Creation of ternary multicomponent crystals by exploitation of charge-transfer interactions

Article abstract of DOI:10.1002/chem.201203578

Four new ternary crystalline molecular complexes have been synthesised from a common 3,5-dinitrobenzoic acid (3,5-dnda) and 4,4′-bipyridine (bipy) pairing with a series of amino-substituted aromatic compounds (4-aminobenzoic acid (4-aba), 4-(N,N-dimethylamino)benzoic acid (4-dmaba), 4-aminosalicylic acid (4-asa) and sulfanilamide (saa)). The ternary crystals were created through the application of complementary charge transfer and hydrogen-bonding interactions. For these systems a dimer was created through a charge-transfer interaction between two of the components, while hydrogen bonding between the third molecule and this dimer completed the construction of the ternary co-crystal. All resulting structures display the same acid...pyridine interaction between 3,5-dnba and bipy. However, changing the third component causes the proton of this bond to shift from neutral OH...N to a salt form, O ^-...HN⁺, as the nature of the group hydrogen bonding to the carboxylic acid was changed. This highlights the role of the crystal environment on the level of proton transfer and the utility of ternary systems for the study of this process. Copyright

Full text of DOI:10.1002/chem.201203578

FULL PAPER
From co-crystal to salt: The creation of
four ternary co-crystals between ben-
zoic acids and bipyridine through the
combination of charge-transfer interac-
tions and hydrogen bonding is
reported (see figure). The altered crys-
tal environment due to structural
changes adjusts the level of proton
transfer between the components.
Thus, variation of a component can be
used to convert a given pair from a co-
crystal to a salt.
Crystal Engineering
C. C. Seaton,* N. Blagden, T. Munshi,
I. J. Scowen .................... &&&& — &&&&
Creation of Ternary Multicomponent
Crystals by Exploitation of Charge-
Transfer Interactions
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DOI: 10.1002/chem.201203578
Creation of Ternary Multicomponent Crystals by Exploitation of Charge-
Transfer Interactions
Colin C. Seaton,*[a] Nicholas Blagden,[b] Tasnim Munshi,[c] and Ian J. Scowen[c]
Abstract: Four new ternary crystalline
molecular complexes have been syn-
thesised from a common 3,5-dinitro-
benzoic acid (3,5-dnda) and 4,4’-bipyri-
dine (bipy) pairing with a series of
amino-substituted aromatic compounds
(4-aminobenzoic acid (4-aba), 4-(N,N-
For these systems a dimer was created
through a charge-transfer interaction
between two of the components, while
hydrogen bonding between the third
molecule and this dimer completed the
construction of the ternary co-crystal.
All resulting structures display the
same acid···pyridine interaction be-
tween 3,5-dnba and bipy. However,
changing the third component causes
the proton of this bond to shift from
neutral OH···N to
a
salt form,
OÀ···HN+, as the nature of the group
hydrogen bonding to the carboxylic
acid was changed. This highlights the
role of the crystal environment on the
level of proton transfer and the utility
of ternary systems for the study of this
process.
dimethylamino)benzoic
acid
(4-
dmaba), 4-aminosalicylic acid (4-asa)
and sulfanilamide (saa)). The ternary
crystals were created through the appli-
cation of complementary charge trans-
fer and hydrogen-bonding interactions.
Keywords: charge transfer · crystal
engineering · hydrogen bonds · mul-
ticomponent crystals · X-ray dif-
fraction
Introduction
Strategies for the creation of ternary co-crystals include
the partial replacement of one component in a known
binary co-crystal by a similarly sized and shaped molecule[2k]
or the introduction of a third component into voids within a
binary co-crystal.[2i] The most commonly used strategy uti-
lises a central linking molecule that can selectively hydrogen
bond to the remaining components. This approach was pio-
neered by Aakerçy et al., initially with isonicotinamide and
pairs of substituted benzoic acids.[2a–f] The ternary co-crystal
is formed with the strongest acid (3,5-dinitrobenzoic acid
(3,5-dnba)) selectively bonding to the best acceptor (pyri-
dine nitrogen) and the weaker acid bonding to the weaker
amide acceptor (Figure 1). Later work expanded on this
The creation of multicomponent crystalline materials has re-
cently been reinvigorated by the potential application of
such materials as novel dosage forms for active pharmaceut-
ical ingredients (APIs).[1] Although much activity has been
undertaken on the creation of binary co-crystals, the crea-
tion of systems with three or more molecules (ternary or
higher) is much less commonplace.[2] In the few examples
available, ternary co-crystals have generally been created
using a deliberate design strategy, but some have been
formed serendipitously. For example, the complex between
2,4,6-trinitrobenzoic acid, 4-aminobenzoic acid and 1,3,5-tri-
nitrobenzene[3] was isolated during the attempted co-crystal-
lisation of 4-aminobenzoic acid and 2,4,6-trinitrobenzoic
acid due to the decarboxylation of the trinitrobenzoic acid
in water.
