Preorientation of olefins toward a single photodimer: Cucurbituril-mediated photodimerization of...

Preorientation of Olefins toward a Single Photodimer:Cucurbituril-Mediated Photodimerization of Protonated Azastilbenes

in Water

Murthy V. S. N. Maddipatla, Lakshmi S. Kaanumalle, Arunkumar Natarajan,Mahesh Pattabiraman, and V. Ramamurthy*

Department of Chemistry, UniVersity of Miami, Coral Gables, Florida 33124

ReceiVed March 19, 2007. In Final Form: April 25, 2007

With the view to establishing the generality of cucurbit[8]uril as a template, the photodimerization of hydrochloridesalts of eight azastilbenes has been investigated in an aqueous medium. Whereas in solution upon excitation all ofthese olefins yield products of geometric isomerization, cyclization, and hydration, in the presence of cucurbit[8]urilthe predominant product is that of dimerization. Such a change in product distribution is attributed to the localizationof the olefins by the host cucurbit[8]uril. Most importantly, instead of a mixture of dimers, predominantly a singledimer was obtained in each case. The nature of the dimer that was formed could be rationalized on the basis of theprinciples of “best fit” and “minimization of electrostatic repulsion”. The superior ability of cucurbit[8]uril comparedto micelles to act as a templating agent is attributed to its ability to provide a reaction cavity that is tight and time-independent.

Introduction

The possibility of various stereo- and regioisomeric dimersobtaining product selectivity during the photodimerization ofolefins such as cinnamic acids has been a challenging task.1

Attempts to control dimerization in the solid state and in solutionhave resulted in success only when the reactant molecules werepreorganized in the ground state toward a particular regioisomer.Both intermolecular and intramolecular crystal-engineeringprinciples have been used to template reactant olefins toward asingle dimer in the solid state.2 In spite of moderate success, theabove templating strategies in the solid state are less general, andin aqueous solution, they remain a challenging task. To ourknowledge, de Mayo was the first to exploit the hydrophobic-hydrophilic interface of a micelle to preorient enones toward asingle dimer.3-5 Although the approach resulted in dimerization,it failed to give significant selectivity. However, Whitten andco-workers succeeded in obtaining a syn head-head dimerselectively from protonated stilbazoles within a reverse micellethat has a much smaller and more rigid reaction cavity.6,7 Thesepioneering studies paved the way for recent studies on the useof well-defined and rigid hydrophobic cavities of cyclodextrins,8-13

calixarenes,14,15 Pd nanocages,16-21 and cucurbiturils22-25 totemplate olefins toward selective photodimers in aqueous solution.In this presentation, we have utilized cucurbit[8]uril as the reactionmedium to achieve selective photodimerization of hydrochloridesalts of bispyridyl ethylenes and stilbazoles.

Cucurbiturils, depending on the number [n] of glycouril unitscoupled during the acid-catalyzed condensation reaction, existas different oligomers (CB[n]).26-29 To date, cucurbiturilscomprising of 5, 6, 7, 8, and 10 glycoluril units have been isolatedand characterized. These moderately water-soluble hosts havingpolar carbonyl groups as portals and hydrophobic interiors canencapsulate organic molecules in aqueous solution. For example,CB[6] having a cavity diameter of 5.7 Å can encapsulate a singlebenzene molecule, whereas CB[7] with a 7.3 Å cavity diametercan accommodate aromatic guests such asortho- and meta-xylenes. CB[8], in particular because of its larger cavity diameter(8.8 Å), can encapsulate two molecules of dimensions similar

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7545Langmuir2007,23, 7545-7554

10.1021/la700803k CCC: $37.00 © 2007 American Chemical SocietyPublished on Web 06/01/2007

to those of stilbene. The exploitation of CB[8] to mediate theselective photodimerization of cationic olefins in solution beganwith the work of Kim and co-workers on diaminostilbenehydrochlorides.30 Recently, we reported the dimerization ofneutral substituted cinnamic acids within CB[8] and demonstratedthat it can facilitate photodimerization selectively to yield synhead-head dimers.24 To explore the templating ability of CB[8]further in an aqueous medium, we have investigated thephotodimerization of azastilbenes1-8 (Scheme 1)31-35 ashydrochloride salts included within the CB[8] cavity. Our maingoals are to establish the generality of CB[8] to control thephotodimerization of olefins in water and, if possible, to formulatea model that would allow one to predict the nature of the dimersthat would be obtained with CB[8] as a template. The olefinsinvestigated as models in this study carry a positive charge;therefore, the model that we propose is restricted to positivelycharged olefins.

