Is Organic Fluorine Really “Not” Polarizable? - American Chemical

Perspective pubs.acs.org/crystal

Is Organic Fluorine Really “Not” Polarizable? Deepak Chopra* Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal 462023, India ABSTRACT: The covalent chemistry of the main group element fluorine is well understood. In contrast, its noncovalent chemistry, which forms the pillar of the paradigm of supramolecular chemistry, is still in its infancy. The latter involves a complete understanding of the different interactions (both intermolecular and intramolecular) involving donor and acceptor atoms. This perspective highlights the recent developments in the understanding of noncovalent interactions in relation to organic fluorine (partially fluorinated compounds) and the versatility and importance of such interactions to the scientific community.

■

INTRODUCTION TO THE C−F BOND Organic compounds are abundant in nature. In addition to the presence of the conventional C−C (single, double, and triple bonds), C−O, C−N, and other C-heteroatom bonds can also be present. However, there are only a dozen natural organic fluorine compounds known. In addition, the important functional groups that form building blocks in organic molecules comprises strong donors, namely, O/N−H, activated C−H (depends on the hybridization of the carbon atom, being most acidic for sp carbon) and strong acceptors, namely, C O/N. The chemical nature of these atoms plays a decisive role in molecular recognition events, particularly in the formation of O/N−H···O/N strong H-bonds.1 In addition to these, weak acceptors exist, namely, π-rich systems involved in the formation of O/N/C−H···π and π···π interactions which contribute to crystal formation.2 In recent years, the phenomenon of molecular association, involving the presence of the C−F bond (termed “organic fluorine”) in organic molecules (partially fluorinated) has assumed extreme significance. It has been envisaged that C−F bonds are the strongest among all the bonds because of the strong orbital overlap between the F 2s and 2p (referred to as “organic fluorine”) with corresponding orbitals of other second period elements.3 The changes in conformational and electronic features (stereoelectronic effects) associated with substitution of a C−H by a C−F bond in organic molecules, with concomitant changes in chemical reactivity, is of interest, and this feature is neatly summarized in a tutorial review.3 Furthermore, this aspect also has its implications in the field of organocatalysis.4 This feature is extremely important in the context of practical application of fluorine-containing compounds because 20% of drugs and 30% of agrochemicals on the market contain organic fluorine.5 Recent reviews6 in this area of research summarize a comprehensive list of the relevant fluorinated compounds with potential applications in pharamaceutics and the agrochemical industry. The area of fluoroorganic chemistry is an emerging field, and the last two decades has witnessed immense growth in this area of research, © 2011 American Chemical Society

both from a synthetic perspective (namely, in the development of reagents and catalysts; selectfluors (1-chloromethyl-4-fluoro1,4-diazoniabicyclo[2.2.2]octane bis-(tetrafluoroborate)) and NFSI (N-fluorobenzenesulfonimide).7 Furthermore in medical applications, the direct impact of fluoro-organic compounds in the field of molecular imaging (namely, 18F PET and MRI), biomaterials, and pharmaceutics has already been realized. All these features and related applications are highlighted in detail in the book titled Fluorine and Health edited by Tressaud and Haufe.8 In addition, the importance of modern fluoroorganic chemistry is comprehensively reviewed in a number of excellent textbooks which bring out the significance of these classes of compounds.9 From pure electronegativity considerations, it is known that fluorine withdraws the electron density in any bond toward itself and is thus highly polarized. On the contrary, the resonance effect observed in C(aromatic)−F bonds, wherein the lone pair of electrons in p-orbital has a weak interaction with the benzene nucleus, enhances the stability of such bonds. This feature introduces an electropositive character on fluorine.10 To illustrate the back-bonding or π-donation from F to C to form CF⊕, Kraka and Kremer have characterized these bonds using the theory of adiabatic internal vibrational modes (AIVM) and evaluated the bond lengths, stretching force constant, and bond order for fluorine-containing molecules. The value of the bond order for fluorobenzene was observed to be 1.18 indicating back bonding.11

■

SUPRAMOLECULAR CHEMISTRY IN ORGANOFLUORINE COMPOUNDS: PAST AND PRESENT (a). An Overview of N−H···F, O−H···F, and C−H···F Intra- and Intermolecular Interactions: Inputs from Theoretical and Experimental Studies. The role of fluorine as a structure-directing element is well established in organoReceived: November 14, 2011 Revised: December 17, 2011 Published: December 19, 2011 541

