Recent Developments on Rotaxane-Based Shuttles: An Update to 2010

Current Organic Chemistry, 2012, 16, 127-160 127

1875-5348/12 $58.00+.00 © 2012 Bentham Science Publishers

Recent Developments on Rotaxane-Based Shuttles: An Update to 2010

Antonio Rescifina,*,a

Ugo Chiacchio,a Antonino Corsaro,

a and Giovanni Romeo

b

aDipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy

bDipartimento Chimico-Farmaceutico, Università di Messina, Viale SS. Annunziata 6, 95168 Messina, Italy

Abstract: This update reviews the major developments on rotaxane-based shuttles during the period of August 2008 to October 2010 and

is organized similarly to the previous review [1].

The progress in the field of chemical controlled shuttles can be summarized as a significant increase of the shuttling rates,

second-generation pH-switchable Pd(II)-complexed rotaxanes, and new synthetic approaches, especially those based on Diels-Alder cy-

cloadditions. The new synthetic routes allow ready access to rotaxanes that feature the template site fully incorporated into the

interlocked product. This template site is unusual for active-template reactions and produces shuttles that exhibit entropy-driven

translational isomerism with remarkably improved positional discrimination as was shown by the incorporation of a hydrogen-bonding

TEG-station into an imine-bridged rotaxane.

With respect to photochemically powered molecular switches, the most important result originated from the synthesis of a degenerate,

donor-acceptor, light-gated, STOP-GO molecular shuttle. For electrochemically controllable bistable rotaxanes, the first example of a

molecular shuttle with three different stations, which dramatically increase the shuttling process rate, has been reported.

Finally, the last study in this review involves redox-driven switching and electrochromic responses of LC films containing a bistable

[2]rotaxane. The presence of a polymer electrolyte provides new prospects for the further development of rotaxane-based molecular ma-

terials by exploiting the dynamic, anisotropic, and coherent properties of liquid crystals.

Keywords: Mechanically interlocked molecules; Click chemistry; Molecular devices; Nanoscale machines.

INTRODUCTION

Due to the expeditious propagation of new and more sophisti-

cated interlocked machines, it is unsurprising that an update of the

previously published review [1], which focused on

[2]rotaxane-based shuttles, is desired. Since the first account

reviewed the literature up to July 2008, this update covers that pub-

lished between August 2008 and October 2010. Moreover, because

there is a plethora of literature related to this field, this update fo-

cuses on the most relevant results. To facilitate the reader, the

organization of this update follows that of the original review and

includes sections regarding chemically, photochemically, and elec-

trochemically induced molecular switching.

Mechanically interlocked molecules attract considerable atten-

tion as the basis for molecular devices and nanoscale machines long

after the first reported syntheses of these chemical curiosities in the

mid-1960s [2]; [n]rotaxanes (rota meaning wheel, axis meaning

axle) are one common form. The number “n” enclosed in square

Address correspondence to this author at the Dipartimento di Scienze Chimiche,

Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy;

Tel: +390957385017; Fax: +3906233208980; E-mail: [email protected]

brackets describes the number of molecular parts involved in

mechanical bonding; for example, a [2]rotaxane is formed when a

thread, dumbbell, or axle component is mechanically interlocked

with a ring component. If the axle component is blocked at both

ends by bulky functional groups to prevent dissociation of the ring

component at ambient temperature (Fig. 1), the system is called a

rotaxane. However, if there are no stoppers on the axle or the stop-

pers are not of sufficient size to preclude dissociation at ambient

temperature, the molecular assembly is referred to as a

[2]pseudorotaxane. A [3]rotaxane is typically formed when two

rings are threaded onto an axle component although two axles with

one ring also satisfies the definition.

There are three common methods of preparing rotaxanes: cap-

ping, clipping, and slipping; however, a recent route via a template

leads to improved yields over those achieved using statistical syn-

theses. The value of rotaxanes as molecular abacuses or transport

agents and their capacity to shuttle (i.e., molecular motion) and

switch (i.e., molecular logic) has caused research to flourish over

the past decade: much effort has been dedicated to improving the

synthetic methodologies to enable enhanced functions [3].

Rotaxanes have emerged as a prototype for a class of molecular

Fig. (1). Schematic representation of a [2]rotaxane.

Stoppers

Stations

Ring

Thread

128 Current Organic Chemistry, 2012, Vol. 16, No. 2 Rescifina et al.

machines as a result of their ability to undergo translational iso-

merization between two or more structures (Fig. 2), which origi-

nates from the translational molecular motion of the macrocyclic

ring along the acyclic component. The equilibration and dynamic

behavior back and forth along the acyclic component similar to the

movement of a bus or train between stations is known as shuttling

and can occur up to 40,000 times per second. Molecular recognition

sites are built into both components to produce thermodynamic

sinks, which form points along the linear component where two or

more components predominantly reside. It is vital for both synthesis

and functionality that the components of a rotaxane system are elec-

tronically complementary. This is the reason for the highly colored

nature of most rotaxanes.

Metal complexing sites, which often feature different denticities

(i.e., bidentate and tridentate), are popular options as “stations” on

axle components with the molecular shuttling driven by electro-

chemical stimulation. Sauvage and co-workers have shown that

stations with the same denticity may also be incorporated into the

axle structure and result in [2]rotaxanes that function via electro-

chemical means [4]. In this example, the axle binding sites include

a highly shielding phenanthroline ligand and a non-sterically hin-

dered bipyridine chelate; a bisquinoline unit in the macrocyclic ring

affords the complementarity via copper complexation (Fig. 3). Al-

though its preparation involves a multi-step synthesis, the electro-

chemically induced shuttling between the two stations is a fast,

clean process and is promising for the development of multi-state

machines in the future.

The successful achievement of this relatively complicated in-

terlocked system arises from the design of the macrocycle. The

positioning of a ligand in the macrocyclic structure provides two

functions: (1) it acts as a ligation site for a transition metal that will

act as a catalyst for the bond formation of the axle components, and

(2) it provides a template for the successive covalent bond forma-

tion of interlocked axle components. This high yielding methodol-

ogy may be applicable to other higher-order interlocked molecular

assemblies, which is important for the development of increasingly

complex molecular machinery. Interest has also been expressed for

potential biological applications of mechanically interlocked rotax-

anes due to the encapsulation or protection of the axle component

provided by the macrocyclic ring. As an example, Leigh and

co-workers reported a rotaxane comprising a pentapeptide axle and

a macrocycle, which protects the axle against peptidase-catalyzed

hydrolysis for several days [5]. The use of oligopeptide axle com-

ponents was reported by Moretto et al. who enabled characteristic

shuttling between stations upon the change of the solvents (Fig. 4)

[6].

Fig. (2). Rotaxanes are able to shuttle between two different states indicating switching (ON/OFF) or binary processes (0/1). Shuttling is a form of transla-

tional isomerism. The challenge is the control of this motion.

Fig. (3). Copper-complexing [2]rotaxane possessing two different bidentate stations. The diphenylbiisoquinoline ligand (DPBIIQ) site in the macrocyclic ring

structure is complementary to either the diphenylphenanthroline (DPP) or bipyridine (BIPY) sites along the threading molecule and shuttling is possible upon

electrochemically-driven complexation events with copper.

Shuttling

State

OFF or 0

ON or 1

N N

O O

O O

N N

Cu

DPP BIPY

DPBIIQ

N N

O O

O O

N N

Cu

Station 1DPP-Cu-DPBIIQ

Station 2BIPY-Cu-DPBIIQ

Recent Developments on Rotaxane-Based Shuttles Current Organic Chemistry, 2012, Vol. 16, No. 2 129

CHEMICALLY INDUCED SWITCHING OF BISTABLE

ROTAXANES

Research devoted to elucidating the effect of structural varia-

tions on the positional bias and kinetics of shuttling, which is im-

portant for the development of rotaxane systems with levels of mo-

tion control beyond that of simple switches, has led to a second

generation of palladium(II)-complexed molecular shuttles. These

shuttles feature structural changes to the size and shape of the mac-

rocycle [7] resulting in significantly increased shuttling rates and

improved co-conformational bias compared to the original system.

A notable feature of the first-generation system, e.g., rotaxane 1

(Scheme 1), was its metastability, i.e., a change of the chemical

state of the thread does not immediately cause a change in the posi-

tion of the macrocycle. Although this allows the system to be held

in an out-of-equilibrium state, which is difficult to achieve using

molecular shuttles that rely on weak non-covalent interactions,

elevated temperatures and extended times are required (up to 16 h

at 383 K to reach equilibrium) to overcome the energy barrier to

shuttling. Furthermore, the positional bias of the Pd-macrocycle

between the 4-dimethylaminopyridine (DMAP) and pyridine (Py)

Fig. (4). Schematic representation of a [2]rotaxane molecular machine possessing an oligopeptide axle that results in a helical structure.

Scheme 1. Operation conditions and positional bias of (a) first generation 1 and (b) second generation 2 molecular shuttles.

CHCl3, CH3CN,

NNO

R OR

NMe2

PdN N

O O

O O

tBu

But tBu

1

R =

NNO

R OR

NMe2

PdN N

O O2

O O

a)

b)

+

1:8383 K,16 h

DMF-d7

+

6:1383 K,1.5 h

DMF-d7

TsOH – TsOH TsOH – TsOH

+

1:32323 K, 4 hDMF-d7

+

12:1323 K,2 hDMF-d7

TsOH – TsOH TsOH – TsOH

N

N

N HN

NH

N

+ +


stations was modest in both the neutral (ca. 6:1) and protonated (ca.

1:8) states of the rotaxane thread (Scheme 1a). In the

second-generation molecular shuttle, e.g., rotaxane 2 (Scheme 1b),

the benzylic amide macrocycle is replaced by a bisanilide ring,

which is larger and has a different shape. The alteration of the steric

environment around the palladium(II) centre in rotaxane 2 leads to

greatly enhanced rates of macrocycle shuttling and improved

positional bias in both chemical states of the thread. In addition to

the minimum energy co-conformers of the two switched systems,

two metastable out-of-equilibrium positional isomers were suffi-

ciently stable to be isolated and characterized using 1H NMR spec-

troscopy.

Rotaxane 2 was prepared via a threading-and-stoppering pro-

cedure. Initially, a palladium-macrocycle-acetonitrile complex was

treated with an unstoppered DMAP end-thread precursor followed

by the reaction of the resulting pseudorotaxane with excess

phenol-based stoppers under Mitsunobu conditions to afford the

[2]rotaxane.

The associative nature of palladium(II) substitution reactions

and the faster shuttling rate of 2 than that of 1 suggest that the

bisanilide macrocycle provides a less sterically demanding envi-

ronment around the metal ion and thus easier access for incoming

coordinating solvent molecules or TsO– counter-anions.

Active-template synthesis involves the construction of me-

chanically interlocked structures with the metal ion acting as both a

template to entwine or thread the components and a catalyst to

capture the interlocked final product by covalent bond formation

[8]. During this process, the metal often changes coordination

strength and the preferred geometry of its ligands several times.

Despite the complexity of this mechanism, several different

metal-catalyzed reactions have already proven suitable for the ac-

tive-metal template synthesis of both rotaxanes and catenanes in-

cluding copper(I)-catalyzed terminal alkyne-azide cycloaddition

(i.e., the CuAAC “click” reaction), palladium- and copper-catalyzed

alkyne homocouplings and heterocouplings, and

palladium-catalyzed oxidative Heck couplings and Michael addi-

tions.

However, unlike traditional “passive” metal-template methods,

permanent intrinsic recognition motifs are not required on each of

the components that will be interlocked during active-template syn-

theses, i.e., the assembly can be traceless. This means that one of

the most widely exploited features of rotaxane template assembly,

i.e., that the intercomponent recognition motif remains in the rotax-

ane to provide preferred binding sites for the ring on the thread as is

used in molecular shuttles, is not inherently present using ac-

tive-template syntheses.

To solve this issue, Leigh’s group reported the active-template

synthesis of rotaxanes using Lewis acid–catalyzed Diels-Alder

cycloaddition [9]. The reaction proceeds in the presence of either

Zn(II) or Cu(II) salts with weakly coordinating triflate anions and

generates[2]rotaxanes in up to 91% yields. The active-template

reaction “selects” 2-substituted cyclopentadienes over 1-substituted

cyclopentadienes, which results in the generation of one rotaxane

isomer with 90%–99% selectivity as opposed to the four isomers

produced in the case of non-interlocked threads. Unusually for an

active-template reaction, the template site is fully incorporated into

the interlocked product; therefore, metal-chelated molecular shut-

tles can readily be prepared. This is exemplified by the synthesis of

a molecular shuttle in which the position of the macrocycle can be

switched by varying the coordination requirements of the metal ion

(e.g., trigonal-bipyramidal Zn(II) or square planar Pd(II)).