Results

In designing this project, we have exploited the efficientbinding ability of CB[7] and CB[8] toward cationic species. Wehave chosen three classes of guest molecules, namely, water-soluble hydrochloride salts of symmetrical bispyridyl ethylenes(1-3), unsymmetrical bispyridyl ethylenes (4-6), and stilba-zoles (7, 8) for photodimerization studies (Scheme 1). Asdiscussed below, all of these guest molecules bind to CB[7] andCB[8]

Complexation Studies.Procedures adopted for the preparationand irradiation of CB[7] and CB[8] inclusion complexes of olefins1-8 are provided in the Experimental Section. To avoid a

repetitive presentation of the results, three olefins, namely,1, 4,and 7, have been chosen as representative examples of eachclass. A turbid solution of CB[8] in water (2.75× 10-4 M)became transparent upon addition of 4-BPE‚2HCl (1) (5.5 ×10-4 M), suggesting a host-guest complexation. The encapsula-tion and stoichiometry of the complexes were confirmed by1HNMR, MALDI-TOF, and UV-vis absorption data. An upfieldshift in guest1H NMR signals relative to that in water suggestedthe complexation of1 with CB[7] and CB[8] (Figure 1). During1H NMR titration experiments, a continuous upfield shift of guestproton signals was observed until the addition of 1 equiv ofCB[7] or 0.5 equiv of CB[8] to 5.5× 10-4 M 1, suggesting theH/G complex ratios to be 1:1 in the case of CB[7] and 1:2 inthe case of CB[8]. Further addition did not result in any shift in1H NMR signals. The extent of the shift was greater in the caseof CB[8] as compared to that for CB[7] possibly because of theinclusion of two molecules within the hydrophobic cavity.MALDI-TOF mass spectral data (peaks at 1346 (BPE@CB[7])and 1693 (2.BPE@CB[8])) were consistent with the abovestoichiometry. In Figure 2,1H NMR spectra of1‚HCl uponaddition of various amounts of CB[8] are shown. As can be seen,there is continuous shift in the NMR signals, and at no stagewere there two sets of peaks, one due to uncomplexed and theother due to complexed olefins. The overall binding constant ofthe complex between1 and CB[8] as estimated by1H NMRtitration experiment was∼108 M-2; K11 ) 8.6× 105 M-1 andK12 ) 1.03 × 103 M-1, whereK11 and K12 are the stepwisebinding constants for 1:1 and 1:2 H/G complexes. (See theExperimental Section for details.)

The inclusion of unsymmetrical bispyridyl ethylene4 withinCB[7] and CB[8] resulted in an upfield shift in the1H NMRsignals of the guest olefin (Figure 3). Relatively large upfieldshifts of Haand Hbprotons suggested the inclusion of the 4-pyridylring within the hydrophobic cavities of CB[7] and CB[8]. Asimilar trend was observed upon the inclusion of 2,4-BPE‚2HCl(5) and 2,3-BPE‚2HCl (6) within CB[7] and CB[8]. The formationof stable inclusion complexes of4 with CB[7] (1:1) and CB[8]

(30) Jon, S. Y.; Ko, Y. H.; Park, S. H.; Kim, H.-J.; Kim, K.Chem. Commun.2001, 1938- 1939.

(31) Williams, J. L. R.J. Org. Chem.1960, 25, 1839-1840.(32) Takagi, K.; Itoh, M.; Usami, H.; Imae, T.; Sawaki, Y.J. Chem. Soc.,

Perkin Trans. 21994, 1003-1009.(33) Shim, S. C.; Kim, M. S.; Lee, K. T.; Jeong, B. M.; Lee, B. H.J. Photochem.

Photobiol. A1992, 65, 121-131.(34) Whitten, D. G.; Lee, Y. J.J. Am. Chem. Soc.1972, 94, 9142-9148.(35) Whitten, D. G.; McCall, M. T.J. Am. Chem. Soc.1969, 91, 5097-5103.

