The Importance of Pi-Interactions in Crystal Engineering: Frontiers in Crystal Engineering

By Edward R. T. Tiekink and Julio Zukerman-Schpector

Crystal engineers aim to control the way molecules aggregate in the crystalline phase and are therefore concerned with crystal structure prediction, polymorphism, and discovering the relative importance of different types of intermolecular forces and their influence on molecular structure. In order to design crystal structures, knowledge of the types, strengths, and nature of possible intermolecular interactions is essential. Non-covalent interactions involving p-systems is a theme that is under extensive investigation as these interactions can be inductors for the assembly of a vast array of supramolecular architectures.

The Importance of Pi-Interactions in Crystal Engineeringcovers topics ranging from the identification of interactions involving p-systems, their impact on molecular and crystal structure in both organic and metallorganic systems, and how these interactions might be exploited in the design of new materials. Specialist reviews are written by internationally recognized researchers drawn from both academia and industry.

The Importance of Pi-Interactions in Crystal Engineeringprovides an essential overview of this important aspect of crystal engineering for both entrants to the field as well as established practitioners, and for those working in crystallography, medicinal and pharmaceutical sciences, solid-state chemistry, physical chemistry, materials and nanotechnology

• Language: English
• Publisher: Wiley
• Release date: Mar 22, 2012
• ISBN: 9781119940920

Edward R. T. Tiekink

Edward R.T. Tiekink is Distinguished Professor and Head of the Research Centre for Crystalline Materials at Sunway University, Malaysia. He is a graduate of the University of Melbourne, Australia (D.Sc. 2006), where his passion for structural chemistry was nurtured. He has published in excess of 2,000 research papers/reviews and co-edited a number of books reflecting his interests in crystallography and metal-based drugs, including Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine (2005), Frontiers in Crystal Engineering (2006), Organic Crystal Engineering—Frontiers in Crystal Engineering (2010), and Multi-Component Crystals: Synthesis, Concepts, Function (2017). He is a Fellow of the Royal Society of Chemistry and the Royal Australian Chemical Institute.

Book preview

1

The CH/π Hydrogen Bond: Implication in Crystal Engineering

Motohiro Nishio¹, Yoji Umezawa², Hiroko Suezawa³ and Sei Tsuboyama⁴

¹The CHPI Institute, Machida-shi, Tokyo, Japan

²Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, Japan

³Ministry of Education, Culture, Sports, Science and Technology, Kasumigaseki, Chiyoda-ku, Tokyo, Japan

⁴The Institute of Physical and Chemical Research, Wako-shi, Saitama, Japan

1.1 Introduction

In the last half of the twentieth century, evidence gradually accumulated to show that weak hydrogen bonds such as CH/n hydrogen bonds [1] and XH/π (X = O [2], N [3]) hydrogen bonds are ubiquitous. The former is the hydrogen bond between CHs (soft acids) and lone-pair electrons of O, N or halogen atoms (hard bases), while the latter is the hydrogen bond occurring between OH or NH (hard acids) and π-systems (soft bases).

More recently, another attractive force, the CH/π hydrogen bond [4], has been shown to play significant roles in a variety of chemical and biological phenomena. This is the hydrogen bond occurring between a soft acid (CH) and a soft base (π group) [5–7].

ch01fig028.eps

In 1952, Tamres reported that the interaction between haloforms and a π-system is attractive [8]. Thus, CHCl3 and CHBr3 dissolve in aromatic solvents, exothermically. Methyl substitution increases the heat of mixing: benzene < toluene < m-xylene < mesitylene. The association between an aromatic compound and haloforms occurs in a one to one ratio. Support for this suggestion soon followed, by IR [9] and NMR studies [10].

ch01fig029.eps

In 1974, Nishio and coworkers reported that the t-butyl group in a sulfoxide diastereoisomer, t-BuS(=O)CH(CH3)C6H4Br-p, 1, orients itself gauche to the phenyl group at the other terminus of the molecule [11]. Subsequent studies by optical rotatory dispersion ORD) [12], NMR [13] and dipole moment measurements [14] revealed a similar conformation is maintained in solution. The gauche R/Ar (R, alkyl; Ar, aryl) and Ar/Ar relationship has also been suggested for solution conformations of structurally related compounds.

ch01fig030.eps

These findings led the authors to suggest that an attractive force was operating between these groups. Theoretical studies supporting the above suggestion followed [15]. According to these findings, a hypothesis was presented that a weak attractive force, the CH/π hydrogen bond, may play important roles in various fields of chemistry and biology [16].

ch01fig031.eps

In 1979, Ungaro and coworkers determined the crystal structure of calix[4]arene, 2, derivatives associated with several neutral molecules, such as toluene, and reported that the guests are tightly held in the cavity of the host, and attributed the observations to the CH/π hydrogen bond [17].