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546

Crystal Growth & Design

Perspective

metallic systems.12 Extending the realm of bonding in fluorine, to understand noncovalent interactions, it was proposed that fluorine cannot participate in the formation of H-bonds, due to the low polarization associated with the tightly held lone pairs (three in number). But it does so “...in exceptional molecular and crystal environments”.13 It has been observed that in case of HF, the crystal structure contains zig-zag chains of these molecules stabilized via (···H−F···H−F···) H-bonds [14]. Furthermore, in the case of KHF2 it was found that the proton in the HF2− ion is symmetrically positioned between both the fluorine atoms and forms very strong hydrogen bonds with the fluorine atom. The obvious question that then arose was are similar bonding features observed in organic compounds containing organic fluorine. Initial investigations by Dunitz and co-workers mention that organic fluorine does not participate in the formation of intermolecular hydrogen bonds as the donor C−H is weak and so is the acceptor C− F.13 The participation of the fluorine atom in the formation of hydrogen bonds has been considered to be a subject of debate. In comparison to the other heavier halogens, namely, chlorine, bromine, and iodine, which are relatively less electronegative and have polarizable electron density, fluorine lacks these properties. These features form the basis of the debate regarding the involvement of organic fluorine in the formation of intra- and intermolecular interactions. An important breakthrough was achieved when Boese and Desiraju determined the crystal structures of fluorobenzenes which are liquids at room temperature wherein C−H…F intermolecular interactions were observed.15 A molecular-pair analysis of the C−H···F interactions in fluorobenzenes by Dunitz proposed that C−H···F interactions have approximately the same structure-directing ability and influence on the intermolecular energy as the corresponding C−H···H interactions in benzene.16 But a recent investigation again by Boese and Desiraju on the crystal structure of 1,2,3,5-tetrafluorobenzene unequivocally established that weak C−H···F−C intermolecular H-bonds were indeed realistic and responsible for supramolecular recognition.17 The paradigm of these “weak” H-bonds was even studied in chemically modified ribonucleic acids.18 Of further significance was the feature that these were highly directional interactions that contributed toward the stability of the crystal packing. The importance of such weak C−H···F interactions being weak, cooperative and flexible in nature has been realized in the absence of strong H-bonds in isoquinolines,19a−d keto-tetrahydroindoles,19e fluorine-rich cyclotriphosphazene hydrazones,19f and all-syn-isomer of 1,2,3,4tetrafluorocyclohexane.19g In the presence of strong H-bond donors, a detailed investigation of C−H···F interactions involving ordered and disordered fluorine has been performed in fluorinated benzanilides,20a N-(2-chloropyridin-4-yl)-N′phenylureas,20b optically active halogenated beta-hydroxysulphoxides,20c tetrahydropyrimidines,20d,e and cocrystals.20f The significant attributes of these interactions have been probed via polymorphism in organic solids21 and via in situ cryocrystallography in molecular liquids (amines,22a halogenated trifluoroacetophenones,22b fluorobenzonitriles,22c and phenylacetylenes.22d,e) A detailed in-depth analysis of the structural features in a series of crystal structures belonging to the aspirin family of molecules containing methoxy, fluoro, and trifluoromethyl groups brings out the significant involvement of weak C−H···F intermolecular interactions which contribute to crystal packing.23 Furthermore, a detailed topological analysis of the experimental electron density features in fluorine containing

solids proves that C−H···F is a weak H-bond.24 Additional evidence from a neutron diffraction study on but-2-yne-1,4-diyl bis(2,3,4,5,6-pentafluorophenylcarbonate), at 90 K, characterizes that a short C(sp3)−H···F contact of distance 2.162(8) Å in the crystal is responsible for the observed cisoid conformation.25 In the past two decades, significant inputs by various researchers have contributed toward the understanding of intraand intermolecular interactions involving organic fluorine, utilizing experimental, theoretical, spectroscopic, and database studies. The relevant literature is contained in a recent highlight.26 Of further significance are the detailed investigations of C−H···F interactions in organic solids, containing organic fluorine, which are in the crystal structures of tricyclic Diels−Alder adducts derived from diarylfulvenes and Narylimides,27a N-phthalimide protected (E)- and (Z)-4-amino2-butenyl 5-substituted pyrimidine derivatives,27b di- and trifluorolactates,27c N-phenylmaleimides and corresponding phthalimides27d wherein the solid state organization of the molecules is dictated by these weak interactions acting in conjunction with other related weak intermolecular interactions, namely, F···F, C−F···π, and aromatic interactions. The nature of these related fluorine-based interactions is discussed in the later sections of this article. Furthermore, extremely short C−H···F hydrogen bonds have been observed in the solid-state structures of 2-fluoro-2-phenylcyclopropane derivatives, and a comparison made with the nonfluorinated analogues reveals that such close contacts are not solely due to crystal forces but are caused by weak X−H···F−C hydrogen bridges.28 The existence of C−H···F weak intramolecular contacts have found relevance with regard to potential applications in the design of catalyst for applications in olefin polymerization reactions.29 The nature of weak and short C−H···F3C−C(sp3) intramolecular interactions, due to restricted rotation around the F3C−C(sp3) bond, has also been exploited in both solution and the solid state in O-alkyl-9-dehydro-9-trifluoromethyl-9-epiquinidine. 30 In an overall perspective, these intra- and intermolecular interactions are of extreme significance and find applications in development of materials,31a electronic and optoelectronic devices,31b design of peptides,31c protein engineering,31d medicinal chemistry,31e and organometallic chemistry.31f To complement the experimental determinations, detailed theoretical investigations have been performed to bring out the nature of such weak interactions. A systematic theoretical study was performed by Hyla-Kryspin, wherein it was proposed that the nature and strength of these interactions depend on the subtle balance between the Lewis acidity of the hydrogen donor and the Lewis basicity of the acceptor.32a In recent times, a detailed theoretical study using the IMPT method and aug-ccpVTZ basis set by Novoa in chemical systems containing organic fluorine proves that C−H···F interaction is indeed a Hbond, the stabilization being approximately 0.43 kcal/mol.32b A combined MP2 and QCISD(T) study on the evaluation of the theoretical interactions energies of weak O−H···F−C, C− H···O, and C−H···F hydrogen bridges brings out the structural features associated with blue-shifted/red-shifted H-bonds which in turn depends on the nature of the donor (strong/weak) and the acceptor (strong/weak).33 The energetics associated with C−H···F weak intermolecular contacts in molecular pairs in diazafluorene crystals were obtained from quantum-chemical calculations at the DFT/PBE/3z level.34 Ab initio molecular dynamics (MD) simulations has been used to investigate the 542

