The Importance of Pi-Interactions in Crystal Engineering (Frontiers in Crystal Engineering) || CH-π...

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JWST146-c03 JWST146-Tiekink January 20, 2012 14:12 Printer: Yet to come

3CH–π and π–π Interactions as

Contributors to the Guest Binding inReversible Inclusion andEncapsulation Complexes

Pablo Ballester1 and Shannon M. Biros2

1Catalan Institution for Research and Advanced Studies (ICREA) & Institute ofChemical Research of Catalonia (ICIQ), Tarragona, Spain

2Department of Chemistry, Grand Valley State University, Allendale, Michigan, USA

3.1 Introduction

Electrostatic factors play a dominant role in most intermolecular binding interactions [1].Therefore, in very general terms one can expect that regions of negative charge in amolecule will be attracted to regions of positive charge in another, independent of theintrinsic physical origin of the charge density. In fact, it is the particular combination ofinteracting partners that is generally used in the classifications of intermolecular forces [2].For example, π -systems (whether belonging to aromatic rings or to isolated double ortriple bonds), are associated with regions of negative density charge. Consequently, it isreasonable to assume that such regions will tend to be involved in a variety of molecularinteractions with other electron-deficient partners. When compared to the average free-enthalpy change of –1.5 to –1.9 kcal/mol for the establishment of a primary N−H···O=Chydrogen bond in chloroform, the intermolecular interactions that involve π -systems can be

The Importance of Pi-Interactions in Crystal Engineering: Frontiers in Crystal Engineering, First Edition.Edited by Edward R. T. Tiekink and Julio Zukerman-Schpector.© 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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80 The Importance of Pi-Interactions in Crystal Engineering

ranked from moderately strong to very weak. In this chapter we will restrain ourselves to thediscussion of only two types of π -binding forces: aromatic–aromatic interactions, whichcan be considered a specific case of π–π interactions, and CH–π interactions. Other typesof interactions involving π -systems include cation–π interactions, anion–π interactions,polar hydrogen–π interactions and electron lone-pair–π interactions. Some of these willalso be present in the examples included in this chapter.

We will present aromatic–aromatic interactions and CH–π interactions in the contextof supramolecular inclusion and encapsulation complexes. Synthetic molecular receptorsare ideal systems for the study of quantitative structure-activity relationships. In some ofthe examples both interactions will occur simultaneously even in combination with otherinteractions involving π -systems, as mentioned above, and it will be difficult to dissecttheir relative importance. However, in other cases only a single type of the two targetedinteractions will be operative due to geometrical constraints imposed by the supramolecularassembly. In this chapter we will present first a short overview of the theoretical investi-gations carried out to unravel the physical nature of these two types of interactions. Next,selected examples of experimental studies evidencing the existence of such interactions willbe discussed. Due to the fact that the topic of the book is centred on crystal engineering,we will place special emphasis on solid-state examples but solution studies will be brieflymentioned when appropriate.

Due to the almost exclusive use of aromatic panels to shape the concave cavities of manysynthetic receptors, aromatic–aromatic interactions and CH–π interactions are commonlyfound as intermolecular forces stabilising the resulting supramolecular complexes. In thesolid-state and in the X-ray structures of supramolecular complexes, evidence for theexistence of these interactions usually stems from the observation of shorter distancesbetween the interacting partners than the sum of their van der Waals radii.

However, solid-state studies provide less convincing evidence than spectroscopic andtheoretical studies on the existence of weak intermolecular interactions, that is, π–π andespecially CH–π , which form the topic of this chapter. In the solid state, these weak bondsare usually competing with stronger interactions like hydrogen bonds, coordinative bondsand charge–charge interactions in addition to the typical van der Waals interactions, whichcan be of comparable energy. When intermolecular interactions of different strengths areinvolved in the crystal packing, the spatial relationship of the atoms or regions that canbe involved in weak interactions might be an artefact of other stronger interactions that aremore relevant to the overall lattice energy. The observed arrangement of molecules in thecrystal packing is a direct result of the interplay of all intermolecular interactions. For thisreason, a particularly important question to address when dealing with weak intermolecularinteractions in the solid state has to do with situations where those interactions, whenpresent in the crystal, are key in determining molecular configuration and packing.

In this chapter, we will focus our attention on two weak intermolecular interactions(aromatic–aromatic interactions and CH–π interactions) within the framework of stoichio-metric and well defined inclusion or encapsulation complexes present in the solid state.In doing so, we try to avoid answering questions about the relative importance of weakinteractions in crystal packing. However, in a few cases we will briefly mention the potentialeffects of such interactions in sustaining the overall supramolecular structure of the crystal.Other chapters in the book will dwell in much greater detail on this subject. In most of thepresented examples, the supramolecular complex observed in the solid state has been used

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CH–π and π–π Interactions as Contributors to Guest Binding 81

as additional evidence to sustain the formation of similar architectures in solution, whichin turn are supported by detailed spectroscopic and/or theoretical results.

3.1.1 Theoretical Considerations of Aromatic–Aromatic (π–π ) Interactionsand CH–π Interactions

Aromatic–aromatic interactions, as any other noncovalent intermolecular interaction, arethe result of the sum of several forces. As mentioned above, electrostatic forces establishedbetween the static molecular charge distributions of the aromatic systems might play asignificant or major role. However, the magnitude of other forces like the van der Waalsinteractions, charge-transfer interactions, induction effects and solvent effects should notbe underestimated. Consequently, it is of prime importance to consider the relative effectof each of these forces to the overall interaction.

For example, since aromatic units usually have large planar surfaces it should be expectedthat the van der Waals interactions would be maximised when two π–aromatic systems stackon top of one another adopting a geometry know as “face-to-face stacked” (Figure 3.1c).

The electrostatic surface potential (ESP) of aromatics constitutes an easy way to visualisetheir Qzz quadrupole moment that measures the charge distribution with respect to an axisperpendicular to the plane of the aromatic ring. The Qzz quadrupole has the adequatespatial orientation to be involved in the formation of π–π interactions in the “face-to-facestacked” geometry of aromatics. Not unexpectedly, the computed ESP of benzene (Gaussian

Figure 3.1 Electrostatic potential surfaces for representative π -aromatic systems, (a) benzene;and (b) hexafluorobenzene. The electrostatic potential range is ±23 kcal/mol for benzene and±29 kcal/mol for hexafluorobenzene. In the center of the aromatic ring the potential is negativefor benzene and positive for fluorobenzene. Different geometries of aromatic interactions, (c)face-to-face or π–π ; and (d) face-to-edge or CH–π .

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09, RMP2-FC/3-21G∗) clearly shows a negatively charged region on the top of the twosides of the π -system, suggesting that to directly stack two benzenes on top of one anotherwill lead to an adverse electrostatic repulsion between them. Nevertheless, a single-pointenergy calculation at the same level of theory for the “face-to-face stacked” geometry ofthe benzene dimer with a distance of 3.5 A between the aromatic centroids (Figure 3.1cleft) affords a calculated favourable interaction energy for the complex of –1.6 kcal/mol.This value reinforces the idea that electrostatic forces, although important, are not the onlyforce to be taken into account when considering π–π aromatic interactions [3].

When the above “face-to-face stacked” geometry is taken as the starting point to performa minimisation of the energy of the complex, the calculation converged into an “offsetstacked” geometry for the complex for which an interaction energy of –1.75 kcal/mol wascomputed (Figure 3.1c right). The “offset stacked” geometry is also referred to as displacedor slipped stack; in this geometry regions of positive electrostatic potential align with regionsof negative potential at the expense of reduced van der Waals contacts. There is also afavourable hydrophobic component to the “offset stacked” geometry since the hydrophobicsurface of the dimer increases with respect to the “face-to-face stacked” geometry. Suchan advantage is more important in larger arenes (i.e. naphthalene or anthracene) thatpreferentially interact in the “offset stacked” geometry.

