Symmetrical bifurcated halogen bond: Design and synthesis

Article abstract of DOI:10.1021/cg200603z

The main purpose of this work is to extend the application of the symmetrical bifurcated halogen bond in crystal engineering. For this purpose, the optimization of this supramolecular synthon was performed first by using quantum mechanical calculations. The results obtained from theoretical calculations showed that 1,4-diiodotetrafluorobenzene, 1,10-phenanthroline-5,6- dione, and 4,4′,6,6′-tetramethyl-2,2′-bipyrimidine are good candidates for the formation of the symmetrical bifurcated halogen bond. This was further confirmed by the successful synthesis of two cocrystals that are composed of the three compounds and formed mainly via symmetrical bifurcated halogen bonds. The good agreement between the theoretical design and the experimental synthesis also indicates that the quantum mechanical calculation can play an important role in increasing the probability of discovering useful supramolecular synthons.

Full text of DOI:10.1021/cg200603z

ARTICLE
pubs.acs.org/crystal
Symmetrical Bifurcated Halogen Bond: Design and Synthesis
Published as part of the Crystal Growth & Design virtual special issue on Halogen Bonding in Crystal
Engineering: Fundamentals and Applications
Baoming Ji,* Weizhou Wang, Dongsheng Deng, and Yu Zhang
College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022, P. R. China
S Supporting Information
b
ABSTRACT: The main purpose of this work is to extend the
application of the symmetrical bifurcated halogen bond in crystal
engineering. For this purpose, the optimization of this supramo-
lecular synthon was performed first by using quantum mechanical
calculations. The results obtained from theoretical calculations
showed that 1,4-diiodotetrafluorobenzene, 1,10-phenanthroline-
5,6-dione, and 4,40,6,60-tetramethyl-2,20-bipyrimidine are good
candidates for the formation of the symmetrical bifurcated halogen
bond. This was further confirmed by the successful synthesis of two
cocrystals that are composed of the three compounds and formed
mainly via symmetrical bifurcated halogen bonds. The good
agreement between the theoretical design and the experimental
synthesis also indicates that the quantum mechanical calculation can play an important role in increasing the probability of
discovering useful supramolecular synthons.
Scheme 1. NO2 Hal Synthons
’ INTRODUCTION
3 3 3
The halogen bond, the noncovalent interaction involving a
halogen atom (Hal; Cl, Br, or I) as an acceptor of electron
density, has been the subject of study by a number of authors.1ꢀ18
Considering, however, that the halogen atom and the halogen
bond electron donor are both negatively charged, the very
existence of halogen bonds is a little surprising. The problem
was recently explained by Politzer et al. who showed the
existence of an electropositive crown called σ-hole at the top
of the halogen atom directed to the electron donor.7 In recent
years, many studies have focused on the role of halogen bonds in
the field of crystal engineering and showed that the halogen bond
could be used as an alternative to the hydrogen bond and metal
ion coordination in crystal engineering applications.1 In fact,
Desiraju and co-workers found that the noncovalent interactions
involving chlorine, bromine, and iodine may be used for con-
structing three-dimensional (3D) hostꢀguest solids and that
these interactions, which were defined as supramolecular syn-
thons at a later time, seem to have much of the directional
specificity that is required for such geometry-based design.14
Among the halogen bond supramolecular synthons14c proposed
Structure Database searches and high-level ab initio molecular
orbital calculations.14d After examining the geometrical prefer-
ences of NO2
Hal synthons, they concluded that the
3 3 3
O angle tends to linearity as the Hal
CꢀHal
O distance
3 3 3
3 3 3
becomes shorter.14d This indicates that the monocoordinate halogen
bond (I) should be stronger than the asymmetric bifurcated halogen
bond (II) and the symmetric bifurcated halogen bond (III) is the
weakest one. The results obtained from the quantum chemical
calculations and the topological analysis of the electron density
further confirmed this conclusion.9b,14d
As the number of crystal structures determined has increased
hugely in recent years, we conducted a new statistical analysis of
the three different motifs also employing the Cambridge
by Desiraju et al., the robustness of the NO2 Hal synthons is
3 3 3
noted. Allen et al. classified the NO2 Hal synthons into three
3 3 3
different motifs [(I) the halogen bond in which the halogen atom
forms monocoordinate interaction with one nitro O atom, (II)
the asymmetric bifurcated halogen bond, and (III) the symmetric
bifurcated halogen bond (Scheme 1)] and analyzed in detail
the three different motifs using a combination of Cambridge
Received: May 11, 2011
Revised:
June 15, 2011
Published: July 05, 2011
r
2011 American Chemical Society
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Table 1. Number of Crystal Structures Containing Supra-
Structure Database (CSD version 5.22 + 29 updates).19,20
ConQuest,21 part of the CSD, was used to construct each
interaction search because it offers a user-friendly interface.
