An intimate interplay of O–H     O/C–H     F hydrogen bonds and p–p stacking interactions allows a phenyleneethynylene based dendritic molecule to fold and self-assemble into two distinctively different molecular crystals as pseudopolymorphs

Lee, Dongwhan

Lee, Ho Yong

Olasz, Andras

Park, Hyunsoo

Pink, Maren

English

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The art of stacking: structural folding and self-assembly of branched
p-conjugation assisted by O–H  O and C–H  F hydrogen bondswz
Ho Yong Lee, Andra´s Olasz, Maren Pink, Hyunsoo Park and Dongwhan Lee*
Received 29th June 2010, Accepted 22nd September 2010
DOI: 10.1039/c0cc02177f
An intimate interplay of O–H  O/C–H  F hydrogen bonds
and p–p stacking interactions allows a phenyleneethynylene-
based dendritic molecule to fold and self-assemble into two
distinctively diﬀerent molecular crystals as pseudopolymorphs.
Polymorphism describes the ability of molecules to adopt
more than one structure in the solid state.1 When polymorphs
occur with variations in solvent contents in the unit cell, the
term pseudopolymorphism is used.2 A practical importance of
this phenomenon has been recognised in the ﬁeld of pharma-
ceuticals since (pseudo)polymorphs often display diﬀerent
physicochemical properties.1a,1c,3,4 In this communication,
we report pseudopolymorphism of a phenyleneethynylene-
based C3-symmetric p-conjugated molecule. Structure analysis
on two distinctively diﬀerent molecular crystals revealed an
intimate interplay of strong O–H  O and weak C–H  F
hydrogen bonds in structural folding and solid-state self-
assembly (Scheme 1), a detailed understanding of which was
also aided by theoretical studies.
Hydrogen bonding is one prominent type of non-covalent
interaction, the directional nature of which is proven to play a
critical role in the spontaneous structural ordering of many
chemical architectures.5 While strong hydrogen bonds are
typically constructed using N–H  O, O–H  O, or O–H  N
motifs, weak hydrogen bonds involving C–H  O, C–H  N,
or C–H  p contacts have recently been recognised as an
important class of non-covalent interactions.6 Recent examples
of linear foldamers and heterodimers that are stabilised by
N–H  F hydrogen bonding support the notion that organo-
ﬂuorine fragments can also be utilised as a hydrogen bonding
acceptor (HBA) for the assembly of higher-order structures.7
Undoubtedly, the charged F anion is a strong HBA,8 but the
ability of covalently bound ﬂuorine atom, as present in the
C–F group, to function as an eﬀective HBA still remains
controversial.9–12 Statistical analysis on crystallographically
determined structures suggests, however, that C–H  F inter-
actions could be as important as C–H  O or C–H  N
hydrogen bonds.13
Our on-going interest in the conformational switching of
branched p-conjugated structures14 prompted the design and
synthesis of a new phenyleneethynylene-based C3-symmetric
molecule 1 having a ﬂuorinated molecular core (Scheme 2).z
The ﬁnal round of cross-coupling between 4 and 1,3,5-
triﬂuoro-2,4,6-triiodobenzene resulted in a mixture of the
desired product 1, along with partially coupled byproducts
and the homocoupling product of 4. A simple layering of
hexanes over a CHCl3 solution of this material, however,
induced selective crystallization of 1, which was isolated and
fully characterised (Fig. S1).z
Self-association of 1 in solution was subsequently investi-
gated by concentration-dependent 1H NMR studies in CDCl3
at T= 298 K. A systematic downﬁeld shift of the propargylic
O–H resonance from 2.52 to 2.73 ppm with increasing
concentration within the range of 10 to 40 mM could be ﬁtted
with K = 4.1 (0.5) M1 using the EK model.15 This
observation implicated the involvement of O–H  O hydrogen
bonding in the self-association process, which should become
more favorable with decreasing polarity in the CHCl3/hexane
binary solvent mixture used in crystallization.
Scheme 1 Conformational switching to achieve shape comple-
mentarity for self-association.
Scheme 2 Synthetic route to 1.