As early as 1958, Cox et al. noticed that in single crystals of benzene, obtained at−3◦C, the aromatic units packed in “edge-to-face” orientation [4]. Burley and Petsko alsoestablished the importance of this binding geometry for aromatic–aromatic interactions inthe tertiary and quaternary solid-state structure of proteins and peptides [5,6]. Calculationsrevealed that for the benzene dimer the “edge-to-face” tilted geometry is more favourablethan either of the two previous ones involving direct π–π interactions [7]. Other possiblestructures for the benzene dimer not involving direct π–π interactions are the symmetricT-shaped, tilted-T-shaped and face-tilted-T-shape (Figure 3.1d) [8]. The interaction energyfor the “edge-to-face” tilted geometry of the benzene dimer computed with Gaussian 09 atthe RMP2-FC/3-21G∗ level of theory is –3.39 kcal/mol. This value represents an “extra”stabilisation energy of more than 1.5 kcal/mol with respect to the geometries with directπ–π interactions.

In the “edge-to-face” geometries a region of negative electrostatic potential (the faceof the π -system) is placed in contact with a region of positive electrostatic potential (theedge of the π -system). The electrostatic forces are maximised in this arrangement. The“offset-stacked” geometry appears to be more common when the electron density of one orboth aromatic systems is reduced (i.e. by substituent effects). In the case of the interactionof donor–acceptor π -systems or interactions of aromatic compounds having quadrupolemoments of opposite sign, the electrostatic interaction between the faces of the ring becomeattractive and the “face-to-face” stacking geometry is observed [9]. The importance ofthe electrostatic contribution in the “face-to-face” stacking geometry has been clearlydemonstrated by Cozzi and Siegel in a series of studies [10,11]. The relative importanceof electrostatic forces with respect to polarisability and van der Waals interactions inthe “edge-to-face” [12] and “offset-stacked” [13,14] geometries have also been assessedrecently. These two types of geometries are the most abundant in Nature and supramolecularchemistry. Cubberley and Iverson performed an elegant solvent study to indirectly addressthe nature of the aromatic interaction in different types of geometries [15]. The resultsshowed that the solvophobic effect is modulated by the geometry of the interaction that in

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turn is dictated by electrostatic factors in a predictable fashion that depends on the electronicnature of the aromatics involved.

A close inspection of the “edge-to-face” geometries suggests that they are more aptlydescribed as a CH–π interaction in which the π -systems belong to an aromatic ring. Ingeneral, CH–π interactions can be classified into two main groups: a) “typical” CH–π

interactions and b) “activated” CH–π interactions. While the former type of interaction in-volves purely aliphatic CH groups the latter has to do with CH groups attached to multiplebonds or having electron-withdrawing substituents (e.g. the halogens). The magnitude ofany of the two types of CH–π interactions is considerably smaller than the conventionalhydrogen bond. The “typical” CH–π interaction is the weakest of the two and featuresreduced directionality. Ab initio calculations indicated out that the major source for a “typ-ical” CH–π attraction is from dispersion interactions and that the electrostatic contributionis always smaller [16]. In short, the nature of the “typical” aliphatic CH–π interaction canbe considered to be very similar to that of the interaction in van der Waals clusters. Onthe other hand, the nature of “activated” CH–π interactions, especially for the case of veryacidic protons, may have similarities to weak hydrogen bonds in terms of directionality anda large electrostatic contribution.

In the late 1970s, Nakagawa, and coworkers pointed out the important role of the C−Hbonds as potential partners for establishing attractive interactions with π -systems [17].Since then it has been clearly established that these molecular forces play significant rolesin many aspects of chemistry. Phenomena controlled by CH–π interactions [18] include theconformation of organic molecules [19], crystal packing [20], host–guest chemistry [21],reaction selectivity [22] and biological processes [23]. In this chapter the relevance ofboth types of CH–π interactions will be highlighted using the solid-state structures ofsupramolecular inclusion and encapsulation complexes.

3.2 Probing Aromatic–Aromatic (π–π ) Interactions and CH–π

Interactions with Solid-State Structures of Reversible Inclusion andEncapsulation Complexes

3.2.1 Inclusion Complexes

One of the early suggestions of the important role of CH–π interactions in stabilisingsupramolecular complexes was made in 1983 by Andreetti, et al. in the X-ray crystallo-graphic study of a non-inclusion complex of p-(1,1,3,3-tetramethylbutyl)calix[4]arene 1aand toluene 2 (Figure 3.2) [24]. Calix[4]arene 1a exists in the “cone” conformation in thesolid state. This conformation is favoured by the intramolecular cyclic array of hydrogenbonds established between the phenolic OHs in the lower rim of 1a. But in spite of adoptinga cone conformation 1a does not include toluene 2. The para substituents seem to be ratherimportant in determining the noninclusion character of the complex in the solid state. Twoof the four terminal t-butyl groups of the octyl chain in 1a are pointing into the cavitypreventing the inclusion of 2.

The packing of 1a creates intermolecular cavities defined by two adjacent calixarenemolecules and their alkyl chains that extend outside of the cavity (Figure 3.3). These cavitiesare suited to include one molecule of 2. The authors state that it is in fact the presence

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Figure 3.2 Molecular structures of the calix[4]arenes 1.

Figure 3.3 Selected views of sections of the crystal packing structure for the clathrates of1a and 2. (a) Two adjacent molecules of 1a in the same layer form a cavity that includes 2probably via CH–π interactions, left (top view), right side view, and (b) Adjacent layers of 1amolecules form a channel filled with 2. Note the 90◦ twist experienced by the two toluenemolecules of 2 which stack in the channel in order to maintain the CH–π interactions, left (topview), right side view.

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of the aromatic molecule in solution that stabilises the observed crystal structure for theclathrate. The alternate stacking of other two calixarenes with the same relative orientationbut shifted 90◦ with respect to the one below defines a channel connecting adjacent cavities.The stacking motif is driven by van der Waals contacts between the phenolic OHs and theoctyl chains that extend outside of the cavity of 1a. The toluene guest 2 that is found withinthe channels interacts mainly by van der Waals contacts with the aliphatic chains althoughthe existence of CH–π interactions between the methylene protons of 1a and the aromaticring of 2 cannot be ruled out (d[H2C· · ·Phcentroid] = 3.92 A). In fact, the aromatic ring of 2is oriented perpendicularly to the equatorial methylene protons of the calixarenes formingthe cavity and the 90◦ shift of the calixarenes units is also translated to adjacent toluenemolecules in the channel.

Recently, Andreetti, et al. reported that calixarene 1b, where the octyl para-substituentis replaced with a para-t-butyl group, does form an inclusion complex with toluene 2 [25].The size of the para-t-butyl substituent is not too large to occlude the cavity and moreoverattractive CH3–π interactions between the methyl groups of the t-butyl and the aromaticring of the guest were mentioned as the main driving force for complex stability (d[1b • t-Bu-H3C· · ·2 • Phcentroid] ∼ 4.5 A) [26]. Both the included toluene molecule 2 and the t-butylgroups showed some disorder in the crystal structure. The toluene molecule lies on a fourfoldaxis and can have two equivalent orientations. However, in both of them the methyl group of2 is included deep in the aromatic cavity of 1b. The distance from the methyl carbon atomof included 2 to a reference plane defined by the four methylene carbons is 2.57 A [27].Surprisingly, the authors do not mention additional CH–π interactions that are clearlypresent in the 2⊂1b inclusion complex; where ⊂ denotes encapsulation. These unmentionedinteractions occur between the methyl group of toluene guest and the aromatic rings of 1b.Also, their C–Phcentroid distances are significantly shorter (d[1b • Phcentroid· · ·CH3 • 2] ∼3.6–3.7 A) than the measured ones for the t-butyl methyl CHs and the aromatic π -systemof 2 [26].