All searches required that the R-factor be less than 0.05 and
that there be no disorder or errors in the crystal structures, as
defined by ConQuest. For the sake of simplicity, we were
concerned about the number of crystal structures containing
supramolecular synthons IꢀIII. As shown in Table 1, the
percentage occurrence of the symmetric bifurcated halogen
bond in the crystal structures is very low and there is even no
molecular Synthons IꢀIII
synthon
NO2 Cl
NO2 Br
NO2
I
3 3 3
3 3 3
3 3 3
79
I
437
9
180
13
2
II
III
16
4
0
Scheme 2. Molecular Components Used in This Work
symmetric bifurcated NO2
Cl halogen bond to be found,
3 3 3
which is in agreement with experimental and theoretical
results mentioned above.
Applying the same search criteria, except for the symmetric
bifurcated halogen bonds shown in Table 1, we found only two
other types of symmetric bifurcated halogen bonds in the CSD
structures (Refcodes MEZGUT and PEXZEX). Thus, the
weaker symmetric bifurcated halogen bonds seem to play a
minor role in crystal growth and design. Naturally, a challenging
question is whether we can design much stronger symmetric
bifurcated halogen bonds for application in crystal engineering.
To answer this question, in this study, we first designed several
candidates according to the physical nature of the symmetric
Figure 1. Molecular electrostatic potential maps of nitromethane, DAFONE, PDONE, and TMBPM on their respective molecular planes. The black
lines represent the positive parts of the electrostatic potential, and the blue lines represent the negatives part of the electrostatic potential. The contour
interval is 0.005 au. The unit of the axes is angstrom. Numbers in red are the distances between the two local most negative electrostatic potentials.
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Crystal Growth & Design
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Figure 2. Structures and selected geometrical parameters of halogen-
bonded complexes Sym-ClNNO, Sym-BrNNO, Sym-INNO, Asym-
ClNNO, Asym-BrNNO, Asym-INNO, Sym-ClNNOO, Sym-BrNNOO,
Sym-INNOO, Sym-ClOONN, Sym-BrOONN, Sym-IOONN, Sym-
ClNNNN, Sym-BrNNNN, and Sym-INNNN.
Figure 3. Molecular graphs of the halogen-bonded Sym-INNO, Asym-
INNO, Sym-INNOO, Sym-IOONN, and Sym-INNNN complexes.
Small red dots represent the bond critical points.
’ EXPERIMENTAL SECTION
Table 2. CꢀHal Bond Lengths (r, angstroms) and Their
Changes upon Complexation (Δr, angstroms), Distances
between Hal and N(O) [d (d0), angstroms], Sums of the van
der Waals Radii [rw(Hal) + rw(N(O)), angstroms], Numbers
of Imaginary Frequencies (Nimg), and Binding Energies
(kilocalories per mole) for the 15 Studied Halogen-Bonded
Complexes
Quantum Mechanical Calculations. All the structures were
fully optimized with tight convergence criteria and characterized by
frequency computations and wave function stability checks at the B97D/
TZVP level of theory,22 except for the molecular complexes with iodine
atoms, for which the B97D calculations using the TZVPP basis set for I
and the TZVP basis set for the other atoms were performed. An
“ultrafine” integration grid (99 radial, 590 angular points) was used
for all the DFT calculations to prevent possible integration grid errors.