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546

Crystal Growth & Design

Perspective

electronic and vibrational properties of blue-shifted H-bonded CF3H···(HF)n (1 ≤ n ≤ 3) complexes to establish cooperativity among the various interactions.35 A related Fourier transform infrared spectroscopy (FTIR) study in cryosolution combined with ab initio approaches have been used to characterize the nonlinear structures having relatively short C−H···F blueshifted H-bonds in F 2 ClCH·FCD 3 and Cl 2 FCH·FCD 3 complexes.36 The effect of the change in the hybridization of the carbon atom connected to the fluorine acceptor, with associated change in the strength of the C−H···F hydrogen bond, has been studied using a combination of ab initio calculations along with atoms in molecules (AIM) theory.37 The importance of cooperativity among the weak intermolecular H-bonds has been addressed recently in an excellent perspective.38 In addition to these weak interactions, the significance of N−H···F hydrogen bonding has also been realized in foldamers, aromatic amides, and hydrazides,39a−c and in the pairing free energies of fluorinated bases compared with nonfluorinated analogues are greater by 0.5−1.0 kcal/mol.39d The intramolecular N−H···X (X = -Cl, Br, I) H-bonding in heavier halogens has also been studied crystallographically and spectroscopically via 1H NMR.39e (b). Insights into C−F···F−C, X···F (X = Cl, Br, I), C−X: (lp)···π and anion···π Contacts in the Context of Crystal Packing. In addition to C−H···F−C interactions, another important associated interaction is the C−F···F−C contact and this has also been in focus for a long time. Fluorine being highly electronegative should electrostatically repel another fluorine atom. But difluorine does exist, although it is a weak bond and hence reactive. The importance of C−F···F−C contacts has been realized in 5-fluorouracil wherein a new form was obtained after being predicted computationally.40a In another investigation of polymorphism performed on 1-(4-fluorophenyl)-3,6,6-trimethyl-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one, an anti-implantation agent, it was observed that dimorphs were obtained under different conditions of crystal growth, occurring morphologically as plates (monoclinic, non-centrosymmetric) and blocks (tetragonal, centrosymmetric), respectively.40b It is noteworthy that there was a short C−F···F−C contact (Type I across 2-fold axis), not occurring across the center of symmetry, in the tetragonal form, but the given intermolecular contact was absent in the monoclinic plate form. Extending the concept of halogen···halogen interactions beyond organic fluorine, a detailed investigation of X···F (X = -F, -Cl, -Br, -I), namely, homohalogen and heterohalogen interactions in substituted benzanilides, have been performed, and this study brings out the significance of their interactions in crystal packing.41 It was concluded that fluorine prefers Type-I contact, and the heavier halogens prefer Type-II contacts (Figure 1). The presence of fluorine synthons in fluorinated aza-distyrlbenzenes42 bring out the relevance of F···F contacts in crystal packing. The competition existing among different weak interactions, involving halogens, particularly of the X···X type has been investigated in benzils.43 The C−Cl···Cl−C, C−F···F−C, and C−Cl···F−C intermolecular contacts have also been studied topologically (both experimentally and theoretically) using the multipolar atom model, and these are essentially closed-shell interactions.44 The repulsive interaction that exists between two fluorine atoms in a crystal can be altered by a modification of the chemical environment in the molecule (addition of electron withdrawing groups such as nitro, cyano, trifluoromethyl, sulfonyl). This facilitates a resonance effect to dominate in opposition to the

Figure 1. Diagram illustrating Type-I and Type-II contacts involving halogens.

direction of C−F dipole moment. This results in anisotropic distribution of the electron density around the fluorine atom, and this feature has been investigated using electron density studies performed on fluorine-containing organic compounds.44a This introduces a positive electrostatic potential (termed “sigma-hole”), and this electronic feature has been investigated using ab initio calculations.45a This anisotropy can dictate F···F intermolecular bonding to prevail in organic molecules in the solid state. Hence similar to C−H···F, these bonding interactions are also directional, and this stems from the existence of the sigma hole. The electronic features associated with the existence of the sigma hole have been studied theoretically, by Politzer et al.45b−d Latest investigations by Metrangalo and co-workers from crystallographic database and computational studies46a,b also point to the existence of the sigma hole in molecules, particularly in the context of halogen bonding, to be discussed later. In recent years, a new molecular recognition motif, namely, the lone-pair···π interaction, has been considered extremely important in the context of supramolecular recognition.47 This lone pair can come from a fluorine atom and interact with any electrophilic center. The importance of C−F···CO interactions has been recognized by Diederich48a to investigate fluorophobicity in the active thrombin site by incorporation of fluorine atoms on the inhibitor ligands. The coinage of the word “orthogonal interactions” is a geometrical necessity if the lone pair (nucleophile) has to approach a relatively electrondeficient site, and the importance of these interactions are summarized in an excellent review by Diederich.48b The lone pair can also be contributed by a negatively charged ion which can interact electrostatically with an electron-deficient aromatic ring. The anion···π interaction so constituted embodies a key structural element that has been lately deemed to be important in supramolecular chemistry49a,b with implications for drug discovery and biomolecular design.49c These interactions have also been observed experimentally in crystallographic determinations. It has been observed that the nature of anion−π interactions in crystals of fluorobenzyl ammonium bromide salts can be attractive or repulsive, and this depends on the degree of fluorination at the aromatic centers.50 A series of theoretical investigations by Frontera et al. into this structural motif along with inputs from crystallographic database studies depict the stabilizing role these motifs have in the solid state. The directionality associated with this interaction is also performed using RI-MP2/aug-cc-pVDZ level of theory.51 543