[a] Dr. C. C. Seaton
Solid-State Pharmaceutical Cluster
Materials and Surface Science Institute
University of Limerick, Limerick (Ireland)
E-mail: colin.seaton@ul.ie
Figure 1. Bonding of components in the ternary complex between 3,5-di-
nitrobenzoic acid, 4-(dimethylamino)benzoic acid and isonicotinamide.
Atom colouring: carbon, black; oxygen, dark grey; nitrogen, light grey;
hydrogen, white.
[b] Prof. N. Blagden
Lincoln School of Pharmacy
University of Lincoln, Brayford Pool
Lincoln, Lincolnshire, LN6 7TS (UK)
through the development of novel linker molecules with dif-
fering N-heterocyclic groups. These were designed by con-
sideration of the calculated molecular electrostatic potential,
to selectively bind to different acid groups.[2h] Thus the selec-
tivity of the interactions can be controlled by choosing func-
tional groups to alter the strength of the hydrogen-bonding
functionalities. However this requires a strong understand-
[c] Dr. T. Munshi, Prof. I. J. Scowen
Division of Chemical and Forensic Science
University of Bradford, Richmond Road
Bradford, BD7 1DP (UK)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203578.
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Ternary Multicomponent Crystals
FULL PAPER
ing of the competition between potential hydrogen bonds.
One way to expand this approach is to utilise complementa-
ry types of intermolecular interaction to bind the differing
components together. Thus two components may be held to-
gether by hydrogen bonds and the third component can be
bonded to this dimer by an alternative type such as a
charge-transfer interaction. Charge-transfer interactions are
commonly encountered as donor–acceptor interactions
formed by the partial overlap of the HOMO and LUMO or-
bitals of the molecules. These orbitals must display similar
energy and symmetry and are frequently exhibited between
aromatic molecules with electron-donating groups (e.g.,
amine groups) and electron-withdrawing groups (e.g., nitro
groups). The binary co-crystal formed between 3,5-dnba and
4-(N,N-dimethylamino)benzoic acid (4-dmaba) displays such
a charge-transfer interaction (Figure 2a), which is retained
Figure 3. Hydrogen-bonding motifs between bipy and a) 3,5-dnba, b) 3-
aba (1:1), c) 3-aba (3:2) and d) 4-aba.
groups. Binary co-crystals have been reported between bipy
and 3,5-dnba (Figure 3a),[7] 3-aminobenzoic acid (3-aba, Fig-
ure 3b)[8] and 4-aminobenzoic acid (4-aba, Figure 3c),[8a,9]
with the 3-aba system existing in both 1:1 and 3:2 composi-
tions. As 3,5-dnba has the lowest pKa of the benzoic acids
considered, it would be expected to preferentially bind to
the bipy. If a complex with an equimolar composition is
formed, then the creation of a bilayered complex could be
envisioned (Figure 4).
Figure 2. Hydrogen-bonding motifs in 3,5-dinitrobenzoic acid/aminoben-
zoic acid co-crystals: a) 4-(dimethylamino)benzoic acid, b) 4-aminobenzo-
ic acid, c) 3-aminobenzoic acid, d) 3-aminobenzoic acid hydrate and e) 4-
(methylamino)benzoic acid hydrate.
on creation of a ternary co-crystal with isonicotinamide
(Figure 1) and salts of the co-crystal with lithium, sodium
and ammonia,[4] thereby highlighting the robustness of this
interaction. A number of binary co-crystals between 3,5-
dnba and other aminobenzoic acids display such charge-
transfer interactions (Figure 2)[5] and so these systems were
chosen as two of the components of the systems studied to
investigate the potential for ternary co-crystallisation
through a combination of hydrogen bonding and charge-
transfer interactions.