In 1993, Sakaki and coworkers first studied the interaction between methane and benzene, and within the benzene dimer (Figure 1.1), by ab initio molecular orbital (MO) calculations at the correlated level (MP2: Møller–Plesset 2) [18]. It was shown that the energy of typical CH/π hydrogen bonds involving sp³- or sp²-CH groups arises, largely, from dispersion forces. Contributions from electrostatic forces, polarisation or charge-transfer interactions are of relatively minor importance. However, it should be noted that the CH/π hydrogen bond has dual nature. In other words, this attractive molecular force operates in polar as well as in nonpolar environments.

Figure 1.1 Binary molecular clusters (a) CH4/C6H6 and (b) C6H6/C6H6 at various relative orientations.

ch01fig001.eps

In a CH4/C6H6 complex, Figure 1.1, a binary molecular cluster a, which has been shown to be the most stable among the three possibilities a–c, adopts C3v symmetry with the methane-C lying on the C6 axis of benzene and with one C–H bond directed to the centre of the benzene ring. With regard to the benzene dimers, Figure 1.1, structures d–f, geometry d (aromatic CH/π hydrogen bond) is more favourable than geometry e (offset π/π stacking), although only slightly. Owing to electrostatic repulsion, geometry f was found to be destabilising.

The work of Sakaki was followed by high-level ab initio MO calculations by many researchers [19]. DFT (density functional theory) [20] calculations and combined theoretical and spectroscopic studies subsequently appeared [21]. The energy components of the CH/π and related weak hydrogen bonds are given in Table 1.1 [22]. Notice that the proportion of electrostatic energy increases on going from sp³-CH to sp²-CH and then to sp-CH. Comparable trends occur on substitution of hydrogen by a halogen atom.

Table 1.1 Energy components (in kcal mol−1) of the CH/π and related weak hydrogen bonds. EES = electrostatic, EER = repulsive, EPOL = polarisation, ECT = charge transfer and EDISP = dispersion.

Table 1-1

1.1.1 Evidence and the Nature of the CH/π Hydrogen Bond

Evidence for the CH/π hydrogen bond can be obtained by various experimental methods. Calorimetric determinations are known to give good evidence [23], and is one of the surest ways to investigate the substituent effect on the crystal structure [24] and thermodynamic properties [25]. Support for the nature of the hydrogen bond has been provided by the monitoring of electronic substituent effects upon spectroscopic data [26], conformational equilibrium [27], enantiomeric selection [28], selectivity in organic reactions [29], and coordination chemistry [30].

The nature of the hydrogen bond has also been confirmed by a number of theoretical studies [31], including the AIM (atoms-in-molecules) method [32]. To cite a recent example, van der Veken and coworkers examined the interaction of a general anesthetic halothane, 3, with ethene by IR/Raman spectroscopy and MO calculations at the MP2/6-311++G(d,p) level (Figure 1.2) [33]. It is clear that this molecular force between the constituents is a hydrogen bond, in view of the criteria of Koch and Popelier [34]. While this is an example involving an activated CH group, similar conclusions pertain when sp³-CHs interact with a π-groups [35].

ch01fig032.eps

Figure 1.2 AIM analysis of halothane/ethene complex. Reprinted from [33] © 2009, with permission from Elsevier.

ch01fig002.eps

Holme et al. studied, by X-ray photoelectron spectroscopy, the conformation of 1-pentyne and found that the interatomic distance between one of the methyl hydrogens and an acetylenic carbon was shorter, by 0.48 Å, than the van der Waals distance [36]. Figure 1.3 shows some of the X-ray photoelectron spectra of 1-pentyne. Note that the charge on the C² atom is negative and is balanced by the positive charge on a hydrogen atom on C⁵.

Figure 1.3 (a) The vibrational profiles as computed for the gauche (solid line) and anti (dotted line) conformers, and (b) The dotted line indicates the interaction between a CH and a sp-carbon atom. Reprinted from [36] © 2009, with permission from Elsevier.

ch01fig003.eps

From the above, and as further discussed below, the CH/π hydrogen bond should be considered as a true hydrogen bond, as demonstrated by spectral, crystallographic and theoretical studies [37]. This is a proper hydrogen bond, although nonconventional, and is neither the so-called antihydrogen bond [38] nor the so-called improper-hydrogen bond [39]. This type of hydrogen bond is often accompanied with a blue shift in the C–H stretching frequency in IR spectra. While this phenomenon has long been known, as evidenced by experimental data [40,41] and theoretical studies [42], the origin of this effect remains a matter of debate. Barnes wrote a critical account on this issue [43].

Figure 1.4 Scatter plots showing dependence of the C–H–π access angle (α) on the CH/π plane. (a) CHCl3, (b) CH2Cl2, (c) sp-CH, (d) aromatic (sp²-CH), (e) aromatic CH (neutron data), (f) CCH3 (sp³-CH). Reproduced with permission from the Chemical Society of Japan. © 2001.

ch01fig004.eps

Table 1.2 Distance and orientation dependence of the CH/π hydrogen bond.