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546

Crystal Growth & Design

Perspective

(c). Halogen Bonding (X···O/N; X = -F, -Cl, -Br, -I). In addition to the already existing arsenal of intermolecular interactions, another predominantly electrostatic interaction that came into view was “halogen bonding”52 wherein a heavier halogen containing polarizable electron density electrostatically interacts with a more electronegative atom, namely, oxygen and nitrogen. This bonding has been explored in detail via both computational and experimental approaches for complexes of DMAP with di- and tri-iodofluorobenzenes, which exhibit a very short N···I bond in the crystal, the distance being less than 3.00 Å.53 To investigate the geometric and energetic features of halogen bonded complexes between aromatic moieties and to study substituent effects in both rings (halogen bond donor and acceptor molecules) high level ab initio studies (RI-MP2/augcc-pVDZ) have been performed, along with QTAIM approaches and molecular modeling studies in chloroform and water.54a A deeper theoretical evaluation of the sigma bonding of complexes of NF3 with ambidentate electron donor and acceptor molecules, namely, HF, HCl, HNC, HCN, has been performed wherein either nitrogen or fluorine in NF3 can function as donors.54b In a very recent study, compounds containing either pyridyl or N,N-dimethylanilino groups as electron-donor moieties and a p-iodo-tetrafluorophenyl ring as an electron-acceptor group have been synthesized and short halogen bonding N···I have been observed. These compounds exhibit high polarizabilities in solution, and these observations are supported by molecular modeling calculations at the DFT PBE0/6-311++G** and TDDFT SAOP/TZP level.54c Recently, a combined experimental and database studies of threecentered halogen bonds with bifurcated acceptors present in molecular crystals, cocrystals, and salts have been studied with organic iodine as the donor atom and N, O, S, F, Cl, Br, or I atom as acceptors. It was concluded that three-centered halogen bonds are rare compared to hydrogen bonds.54d Furthermore, symmetrical [N−X−N]+ halogen bonds have been observed in solution, and the iodous halogen bond has this symmetry in both solution and the solid state, whereas in the bromous isomer, there is asymmetry in the solid state.54e These interactions have also been investigated in the gas phase by molecular beam scattering experiments and ab initio charge displacement calculations.54f Molecular Dynamics (MD) simulations have also been performed to investigate the sigma hole bonding and account for the strong anisotropy around the covalently bonded halogen atom by introduction of an extra point of charge in the classical force field calculations.54g The results obtained by this method compared well with both the crystallographic investigations and QM/MM calculations.54h,i Electrostatic potentials for the halogen bonding ligands are also generated in order to study the relationship between halogen bond strengths and halogen σ-hole size (and charge). It is found that the strength and character of the protein−ligand halogen bonds investigated here are strongly dependent on geometric factors and σ-hole characteristics.54j Recently, a parallelism between halogen bonds and hydrogen bonds has been explored in protein−ligand complexes.54k These have also been observed in liquid crystals.55 The structure and properties (energy, electronic, and thermodynamic properties) of complexes of pyridine with X−Y [X, Y = halogen] have been investigated at the MP2/aug-cc-pVDZ level to characterize the nature of halogen bonding. It is observed that charge transfer from the pyridine nitrogen to the antibonding X−Y orbital is responsible for the stability of the σ-bonded complex.56

Today, a vast body of literature is available that highlights the relevance of halogen bonding particularly in the context of heavier halogens. It is now of extreme significance to consider the fact that the lightest halogen fluorine can participate in halogen bonding. At the first instance the mention of an F···O contact seems unrealistic as both being electronegative repel each other. However, we know that O2F2 is stable and exists as a solid although the O−F bond is a 3-center-2-electron (3c-2e) bond.57 To substantiate further, the first systematic study employing ab initio intermolecular perturbation theory and crystallographic database studies on understanding of the nature of interactions between halogens with O/N/S indicates that “anisotropic electron distribution around the halogen atom leading to lowering of the repulsive wall and increase in electrostatic attraction is responsible for stability”.58 It was concluded: “If the carbon-bound halogen atom is in a sufficiently electron-withdrawing environment, then a strong attractive overall interaction will exist.”58 The point of consideration here is that when the halogen is fluorine and when the above-mentioned concept is realized in a molecule of interest then attractive F···O contacts will exist. The presence of a sigma hole on the fluorine atom substantiates this observation.44−46 Subsequent topological characterization of this electronic feature in organofluorine compounds containing strong electron withdrawing groups will be the focus of futuristic studies in the area of crystal engineering.