The carboxylic acid···pyridine hydrogen bond is a fre-
quently utilised supramolecular synthon in crystal engineer-
ing[6] and offers a robust hydrogen bond to the benzoic acids
selected previously. The symmetric 4,4’-bipyridine (bipy)
molecule was selected as the final component of the systems
studied, as this would offer two hydrogen-bond acceptors of
equal strength and so differences in selectivity towards the
acids would be driven by the differing strengths of two acid
Figure 4. Proposed interaction between species within the ternary co-
crystal shown for the 3,5-dnba/bipy/4-dmaba system.
The creation of ternary crystalline molecular complexes
was initially undertaken between 3,5-dnba and bipy with 2-
aminobenzoic acid (2-aba), 3-aba, 4-aba and 4-dmaba. To in-
vestigate the influence of the functional group on the ob-
served interactions, 4-aminosalicylic acid (4-asa) and sulfani-
lamide (saa) were also tested. The ternary crystals were
grown through solution crystallisation routes and the ob-
tained materials were identified by single-crystal X-ray dif-
fraction.
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C. C. Seaton et al.
Results and Discussion
display differing levels of hydrogen disorder in these bonds.
One appears to be a neutral pair with the hydrogen located
close to the 3,5-dnba molecules on either side of the bipy.
The other pair displays a more saltlike behaviour; the hy-
drogen is located either by the bipy nitrogen or located cen-
trally in the bond (Figure 7). The oxygen to nitrogen dis-
Complex 3,5-dnba/bipy/4-dmaba (I): The ternary complex I
has a 2:1:2 (3,5-dnba/bipy/4-dmaba) composition despite
being grown from a solution with an equimolar composition.
The 3,5-dnba and bipy molecules are bound together by a
CO2H···Npyridine hydrogen bond, while the charge-transfer in-
teraction holds the 4-dmaba and 3,5-dnba molecules togeth-
er (Figure 5). A second charge-transfer interaction occurs
Figure 5. Packing of the three components in complex I (atom colouring
as in Figure 1).
Figure 7. Asymmetric unit cell of complex II showing the differing hydro-
gen-bonding motifs of the 3,5-dnba molecules (atom colouring as in
Figure 1).
between the 4-dmaba and the bipy molecules between the
amino N and the pyridine N. The expected addition of a
second bipy molecule between the 4-dmaba dimers, howev-
er, does not occur. Instead the homo-molecular R22(8) hydro-
gen bond between the 4-dmaba molecules is maintained.
The same interaction occurs in both the single-component
phase and the binary complex with 3,5-dnba (Figure 1d).
The level of proton disorder depends on the crystal state
and has been investigated further by variable-temperature
X-ray and neutron diffraction studies.[10] The creation of ter-
nary co-crystals thus offers the possibility for future study
into the role of the crystal structure upon proton disorder if
the same hydrogen bond can be retained through a set of
ternary co-crystals with variations in the third component.
The three components form 2D sheets in the (203) plane
tance for all four pairs is the same, whereas the carbon to
oxygen bond lengths in the carbonyl fragments display the
variation expected by the formation of neutral and salt
structures (Table 1), however full confirmation would re-
quire neutron diffraction studies.
Table 1. Bonds lengths for the carbonyl fragments in II.
À
Fragment
C=O [ꢁ]
C OH [ꢁ]
O···N [ꢁ]
À
C7H
À
C7F
O
11HO12H
1.207
1.218
1.288
1.285
2.548
2.544
O
21FO22F
À
through weak C H···O=N interactions (Figure 6). The final
crystal is formed from the stacking of these sheets along the
b axis by the combination of charge-transfer and p···p inter-
actions.
