ChemPhysChem2013-14-500

DOI: 10.1002/cphc.201300001

A Design Strategy for Motion Control Systems withIdentical Binding SitesWei-Tao Peng, Yu-Chang Chang, and Ito Chao*[a]

Stimuli-responsive supramolecular systems with tunable bind-ing ability have been intensely pursued. One of their merits isthat they provide opportunities in synthesizing motion controlsystems on the basis of controlled association/dissociation ofsupramolecular complexes. These motion-controllable systemscan potentially lead to the design of molecular-based electron-ic devices,[1] molecular nanovalves for drug deliveries,[2] andstimuli-triggered supramolecular assemblies.[3] In the literature,most motion controls are accomplished through receivingstimuli on the binding sites to vary their binding ability. For ex-ample, Stoddart et al. have constructed redox-switchable bista-ble[2]rotaxanes with tetrathiafulvalene (TTF) and dioxynaph-thalene (DNP) as the binding sites (blue and red objects in Fig-ure 1a), and cyclobis(paraquat-p-phenylene) (CBPQT4+) as thebinding partner.[4] In these systems, CBPQT4+ can be reined toenclose one of the binding sites since TTF takes on the respon-

sibility to receive the external stimulus and thus alters its bind-ing strength (by charge transfer interaction at the neutral stateor electrostatic repulsion at the oxidized state) to CBPQT4+ .

Rather than directly altering the property of a binding site,we have proposed a concept of remote control of binding inwhich the stimulus-responsive reaction site is not directly in-volved in binding.[5] Instead, a conjugated bridge is employedto link the binding and reaction sites (see Figures 1b and 1c).The concept of remote control of binding has gained supportthrough theoretical investigations[5,6] and experimental evi-dence.[7] Sessler et al. have made a metallation-enhanced fluo-ride binder in which the dipyrrole binding sites are not in theimmediate proximity of the phenanthroline metallation site.With and without Co3+ (stimulus) bound to the phenanthrolinesite, a more than hundred-fold difference in fluoride binding insolution has been reported.[7a]

The concept of remote control has several advantages. Firstof all, it can be applied to supramolecular systems whose bind-ing sites are inert to external stimuli. Moreover, it makes thedesign of a multivalence binding system with only one controlcenter conceptually easy. In Figures 1b and 1c we have at-tached two binding sites to a control center. However, it isconceivable that one can attach more than two binding sites.In a study of molecular elevator, three protonation sites wereneeded to control the movement of a tripod elevator.[8] Withinthe concept of remote control of binding, one stimulus-recep-tive site may achieve the same control. Using one controlcenter to manipulate several sites can be viewed as one formof atom economy. Finally, a stimulus-responsive motion controlsystem capable of swapping preferential binding sites are usu-ally realized with binding sites of different chemical composi-tions (as in the rotaxane depicted in Figure 1a). However,within the concept of remote control, one can keep the bind-ing sites the same but utilize different conjugated bridges torealize the goal (Figure 1c), because a bridge can influence thebinding behavior of a binding site.[5]

In this study, we adopt a same binding site/same bridgestrategy (see Figure 1d) to go beyond the different bindingsite/same bridge or same binding site/different bridge ap-proaches depicted in Figures 1b and 1c. Identical chemicalcomposition of bridges/binding sites means less ponderingover what moieties can be used while designing a system. Thefoundations of the current design to achieve stimulus-respon-sive motion control are a three-stage redox reaction centerand the position effect in this center. As shown in the Fig-ure 1d, identical bridges and binding sites are attached toa binding control center at chemically distinct postions (i.e.alpha vs. beta or para vs. meta) ; the reaction center is repre-sented by a rhombus to emphasize that not all connection po-

Figure 1. a) Model of an axle of a rotaxane without showing the macrocyclicring (CBPQT4+). One of the binding sites plays the role of the stimulus-re-sponsive reaction center. b) Remote motion-controllable system with differ-ent binding sites linked to a reaction center (solid gray circle). c) With thesame binding site but different bridges. d) With the same binding site andbridges, but the bridges are linked to chemically distinct positions of the re-action center.

[a] W.-T. Peng, Dr. Y.-C. Chang, Prof. I. ChaoInstitute of ChemistryAcademia SinicaTaipei 11529 (Taiwan)Fax: (+886)2-2783-1237ca.edu.twE-mail : [email protected]

Supporting information for this article is available on the WWW underhttp://dx.doi.org/10.1002/cphc.201300001.