■

CONCLUSIONS In conclusion, it is to be realized that the realm of chemical bonding present in organic molecules containing fluorine is not “weak”. Fluorine is special as in the presence of activated hydrogen bond donors it forms H-bonds, can donate a lone pair to electrophilic center, and hence has both donor and acceptor characteristics. It is of extreme importance that all these forces albeit weak can cooperatively play a pivotal role in formation of crystalline molecular solids. Their contribution in addition to the already present arsenal of relatively stronger Hbonds is indeed noteworthy. It is of interest to investigate these noncovalent forces as a function of the hybridization of the carbon atom to which fluorine is connected in organic compounds. A detailed working knowledge of the geometrical features, along with the associated energetics of such noncovalent forces (also subsequent changes due to functional group modifications), can benefit the molecular, crystal, and protein engineering community in the future.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Fax: (+) 91-07554092392. Web: http://home.iiserbhopal.ac.in/∼dchopra/.

■

ACKNOWLEDGMENTS D.C. thanks IISER Bhopal for facilities and DST, India, for research funding under the fast track scheme.

■ ■

DEDICATION Dedicated to the 60th birthday of Prof T.N. Guru Row REFERENCES

(1) (a) Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University Press Inc: New York, 1997. (b) Guru Row, T. N. Coord. 544

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546

Crystal Growth & Design

Perspective

Chem. Rev. 1999, 183, 81−100. (c) Khan, M.; Enkelmann, V.; Brunklaus, G. Cryst. Growth Des. 2009, 9, 2354−2362. (2) (a) Desiraju, G. Angew. Chem., Int. Ed. 2011, 50, 52−59 andreferences therein. (b) Nishio, M.; Umezawa, Y.; Honda, K.; Tsuboyama, S.; Suezawa, H. CrystEngComm 2009, 11, 1757−1788 and referencestherein. (3) (a) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308−319. (b) Smart, B. E. J. Fluorine Chem. 2001, 109, 3−11. (4) Zimmer, L. E.; Sparr, C.; Gilmour, R. Angew. Chem., Int. Ed. 2011, 50, 11860−11871. (5) Roesky, H. Nat. Chem. 2011, 2, 240. (6) (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881− 1886. (b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320−330. (c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359−4369. (d) Kirk, K. L. Org. Proc. Res. Dev. 2008, 12, 305−321. (e) Jeschke, P. Pest Manag. Sci. 2010, 66, 10−27. (f) O’Hagan, D. J. Fluorine Chem. 2010, 131, 1071 − 1081. (7) Justik, M. W. Annu. Rep. Prog. Chem., Sect. A 2011, 107, 125−134. (8) Tressaud, A.; Haufe, G. Fluorine and Health: Molecular Imaging, Biomedical Materials and Pharmaceuticals; Elsevier: Amsterdam, 2008. (9) (a) Kirsch, P. Modern Fluoroorganic Chemistry, Synthesis, Reactivity and Applications; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2004. (b) Uneyama, K. Organofluorine Chemistry; Blackwell Publishing: Oxford, 2006. (c) Ojima, I. Fluorine in Medicinal Chemistry & Chemical Biology; Wiley-Blackwell: Chichester, 2009. (10) (a) Ernet, T.; Maulitz, A. H.; Würthwein, E. -U.; Haufe, G. J. Chem. Soc. Perkin Trans. 1 2001, 1929−1938. (b) Chambers, R. D.; Vaughan, J. F. S. Top. Curr. Chem. 1997, 192, 1−38. (c) Reinke, D.; Baumgärtel, H.; Cvitakš, T.; Klasinc, L.; Güsten, H. Ber. Bunsen-Ges. Phys. Chem. 1974, 78, 1145. (d) Heaton, M. M.; El-Talbi, M. R. J. Chem. Phys. 1986, 85, 7198−7210. (11) Kraka, E.; Cremer, D. ChemPhysChem 2009, 10, 686−698. (12) Roesky, H. W.; Haiduc, I. J. Chem. Soc., Dalton Trans. 1999, 2249−2264. (13) (a) Dunitz, J. D.; Taylor, R. Chem.Eur. J. 1997, 3, 89−98. (b) Dunitz, J. D. ChemBioChem 2004, 5, 614−621. (14) Atoji, M.; Lipscomb, W. N. Acta Crystallogr. 1954, 7, 173−175. (15) Thalladi, V. R.; Weiss, H.-C.; Blaser, D.; Boese, R.; Nangia, A.; Desiraju, G. R. J. Am. Chem. Soc. 1998, 120, 8702−8710. (16) Dunitz, J. D.; Schweizer, W. B. Chem.Eur. J. 2006, 12, 6804− 6816. (17) Thakur, T. S.; Kirchner, M. T.; Blaser, D.; Boese, R.; Desiraju, G. R. CrystEngComm 2010, 12, 2079−2085. (18) Parsch, J.; Engels, J. W. J. Am. Chem. Soc. 2002, 124, 5564− 5672. (19) (a) Choudhury, A. R.; Urs, U. K.; Nagarajan, K.; Guru Row, T. N. J. Mol. Struct. 2002, 605, 71−77. (b) Choudhury, A. R.; Nagarajan, K.; Guru Row, T. N. Cryst. Eng. 2003, 6, 145−152. (c) Choudhury, A. R.; Guru Row, T. N. CrystEngComm 2006, 8, 265−274. (d) Choudhury, A. R.; Guru Row, T. N. Cryst. Growth. Des. 2004, 4, 47−52. (e) Chopra, D.; Nagarajan, K.; Guru Row, T. N. J. Mol. Struct. 2008, 888, 70−83. (f) Chandrasekhar, V.; Thilagar, P.; Krishnan, V.; Bickley, J. F.; Steiner, A. Cryst. Growth Des. 2007, 7, 668−675. (g) Durie, A. J.; Slawin, A. M. Z.; Lebl, T.; Kirsch, P.; O’Hagan, D. Chem. Commun. 2011, 47, 8265−8267. (20) (a) Chopra, D.; Guru Row, T. N. CrystEngComm 2008, 10, 54− 67. (b) Abad, A.; Agulló, C.; Cuñat, A. C.; Vilanova, C.; Ramírez de Arellano, M. C. Cryst. Growth Des. 2006, 6, 46−57. (c) Asensio, G.; Medio-Simon, M.; Alemán, P.; Ramírez de Arellano, C. Cryst. Growth Des. 2006, 6, 2769−2778. (d) Nayak, S. K.; Venugopala, K. N.; Chopra, D.; Vasu.; Guru Row, T. N. CrystEngComm 2010, 12, 1205− 1216. (e) Nayak, S. K.; Venugopala, K. N.; Chopra, D.; Guru Row, T. N. CrystEngComm 2011, 13, 591−605. (f) Sunil, S. L.; Nayak, S. K.; Hathwar, V. R.; Chopra, D.; Guru Row, T. N. Role of Fluorine in Weak Interactions in Co-crystals. In Pharmaceutical Salts and Cocrystals; Wouters, J., Quere, L., Eds.; RSC, London, U.K., 2012; Chapter 3. (21) (a) Lee, H. Y.; Olasz, A.; Pink, M.; Park, H.; Lee, D. Chem. Commun. 2011, 47, 481−483. (b) Coste, S.; Schneider, J. -M.; Petit,