Table 1-2

1.1.2 Directionality of the CH/π Hydrogen Bond

Directionality and charge assistance are requisites for the hydrogen bond. Figure 1.4 shows the results obtained by CSD (Cambridge Structural Database) [44] analyses and Table 1.2 summarises the results [45]. While these analyses date from 2001, the conclusions are still valid. Orientation dependence of an interacting system follows the order of the strength: the stronger the bond, the stronger the trend for the linearity [46,47]. Notice that the C–H–π access angle (α) and the CH/π-plane distance (DPLN) correlate well, depending on the strength of the proton donor.

1.2 Cooperative Effect of the CH/π Hydrogen Bond

1.2.1 Cooperative Effect as Evidenced by High-Level Ab Initio MO Calculations

One of the outstanding features of the CH/π hydrogen bond, among others, is that it works cooperatively. Ran and Wong studied the CH/π hydrogen bond, by MO calculations at the CCSD(T)/aug-cc-pVTZ//MP2/aug(d,p)-6-311G(d,p) level, between benzene and various alkanes [35]; Table 1.3 and Figure 1.5. A number of CH groups concurrently interact with the benzene aromatic ring in many cases, as shown in Figure 1.6 for benzene complexes of cyclohexane and isobutane.

Table 1.3 Energy, atomic distance, atomic charges, and charge transfer of the hydrocarbon-benzene complexes. Adapted from Tables 1 and 4 of Ran and Wong, J. Phys. Chem. A, 2006, 110, 9702–9729.

Table 1-3

Figure 1.5 Atomic distance of the CH/π hydrogen bonds. Reprinted with permission from [35]. © 2006 American Chemical Society.

ch01fig005.eps

1.2.2 Cooperative Effect as Evidenced by Periodic Ab Initio MO Calculations

The cooperative effect of the CH/π hydrogen bond is most prominent in crystals. For example, Kobayashi and Saigo examined the CH/π hydrogen bond using the periodic ab initio MO method compared crystal structures of diastereomeric salts of mandelic acid derivatives, 4 and 5, with p-methyl-1-phenylethylamine 6, and amino alcohols 7 and 8 [48]. Figure 1.7 shows different aspects of the crystal structure of a less-soluble salt formed between 4 and an amino alcohol 7, that is, (a) a monomer unit, (b) a 1D supramolecular chain, and (c) a 3D network.

ch01fig033.eps

Figure 1.6 Multiple interactions in benzene complexes of cyclohexane and isobutane. Reprinted with permission from [35]. © 2006 American Chemical Society.

ch01fig006.eps

Figure 1.7 Partial crystal structure of the less-soluble salt of 4 with 7. (a) Minimum molecular unit, (b) 1D helical column, and (c) 3D network. Reprinted with permission from [48]. © 2005 American Chemical Society.

ch01fig007.eps

The packing modes of the crystals 4 with 7 versus 5 with 8 are significantly different, in view of the variety of the CH/π and conventional hydrogen bonds, Figure 1.8. It was concluded that the characteristics of the aromatic CH/π hydrogen bond resembles a conventional hydrogen bond in terms of the following features: the energy, the polarisation of the bond, and the shortening of the atomic distance. This similarity is caused by the cooperative effect in the crystals, which does not persist in the gas phase.

Figure 1.8 Packing modes of helical columns in crystals of 4 and 7, and 4 and 8 salts. The arrows and dotted lines show CH/π hydrogen bonds and the circles indicate the hydrogen bonding columns. Reprinted with permission from [48]. © 2005 American Chemical Society.

ch01fig008.eps

1.2.3 Cooperative Effect as Evidenced by Stabilisation of Materials in Aromatic Nanochannels

Sozzani and coworkers reported that cooperation of CH/π hydrogen bonds greatly increases the stability of organic compounds. Inclusion of organic compounds into an aromatic nanochannel, composed of tris(o-phenylenedioxy)spirocyclotriphosphazene, 9, formed robust structures melting at temperatures some 200 K higher than that of the pure guests [49]. CH/π hydrogen bonds induce a single-chain structure for macromolecules, such as polyethylene [50] and synthetic rubber [51], to accommodate the aromatic nanocylinders, competing against the tendency to assume multiple conformations, rather adopt the entropically unfavourable extended chain helical conformation, Figure 1.9.

ch01fig034.eps

Figure 1.9 (a) Tris-(o-phenylenedioxy)spirocyclotriphosphazene 9, (b) aromatic nanochannel, and (c) polybutadiene included in the nanochannel. Reprinted with permission from [41] © 2004 The Royal Society of Chemistry.

