781

215 Kitagawa D Kobatake S Crystal Thickness Dependenceof the Photoinduced Crystal Bending of 1-(5-methyl-2-(4-( p-vinylbenzoyloxymethyl)phenyl)-4-thiazolyl)-2-(5-methyl-2-phenyl-4-thiazolyl)per1047298uorocyclopentenePhotochem Photobiol Sci 2014 13 764ndash769

216 Morimoto M Irie M A Diarylethene Cocrystal thatConverts Light into Mechanical Work J Am Chem Soc

2010 132 14172ndash

14178217 Terao F Morimoto M Irie M Light-Driven Molecular-Crystal Actuators Rapid and Reversible Bending of Rod-like Mixed Crystals of Diarylethene Derivatives AngewChem Int Ed 2012 51 901ndash904

218 Kitagawa D Kobatake S Photoreversible CurrentONOFF Switching by the Photoinduced Bending of Gold-Coated Diarylethene Crystals Chem Commun2015 51 4421ndash4424

219 Zhu L Y Al-Kaysi R O Bardeen C J Reversible Photo-induced Twisting of Molecular Crystal Microribbons

J Am Chem Soc 2011 133 12569ndash12575220 Kim T Al-Muhanna M K Al-Suwaidan S D Al-Kaysi

R O Bardeen C J Photoinduced Curling of OrganicMolecularCrystal Nanowires Angew Chem Int Ed201352 6889ndash6893

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221 Kim T Zhu L C Mueller L J Bardeen C J Mechanismof Photoinduced Bending and Twisting in CrystallineMicroneedles and Microribbons Composed of 9-Methyl-anthracene J Am Chem Soc 2014 136 6617ndash6625

222 KoshimaH MatsuoR Matsudomi M UemuraY ShiroM Light-Driven Bending Crystals of Salicylidenephenyl-ethylamines in Enantiomeric and Racemate Forms CrystGrowth Des 2013 13 4330ndash4337

223 Kumar A S Ye T Takami T Yu B C Flatt A K Tour

J M Weiss P S Reversible Photo-Switching of SingleAzobenzene Molecules in ControlledNanoscale Environ-ments Nano Lett 2008 8 1644ndash1648

224 ZhengY BPaytonJ LChung CH Liu RCheunkarSPathem B K Yang Y Jensen L Weiss P S Surface-Enhanced Raman Spectroscopy to Probe ReversiblyPhotoswitchable Azobenzene in Controlled NanoscaleEnvironments Nano Lett 2011 11 3447ndash3452

225 Vapaavuori J Goulet-Hanssens A Heikkinen I T SBarrett C J Priimagi A Are Two Azo Groups Better thanOne Investigating the Photoresponse of Polymer-Bisazobenzene Complexes Chem Mater 2014 265089ndash5096

226 Goulet-Hanssens A Barrett C J Photo-Control of Bio-logical Systems withAzobenzene Polymers J Polym SciPart A Polym Chem 2013 51 3058ndash3070

227 Ikeda T Tsutsumi O Optical Switching and Image

Storage by Means of Azobenzene Liquid-Crystal FilmsScience 1995 268 1873ndash1875

228 Koshima H Ojima N Uchimoto H Mechanical Motionof Azobenzene Crystals upon Photoirradiation J AmChem Soc 2009 131 6890ndash6891

229 Bushuyev O S Singleton T A Barrett C J FastReversible and General Photomechanical Motion inSingle Crystals of Various Azo Compounds Using VisibleLight Adv Mater 2013 25 1796ndash1800

230 Bushuyev O S Tomberg A Friscic T Barrett C JShaping Crystals with Light Crystal-to-Crystal Isomeriza-tion and Photomechanical Eff ect in Fluorinated Azoben-zenes J Am Chem Soc 2013 135 12556ndash12559

231 Bushuyev O S Corkery T C Barrett C J Friscic TPhoto-Mechanical Azobenzene Cocrystals and in situX-Ray Diff raction Monitoring of their Optically-InducedCrystal-to-Crystal Isomerisation Chem Sci 2014 5

3158ndash3164232 Warner M Mahadevan L Photoinduced Deformations

of Beams Plates and Films Phys Rev Lett 2004 92134302

233 Nath N K Pejov L Nichols S M Hu C H Saleh NKahr B Naumov P Model for Photoinduced Bending of Slender Molecular Crystals J Am Chem Soc 2014 1362757ndash2766

234 Luber E J Buriak J M Reporting Performance inOrganic Photovoltaic Devices ACS Nano 2013 7 4708ndash

4714235 Gogotsi Y What Nano Can Do for Energy Storage ACS

Nano 2014 8 5369ndash5371236 Haines C S Lima M D Li N Spinks G M Foroughi J

Madden J D WKim S HFangS Jung de Andrade MGoumlktepe F Goumlktepe euroO Mirvakili S M Na1047297cy S LeproacuteX Oh J Kozlov M E Kim S J Xu X Swedlove B J

Wallace G G Baughman R H Arti1047297cial Musclesfrom Fishing Line and Sewing Thread Science 2014343 868ndash872

237 Lee J A Kim Y T Spinks G M Suh D Leproacute X LimaM D Baughman R H Kim S J All-Solid-State CarbonNanotube Torsional and Tensile Arti1047297cial Muscles NanoLett 2014 14 2664ndash2669