Rotaxane formation from dienophile 4, diene 5, and complexes

of macrocycle 3 with various Lewis acids, which were formed in

situ in CH2Cl2, was investigated [9]. The addition of acryloyl imi-

dazolidone 5 at room temperature and diene 5 at –78 °C to the

CH2Cl2 solution of the macrocycle-Lewis acid complexes was fol-

lowed by stirring at –78 °C for 20 h and at room temperature for a

further 4 h. Initial experiments with ZnCl2 were unsuccessful,

which is likely because the two chloride ligands are too strongly

coordinated to the metal. However, the use of Zn(OTf)2 afforded

[2]rotaxane 6 in 8% yield. Changing the Lewis acid from zinc tri-

flate to copper triflate increased the yield of 6 to 47%, whereas

increasing the amounts of 4 and 5 and extending the reaction time

(48 h at –78 °C followed by 48 h at room temperature) improved

the yield of 6 to 42% with Zn(OTf)2 and 83% with Cu(OTf)2. Using

the same optimized reaction conditions with only 30 mol% copper

triflate reduced the yield of 6 to 37%, which indicates that 6 se-

questers the metal ion thereby preventing turnover of the active

template to any significant extent during the reaction.

The proposed mechanism for rotaxane formation is shown in

Scheme 2. Replacement of the two labile ligands with oxygen at-

oms of the acryloyl imidazolidone unit affords threaded complex II;

in this complex, the activated double bond must react with

stoppered cyclopentadiene 5 on the macrocycle face opposite the

dienophile stopper group. Demetalation with ammonia [for Cu(II)]

or Na4EDTA [for Zn(II)] generates the metal-free rotaxane, 6.

The utility of the metal binding site in the rotaxane-forming Di-

els-Alder cycloaddition remains essentially unchanged in the ro-

taxane product, as was demonstrated during the synthesis of more

complex rotaxanes. Molecular shuttle 10:10 was prepared from

Py-containing dienophile building block 9 and diene 5 (Scheme 3).

The 42% yield of [2]rotaxane 10:10 was remarkably good, and a

high (1,4)/(1,3) ratio (95:5) was maintained despite the presence of

the Py unit, which can compete with the macrocycle for complexa-

tion with the Lewis acid. In this reaction, the building blocks offer

an unhindered site for the Lewis acid–catalyzed reaction to form the

thread. Additionally, the Py unit and -carbonyl imidazolidone

functionalities, which persist in [2]rotaxane 10:10 , could be used as

binding sites with different preferred coordination geometries to

control the position of the metal-coordinated macrocycle on the

thread (Scheme 4).

As with the simpler rotaxane, 6:6 , the room-temperature 1H

NMR spectrum of 10:10 (298 K, 9:1 CD2Cl2/CD3CN) shows an

upfield shift of the aliphatic and Py signals with respect to those of

the non-interlocked thread. This is particularly evident for the Hf–h,

H , and Hk–m protons, which indicates that the macrocycle moves

freely but spends most of its time on the less-hindered portions of

the thread. Upon the addition of Zn(OTf)2 to the NMR tube con-

taining 10:10 , the 1H NMR spectrum increased in complexity sug-

gesting that multiple coordinated species were present and likely

interchanging. However, the saturation of the rotaxane binding sites

by adding excess Zn(OTf)2 led to a greatly simplified spectrum.

This spectrum shows significant upfield shifts of the -carbonyl

imidazolidone moiety signals (i.e., H , Hv, Hu, and Hz) and down-

field shifts of the Py moiety (i.e., Hj–n) with respect to the metal-

free rotaxane. This indicates that the macrocycle is positioned over

the -carbonyl imidazolidone unit as part of a trigonal bipyramidal–

coordinated Zn(II) complex and the thread Py group is coordinated


Scheme 2. Diels-Alder active-metal-template synthesis of [2]rotaxane 6 from macrocycle 3, dienophile 4, and diene 5.

MO

N

O

O O3

O

N

O

O O

L L

MO

N

O

O O

O O

NNRO

O O

NN

RO

MO

N

O

O O

O O

NN

RO

OR

R = (t-BuC6H4)3C(C6H4)

M = Cu(II), Zn(II)

L = Cl, OTf

I

4

II

ML2

O O

NNRO

OR

OR

H

O

N

O

O O

O O

NN

RO

ORH

2 TfO

L = TfO– 2 L

2 TfO

5(2) only

O O

NNRO

+

OR

OR

OR

[1,5]-shift

5(2)

5'(1)

5(2):5'(1)55:45

7(1,4):7'(1,3)95:5

8(1,2): major8'(1,5): minor

1

2

1

1

H

H

3

4

2

5

7

8

7:861:39

NH3[Cu(II)]or

Na4EDTA[Zn(II)]

[Cu(NH3)6](OTf)2or

Na2[Zn(EDTA)] + 2 NaOTf

1 3

4

M = Zn: 42%M = Cu: 83%

6(1,4):6'(1,3)9:1

non-interlockedthread production


N

RO

NN

O

O

N

RO

N

O

O

H

OR

N

RO

NN

O

O

H

OR

N

RO

NN

O

O

H

OR

OR

3, 5, Cu(OTf)2

–78 °C, 48 h

then r.t. 48 h

42%

10(1,4):10'(1,3)

95:5

+ non-interlocked threads 11 and 12

42%

11(1,4):11'(1,3)

86:14

12(1,2): major

12'(1,5): minor

11:12

68:32

R = (t-BuC6H4)C(C6H4)

O

N

O

OO

N

9

Scheme 3. Assembly of molecular shuttle 10:10 from the Diels-Alder active-metal-template reaction of macrocycle 3, dienophile 9, and diene 5.

to a second Zn(II) ion (structure [10:10 Zn2]L2(OTf)4 in Scheme

3a). Demetalation (Na4EDTA, RT, 1 h) of the zinc complex liber-

ated metal-free rotaxane 10:10 .

The addition of PdCl2 to 10:10 results in the formation of a

different rotaxane complex, i.e., [10:10 Pd]Cl2 (Scheme 3c). How-

ever, in the 1H NMR spectrum of [10:10 Pd]Cl2, the signals of the

protons adjacent to the thread Py unit (Hj and Hn) are shielded by

the aromatic rings of the macrocycle and are consistent with the

chemical shifts of a previously reported palladium-complexed ro-

taxane [10] while the signals of the -carbonyl imidazolidone moi-

ety are similarly shifted to those of the non-interlocked thread.

Demetalation of [10:10 Pd]Cl2 with KCN (MeOH/CH2Cl2 1:1, RT,

1 h) again affords the metal-free [2]rotaxane, 10:10 .

This mechanism can be exploited to construct molecular shut-

tles in which the position of the macrocycle can be controlled by

the coordination requirements of the metal ions coordinated to the

rotaxane. Such metal ion–switchable systems historically require

lengthy syntheses (10–20 steps); therefore, the active-template Di-

els-Alder reaction is a valuable addition to the methods for the as-

sembly of interlocked molecular-level architectures.

Novel examples of molecular shuttles (13a,b) that exhibit en-

tropy-driven translational isomerism with remarkable positional

discrimination feature an imine-bridged attached to triethylene gly-

col ether (TEG) stations. These compounds can be completely

transformed to hydrolyzed [2]rotaxanes under hydrolytic conditions

due to hydrogen-bond formation between the macrocycle and the


TEG station [11]. Analysis of the thermodynamic parameters

revealed that imine-bond hydrolysis and the formation of hydrogen

bonds between the macrocycle and the station are thermodynami-

cally matched processes because they are both enthalpically favored

and accompanied by a loss of entropy. The combination of

imine-bonding and hydrogen-bonding stations in a rotaxane system

is key to the observed entropy-driven positional switching of the

macrocycle.

N

RO

NN

O

O

H

OR

R = (t-BuC6H4)C(C6H4)

O

N

O

OO

N

RO

N N

OO

H OR

Zn

O

N

O

OO

PdCl Cl

2 TfO

ZnL L

TfO OTf

N

RO

N

O

O

H

OR

O

N

O

OO

N

Zn(OTf)2 EDTA

KCN PdCl2

[10:10'Zn2]L2(OTf)4

L = H2O, solvent or pyridine

from another [2]rotaxane

A

B

C

D

E

F

G

HI

J

K

a–e

f

g

h

i

j

k

lm

n op

q

r

s

t u

v

yw

x

z–

10(1,4):10'(1,3)

95:5

[10:10'Pd]Cl2

a)

b)

c)

Scheme 4. Determination of the macrocycle position by the metal coordination geometry in molecular shuttle 10:10 . (a) Macrocycle position upon coordina-

tion to Zn(II): [10:10 Zn2]L2(OTf)4. (b) Metal-free rotaxane 10:10 . (c) Macrocycle position upon coordination to Pd(II): [10:10 Pd]Cl2.


Imine bonds can be equilibrated with an amine-aldehyde pair

under hydrolytic conditions; their cleavage under dynamic acidic

hydrolytic conditions is assisted by the formation of hydrogen

bonds between the resulting primary ammoniums (–NH3

+) and suit-

able, newly attached hydrogen-bonding acceptors [12].

From the perspective of thermodynamic contributions, imine

bonding and hydrogen bonding must work synergistically to enable

entropy-driven positional switching of the macrocycle in a rotaxane

structure (Scheme 5). Hydrogen bond formation is enthalpically

favored and is accompanied by a loss of entropy, whereas imine

bond formation is entropically favored in a rotaxane structure. Gi-

useppone and Lehn reported that the equilibrium ratio of the imine

form in dynamic combinatorial libraries (DCLs) increased with

increasing temperature under low acidic conditions [13]. Thus,

imine bond cleavage and hydrogen bond formation are thermody-

namically matched processes (i.e., enthalpically favored and en-

tropically disfavored processes). Therefore, the reverse processes of

hydrogen bond cleavage and imine bonding must also be matched

processes (i.e., enthalpically disfavored and entropically favored

processes). Accordingly, it is expected that the incorporation of

both imine bridging and hydrogen bonding stations on a rotaxane

axle would result in a novel rotaxane-based molecular shuttle that

exhibits entropy-driven translational isomerism [14].

Shuttles 13a,b, which feature TEG units as hydrogen-bonding

stations, were prepared by introducing end groups with TEG units,

17b, into imine-bridged pseudorotaxane 16, which was prepared

from a hydrindacene axle and a macrocyclic diamine using a

threading method directed by imine bond formation (Scheme 6).

Neutral dithioacetalized [2]rotaxanes 16b were obtained by treating

the solution of 13b with ethanedithiol under acidic hydrolytic con-

ditions.

Subsequently, the dynamic equilibrium between 13a,b and

14a,b·2H2+

with TEG stations under acidic hydrolytic conditions

was investigated to determine whether the preferred position of a

macrocycle could be switched from the imine-bridging hydrin-

dacene station to the TEG station on the rotaxane axle (Scheme 7).

Upon addition of TFA to a solution of 13a, which features a

TEG and xylylene (XYL) station, in wet CDCl3, the 1H NMR spec-

trum revealed the disappearance of the signals derived from

bis-imine 13a and the appearance of a new set of signals including

CHO signals (Ha,a ) at 9.4 ppm even at 298 K that were assigned

to a single species. The signals for the protons around the TEG

station (Hi–n, Ho, and Hh) of the newly generated species appeared

upfield of those of bis-imine 13a, whereas those for the protons

around the XYL station (Hh ,o and Hq,t) remained unchanged. Thus,

the newly generated species was assigned as a [2]rotaxane,

14a·2H2+

, in which the macrocycle is located at the TEG station on

the axle due to hydrogen-bond formation. The exclusive generation

of [2]rotaxane 14b·2H2+

from 13b was observed under acidic hy-

drolytic conditions at 295 K.

The rate (k) and energy barrier ( G‡) for the shuttling of the

macrocycle of 14b·2H2+

were determined to be 574 s–1

and 12.5 ±

0.2 kcal mol–1

at 273 K (Tc), respectively, using the coalescence

method via variable-temperature (VT) NMR. When the acidic solu-

tions containing 4a,b·2H2+

were subjected to dehydrating condi-

tions, bis-imines 13a,b were quantitatively regenerated.

In addition to the successful hydrolytically controlled switching

of bis-imines 13 and [2]rotaxanes 14·2H2+

, it was found that they

could also be switched by simply changing the temperature under

acidic hydrolytic conditions. In particular, 13a,b/14a,b·2H2+

can be

completely switched from one TEG station to another as a function

of temperature, thereby demonstrating entropy-driven positional

switching of the macrocycle in a molecular shuttle.

The release of water molecules accompanied by the in-

tramolecular imine-bond formation from 14a,b·2H2+

to 13a,b seem-

ingly contributes to the entropy gain during heating. Thus, the equi-

Scheme 5. Thermodynamic interplay of imine- and hydrogen-bonding in a rotaxane-based molecular shuttle exhibiting entropy-driven translational isomerism.