ch01fig009.eps

1.2.4 Optical Resolution

In 1990, Ogura et al. first pointed out the importance of CH/π hydrogen bonds in enantiomer discrimination. Noteworthy is the selective formation of one of the optical isomers of sulfoxides by (R)-phenylglycil-(R)-phenylglycine, 10 [52], and related naphthyl analog, 11 [53]. The resolution was attributed to the CH/π hydrogen bonds formed between the CHs of the guest and the host aromatic rings [54,55]. Saigo et al. studied the mechanism of optical resolution using diastereomeric salts of mandelic acid derivatives such as 4 and 5, and optically active amines [56]. Fujii and Hirayama studied the chiral recognition of amino acids by optically active 1,1′-binaphthalene-2,2′-diyl phosphate, 12. They concluded that CH/π hydrogen bonds are responsible for the molecular recognition allowing fractional crystallisation of L-amino acids [57].

ch01fig035.eps

Saigo and Kobayashi suggested that the characteristics of the observed aromatic CH/π hydrogen bonds resemble a conventional hydrogen bond in view of the energy, polarisation and the shortening of the interatomic distance [58], as noted in Section 1.2.2. In each diastereomeric salt, an aromatic CH of 6 was shown to be associated to the aromatic ring of 5 via CH/π bonds. However, the relative orientations of the interactions are quite distinct, indicating different strengths of these interactions (see Section 1.1.2). More specifically, in the less-soluble (more stable) salt, the dihedral angle between the aromatic moieties is approximately 84°, whereas in the more-soluble (less stable) salt the comparable angle is 54°, as illustrated in Figure 1.10. In the absence of any other factors, the differing solubility was attributed primarily to the different CH/π hydrogen bonds.

Figure 1.10 Aromatic CH/π hydrogen bonds (arrows) in (a) the less-soluble, and (b) the more-soluble salt of 5 and 6. Reprinted with permission from [58] © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

ch01fig010.eps

In a related study, Tsuboyama and coworkers compared crystal structures of diastereomeric pairs (less- and more-soluble) salts of mandelic acid with basic resolving agents such as 1-phenylethylamine or cinchonidin [59]. Two examples are shown in Figure 1.11.

Figure 1.11 CH/π short contacts disclosed in the crystal structures of less-soluble diastereomeric salts: (a) (S)-1-phenylethylammonium (S)-manderate, and (b) cinchonidinium (S)-manderate. Dotted lines indicate short CH/π contacts. Reprinted with permission from [59] © 2004, John Wiley & Sons, Ltd.

ch01fig011.eps

Martin and coworkers reported that the high chiral discrimination displayed by chiral cation receptors bearing a cis-2-oxymethyl-3-oxy-tetrahydropyran, 13, occurs mainly as a result of CH/π hydrogen-bond formation [60].

ch01fig036.eps

Ichikawa et al. determined the crystal structure of (S)-2-methoxy-2-(1-naphthyl)propanoic acid, 14 [61]. The 9-phenanthryl groups were shown to form a herringbone structure via aromatic CH/π hydrogen bonds and this was argued as the basis for the chiral discrimination.

ch01fig037.eps

Other examples reporting on the significant role of CH/π hydrogen bonds in optical resolution include 2,3-di-O-(phenyllcarbonyl)tartaric acid, 15 [62], and O-substituted phenylphosphonothiotic acids, 16 and 17 [63].

ch01fig038.eps

It seems that the surface area of the π ring is an important factor in the chiral recognition. The resolving agents such as 2-naphthylglycolic acid, 5, cis-1-aminobenz[f]indan-2-ol, 8, (R)-naphthylglycil-(R)-phenylylglycine, 11, 1,1′-binaphthalene-2,2′-diyl phosphate, 12, and (S)-2-methoxy-2-(1-naphthyl)propanoic acid, 14, bear naphthyl group(s), and have been reported to be efficient resolving agents for chiral discrimination. A naphthyl group presents a larger surface area, compared to a phenyl ring for example, available for interaction with CHs. Saigo and Kobayashi argued that enlargement of the aromatic ring of conventional resolving agents would be a good approach for the development of new resolving agents.

1.3 CH/π Hydrogen Bonds in Supramolecular Chemistry

Papers related to CH/π hydrogen bonds in supramolecular chemistry appearing before 2008 were summarised in our previous reviews [64]. Desiraju wrote several reviews elaborating on CH/O hydrogen bonds in relation to concepts in crystal engineering [65]. Similarly, Steiner [66], Diederich and coworkers [67], and Schneider [68] have all written excellent reviews on the topic. Brotin and Dutasta reviewed the complexation of cryptophanes [69]. Aakeröy, Champness and Janiak highlighted the state-of-the-art and new trends in developing areas of crystal engineering in organometallic chemistry [70].

1.3.1 Crystal Packing

Weber and coworkers studied the molecular structure of 4-(4-methoxyphenyl)-2-methylbut-3-yn-2-ol [71]. The molecules are connected via hydrogen bonds and aromatic CH/π contacts. Further stabilisation results from weaker CH3…acetylene interactions between different strands.