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advancing the development of arti1047297cial molecularmachines We 1047297rst summarize some of the key ad-vances in the development of molecular switches androtors ranging from simple hydrazone switches tocomplex deoxyribonucleic acid (DNA)-based nano-mechanical walkers Although these systems in isola-tion are distinct from scaled-up arti1047297cial machines

recent progress in the diversity and complexity of theirdesign has facilitated greater control over mechanicalmotion at the molecular level This control has enabledthe conversion of simple molecular components intofunctional tools that can interact with one another orcouple to their environment to operate as machines atthe nanoscale We highlight some of the most prom-ising examples of the organization of switches androtors into linear assemblies then two-dimensionalarrays on surfaces and 1047297nally polymeric networksand dynamic three-dimensional crystals Ultimatelythe precise and robust integration into higher dimen-sional architectures that take advantage of mechanicalaction by many components is essential to bridge thegap between actuating molecular motion and per-forming microscopic mesoscopic and macroscopicwork Throughout we address fundamental obstaclesyet to beovercometo advance the 1047297eldand to convertthese molecular systems into functioning machinesand off er a glimpse into the untapped potential of these versatile systems in an eff ort to identify some of the most viable directions toward future molecularmachine design and implementation

MOLECULAR SWITCHES ROTORS AND MOTORS

Increasing Sophistication of Molecular Design Numerousclasses of molecules that reversibly isomerize betweenmultiple structuralconfigurations in responseto externalstimuli fall within the realm of molecular switchesCommonexamples of photochromic molecularswitchesaredisplayed in Figure 1 Some of the most extensivelystudied small-molecule motifsinclude (but arefar fromlimited to) azobenzenes whose isomerization be-tween E and Z conformations about a double bondmimics flapping motions1314 diarylethenes and spiro-pyrans in which conformational changes are accom-panied by ring-opening or ring-closing reactions1518

anthracene and coumarin derivatives that reversibly

dimerize with one another1921 and overcrowdedalkenes hydrazones and imines which behave asrotors that can revolve about a rigid internal axis2225

Covalent modification of parent switch and rotormolecules provides near infinite opportunities to de-sign alternate isomerization pathways and to tuneactuation stimuli Additionally noncovalent interac-tions between molecules such as hydrogen bondinghydrophobic effects and π π stacking enable theconstruction of dynamic hostguest systems expand-ing the versatility of switches via supramolecular self-assembly of twoor more components26 Thesedynamic

molecules represent the smallest building blocks avail-able for a bottom-upapproach to synthesize functionalmechanical devices that exhibit motion Increasinglycomplex mechanically interlocked molecules (MIMs)such as catenanes rotaxanes and pseudorotaxanesrepresent another class of switches and rotors andhave regularly been targeted as promising architec-tures in the design of molecular muscles that facilitate

contractile and extensile motions due to theirmechanostereochemistry2729 Catenanes are MIMsconstructed from two or more interlocked macrocyclesin a chain-like architecture that may be designed toadopt distinct and stable conformations with control-lable rotary motions (Figure 2a) Alternatively rotax-anes pseudorotaxanes and their derivatives aremolecules composed of a linear rod-like componentthreaded through a cyclic host the exact position andorientation (station) of the relative components in themechanically interlocked compound can be controlledby external stimuli The macrocycle host may besterically constrained bybulkyend groupson thelinear

species as in rotaxanes or designed to possess suffi-cient free energy to dethread from the rod-like com-ponent as in pseudorotaxanes (Figure 2bc) Finallynanomechanical switches rotors and walkers com-posed of a few to hundreds of DNA biopolymerstrands whose design and synthesis have developedinto a rapidly burgeoning field of its own offer thecapability to extend the dynamic boundaries of indivi-dual molecular components to the submicrometerscale3032

While diverse all of the aforementioned switchand rotor components operate on similar principles33

VOCABULARYMolecular machine - a multicomponent

molecular system with de1047297ned energy input that is cap-

able of performing a measurable and useful secondary

function reversibly either at the nanoscale or if ampli1047297ed

through collective action at larger scales Hierarchical

assembly - the bottom-up arrangement or ordering of

individual components that results in increased overall

size dimensionality complexity andor functionality

Cooperativity - the property of complex action within

coupled molecular systems that yields diff erent results

from isolated or ensemble (collective) switching events

Mechanostereochemistry - the relative spatial arrange-

mentof atoms within mechanically interlocked molecules

Amphidynamic crystal - an ordered solid that has both

rigid ordered lattice constraints and highly mobile com-

ponents simultaneously Thermophotosalient crystal -

an orderedsolidthatexhibits rapid phase transitionsupon

heating or irradiation resulting in jumping of the crystal

which may be accompanied by fracturing Photomecha-

nical crystal - an ordered solid that changes shape(expands bends or twists) under ultraviolet (UV) or visible

light irradiation in the process of crystal-to-crystal chemi-

cal transformation

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R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7752













R E V I E

W




wwwacsnanoorg

7753







ORGANIZATION





R E V I E

W




wwwacsnanoorg

7754










R E V I E

W




wwwacsnanoorg

7755










R E V I E

W




wwwacsnanoorg

7756












R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7753







ORGANIZATION





R E V I E

W




wwwacsnanoorg

7754










R E V I E

W




wwwacsnanoorg

7755










R E V I E

W




wwwacsnanoorg

7756












R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7754










R E V I E

W




wwwacsnanoorg

7755










R E V I E

W




wwwacsnanoorg

7756












R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7755










R E V I E

W




wwwacsnanoorg

7756












R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7756












R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7757











R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7758









R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7759














R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7760











R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7761










R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7762


































R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7763













































2014 136 2178ndash





R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7764


























300 2061ndash

































R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7765

















































R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7766



















J Chem 2010 50 333ndash346





























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W




wwwacsnanoorg

7767











































2010 132 14172ndash






R E V I E

W

























R E V I E

W

























R E V I E

W

MolrMachNN15

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Transcript of MolrMachNN15