2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim ChemPhysChem 2013, 14, 500 504 500

CHEMPHYSCHEMCOMMUNICATIONS

sitions are equivalent. A redox-active molecule, the phenalenylradical (Figure 2a), is employed as the reaction center. Phena-lenyl is a persistent hydrocarbon radical of which neutral radi-cal, cationic and anionic states have been generated and char-acterized spectroscopically.[9] Through proper modification,crystals of phenalenyl derivatives have been acquired at ambi-ent conditions.[10] Phenalenyl derivatives have attracted muchattention as they are promising building blocks for construc-tion of molecular metals[11] and other functional materials.[12]

Since the singly occupied molecular orbital (SOMO) of phena-lenyl is only distributed on the six a-carbons and not the b-car-bons (Figure 2b),[11b,12a,b,d] the a/b position effect underlie dif-ferential bridge efficiency in transmitting the impact of a redoxreaction on a binding site. This a/b position effect has been in-dicated as the origin of the conducting/semiconducting quan-tum transport behavior of phenalenyl.[13] In this study, bridgesand binding sites are attached to a- or/and b-positions asshown in Figure 3 (model compounds 1 to 4). As in our previ-ous studies, pyrrole is used as a binding site, whose NH hy-drogen-bond-donating ability is probed with ammonia.[5]

In the literature there are molecular switches that undergoelectrochemical control of strengthening/weakening or com-plexing/decomplexing of hydrogen-bonded hostguest ad-ducts in a reversible manner.[1416] Among them, some systemspossess multi-stage and/or multiple binding sites.[1516] Howev-er, to the best of our knowledge, there is no case in which thehydrogen bonding strengths of two identical binding sites aretuned asymmetrically with electrochemical means. Further-more, the charged states of most three-stage redox systemsdo not change sign. For example, the charged states of theoften employed TTF vary between 0, +1, +2. On the otherhand, the charged states of amphoteric phenalenyl (+1, 0, 1)change sign. This means the reaction center can be switchedbetween electron-withdrawing and electron-donating. For1 and 2, an electron-withdrawing center will enhance theproton-donating ability of the pyrrole binding site, while anelectron-rich center will do the opposite. If the a- and b-car-bons of phenalenyl molecule can tune the bridge efficiencythrough the position effect, with the a-bridge being more effi-cient than the b-bridge, when the reaction center is electron-deficient, an a-binding site (as in 1) would be a strongerbinder than a b-binding site (as in 2). Conversely, when the re-action site becomes electron-rich, the a-binding site is thena poorer binder because an a-bridge transmits greater elec-tron-donating effect than a b-bridge does onto the proton-do-nating binding site.

Calculated ammonia binding energies to the pyrrole moietyof 1 and 2 at B3LYP, M05-2X and MP2 levels confirm the posi-tion effect and the above postulation. Table 1 shows theB3LYP/6-31+G(d) results (see the Supporting Information forthe M05-2X and MP2 results). The binding energies of 1 and 2at the neutral state (DEb(N)) are almost the same in each com-pound, all between 6.78 kcalmol1 to 6.98 kcalmol1. Ata given bridge length, DEb(N) of 1 and 2 differ by only 0.06~

Figure 2. a) Phenalenyl radical with carbon labels and b) SOMO of phenalen-yl.

Table 1. Ammonia binding energies (DEb, in kcalmol1) of 1 and 2 at the

B3LYP/6-31+G(d) level

Compound Site type DEb(N) DEb(+) DEb()

1a a-site 6.86 12.39 3.331b a-site 6.93 11.89 3.681c a-site 6.97 11.48 4.021d a-site 6.98 11.11 4.292a b-site 6.78 10.18 4.132b b-site 6.86 9.83 4.622c b-site 6.90 9.83 4.942d b-site 6.92 9.84 5.203 a-site 6.84 11.40 3.82

b-site 6.68 8.79 4.894 a-site 6.89 11.38 3.85

b-site 6.77 8.82 4.94

Figure 3. Model compounds 1ad, 2ad, 3 and 4.