Department of Chemistry, Indiana University,
800 East Kirkwood Avenue, Bloomington, IN 47405, USA.
E-mail: dongwhan@indiana.edu; Fax: +1 812-855-8300;
Tel: +1 812-855-9364
w This article is part of the ‘Emerging Investigators’ themed issue for
ChemComm.
z Electronic supplementary information (ESI) available: Details of the
synthetic procedures, crystallographic data, and DFT calculations.
CCDC 783201 and 783202. For ESI and crystallographic data in CIF
or other electronic format, see DOI: 10.1039/c0cc02177f
This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 481–483 | 481
COMMUNICATION www.rsc.org/chemcomm | ChemComm
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Intriguingly, two diﬀerent kinds of single crystals of 1
were obtained depending on the method of crystallization.y
Speciﬁcally, colorless blocks of the completely ‘‘unfolded’’
conformer 1U (Fig. 1a) were obtained by slow diﬀusion of
hexane into a CHCl3 solution of 1.
16 On the other hand, an
instant mixing of a CHCl3 solution of 1 with hexane or
benzene produced colorless needles of the ‘‘folded’’ conformer
1F (Fig. 1b),16 which was also characterised by single crystal
X-ray crystallography. As shown in Fig. 1 and S2 (ESIz), the
ﬂuorinated benzene core and peripheral aryl groups in 1U are
disposed in an essentially perpendicular manner with dihedral
angles of t = 79.3(2) and 83.4(7)1.17,18 For the other
conformer 1F, however, two of the three ethynyl-extended
‘‘wingtip’’ O–H groups engage in an intramolecular O–H  O
hydrogen bond (O  O = 2.731(4) A˚), which, along with
C–H  F contact to the ﬂuorinated core (C  F = 3.209(5) A˚),
eﬀectively ﬂattens the entire structure with relatively small t
values of 9.0(2), 14.1(2), and 35.5(1)1.18
A close inspection of the intermolecular packing in the
lattice provided an initial clue to the origin of conformational
isomerism of 1. Instead of making intramolecular O–H  O
bond as in 1F (Fig. 1b), 1U uses strong intermolecular
O–H  O hydrogen bonds (O  O = 2.689(5) A˚) to form a
discrete dimeric structure (1U)2. As shown in Fig. 2 and S3
(ESIz), the two 1U units comprising the dimer maximise their
shape complementarity by adopting an essentially ‘‘staggered’’
orientation, in which two C3-symmetric molecules are rotated
by 60 degrees with respect to each other to achieve a tight
docking.
An interdigitated arrangement of phenyleneethynylene
fragments in the dimeric (1U)2 thus provides a well-shielded
hydrophobic cavity that encapsulates a cyclic hydrogen
bonding network constructed by six ‘‘wing-tip’’ OH groups
(Fig. 2c and d). A more fascinating feature of the dimeric (1U)2
is additional stabilization provided by six C–H  F contacts
between the propargyl C–H groups and the ﬂuorinated
benzene core (Fig. 2a and c). The relatively short C  F
distance of 3.228(8) A˚ observed here lies toward the shorter
end of the values determined for previously reported
structures.13a,13c–e,19–21
The functional relevance of such C–H  F contacts in
the self-assembly process was evaluated further by density
functional theory (DFT) computational studies on the
simpliﬁed model compounds 10 and 5 (at B3LYP/6-31G**
theory level). The pseudo D3d-symmetric optimised geometry
(Fig. S4, ESIz) of (10)2 provided an average value of d(F  H) =
2.45 A˚ along the C–H  F contacts, which is ca. 0.17 A˚ shorter
than the sum of van der Waals radii of F and H.
Energy evaluation at the B3LYP/cc-pVTZ(-f) level further
supported the notion that such C–H  F interactions contribute
to the thermodynamic stability of the dimer. Speciﬁcally, (10)2
is stabilised by 7.4 kcal mol1 relative to the essentially
isostructural (5)2 lacking the C–F units (Fig. S5, ESIz), when
the energy diﬀerence between the individual monomers and
the corresponding dimers was compared (Fig. S6, ESIz).
Divided by the total number of contacts within the dimer,
each C–H  F interaction contributes to the overall stability
by ca. 1.2 kcal mol1.
Similarly to the self-association of 1U, its conformational
isomer 1F also forms a dimeric structure in the solid state, but