In 1998 Arduini et al. published an interesting study on the temperature dependence ofthe CH3–π interactions of the 2⊂1b complex. Again, only the CH3–π interactions betweenthe methyl groups of the t-butyl and the aromatic ring of the guest were mentioned [27].They found that at 220 K the 2⊂1b complex exists in two different conformations of thehost that in turn exhibited slightly different host–guest structural relationships (Figure 3.4a).By comparing the distances between the carbon of one of the methyl groups of 1b andone aromatic carbon of 2, the authors concluded that the CH3–π interactions are weaker at220 K than at RT. They reported that a distance of 3.34 A measured in the 2⊂1b complexat RT increased to −3.75–4 A at 220 K. These results were rationalised by suggesting adifferent temperature dependence of two driving forces for the inclusion of 2 in 1b. Theauthors stated “As the temperature decreases the van der Waals forces, which depend onT−1, increases whereas the CH3–π interaction do not follow the same trend. Thus thecalixarene host molecule is distorted mainly by the gain of van der Waals lattice energyand the CH3–π interactions decrease as the host–guest interatomic contacts increase, evenif toluene guest still remains inside the intramolecular cavity of the host”. However, whenthe distances between the carbon atom of the methyl group of guest 2 and the aromaticrings of the host of 1b for the two structures of the inclusion complexes obtained at220 K and at RT are compared a different picture emerge. In all three structures these

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Figure 3.4 (a) Side view (up) and top-view (down) of the two different conformations foundin the solid-state structure of 2⊂1b complex at 220 K, and (b) Top view of the X-ray structureof 1b involved in the 2⊂1b complex at RT.

distances daverage [1b • Phcentroids···CH3 • 2] are in the range of 3.6–3.7 A and consequentlythe corresponding CH3–π interactions seem to have a reduced temperature dependence. Inaddition, our analysis of the crystal structures of the complexes obtained at 220 K indicatesthat while one of the distances between opposite carbon atoms of the methyl group inthe t-butyl substituent increases compared to the structure at RT (9.0 to 9.45–9.91 A)the diagonally opposed one shortens (9.0 to 8.20–8.36 A). In all likelihood, the CH3–π

interactions that take place in the upper rim of the 2⊂1b inclusion complex are moresensitive to the interplay between the molecular interactions that control the packing of thelattice and the structure of the inclusion complex in the solid state. Conversely, the CH3–π

interactions that occur inside the cavity are less affected by small changes in the crystalpacking. It is likely that the latter are also stronger due to both the higher acidity of theCHs and higher basicity of the aromatic rings involved, which also explain why they areless affected by temperature.

When para-t-butylcalixarene 1b was crystallised from anisole a cage inclusion complexwas obtained. Two molecules of 1b in the cone conformation facing their methyl groupsof the para-t-butyl substituents create a supramolecular capsule that includes one moleculeof anisole 3 [28]. Anisole was found to be disordered in the cavity in at least eight equiva-lent orientations and no positions were retained during the analysis of the diffraction data.Nevertheless, the authors noted that they were confronted with another piece of experi-mental evidence for attractive interactions between the t-butyl CH3 groups of 1b and theπ -electrons of 3, which are responsible for the stability of the 2 : 1 inclusion complex andits intermolecular character. Not having at hand the position of the included guest, we mod-elled and minimised the structure of the 3⊂1b2 complex constraining the two calixarene

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Figure 3.5 (a) CAChe minimised structure of the 3⊂1b2 complex 1b is shown in stick repre-sentation and 3 as a CPK model, and (b) Focus on a region in the crystal packing of the 3⊂1b2

complex highlighting the CH–π interactions between adjacent supramolecular capsules.

units to the X-ray data [29]. The minimised structure of the complex is shown in Figure 3.5and serves to highlight additional CH–π interactions between the aromatic CHs and thehydrogens of the OCH3 substituent of guest 3 with the aromatic rings of the two dimerisedcalixarene units that are involved in the inclusion complex. The role of CH–π interactionsin the crystal packing is also important, the dimer packs into layers and adjacent layers ofdimers pile through CH–π interactions as shown in Figure 3.5b.

In 1984, Ungaro et al. reported a 1 : 1 inclusion complex of acetone 4 and the unsubstitutedcalixarene 1c [30]. The building block of the crystal is the 4⊂1c inclusion complex in whicha CH3 of the guest point into the calixarene cavity. Most likely, CH–π interactions are alsoresponsible for the stabilisation of the complex, Figure 3.6.

The donor strength of C−H groups has a wide range that spans from very weak donorsto the strengths of weaker types of O−H groups [31]. In consequence, and as mentionedabove, the more acidic C−H types can establish interactions with Ph acceptor rings thatare as strong as weak hydrogen bonds. When the C−H acidity diminishes, the strength ofthe C−H–π interaction decreases and the nature of the interaction blurs into the van derWaals region. To substantiate this fact a search in the Cambridge Structural Database (CSD)revealed that the mean distance for the hydrogen atoms of chloroform to the Ph plane was2.38 A but increased to 2.75 A for methyl groups [32].

In this sense, interactions between the hydrogen atoms of haloforms and phenyl ringsin inclusion complexes have also been reported. In particular, Atwood et al. described in

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Figure 3.6 Molecular structure of the 4⊂1c complex. 1c is shown in stick representation and4 as a CPK model.

1992 the inclusion of a dichloromethane molecule in the interior of each one of the twoaromatic cavities of an aluminium-fused bis calixarene 5 derivative of 1b, Figure 3.7 [33].Both calixarenes units are in the cone conformation and in each one of them the methylenechloride H-atoms interact with two opposite host aromatic rings with a H3C···Phcentroid

distance of 3.54 A. The stability of the inclusion complex is probably assisted by additionalCH-n interactions between the lone pair of electrons of the chlorine atoms and the t-butylhydrogens of the host [31]. From a search in the CSD, the authors claimed that theirwork constituted the first example of a haloform-included complex with such a host–guest interaction.

A related example of a macrocyclic oligophenylene host 6 including a chloroformmolecule through a CH–π interaction was reported by Hensel et al. in 1997 [34]. Theasymmetric unit is formed by two molecules of 6 with slightly different conformations,but in both of them a chloroform molecule is included that has the hydrogen atom directedtoward one of the tetrasubstituted phenyl rings with a daverage [6 • Phcentroid···HCl3] = 3.46A. In this case, CH–n interactions between the lone-pair electrons of the chlorine atoms

Figure 3.7 (a) Synthesis of dimer 5, and (b) Molecular structure of one of the calixarene unitsin the dimer 5 containing the methylene chloride molecule. The calixarene is shown in stickrepresentation and the CH2Cl2 molecule as a CPK model.

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Figure 3.8 Molecular structure of the Cl3CH⊂6 complex. Oligophenylene 6 is shown in stickrepresentation and the chloroform molecule as a CPK model. Some hydrogen atoms in 6 areomitted for clarity.

and the aromatic CHs of host 6 might also play an important role in the thermodynamicstability of the complex, Figure 3.8. It is also possible that additional n–π interactions areoperative between the lone pairs of the chlorine atoms and the phenyl ring opposite to theone at which the hydrogen is directed [35].

An interesting example of the interplay between CH3–π interactions and other inter-molecular forces in controlling the packing of the lattice and the solid-state structure of aninclusion supramolecular complex was recently described by Ballester et al. [36]. In 2002,the authors described two tripodal amidopyridine receptors 7 capable of selective recogni-tion of methylmethanetriacetic acid 8 (MMTA) in organic solvents. Receptors 7 can adopta syn conformation that is very well suited for the complexation of MMTA (Figure 3.9).In this conformation, the hydrogen-bonding groups in the amido-pyridine units convergeand act simultaneously “grasping” the guest molecule in the induced cleft of the receptor.Molecular modelling studies suggested two possible geometries for the complexes 8⊂7.In geometry A, the methyl group of 8 is endo to the cavity, while in geometry B it is exo.On the one hand, the exo geometry can be expected to be more favourable than the endobecause of the potential steric hindrance of the methyl group. On the other hand, the endobinding mode can benefit from favourable CH–π interactions between the methyl group ofthe MMTA and the central aromatic ring of the receptor.