CHEMPHYSCHEMCOMMUNICATIONS www.chemphyschem.org

0.08 kcalmol1 (1a vs. 2a, 1b vs.2b, and so on). In this situa-tion, we call it an off state. In other words, if the amount ofcompounds 1, 2 and ammonia are equivalent (1:1:1), ammoniawill bind to both compounds in similar percentages. We canthen convert this off state to an on state by redox reactions.In the oxidation state, the binding strengths DEb(+) of 1 and 2are several kcalmol1 stronger than DEb(N) at the neutral state,revealing the electron-withdrawing effect of the reactioncenter. More importantly, DEb(+) of 1 are always larger thanthat of 2 as expected, regardless of the bridge length. Withthe longest bridge (n=4), the binding strength of 1d is still1.27 kcalmol1 higher than that of 2d. Therefore, preferentialbinding of ammonia to 1 can be turned on. On the otherhand, in the reduction state, the binding strength DEb() of 2 islarger than that of 1 for nearly 1 kcalmol1 at a given bridgelength. At this stage, 2 is the preferential host to bind ammo-nia. In the literature, a similar switch between preferentialbinding between two hosts has been achieved by Rotello withthe help of redox reactions and p-stacking interactions.[17] It isnoted that for a given compound, the binding enhancementfrom the neutral to the oxidation state (e.g. 5.53 kcalmol1 for1a) is more significant than the binding attenuation from theneutral to the reduction state (e.g. 3.53 kcalmol1 for 1a). Weascribe this phenomenon to the fact that pyrrole is an elec-tron-rich moiety; it has better ability to donate electron (oxida-tion state) than to accept electron (reduction state).

As our goal is to construct a three-stage/two-site motioncontrol system with identical binding sites, the ammonia bind-ing energies of 3 and 4 were calculated (Figure 3). In 3 and 4,bridges are attached to the a- and b-positions to enable tuna-ble preferential binding with one stimulus-receptive center. Inthe off state, all DEb(N) values are again quite similar (Table 1).In the oxidation on state, DEb(+) in 3 and 4 are somewhatweaker than that in the corresponding one-bridge systems 1band 2b, as the electron-withdrawing effect is shared by twobridges in 3 and 4. However, the a-site is still significantly pre-ferred by ca. 2.5 kcalmol1 for both 3 and 4 (cf. 2.1 kcalmol1

for 1b vs. 2b). In the reduction state, the strength of the hy-drogen bond of the a-site decreases more than that of b-site,so b-site is the superior binding site and the binding prefer-ence is ca. 1.1 kcalmol1 for 3 and 4, not very different fromthat between 1b and 2b (ca. 1.0 kcalmol1). The above resultsshow that 3 and 4 can function as molecular switches and themotion of the hydrogen-bond partner can be controlled re-motely.

The success of the switches relies on the differential bridgeefficiency caused by the position effect. The frontier orbitals of3 and 4 show electron distribution on the phenalenyl moietyand the a-branch of bridge/binding site, but not on the b-branch (Figure 4), in accord with the inferior bridge efficiencyof the b-bridge. Molecular electrostatic potentials (MEPs)around the pyrrole moieties of 3 and 4 at different chargedstates predict the preferred binding site well (see the Support-ing Information) and can be employed for future moleculardesign.

In the current model study, simple binding partners wereemployed to examine whether some local properties can be

tuned remotely and whether asymmetric control can be realiz-ed. The results are positive. In nature, molecular recognitionwith good fidelity often relies on multiple hydrogen bonds.Therefore, we propose that future endeavors along this direc-tion may employ strong binding partners and delocalized reac-tion center. In this way, binding complications caused by thechange of the charge states of a reaction center can be mini-mized, because a charged reaction center may also play therole of a binding site.[18]

In summary, based on the concept of remote control, wehave demonstrated a strategy to design electrochemically con-trolled three-stage/two-site hydrogen-bonding systems. Thebinding ability of two identical hydrogen-bonding sites can betuned symmetrically (the off state) or asymmetrically (thetwo on states). According to the sign of the charged states,the preferred binding site can be swapped. The essence of thisstudy is not the use of phenalenyl radical or a pyrrolic hydro-gen-bonding site as such. Rather, it is the usage of positioneffect and of a redox-active unit with charged states of differ-ent signs. With commonly used redox unit whose chargedstates do not change sign (e.g. TTF), the aforementioned bind-ing control cannot be achieved. In a broader perspective, theasymmetrically controlled property needs not to be limited tobinding, but can also be other properties that can be tuned byelectronic effects (i.e. tuned by electron-donating or -withdraw-ing ability of the control center). It will be interesting to buildfunctional molecular devices using such multi-stage/multi-siteapproach.

Figure 4. The SOMO of 3 and 4 at the neutral state at B3LYP/6-31+G(d)level.



Computational Methods

All calculations were performed with Gaussian 03.[19] The geome-tries of all systems were fully optimized with the 6-31+G(d) basisset at the B3LYP and M05-2X levels. This basis set was chosen be-cause we have shown in previous studies that the basis sets donot change the trends in ammonia binding energy of similar con-jugated pyrrolic systems.[5] Single-point MP2/6-31+G(d)//B3LYP/6-31+G(d) calculations have been carried out to confirm the trends.The binding energies (DEb) were corrected for basis set superposi-tion error (BSSE) with the counterpoise (CP) method.[20] Stationarypoints were confirmed to be local minima by means of frequencyanalysis.

