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Article
Expanding the pool of multicomponent crystal forms of the antibiotic
4-aminosalicylic acid: the influence of crystallization conditions
Vania Andre, Oleksii Shemchuk, Fabrizia Grepioni, Dario Braga, and M. Teresa Duarte
Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b01075 • Publication Date (Web): 25 Oct 2017
Downloaded from http://pubs.acs.org on October 27, 2017
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Crystal Growth & Design
Expanding the pool of multicomponent crystal forms of the antibiotic 4aminosalicylic acid: the influence of crystallization conditions
Vânia Andréa*, Oleksii Shemchukb, Fabrizia Grepionib*, Dario Bragab, M. Teresa
Duartea
a
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1,
1049-001 Lisbon, Portugal; bDipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via
Selmi 2, 40126 Bologna, Italy
* vaniandre@tecnico.ulisboa.pt, fabrizia.grepioni@unibo.it
ABSTRACT
Finding new multicomponent crystal forms of commercially available pharmaceuticals
is important, as they represent a straightforward way to drastically influence the solidstate properties of a drug. The antibiotic 4-aminosalicylic acid (ASA) is known to exist
in several multicomponent crystal forms, and in this work we expand the world of ASA
cocrystals
and
salts
by
reporting
new
crystalline
forms
comprising
diazabicyclo[2.2.2]octane (DABCO), and caffeine. All species were characterized by Xray single crystal, powder diffraction and thermal behaviour. This study contributes to
the rationalization of preferred functional groups for the synthesis of 4-aminosalicylic
acid new multicomponent crystal forms and highlights the relevance of the reaction
conditions in the achievement of those forms.
INTRODUCTION
The non-steroid anti-inflammatory drug (NSAID) 4-aminosalicylic acid (ASA)
has been used as an antibiotic in the treatment of tuberculosis since the 1940s.1 It has
also shown to be safe and effective in the treatment of inflammatory bowel diseases,
namely distal ulcerative colitis2, 3 and Crohn’s disease.4 Several prodrugs of this active
pharmaceutical ingredient (API) have been exploited to slow down its absorption in the
upper intestinal tract in order to make it suitable for the treatment of active ulcerative
proctitis or left sided ulcerative colitis.2, 5 Azo6 and phenol-class azo derivatives7 have
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been synthesized in the quest for a better ASA prodrug against inflammatory bowel
disease; additionally ASA conjugates of EDTA (ethylenediaminetetraacetic acid)
chelating to Cu(II) were reported not only as potential anti-inflammatory prodrugs but
also as promising drugs with anti-cancer properties, due to their proteolytic attack
resistance.4
Also worth mentioning are ASA:α-cyclodextrins complexes that have shown an
improvement in ASA solubility (up to 100 mM),8 and the novel ASA:konjac
glucomannan (KGM) pH-sensitivity complex synthesized based on the advantage of the
biodegradability of KGM,9,
10
a high-molecular weight polysaccharide known for
reducing the risk of developing diabetes and heart diseases.11
To the best of our knowledge only one crystal form of this API has been reported
(Figure 1),12,
13
whose crystal packing is characterized by an intramolecular synthon
between the hydroxyl and carboxyl groups, the carboxyl···carboxyl homosynthon and a
N-H···OOH interaction promoting a 3-dimensional network.
a
b
c
Figure 1 (a) 4-aminosalicylic acid (ASA), and its crystal packing showing (b) a
detailed view of the hydrogen-bonds and (c) a global arrangement in a view along a.
Several multicomponent crystal forms of ASA have been reported in recent years.