Crystal structures of the complexes 8⊂7a and 8⊂7b were obtained from crystals grownfrom slow diffusion of cyclohexane into 1 : 1 chloroform solutions either of 8 : 7a or 8 : 7bat room temperature, Figure 3.10. Each complex had a different binding geometry in thesolid state that was in complete agreement with its predominant structure determined in

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Figure 3.9 Molecular structures of triacid 8, the tripodal amidopyridyne receptors 7, andthe complexation equilibrium between the free and bound states. The two possible bindinggeometries for the 8⊂7 complexes, A endo and B exo involving a tritopic interaction betweenthe binding partners are shown.

solution using 1D and 2D 1H-NMR spectroscopy and variable-temperature experiments.The geometric parameters derived from the X-ray data clearly support a subtle balanceof intermolecular and intramolecular interactions as being responsible for the differentbinding modes and packing of the lattice. In both cases triadic 8 is docked into the receptorvia six intramolecular hydrogen bonds. The maximisation of the intermolecular interactionsin the 8⊂7a (CH3/π and hydrogen bonding) forces a tilting of the amides away from thecoplanarity with the aromatic phenyl ring. By contrast, the intramolecular hydrogen bondspresent between the phenolic OHs and the carbonyl oxygen of the carboxamides in 7binduces the coplanarity of the amide with the aromatic rings. This requirement provokesa dramatic change in the binding geometry for the 8⊂7b complex compared to 8⊂7a. Thefree-enthalpy gain on complex formation for 8⊂7b is maximised in an exo binding modeeven at the expense of losing favourable CH3–π interactions. However, it was observed thatin solution and at low temperature (220 K) the 8⊂7b complex also prefers the endo binding

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Figure 3.10 Partial packing of the solid-state structure of the complexes: (a) 8⊂7a, and(b) 8⊂7b. (Left) tail-to-tail dimers are stabilised through π–π interactions. The endo methylgroup is highlighted in white. Notice that this mode of packing is very similar for both complexes8⊂7a and 8⊂7b. (Right) Adjacent dimers formed by the 1 : 1 complexes interact throughCH···O and CH–π interactions for 8⊂7a but π–π interactions are established in the case of8⊂7b.

mode. Most likely, at this temperature the energy gain of the intermolecular interactionsmore than compensates for the energy penalty of disrupting the intramolecular hydrogenbonding. The CH3–π interactions present in the solid state of the 8⊂7a complex werelater analysed computationally by Frontera, et al. [37] concluding that the endo bindingmode of this complex is a direct consequence of the existence of these weak nonbondedinteractions. The computed distance between the carbon atom of the methyl group inMMTA and the centroid of the aromatic ring in an optimised MMTA • benzene complexwas 3.49 A and the binding energy was −0.58 kcal/mol. The change in the binding modeof the 8⊂7 complexes has a profound impact in the packing of the lattice. Although bothcomplexes pack in tail-to-tail dimers stabilised through π–π interactions of the central1,3,5-substituted aromatic benzene rings, only the 8⊂7b complex features additionalπ–π interactions with the arms of an adjacent inclusion complex as intermolecular forcesinfluence the packing of the lattice. In the case of the 8⊂7a complex, the packing of thelattice is stabilised by CH···O and CH–π interactions but not π–π interactions.

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Figure 3.11 Molecular structures of the aryl extended calix[4]pyrroles and their N-oxideguests.

An interesting combination of CH–π and π–π interactions can be observed in the X-raycrystal structures of the inclusion complex formed by aryl-extended calix[4]pyrroles 9 withpyridine-N-oxide 10 and its para phenyl derivative 11, Figure 3.11 [38]. Calix[4]pyrroles aremacrocyclic species having an array of four NHs that act as a binding site for anionic [39] andelectron-rich neutral guests [40] in organic solvents. The formation of the complex is usuallyaccompanied by a change of conformation from 1,3-alternate to cone [41]. Aryl-extendedcalixpyrroles bear an aryl group substituent at each of the four meso-carbons [42,43]. Inthe cone conformation, the α,α,α,α isomers of aryl extended calix[4]pyrroles can achieveselective binding of neutral aromatic guests (i.e. N-oxides) by a combination of hydrogenbonding, CH–π and π–π interactions. Water-soluble calix[4]pyrroles should also benefitfrom the hydrophobic effect on formation of the corresponding inclusion complexes. Thearrangement of all these intermolecular forces is usually observed in the protein-bindingpockets. To gain access to water-soluble calix[4]pyrroles ionising and water solubilisinggroups such as those in carboxy 9b and amino 9c were appended to the upper rim using thehydroxyl functionalities already present in 9a.

The geometry assigned to the inclusion complexes 10-11⊂9a in solution was also ob-served in the solid state, Figure 3.12. The X-ray structures of crystals obtained by slowevaporation of acetonitrile solutions containing the tetraester 9a and an excess of N-oxides10 or 11, showed that the receptor adopted a cone conformation with the N-oxide includeddeep in the aromatic cavity. The oxygens of the N-oxides are symmetrically bound tothe four pyrrolic NHs, with an average distance of 2.92 A for the N···O hydrogen bonds.Furthermore, the meso phenyl substituents and the pyridine core of 10 are at a distancethat is appropriate for establishing offset π–π interactions (daverage[Pycentroid. . .Phplane] =3.7 A) and CH–π interactions (daverage[10-αCH···Phcentroid] = 3.25 A). Similar distancesare observed for the 11⊂9a complex.

The crystal packing of each complex was found to be very similar. The inclusion com-plexes 10-11⊂9a pile into columns forming a top-to-bottom arrangement that is separatedby two molecules of acetonitrile in the case of 10 but only one molecule of solvent for 11.The volume of the additional molecule of acetonitrile observed in the stacking of 10⊂9a is

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Figure 3.12 Top view and side view of the solid-state structure of the inclusion complex(a) 10⊂9a, and (c) 11⊂9a. (b) and (d) Partial packing of the corresponding crystal highlight-ing the CH–π and aromatic–aromatic interactions involved. In the inclusion complexes thedistances of the aromatic–aromatic interactions are measured form the centroid of the pyridylring to the mean plane of the meso-Ph substituent while CH–π distances are measured fromthe centroid of the meso-Ph to the carbon alfa to the pyridine nitrogen.

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filled by the phenyl group of 11 in the 11⊂9a complex. Columns with the same orientationpack into layers mainly through van der Waals interactions. Adjacent layers are packedby inverting the direction of the inclusion complex and thus cancelling the overall dipolemoment of the crystal. In the case of the 10⊂9a complex, it is worthwhile to note thatin the packing between adjacent layers of inclusion complexes with opposite directionCH–π interactions are operative d[OCH3···mesoPhcentroid] = 3.53 A. By contrast, therelated packing observed in the 11⊂9a complex, in which two methyl acetate substituentsare tilted, displays a distance of 4.34 A between the meso-CH3 and the meso-Phcentroid

hinting to a reduced importance of CH–π interactions in the packing of the lattice forthis case.