No imaginary frequency was present in the B3LYP calculations. Asmall imaginary frequency (

[12] For reviews, see: a) Y. Morita, S. Nishida in Stable Radicals : Fundamentaland Applied Aspects of Odd-electron Compounds (Ed. : R. Hicks), Wiley-Blackwell : New York, 2010, Chapter 3; b) Y. Morita, S. Suzuki, K. Sato, T.Takui, Nat. Chem. 2011, 3, 197204; c) R. G. Hicks, Nat. Chem. 2011, 3,189191; d) I. Ratera, J. Veciana, Chem. Soc. Rev. 2012, 41, 303349.

[13] a) K. Tagami, L. G. Wang, M. Tsukada, Nano Lett. 2004, 4, 209212; b) L.Wang, K. Tagami, M. Tsukada, Jpn. J. Appl. Phys. 2004, 43, 27792785;c) S. K. Maiti, Physica E 2008, 40, 27302735; d) Z.-Q. Fan, K.-Q. Chen,Appl. Phys. Lett. 2010, 96, 053509/1053509/3.

[14] a) E. Breinlinger, A. Niemz, V. M. Rotello, J. Am. Chem. Soc. 1995, 117,53795380; b) Y. Ge, R. R. Lilienthal, D. K. Smith, J. Am. Chem. Soc. 1996,118, 39763977; c) T. Kajiki, H. Moriya, S. Kondo, T. Nabeshima, Y. Yano,Chem. Commun. 1998, 27272728; d) A. Niemz, V. M. Rotello, Acc.Chem. Res. 1999, 32, 4452; e) J. D. Carr, S. J. Coles, M. B. Hursthouse,M. E. Light, J. H. R. Tucker, J. Westwood, Angew. Chem. 2000, 112, 34343437; Angew. Chem. Int. Ed. 2000, 39, 32963299; f) Y. Ge, L. Miller, T.Ouimet, D. K. Smith, J. Org. Chem. 2000, 65, 88318838; g) Y. Ge, D. K.Smith, Anal. Chem. 2000, 72, 18601865; h) Y. M. Legrand, M. Gray, G.Cooke, V. M. Rotello, J. Am. Chem. Soc. 2003, 125, 1578915795; i) A. Al-tieri, F. G. Gatti, E. R. Kay, D. A. Leigh, D. Martel, F. Paolucci, A. M. Z.Slawin, J. K. Y. Wong, J. Am. Chem. Soc. 2003, 125, 86448654; j) J. Bu,N. D. Lilienthal, J. E. Woods, C. E. Nohrden, K. T. Hoang, D. Truong, D. K.Smith, J. Am. Chem. Soc. 2005, 127, 64236429; k) B. J. Jordan, M. A.Pollier, L. A. Miller, C. Tiernan, G. Clavier, P. Audebert, V. M. Rotello, Org.Lett. 2007, 9, 28352838.

[15] a) C. Bourgel, A. S. F. Boyd, G. Cooke, H. A. de Cremiers, F. M. A. Duclair-oir, V. M. Rotello, Chem. Commun. 2001, 19541955; b) G. Cooke, H. A.de Cremiers, F. M. A. Duclairoir, J. Leonardi, G. Rosair, V. M. Rotello, Tetra-hedron 2003, 59, 33413347; c) G. Fioravanti, N. Haraszkiewicz, E. R.Kay, S. M. Mendoza, C. Bruno, M. Marcaccio, P. G. Wiering, F. Paolucci, P.Rudolf, A. M. Brouwer, D. A. Leigh, J. Am. Chem. Soc. 2008, 130, 25932601.

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[17] R. Deans, A. Niemz, E. C. Breinlinger, V. M. Rotello, J. Am. Chem. Soc.1997, 119, 1086310864.

[18] At the B3LYP/6-31+G(d) level of theory, the ammonia binding energiesof the charge-assisted CH binding sites around the phenalenyl moietyare ca. 4.4 kcalmol1 for 3 and 4 at the oxidation state. At the reduc-tion state, the p face of phenalenyl interacts with hydrogens of ammo-nia with binding energies ca. 3.5 kcalmol1 for 3 and 4.

[19] Gaussian 03 (Revision E.01), M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr. , T. Vreven,K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone,B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsu-ji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Na-kajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts,R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Och-terski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K.Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui,A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko,P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W.Chen, M. W. Wong, C. Gonzalez, and J. A. Pople, Gaussian, Inc. , Walling-ford CT, 2004.

[20] S. F. Boys, F. Bernardi, Mol. Phys. 1970, 19, 553566.

Received: January 1, 2013Published online on February 5, 2013



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ChemPhysChem2013-14-500