The carbonyl oxygen of the neutral 3,5-dnba acts as a hy-
drogen-bond acceptor from the NH2 group of 4-aba, while
the carbonyl group of the deprotonated 3,5-dnba is an ac-
ceptor for the CO2H group of 4-aba. This difference in inter-
action distinguishes the two 3,5-dnba/bipy dimers. The re-
maining hydrogen of the 4-aba functional group acts as a hy-
drogen-bond donor to the CO2H group of a 4-aba molecule
to form a C(8) motif along the a axis. The interactions be-
tween the 3,5-dnba/bipy dimers and this 4-aba chain form a
ribbon structure. The final 3D structure is constructed
through p···p and charge-transfer interactions between these
ribbons.
Figure 6. Formation of the 2D sheet structure in complex I through the
combination of hydrogen-bonding interactions.
Complex 3,5-dbna/bipy/4-aba (II): Complex II has a 2:1:1
(3,5-dbna/bipy/4-aba) composition, again differing from the
solution composition. The asymmetric unit cell of the struc-
ture contains two independent ternary fragments each with
similar hydrogen bonding. The 3,5-dnba molecules again
bind to the bipy molecules through CO2H ··· Npyridine hydro-
gen bonding. However, the two symmetry-independent pairs
Complex 3,5-dnba/bipy/saa (III): The ternary complex III
has a 1:1:1 composition, in which 3,5-dnba binds to bipy
through a discrete CO2H···Npyridine hydrogen bond and the
sulfanilamide molecules form a homo-dimer by a R22(8)
NH2···O=S interaction. During the refinement of III a disor-
dered proton site between the acid of the 3,5-dinitrobenzoic
acid and the pyridine of bipy was indicated. The difference
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Ternary Multicomponent Crystals
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Figure 8. Fourier difference map for III showing the broad peak for the
proton located between O3 and N1. A colour version of this graphic is
available in the Supporting Information (Figure S1).
Figure 9. Infrared spectra for III (grey line) and 3,5-dnba (black line):
map between these sites was visualised in MapView within
the program WinGX (Figure 8).[11] This indicated that the
proton was bound to the nitrogen, although it is spread
across a wide minimum. The infrared spectrum of this com-
plex supports this interpretation, as it displays both a broad
peak in the NH/OH stretch region (3300–3200 cmÀ1, Fig-
ure 9a) and the shift in the C=O stretch to lower wavenum-
ber compared to free 3,5-dnba (1698 to 1673 cmÀ1, Fig-
ure 9b). These changes indicate the formation of a saltlike
interaction between the carboxylic acid and the bipyridine.
In this case the proton is transferred from the carboxylic
acid to the bipyridine molecule to form a mixed co-crystal/
salt. Once again the crystal-packing environment alters the
level of proton disorder within the 3,5-dnba/bipy dimer.
Two 3,5-dnba/bipy dimers bind to the sulfanilamide dimer
through a NH2···O=C hydrogen bond forming a six-molecule
cluster (Figure 10). These clusters form ribbon structures
À
a) N/O H stretch and b) C=O stretch regions.
Figure 10. Packing of the three components in complex III (atom colour-
ing as in Figure 1).
À
along the (110) axis through NH2···O N hydrogen bonds.
These ribbons then form stacks along the a axis through
À
NH2···O N hydrogen bonds. The final 3D structure is con-
structed by a stacking of the sheets along the c axis through
molecules bonding to both pyridine groups of the bipy mole-
cule. However, the nature of the bond at either component
À
À
weaker Caromatic H···Npyridine
,
Caromatic H···Onitro hydrogen
À
bonds (Figure 11). Unlike the benzoic acid systems in which
the amino and nitro groups lie parallel to each other, here
the groups are perpendicular to each other (Figure 10), how-
ever the crystals do exhibit a yellow colouration suggesting
some level of charge transfer.
differs. One end binds through a neutral O H···N hydrogen
bond, whereas at the other proton transfer has occurred re-
À
+
À
sulting in an O ···H N hydrogen bond. The difference in
binding mode is reflected in the bond lengths of the carbox-
ylic group (Table 2), while the secondary bonding environ-
ment of these groups is different as in II. Visualisation of
the difference map at the protonated pyridine confirms the
localisation of the proton on the nitrogen (Figure 12).
Complex 3,5-dnba/bipy/4-asa (IV): Ternary complex IV has
a 2:1:1 composition with the two 3,5-dinitrobenzoic acid
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C. C. Seaton et al.