The binding energies of the halogen-bonded dimers were calculated
using the supermolecule method, and all of them are corrected for the
basis set superposition error using the counterpoise method of Boys and
Bernardi.23 The bonding characteristics of the different complexes were
analyzed by using the “atoms in molecules” (AIM) theory of Bader,24
which is based on a topological analysis of the electron charge density
and its Laplacian. The AIM theory has proved itself to be a valuable tool
for conceptually defining what an atom is and above all what a bond is in
a quantum calculation of a molecular structure. Electronic structure
calculations were conducted using the Gaussian 09 suite of electronic
structure programs.25 AIM analysis was performed with the AIM2000
software package.26 Here we will note that the value of the bond length
change is given as the difference in the bond length between the complex
and the monomer, so that a negative value of the bond length change
refers to a bond contraction and a positive value of the bond length
change indicates a bond elongation.
rw(Hal) +
complex
r
Δr
d (d0)
rw(N(O)) Nimg ΔECP
Sym-ClNNO
Sym-BrNNO
Sym-INNO
1.7334 ꢀ0.0046 3.41
3.32
3.47
3.61
3.32
3.47
3.61
3.32
3.47
3.61
3.29
3.44
3.58
3.32
3.47
3.61
1
1
1
0
0
0
1
1
0
1
1
0
1
1
0
2.78
4.64
6.75
2.85
4.89
7.38
3.60
5.89
8.35
1.88
3.18
4.68
4.74
7.44
9.96
1.9000
2.1135
0.0015 3.39
0.0104 3.43
Asym-ClNNO 1.7343 ꢀ0.0038 3.22 (3.68)
Asym-BrNNO 1.9050
Asym-INNO 2.1253
0.0065 3.04 (3.81)
0.0221 2.98 (3.78)
Sym-ClNNOO 1.7348 ꢀ0.0032 3.29
Sym-BrNNOO 1.9030
Sym-INNOO 2.1182
0.0045 3.24
0.0150 3.28
Sym-ClOONN 1.7334 ꢀ0.0046 3.37
Sym-BrOONN 1.8983 ꢀ0.0002 3.34
Sym-IOONN 2.1095
0.0064 3.37
Sym-ClNNNN 1.7352 ꢀ0.0028 3.30
Sym-BrNNNN 1.9044
Sym-INNNN 2.1200
0.0059 3.24
0.0169 3.28
Cocrystallization. The structural formulas of the molecular com-
ponents considered in this work are shown in Scheme 2. 1,4-Dichlorote-
trafluorobenzene (F4DClB), 1,4-dibromotetrafluorobenzene (F4DBrB),
1,4-diiodotetrafluorobenzene (F4DIB), 4,5-diazafluoren-9-one (DAFONE),
1,10-phenanthroline-5,6-dione (PDONE), and the solvents for crystal-
lization were purchased from Aldrich Chemical Co. and used as received.
4,40,6,60-Tetramethyl-2,20-bipyrimidine (TMBPM) was prepared by the
method reportedpreviously(see the SupportingInformation). The donor
and acceptor in a molarratioof1:1 were dissolvedin approximately 50 mL
bifurcated halogen bond and then predicted their stability on
the basis of the quantum chemical calculations and, finally,
synthesized and characterized successfully three new binary
cocrystals driven by the desired symmetric or asymmetric
bifurcated halogen bonds.
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Table 3. Crystallographic Data and Structure Refinement Parameters for INNO, INNOO, and INNNN
INNO
INNOO
INNNN
C9H7F2IN2
formula
C
17H6F4I2N2O
C9H3F2INO
306.02
formula weight
crystal size (mm3)
crystal system
space group
a (Å)
584.04
308.07
0.50 ꢁ 0.18 ꢁ 0.14
triclinic
0.50 ꢁ 0.19 ꢁ 0.16
monoclinic
P21/m
0.40 ꢁ 0.18 ꢁ 0.14
monoclinic
C2/m
P1
4.9382(7)
12.6849(18)
14.696(2)
108.0410(10)
92.996(2)
97.953(2)
862.5(2)
2
5.3613(13)
15.321(4)
11.904(3)
90
13.985(2)
15.550(3)
4.6026(7)
90
b (Å)
c (Å)
R (deg)
β (deg)
101.207(2)
90
101.769(2)
90
γ (deg)
volume (Å3)
959.1(4)
4
979.8(3)
4
Z
F
calc (g/cm3)
2.249
2.119
2.088
T (K)
296(2)
296(2)
296(2)
θ range for data collection (deg)
no. of reflections collected
no. of unique data [R(int)]
final R [I > 2σ(I)]
2.59ꢀ25.50
6402
2.66ꢀ25.50
7063
2.62ꢀ25.49
3661
3171 (0.0165)
0.0250
1865 (0.0262)
0.0267
951 (0.0158)
0.0183
final wR2 (all data)
goodness of fit
0.0626
0.0732
0.0460
1.035
1.008
1.049
of chloroform with gentle stirring at room temperature. The undissolved
materials were removed by filtration. The filtrate was set aside for
crystallization at 6ꢀ10 °C. After a few days, single crystals suitable for
X-ray analysis were obtained.