Scheme 1

7546 Langmuir, Vol. 23, No. 14, 2007 Maddipatla et al.

(2:1) was also suggested by the observation of peaks atm/z1346and 1693 in the MALDI-TOF mass spectra.

1H NMR titration and MALDI-TOF mass spectral datasuggested the complexes of stilbazole hydrochlorides7 and8with CB[7] and CB[8] to be 1:1 and 2:1. Because the shift ofthe phenyl ring protons alone was observed in the case of theCB[7] complex, we believe the phenyl ring of7 to be encapsulatedwithin the CB[7] cavity (Figure 4). This is consistent with therelatively more hydrophobic nature of the phenyl ring comparedto that of the pyridinium ring. In case of CB[8], the upfield shiftsfor both phenyl and pyridyl protons of the guests were observed,indicating the inclusion of both rings within the cavity(Figure 4).

1H NMR and mass spectral data presented above are consistentwith the conclusion that1, 4, and7 form a 1:1 complex withCB[7] and a 2:1 complex with CB[8] with more hydrophobicgroup residing within the cavity of the host. In all three examples,because there were no signals due to free olefins even at low

concentrations of the host (Figure 2), we believe that the exchangebetween bound and free guest is fast on the1H NMR (400 MHz)time scale. The lack of shift in1H NMR signals upon the additionof more than 1 equiv of CB[7] or 0.5 equiv of CB[8] suggestedthat under our irradiation conditions (to be described in the nextsection) no free olefins existed. Although we did not measurethe binding constant for any olefin except1‚HCl, we anticipatethe K measured for1‚HCl@CB[8] to be representative of allsubstrates investigated here.

Photochemistry of CBs Encapsulated Guests.Becausephotochemical results for all symmetrical olefins1-3were similar(Table 1), to avoid repetition we present the results on 4-BPE‚2HCl (1) in detail. The irradiation oftrans-1,2-bis(4-pyridyl)-ethylene dihydrochloride (5.5× 10-4 M) in water under aeratedconditions for 2 h produced11 as the major product (78%) andcorresponding cis isomer9 and 2,9-phenanthroline10as minorproducts (17 and 5%, respectively; Scheme 2, Table 1). However,the irradiation of an aqueous solution containing 0.5 equiv of

Figure 1. 1H NMR spectra of (a) 4-BPE‚2HCl (1) in D2O, (b) in 1 equiv of CB[7], and (c) in 0.5 equiv of CB[8] in D2O.

Figure 2. 1H NMR spectra of (a) 4-BPE‚2HCl (1) in D2O, (b) in 0.15 equiv of CB[8], (c) in 0.25 equiv of CB[8], (d) in 0.35 equiv of CB[8],and (e) in 0.5 equiv of CB[8].

Preorientation of Olefins toward a Photodimer Langmuir, Vol. 23, No. 14, 20077547

CB[8] and 1 equiv of 4-BPE‚2HCl resulted insyndimer12 asthe main product. Similarly, the irradiation oftrans-1,2-(3-pyridyl)ethylene dihydrochloride2 (3-BPE‚2HCl) and trans-1,2-(2-pyridyl)ethylene dihydrochloride3 (2-BPE‚2HCl) in the

presence of 0.5 equiv of CB[8] gave predominantly syn dimers16 and20 (Scheme 3, Table 1). The irradiation of olefins1, 2,and3 in the presence of CB[7] gave only the corresponding cisisomers9, 14, and18 and cyclized products10, 15, and19; nodimers were obtained.

To explore the use of CB[8] further as a template in bimolecularreactions,we investigated thephotodimerizationofunsymmetricalbispyridylethylene dihydrochlorides4-6(Scheme 1), where fourdimers are possible. The irradiation oftrans-3,4-BPE‚2HCl (4)in water (7.8× 10-4 M, for 2 h) under aerated conditions gavehydration product24(66%), corresponding cis isomer22(28%),and 2,8-phenanthroline23(6%) (Scheme 4, Table 2). In contrast,the irradiation of an aqueous solution of4 in the presence of 0.5equiv of CB[8] (7.8× 10-4 M of 4 and 3.9× 10-4 M of CB[8])led toanti-HT dimer27 in 80% yield along withsyn-HH dimer25(15%) and cis isomer22(5%). The irradiation of a 1:1 CB[7]complex of4gave cis isomer22as the major product along withminor amounts of cyclization and hydration products23and24,respectively. The irradiation of an aqueous solution of5 and6resulted in cis, cyclized, and hydrated products (Scheme 5, Table2). However, the irradiation of5 and6 as complexes of CB[8]gaveanti-HT dimers31 and35, but in the presence of 1 equivof CB[7], they gave isomerization products29 and 33(Table 2).