Guru Row and coworkers examined, by in situ cryocrystallographic studies, the packing of a series of benzylic compounds C6H5CH2-X, for X = H (Figure 1.12), OH, NH2, SH, Cl, Br, CN). The packing mode is influenced by CH/π hydrogen bonds occurring between the benzene ring and sp² and sp³ CHs, depending on the acidity of the benzyl proton [72].

Figure 1.12 Crystal structure of toluene at 150 K. (a) ORTEP diagram, and (b) Molecular network stabilised through CH/π hydrogen bonds. Reprinted with permission from [72] © 2010 The Royal Society of Chemistry.

ch01fig012.eps

Katrusiak et al. studied the molecular arrangement of benzene at the lowest limits of pressure ranges [73]. In phase I (0.15 GPa), the benzene molecules are arranged in an approximately perpendicular fashion allowing for the formation of CH/π hydrogen bonds; there are substantial voids between the molecules within the sheets. The mechanism of transition from phase I to phase II (0.91 GPa) involves a collapse of the voids with a shift of the CH/π hydrogen-bonded sheets.

Chopra and coworkers studied the crystal structures of a series of compounds related to structure 18, that is, with X = F, Cl, Me, OMe, NMe2, and Y = O [74] and S [75]. These compounds pack via the cooperative interplay of NH/O, CH/O, NH/S, and CH/π hydrogen bonds.

ch01fig039.eps

Guru Row and coworkersstudied the crystal structures of a series of fluorinated compounds; Figure 1.13 shows that CH/π, CH/F and CH/O hydrogen bonds cooperatively work in stabilising the crystal conformation and network [76].

Dupont and coworkers studied the crystal structure of 3-benzyl-2-phenyl-1,3,2-oxazaphospholidin-2-one derivatives, 19, for R = H, alkyl or Ph. The packing is ensured by π/π stacking and CH/π hydrogen bonds, for example, Figure 1.14 [77].

ch01fig040.eps

Figure 1.13 CH/π, CH/F, and CH/O hydrogen bonds are cooperatively working in stabilising the network. Reprinted with permission from [76] © 2011 The Royal Society of Chemistry.

ch01fig013.eps

Figure 1.14 Stabilisation by π/π stacking and CH/π hydrogen bonds in the crystal structure of 3-benzyl-2-phenyl-1,3,2-oxazaphospholidin-2-one, 19. Reprinted from [77] © 2010, with permission from Elsevier.

ch01fig014.eps

Other recent examples highlighting the importance of CH/π in stabilising their crystal structures include N,N′-dihexylbenzimidazolium salts [78], copper complexes of a pyrimidine ligand [79], tris(1-organo-imidazol-2-ylthio)methane [80], 1-formyldipyrromethanes [81], an alkynyl-substituted ferrocene [82], a zinc porphyrin-1,2-3-triazole conjugate [83], a dicyclopentadienylaluminum complex [84], 3-sec-butyl-2,3-dihydro-1H-(isoquinolin-4-ylidene)acetic acid [85], a silver complex [86], 3,4-dichloro-2′,4,6′-triethylbenzophenone [87], hexaaryltriindoles [88], a pyrazolo[3,4-d]pyrimidine [89], [Ru(η⁶-bip)2]+2, [Os(η⁶-bip)2]+2 (bip is biphenyl) [90], [(Ph)4As]+[Co(NCS)2Cl2]²− [91], a dinuclear aluminium complex containing two pyrazole groups [92], N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)toluenesulfonamide [93], trimetallo-macrocycles with naphthanoimidazolate and benzoimidazolate anions [94].

1.3.2 Lattice Inclusion Type Clathrates

As mentioned earlier in Section 1.2.3, Sozzani and coworkers reported that cooperation of CH/π hydrogen bonds greatly increases the stability of organic inclusion compounds. Thus, the inclusion of organic compounds into an aromatic nanochannel, composed of tris(o-phenylenedioxy)spirocyclotriphosphazene, 9, formed robust structures melting at temperatures some 200 K higher than the pure guests [49]. Other examples will be discussed here to emphasise the importance of CH/π hydrogen bonds in organic clathrates.

Bracco et al. studied self-assembled supramolecular crystals fabricated by solvent-free mechanochemical treatments of a crystalline host [95]. A rubbery polymer is stabilised by cooperative CH/π hydrogen bonds as revealed by ¹H fast-MAS and 2D solid-state NMR. Methane was also shown to be effectively included within the host lattice [96].