X-ray Diffraction. Crystallographic data were collected on a Bruker
Smart Apex-II CCD area detector equipped with graphite-monochro-
matic Mo KR radiation (λ = 0.71073 Å) at room temperature. An
empirical absorption correction was applied. All structures were deter-
mined and refined by a combination of direct methods and difference
Fourier syntheses, using SHELXTL.27,28 Anisotropic thermal para-
meters were assigned to all non-hydrogen atoms. The hydrogen atoms
were set in calculated positions and refined as riding atoms with a
common isotropic thermal parameter.
distance as the halogen atom acceptors. Figure 1 shows the mol-
ecular electrostatic potential maps of nitromethane, DAFONE,
PDONE, and TMBPM on their respective molecular planes. It
can be clearly seen from Figure 1 that, in molecules PDONE and
TMBPM, the distances between the two local most negative
electrostatic potentials are all shorter than 1.5 Å whereas the
distances are larger than 2.0 Å in nitromethane and DAFONE.
Evidently, PDONE and TMBPM should be better halogen
atom acceptors for the formation of the symmetrical bifurcated
halogen bond.
Further, we studied theoretically the geometry and stabiliza-
tion of the complexes formed by F4DClB, F4DBrB, and F4DIB
with DAFONE, PDONE, and TMBPM, respectively. During the
geometry optimizations, the asymmetrical bifurcated halogen-
bonded structures are all transformed into the symmetrical
bifurcated halogen-bonded structures for the complexes formed
by F4DClB, F4DBrB, and F4DIB with PDONE and TMBPM.
The symmetrical bifurcated halogen-bonded structures and the
asymmetrical bifurcated halogen-bonded structures coexist only
in the complexes formed by F4DClB, F4DBrB, and F4DIB with
DAFONE. These results are in accord with the prediction given
above, which suggests that PDONE and TMBPM are better
halogen atom acceptors for the formation of the symmetrical
bifurcated halogen bonds. Finally, we obtained only 15 dimer
structures. The structures of the 15 complexes can be seen in
Figure 2. Some selected geometrical parameters, the number of
imaginary frequency and binding energies of the 15 studied
halogen-bonded complexes, are listed in Table 2. For compar-
ison, the sums of the van der Waals radii29 of the Hal atom and
the Y atom are also listed in Table 2.
’ RESULTS AND DISCUSSION
Design of the Symmetrical Bifurcated Halogen Bond. A
large number of experimental as well as computational studies
indicate that the XꢀHal Y halogen bond is typically near-
3 3 3
linear (the XꢀHalꢀY angles are close to 180°). The direction-
ality of the halogen bond can be explained by its electrostatic
nature.7 Let us add here that, although the electrostatic effect is
proven to be the dominant factor, the polarization, charge
transfer, and dispersion contributions also play a significant role
in describing the geometry and stabilization of the halogen bond.