Figure 3. 1H NMR spectra of (a) 3,4-BPE‚2HCl (4) in D2O, (b) in 1 equiv of CB[7], and (c) in 0.5 equiv of CB[8] in D2O.

Figure 4. 1H NMR spectra of (a) 4-Stb‚HCl(7) in D2O, (b) in 1 equiv CB[7], and (c) 0.5 equiv of CB[8].

Table 1. Product Distributiona (Percent) upon Irradiation ofSymmetric Bispyridyl Ethylene Dihydrochlorides 1-3 in

Various Mediab,c

4-BPE‚2HCl (1) 9 10 11 12 13

water 17 05 78CB[7] 67 12 21CB[8] 02 04 90 04

3-BPE‚2HCl (2) 14 15 16 17

water 82 18CB[7] 91 09CB[8] 08 03 87 02

2-BPE‚2HCl (3) 18 19 20 21

water 86 14CB[7] 89 11CB[8] 04 02 88 06

a The percentage was calculated on the basis of the integration of1HNMR signals at 90% conversion.b See Schemes 2 and 3 for the structuresof 9-21. c Concentration of the guest: 5.5× 10-4 M.


To complete the study, we investigated the photobehavior oftrans-n-stilbazole hydrochlorides7 and 8 (Scheme 1). Theirradiation of7and8 in aqueous solution (5.6× 10-4 M) resultedmainly in the cis isomer along with a mixture ofanti-HH andanti-HT dimers in∼4% yield. The irradiation of7 and 8 ascomplexes of CB[8] in water gaveanti-HT dimers42 and46(Scheme 6, Table 3). On the basis of the results with eight olefins,we believe that macrocyclic synthetic host CB[8] can selectivelydirect olefins to either a syn or anti dimer.

Discussion

The main excited-state reactions of the eight olefins (1‚HClto 8‚HCl) investigated here are geometric isomerization, cy-clization, and addition to water (Schemes 2 and 4). Under normalconditions, these three unimolecular processes are apparentlytoo fast for bimolecular dimerization to compete. Our aim is toreverse the above trend and make the latent photoreaction, namely,dimerization dominate the excited-state chemistry of these olefins.Furthermore, we were interested in templating the reactant olefinsto a single dimer. We have established in this study thathydrochloride salts of azastilbenes1-8 could be dimerized inwater provided that their local concentration is increased and the

excited CdC bond of the olefin is protected from water.Furthermore, we have demonstrated that a stereochemicallyselective dimer could be obtained if the olefins were preorientedin the ground state. The results presented above raise the followingquestions: (a) Why were there no products of water addition inthe presence of hosts CB[7] and CB[8]? (b) Why were the dimersformed only in the presence of CB[8] but not in the presence ofCB[7]? (c) When there was more than one dimer possible, whywas a single isomer preferentially formed within CB[8]? (d)Could an intuitive model be developed to predict the stereo-chemistry of the dimer that would be formed in the presence ofCB[8]?

Olefins 1‚HCl and4‚HCl upon irradiation in water yieldedhydrated products11and24in greater than 60% yield. However,when these olefins as complexes of CB[8] and CB[7] wereirradiated, negligible amounts of hydrated products were formed.Given the fact that the cavities of CB[7] and CB[8] arehydrophobic, no water molecules are expected to be presentwithin their cavities, especially when the olefins occupy them.Therefore, the absence of hydration products is not surprising.Clearly, the two hosts serving as molecular sleeves protected theexcited CdC bond of1‚HCl to 8‚HCl from water. The fact that

Scheme 2

Scheme 3


CB[8] completely suppressed the hydration suggested that allolefin molecules were fully complexed under our conditions andat no stage did the excited olefin leave the hydrophobic cavityto face water molecules. This observation is consistent with the1H NMR results. Suppression of the hydration process allowedus to pursue our main goal of obtaining selective dimers fromolefins 1‚HCl to 8‚HCl. Within CB[7], the only observedphotoreaction was the isomerization to the corresponding cisisomers (and subsequent cyclization). The absence of dimerswithin the CB[7] cavity is consistent with the dimensions of thehost cavity and with1H NMR and mass spectral data thatsuggested that olefins1-8‚HCl formed a 1:1 complex.