M.-N.; Coquerel, G. Cryst. Growth Des. 2004, 4, 1237−1244. (c) Kato, T.; Okamoto, I.; Masu, H.; Katagiri, K.; Tominaga, M.; Yamaguchi, K.; Kagechika, H.; Azumaya, I. Cryst. Growth. Des. 2008, 8, 3871−3877. (d) Chopra, D.; Guru Row, T. N. Cryst. Growth Des. 2005, 5, 1679− 1681. (e) Chopra, D.; Guru Row, T. N. Cryst. Growth Des. 2006, 6, 1267−1270. (d) Chopra, D.; Guru Row, T. N. Cryst. Growth Des. 2008, 8, 848−853. (22) (a) Chopra, D.; Thiruvenkatam, V.; Guru Row, T. N. Cryst. Growth Des. 2006, 6, 843−845. (b) Chopra, D.; Thiruvenkatam, V.; Manjunath, S. G.; Guru Row, T. N. Cryst. Growth Des. 2007, 7, 868− 874. (c) Vasylyeva, V.; Merz, K. Cryst. Growth Des. 2010, 10, 4250− 4255. (d) Thakur, T. S.; Sathishkumar, R.; Dikundwar, A. G.; Guru Row, T. N.; Desiraju, G. R. Cryst. Growth. Des. 2010, 10, 4246−4249. (e) Dikundwar, A. G.; Sathishkumar, R.; Guru Row, T. N.; Desiraju, G. R. Cryst. Growth. Des. 2011, 11, 3954−3963. (23) Hursthouse, M. B.; Montis, R.; Tizzard, G. J. CrystEngComm 2011, 13, 3390−3401. (24) Chopra, D.; Cameron, T. S.; Ferrara, J. D.; Guru Row, T. N. J. Phys. Chem. A 2006, 110, 10465−10477. (25) Dikundwar, A. G.; Venkateswarlu, C.; Piltz, R. O.; Chandrasekaran, S.; Guru Row, T. N. CrystEngComm 2011, 13, 1531−1538. (26) Chopra, D.; Guru Row, T. N. CrystEngComm 2011, 13, 2175− 2186. (27) (a) Schwarzer, A.; Bombicz, P.; Weber, E. J. Fluorine Chem. 2010, 131, 345−356. (b) Cetina, M.; Nagl, A.; Krištafor, V.; Benci, K.; Mintas, M. Cryst. Growth Des. 2008, 8, 2975−2981. (c) Takahashi, S.; Jukurogi, T.; Katagiri, T.; Uneyama, K. CrystEngComm 2006, 8, 320− 326. (d) Schwarzer, A.; Weber, E. Cryst. Growth. Des. 2008, 8, 2862− 74. (28) Frohlich, R.; Rosen, T. C.; J. Meyer, O . G.; Rissanen, K.; Haufe, G. J. Mol. Struct. 2006, 787, 50−62. (29) (a) Kui, S. C. F.; Zhu, N.; Chan, M. C. W. Angew. Chem., Int. Ed. 2003, 42, 1628−1632. (b) Chan, M. C. W.; Kui, S. C. F.; Cole, J. M.; McIntyre, G. J.; Matsui, S.; Zhu, N.; Tam, K.-H. Chem.Eur. J. 2006, 12, 2607−2619. (c) Chan, M. C. Chem. Asian J. 2008, 3, 18−27. (30) Surya Prakash, G. K.; Wang, F.; Rahm, M.; Shen, J.; Ni, C.; Haiges, R.; Olah, G. A. Angew. Chem., Int. Ed. 2011, 50, 11761−11764, DOI: . (31) (a) Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J. Chem. Soc. Rev. 2011, 40, 3496−3508 and references therein. (b) Babudri, F.; Farinolo, G. M.; Naso, F.; Ragni, R. Chem. Commun. 2007, 1003−1022. (c) Zheng, H.; Comeforo, K.; Gao, J. J. Am. Chem. Soc. 2009, 131, 18−19. (d) Jackel, C.; Koksch, B. Eur. J. Org. Chem. 2005, 4483−4503. (e) Campbell, N. H.; Smith, D. L.; Reszka, A. P.; Neidle, S.; O'Hagan, D. Org. Biomol. Chem. 2011, 9, 1328−1331. (f) Hughes, R. P. J. Fluorine Chem. 2010, 131, 1059−1070. (32) (a) Hyla-Kryspin, I.; Haufe, G.; Grimme, S. Chem.Eur. J. 2004, 10, 3411−3422. (b) O’Oria, E. D.; Novoa, J. J. CrystEngComm 2008, 10, 423−436. (33) Hyla-Kryspin, I.; Haufe, G.; Grimme, S. Chem. Phys. 2008, 346, 224−236. (34) Rybalova, T. V.; Bagryanskaya, I. Y. J. Struct. Chem. 2009, 50, 741−753. (35) Rodziewicz, P.; Rutkowski, K. S.; Melikova, S. M.; Koll, A. Chem. Phys. 2009, 361, 129−136. (36) Rutkowski, K. S.; Herrebout, W. A.; Melikova, S. M.; van der Veken, B. J.; Koll, A. Chem. Phys. 2008, 354, 71−79. (37) Checinska, L.; Grabowski, S. J. Chem. Phys. 2006, 327, 202−208. (38) Melandri, S. Phys. Chem. Chem. Phys. 2011, 13, 13901−13911. (39) (a) Li, C.; Ren, S.-F.; Hou, J.-L.; Yi, H. P.; Zhu, S.-Z.; Jiang, X.K.; Li, Z.-T. Angew. Chem., Int. Ed. Engl. 2005, 44, 5725−5729. (b) Li, C.; Zhu, Y.-Y.; Yi, H.-P.; Li, C.-Z.; Jiang, X.-K.; Li, Z.-T.; Yu, Y.-H. Chem.Eur. J. 2007, 13, 9990−9998. (c) Zhu, Y.-Y.; Wu, J.; Li, C.; Zhu, J.; Hou, J.-L.; Li, C.-Z.; Jiang, X.-K.; Li, Z.-T. Cryst. Growth Des. 2007, 7, 1490−96. (d) Koller, A. N.; Bozilovic, J.; Engels, J. W.; Gohlke, H. Nucleic Acids Res. 2010, 38, 3133−3146. (e) Zhu, Y.-Y.; Yi, H.-P.; Li, C.; Jiang, X.-K.; Li, Z.-T. Cryst. Growth Des. 2008, 8, 1294− 1300. 545