the topology of (1F)2 is determined by a quite diﬀerent set of
non-covalent interactions. As shown in Fig. 1b, 1F adopts a
planar conformation, which is anticipated to promote cofacial
stacking. Indeed, the assembly of dimeric (1F)2 is assisted by
p–p stacking (ca. 3.38 A˚) between electron-deﬁcient ﬂuorinated
benzene core and electron-rich tert-butyl-substituted phenyl
ring, the complementarity of which is further strengthened by
the existence of two such contacts within the dimer (Fig. 3a–c).
In addition, the ‘‘dangling’’ OH group in the monomeric 1F
(Fig. 1b) engages in an intermolecular hydrogen bond
(O  O = 2.654(4); 2.670(4) A˚) to the O–H  O–H unit of the
stacking partner (Fig. 3a and c) to complete an extended
O–H  O–H  O–H array. Intriguingly, this crescent-shaped
O–H  O–H  O–H motif on each side of (1F)2 can further
associate with the complementary O–H  O–H  O–H unit of
the neighboring dimer to close up the six-membered cyclic
Fig. 1 X-Ray structures of 1U (a) and 1F (b) with thermal ellipsoids
at 50% probability, where O is red and F is blue. The O–H  O and
C–H  F interactions are represented by red and blue dotted lines,
respectively.
Fig. 2 Capped stick (a) and space-ﬁlling (b) representations of the
solid-state structure of dimeric (1U)2 generated using X-ray coordinates.
The O–H  O and C–H  F interactions are represented by dotted
lines, the close-up views of which are provided in partial structures
(c) and (d).
482 | Chem. Commun., 2011, 47, 481–483 This journal is c The Royal Society of Chemistry 2011
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hydrogen bond (Fig. 3d). The crystal structure of 1F
also revealed an intermolecular C–H  F contact (C  F =
3.207(5) A˚).
In summary, an intimate interplay of O–H  O/C–H  F
hydrogen bonds and p–p stacking collectively gives rise to
conformational pseudopolymorphs of a dendritic p-conjugated
molecule (Scheme 1). For the highly symmetric and non-
planar conformer 1U, a maximum number of O–H  O and
C–H  F contacts is achieved by shape complementarity in
monomer–monomer docking. For the less symmetric and
largely planar conformer 1F, the molecule takes a diﬀerent
strategy to maximise monomer–monomer contacts by using
predominantly a combination of p–p stacking and O–H  O
interactions. Eﬀorts are currently underway in order to
prepare chiral derivatives of the parent system and to explore
further the functional role of C–H  F hydrogen bonds in
supramolecular chemistry.
This work was supported by the National Science
Foundation (CAREER CHE 0547251) and DTRA/US Army
Research Oﬃce (W911NF-07-1-053).
Notes and references
y Crystal data. 1U (CCDC 783202) C53.27H47.27Cl6.82F3O3
M = 1034.63, trigonal R3, a = 17.1496(12) A˚, c = 33.798(2) A˚,
V = 8608.5(9) A˚3, T = 150(2) K, Mo-Ka, 26 759 reﬂections, 3403
unique (Rint = 0.025). R1 = 0.0905, wR2 = 0.2683 (for 2596 observed
reﬂections with I > 2s(I) and 276 parameters, 784 restraints).
1F (CCDC 783201) C51H45F3O3 M = 762.87, triclinic P1, a =
10.4830(8) A˚, b = 14.9544(12) A˚, c = 15.7398(13) A˚, a =
89.095(2)1, b = 86.983(2)1, g = 71.805(2)1, V = 2340.9(3) A˚3,
T = 150(2) K, Mo-Ka, 29 791 reﬂections, 7914 unique (Rint =
0.045). R1 = 0.0691, wR2 = 0.2059 (for 5124 observed reﬂections
with I> 2s(I) and 523 parameters, 12 restraints). The contribution of
the diﬀuse contributing solvent (=two CHCl3 per molecule of 1F) to
the structure factors was assessed by back-Fourier transformation,
and the data were corrected accordingly using Platon/SQUEEZE.
The sum formula of 1F excludes these solvent molecules.
1 (a) J. Bernstein, Polymorphism in Molecular Crystals, Oxford
University Press, New York, 2002; (b) R. J. Davey, Chem.
Commun., 2003, 1463–1467; (c) G. P. Stahly, Cryst. Growth Des.,
2007, 7, 1007–1026; (d) J. Bernstein, J. D. Dunitz and
A. Gavezzotti, Cryst. Growth Des., 2008, 8, 2011–2018;
(e) G. R. Desiraju, Angew. Chem., Int. Ed., 2007, 46, 8342–8356;
(f) L. Yu, Acc. Chem. Res., 2010, 43, 1257–1266.
2 A. Nangia, Cryst. Growth Des., 2006, 6, 2–4 and references cited
therein.