Our goal of obtaining controlled photodimerization wasachieved with CB[8] as the host. Before going into the details,it is important to note the nomenclature used in this presentation.The names of the four dimers shown in Scheme 7 are dictatedby the relative stereochemistry and location of the groups A andB. Also included in the Scheme are the conventional names usedin the literature that do not make the stereochemistry obvious.In olefins1, 2, and3, A and B are the same whereas in4-8 they

are different. Because of this, in the cases of1, 2, and3 onlytwo dimers are possible (syn-HH ) anti-HT andsyn-HT ) anti-HH) whereas in4-8 four dimers can be formed.

As would be expected, the four dimers shown in Scheme 7have different dimensions. The energy-optimized (Spartanprogram at the MM1 level) structures of the four dimers areshown in Figure 5. In the same Figure, the required prearrange-ments of the olefins to form the dimers are also shown. In synhead-tail and anti head-head dimers, the two hydrophobic arylrings present on the same side at the 1 and 3 positions are farapart (>11 Å) whereas in syn head-head and anti head-taildimers the aryl rings present on the same side at the 1 and 2positions are within∼8 Å. Within CB[8], whose internal cavitydiameter is∼8 Å, only the syn head-head and anti head-taildimers could fit. More importantly, the two olefin moleculesthat are prearranged to form syn head-head and anti head-taildimers would fit better within the CB[8] cavity than the ones thatare set to form syn head-tail and anti head-head dimers. In thelatter two arrangements, a substantial part of the hydrophobicgroups of the olefin would be exposed to water. On the basis ofthe above argument and conventional knowledge that hydrophobicaryl groups would prefer to stay within a hydrophobic cavity,we believe that irradiation of the hydrochloride salts of olefins1-8should give only syn head-head and anti head-tail dimers.With this model in mind, we explored the use of CB[8] to templatethe dimerization of the hydrochloride salts of1-8.

Scheme 4

Table 2. Product Distributiona (Percent) upon Irradiation ofBispyridyl Ethylene Dihydrochlorides 4-6 in Various Mediab,c

3,4-BPE‚2HCl (4) 22 23 24 25 27

water 28 06 66CB[7] 78 19 03CB[8] 05 15 80

2,4-BPE‚2HCl (5) 29 32 37 30 31

water 35 40 25CB[7] 91 09CB[8] 05 30 65

2,3-BPE‚2HCl (6) 33 36 38 34 35

water 39 47 14CB[7] 81 19CB[8] 05 30 10 55

a The percentage was calculated on the basis of the integration of1HNMR signals at 80% conversion.b See Schemes 4 and 5 for the structuresof 22-38. c Concentration of the guest: 7.8× 10-4 M.

Table 3. Product Distributiona (Percent) upon Irradiation ofStilbazole Hydrochlorides 7 and 8 in Water and within CB[8]b,c

4-SA‚HCl (7) 39 40 41 42

water 93 02 03 02CB[8] 04 01 05 90

2-SA‚HCl (8) 43 44 45 46

water 95 01 02 02CB[8] 17 02 81

a The percentage was calculated on the basis of the integration of1HNMR at 90% conversion.b See Scheme 6 for the structures of39-46.c Concentration of the guest: 5.6× 10-4 M.


We believe that three factors play a major role in determiningthe stereochemistry of the dimer being formed within CB[8].These are the “best fit” of the two olefins within the reactioncavity, minimization of electrostatic repulsion, and maximizationof weak attractions between the reactive olefins present withinCB[8]. Results of olefins1‚HCl, 2‚HCl, and3‚HCl emphasizethe importance of best fit in controlling the dimerization process.

One would expect the electrostatic repulsion to be lower in theanti dimer where the pyridinium groups are at the 1 and 3 positionsthan in the syn dimer where these groups are attached to adjacentcarbons (1 and 2 positions). On the basis of the principle ofminimization of electrostatic repulsion between pyridiniumgroups, one would expect the anti dimer to be formed withinCB[8]. However, the principle of best fit suggests that we shouldget only the syn dimer. (See above.) As seen in Table 1, in allthree cases the main dimer (>85%) is syn. Clearly the firstcondition for selective dimerization is “fit within the reactioncavity”.