Evidently, the electrostatic nature of the halogen bond leads to
most of the bifurcated halogen bonds, especially the symmetrical
bifurcated halogen bonds, being weaker than the corresponding
monocoordinate halogen bonds. On the other hand, the electro-
static nature of the halogen bond also indicates that the symme-
trical bifurcated halogen bond will become stronger and stronger
if the distance between the two electron-rich atoms (YY
commonly) in the bifurcated halogen bond becomes shorter
and shorter. Hence, to design the symmetrical bifurcated halogen
bond, we must select the molecules containing the shorter YY
Table 2 shows that, upon formation of the complexes, all the
CꢀCl bonds are contracted whereas the CꢀBr and CꢀI bonds
are all elongated except the CꢀBr bond in the Sym-BrOONN
complex. This is consistent with our previous results for the
monocoordinate halogen bond.13d The rigorous AIM theory has
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Crystal Growth & Design
ARTICLE
method of judging the existence of the halogen bond with the
empirical van der Waals radii.
The last column in Table 2 gives the values of the BSSE-
corrected binding energies for the 15 complexes. We know that
the combined effect of polarizability and electronegativity is to
make the halogen potential more positive in the following order:
Cl < Br < I. Table 2 shows that, for a given halogen atom
acceptor, the binding energy increases in the following order:
F4DClB < F4DBrB < F4DIB. This reflects the fact that the
strength of the halogen bond correlates well with the magnitude
of the halogen positive potential. Again, the electrostatic nature
of the halogen bond makes F4DIB a better halogen atom donor
for the formation of the symmetrical bifurcated halogen bond. In
a recent paper, Riley and co-workers investigated the halogen
bonding interactions involving halobenzene, m-difluorohaloben-
zene, o-difluorohalobenzene, and pentafluorohalobenzene. The
results are very similar for both.
The numbers of imaginary frequencies in Table 2 further prove
that F4DIB, PDONE, and TMBPM are better candidates for the
formation of the symmetrical bifurcated halogen bond. We notice
because of Table 2 that the symmetrical bifurcated halogen-
bonded structures are all transition states (only one imaginary
frequency) on their respective potential energy surfaces except the
three formed by F4DIB with PDONE and TMBPM (all real
frequencies). Although the interactions in the crystal may be a little
different from those calculated here in the gas phase, at least it
indicates that the symmetrical bifurcated halogen-bonded struc-
tures studied here will be not stable in the crystal except the three
formed by F4DIB with PDONE and TMBPM.
In summary, we have designed two new supramolecular
synthons in this section. Further, we predicted that two binary
cocrystals should be easily synthesized: one cocrystal composed
of F4DIB and PDONE and the other composed of F4DIB
and TMBPM. Both of them are formed mainly via symmetrical
bifurcated halogen bonds.
Crystal Structures. To verify our theoretical predictions, we
selected F4DClB, F4DBrB, and F4DIB as halogen atom donors
and DAFONE, PDONE, and TMBPM as halogen atom accep-
tors to synthesize the adducts. It was found that F4DIB crystal-
lizes readily with DAFONE, PDONE, and TMBPM in a
chloroform solvent, yielding cocrystals INNO, INNOO, and
INNNN, respectively (see the Supporting Information). The
crystallographic data and structure refinement parameters are
listed in Table 3. However, many attempts to cocrystallize
F4DClB and F4DBrB with DAFONE, PDONE, and TMBPM
were all unsuccessful. These experimental results are consistent
with our theoretical predictions.
Figure 4. Packing diagrams for cocrystals INNO (a), INNOO (b), and
INNNN (c). The red dotted lines represent the halogen bonds.
been successfully applied in characterizing halogen bonds of
different strengths in a wide variety of molecular complexes.13a
Figure 3 shows the molecular graphs of the halogen-bonded com-
plexes Sym-INNO, Asym-INNO, Sym-INNOO, Sym-IOONN,
and Sym-INNNN. The molecular graphs for 10 other com-
plexes were omitted because they are very similar to the
corresponding ones shown in Figure 3. Figure 3 clearly demon-
strates the existence of a bond critical point (BCP) for each
noncovalent bond. The expected bond paths associated with
the noncovalent bond BCPs can also be visualized in Figure 3.