3 Polymorphism in the Pharmaceutical Industry, ed. R. Hilﬁker,
Wiley-VCH, Weinheim, 2006.
4 (a) H. G. Brittain, J. Pharm. Sci., 2009, 98, 1617–1642;
(b) A. Nangia, Acc. Chem. Res., 2008, 41, 595–604.
5 (a) G. A. Jeﬀrey, An Introduction to Hydrogen Bonding, Oxford
University Press, New York, NY, 1997; (b) L. J. Prins,
D. N. Reinhoudt and P. Timmerman, Angew. Chem., Int. Ed.,
2001, 40, 2382–2492; (c) T. Steiner, Angew. Chem., Int. Ed., 2002,
41, 48–76.
6 (a) G. R. Desiraju, Acc. Chem. Res., 1991, 24, 290–296;
(b) G. R. Desiraju, Acc. Chem. Res., 1996, 29, 441–449;
(c) P. Hobza and Z. Havlas, Chem. Rev., 2000, 100, 4253–4264.
7 (a) X. Zhao, X.-Z. Wang, X.-K. Jiang, Y.-Q. Chen, Z.-T. Li and
G.-J. Chen, J. Am. Chem. Soc., 2003, 125, 15128–15139; (b) C. Li,
S.-F. Ren, J.-L. Hou, H.-P. Yi, S.-Z. Zhu, X.-K. Jiang and
Z.-T. Li, Angew. Chem., Int. Ed., 2005, 44, 5725–5729; (c) C. Li,
Y.-Y. Zhu, H.-P. Yi, C.-Z. Li, X.-K. Jiang, Z.-T. Li and Y.-H. Yu,
Chem.–Eur. J., 2007, 13, 9990–9998.
8 S. A. Harrell and D. H. McDaniel, J. Am. Chem. Soc., 1964, 86,
4497–4497.
9 Understanding the supramolecular chemistry of C–F group is thus
considered as one of the last frontiers in intermolecular
interactions1e.
10 J. A. K. Howard, V. J. Hoy, D. O’Hagan and G. T. Smith,
Tetrahedron, 1996, 52, 12613–12622.
11 J. D. Dunitz and R. Taylor, Chem.–Eur. J., 1997, 3, 89–98.
12 (a) E. A. Meyer, R. K. Castellano and F. Diederich, Angew. Chem.,
Int. Ed., 2003, 42, 1210–1250; (b) F. Hof and F. Diederich, Chem.
Commun., 2004, 477–480.
13 (a) V. R. Thalladi, H.-C. Weiss, D. Bla¨ser, R. Boese, A. Nangia
and G. R. Desiraju, J. Am. Chem. Soc., 1998, 120, 8702–8710;
(b) G. R. Desiraju, Acc. Chem. Res., 2002, 35, 565–573;
(c) A. R. Choudhury and T. N. Guru Row, Cryst. Growth Des.,
2004, 4, 47–52; (d) A. Schwarzer, W. Seichter, H. Stoeckli-Evans,
M. Losada and J. Hulliger, CrystEngComm, 2004, 6, 567–572;
(e) M. Hyacinth, M. Chruszcz, K. S. Lee, M. Sabat, G. Gao and
L. Pu, Angew. Chem., Int. Ed., 2006, 45, 5358–5360.
14 (a) X. Jiang, Y.-K. Lim, B. J. Zhang, E. A. Opsitnick, M.-H. Baik
and D. Lee, J. Am. Chem. Soc., 2008, 130, 16812–16822;
(b) E. Opsitnick and D. Lee, Chem.–Eur. J., 2007, 13, 7040–7049;
(c) H. Y. Lee, X. Song, H. Park, M.-H. Baik and D. Lee, J. Am.
Chem. Soc., 2010, 132, 12133–12144.
15 R. B. Martin, Chem. Rev., 1996, 96, 3043–3064.
16 In analogy to protein secondary structures, the term ‘‘folding’’ here
describes conformational restrictions imposed by non-covalent
bonds.
17 The structure of 1F is disordered over two positions, for which only
one model is shown in Fig. 1 and 2. See ESIz.
18 The dihedral angle here is the angular relationship between the
central C6F3 fragment and the peripheral aryl rings, all treated as
least squares planes calculated from crystallographic data. In this
analysis, t = 901 corresponds to a perfectly orthogonal arrange-
ment, whereas t = 01 corresponds to a perfectly coplanar
arrangement.
19 A. R. Choudhury, K. Nagarajan and T. N. G. Row,Acta Crystallogr.,
Sect. C: Cryst. Struct. Commun., 2004, 60, o644–o647.
20 A. J. Mountford, D. L. Hughes and S. J. Lancaster, Chem.
Commun., 2003, 2148–2149.
21 H.-C. Weiss, R. Boese, H. L. Smith and M. M. Haley, Chem.
Commun., 1997, 2403–2404.
Fig. 3 Capped stick and space-ﬁlling representations of the solid-
state structure of dimeric (1F)2 generated using X-ray coordinates: (a)
and (b) top view; (c) side view. In (d) is shown the extended structure
of hydrogen-bonded (1F)2 with hexameric OH cluster motif high-
lighted within a red box. The O–H  O and C–H  F interactions are
represented by dotted lines.
This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 481–483 | 483
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The art of stacking: structural folding and self-assembly of branched p-conjugation assisted by O–H...O and C–H...F hydrogen bonds

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The art of stacking: structural folding and self-assembly of branched p-conjugation assisted by O–H...O and C–H...F hydrogen bonds

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