3.2.2 Hydrogen-Bonded, Electrostatically Driven and Metal-MediatedMolecular Capsules

Up until this point this chapter has been dedicated to the relevance of CH–π and π–π

interactions in inclusion complexes. In several examples, we have also briefly consideredthe overall packing motif of a cell. With discrete and fully closed self-assembled systems,often it is just as insightful to focus on discrete interactions between the host and its guestmolecule(s). While we will also highlight situations where crystal packing stems fromCH–π and π–π interactions between assembled complexes, the focus of this portion of thechapter will be upon the influence of CH–π and π–π interactions in driving self-assemblyand complex formation in capsular assemblies. The first few examples will demonstratehow CH–π interactions can help to support and drive complex assembly, but with carefuldesign the resulting assemblies can interact with each other and generate supramolecular“materials” linked together by aromatic stacking interactions.

An α,α,α,α aryl-extended calix[4]pyrrole has been functionalised with four benzyl ureasin the para positions of their meso phenyl substituents affording tetraurea 12, Figure 3.13. Indichloromethane solution and in the presence of 4,4′-bipyridine,1,1′-dioxide 13, the tetrau-rea 12 dimerises reversibly forming a cyclic array of 16 hydrogen bonds and encapsulatingone molecule of bis-N-oxide [44]. The structure of the 13⊂122 encapsulation complex wasdetermined on crystals obtained from slow evaporation of its toluene solution [45]. Thedistances and angles for the hydrogen bonds in the urea belt are similar to those reportedfor the analogous dimer of a tetraurea calix[4]arene [46]. Due to the benzylic tetrahedralcarbons in 12, the tolyl units bend slightly to accommodate two intermolecular CH–π

interactions (edge-to-face-tilted-T geometry) with the protons of the aromatic ring of theadjacent calixpyrrole core in the dimer. Consequently, at least sixteen intermolecular CH–π

interactions between the aromatic CHs of the meso-phenyls and the aryl rings of the tolylsubstituents are observed in the solid-state structure of the assembly 13⊂122. These typesof interactions, absent in the dimer formed by phenyl-substituted tetraurea calix[4]arenes,are likely to play an important role for controlling the conformation adopted by the cal-ixpyrrole monomer in the capsule, as well as accounting for its high thermodynamic andkinetic stability.

The asymmetric unit of the crystal structure comprises two slightly different capsules andseven molecules of toluene, some of them highly disordered. The capsules pack into infinitelayers and the layers pile on top of another. The packing of the lattice reveals that four

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Figure 3.13 (a) Line structures of tetraurea calix[4]pyrrole 12 and bis-N-oxide 13, (b) Sideview and top view of the encapsulation complex 13⊂122. The intracapsule CH–π interactionsare highlighted in yellow and the two aromatic ring involved are shown as the van der Waalssurface, (c) Partial packing of the solid-state structure of 13⊂122 showing the nanospacegenerated by the packing in which four toluene molecules are trapped, and (d) Zoom-in ofthe four toluene molecules shown as CPK models to highlight the CH–π interactions involvedin their packing.

95

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Figure 3.14 (a) Schematic, and (b) solid-state structures of heterodimeric capsule 14 assem-bled through electrostatic interactions [49]. The solid-state structure shows one propyl chain ofthe amidinium monomer acting as a guest using CH–π interactions. (The pendant alkyl chainsof the solid-state structure have been omitted for clarity.).

molecules of toluene are included between four adjacent capsules of one layer, while twoother capsules of adjacent layers serve to seal this nanospace of toluene solvent. The toluenemolecules display a great variety of geometries for the CH–π interactions involved.

The Reinhoudt and Schrader groups independently developed self-assembled, het-erodimeric capsules based on calix[4]arenes that were designed to associate throughfavourable electrostatic interactions [47–52]. These capsules were an exciting additionto the supramolecular literature due to their solubility in water and other polar proticsolvents such as methanol. The Reinhoudt group was able to grow crystals suitable forX-ray diffraction of one complex as shown in Figure 3.14. These capsules were designedwith the intention to drive complex formation by favourable ionic interactions betweenthe amidinium and sulfonate groups on each calix[4]arene. However, solution [51] andsolid-state [49] analysis reveals that a propyl side chain from an amidinium group acts as aguest to facilitate complex assembly via CH–π interactions.

Another elegant example of an inclusion complex exhibiting discrete CH–π andhydrogen-bonding interactions was reported by Rebek and coworkers [53,54]. This self-assembled tetramer is held together with 24 hydrogen bonds between host monomers and, inthis example, eight hydrogen bonds between host and guest (Figure 3.15). While the crystalstructures of many supramolecular assemblies held together with metal–ligand interactionsand covalent bonds have been reported in the literature, it is rare to gain insight into thedetails involved in a hydrogen-bonded assembly in the solid state. While it is apparent the

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Figure 3.15 Solid-state structure of a tetrameric, hydrogen-bonded assembly with adaman-tanedione as a guest. Assembly is shown as CPK sticks with the guest as CPK spheres. Thependant aryl groups (Ar) have been omitted from the crystal structure for clarity and hydrogenbonds are highlighted with yellow dashed lines.

dominant interactions influencing complex formation are hydrogen bonds, the adamantylguest is ordered in the crystal structure and oriented in such a way as to take advantage ofdiscrete CH–π interactions with the aromatic walls of the host. Average distances betweenguest H-atoms and the aromatic rings of the host are ∼3.0 A, providing strong evidence forCH–π interactions.

A second example of a tetrameric, self-assembled supramolecular structure that takesadvantage of CH–π interactions is the metal–ligand cluster developed by the Raymondgroup. While the Raymond group has designed a series of elegant and diverse metal–ligandassemblies [55,56], it is the water-soluble M4L6 tetramer that has received the majorityof attention. This structure has served as, among others, a host for cationic [57] andneutral guests [58,59], a resolving agent for chiral ruthenium complexes [60], as well as acatalyst for C–H bond activation [61], the aza-cope rearrangement [62] and orthoformatehydrolysis [63].

The crystal structure of the M4L6 tetramer 16 (Figure 3.16) has been determined with aselection of metals and a variety of cationic guests (e.g. NR4

+, Cp2Co+, Cp*2Co) [56,57,64].

Three of these structures will be highlighted in this chapter; for an excellent detailedstructural analysis of this assembly in the solid state, refer to the article by Pluth et al. [56].

When the M4L6 cluster is constructed with M = TiIV, the Ti4L6 cluster carries anoverall 8-charge. The resulting complex is associated with one interior Et4N+ guest and7 exterior Et4N+ cations. Although the interior Et4N+ guest is disordered in the crystalstructure, modelling of the guest position shows that the CH’s of the guest come intoproximity with the aromatic walls of the host and have the ability to engage in cation–π

and CH–π interactions (Figure 3.16). Exterior cations (not shown) are also associated with

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(a) (b) (c)

Figure 3.16 Raymond’s M4L6 self-assembled cluster (M = GaIII, TiIV, AlIII, InIII, FeIII, GeIV;L = N,N’-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene). (a) Schematic representationof the cluster showing only one ligand for clarity; (b) crystal structure of Ti4L6 cluster with oneEt4N+ guest viewed down the fourfold axis; and (c) down the opening of the threefold axis(note: this figure depicts a “modelled” Et4N+, as it was disordered in the crystal structure [56].The M4L6 cluster is shown as CPK sticks, Et4N+ as CPK spheres.

the aromatic walls and anionic metal centres of the host, most likely through cation–π ,CH–π and electrostatic interactions [56].

When the guest is changed from Et4N+ to BnMe3N+, analysis of the solid-state assemblyreveals both cation–π and π–π interactions between the aromatic walls of the host andthe guest (Figure 3.17). The assembly used in this analysis was the Ga4L6 host, bearing anoverall 12– charge. This creates a complex with one BnMe3N+ on the interior of the hostand 11 BnMe3N+ cations associated with the exterior. Interestingly, all of the cations arecrystallographically ordered so the assembly crystallises in a lower symmetry space group(P21/n) than the complex with Et4N+ (R3c).