O O

N

O O O O

H < 0 S < 0

H > 0 S > 0

NH3

CHO

NH3

CHO

H < 0 S < 0

H > 0 S > 0

thermodinamically matched

imine-bonding cleavage hydrogen-bonding

OOOO

N

N

OOO

CHO

CHO NH3

H3NO

low T

high T

imine-bridged rotaxane 13a hydrogen-bonded [2]rotaxane 14a•2H2+

translocation of the macrocycle by temperature

entropy-driven switching


OTBSTBSO

N

N

CH2OOCH2

CH2OOCH2

(CH2)4

(CH2)4

A X

17a: X = Br, A =

17b: X = I, A =

CH2H2C

O

O

N

N

CH2OOCH2

CH2OOCH2

(CH2)4

(CH2)4

A2 A1

R

R R

CHO

NH3

OHC

NH3

OO

OO

(CH2)6

(CH2)6

A2 A1R R

NH2

NH2

OO

OO

(CH2)6

(CH2)6

A2 A1R R

SS

S S

TBAF

Cs2CO3

THF/DMF

16

13a,b; a = 25%, b = 76%

TFA, wet CDCl3

+ H2O– H2O

[mono-imine 15]

+ H2O – H2O

(CH2SH)2

for 14b

16b; 66%

14a,b•2H2+

Ha

O O

O O O O

t

s r

q

i j k l m n

O O O O

i j k l m n

O O O O

n' m' l' k' j' i'

A2 A1

a:

b:

2

2

2

R =

17a,b

o' h' g h o p

AB

C

D

E

Ha

Hb Hc d e

f

Scheme 6. Synthesis of imine-bridged rotaxanes 13a,b, hydrogen-bonded [2]rotaxanes 14a,b•2H2+

, and dithioacetalized [2]rotaxanes 16a,b.


Scheme 7. Transformation between imine-bridged rotaxanes 13a,b and [2]rotaxanes 14a,b under acidic hydrolysis/dehydration conditions.

librium ratio of 13a,b/14a,b, which determines the preferred posi-

tion of the macrocycle between the imine-bridging and hydro-

gen-bonding stations, could be completely reversed as a function of

temperature (the ratios of 13a,b/14a,b·H2+

= <5/95 at 273 K and

>95/5 at 373 K).

The changes in both enthalpy and entropy between 13a and

14a·2H2+

( H = –16.7 ± 0.7 kcal mol–1

and S = –52.2 ± 2.1 cal

mol–1

K–1

) were larger than those for the analogs incorporating the

non-hydrogen-bonding XYL station [10]. This difference originates

from the incorporation of a TEG station instead of a XYL station,

i.e., the additional enthalpic stabilization and loss of entropy due to

hydrogen bonding of the macrocycle with the TEG station in

14a·2H2+

. The conformational restriction of the TEG moiety that

accompanies hydrogen bonding might contribute to the negative

value of the S term. Consequently, the incorporation of a TEG

station with hydrogen-bonding abilities into imine-bridged rotax-

anes not only biases the 13a/14a·2H2+

equilibrium towards the hy-

drolyzed [2]rotaxane under acidic hydrolytic conditions but also

enables entropy-driven positional switching of the macrocycle by

supplying additional enthalpic and entropic differences.

Chemically driven shuttles, excluding those controlled by

acid-base proton transfer (i.e., pH-controlled reactions), remain

scarce. Catalytic reactions are considered to be prime candidates for

integrating this type of control into synthetic molecular machines

that work via an energy ratchet mechanism.

Berna et al. synthesized azo-functionalized hydrogen bond–

assembled [2]rotaxanes 20 and 21 that comprise a dumbbell com-

ponent, which contains an azodicarboxamide and a succinic amide

ester binding site, threaded through a tetrabenzylic amide macrocy-

cle (Scheme 8) [15]. These binding sites can be reversibly and effi-

ciently interconverted to their hydrazo forms through hydrogena-

tion-dehydrogenation of the nitrogen-nitrogen bond. This type of

chemically switchable control element has been implemented in

stimuli-responsive molecular shuttles that function through a re-

versible azo/hydrazo interconversion and produce large net

positional changes with good discrimination between the binding

sites of the macrocycle in both states of the shuttle. These molecu-

lar shuttles operate by two different mechanisms: (1) a discrete

mode through two reversible and independent chemical events and,

importantly, (2) a continuous regime through a catalyzed ester

bond–formation reaction in which the shuttle acts as an organo-

catalyst. In the latter mechanism, the incorporation of both states of

the shuttle into the simple chemical reaction network promotes

dynamic translocation of the macrocycle between two nitrogen- and

carbon-based stations of the thread, which allows an energetically

uphill esterification process to occur.

Molecular shuttles 20 and 21 were prepared as outlined in

Scheme 8. Threads 18 and 19 were synthesized by standard proce-

dures from diphenyl hydrazodicarboxylate, which was sequentially

aminated with commercially available 2,2-diphenylethylamine or

dibenzylamine and 2,2-diphenylethyl 3-(12-aminododecylcar-

bamoyl)propanoate, which already contains a succinic amide ester

station. The obtained hydrazo compounds, [2H]-18 and [2H]-19,

were dehydrogenated with NBS/Py to form azo threads 18 and 19

in 32 and 51% overall yields, respectively. Compounds 18 and 19

were subjected to rotaxane-forming reagents and conditions (i.e.,

p-xylylenediamine, isophthaloyl dichloride, triethylamine, chloro-

form; 4 h, high dilution) to produce molecular shuttles 20 and 21 in

34 and 45% yields, respectively.

Molecular shuttle 20 was quickly, cleanly, and quantitatively

converted into its hydrazo derivative [2H]-20 by reduction with

hydrazine: hydrogenation was complete in less than five minutes

and a rapid loss of the initial orange color of the azo compounds

was observed concomitant with the translocation of the macrocycle

to the succinic amide ester station.

OOOO

N

N

OOO

CHO

CHO NH3

H3NO

low T

high T

A2

A2

H

+ H2O

H

– H2O

13a,b

14a,b•2H2+

[15a,b•H+]

H

+ H2O

H

– H2O

13a,b:14a,b>95:5 at 373 K

<5:95 at 273 K

fixed

high temperature

low temperature slow shuttling

a:

b:OO

OO

O O

A2


A comparable series of shifts occur in the 1H NMR spectra of

molecular shuttle 21/[2H]-21. The translocation of the macrocycle

is fully reversed upon oxidation with NBS/Py to regenerate the

azodicarboxamide site and trigger ring movement to this station via

biased Brownian motion.

The successful implementation of energy ratchet mechanisms in

molecular-level structures has become essential to the development

of functional molecular machines that are more complex than sim-

ple switches. Thus, a chemically driven machine that works cycli-

cally to generate synthetically useful covalent bonds was designed

as a novel strategy to incorporate a new type of control over the

switching periodicity of the potential energy surface of a bistable

[2]rotaxane. In particular, the Mitsunobu protocol [16] takes ad-

vantage of the transformation of the azodicarboxamide function

PhOHN

NH

OPh

O

O

R1N

HN

NH

NH

HN

OPh

R2

O

O

Ph

O

O

( )7

R1N N

N NH

HN

O

Ph

R2

O

O

Ph

O

O

( )7

R1N N

N NH

HN

O

Ph

R2

O

O

Ph

O

O

( )7

R1N

HN

NH

NH

HN

O

Ph

R2

O

O

Ph

O

O

( )7

[2H]-18: R1 = Ph2CHCH2; R2 = H

[2H]-19: R1 = R2 = PhCH2

18: R1 = Ph2CHCH2; R2 = H

19: R1 = R2 = PhCH2

20: R1 = Ph2CHCH2; R2 = H

21: R1 = R2 = PhCH2

[2H]-20: R1 = Ph2CHCH2; R2 = H

[2H]-21: R1 = R2 = PhCH2

NH

NH

HN

HN

O

O

O

O

NH

NH

HN

HN

O

O

O

O

a,b

c

d

e c

Scheme 8. Synthesis of bistable molecular shuttles based on azodicarboxamide binding sites 7 and 8 and their corresponding 1,2-hydrazodicarboxamides

[2H]-20 and [2H]-21. Reagents and conditions: (a) Ph2CHCH2NH2 or (PhCH2)2NH, Et3N, CHCl3; (b) Ph2CHCH2O2C(CH2)2CONH(CH2)12NH2

(2,2-diphenylethyl-3-(12-aminododecylcarbamoyl)propanoate), Et3N, CHCl3, [2H]-18, 35%; [2H]-19, 54%; (c) NBS, Py, CH2Cl2, 18, 91%; 19, 95%; 20, 86%;

21, 93%; (d) isophthaloyl dichloride, p-xylylenediamine, Et3N, CHCl3, 20, 34%; 21, 45%; (e) N2H4 ·H2O, CHCl3, [2H]-20, 88%; [2H]-21, 92%.


integrated in the thread through the catalytic formation of ester

bonds [15]. During this process, the macrocycle continuously

translocates between the nitrogen- and carbon-based stations as-

sisted by triphenylphosphine, which acts as a chemical activator of

the azo group, and iodosobenzene diacetate, which is a stoichiomet-

ric oxidant of the resulting hydrazo unit (Scheme 9). Fortunately,

molecular shuttle 21 is a successful organocatalyst for the ester

bond formation and gives the product in 65% yield.

Although the hydrogen bonds between the azodicarboxamide

station and the macrocycle persist even in relatively polar solvents

such as THF or acetonitrile [17], these solvents may compete with

the hydrogen-bond donors on the thread. In such cases, the

Brownian macrocycle escapes from the azo station and allows

phosphane attack to form the corresponding Morrison-Brunn-

Huisgen betaine [18] like III (Scheme 9). This betaine was detected

by high-resolution mass spectrometry. The addition of triphenyl-

phosphane to the azodicarboxamide station alters its affinity for the

macrocycle and notably increases the steric bulk between the amide

groups. Accordingly, this intermediate follows the well known

mechanistic pathway of the Mitsunobu reaction to give the ester

and hydrazo [2]rotaxane [2H]-21, which, after in situ reoxidation,

recycles co-conformer 21 using excess bis(acetoxy)iodobenzene;

therefore, the catalytic wheel of ester bond formation is ready to

begin again. From a thermodynamic perspective, it should be noted

that, although the esterification reaction is endergonic, the oxidation

of phosphane promoted by the reduction of the azodicarboxamide

binding site makes the overall process exergonic. In these reaction

conditions, the molecular shuttle operates in a cyclic manner as

long as the fueling chemicals are accessible.

These molecular shuttles operate by two different mechanisms:

(1) a discrete mode through two reversible and independent chemi-

cal events that trigger reduction and oxidation reactions and (2) a

continuous mode via a catalyzed ester bond formation reaction in

which the shuttle acts as an organocatalyst.

Two novel multilevel switchable [2]rotaxanes containing

ammonium and 1,2,3-triazole (TZ) stations have been constructed

using a Cu(I)-catalyzed azide-alkyne cycloaddition reaction [19]

(Schemes 10, 11). In the protonated form, the macrocycle of

[2]rotaxane, which contains a C6-chain bridge between the two

hydrogen bonding stations, exhibits high selectivity for the ammo-

nium cation (Scheme 12). Interestingly, the macrocycle is able to

interact with two recognition stations when the bridge between

them is short. Upon deprotonation of both [2]rotaxanes, the macro-

cycle moves towards the TZ recognition site due to the hydrogen

bond interaction between the TZ nitrogen atoms and the amide

groups in the macrocycle. Upon addition of chloride anions, the

conformation of [2]rotaxane changes because of the cooperative

recognition of the chloride anion by favorable hydrogen-bond do-

nors from both the macrocycle isophthalamide and thread TZ CH

protons (Scheme 13).

TZ, which is generated by a click reaction, is still rare as a mo-

lecular station [20]. In this system, the click reaction is not only a

key step of stopping the reaction but also provides a potential alter-

Bn

N N

N NH

HN

O

Ph

Bn

O

O

Ph

O

O

( )9 Bn

N N

NH

N

HN

O

Ph

Bn

O

O

Ph

O

O

( )9

NH

NH

HN

HN

O

O

O

O

NH

NH

HN

HN

O

O

O

O

PPh3

Bn

N N

NH

NH

HN

O

Ph

Bn

O

O

Ph

O

O

( )9

NH

NH

HN

HN

O

O

O

O

PPh3

Bn

NHN

NH

NH

HN

O

Ph

Bn

O

O

Ph

O

O

( )9

NH

NH

HN

HN

O

O

O

O

PPh3

21

[2H]-21

III

ArCO2H

ROH

ArCO2

PhI(OAc)2

PhI + 2 AcOH

ArCO2R + O=PPh3

Scheme 9. Proposed cyclic chemical functioning of the shuttle 21 by means of an ester bond formation reaction between an acid, ArCO2H (Ar = 4-NO2C6H4),

and an alcohol, ROH (R = C6H5CH2) mediated by a classical Mitsunobu protocol with triphenylphosphane followed by an in situ oxidation of the hydrazo

generated shuttle [2H]-21.


RO

O

Br

OHC

O

OHC

O

ROHBr Br

RO N3

RO NH2

t-Bu

t-Bu

t-Bu

R =

RO NH2

O

O

O

OO

O

O

O

NH

HNO

O

OH

OH

Br

b) NaN3

a)

Pd/C

MeOH/EtOAc

a)b)

a) toluene/reflux b) MeOH/NaBH4

c) CF3CO2H, acetone, then NH4PF6, water

25

26

27

28

29

24

H-22

H-23

N

O

O

O

N

N

N

OR

RO NH2

O

O

O

N

N

N

OR

PF6

PF6

PF6

b c

d

e

f gh

i

jk

l

m

n o

p

HH

OO

O

O

O

NH

HNO

O

25

CH2Cl2

CuBF4(CH3CN)4

A B

C

D E

F

G

H

I

J

K

Scheme 10. Synthesis of H-22 and H-23.