Figure 13. The hydrogen bonding between the molecular components in
IV (atom colouring as in Figure 1).
Figure 11. View along the c axis showing the formation of the 3D struc-
ture of complex III.
À
atoms, while the deprotonated group forms an O H···O hy-
drogen bond from the carboxylic acid group of 4-asa
(Figure 13). These are the same interactions as in II, but in
this case they occur on either side of the same bipy mole-
cule, whereas in II they are bound to two different bipy mol-
ecules. The OH group on 4-asa forms an intramolecular hy-
drogen bond with the carboxylic acid group, while the re-
Table 2. Bonds lengths for the 3,5-dinitrobenzoic acid carbonyl fragments
in IV.
À
Fragment
C=O [ꢁ]
C OH [ꢁ]
À
C1A
À
C1B
O
O
10AO11A
10BO11B
1.225
1.249
1.306
1.271
À
maining amine proton forms a N H···O hydrogen bond with
the carbonyl group of an 4-asa molecule resulting in a C(8)
motif along the c axis, which then links the previously iden-
tified molecular clusters into the final 3D crystal structure.
Influence of growth conditions: The role of the growth con-
ditions on the final crystal phase was investigated by under-
taking a limited crystallisation screen by variation of the sol-
vent (acetone, ethanol, nitromethane, acetonitrile) for sys-
tems I and II. The previously obtained ternary complex was
obtained in most cases, either as the only product or a mix-
ture with one of the binary complexes. The only exception
was the 3,5-dnba/bipy/4-aba mixture from nitromethane that
resulted in the binary 3,5-dnba/bipy co-crystal (Table 3).
Table 3. Results of the solvent screening.
System
Solvent
Product
3,5-dnba/bipy/4-dmaba
3,5-dnba/bipy/4-dmaba
3,5-dnba/bipy/4-dmaba
3,5-dnba/bipy/4-dmaba
3,5-dnba/bipy/4-aba
3,5-dnba/bipy/4-aba
3,5-dnba/bipy/4-aba
3,5-dnba/bipy/4-aba
acetone
ethanol
nitromethane
acetonitrile
acetone
ethanol
nitromethane
acetonitrile
I
I
3,5-dnba/bipy
I
II
II+3,5-dnba/bipy
II
II
Figure 12. Fourier difference map of IV showing the greater localisation
of the proton on the bipy nitrogen compared to the 3,5-dnba carboxylate
oxygen ion. A colour version of this graphic is available in the Support-
ing Information (Figure S2).
This indicates that the choice of solvent and changes in the
solution speciation do not influence the level of proton
transfer in the final crystal product. However, as with binary
systems[12] the location of the region of thermodynamic sta-
bility of the multicomponent material varies with the solu-
bility of the components.
Both carboxylic acid groups are involved in hydrogen
bonds to 4-asa molecules: the neutral group forms a
À
N H···O hydrogen bond with one of the amino hydrogen
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Ternary Multicomponent Crystals
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Computational study: To support the experimental evidence
for a charge-transfer interaction between the components
and to identify whether the proton transfer observed within
the system is due to the local chemical environment dis-
played within the crystal structure, a series of computational
studies was carried out. The HOMO orbitals for 4-dmaba,
4-aba, saa and 4-asa and the LUMO orbitals for 3,5-dnba
and 3,5-dnba/bipy dimer (with the hydrogen bonded to both
oxygen and nitrogen) were calculated (Figure 14). Only the
Figure 15. Optimised geometries of a) 4-dmaba/3,5-dnba, b) 4-aba/3,5-
dnba, c) saa/3,5-dnba, d) 4-asa/3,5-dnba acid/acid CT dimers and e) the
3,5-dnba/bipy hydrogen-bond dimer. N-to-N distances are indicated for
the acid/acid dimers.
interactions, whereas for the 4-asa and saa systems this proc-
ess weakens the bonds. This may be a reason why the
stacked motif is not observed in the saa complex structure.
However, the geometry obtained from the optimisation
does display greater deviation from the experimental struc-
ture (Figure 16).
Figure 14. Calculated HOMO molecular orbitals for a) 4-dmaba, b) 4-
aba, c) saa, d) 4-asa; and LUMO molecular orbitals for e) 3,5-dnba,
f) 3,5-dnba/bipy co-crystal dimer and g) 3,5-dnba/bipy salt dimer.