The crystal structure of the (BnMe3N+)11[BnMe3N+⊂Ga4L6] shows the encapsulatedguest adopting an orientation that allows the guest’s aromatic ring to interact in a nearlycoplanar manner with the naphthalene ring of the host. The distance between these rings is∼3.63 A, a strong indication of a face-to-face π–π stacking interaction between host andguest. With the guest locked in this orientation, the protruding methyl groups are then freeto engage in cation–π and CH–π interactions with the catechol rings of the host.

The eleven exterior BnMe3N+ cations associate with the host via either cation–π orπ–π interactions. The phenyl ring of BnMe3N+ π -stacks with the naphthalene rings of thehost, while the positively charged Me3N+ moiety interacts with the catecholate rings viacation–π interactions (Figure 3.17). It should be noted that the aromatic ring of the hostengaged in π–π interactions with an interior guest does not interact with cations on thehost’s exterior. It is also interesting to note point out that the exterior BnMe3N+ cations are“monogomists”, as they associate with only one Ga4L6 assembly and do not interact withmultiple hosts in the crystal structure.

When the guest included in the Ti4L6 cluster contains two aromatic rings (Cp2Co+),hosts can be “bridged” in the solid state through stacking π–π interactions (Figure 3.18).While the interior Cp2Co+ guest is disordered, exterior Cp2Co+ cations are ordered in the

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Figure 3.17 Molecular structure of the Ga4L6 cluster (CPK sticks) viewed down the fourfoldaxis with one interior and two exterior BnMe3

+ guests (CPK spheres) [56]. Aromatic surfaces ofthe guest and host that are engaged in π–π stacking interactions have approximate interfacialdistances shown in A.

Figure 3.18 Two Cp2Co+⊂Ti4L6 clusters bridged by one exterior Cp2Co+ via π–π stackinginteractions [56]. Cp2Co+ cations are shown as CPK spheres, while the ligands of the clusterare shown as sticks. Reprinted with permission. © 2009 American Chemical Society.

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crystal lattice and π -stack with the napthalene rings of adjacent assemblies. The interfacialdistance between the aromatic ring of the exterior Cp2Co+ and the host’s naphthalene ringis ∼3.3 A, again supporting a strong π–π interaction. This “bridging” occurs in threedimensions, so that each assembly interacts with three exterior Cp2Co+ cations. The resultis a grouping of four [Cp2Co+⊂Ti4L6] clusters and three external Cp2Co+ that make upthe crystal lattice.

3.2.3 Approaching Supramolecular Materials – Aromatic Towers

Recent work by the Fujita group has been focused on building discrete towers of aro-matic rings using a series of self-assembled metal–ligand complexes. While this grouphas published many fascinating examples in this area, a small selection is highlightedherein, in the interest of space. The reader is directed to an excellent review for a morecomprehensive discussion [65]. The basis of this work stems from the pyridyl-palladiumsystem shown in Figure 3.19 [66,67]. This assembly exists as an equilibrium in solu-tion between the square 19 and the triangle 20, depending on the stoichiometry of eachof the components [66]. This equilibrium can also be influenced by the presence of an

Figure 3.19 Fujita’s self-assembled Pd(II) linked complexes [67]. (a) Complex components –organic “linker 17”, metal “corner 18”, and (b) the triangle and square assemblies 19 and 20each shown with a guest that favours their formation.

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Figure 3.20 Crystal structure of aromatic cage 28 along with a schematic of its components[69]. Interfacial distances between each aromatic ring clearly demonstrate that these rings areengaged in π–π stacking interactions, driving the assembly of the complex shown. Two cagecomplexes are shown π -stacked into columns as they pack in the crystal structure. Hydrogenatoms and solvent molecules have been omitted for clarity.

appropriate guest – 1,4-dimethoxybenzene will selectively form the triangle, while thelarger 1,3-adamantanedicarboxylic acid will favour square formation [68].

In 2003 Fujita and coworkers began altering the structure of these two-dimensional as-semblies to create three-dimensional cages. By slightly changing the linker and includingan electron-poor aromatic “cap” along with an electron-rich aromatic guest to act as atemplate, cage 28 was isolated and characterised in both solution and the solid state (Fig-ure 3.20) [69]. Interestingly, the presence of guest 27 is necessary for the initial assembly ofthe cage; solution studies reveal that in its absence only homotopic tetrahedra and squaresare formed. As is evident from the solid-state structure of cage 28, the aromatic cap andguest are engaged in favourable face-to-face π–π stacking interactions that provide thedriving force for this assembly. It is also interesting to note that in the crystal structure,the host–guest complexes stack into columns to maximise favourable π–π interactionsbetween each cage. The cages are offset by 120◦, most likely due to steric effects from theethylenediamine ligands on the Pt corners.

With these results in hand, the Fujita group extended the length of this cage by replacingthe simple pyrazine pillar with a variety of di- and triaromatic linkers to create cages with avariety of shapes and sizes [70–72]. As expected from the design, the longer the cavity, themore stacked aromatic guests each cage binds. Once again, in the absence of an aromaticintercalating plate (“guest”), cages failed to form and only octahedron and squares (e.g. 19)were isolated.

Interestingly, if the linker included in these cages is nonlinear or somewhat flexibleas in bipyridines 17 and 30 (Figure 3.21), the resulting cages can “interpenetrate” andform pillars with discrete sizes. In pillars 31 and 32, the cavity size contained betweenthe two interpenetrated cages is varied to allow one or two molecules, respectively, ofintercalated pyrene “guest” to be included [73]. For each pillar the aromatic rings layer toachieve maximum overlap of their π systems with interplanar distances of 3.3 A resultingin “aromatic columns”. This discrete aromatic network is extended in the overall crystalstructure – each pillar is π -stacked with an adjacent pillar to create infinite columns.

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Figure 3.21 Partial crystal structure of self-assembled, interpenetrated, aromatic pillars 31 and32 with their components. Reprinted with permission from [73]. © 2008 American ChemicalSociety.

With the supramolecular cages described above available to them, the Fujita group beganexploring the effect of polarised aromatic rings on the packing structure within each cage.The subject of this study was the aromatic pyrene-4,5-dione 33 (Figure 3.22). Likely dueto its large dipole moment (6.1–6.7 D), dione 33 stacks in an alternating head-to-tail arrayin the solid state [74]. These stacks are infinite columns with almost complete overlapbetween adjacent π -surfaces. As a way to separate the effects of dipole–dipole interactionsand crystal-packing effects, the Fujita group employed two metal–ligand cages that wouldencapsulate only two or three dione guests 33 at a time.

In order to study a discrete dimer, cage 35 was constructed in the presence of a slightexcess of dione 33 (Figure 3.23). Following detailed 1H NMR solution studies, singlecrystals were grown and analysed [75]. The X-ray analysis revealed that, as designed, thecage bound two dione guests and that these guests were stacked in an alternating, head-to-tailfashion (Figure 3.23). This orientation strongly resembles that of the free dione in the solidstate [74] and the result of this stacking is that the overall dipole moment is cancelled out.

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Figure 3.22 (a) Packing of pyrene-4,5-dione 33 in its crystal structures viewed through thearomatic face (lower left corner) and down a column (right) [74]. Note the 180◦ offset of eachdione molecule relative to its neighbours above and below.

Figure 3.23 Molecular structure of dione 33 (CPK spheres) encapsulated as a dimer (35) anda trimer (36) in Fujita’s molecular cages (sticks) [75].

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Figure 3.24 Structure of Fujita’s stacks of aromatic pillars 39 with its components. (a) Crystalstructure of two cages intercalated to form a pillar, and (b) partial packing found in crystalstructure. Reprinted with permission from [73]. © 2008 American Chemical Society.