RO

OO

O

O

O

NH

HNO

O

H-22

22

N

O

O

O

N

N

N

OR

RO NH

O

O

O

N

N

OR

PF6

HH

O

O

O

O

O

N

N

O

O

H

N

H

H

CF3CO2H i-Pr2NEt

Scheme 11. Movement process of multistable rotaxane H-22 under acid/base stimuli.

native binding site, which is directly introduced by a coupling pro-

cedure.

The large dipole (5D) of TZ, which is oriented with the positive

end toward the H atom, contributes to its unexpectedly strong hy-

drogen-bonding capabilities.

Shuttle H-22 was synthesized according to Scheme 10. In

CH2Cl2, macrocycle 24 was assembled with monostoppered

ammonium-containing compound 29 to form a pseudorotaxane.

Covalent capture of the threaded intermediate using a click reaction

at room temperature in the presence of [Cu(CH3CN)4]BF4 catalyst

afforded thread H-23 and [2]rotaxane H-22 in 50% and 35% yields,

respectively, after chromatographic column purification.

The position of macrocycle 24 in the rotaxane was determined

by comparing the 1H NMR spectra of the uncomplexed dumb-

bell-shaped thread and the rotaxane since the XYL parts of the

macrocycle shield the encapsulated regions of the thread. The 1H

NMR spectra of thread H-23, rotaxane H-22, and macrocycle 24 in

acetonitrile confirm the interlocked structure. As expected, the pro-

tons adjacent to the ammonium unit are upfield shifted (He: 0.24

ppm; Hd: 0.14 ppm) relative to those in free H-23 due to the aro-

matic shielding effect of the macrocycle, whereas no shifts of the

signals corresponding to the protons near the TZ ring is evident.

This confirms that the macrocycle, 24, in rotaxane H-22 is pre-

dominantly localized on the alkyl ammonium region of the thread

under acidic conditions.

Upon addition of i-Pr2NEt to H-22, the ammonium group is

neutralized, which breaks the hydrogen bonds between the poly-

ether moiety and the ammonium group (Scheme 12). Upon addition

of CF3COOH to deprotonated rotaxane 22, the methylene protons,

Hl and Hn, appear at 4.98 and 4.45 ppm, respectively, while the

signal for the TZ ring resonates at 7.75 ppm; this suggests that 24

shuttles completely to the NH2

+ recognition site following reproto-

nation.

To verify the hydrogen bonding between macrocycle 24 and the

TZ ring, rotaxane H-30, which contains a short bridge between the

two recognition sites, was synthesized using a similar reaction

process (Scheme 11).

Interestingly, in contrast to rotaxane H-22, aromatic shielding

of the proton adjacent to the TZ ring (Hh: 0.25 ppm) in H-30 is

observed. Moreover, the ring amide protons, HD, experience a

downfield shift of 0.25 ppm in H-30 in comparison to 24, which is

ascribed to the formation of hydrogen bonds between the amide

group and the hydrogen-bond acceptor, i.e., the TZ nitrogen atoms.

These features indicate that the isophthalamide group interacts

with the TZ ring to some extent due to the hydrogen bonds between

them. The signals corresponding to the phenylene protons (Hf: 0.3

ppm and Hg: 0.4 ppm) and the macrocycle benzyl groups (HF:

0.21 ppm and HG: 0.31 ppm) experience a significant upfield shift

due to the aromatic shielding between them. Therefore, macrocycle

24 also forms a sandwich structure with the phenylene spacer in

thread H-31 via weak – stacking interactions. Thus, the 1H NMR

spectra support the fact that the isophthalamide group interacts with

TZ while the polyether moiety interacts with the ammonium cation.

Essentially, the macrocycle spans two potential hydrogen-bonding


recognition stations and forms a short bridge between them

(Scheme 13).

Deprotonation of H-30 with i-Pr2NEt resulted in significant

changes to the 1H NMR spectrum in acetonitrile: He was shifted

upfield by 0.46 ppm due to the deprotonation of the neighboring

ammonium center and shuttling of the macrocycle.

Upon addition of CF3COOH to fully deprotonated H-30, the

signals for Hj and the TZ hydrogen, Hi, shift downfield by 0.19 and

0.16 ppm relative to those for the same protons in 30, which indi-

cates that the isophthalamide group of 24 interacts with TZ and the

polyether moiety switches between the two recognition sites via a

de-/re-protonation process. Upon addition of chloride anions in the

form of tetrabutylammonium (TBA) salts to a solution of

[2]rotaxane 30, dramatic changes in the 1H NMR spectrum were

observed. The isophthalamide protons, HC and HD, shift downfield

by 0.68 and 1.54 ppm, respectively, which is due to the formation

of hydrogen bonds between them. The signal for the TZ proton

undergoes a downfield shift of 0.2 ppm due to hydrogen bonding to

the chloride anion. These phenomena are attributed to the coopera-

RO

t-Bu

t-Bu

t-Bu

R =

O

O O

O

O

N

N

O

O

a) toluene/reflux

b) MeOH/NaBH4

c) CF3CO2H, acetone,

then NH4PF6, water

24

H-30

H-31

N

O

NN

N

OR

RO NH2

O

N

N

N

OR

PF6

PF6

b c

d

e

f gh

i

j k

l

H H

OO

O

O

O

NH

HNO

O

25

CH2Cl2

CuBF4(CH3CN)4

A B

C

D E

F

G

H

I

J

K

26

OHC O

O

NH2RO

PF6

H

H

Scheme 12. Synthesis of H-30 and H-31.


tive recognition of the chloride anion by favorable hydrogen-bond

donors from both the macrocycle isophthalamide protons (HC and

HD) and the thread TZ proton. In addition, proton Hh is shifted

downfield by 0.14 ppm relative to the corresponding signal in 30;

however, the signal is still less than 5.12 ppm. This suggests that

the shielding effect of the macrocycle is reduced due to the confor-

mational change upon cooperative recognition of the chloride anion

(Scheme 13).

To demonstrate that chloride anions are the most effective ani-

ons for altering the conformation of 30, the addition of TBA salts of

bromide and iodide anions was also investigated by 1H NMR spec-

tra.

Based on the Job-plot determination of 1:1 binding stoichiome-

try, the association constants for all anions were obtained by fitting

the changes in the chemical shift of proton C to the binding iso-

therm. Accordingly, the strength of anion association increased in

the order of I–<Br

–<Cl

–, which is consistent with the increasing

hydrogen bond–acceptor ability of the anions (I–<Br

–<Cl

–). It also

reflects that the size and shape of the interlocked binding cavity

generated by 30 is ideally matched to the chloride anion. These data

suggest that the macrocycle isophthalamide protons (HC and HD)

and thread TZ proton surround the chloride anion through coopera-

tive hydrogen-bonding interactions, which leads to conformational

alteration of the macrocycle in 30.

Harada et al. reported unprecedented control of the shuttling of

rotors by reeling an axis molecule into the cavity of a host mole-

cule. Thus, a [2]rotaxane was designed with an -cyclodextrin

( -CD) moiety that functions as both a stopper and a rotor [21].

This [2]rotaxane forms a pseudo[2]rotaxane in D2O due to tumbling

of an altropyranose unit of the altro- -CD stopper. The conforma-

tional change of the [2]rotaxane resembles the action of a reel,

which rotates to reel the decamethylene chain into the cavity of the

altro- -CD stopper.

[2]Rotaxane 32 was prepared as outlined in Scheme 14. The

starting material is an axis molecule with an altro- -CD group (al-

tro- -CD stopper) and a stilbene unit linked via a decamethylene

group. This axis molecule undergoes condensation with adaman-

tane carboxylic acid in the presence of the -CD rotor in aqueous

solution to afford the rotaxane products.

The location and direction of the rotor on the axis were deter-

mined using 2D NOESY and 2D ROESY NMR spectroscopy. The

resonance peaks of 32 were assigned using COSY, TOCSY, and

ROESY measurements. When the 1D NMR spectra of [2]rotaxane

and a dumbbell molecule in DMSO-d6 were compared, only the

signals for the protons of the decamethylene group of the

[2]rotaxane were shifted; the protons of the stilbene and adamantyl

groups of the [2]rotaxane did not shift in this solvent. A dumbbell

molecule without a rotor molecule does not show ROE correlation

RO

O

O O

O

O

N

N

O

O

H-30

30

N

O

NN

N

OR

RO NH

ON

NNOR

PF6

H H

H

H

O

O O

O

O

N

N

O

O

HH

RO NH

ON

NNOR

O

OO

O

O

NN

O

O

HH

H

H

Cl

CF3CO2H

i-Pr2NEt

Cl

30-Cl

Scheme 13. Movement process of multistable rotaxane H-30 under different

stimuli.

Scheme 14. Preparation of [2]rotaxanes 32 and 33. DMT-MM = (4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride.


peaks between the inner protons of the altro- -CD stopper and the

protons of the axis group. The 2D ROESY NMR spectrum of 32 in

DMSO-d6 shows no correlation between the protons of the stilbene

group and the inner protons (C3-H, C5-H, and C6-H) of the -CD

rotor. However, the protons of the decamethylene group strongly

correlate to the protons of the -CD rotor. These results indicate

that the decamethylene group was incorporated within the -CD

rotor when [2]rotaxane 32 was dissolved in DMSO-d6.

The 2D NOESY NMR spectrum of 32 in D2O shows a clear

correlation between the C3-H inner proton of the -CD rotor and

protons A and B of the stilbene group adjacent to the decamethylene

group. However, only a weak correlation between the C3-H proton

Scheme 15. Formation of pseudo[2]rotaxane 34 from [2]rotaxane 32 via tumbling an altropyranose unit.

OAc

OAc

AcO

OAcN

N

O

R

N3

t-Bu

t-BuNH2

PF6

PF6+

OAc

OAc

AcO

OAcN

N

O

Rt-Bu

t-Bu

PF6

PF6

N

N

N

O

O

O

O

O

O

O

O

NH2

DB24C8

[Cu(CH3CN)4]PF6

2,6-lutidine

dry CH2Cl2, 24 h, r.t.

35a: R = H

35b: R = Me (50:50 cis/trans)

37a: R = H, 75%

37b: R = Me, 75% (50:50 cis/trans)

36

Scheme 16. Synthesis of rotaxanes 37.


and protons C–F of the stilbene group is evident. The C5-H and

C6-H protons correlate to protons C–E and proton E, respectively.

A correlation between proton F and the protons on the adamantyl

group was also observed. These results suggest that the -CD rotor

is located on the stilbene group and the narrow rim of the -CD

rotor is directed toward the adamantyl stopper. It should be noted

that the inner protons of the altro- -CD stopper show strong corre-

lation to the protons of the decamethylene group. This provides

evidence that [2]rotaxane 32 forms pseudo[2]rotaxane 34 in D2O

through tumbling of the altro- -CD stopper to include the de-

camethylene axis.

The conformational change of 32 via tumbling of an altro-

pyranose unit is shown in Scheme 15. The free activation energy

( G‡

288 K) for the conformational change from 32 to 34 was deter-

mined by observing the time-resolved UV spectral changes for the

process in D2O at 288 K. Assuming a two-site exchange process,

the G‡

288 K value was calculated to be 89.4 kJ·mol–1

using single

exponential fitting. The calculated G‡ value for the tumbling of

the altropyranose residue is higher than the reported value for

calix-[4]arene tumbling ( G‡ = 65.7 kJ·mol

–1) [22]. The glu-

copyranose units of permethylated CDs easily tumble because hy-

drogen bonds between neighboring permethylated glucopyranose

units cannot be formed by the deprotonation of hydroxyl groups. In

contrast, normal glucopyranose and altropyranose units are unable

to tumble easily due to the formation of hydrogen bonds between

neighboring units. Regardless, the G‡ value for this tumbling

process has not yet been determined.

A new class of rotaxanes that incorporate dibenzo[24]crown-8

(DB24C8) as the macrocycle and feature three different molecular

stations, i.e., anilinium, N-methyltriazolium, and either a mono- or a

disubstituted pyridinium amide, in the thread have been reported

[23].

These rotaxanes (37) [23] were synthesized from mono- or di-

substituted mannosyl pyridinium amide azide 35 and ammonium

compound 36 by copper(I)-catalyzed Huisgen alkyne-azide 1,3-

dipolar cycloaddition, which is also known as CuAAC click chem-

istry (Scheme 16). The reaction between DB24C8, azido compound

35, alkyne 36, Cu(CH3CN)4PF6, and 2,6-lutidine was performed in

dichloromethane at ambient temperature over 24 h. In the case of

rotaxane 37b, a 1:1 mixture of two stereoisomers was observed due

to cis/trans isomerism of the disubstituted amide.