At the same time, it is also found that the values of the Laplacian
of the electron density at the noncovalent bond BCPs are all
positive. According to the “atoms in molecules” (AIM) theory
of Bader, the contacts between Hal and Y are all true halogen
bonds, which rationalizes the terms monocoordinate halogen
bond, asymmetric bifurcated halogen bond, and symmetric
bifurcated halogen bond. Table 2 lists both the calculated
distances between Hal and Y and the values of the sums of
the van der Waals radii of Hal and Y. We notice that in the
Asym-INNO complex the calculated distance between I and N2
(3.78 Å) is larger than the sum of the van der Waals radii of I and
N2 (3.61 Å). This means that the contact between I and N2 is
not a halogen bond, which is obviously different from the AIM
result. The case shown here is a warning about the conventional
F4DIB with DAFONE formed 1:1 cocrystal INNO in triclinic
space group P1. The propagation of the monocoordinate halogen
bond constructs a one-dimensional (1D) chain, as depicted in
Figure 4a. The 1D chains pack on each other via π π stacking
3 3 3
interactions between the two DAFONE molecules, generating a
two-dimensional (2D) layer structure. According to our theore-
tical calculation, the CP-corrected binding energy of the parallel-
displaced DAFONE dimer in the crystal structure of INNO is
∼4.16 kcal/mol, larger than that of the parallel-displaced benzene
dimer.30 The CꢀH I and F F interactions are also observed
3 3 3
3 3 3
in the crystal structure of INNO, and these interactions further
extend the 2D layer structures to 3D networks. As expected, there
is no symmetric bifurcated halogen bond in the crystal structure of
INNO. However, we noticed that the distance between I and N1 is
only 2.924 Å whereas the distance between I and N2 is increased to
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Crystal Growth & Design
ARTICLE
4.137 Å (Figure 4a). Evidently, in cocrystal INNO, the mono-
Foundation of Henan Province (Grant 082300420040) for
financial support. This project was also partly supported by the
Scientific Research Foundation for the Returned Overseas
Chinese Scholars, Ministry of Education of China (Grant
20091341), and the Natural Science Foundation of Henan
Educational Committee (Grant 2010A150017).
coordinate CꢀI N halogen bond is preferred over the asym-
3 3 3
metric bifurcated CꢀI NN halogen bond. This is slightly
3 3 3
different from our theoretical prediction that indicates that the
asymmetric bifurcated CꢀI NN halogen bond should be
3 3 3
formed. Inspection of the crystal structure of INNO reveals it
is the greater steric hindrance at the N2 atom that prevents the
formation of the other weaker CꢀI N2 halogen bond.
3 3 3
Crystallization of F4DIB with PDONE and TMBPM in a
chloroform solvent yielded cocrystals INNOO and INNNN,
respectively. Cocrystal INNOO has the symmetry of mono-
clinic space group P21/m, and cocrystal INNNN has the
symmetry of monoclinic space group C2/m. It can be clearly
seen in panels b and c of Figure 4 that the symmetric bifurcated
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INNNN is ∼7.70 kcal/mol. Finally, the 2D layer structures further
assemble into 3D networks via the CꢀH F interactions.
3 3 3
’ CONCLUSION
The CSD searches show that the number of crystal structures
that contain the symmetrical bifurcated halogen bond is very
small. To extend the application of the symmetrical bifurcated
halogen bond in crystal engineering, we successfully designed
and synthesized two cocrystals formed mainly by the symme-
trical bifurcated halogen bonds in this study. One cocrystal is
composed of F4DIB and PDONE and the other of F4DIB and
TMBPM. Both the experimental results and the theoretical
analyses showed that the symmetrical bifurcated halogen bond
may be stronger than the asymmetrical bifurcated halogen bond
and even the monocoordinate halogen bond. This means that the
symmetrical bifurcated halogen bond can also be an excellent
supramolecular synthon in crystal engineering. Symmetry is
beauty. We hope more applications of the symmetrical bifurcated
halogen bond will be revealed in the near future.
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’ ASSOCIATED CONTENT
S
Supporting Information. Cartesian coordinates of all the
b
halogen-bonded complexes in Table 1, synthesis of 4,40,6,60-
tetramethyl-2,20-bipyrimidine, and CIF files for INNO, INNOO,
and INNNN. This material is available free of charge via the
Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: lyhxxjbm@126.com.
’ ACKNOWLEDGMENT
We are grateful to the Natural Science Foundation of China
(Grants 20872057 and 21072089) and the Natural Science
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