Now the question is when the two possible dimers and theprecursor olefin arrangements are similar in size which one wouldbe preferred. We have experimented with4‚HCl, 5‚HCl, and6‚HCl to address this question. In these examples, the two ends,although positively charged, are not the same. These olefins inprinciple can give four dimers (Scheme 4). Of these four dimers,syn head-tail and anti head-head dimers are too large to fitwithin the CB[8] cavity. Indeed they were not formed. However,

Scheme 5

Scheme 6

Scheme 7


the remaining two dimers, syn head-head and anti head-tail,are similar in size, and they both, as well as their precursorolefins, could fit within the CB[8] cavity. A closer examinationof the structures reveals that in the anti head-tail dimer thelocation of positive charge is slightly offset and therefore theelectrostatic repulsion is expected to be lower than in the synhead-head dimer (Scheme 4). The fact that the anti head-tailis the major product in each of these examples (Table 2) suggeststhat the minimization of electrostatic repulsion plays an importantrole in determining which of the two dimers of equal size isformed.

The above qualitative model is further supported by thephotobehavior of7‚HCl and8‚HCl (Scheme 7). The irradiationof these olefins as complexes of CB[8] gave a single dimer,namely, anti head-tail 42 and46 (Table 3). The preference forthis dimer is easily understood on the basis of the minimizationof electrostatic repulsion between like charges and fit within thecavity. In the syn head-head arrangement, the positively chargedpyridinium groups would be closer (adjacent) than in the antihead-tail arrangement.

Achieving photodimerization of olefins that normally do notdimerize in solution requires an increase in the local concentrationof the olefin in a given medium. This could be achieved by usingwater as the solvent where olefins often tend to aggregate as aresult of hydrophobic forces.42-46 Increasing the local concentra-tion alone is insufficient to obtain a selective dimer. Molecules

need to be preorganized, and this is often achieved at an interfacebetween hydrophobic and hydrophilic phases. Although con-ventional micelles provide an interface, they most often do notyield a single dimer.3-5,32,47-51 A study by Whitten and co-workers on the photodimerization of 4-stilbazolium and 2-stil-bazolium cations in micelles, reverse micelles, monolayers, andclays highlights the importance of one more factor that must becontrolled during the photodimerization process.6,7Although onlyisomerization occurred within conventional micelles, surprisinglywithin an AOT reverse micelle a syn head-head dimer wasobtained as the major product from 4-stilbazolium and 2-stil-bazolium cations. The more rigid reaction cavity of a reversemicelle not only helped to increase the local concentration andalign molecules at an interface but also favored a single dimerby restricting the freedom of the preorganized reactive olefins.Thus, it is important to use a reaction cavity that is tight andtime-independent (micelles unfortunately are dynamic and loose)to obtain a selective dimer. To predict the dimer that would beformed in a given medium, one needs to have an intuitive modelon hand. We have generated one in this study.

In this presentation, we have demonstrated that CB[8] has theability to template the hydrochloride salts of various bispyridylethylenes and stilbazoles toward a single dimer. Unlike micelles,modestly water-soluble CB[8] did not provide freedom to reactiveolefins that helped to maintain the preorientation of olefins untilthe completion of the dimerization process. Before closing, wewish to point out that cucurbiturils are not unique in orientingolefins toward a single photodimer. Hosts such as cyclodextrins,calixarenes, and a Pd nanohost with features similar to that ofcucurbiturils have been used to template photodimerizations inwater, and the model developed here correctly predicts the dimerbeing formed in each case.8-25

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Hamilton, T. D.Top. Curr. Chem.2005, 248, 201-221.(42) Breslow, R.Acc. Chem. Res.2004, 37, 471-478.(43) Lindstrom, U. M.; Andersson, F.Angew. Chem., Int. Ed.2006, 45, 548-

551.(44) Muthuramu, K.; Ramamurthy, V.J. Org. Chem.1982, 47, 3976-3979.(45) Syamala, M. S.; Ramamurthy, V.J. Org. Chem.1986, 51, 3712-3715.(46) Devanathan, S.; Ramamurthy, V.J. Photochem. Photobiol.1987, 40,

67-77.