A low pH, the macrocycle resides exclusively around the

anilinium moiety. Deprotonation of 37 was executed by adding

excess diisopropylethylamine (DIEA) at room temperature (Scheme

17) and results in a large-amplitude displacement of DB24C8 from

Me

O

OAc

OAc

AcO

OAcN

N

O

Rt-Bu

t-Bu

PF6

PF6

N

N

N

O

O

O

O

O

O

O

O

NH2

37a: R = H

37b: R = Me

O

OAc

OAc

AcO

OAcN

N

O

Ht-Bu

t-Bu

PF6

N

N

N

O

O

O

O

O

O

O

O

NH

38a

37a: R = H, 75%

37b: R = Me, 75% (50:50 cis/trans)

O

OAc

OAc

AcO

OAcN

N

O

Rt-Bu

t-Bu

PF6

PF6

N

N

N

O

O

O

O

O

O

O

O

NH2

Me

PF6

N

NO

Me t-Bu

t-Bu

N

N

N

NH

OAcO

OAc

OAc

AcO

O

OO

O

OO

O

O

O

O

O O

O

O

OPF6

O

OAc

OAc

AcO

OAcN

N

O

Ht-Bu

t-Bu

PF6

N

N

N

NH

Me

PF6

O

OAc

OAc

AcO

OAcN

N

O

Met-Bu

t-Bu

PF6

N

N

N

NH

PF6

O

O O

O

O

OO

O O

1) HCl

2) NH4PF6, CH2Cl2/H2ODIEA 1) HCl

2) NH4PF6, CH2Cl2/H2O

DIEA

1) HCl

2) NH4PF6, CH2Cl2/H2ODIEA

1) HCl

2) NH4PF6, CH2Cl2/H2O

DIEA

38a (50:50 cis/trans)

40b (42:58 cis/trans)40a

1) MeI, 3 d, r.t.

2) NH4PF6, CH2Cl2/H2O, 30 min

4C1

1C4

1

234

5

6

7

8

910

11

12

13

14

15

16

17

18 19

20

21

22

23

24

25

2627 28

29

3033

Scheme 17. Synthesis of 39a,b, and molecular machinery by deprotonation/protonation of rotaxanes 37a,b, and 39a,b.


one end of the molecule to the other. The macrocycle is located

around the mono- or di-substituted pyridinium amide station in 38a

and 38b, respectively (Scheme 17).

The location of the macrocycle around the pyridinium moiety

differs slightly depending on the substitution of the amide. Indeed,

in the mono-substituted series 38a, DB24C8 interacts with H8 and

H11 via hydrogen bonding. However, in the di-substituted series

38b, DB24C8 does not interact with H8; instead, it interacts with

the H7 hydrogen atoms, which are closer to the cationic charge. In

this latter case, flipping of the chair-like mannopyranosyl ring from

the 1C4 to the

4C1 conformation was observed as a result of turning

off the reverse anomeric effect [24].

Subsequently, the introduction of a triazolium moiety between

the two previously studied molecular stations was envisaged. Re-

gioselective N-alkylation of the 1,4-disubstituted TZ moiety with

iodomethane followed by cation exchange provided three-station

triazolium rotaxanes 39a and 39b in 93% and 91% yields, respec-

tively (Scheme 17). Each [2]rotaxane molecular machine, 39a and

39b, contains three different sites for interaction with DB24C8:

anilinium, triazolium, and mono- or disubstituted pyridinium am-

ide.

Upon deprotonation of both rotaxanes 39a and 39b (Scheme

17), the macrocycle is displaced from its initial anilinium position;

however, its behavior differs depending on the degree of substitu-

tion of the pyridinium amide station.

In the di-substituted pyridinium amide series, the molecular

machine behaves as a pH-sensitive bistable [2]rotaxane and the

macrocycle shuttles between the anilinium and triazolium stations.

The macrocycle initially resides around the anilinium station in

39b. After deprotonation, the position of the macrocycle was de-

duced by comparing the 1H NMR spectra of rotaxanes 39b and 40b.

The significant upfield shifts for H25 ( = –1.06 ppm), H28 ( =

–0.88 ppm), and H30 ( = –0.69 ppm) in rotaxane 40b result from

the deprotonation of the anilinium moiety and shuttling of the mac-

rocycle. Concurrently, the signal for H18 is shifted downfield in 40b

( = +0.73 ppm). These two observations unambiguously

demonstrate the ability of rotaxane 40b to behave as a pH-sensitive

bistable molecular machine. After deprotonation, the macrocycle

resides on the triazolium station due to its better binding affinity for

DB24C8 than for the disubstituted pyridinium amide. This study

discussed the higher affinity of DB24C8 for triazolium than for the

disubstituted pyridinium amide station.

Similarly, in the mono-substituted pyridinium amide series, the

macrocycle initially resides on the anilinium station in protonated

rotaxane 39a; however, the macrocycle shuttles very differently

after deprotonation. The shuttling in rotaxane 40a at room tem-

perature results in a degenerate molecular machine: the macrocycle

continuously oscillates between the triazolium and monosubstituted

pyridinium amide stations. This result suggests a similar affinity of

the two stations for DB24C8. This is in contrast to rotaxane 40b,

which features a disubstituted pyridinium amide, wherein the mac-

rocycle shuttles around the sole triazolium station.

Kinetic and thermodynamic studies demonstrated that the two

translational isomers have very similar free enthalpy values at room

temperature. However, lowering the temperature increases G and

thus forces DB24C8 to reside more frequently around the energeti-

cally favorable pyridinium amide station. Around 223 K, oscillation

between the two stations ceases and DB24C8 is located primarily

around the monosubstituted pyridinium amide station, as in a bista-

ble molecular machine.

Additionally, hydrogen-bonding interactions between DB24C8

and the monopyridinium amide station in the deprotonated rotaxane

impair the rotation of the threaded pyridinium amide bond, i.e.,

DB24C8 acts as a molecular brake (Fig. 5).

Finally, the implementation of molecular rotaxanes for the gen-

eration of controllable nanostructures was reported [25]. This is

important to better understand the solid-state applications of mo-

lecular shuttles.

[2]Rotaxane 47 was prepared by Li et al. [25] according to

Scheme 18. The tetracyanobutadiene (TCBD) unit was chosen as

the stopper and aggregation core because its derivatives easily form

regular nanostructures due to intermolecular dipole–dipole interac-

tions [26]. Thread 46 was prepared in a high yield using a

[2+2]cycloaddition reaction that occurs at room temperature and in

apolar solvents without the help of a catalyst, which was developed

Diederich [27]. The treatment of 46 with p-xylylene diamine and

highly diluted isophthaloyl dichloride provided 47 in 5% yield. The

low yield of this process is ascribed to the weaker interactions be-

tween the peptide units and macrocycle precursors in the clipping

process: the less electron-donating aniline N-atom significantly

reduces the hydrogen-bond accepting ability of its adjacent car-

bonyl group.

The position of the macrocycle was determined by comparing

the chemical shifts of the protons in the rotaxane with those in the

corresponding thread. The 1H NMR spectra of thread 46 and rotax-

ane 47 confirm the interlocked structure and show that the macro-

cycle is primarily localized on the peptide region of the thread of 47

(Scheme 18).

When CD3OD is added to a CDCl3 solution of 47, minor

changes occurred in the 1H NMR spectrum. The methylene reso-

nances of the Hd and Hf protons of the peptide station have the same

chemical shifts as those in neat CDCl3, which indicates that the

macrocycle still resides at the peptide station in CDCl3/CD3OD

(1/1, v/v). This suggests that the intramolecular hydrogen bonds

Fig. (5). Schematic representation of the role of DB24C8 as a molecular brake for rotation of the C9–C10 bond in a) uncomplexed 39a, b) 38b, and c) 38a and

40a.

+ Py + Py+ Py

C7 C8

C9C10

O10

N11

Fast motion Fast motion Slow motiona) b) c)

Molecular brake


between the macrocycle and the peptide are stronger than the in-

termolecular hydrogen bonds between the peptide and CD3OD.

This is attributed to the excellent fit between the thread and macro-

cycle in terms of both the steric interactions and complementary

positioning of the hydrogen-bonding amide groups on the two

components.

The macrocycle can be dissociated from the peptide by

dissolving the rotaxane in a highly polar solvent: the solvent

solvates the hydrogen-bonding sites of the macrocycle and peptide

and breaks the intramolecular hydrogen bonds. In the DMSO-d6

solvent, the methylene resonances of Hf and Ho experience a sig-

nificant upfield shift of 0.52 and 0.51 ppm, respectively, and the

signals assigned to the alkyl chain exhibit a clear upfield shift,

which could be attributed to the shielding effect of the macrocycle.

The signal for Hd in 47 remains at the same chemical shift as in 46.

All these features indicate that the macrocycle departs from the

peptide station and resides on the alkyl chain in DMSO (Scheme

19).

The aggregation of 46 and 47 in different solvents was

determined to demonstrate the effect of the shuttling of the macro-

cycle on the aggregation behavior. One drop of solutions of 46 and

47 in different solvents was evaporated on silicon slides to assess

RNH2

Ph

Ph

Ph

Cl

O

Cl

I OH

NMe2

NH2

H2N

Cl Cl

OO

CNNC

NC CN

1)

2)

PPh3

THF/H2ONaN3

R

NH

O

N3 R

NH

O

NH2

R

NH

O

HN

O

O I( )

10

R

NH

O

HN

O

Br( )

10

Br(CH2)10CO2H

EDC, DMAP

RNH

O

HN

O

NMe2O

NH

O

HN

O

NMe2

O

NC

CN

CN

NC

Pd(PPh3)4

CuI

R

NH

O

HN

O

NMe2

O

NC

CN

CN

NC

41 42

4344

45

46

47

R =

NH

NH

HN

HN

O

O

O

O

R

a b

cd

ef

g

h

i

j

k

l

m

n

o p q

r st

u

v

w

x

y

z

Scheme 18. The synthesis route of 46 and 47.


the nanostructures in the solid state. The morphologies of the ag-

gregates of 46 and 47 on the substrate were examined by scanning

electron microscopy (SEM) (Fig. 6). Figs. 6a and 6b show the typi-

cal morphologies of the 46 and 47 nanostructures formed in a

CHCl3/n-C6H14 (1:1, v/v) solvent, which was used to facilitate

molecular aggregation. The addition of n-C6H14 to a CHCl3 solution

does not affect the location of the macrocycle because it has a lower

polarity. Large-scale spherical particles with uniform diameters of

about 300 nm and interlaced fibers were observed for 46 and 47,

respectively. Figs. 6c and 6d present the morphologies of the 46

and 47 nanostructures formed in a CHCl3/MeOH (1;1, v/v) solvent.

Spherical nanoparticles with diameters of about 500 nm were ob-

served for 46 and 47.

Interestingly, most of the particles feature open holes on their

surfaces, which indicates that they may have hollow interiors. The

wall thicknesses of the vesicles of 46 and 47 were estimated to be

about 100 nm. This is sufficient to contain approximately 12 bilay-

ers with molecular dimensions of 4 nm, as estimated by 3D mo-

lecular structural modeling of 46 and 47. These results indicate that

the membrane structures of the hollow spherical vesicles of both 46

and 47 in methanol are most likely shell-like complex multilayer

structures. In DMSO, nanobundles and worm-like nanoparticles

were observed for 46 and 47, respectively, as shown in Figs. 6e and

6f.

UV-Vis absorption spectra provide information on the mecha-

nism of the formation of the nanostructures. Dilute CHCl3 solutions

of 46 and 47 display two intramolecular charge-transfer (ICT)

bands centered at 384 and 470 nm. When 46 and 47 aggregate into

stable and well-suspended nanostructures in CHCl3/hexane (1:1,

v/v), the two ICT bands of 46, which are assigned to the TCBD

unit, undergo a bathochromic shift to 389 and 480 nm while those

of 47 undergo a bathochromic shift to 389 and 490 nm. These

red-shifted absorption spectra indicate that J-type aggregation

occurs in both compounds; the larger bathochromic shift of 47 in-

dicates that its nanoaggregates feature more extended or ordered

stacking. In CHCl3/MeOH (1:1, v/v), the first ICT band of both 46

and 47 exhibits a blue-shift of 5 nm compared with those in CHCl3

while the second ICT bands of both 46 and 47 remain at the same

position as those in CHCl3. These results suggest that 46 and 47

experience similar H-type aggregation under these conditions. To

study the aggregation behavior of 46 and 47 in DMSO, a mixed

solvent of DMSO/H2O (1:1, v/v) was adopted to facilitate

aggregation. The absorption spectrum of 46 was red-shifted by 8

nm compared to that of 47 and high energy tails were evident only

in the spectrum of 46, which suggests that the nanoaggregates of 46

have more extended or ordered stacking under these conditions.

Additionally, the spectra of 46 and 47 in DMSO/H2O (1:2, v/v) are

similar to those in DMSO/H2O (1:1, v/v), which indicates that 46

and 47 are fully aggregated in DMSO/H2O (1:1, v/v).