Figure 1.15 An example of crystal packing in a hexaphenylbenzene structure. Reprinted with permission from [97]. © 2010 American Chemical Society.

ch01fig015.eps

Wuest and coworkers studied the crystal structure of hexaphenylbenzene and its ethynyl analogs [97]. Figure 1.15 shows the structure of a cocrystal of 20 (R = H) with PhC≡CH. It is noteworthy that PhC≡CH acts as a strong donor by using its sp-CH to form a CH/π hydrogen bond with the central benzene ring of hexaphenylbenzene.

ch01fig041.eps

Fonari et al. reported CH/π hydrogen bonds in mefenamic acid, 21, complexes with cyclic and acyclic amines [98]. Persistent CH/π hydrogen bonds involving the aromatic rings were found to play an important role in the formation of final structures, Figure 1.16.

ch01fig042.eps

Barooah and Baruah determined the crystal structure of complexes of pyromellitic diimide, 22, with aromatic guests (Figure 1.17) [99].

ch01fig043.eps

The importance of CH/π hydrogen bonds has also been shown in the structural chemistry of fullerenes [100]. Thus, Atwood et al. reported that calix[8]arene [101] and cyclotriveratrylene derivatives [102] effectively include C60 in their cavity. Schulz-Dobrick and Jansen determined the crystal structure of a complex of triarylphosphine ligand bound to gold formed with C60, Figure 1.18 [103].

Figure 1.16 Persistent CH/π hydrogen bonds in mefenamate salts. Reprinted with permission from [98]. © 2010 American Chemical Society.

ch01fig016.eps

Figure 1.17 Two different types of CH/π hydrogen-bond networks in two cocrystals. Reprinted from [99] © 2008, with permission from Elsevier.

ch01fig017.eps

Figure 1.18 The cocrystal formed by a triarylphosphine moiety and C60. Reprinted with permission from [103] © 2008 The Royal Society of Chemistry.

ch01fig018.eps

Other recent examples showing CH/π hydrogen bonds in clathrates are a CH2Cl2 complex of a porphyrin derivative [104], a CH3CN complex of a metallomacrocyle [105], an ethyne complex of a benzoyltricamphor derivative [106], a dicyclopentadienylaluminum complex [107], tetraarylpyrenes [108], 3-amino-2-(4-dimethylaminophenyldiazenyl)-1-phenylbut-2-en-1-one [109], iron and nickel complexes of 4-p-tolyl-2,6-di(2-pyrazinyl)pyridine [110], [Cu2(4,4′-bpy)5(H2O)4](ClO4)4(4,4′-bpy)(DMF)2(H2O) [111], copper complexes with pyrazolylpyrimidines as ligands [112], and host–guest complexes of cucurbit[8]uril [113]. Toda wrote excellent reviews on this issue [114]. Chopra and Guru Row wrote a review on the role of organic fluorine in crystal engineering [115]. Reviews focusing on weak interactions in crystal engineering are also available [116].

1.3.3 Cavity Inclusion Type Clathrates

A significant progress in this field has been achieved from the study of the structural chemistry of calix[4]arenes [117], calix[6]arene [118] and molecular capsules derived from resorcinarenes [119,120]. In each investigation, the important contribution of CH/π hydrogen bonds has been recognised.

Ugozzoli and coworkers reported calix[4]arene as receptors for pyridinium and viologen ions [121]. Figure 1.19 illustrates the inclusion mode of the guest in one example.

Figure 1.19 Calix[4]arene receptor including pyridinium guest. Reprinted with permission from [117] © 2009 The Royal Society of Chemistry.

ch01fig019.eps

Choi et al. reported a deep cavitand based on imidazoquinoxaline and the formation of helical alkane inclusion complexes by CH/π hydrogen bonds, Figure 1.20 [122].

Figure 1.20 (a) Energy-minimised structure (B3LYP/6-31G*) of an n-octane complex of 5, showing the helical conformation, and (b) proton NMR data calculated at the B3LYP/6-31G* level of theory. Reprinted with permission from [122] © 2009 The Royal Society of Chemistry.

ch01fig020.eps

Tedesco et al. studied the methane adsorption properties of a new microporous organic zeolite by volumetric adsorption analysis and high-resolution powder XRD [123]. Methane molecules are located inside the host channels and a ring of eight methane and eight calixarene molecules is formed through CH/π bonds, as illustrated in Figure 1.21.

Figure 1.21 Methane molecules are located inside the host channels and a ring of eight methane and eight calixarene molecules is formed through CH/π bonds. Reprinted with permission from [123] © 2010 John Wiley & Sons, Ltd.

ch01fig021.eps

Weber and coworkers found that allyloxy-5,11,17,23-tetra-tert-butyl-26,27,28-trihydroxycalix[4]arene displays an almost undistorted cone conformation, stabilised by three hydrogen bonds at the calixarene's lower rim [124]. One chloroform solvent molecule is fixed in the cavity by CH/π hydrogen bonds, while the second is accommodated in a clathrate-like mode in elliptical packing voids.

Kim and coworkers found that 1,12-dodecane diammonium was encapsulated in cucurbit[8]uril in an unconventional U-shaped conformation [125]. Favourable host–guest interactions seem to overcome the charge/charge repulsion of the ammonium groups in close proximity. An inspection of the X-ray structure of the complex indicates a clear role played by CH/π hydrogen bonds, Figure 1.22.