(47) Nakamura, Y.; Kato, T.; Morita, Y.Tetrahedron Lett.1981, 22, 1025-1028.

(48) Nakamura, Y.J. Chem. Soc., Chem. Commun.1988, 477-478.(49) Berenjian, N.; de Mayo, P.; Sturgeon, M.-E.; Sydnes, L. K.; Weedon, A.

C. Can. J. Chem.1982, 60, 425-436.(50) Muthuramu, K.; Ramanath, N.; Ramamurthy, V.J. Org. Chem.1983, 48,

1872-1876.(51) Mayer, H.; Schuster, F.; Sauer, J.Tetrahedron Lett.1986, 27, 1289-

1292.

Figure 5. Energy-optimized structures of the dimers of 3,4BPE‚2HCl (4).


Experimental Section

Materials. Cucurbiturils were synthesized according to theprocedure reported by Day et al.52Symmetrical bispyridyl ethylenes1 and3 and unsymmetrical bispyridyl ethylenes4-6 obtained fromSigma-Aldrich were used without further purification.trans-1,2-Bis-(3-pyridyl) ethylene (2) and stilbazoles7and8were synthesizedaccording to the procedure reported in the literature.53,54 Thehydrochloride form of olefins1-8was obtained by dissolving themin a minimal amount of a methanol/10% HCl solution and evaporatingthe methanol under reduced pressure.

Preparation and Irradiation of trans-Bispyridyl EthyleneComplexes with Cucurbiturils (CBs) in Water. Two milligramsof bispyridyl ethylene dihydrochloride taken in 50 mL of deionizedwater was sonicated at 70°C for 5-10 min. Half an equivalent ofCB[8] (or 1 equiv of CB[7]) was added to this solution and sonicatedfor an additional 1 h to obtain a clear solution. The solution wascooled to room temperature and filtered through a Whatmann filterpaper of fine porosity to remove any insoluble particles. Thecomplexes were irradiated for 1 h using a 450 W medium-pressuremercury lamp immersed in a water-cooled Pyrex jacket. Followingirradiation, the solution was transferred to a separatory funnel, and10% NaOH(aq) was added dropwise until basic pH (>9) wasobtained; then extraction was carried out with chloroform. The organiclayer was separated, dried over anhydrous Na2SO4, filtered, vacuumdried, and analyzed by1H NMR.

Titration Studies of Bispyridylethylene Dihydrochlorides withCB[8]. One milligram of the guest (1-8) was dissolved in 0.6 mLof D2O, and the solution was transferred to an NMR tube. To the

guest solution, finely powdered CB[8] was added in 0.1 equivincrements, and1H NMR was recorded after each addition.

Determination of Binding Constants by 1H NMR Titration.1H NMR titration experiment of1‚HCl@CB[8] was conducted onthe basis of the model depicted in Scheme 8. The upfield shift ofthe olefinic proton (Hc) of guest1‚HCl (compared to the free guestin D2O) was measured as a function of the concentration of guestadded to a fixed concentration of host CB[8]. This complexation canbe explained by the stepwise mechanism (Scheme 8) involving theinitial formation of the 1:1 host/guest complex as represented by eq1, followed by the addition of a second host to give the 2:1 host/guest complex described in eq 3.1H NMR titration results (changein chemical shift (δ) vs [guest]) of the H/G complex were fit to eq5 using nonlinear least-square fitting program Graphpad prismsoftware. The nonlinear nature of the curve, which was plottedbetween changes in the chemical shift of the olefinic proton signalagainst the concentration of the guest added at fixed concentrationof the host, indicates the presence of higher-order inclusion

(52) Day, A.; Arnold, A. P.; Blance, R. J.; Snushall, B.J. Org. Chem.2001,66, 8094-8100.

(53) Gromov, S. P.; Vedrinikov, A. I.; Ushakov, E. N.; Lobova, N. A.;Botsmanova, A. A.; Kuz’mina, L. G.; Churakov, A. V.; Strelenko, Y. A.; Alfimov,M. V.; Howard, J. A. K.; Johnels, D.; Edlund, U. G.New J. Chem. 2005, 29,881-894.

(54) Williams, J. L. R.; Adel, R. E.; Carlson, J. M.; Reynolds, G. A.; Borden,D. G.; Ford, J. A., Jr.J. Org. Chem. 1963, 28, 387-390.