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546

Crystal Growth & Design

Perspective

(40) (a) Hulme, A. T.; Price, S. L.; Tocher, D. A. J. Am. Chem. Soc. 2005, 127, 1116−1117. (b) Chopra, D.; Nagarajan, K.; Guru Row, T. N. Cryst. Growth Des. 2005, 5, 1035−1039. (41) Nayak, S. K.; Reddy, M. K.; Guru Row, T. N.; Chopra, D. Cryst. Growth Des. 2011, 11, 1578−1596. (42) Collas, A.; Borger, R. D.; Amanova, T.; Blockhuys, F. CrystEngComm 2011, 13, 702−710. (43) Felsmann, M.; Eissmann, F.; Schwarzer, A.; Weber, E. Cryst. Growth Des. 2011, 11, 982−989. (44) (a) Hathwar, V. R.; Guru Row, T. N. Cryst. Growth. Des. 2011, 11, 1338−1346. (b) Hathwar, V. R.; Guru Row, T. N. J. Phys. Chem. A. 2010, 114, 13434−13441. (c) Hathwar, V. R.; Thakur, T. S.; Dubey, R.; Pavan, M. S.; Guru Row, T. N.; Desiraju, G. R. J. Phys. Chem. A. 2011, 115, 12852−12863. (45) (a) Murray, J. S.; Lane, P.; Clark, T.; Politzer, P. J. Mol. Model. 2007, 13, 1033−1038. (b) Politzer, P.; Murray, J. S.; Concha, M. C. J. Mol. Model. 2008, 14, 659−665. (c) Murray, J. S.; Lane, P.; Politzer, P. J. Mol. Model. 2009, 15, 723−729. (d) Murray, J. S.; Lane, P.; Clark, T.; Riley, K. E.; Politzer, P. J. Mol. Model. 2011, DOI: 10.1007/s00894011-1089-1. (46) (a) Metrangolo, P.; Murray, J. S.; Pilati, T.; Politzer, P.; Resnati, G.; Terraneo, G. CrystEngComm 2011, 13, 6593−6596. (b) Metrangolo, P.; Murray, J. S.; Pilati, T.; Politzer, P.; Resnati, G.; Terraneo, G. Cryst. Growth Des. 2011, 11, 4238−4246. (47) (a) Mooibroek, T. J.; Gamez, P.; Reedijk, J. CrystEngComm 2008, 10, 1501−1515. (b) Robertazzi, A.; Krull, F.; Knapp, E. −W.; Gamez, P. CrystEngComm 2011, 13, 3293−3300. (c) Choudhury, S. R.; Dey, B.; Das, S.; Gamez, P.; Robertazzi, A.; Chan, K. T.; Lee, H. M.; Mukhopadhyay, S. J. Phys. Chem. A 2009, 113, 1623−1627. (d) Granifo, J.; Toledo, D.; Garland, M. T.; Baggio, R. J. Fluorine Chem. 2010, 131, 510−516. (48) (a) Olsen, J. A.; Banner, D. W.; Seiler, P.; Obst-Sander, U.; D’Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. Angew Chem. Int. Ed. 2003, 42, 2507−2511. (b) Paulini, R.; Muller, K.; Diederich, F. Angew. Chem., Int. Ed. 2005, 44, 1788−1805. (49) (a) Estarellas, C.; Frontera, A.; QuiÇ onero, D.; Deya, P. M. Chem.Asian J. 2011, 6, 2316−2318. (b) Das, A.; Choudhury, S. R.; Estarellas, C.; Dey, B.; Frontera, A.; Hemming, J.; Helliwell, M.; Gamez, P.; Mukhopadhyay, S. CrystEngComm 2011, 13, 4519−4527. (c) Lu, Y.; Wang, Y.; Zhu, W. Phys. Chem. Chem. Phys. 2010, 12, 4543−4551. (50) Giese, M.; Albrecht, M.; Bannwarth, C.; Raabe, G.; Valkonen, A.; Rissanen, K. Chem. Commun. 