Huang and coworkers prepared a series of pillar[5]arenes, 23 [126]. Pseudorotaxane-type threaded structures were obtained in the solid state by inclusion of an n-hexane molecule into the cavity. Methylene chloride was also found effectively included. Stabilisation of the host–guest complexes by CH/π hydrogen bonds has been proven by X-ray data.

ch01fig044.eps

This group also reported that a linear supramolecular polymer was constructed in solution from the self-assembly of pillar[5]arene monomers (R = n-octyl) [127]. X-ray analysis and NMR spectroscopy demonstrated that the aggregation proceeded enthalpically, by cooperative CH/π hydrogen bonds that occur between the n-octyl chain and the aromatic cavity. The n-octyl group of the guest penetrates deeply into the electron-rich cavity of another adjacent co-pillararene monomer and the monomers align along an axis to form a head-to-tail linear supramolecular polymer throughout the entire crystal, as illustrated in Figure 1.23.

Figure 1.22 1,12-Dodecane diammonium encapsulated in cucurbit[8]uril. Reprinted with permission from [125] © 2010 The Royal Society of Chemistry.

ch01fig022.eps

Figure 1.23 Linear supramolecular polymer of the complex (R = n-C8H17) as revealed by X-ray crystallography. The dotted lines indicate CH/π short contacts. Reprinted with permission from [127] © 2011 Wiley-VCH Verlag GmbH & Co. KGaA.

ch01fig023.eps

1.4 Crystallographic Database Analyses

The observation of a short atomic distance in the crystal structure is not necessarily evidence for a weak hydrogen bond. Unequivocal proof is obtained by statistical analyses on a large number of data points obtained from, for example, the Cambridge Structural Database (CSD) [44].

To obtain a clear understanding of weak hydrogen bonds, a comparison of histograms with angular frequencies for different donor types is required. For example, the sequence of histograms reported by Steiner and Desiraju shows a gradual decrease of directionality for CH/O hydrogen bonds with decreasing C–H acidity [128]; angular distribution of the C≡CH/O hydrogen bond is only slightly broader than that of the ordinary hydrogen bond. Ciunik and Desiraju demonstrated the importance of area correction for multi-atom-acceptor hydrogen bonds such as CH/π, NH/π and OH/π [129].

1.4.1 CH/π Hydrogen Bonds as Evidenced by CSD Analyses

Hunter et al. studied the crystal structure of clathrates of MeP+Ph3 salts with furan [130]. A number of short CH/π distances were noted in these sandwich-type clathrates. Kochi and coworkers reported on the charge-assistance in the distance parameter for a number of Ph4B− salts [131]. We noted CH/π contacts in almost every case for organic salts having Ph4B− as the anion component, for example, Figure 1.24 [132]. This may explain why good crystals often grow using tetraphenylborate as the counterion.

Figure 1.24 CH/π short contacts disclosed in a Ph4B− salt. Reprinted with permission from [132] © 2001 The Royal Society of Chemistry.

ch01fig024.eps

Steiner studied the crystal structures of several compounds bearing a terminal C≡CH group and found a number of short CH/π distances [133]. Combined database and MO studies were reported for aromatic CH/π [134] and C≡CH…π(C≡C) [135] interactions. CSD analyses for hexahelicenes [136] and nitrogen-containing heterocycles (isoxazole, imidazole, indole) have also been reported [137].

1.4.2 Systematic CSD Analyses

In a survey of cyclohexanonyl, cyclohexyl and cyclopentyl clathrates with C6 aromatics, Ciunik et al. found a number of structures bearing short CH/π short distances [138].

Braga et al. examined XH/π hydrogen bonds (π: C≡C, cyclopentadienyl, phenyl) in transition-metal compounds [139]. The XH/π distance was found to follow the order O < N < C. In every case the distance versus angle scattergrams showed the characteristic features of weak hydrogen bonds. Namely, trends were noted for the shortening of the interatomic distance when the acceptor is more negatively charged or when the donor hydrogen is more positively charged.

Janiak examined the interaction in coordination and organometallic entries and reported that the complete stacking of planar ligands is rare; offset π/π stacks or aromatic CH/π hydrogen bonds dominate, instead [140]. Reger and coworkers et al. reported that the offset π/π stacking and CH/π hydrogen bond are commonly observed in metal complexes of 1,1′,3,3′-tetrakis(pyrazol-1-yl)propane [141].

Zari and coworkers have described CH/π hydrogen bonds where the π-system is a chelate ring of transition metal complexes [142]; a number of reports dealing with this subject followed [143]. In the work of Zaric and coworkers et al., analysis of the geometrical parameters in the crystal structures of square-planar complexes of transition metals obtained from the CSD showed that the geometry of the stacking interaction between phenyl and chelate rings is similar to the geometry of the stacking interaction of two benzene rings, indicating that the chelate rings behave similarly to organic aromatic rings. Xi and Niclós-Gutiérrez and their respective groups also discussed the metalloaromaticity of chelate rings by examining ruthenium complexes [144].