A
colour version of this graphic is available in the Supporting Information
(Figure S3).
co-crystal form of the dimer displays a comparable symme-
try and energy to the HOMO molecules and so charge-
transfer interactions would only be expected in these cases.
This is reflected in the crystal structures in which charge-
transfer interactions are only observed in the co-crystal
cases. The energetics of the observed interactions were in-
vestigated by DFT ab initio calculations. Optimisation of the
charge-transfer acid pair confirms the stability of this inter-
action (Figure 15) and as expected this interaction is weaker
than the hydrogen-bonding dimer (Table 4). For the 4-
dmaba and 4-aba system trimer, formation strengthens both
Figure 16. Optimised geometries for trimers between bipy and a) 4-
dmaba/3,5-dnba, b) 4-aba/3,5-dnba, c) saa/3,5-dnba and d) 4-asa/35dnba.
N-to-N distances are indicated for the benzoic acid/acid dimers.
Table 4. Energetics of the dimer and trimer formation.[a]
System
DECT dimer [kJmolÀ1
]
DEH
dimer [kJmolÀ1
]
DECT trimer [kJmolÀ1
]
DEH
trimer [kJmolÀ1
bond
]
bond
3,5-dnba/bipy/4-dmaba
3,5-dnba/bipy/4-aba
3,5-dnba/bipy/4-asa
3,5-dnba/bipy/saa
À28.92
À25.24
À29.65
À28.77
À58.13
À58.13
À58.13
À58.13
À29.26
À27.50
À26.72
À22.64
À58.46
À60.39
À55.20
À52.00
[a] For dimer energies, DECT =ECT dimerÀ(Eacid1+Eacid2), DEH bond =EH-bond dimerÀ(Eacid1+Ebipy), whereas for trimer energies, DECT =EtrimerÀ(EH-bond
+
dimer
Eacid2), DEH bond =EtrimerÀ(ECT dimer +Ebipy).
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C. C. Seaton et al.
Modelling of the energy landscape for the proton transfer
between the 3,5-dnba/bipy molecules indicates that the local
chemical environment adjusts both the position and shape
of the minima in this case (Figure 17). For the isolated
from an amino group (4-asa, 4-aba). In contrast to when the
proton is transferred to bipy, the third component has
formed a hydrogen bond through donation of hydrogen
from a carboxylic acid (4-aba, 4-asa) or sulfonamide group
(saa). The change in interaction strength alters the donating
ability of the 3,5-dnba group. Computational studies confirm
the strength of both the charge-transfer and hydrogen-bond-
ing interactions in these cases for both the dimer and trimer
formation. Thus, the creation of such ternary co-crystals
offers a route to investigate proton transfer within a selected
hydrogen bond since it may be possible to construct the
same hydrogen-bond interaction (same chemical environ-
ment) in different crystal structures. However, given the cur-
rent inability to predict whether two molecules would suc-
cessfully form a binary co-crystal, the designed creation of
ternary co-crystals appears to still remain a significant chal-
lenge.
Experimental Section
Figure 17. Calculated energy landscape for the gas-phase proton transfer
between 3,5-dnba and bipy molecules: a) isolated dimer pair, b) trimer
with 4-aba bonding through the NH2 group and c) trimer with 4-aba
bonding through the CO2H group.
Preparation of single crystals
Complex I: 3,5-Dinitrobenzoic acid (0.206 g, 1.0 mmol), 4-(dimethylami-
no)benzoic acid (0.157 g, 1 mmol) and 4,4’-bipyridine (0.183 g, 1.1 mmol)
were dissolved in methanol (30 mL) with sufficient heating to ensure
complete dissolution. The resulting yellow solution was left to cool to
room temperature and red crystals of the complex were obtained.