To elucidate the distinct morphologies of 46 and 47 in different

solvents, a mechanism that correlates the molecular structures with

the morphologies of the nanostructures is proposed. In 47, the mac-

rocycle resides in the peptide station, which obstructs hydrogen

bonding between the peptide and TCBD. Additionally, molecules

RNH

O

HN

O

NMe2

O

NC

CN

CN

NC

NH

NH

HN

HN

O

O

O

O

R

NH

O

HN

O

NMe2

O

NC

CN

CN

NC

NH

NH

HN

HN

O

O

O

O

MeOH or

CH2Cl2DMSO

Scheme 19. The shuttling movement process of 47 in different solvents.


of 47 exhibit linear structures in solution, which facilitates the ag-

gregation of the TCBD units. The extended intermolecular di-

pole–dipole interactions between TCBD units induce 1D molecular

stacking. As a result, the TCBD units in rotaxane 47 aggregate in an

orderly fashion to form 1D nanofibers. For the formation of hollow

vesicle structures, the coexistence of hydrophilic and hydrophobic

units in a single low weight molecule or blocks with different solu-

bilities in copolymers or codendrimers are considered essential

[28]. For 46 and 47, the hydrophobic tetraphenyl unit and long alkyl

chain at one end of the molecule favor the non-polar CHCl3 solvent

while the other end favors the polar MeOH solvent due to the pres-

ence of a TCBD moiety, which is polar as a result of the in-

tramolecular charge transfer [27]. Accordingly, in the combined

solvent system, 46 and 47 are amphiphilic molecules that can as-

semble into layered structures that close to form vesicles. In

DMSO, all intramolecular hydrogen bonds are broken because of

the high polarity of the solvent; therefore, the only driving force for

aggregation is the dipole–dipole interactions of the TCBD units.

However, in 47, the macrocycle moves along the long alkyl chain

and hinders these interactions. Upon evaporation of the solvent, the

van der Waals driving forces between the independent molecules

induce the formation of disordered worm-like nanoparticles.

PHOTOCHEMICALLY POWERED MOLECULAR

SWITCHES

Degenerate [2]rotaxanes, which feature two identical binding

sites, generally exhibit equilibrium dynamics and have free energies

of activation ( G‡) for the shuttling process as low as 10 kcal mol

–1

[29]. This G‡ value can be significantly increased by inserting

“speed bumps” in the form of steric [30] and/or electrostatic [31]

barriers into the linkage between the two identical binding sites.

Stoddart et al. demonstrated that light can be used in conjunc-

tion with thermal energy to raise and lower the free energy barrier,

thus imparting STOP and GO instructions to the molecular shuttle

[32].

This shuttle was based on a 4,4 -azobiphenyloxy (ABP) unit

that acts as a binding site for a tetracationic cyclobis(paraquat-p-

phenylene) (CBPQT4+

) ring. Independently, four methyl groups and

four fluorine atoms were introduced at the 3,5,3 ,5 -positions of the

ABP unit to curtail binding by the CBPQT4+

ring via steric and

electronic interactions, respectively. The first approach forms a gate

(i.e., ABP-Me4) that remains closed, whereas the second approach

affords a gate (i.e., ABP-F4) that closes and opens upon irradiation

with UV light and visible light, respectively. The ABP-F4 gate can

also open in response to thermal energy in its surroundings.

Fig. (6). SEM images of 46 nanoscale aggregates in CHCl3/n-C6H14 (1:1, v/v) (a), in CHCl3/MeOH(1:1, v/v) (c), and in DMSO (e). The SEM images of 47

nanometer-scale aggregates in CHCl3/n-C6H14 (1:1, v/v) (b), in CHCl3/MeOH (1:1, v/v) (d), and in DMSO (f). The insets in (c) and (d) are the corresponding

TEM images.


Scheme 20.

The syntheses of degenerate [2]rotaxanes trans-48·4PF6 and

trans-49·4PF6 are outlined in Scheme 20. Azide 50, which incorpo-

rates a 1,5-dioxynaphthalene (DNP) unit in the middle of an oligo

ether chain that is capped with a 2,6-diisopropylphenyl stopper and

an azide moiety, was obtained in a high yield in three steps starting

from the known monotosylate of 1,5-bis[2-(2-(2-(2-hy-

droxyethoxy)ethoxy)ethoxy)ethoxy]-naphthalene (BHEEEEN).

Tetramethylazobenzene derivative 51 was produced by reductive

coupling of 3,5-dimethyl-4-propargyloxynitrobenzene in 23% yield

using LiAlH4 as the reductant while tetrafluoroazobenzene deriva-

tive 52 was prepared from 3,5-difluoro-4-methoxyaniline and 2,6-

difluorophenol in three steps. Degenerate [2]rotaxanes trans-

48·4PF6 and trans-49·4PF6 were isolated in 68% and 55% yields,

respectively, following the reaction of 50 with the appropriate

azobenzene derivative, 51 or 52, in Me2CO via copper(I)-catalyzed

azide-alkyne cycloadditions in the presence of CBPQT·4PF6.

The absorption spectra for the * and n * bands of 51

( max = 345 and 437 nm, respectively) and 52 ( max = 340 and 437

nm, respectively) were recorded in MeCN at room temperature.

For comparison, the absorption spectra of 4,4 -dimethoxydiazo-

benzene, BHEEEEN, and CBPQT·4PF6 feature max values of 355,

295, and 260 nm, respectively, in MeCN. The fluorine substituents

on the azobenzene ring system in 52 cause a 15 nm hypsochromic

shift; similar behavior was observed for the methyl-substituted

derivative 51. Irradiation of the two ABP derivatives with UV light

( = 365 nm, 7 mW·cm–2

) caused efficient photoisomerization to

give the corresponding cis isomers of 51 and 52 almost quantita-

tively. The trans configurations were restored upon irradiation with

visible light. 1H NMR spectroscopic investigations in CD3CN re-

vealed that the CBPQT4+

ring prefers to reside on the DNP units

rather than on the ABP-Me4 or ABP-F4 units in both trans-48·4PF6

and trans-49·4PF6. The 1H NMR spectra of trans-48·4PF6 recorded

in CD3CN within the temperature range of 238–350 K show that the

CBPQT4+

ring resides exclusively on one of the two degenerate

DNP units, i.e., shuttling is not occurring on the 1H NMR time scale

even at 350 K. This implies that the free energy of activation re-

quired for shuttling in trans-484+

is in excess of 30 kcal·mol–1

. In

contrast, the 1H NMR spectra of trans-49·4PF6 recorded in CD3CN

in the range of 238–350 K feature temperature-dependent

resonances corresponding to the CHMe2, CHMe2, and TZCH2O

protons which undergo coalescence at temperatures (Tc) of 309,

322, and 311 K, respectively. The rate constants (kc) and corre-

N

N

O

N

N N

OOOO

OOOOO

O

N

NN

O O O O

O O O O O

N

N

N

N

N

N

N

N

N

N

O

O

N

N

O

O

N

N

O

N

N N

OOOO

OOOOO

O

N

NN

O O O O

O O O O O

N

N

N

N

Me

Me

Me

Me

Me

Me

Me

Me

F

F

F

F

F

F

F

F

O O O O

O O O O O

N3OOOO

OOOOO

N3

Cu(MeCN)4PF6

TBTA/Me2CO

24 h/r.t.

51

52

50 50

Cu(MeCN)4PF6

TBTA/Me2CO

24 h/r.t.

CBPQT•4PF6

CBPQT•4PF6

trans-48•4PF6 (68%)

trans-49•4PF6 (55%)

4PF6

4PF6

4PF6


sponding G‡

c values calculated at these temperatures are listed in

Table 1. At 15.6 kcal·mol–1

, the free energy of activation ( G‡

c) for

the shuttling process is similar in magnitude to the G‡

c values

observed for other degenerate molecular shuttles [33] where the

links between the two identical recognition units are, for example,

polyether chains or terphenyl linkers. The 1H NMR spectrum of

trans-49·4PF6 recorded at 309 K showed that the Tc of the HCHMe2

probe protons dramatically changed upon irradiation with UV light

for 14 min. New well-resolved signals appeared for cis-494+

indi-

cating that the cis configuration of the ABP-F4 gate stops the shut-

tling of the CBPQT4+

ring.

In the 1H NMR of cis-49

4+, the two singlets at 5.16 and 5.22

ppm and two doublets at 1.13 and 1.17 ppm, which correspond to

the TrCH2O and CHMe2 protons, respectively, indicate that the

CBPQT4+

ring resides on only one of the two DNP units along the

dumbbell component. Irradiation of cis-494+

with a halogen lamp

for 20 min effected an 80% reversion to trans-494+

; its characteris-

tically broad resonances are commensurate with slow shuttling of

the CBPQT4+

ring at 309 K on the 1H NMR time-scale. By

alternatively irradiating gate 494+

with UV and visible light to

switch between its trans and cis isomers, the shuttling of the

CBPQT4+

ring undergoes a repeating STOP-GO sequence. Com-

plete isomerization of cis-494+

back to its trans isomer can also be

achieved by heating cis-49·4PF6 at 350 K for 60 min. An alternating

process of UV light and heat can also be applied.

The rate of the thermal gate-opening process at 350 K was de-

termined using 1H NMR spectroscopy. The first order rate constant,

kc t, was determined to be 0.124 s–1

at 350 K, which results in a

G‡ value of ca. 22 kcal·mol

–1. This free energy barrier is consis-

tent with cis-to-trans thermal relaxation of electron-deficient

azobenzene derivatives [34] including that of the corresponding

dumbbell, which was found to be ca. 20 kcal·mol–1

, as determined

from the kc t value of 0.098 s–1

at 350 K.

Tian et al. [35] designed a novel thermo- and photo-driven

[2]rotaxane, (Z)-60, comprising two fluorescent groups, i.e., por-

phyrin and fluorene, which are used as stoppers at the two ends of

the dumbbell, and two stations, i.e., fumaramide and succinimide,

which are inserted on the thread; the double bond of the fumara-

mide station undergoes photo-isomerization. Finally, two symmet-

rical reactive points such as alkyne groups are situated on the ring

of the rotaxane and are ideal for further substitution. With the active

alkyne groups appended on the ring, different compounds can be

introduced by, e.g., “click” reactions and Sonogashira coupling, to

change the optical properties of the porphyrin and fluorene moieties

on the thread. Additionally, the two symmetrical alkyne groups can

undergo polymerization.

The synthesis of thread 59 in the Z form is shown in Scheme

21. 5-(4-Aminophenyl)-10,15,20-triphenyl-porphyrin (53) reacts

with succinic anhydride to obtain succinic derivative 54. Derivative

54 is coupled with (8-amine-oxtal)-carbamic acid tert-butyl ester

(55) using EDCI/DMAP. After deprotection, the tert-butyl ester is

transformed to a free amine, which finally couples with fluorene

derivative 58.

Rotaxane (Z)-60 was assembled by slow addition of isophtha-

loyl chloride and p-xylylenediamine in the presence of Et3N

(Scheme 21). Since the double bond of the fumarimide is in the Z

form, this structure could not form hydrogen bonds with the ring

[17]. Therefore, the ring of rotaxane (Z)-60 resides on the suc-

cinimide group, which is close to the porphyrin part and distant

from the fluorene moiety. The E form of the fumarimide portion of

the thread is more suitable to form hydrogen bonds with the ring

[17] so the ring shuttles from the porphyrin to the fluorene.

Comparison of the 1H NMR spectra of rotaxanes (E)-60 and

(Z)-60 with their respective threads, (E)-59 and (Z)-59, reveals the

location of the ring on the thread. The 1H NMR spectrum of rotax-

ane (Z)-60 in CDCl3 features an upfield shift of the protons of the

succinimide moiety from 3.30 (Hi) and 2.70 (Hj) ppm to 1.90

and 1.88 ppm, respectively, compared with the same protons in

(Z)-59. This effect was observed due to shielding of the benzyl

aromatic rings on the macrocycle over the thread. A shift of the

amide protons near the succinimide moiety to the aromatic region,

i.e., from 6.10 (He) and 5.95 (Hf) ppm to 7.00 and 6.58 ppm,

respectively, was observed in the spectrum of rotaxane (Z)-60 in

CDCl3; this is caused by hydrogen bonding with the ring. Mean-

while, the signals corresponding to Ha, Hb, Hg, and Hh, which are

associated with the fumaramide potion, did not shift. These results

prove that the macrocycle of rotaxane (Z)-60 resides on the suc-

cinimide moiety. In contrast, the differences in the 1H NMR spectra

of (E)-59 and (E)-60 are opposite to those described above for

(Z)-59 and (Z)-60. This confirms that the macrocycle of rotaxane

(E)-60 resides on the fumaramide moiety. Additionally, there are no

differences among the absorption and fluorescent spectra of rotax-

anes (Z)-60 and (E)-60 and their threads, (Z)-59 and (E)-59, in

CH2Cl2.

Using thread (Z)-59 and exchanging the shuttling macrocycle

with a benzylic-amide macro-ring incorporating two Py groups, the

same authors exploited the properties of the porphyrin moieties to

coordinate with a variety of metal ions. By synthesizing an inter-

locked molecule that is able to interact with the Py groups of an-

other rotaxane monomer via intermolecular metal coordination, a

self-organized rotaxane nanostructure was achieved [36].