Scheme 8. Stepwise Binding Model for the Formation of a 1:2 Host/Guest Complex

Figure 6. Nonlinear fitting curve obtained for the observed trendin the chemical shift of guest olefinic (Hc) protons.


complexes. Fitting yielded anR2 value of 0.9908, indicating that theassumed stepwise equilibrium model fits the observed experimentaltrend and is adequately represented by the equilibrium constantexpression (eq 5)

where∆ is the observed chemical shift of the complex, [L]) [BPE],∆11 ) δHG - δG, ∆12 ) δHG2 - δG, andδG is the1H NMR chemicalshift of guest in D2O.

The best fit presented in Figure 6 was obtained with the parameters∆11) -1.356 and∆12 ) 0.089. The binding constants,K1 andK2,were calculated to be 1.03×103M-1and 8.6×105M-1, respectively.The overall binding constant was calculated to be 8.85× 108 M-2.The calculated binding constantsK1 andK2 are reasonable, andK2

> K1 means that the formation of the 1:2 H/G complex is morefavorable.

1H NMR Data for Dimers. Syn dimer of4BPE‚2HCl (12): 1HNMR (400 MHz, CDCl3, TMS) δ 4.52 (d, 4H), 6.95 (d, 8H,J )8.4 Hz), 8.42 (d, 8H,J ) 8.4 Hz).

Anti Dimer of 4BPE ‚2HCl (13). 1H NMR (400 MHz, CDCl3,TMS) δ 3.72 (s, 4H), 7.12 (d, 8H,J ) 8.4 Hz), 8.52 (d, 8H,J )8.4 Hz).

Syn Dimer of 3BPE‚2HCl (16). 1H NMR (400 MHz, CDCl3,TMS) δ 4.53 (s, 4H), 7.07 (m, 4H), 7.38 (d, 4H), 8.35 (d, 4H), 8.42(s, 4H) 6.95.

Anti Dimer of 3BPE ‚2HCl (17). 1H NMR (400 MHz, CDCl3,TMS) δ 3.71 (s, 4H), 7.15 (m, 4H), 7.45 (d, 4H), 8.4 (m,8H).

Syn Dimer of 2BPE‚2HCl (20). 1H NMR (400 MHz, CDCl3,TMS) δ 5.18 (s, 4H), 6.90 (q, 4H), 7.07 (d, 4H), 7.39 (t, 4H), 8.6(d, 4H).

Anti Dimer of 2BPE ‚2HCl (21). 1H NMR (400 MHz, CDCl3,TMS) δ 4.39 (s, 4H), 7.1 (q, 4H), 7.25 (d, 4H), 7.55 (d, 4H), 8.65(d, 4H).

Anti HT Dimer of 2,4BPE ‚2HCl (31). 1H NMR (400 MHz,CDCl3, TMS) δ 4.75 (dd, 2H), 4.95 (dd, 2H), 7.1-7.8 (m, 12 H),8.40 (d, 4H).

Anti HT Dimer of 2,3BPE ‚2HCl (35). 1H NMR (400 MHz,CDCl3, TMS) δ 4.71 (dd, 2H), 4.98 (dd, 2H), 7.1-7.8 (m, 12 H),9.00 (d, 2H), 9.15 (s, 2H).

Syn HH Dimer of 2,3BPE‚2HCl (34). 1H NMR (400 MHz,CDCl3, TMS)δ 4.65 (d, 2H), 5.00 (dd, 2H), 7.1-7.8 (m, 12 H), 8.86(d, 2H), 9.38 (s, 2H).

Anti HT Dimer of 4SA ‚HCl (42). 1H NMR (400 MHz, CDCl3,TMS) δ 4.48 (m, 4H), 7.08-7.4 (m, 14 H), 8.35 (d, 4H).

Anti HT Dimer of 2SA ‚HCl (46). 1H NMR (400 MHz, CDCl3,TMS) δ 4.9-5.0 (bs, 4H), 7.1-7.6 (m, 16 H), 8.42 (d, 2H).

Acknowledgment. V.R. thanks the NSF for financial support(CHE-0213042 and CHE-0531802).

LA700803K

∆ )∆11 K1 [L] +∆12 Κ1 Κ2 [L] 2

1+ K1 [L] + K1 K2 [L] 2(5)


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