À
dimer, a minima with an O H distance of 1.06 ꢁ was locat-
ed on a relatively narrow surface. The presence of a 4-aba
molecule bonding through the carboxylic acid group shifts
the minima to 1.12 ꢁ and significantly broadens the minima
out, which indicates a greater probability of proton move-
ment. In contrast, the presence of 4-aba bonding through
the amino hydrogen does not move the location of the hy-
drogen atom (1.07 ꢁ) but again broadens the energy sur-
face. Thus, even simple gas-phase calculations indicate that
in these systems the presence of a strong acid functional
group bonding onto the acid/pyridine dimer is enough to
adjust the bonding preferences. Further study is required to
see whether high-level solid-state calculations as applied to
other systems support these conclusions.[13]
Complex II: 3,5-Dinitrobenzoic acid (0.207 g, 1.0 mmol), 4-aminobenzoic
acid (0.158 g, 1.0 mmol) and 4,4’-bipyridine (0.138 g, 1.0 mmol) were dis-
solved in methanol (30 mL) with heating. Upon cooling of the yellow sol-
ution to room temperature, orange crystals of the complex were pro-
duced.
Complex III: 3,5-Dinitrobenzoic acid (0.594 g, 2.8 mmol), sulfanilamide
(0.426 g, 2.7 mmol) and 4,4’-bipyridine (0.510 g, 3 mmol) were dissolved
individually in methanol (3ꢃ10 mL). The methanolic solutions were then
mixed. Upon standing, a clear powder initially precipitated followed by
the formation of yellow block crystals of the ternary complex.
Complex IV: 3,5-Dinitrobenzoic acid (0.169 g, 0.8 mmol), 4-aminosalicyl-
ic acid (0.234 g, 1.0 mmol) and 4,4’-bipyridine (0.147 g, 1 mmol) were dis-
solved together in methanol (30 mL) with gentle heating. Upon cooling
to room temperature yellow crystals of the ternary complex were ob-
tained.
Complex V: 3,5-Dinitrobenzoic acid (0.239 g, 1.1 mmol), 2-aminobenzoic
acid (0.200 g, 1.2 mmol) and 4,4’-bipyridine (0.150 g, 1.1 mmol) were dis-
solved individually in methanol (3ꢃ10 mL). The methanolic solutions
were mixed and upon standing colourless block crystals were obtained.
Conclusion
Complex VI: 3,5-Dinitrobenzoic acid (0.168 g, 0.08 mmol), 3-aminoben-
zoic acid (0.278 g, 2 mmol) and 4,4’-bipyridine (0.232 g, 1 mmol) were dis-
solved individually in methanol (3ꢃ10 mL). The methanolic solutions
were mixed and upon standing colourless block crystals were obtained.
The successful creation and single-crystal structure determi-
nation of four ternary multicomponent crystals, which all
utilise a combination of charge-transfer interactions and hy-
drogen bonding, has demonstrated a targeted route to new
materials. Overall, the expected charge-transfer interactions
were maintained, whereas the hydrogen bonding exhibited
was complex dependent. In all of the co-crystals the stron-
gest hydrogen-bond donor (3,5-dnba) binds to the strongest
hydrogen-bond acceptor (bipy) as expected by Etterꢂs rules.
However, the nature of this hydrogen bond was found to
vary depending on the third component. In cases in which
the proton is located on the 3,5-dnba molecule, the third
component either does not hydrogen bond to the carboxylic
acid group of 3,5-dnba (4-dmaba) or donates a hydrogen
Characterisation: For both systems V and VI, initially colourless crystals
were formed and were identified as the 3,5-dinitrobenzoic acid/4,4’-bipyr-
idine binary complex by powder X-ray diffraction (PXRD). Upon stand-
ing, orange-yellow crystals were produced during which time the crystals
of the binary complex dissolved. Crystal structure analysis indicated that
the crystal features a channel structure built from the 3,5-dinitrobenzoic
acid/4,4-bipyridine complex with a disordered species within the channel.
Further study is currently underway to fully identify this material. Differ-
ential scanning calorimetry (DSC) and thermogravimetric analysis
(TGA) on all the samples indicated that they decomposed before melt-
ing.