This molecular shuttle, (Z)-61, was prepared in 25% yield from

thread (Z)-59 (Scheme 22) and then converted into (E)-61 by heat-

ing. This compound can reconvert to (Z)-61 by irradiation at 254

nm. The addition of Zn2+

to a solution of rotaxane (Z)-61/(E)-61

leads to the replacement of the central hydrogen atoms in the por-

phyrin moiety with the metal center. Thus, the zinc porphyrin moi-

ety of one rotaxane monomer axially connects to a pyridyl unit of

another monomer. Since there are symmetrical pyridyl moieties on

either side of the macrocycle, the self-assembled supramolecular

structure extends to form a large network.

Table 1. Kinetic and Thermodynamic Parameters Obtained from Temperature-Dependent 1H NMR Spectra of Degenerate [2]Rotaxane 49·4PF6

Recorded in CD3CN.

Proton (ppm) (Hz) kc (s–1

) Tc (K) G‡ (kcal·mol

–1)

c

HCHMe2 3.35 86 191 322a 15.6

HCHMe2 1.18 31 69 309b 15.5

HTrCH2O 5.36 25 56 311b 15.7

a Calibrated using neat ethylene glycol. b Calibrated using neat MeOH.

c Value ±0.1.


R NH2

N

NH N

HN

Ph

Ph

Ph

NH

O

OH

O

R NH

O

HN

O

( )6

R

OO O

i

HN BOC

H2N ( )6 NH

BOC

ii

R NH

O

HN

O

( )6

NH2

R

NH

O

HN

O

( )

HN

6

O

O NH

OH

O

O

NH

( )6

( )6

( )6

( )6

iii

R =

R

NH

O

HN

O

( )

HN

6

O

O

NH

( )6

( )6

iv

v

vi

R

NH

O

O

( )

HN

6

O

O NH

( )6

( )6

R

NH

O

HN

O

( )

O

O

NH

( )6

( )6

v

vi

O

Cl

O

Cl

O

vii

HN

HN

NH

NH

O

O

O

O

O

O

NH

NH

HN

HN

O

O

O

O

O

O

HN

HN

53 5455

56

57

58

(Z)-59 (E)-59

(Z)-60 (E)-60

a

bc de

f g

h

i

j

6

Scheme 21. Synthesis of bistable rotoxanes (Z)-60 and (E)-60. Reagents and conditions: (i) CHCl3/Et3N, room temperature, 95%; (ii) DMAP, EDCI, CHCl3, 0

°C, 65%; (iii) trifluoroacetic acid, CH2Cl2, room temperature, 99%; (iv) DMAP, EDCI, CHCl3, 0 °C, 35%; (v) 1,1,2,2-tetrachloride ethylene, 400 K, 50%; (vi)

CH2Cl2, 254 nm, 30%; (vii) p-xylylenediamine, Et3N/CHCl3, 0 °C, 8%; DMAP = 4-dimethylaminopyridine, EDCI =

1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride, Boc = tert-butoxycarbonyl.


N

NH N

HN

Ph

Ph

Ph

i

ii

R2

NH

O

HN

O

( )

HN

6

O

O NH

( )6

( )6

iii

R1 =

R2

NH

O

HN

O

( )

HN

6

O

O

NH

( )6

( )6

R1 or R2

NH

O

O

( )

HN

6

O

O NH

( )6

( )6

R1 or R2

NH

O

HN

O

( )6

O

O

NH

( )6

( )6

HN

HN

NH

NH

O

O

N

N

O

O

NH

NH

HN

HN

O

O

N

N

O

O

HN

HN

(Z)-59-Zn (E)-59-Zn

(Z)-61; R1

(Z)-61-Zn; R2

i

ii

i

ii

(Z)-59 (E)-59

N

N N

N

Ph

Ph

PhR2 = Zn;

(E)-61; R1

(E)-61-Zn; R2

Scheme 22. Synthesis of bistable rotaxane (Z)-61/(E)-61. (i) 400 K, 51/49 for (E)-59/(Z)-59 and 43/57 for (E)-61/(Z)-61 in 1,1,2,2-tetra-chloride ethylene; (ii)

254 nm, 25/75 for (E)-59/(Z)-59 and 18/82 for (E)-61/(Z)-61 in CH2Cl2; (iii) p-xylylene diamine, 3,5-pyridinedicarbonyl dichloride, Et3N/CHCl3, 0 °C, 25%.

Rotaxane (E)-61 was obtained in 43% yield by thermal iso-

merization of rotaxane (Z)-61 at 400 K in 1,1,2,2-tetrachloride eth-

ylene. Photoisomerization of rotaxane (E)-61, which was achieved

via irradiation at 254 nm, furnished 18% yield of (Z)-61.

After replacing the hydrogen atoms of the porphyrin moiety

with the zinc ion to form (E)-61-Zn and (Z)-61-Zn, the 1H NMR

signals broaden and the spectra were quite different from those of

the corresponding monomers. The protons of the benzylic amide

macrocycle, especially the HA protons on the Py groups, underwent

a significant upfield shift due to the shielding effects of the zinc

porphyrin, which attaches to the macrocycle ring. These changes

confirmed that the zinc porphyrin stopper of one rotaxane monomer

was axially connected to the pyridyl unit of another.

Furthermore, the optical properties of (E)-61-Zn and (Z)-61-Zn

were investigated with respect to those of their reference threads

(E)-59-Zn and (Z)-59-Zn. It is interesting that the fluorescence of

the metalized (E)-61/(Z)-61 assemblies was red-shifted as compared

to that of (E)-59-Zn/(Z)-59-Zn due to the formation of self-

assemblies of the rotaxane monomers. It is also notable that

assembled rotaxane (Z)-61 displays much stronger fluorescence

than (Z)-59-Zn. This suggests that the fluorescence of (Z)-59-Zn is

weaker due to the intermolecular – stacking of the porphyrin

zinc(II) moieties. Accordingly, the fluorescence intensifies when

the porphyrin zinc(II) segments are primarily axially coordinated to

the pyridyl residues via complexation and the – stacking of the

porphyrins is eliminated.

The interior morphologies of the metalized rotaxane (E)-61 and

(Z)-61 assemblies were studied using SEM. The leaner rotaxane

monomer, i.e., (E)-61, self-aggregates to some extent to form the

rod structures observed in Fig. 7A. On the other hand, annular

structures were formed by the self-aggregation of curly monomer

(Z)-61 (Fig. 7C). This reveals that both conformations of the two

isomers of the rotaxane form self-aggregated structures, which may

be the result of intermolecular H–H bonding and – stacking of

the chromophores at the two ends of the thread subunit. The

coordination-driven self-organization process of the rotaxane

monomers occurs after mixing zinc(II) ion with the rotaxane at a

1:1 molar ratio, which corresponds to the formation of axle-


macrocycle-type nanostructures. Fig. 7B shows the SEM image of

the self-organization of rotaxane (E)-61 after metal coordination: a

regular formed network is clearly evident.

The average diameter of a single annular cavity is ~120 nm

while the width of the edge of the hole is estimated to be ~20 nm,

as observed using SEM. However, the organization of metalized

rotaxanes (Z)-61 and (E)-61 differs.

Fig. 7D shows SEM images of rotaxane (Z)-61 after

metalization, which demonstrate an irregular assembly rather than

networks. The self-organized morphology is an enlarged result,

which also reflects the significant influence of the conformational

structures of the rotaxane monomers on the integrative morphology

of the nanostructure as a result of the axle-macrocycle-type coordi-

nation. Linear (E)-61 is prone to form small networks while the

structurally curly (Z)-61 forms block structures.

ELECTROCHEMICALLY CONTROLLABLE BISTABLE

ROTAXANES

The first molecular shuttle with three distinct stations was re-

ported by Sauvage et al. [37] (Scheme 23). In their paper, they

demonstrated that the introduction of a 2,2 -bipyridine (BIPY) sta-

tion between the two terminal chelating groups results in much

faster gliding motion of the metal-complexed ring. In this three-

station system, the distance between the terminal stations is ap-

proximately 23 Å. The chelating units on the axis are 2,9-diphenyl-

1,10-phenanthroline (DPP), BIPY, and 2,2 ,6 ,2 -terpyridine

(TERPY), which is a tridentate ligand. The ring includes an 8,8 -

diphenyl-3,3 -biisoquinoline (DPBIIQ) bidentate ligand. This en-

docyclic, non-sterically bulky chelate is a key component that fa-

vors fast translational or rotational motions within shuttle-like ro-

taxanes or pirouetting systems, respectively. The principle of

electrochemically driven motion relies on the relative stabilities of

the copper(I) and copper(II) complexes formed with the various

ligands.

The thermodynamic stability of copper(I) complexes increases

in the following order: [Cu(TERPY)(DPBIIQ)]+<[Cu(BIPY)

(DPBIIQ)]+<[Cu(DPP)(DPBIIQ)]

+. The stability sequence is re-

versed for copper(II) complexes. The relative stabilities of the com-

plexes within these two sequences reflect the electrochemical prop-

erties of the complexes and, in particular, their redox potentials.

Upon oxidizing or reducing a given thermodynamically stable

state, the complex switches from one form to another to attain the

most stable form of the compound, i.e., [Cu(DPP)(DPBIIQ)]+ (four-

coordinate) for the reduced state or [Cu(TERPY)(DPBIIQ)]2+

(five-

coordinate) for the oxidized state. The general principle of the shut-

tling rotaxane is represented in Fig. (8).

This system was further studied using cyclic voltammetry (CV).

By varying the potential scan rate, the rate constant for the rear-

rangement of four-coordinate 62(4)

2+ to five-coordinate 62(5)

2+ was

estimated to be 0.4 s–1

. Accordingly, an upper value of 50 s–1

was

estimated for the conversion of five-coordinate 62(5)

+ to four- coor-

dinate 62(4)

+ (Scheme 23). The rates of the translational motion over

a distance of 23 Å compare favorably with those of other related

shuttles with shorter distances. This illustrates the importance of the

intermediate energy states provided by appropriate ligands.

Fig. (7). Scanning electron micrograph of the rotaxane (E)-61 before (A) and after (B) metalization by adding zinc acetate; (Z)-61 before (C) and after (D)

metalization by adding zinc acetate.


O

N N

O O

OO

62(4)+

O

OO

O

(p-But-C6H4)3C N N

N

N N

OO

O

O

(p-But-C6H4)3C

Cu

N

N

62(5)2+

O

OO

O

(p-But-C6H4)3C N N

N

N N

OO

O

O

(p-But-C6H4)3C

N

N

N

N

OO

O

Cu2

+ e – e

Scheme 23. Structures of the four-coordinate Cu(I) [62(4)

+] and five-coordinate Cu(II) [62(5)

2+] molecular shuttles in their thermodynamically stable forms. The

subscripts 4 and 5 indicate the coordination number of the copper center, excluding possible solvent molecules or counterions.


Fig. (8). Principle of the electrochemically driven molecular shuttle based on copper(I) and copper(II) coordination.

Redox-responsive bistable [2]rotaxanes incorporating CD rings

have been investigated [38] as they might be able to interface with

redox-active enzymes or even act as switching components in im-

plantable medical devices. Accordingly, bistable [2]rotaxane 65

[38], which features an -CD ring that moves in response to the

redox properties of a tetrathiafulvalene (TTF) unit located in the

dumbbell component, was obtained from aqueous solution (Scheme

24). The synthesis employs a recently developed thread-

ing-followed-by-stoppering approach [39] that relies on the effi-

ciency of copper(I)-catalyzed azide-alkyne cycloaddition.

1H NMR and UV-vis spectroscopy in conjunction with CV and

induced circular dichroism (ICD) experiments were employed to

show that the TZ ring, which is installed during the synthesis of 65,

serves as a second station for the -CD ring when the TTF unit,

which is the preferred location for the -CD ring, is oxidized either

to a radical cation or to a dication. According to the ICD spectrum

of 65, which reveals a positive Cotton effect peak around the ab-

sorption band of the TTF unit, the latter is included in the cavity of

the -CD ring [40].

The oxidization of 65 by the addition of Fe(ClO4)3 solution was

monitored by UV-vis spectroscopy. The peak for the TTF unit at

457 nm shifts to 432 nm after the addition of the oxidant (0.2

equiv), which indicates that the -CD ring moves away from the

TTF unit immediately after oxidation. A peak at 595 nm, which

indicates the presence of the TTF·+

radical cation in the [2]rotaxane

[41], emerges after the further addition of Fe(ClO4)3 (0.2–1.0

equiv).

CV experiments on both 65 and 68 demonstrate that 68 exhibits

two one-electron reversible oxidation processes at +0.17 and +0.54

V for the first and second oxidization peaks of the TTF unit, respec-

tively. In contrast, in the spectrum of 65, the first oxidization peak

for shifts dramatically to +0.32 V, whereas the second oxidization

peak is at +0.55 V, which is very similar to that observed for the

dumbbell. These results support those obtained using UV-vis spec-

troscopy, i.e., the -CD ring moves away from the TTF unit of the

[2]rotaxane upon generation of the TTF·+

radical cation.