1.5 Systematic CSD Analyses of the CH/π Hydrogen Bond

In systematic explorations for CH/π hydrogen bonds in the literature crystal structures have been conducted. The key result was that short CH/π distances were evident in more than three quarters of the CSD entries bearing at least one C6 aromatic ring in the molecular structure [145].

1.5.1 Method and General Survey of Organic Molecules

Figure 1.25 shows the original search method probing the CSD. The data for the intermolecular interaction in organic crystals are listed in Table 1.4 [146].

Figure 1.25 Method for exploring CH/π contacts. (a) O: centre of the plane. C¹ and C²: nearest and second nearest sp²-carbons, respectively, to H. ω: dihedral angle defined by C¹OC² and HC¹C² planes. θ: ∠H-C-C¹. DPLN: H/π-plane distance (H/I). DATM: interatomic distance (H/C¹). DLIN: distance between H and line C¹-C² (H/J), and (b) 1: region where H is above the aromatic ring. 2 and 3: regions where H is out of region 1 but may interact with π-orbitals. The program was run to search for H/π distance shorter than a cut-off value DMAX in every region: DPLN < DMAX, θ < 60°, |ω| < 90° for region 1, DLIN < DMAX, θ < 60°, 90° < |ω| < 130° for region 2, and DATM < DMAX, θ < 60°, ω = 180°- ϕ (ϕ: ∠H-C¹-I), 90° < ω < 130° for region 3. This program was originally written by us (Y. Umezawa and M. Nishio: Bioorg. Med. Chem., 1998, 6, 493-504) and has recently been implemented in ABINIT-MP software (BioStation Viewer), developed by Center for Research on Innovative Simulation Software: http://www.ciss.iis.u-tokyo.ac.jp/english/dl/index.php. Reprinted from [146] © 1999 with permission from Elsevier.

ch01fig025.eps

Table 1.4 XH/π contacts present in the crystal structures of all-organic compounds.

Table 1-4

It should be noted that the distance cut-off, that is, 3.05 Å = (1.7 for sp²-C + 1.2 for H) × 1.05, was employed only as a working criterion. This does not mean to imply that CHs remoter than the cut-off value is not CH/π bonded but represent a conservative value, as a longer cut-off distance will give a higher ratio of the hits. Further, the data reported in Table 1.4 are minimum estimates since included in these entries are structures bearing no atomic coordinates.

The key finding of this work is that short CH/π distances are recorded in more than three quarters of the CSD entries, which bear at least one C6 aromatic ring in the molecule. Another important conclusion is that the ratio of entries bearing at least one short CH/π contact is much larger than that of the OH/π and NH/π hydrogen bonds. This is understandable because the CH group is usually more abundant, for a given molecule, compared to OH and NH groups. Another reason is that OH and NH prefer O or N as acceptors and thereby normally form conventional hydrogen bonds rather than OH/π and NH/π hydrogen bonds.

The importance of CH/π contacts in peptides was also investigated [147]. The number of crystals with at least an intermolecular contact shorter than the van der Waals distance was 122 among 130 entries bearing phenylalanine, tyrosine or tryptophan (94%). There were 55 entries featuring short intramolecular CH/π from the 130 entries (42%). Early data were also obtained from the crystal structures of cavity inclusion-type clathrates such as cyclodextrin, calix[4]arene complexes, cryptophane complexes, and pseudorotaxanes [148].

The interaction of solvent molecules with other constituents in their crystal structures was also investigated. A series of database subsets were edited by monitoring the entire CSD seeking structures with included solvents, for example, CHCl3, CH2Cl2, MeNO2, MeCN, MeOH, Me2CO, DMF, DMSO, 1,4-dioxane, benzene, toluene, and p-xylene. Short CH/π contacts were then searched in these solvates. Table 1.5 lists the number of entries bearing short CH/π distances in these database subsets.

Column 5 of Table 1.5 summarises the results for interactions revealed between the guest CH and host π-groups. A variety of solvents are included by CH/π hydrogen bonds. The proportion of hits is unexpectedly small for the chloroform solvates (26%). This may be because CHCl3 has only one CH atom, while the other solvents bear more than two CHs as potential hydrogen donors. In support of this, the ratio of 56% of hits for CH2Cl2 solvates is about twice that of CHCl3 (26%). Similarly, toluene is included at a ratio of 38%, which is about half that of the p-xylene complexes (69%).

In related investigations [132], many clathrates composed of 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6-diol, 24, for example, with Me2CO, Me2CO, nicotine and Ph2CO, illustrated in Figure 1.26, were found.

ch01fig045.eps

Table 1.5 CH/π contacts formed between common solvent molecules and all-organic guests in their crystal structures.

Table 1-5