Interestingly, when dione 33 is encapsulated as a trimer it seems that dipole–dipoleinteractions again determine the orientation of the aromatic stack. The three dione guests incage 36 are oriented with 120◦ rotation relative to one another, again resulting in an overallnet dipole of zero for the stack. Note how the ligands of the cage flex inward to maximisevan der Waals and CH–π contacts with the guests. For both dione–cage complexes, theinterplane distance between each dione guest is 3.3 A, again suggesting strong interfacialπ–π interactions. This distance is slightly shorter than that observed in the structure of freedione 33, a result likely due to the physical constraints of the cage.

Finally, the Fujita group linked all of the above work together to create a materialbased on the π–π stacking interactions between their self-assembled metal–ligand cages(Figure 3.24). Modification of the cage ligand to the diazene 37 gave interpenetrated pillarssimilar to those discussed earlier. Attached to the new ligand are alkyl groups incorporatedto enhance the resulting assembly’s solubility in organic solvents. As can be seen inFigure 3.24, the pillars are interpenetrated with one aromatic guest intercalated in theremaining space. This structure is supported by 1H NMR solution studies as well as X-raydiffraction data. In the crystal structure, the pillars π -stack on top of one another making“towers” of self-assembled cages.

The physical result of this stacking is evident when a saturated solution of pillar 39in water is viewed through an optical polarising microscope. Preliminary results fromthe Fujita group suggest that these supramolecular assemblies interact through aromaticstacking interactions to form a lyotropic nematic columnar phase with only 1D orientationalorder [76]. This observation agrees with the solid-state analysis shown in Figure 3.24.

3.3 Summary and Outlook

Evidence and discussion of the significance of aromatic–aromatic (π–π ) and CH–π interac-tions using solid-state structures of reversible supramolecular inclusion and encapsulationcomplexes was presented. It is concluded that both types of interactions are highly useful

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in the thermodynamic stabilisation of the supramolecular complexes. Aromatic–aromatic(π–π ) interactions are stronger forces than CH–π interactions and possess greater require-ments of directionality in their binding geometries. Since CH–π interactions are weakerthey display a greater variety of binding modes. Nevertheless, the effect of multiple CH–π

interactions acting in concert lends these weak interactions an important role in the energet-ics and the structural properties of inclusion and encapsulation supramolecular complexes.While both types of interactions have many implications in controlling the conformationalproperties of molecules at the molecular and mesoscopic level, our current knowledge of thephysical nature of aromatic–aromatic (π–π ) interactions makes their use more appropriatefor the rational design of molecular receptors, liquid crystals and crystal engineering thanCH–π interactions. Recently, the importance and interest of CH–π interactions is increasingbecause they seem to be phenomenologically apparent. Clearly, “activated” CH–π interac-tions having geometrical requirements closer to hydrogen bonds are more easily taken intoaccount in molecular engineering. The importance of “typical” CH–π interactions is a morespeculative arena due to the fact that their physical origins blur with van der Waals forcesand the hydrophobic effect. Molecular interactions between π -systems as well as thosebetween hydrogen atoms and π -systems are key to the properties of molecules, biologicalsystems and materials. The study of such interactions computationally, in solution and inthe solid state constitutes a challenging worthwhile objective. An indepth knowledge ofthese interactions would allow us to use them to control and better understand bindingstrength and selectivity, but it will also aid in the design and development of new functionalsupramolecular materials.

Acknowledgments

PB thanks MICINN (CTQ2008-00222/BQU, CTQ2011-23014, Consolider Ingenio 2010Grant CSD2006-0003), DURSI (2009SGR6868) and ICIQ Foundation for generous finan-cial support of our research.

References

1. C.A. Hunter, Angew. Chem., Int. Ed., 43, 5310–5324 (2004).2. E.V. Anslyn and D.A. Dougherty, Modern Physical Organic Chemistry, University Science

Books, Sausalito, 2006.3. P. Hobza, H.L. Selzle and E.W. Schlag, Chem. Rev., 94, 1767–1785 (1994).4. E.G. Cox, D.W.J. Cruickshank and J.A.S. Smith, Proc. R. Soc. London, A, 247, 1–21 (1958).5. S.K. Burley and G.A. Petsko, Science, 229, 23–28 (1985).6. S.K. Burley and G.A. Petsko, Adv. Protein Chem., 39, 125–189 (1988).7. P. Hobza, H.L. Selzle and E.W. Schlag, Potential-energy surface of the benzene dimer – ab initio

theoretical-study. J. Am. Chem. Soc., 116, 3500–3506 (1994).8. W.B. Jennings, B.M. Farrell and J.F. Malone, Acc. Chem. Res., 34, 885–894 (2001).9. C.R. Patrick and G.S. Prosser, Nature, 187, 1021 (1960).

10. F. Cozzi, M. Cinquini, R. Annunziata, T. Dwyer and J.S. Siegel, J. Am. Chem. Soc., 114,5729–5733 (1992).

11. F. Cozzi and J.S. Siegel, Pure Appl. Chem., 67, 683–689 (1995).12. S.E. Wheeler and K.N. Houk, Mol. Phys., 107, 749–760 (2009).

P1: TIX/XYZ P2: ABC



13. F. Cozzi, R. Annunziata, M. Benaglia, M. Cinquini, L. Raimondi, K.K. Baldridge and J.S. Siegel,Org. Biomol. Chem., 1, 157–162 (2003).

14. F. Cozzi, R. Annunziata, M. Benaglia, K.K. Baldridge, G. Aguirre, J. Estrada, Y. Sritana-Anantand J.S. Siegel, Phys. Chem. Chem. Phys., 10, 2686–2694 (2008).

15. M.S. Cubberley and B.L. Iverson, J. Am. Chem. Soc., 123, 7560–7563 (2001).16. S. Tsuzuki and A. Fujii, Phys. Chem. Chem. Phys., 10, 2584–2594 (2008).17. Y. Kodama, K. Nishihata, M. Nishio and N. Nakagawa, Tetrahedron Lett., 2105–2108 (1977).18. M. Nishio, M. Hirota and Y. Umezawa, CH/pi Interaction: Evidence, Nature, and Consequences,

Wiley-VCH, New York, 1998.19. O. Takahashi, Y. Kohno and M. Nishio, Chem. Rev., 110, 6049–6076 (2010).20. M. Nishio, CrystEngComm, 6, 130–158 (2004).21. M. Nishio, Y. Umezawa, K. Honda, S. Tsuboyama and H. Suezawa, CrystEngComm, 11,

1757–1788 (2009).22. M. Nishio, Tetrahedron, 61, 6923–6950 (2005).23. M. Nishio, Y. Umezawa, M. Hirota and Y. Takeuchi, Tetrahedron, 51, 8665–8701 (1995).24. G.D. Andreetti, A. Pochini and R. Ungaro, J. Chem. Soc., Perkin Trans. 2, 1773–1779 (1983).25. G.D. Andreetti, R. Ungaro and A. Pochini, J. Chem. Soc., Chem. Commun., 1005–1007 (1979).26. The BHMPYC.cif file deposited in the CCDC database corresponds to analysis of the X-ray

diffraction data for the 2(1b complex carried out at RT, see ref. 25. Due to guest disorder nopositions are described for the toluene guest. The distance reported here for the CH3–π interac-tions of 1b • t-Bu-H3C is half the value of the shorter distance measured between opposite CH3

carbon atoms (9.05 A) in BHMPYC.cif. For the 1b • Phcentroid···CH3 • 2 distance the calixarenestructure described at RT was superimposed to the 2(1b complex obtained at 220 K in which thedistance of the carbon of the methyl group of the toluene to the reference plane is 2.54 A.