In the reducing cycle, the first reduction peaks of the TTF2+

di-

cation at +0.46 and +0.48 V for 65 and 68, respectively, are at very

similar voltages. The difference between the second reduction

peaks for 65 and 68 of 0.14 V suggests that the -CD ring is already

sufficiently close to the TTF unit in the [2]rotaxane to influence the

reduction of the TTF·+

radical cation back its neutral form. The -

CD ring might also facilitate the desolvation of the TTF·+

radical

cation in aqueous solution [42]. This dynamic property affects the

design, synthesis, and fabrication of nanoscale systems and devices.

These findings have implications for the production of mechanized

nanoparticles for drug delivery systems that exploit the unique re-

dox states that are often present within diseased cells but not in

healthy cells.

To further elucidate the details of the mechanism in this redox

switchable molecular shuttle, a theoretical free-energy profile ap-

proach from all-atom molecular dynamics simulations was con-

ducted [43]. Employing an umbrella sampling technique, free en-

ergy profiles were calculated for three oxidation states (i.e., 0, +1,

+2) of the TTF unit both in vacuo and in water. While the free en-

ergy profiles in vacuo do not explain the experimental observations,

the free energy profiles in water are in good agreement with the

observed binding preferences, which reveals the importance of the

water environment in theoretical calculations.

In the neutral state, the -CD@TTF isomer is calculated to be

energetically favored by 2.5 kJ/mol over the -CD@TZ isomer; this

result is in fair accordance with the experimental value of 5.5 kJ/

mol. In the oxidized states, the -CD@TZ isomer becomes the pre-

ferred co-conformation. Additionally, the free energy profile re-

veals that the shuttling of the -CD ring from the TTF unit to the

TZ unit is barrierless for the oxidized +2 state, which suggests that

the response time of this rotaxane is only slightly dependent on the

oxidization of TTF. The interactions between water and the rotax-

ane components induces the shuttling of the -CD ring from the

– e

+ e

Cu Cu2

translation

translation

translation

translation

= == TERPY= BIPY= DPP = DPBIIQ


TTF unit to the TZ unit in the oxidized states despite the increased

attractive interactions between the -CD ring and the dumbbell.

To realize the full potential of these functional molecules at the

nanoscale level [44], Stoddart directly observed electrochemically

driven single-molecule station changes within bistable rotaxane

molecules anchored laterally on gold surfaces [45].

Rotaxane molecule 694+

, which has disulfide groups attached to

the stoppers on the dumbbell termini (Fig. 9), was designed to bind

to Au{111} at each end. The sample was prepared with the desired

coverage of 5–6 molecules/1000 Å2 for STM imaging with the

thread section of the dumbbell assembled parallel to the surface

[46]. The distance between the two stations, i.e., TTF and 1,5-

dioxynaphthalene (DNP), in the fully stretched dumbbell is 36 Å. In

situ STM images of the bistable rotaxane molecules attached to

Au{111} showed ~3 Å high and 10–12 Å wide protrusions. No

protrusions were observed when a bare gold surface and a control

molecule, which comprised the dumbbell compound without the

CBPQT4+

ring, were treated and imaged under the same conditions

as the bistable rotaxane. The dumbbell component was apparently

not sufficiently conductive to be resolved by STM. However, the

CBPQT4+

rings, which have a higher electrical conductivity and

greater height relative to the dumbbell, appear as protrusions in the

STM images. The protrusions are therefore assigned to be the

CBPQT4+

rings, which is consistent with prior STM studies [47].

To study the station changes in 694+

, the same surface region

was repeatedly imaged to track the positions of the protrusions us-

ing image processing routines that were developed previously [48].

The molecules were imaged at two different electrode potentials,

i.e., –0.12 and –0.53 V, to view the TTF station in the reduced (neu-

tral) state and oxidized (cationic) state, respectively. Significant

displacement was observed when the potential was stepped from –

0.12 to –0.53 V (vs. Ag/AgCl). The correlations between the poten-

tial change and the motion of the CBPQT4+

ring suggest that the

positive charge of the cationic TTF station repels the CBPQT4+

ring. Subsequently, the potential was stepped down from –0.53 to –

0.12 V and the protrusions were again displaced, which suggests

that the CBPQT4+

ring returns to its thermodynamically favored

position encircling the neutral TTF station [46].

Using electrochemical scanning tunneling microscopy

(ECSTM), electrochemically controlled station changes of individ-

ual bistable rotaxane molecules were observed in situ. The motions

of the CBPQT4+

rings correlated with the redox states of the TTF

O O O

HO2C

HO2C

S

S

S

S

O

CO2H

CO2H

N

N N

OO

68 (80%)

65 (23%)

O O O

RO2C

RO2C

S

S

S

S

N3OO O

CO2R

CO2R

O O O

HO2C

HO2C

S

S

S

S

O

CO2H

CO2H

N

N N

OO

63 (R = H)

66 (R = Me)

64 (R = H)

67 (R = Me)

+

-CD HO

OH

OOH

6

1) CuSO4•5H2O/ascorbic acid/DMF

2) MeONa/MeOH

1) CuSO4•5H2O/H2O

sodium ascorbate

Scheme 24. Syntheses of the [2]rotaxane 65 and the corresponding dumbbell compound 68.


station and displayed partial reversibility. The trajectories of the

rings suggest after adsorption of the bistable rotaxane molecule on a

surface, the motion of the CBPQT4+

ring relative to the dumbbell is

affected by its local environment and the flexibility of the molecule:

bistable rotaxane molecules with rigid dumbbells enable consistent

and fully reversible motions as well as direct visualization of the

rings and the shafts of the molecules.

Once again, Stoddart introduced an innovative idea to induce

mechanical movement in molecular assemblies by redox stimuli

using the dynamic properties of liquid crystals (LC). Thus, he de-

veloped a new class of LC materials based on a bistable [2]rotaxane

in which dendritic bistable LC [2]rotaxane 70 (Fig. 10) with TTF

and DNP recognition units encircled by a single CBPQT4+

ring

responded to redox signals. This system was switched electro-

chemically in dilute solution, i.e., in a molecularly dispersed state

[49]. Recently, Stoddard described the redox-driven switching and

electrochromic response of LC films comprising bistable

[2]rotaxane 70 and a polymer electrolyte [50].

[2]Rotaxane 70 forms a smectic A phase in the ranging of

10–150 °C, as previously reported [49]. Therefore, LC films of 70

with polydomain morphologies were readily prepared by casting or

spin-coating onto indium-tin-oxide (ITO) glass electrodes at ambi-

ent temperature. The thickness of the films was estimated to be 2–3

mm by SEM. The shuttling behavior of 70 in the LC film was stud-

ied using CV. The results suggest that the -accepting CBPQT4+

ring initially encircles the -donating TTF unit. After oxidation of

the TTF recognition unit, which is represented by the right central

dark grey cylinder in Fig. (11), the CBPQT4+

ring moves away due

to Coulombic repulsion and resides around the DNP unit, which is

represented by the left central light grey cylinder in Fig. (11), even

in a condensed and coherent environment. In this case, each

CBPQT4+

ring moves an estimated 1.4 nm between the two recog-

Fig. (9). Structure and motion of a bistable rotaxane molecule, adsorbed on Au{111} investigated using electrochemical scanning tunneling microscopy.

Fig. (10). Molecular structure of the smectic A liquid-crystalline bistable [2]rotaxane 70 having forklike mesogenic stoppers whose macrocycle is mobile

along the dumbbell under the influence of redox stimuli.

O O OOO

OOOO

O

S

S

– e

+ e

694

~36Å~20Å

DNP TTF

S

S

S

SOOO

OO

NN

N

O

R

O

O O

N N

N

O

R

O

N

N

N

N

4PF6

70

R =

O

O

O O O C5H

11

F F

O O O C5H

11

F F

O O O C5H

11

F F

O


nition units along the linear portion of the dumbbell component in

the layered smectic A phase.

Electrochromic cells based on the LC films of 70 were fabri-

cated by combining the [2]rotaxane with a polymer electrolyte pre-

pared from a solution of polymethylmethacrylate (PMMA; 7 wt%,

Mw = 120,000 and 350,000), propylene carbonate (PC; 40 wt%),

and LiPF6 (3 wt%) in CH3CN (50 wt%). The resultant transparent

viscous solution was spread over an ITO counter electrode, which

was then stored for one day at room temperature to enable forma-

tion of the self-supporting film. For the fabrication of a

two-electrode electrochromic cell, the ITO counter electrode with

the polymer electrolyte was set on the LC film–coated side of the

ITO working electrode.

Spectroelectrochemical studies of the cells support redox-driven

shuttling behavior in the LC state. The UV-vis-NIR spectrum of the

cell recorded at 0 V vs. the counter electrode (CE) displays a broad

absorption band centered around 850 nm due to charge-transfer

(CT) interactions between the TTF unit and the CBPQT4+

ring (Fig.

11, upper part). The application of positive potentials up to +1.6 V

vs. CE leads to a decrease in the intensity of the CT absorption band

at 850 nm. Concurrently, new absorption peaks appear at 400 and

770 nm and are assigned to the -dimer of TTF·+

radical cations

[51] (Fig. 11, lower part). The small absorption evident at 530 nm is

characteristic of the CT complex of the DNP unit with the

CBPQT4+

ring. These observations confirm the mechanical move-

ment of the macrocycle within [2]rotaxane 70 as a result of oxida-

tion of the TTF unit. Since the formation of the monomeric TTF·+

radical cation ( max = 448 and 600 nm) has been observed by

one-electron oxidation in dilute solution of the [2]rotaxane 70, the

dimerization of the oxidized TTF units is enhanced by their

face-to-face organization in the layered LC nanostructure.

It is noteworthy that the LC undergoes a visible color change

from greenish brown to reddish purple within 10 s of the applica-

tion of the oxidizing bias. When negative potentials are applied, 70

is reduced to its original form and the LC film in the cell recovers

its initial greenish brown color, which indicates that the redox-

driven mechanical movement is reversible in the LC film. In the

reduction process, the electrochromic switching requires a longer

period of time (ca. 40–50 s) for relaxation from the metastable state

back to the initial ground state as a result of the attractive interac-

tions of the CBPQT4+

ring with the DNP unit.

This approach offers new prospects for the further development

of rotaxane-based molecular materials by exploiting the dynamic,

anisotropic, and coherent properties of liquid crystals.

CONCLUSIONS

In this updated review, major recent developments on

[2]rotaxane-based shuttles based on chemically, photochemically,

and electrochemically induced molecular switching were described.

Among the chemically controlled shuttles, a significant increase of

the shuttling rates was achieved using second-generation pH-

switchable Pd(II)-complexed rotaxanes while new synthetic ap-

proaches, especially those based on the Diels-Alder cycloaddition,

allow ready access to rotaxanes with template sites incorporated

into the interlocked product, which is unusual for active-template

reactions. Moreover, the incorporation of a hydrogen-bonding TEG

station into an imine-bridged rotaxane resulted in shuttles that ex-

hibit entropy-driven translational isomerism with remarkable im-

proved positional discrimination. Finally, a molecular reel based on

the shuttling of a rotor by tumbling of an altro- -CD macrocycle

upon the change of solvent has been realized.

With respect to photochemically powered molecular switches,

the most important result was the synthesis of a degenerate donor-

acceptor light-gated STOP-GO molecular shuttle. This approach

could permit the isolation and identification of metastable and

ground-state co-conformations of bistable donor-acceptor

[2]rotaxanes in the near future.

For electrochemically controllable bistable rotaxanes, the first

example of a molecular shuttle with three different stations was

reported. In this case, the presence of an intermediate BIPY group

between two terminal chelating groups, i.e., DPP and TERPY, dra-

matically influences the shuttling process rate. Moreover, the use of

Fig. (11). Schematic representation of the redox-driven mechanical movement induced in the LC film of 70 on the electrode surface.


use of ECSTM allowed the in situ observation of electrochemically

controlled station changes of individual bistable shuttles. For a

bistable rotaxane molecule adsorbed on a surface, the motion of the

CBPQT4+

macrocyclic ring relative to the dumbbell is affected by

its local environment and by the flexibility of the molecule.

The last reported study regards the redox-driven switching and

electrochromic response of LC films comprising a bistable

[2]rotaxane and a polymer electrolyte. This approach offers new

prospects for the further development of rotaxane-based molecular

materials by exploiting the dynamic, anisotropic, and coherent

properties of liquid crystals.

Although the community has witnessed tremendous progress

since the first proof-of-principle studies, there is still a long way to

go to achieve mature devices employing functional supramolecular

systems that are applicable in daily life. Therefore, more effort

needs to be exerted in this research field.

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Schill, G. Catenanes, Rotaxanes and Knots; Academic Press: New York,

1971.

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Received: December 02, 2010 Revised: June 21, 2011 Accepted: August 08, 2011

Recent Developments on Rotaxane-Based Shuttles: An Update to 2010

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