Infrared spectra were collected on a ThermoNicolet Avatar 360 ESP
FTIR with Golden Gate ATR attachment using the Omnic software for
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Ternary Multicomponent Crystals
FULL PAPER
Table 5. Crystallographic details for single-crystal structure determinations.[18]
I
II
III
IV
formula
C10H10N2·2(C7H4N2O6)·2(C9H10NO2) C10H10N2·C10H8N2·2(C7H4N2O6)·2(C7H3N2O6)· C7H3N2O6·C10H9N2·C6H8N2O2S C7H4N2O6·C7H3N2O6·
2(C7H7NO2)
1435.13
monoclinic
P21/n
C10H9N2·C7H6NO3
733.56
monoclinic
P21/c
Mr
910.80
540.52
crystal system
space group
T [K]
a [ꢁ]
b [ꢁ]
c [ꢁ]
triclinic
triclinic
¯
¯
P1
P1
296
296
100
296
7.8741(2)
8.6773(3)
15.6094(5)
80.213(2)
81.932(2)
88.145(2)
1040.56(6)
1
13.9354(3)
24.3274(6)
18.7646(5)
90
92.218(1)
90
6356.7(3)
4
0.121
6.9161(3)
9.7440(4)
17.9311(6)
78.098(3)
87.768(3)
79.210(4)
1161.50(8)
2
19.0085(9)
12.0413(7)
13.7850(7)
90
90.755(2)
90
3154.9 (3)
4
0.13
a [8]
b [8]
g [8]
V [ꢁ3]
Z
m [mmÀ1
]
0.114
0.204
crystal size [mm]
reflns measured
independent reflns 4766
0.25ꢃ0.18ꢃ0.14
44095
0.62ꢃ0.20ꢃ0.15
189236
9834
0.45ꢃ0.35ꢃ0.30
7922
4098
0.34ꢃ0.31ꢃ0.24
88362
7516
reflns obsd
(I>2s(I))
Rint
2503
6697
3285
6140
0.0460
0.0465
0.1136
0.967
0.044
0.045
0.167
1.03
0.026
0.0376
0.1040
1.04
0.030
0.047
0.152
1.01
RACHTUNGTRENNUNG
(F2>2s(F2))
wR(F2)
S
no. reflns
no. params
no. restraints
largest diff. peak,
4766
306
0
0.155, À0.171
9834
977
0
0.25, À0.18
4098
423
0
0.50, À0.51
7516
494
4
0.52, À0.24
hole [eꢁÀ3
]
collection and processing. DSC and TGA data were collect using TA in-
struments Q2000 and Q5000, respectively.
dnba/bipy dimer and two 3,5-dnba/bipy/4-aba trimers were extracted
from the crystal structure and all the hydrogen atoms were optimised in
a DFT calculation at the PBE-D3/TZVP level. The energy surface for
the proton transfer from 3,5-dnba to bipy was then constructed by calcu-
lation of the energy of various structures as the proton was moved be-
tween the molecules. The energy calculations were carried out at the
PBE-D3/TZVPP level.[20]
Single-crystal structure determination: The crystallographic details for all
co-crystals are given in Table 5. The data for I, II and IV was collected
on a Bruker X8 Apex II diffractometer using graphite monochromated
MoKa radiation at 296 K. The data was collected and reduced using
Bruker SMART software.[14] The structures of I and II were solved and
refined using ShelxTL, whereas the structure of IV was solved and re-
fined in Olex2[15] using ShelxS97 and ShelxL97.[16] The data for III was
collected on an Oxford Diffraction Xcalibur using graphite monochro-
mated MoKa radiation at 100 K. The data was collected and reduced
using CrysAlisPro; the structures were solved using ShelxS97 and refined
in Crystals.[17]
Acknowledgements
Dr. Chris Muryn (University of Manchester) is thanked for his help with
the collection of the data for sample III. Computational portions of this
work were undertaken as part of the Solid State Pharmaceutical Cluster
supported by the Science Foundation Ireland (grant: 07/SRC/B1158).
Crystal growth conditions screening of
I and II: 3,5-dnba (0.212 g,
1.0 mmol), bipy (0.156 g, 1.0 mmol) and the relevant aminobenzoic acid
(4-dmaba (0.165 g, 1.0 mmol) or 4-aba (0.165 g, 0.7 mmol)) were dis-
solved with heating in the selected solvent (30 mL; acetone, ethanol, ni-
tromethane or acetonitrile). The solutions were left to slowly cool and
the final crystalline product was collected and identified through PXRD.
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Revised: May 15, 2013
Published online: && &&, 0000
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Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!