27. A. Arduini, R. Caciuffo, S. Geremia, C. Ferrero, F. Ugozzoli and F. Zontone, Supramol. Chem.,10, 125–132 (1998).

28. R. Ungaro, A. Pochini, G.D. Andreetti and P. Domiano, J. Chem. Soc., Perkin Trans. 2, 197–201(1985).

29. Scigress 2.1.0, Mechanics Version 1.0, 2008-2010 Fujitsu Limited.30. R. Ungaro, A. Pochini, G.D. Andreetti and V. Sangermano, J. Chem. Soc., Perkin Trans. 2,

1979–1985 (1984).31. G. Desiraju and T. Steiner, The Weak Hydrogen Bond: Applications to Structural Chemistry and

Biology, Oxford University Press Inc., New York, 1999.32. Y. Umezawa, S. Tsuboyama, K. Honda, J. Uzawa and M. Nishio, Bull. Chem. Soc. Jpn., 71,

1207–1213 (1998).33. J.L. Atwood, S.G. Bott, C. Jones and C.L. Raston, J. Chem. Soc. Chem. Commun., 1349–1351

(1992).34. V. Hensel, K. Lutzow, A.-D. Schluter, J. Jacob, K. Gessler and W. Saenger, Angew. Chem., Int.

Ed., 36, 2654–2656 (1997).35. D. Schollmeyer, O.V. Shishkin, T. Ruhl and M.O. Vysotsky, CrystEngComm, 10, 715–723

(2008).36. P. Ballester, M. Capo, A. Costa, P.M. Deya, R. Gomila, A. Decken and G. Deslongchamps,

J. Org. Chem., 67, 8832–8841 (2002).37. A. Frontera, C. Garau, D. Quinonero, P. Ballester, A. Costa and P.M. Deya, Org. Lett., 5,

1135–1138 (2003).38. B. Verdejo, G. Gil-Ramirez and P. Ballester, J. Am. Chem. Soc., 131, 3178–3179 (2009).39. P.A. Gale, J.L. Sessler, V. Kral and V. Lynch, J. Am. Chem. Soc., 118, 5140–5141 (1996).40. W.E. Allen, P.A. Gale, C.T. Brown, V.M. Lynch and J.L. Sessler, J. Am. Chem. Soc., 118,

12471–12472 (1996).41. J.R. Blas, J.M. Lopez-Bes, M. Marquez, J.L. Sessler, F.J. Luque and M. Orozco, Chem. Eur. J.,

13, 1108–1116 (2007).42. P. Anzenbacher, K. Jursikova, V.M. Lynch, P.A. Gale and J.L. Sessler, J. Am. Chem. Soc., 121,

11020–11021 (1999).43. L. Bonomo, E. Solari, G. Toraman, R. Scopelliti, M. Latronico and C. Floriani, Chem. Commun.,

2413–2414 (1999).

P1: TIX/XYZ P2: ABC



44. P. Ballester and G. Gil-Ramirez, Proc. Natl. Acad. Sci. U. S. A., 106, 10455–10459 (2009).45. M. Chas, G. Gil-Ramirez, E.C. Escudero-Adan, J. Benet-Buchholz and P. Ballester, Org. Lett.,

12, 1740–1743 (2010).46. O. Mogck, E.F. Paulus, V. Bohmer, I. Thondorf and W. Vogt, Chem. Commun., 2533–2534

(1996).47. R. Zadmard, M. Junkers, T. Schrader, T. Grawe and A. Kraft, J. Org. Chem., 68, 6511–6521

(2003).48. R. Zadmard, T. Schrader, T. Grawe and A. Kraft, Org. Lett., 4, 1687–1690 (2002).49. F. Corbellini, L. Di Costanzo, M. Crego-Calama, S. Geremia and D.N. Reinhoudt, J. Am. Chem.

Soc., 125, 9946–9947 (2003).50. F. Corbellini, R. Fiammengo, P. Timmerman, M. Crego-Calama, K. Versluis, A.J.R. Heck, I.

Luyten and D.N. Reinhoudt, J. Am. Chem. Soc., 124, 6569–6575 (2002).51. F. Corbellini, R.M.A. Knegtel, P.D.J. Grootenhuis, M. Crego-Calama and D.N. Reinhoudt, Chem.

Eur. J., 11, 298–307 (2005).52. F. Corbellini, F.W.B. van Leeuwen, H. Beijleveld, H. Kooijman, A.L. Spek, W. Verboom, M.

Crego-Calama and D.N. Reinhoudt, New J. Chem., 29, 243–248 (2005).53. T. Martin, U. Obst and J. Rebek, Science, 281, 1842–1845 (1998).54. D.W. Johnson, F. Hof, P.M. Iovine, C. Nuckolls and J. Rebek, Angew. Chem., Int. Ed., 41,

3793–3796 (2002).55. D.L. Caulder and K.N. Raymond, Acc. Chem. Res., 32, 975–982 (1999).56. M.D. Pluth, D.W. Johnson, G. Szigethy, A.V. Davis, S.J. Teat, A.G. Oliver, R.G. Bergman and

K.N. Raymond, Inorg. Chem., 48, 111–120 (2009).57. D.L. Caulder, R.E. Powers, T.N. Parac and K.N. Raymond, Angew. Chem., Int. Ed., 37, 1840–1843

(1998).58. S.M. Biros, R.G. Bergman and K.N. Raymond, J. Am. Chem. Soc., 129, 12094–12095 (2007).59. C.J. Hastings, M.D. Pluth, S.M. Biros, R.G. Bergman and K.N. Raymond Tetrahedron, 64,

8362–8367 (2008).60. D. Fiedler, D.H. Leung, R.G. Bergman and K.N. Raymond, J. Am. Chem. Soc., 126, 3674–3675

(2004).61. D. Fiedler, D.H. Leung, R.G. Bergman and K.N. Raymond, Acc. Chem. Res., 38, 349–358 (2005).62. D. Fiedler, R.G. Bergman and K.N. Raymond, Angew Chem Int Edit, 43, 6748–6751 (2004).63. M.D. Pluth, R.G. Bergman and K.N. Raymond, Science, 316, 85–88 (2007).64. A.J. Terpin, M. Ziegler, D.W. Johnson and K.N. Raymond, Angew. Chem., Int. Ed., 40, 157–160

(2001).65. J.K. Klosterman, Y. Yamauchi and M. Fujita, Chem. Soc. Rev., 38, 1714–1725 (2009).66. M. Fujita, O. Sasaki, T. Mitsuhashi, T. Fujita, J. Yazaki, K. Yamaguchi and K. Ogura, Chem.

Commun., 1535–1536 (1996).67. M. Fujita, Chem. Soc. Rev., 27, 417–425 (1998).68. S.B. Lee, S.G. Hwang, D.S. Chung, H.S. Yun and J.I. Hong, Tetrahedron Lett., 39, 873–876

(1998).69. K. Kumazawa, K. Biradha, T. Kusukawa, T. Okano and M. Fujita, Angew. Chem., Int. Ed., 42,

3909–3913 (2003).70. M. Yoshizawa, M. Nagao, K. Kumazawa and M. Fujita, J. Organomet. Chem., 690, 5383–5388

(2005).71. M. Yoshizawa, J. Nakagawa, K. Kurnazawa, M. Nagao, M. Kawano, T. Ozeki and M. Fujita,

Angew Chem Int Edit, 44, 1810–1813 (2005).72. T. Murase, K. Otsuka and M. Fujita, J. Am. Chem. Soc., 132, 7864–7865 (2010).73. Y. Yamauchi, M. Yoshizawa and M. Fujita, J. Am. Chem. Soc., 130, 5832–5833 (2008).74. Z.H. Wang, V. Enkelmann, F. Negri and K. Mullen, Angew. Chem., Int. Ed., 43, 1972–1975

(2004).75. Y. Yamauchi, M. Yoshizawa, M. Akita and M. Fujita, J. Am. Chem. Soc., 132, 960–966 (2010).76. Y. Yamauchi, Y. Hanaoka, M. Yoshizawa, M. Akita, T. Ichikawa, M. Yoshio, T. Kato and M.

Fujita, J. Am. Chem. Soc., 132, 9555–9557 (2010).

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