2011, 47, 8542−8544. (51) (a) Lucas, X.; Quiñonero, D.; Frontera, A.; Deya, P. M. J. Phys. Chem. A 2009, 113, 10367−10375. (b) Estarellas, C.; Bauzá, A.; Frontera, A.; Quiñonero, D.; Deya, P. M. Phys. Chem. Chem. Phys. 2011, 13, 5696−5702. (c) Estarellas, C.; Frontera, A.; Quiñonero, D.; Deya, P. M. J. Phys. Chem. A 2011, 115, 7849−7857. (52) (a) Metrangalo, P.; Resnati, G. Science 2008, 321, 918−919. (b) Parisini, E.; Metrangolo, P.; Pilati, T.; Resnati, G.; Terraneo, G. Chem. Soc. Rev. 2011, 40, 2267−2278. (c) Ojala, W. H.; Lystad, K. M.; Deal, T. L.; Engebretson, J. E.; Spude, J. M.; Balidemaj, B.; Ojala, C. R. Cryst. Growth. Des. 2009, 9, 964−970. (53) Roper, L. C.; Preasang, C.; Kozhevnikov, V. N.; Whitwood, A. C.; Karadakov, P. B.; Bruce, D. W. Cryst. Growth. Des. 2010, 10, 3710− 3720. (54) (a) Bauzá, A.; Quiñonero, D.; Frontera, A.; Deyà, P. M. Phys. Chem. Chem. Phys. 2011, 13, 20371−20379. (b) Blanco, F.; Alkorta, I.; Rozas, I.; Solimannejad, M.; Elguero, J. Phys. Chem. Chem. Phys. 2011, 13, 674−683. (c) Cariati, E.; Cavallo, G.; Forni, A.; Leem, G.; Metrangolo, P.; Pilati, T.; Paolo Resnati, G.; Righetto, S.; Terraneo, G.; Tordin, E. Cryst. Growth. Des. 2011, 11, 5642−5648. (d) Cincic, D.; Friscic, T.; Jones, W. CrystEngComm 2011, 13, 3224−3231. (e) Carlsson, A.-C. C.; Gräfenstein, J.; Laurila, J. L.; Bergquist, J.; Erdélyi, M. Chem. Commun. 2011, DOI: 10.1039/c1cc15839b. (f) Cappelletti, D.; Candori, P.; Pirani, F.; Belpassi, L.; Tarantelli, F. Cryst. Growth Des. 2011, 11, 4279−4283. (g) Ibrahim, M. A. A. J. Comput. Chem. 2011, 32, 2564−2574. (h) Rendine, S.; Pieraccini, S.; Forni, A.; Sironi, M. Phys. Chem. Chem. Phys. 2011, 13, 19508−19516.

(i) Ibrahim, M. A. A. J. Chem. Inf. Model. 2011, 51, 2549−2559. (j) Riley, K. E.; Hobza, P. Cryst. Growth Des. 2011, 11, 4272−4278. (k) Voth, A. R.; Khuu, P.; Oishi, K.; Ho, P. S. Nat. Chem. 2009, 1, 74− 79. (55) Metrangolo, P.; Präsang, C.; Resnati, G.; Liantonio, R.; Whitwood, A. C.; Bruce, D. W. Chem. Commun. 2006, 3290−3292. (56) Wang, Z.; Zheng, B.; Yu, X.; Li, X.; Yi, P. J. Chem. Phys. 2010, 132, 164104−164105. (57) Jackson, R. H. J. Chem. Soc. 1962, 4585. (58) Lommerse, J. P. M.; Stone, A. J.; Taylor, R.; Allen, F. H. J. Am. Chem. Soc. 1996, 118, 3108−3116.

546

dx.doi.org/10.1021/cg201498u | Cryst. Growth Des. 2012, 12, 541−546