Chloride,13 sulfate and methanesulfonate14 salts have been synthesized. Cocrystals and
molecular salts with 3,5-dinitrobenzoic acid,15 4,4’-bipiridine,16,
pyridyl)ethane,17,
18
3-hydroxypiridine,
4-aminopiridine,17
17
1,2-bis(4-
nicotinamide,19
isonicotinohydrazide, isoniazid, pyrazine-2-carboxamide,20 cystosine, nicotinamide,14
sulfadimidine21 and with a codified compound reported as VX-95022 are described in
the literature. Also two private communications by Callear and co-workers with 2aminopyridine (one salt and one cocrystal) are available at Cambridge Structural
Database.23 We have further reported multicomponent crystal forms with morpholine,
dioxane and piperazine24 as well as three polymorphs of its ammonium salt.25 A ternary
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multicomponent crystal was prepared in 2013 by Seaton and co-workers, involving
ASA, 3,5-dinitrobenzoic acid and 4,4’-bipyridine.26 Very recently also drug-drug
cocrystals involving ASA have also been reported.27,
28
The most recurrent hydrogen
bonding interaction in these multicomponent crystal forms is between the OHCOOH/COOof ASA and the Npyridine groups of the coformers.
The work reported herein integrates our previous results24,25 and, along with all
the published data, intends to clearly show the great propensity of this API to form
multicomponent crystal forms with amines via O-H···N and/or N-H···O interactions.
Novel forms of this API were synthesized with diazabicyclo[2.2.2]octane (DABCO)
and caffeine. Valuable information can be drawn from this work on the type of
interactions favouring the formation of solvates/cocrystals/salts of this API and will
now be applied into the search of more GRAS co-formers, including possible
excipients, having in perspective a potential application in the pharmaceutical field.29-31
RESULTS AND DISCUSSION
Synthesis of the new multicomponent crystal forms was based on the
supramolecular synthon approach, on datamining and our previous experience with the
system. Multiple salts, cocrystals and ionic cocrystals were analysed in this search
(Table I).
Table I – List of multicomponent crystal forms of ASA
CSD code
ASALAC
BEYZAI
COLKUL
CUKVIO
CUKVOU
CUKVAG
CUKVEK
ICEBOK
ISIFUM
KEBGAB
KEBGAB01
KEBGAB02
MOYYOQ
MOYZUX
OBOVAF
OFUYIZ
PEXNOX
PEXNUD
PEXPAL
PEXPEP
Crystal form
Salt
Ionic cocrystal
Cocrystal
Salt
Salt
Salt
Cocrystal
Cocrystal solvate
Ionic cocrystal
Salt
Salt
Salt
Salt
Cocrystal
Cocrystal
Cocrystal
Salt
Salt
Salt
Cocrystal
Coformer/counterion
Chloride
4,4’-bipyridine; 3,5-dinitrobenzoic acid
3,5-dinitrobenzoic acid
Piperazine
Piperazine
Morpholine
Dioxane
Caffeine; methanol
4,4’-bipyridine
Ammonium
Ammonium
Ammonium
2-aminopyridine
2-aminopyridine
Isonicotinamide
Nicotinamide
1,2-bis(4-pyridyl)ethane
3-hydroxypiridine
4-aminopiridine
4,4’-bipyridine
Reference
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15
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19
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PEXNAJ
PEXPIT
URUDER01-10
URUGIY
YUJLOG01
VATXOF
VATXOF01
VATXOF02
VUGMOZ
XICRIM
XICROS
XICQOR
XICRAE
XICREI
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Cocrystal
Ionic cocrystal
Salt
Ionic cocrystal
Cocrystal
Salt
1,2-bis(4-pyridyl)ethane
4,4’-bipyridine
Isoniazid
Pyrazine-2-carboxamide
Theophylline
1,2-bis(4-pyridyl)ethane
1,2-bis(4-pyridyl)ethane
1,2-bis(4-pyridyl)ethane
Sulfadimidine
Cytosine
Cytosine
Sulfate
Nicotinamide
Methanesulfate
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Results show that the acid···pyridine synthon is the most recurrent synthon; for
this reason, we have further explored mainly N-containing heterocyclic coformers that
we expected to interact with ASA as shown in Scheme I. GRAS coformers containing
carboxylic acids were also tested.
Scheme I Predicted synthons containing neutral and charged groups,
characteristic of possible cocrystals (I) or molecular salts (II) of ASA with DABCO.
New forms of ASA were obtained with DABCO and caffeine (Scheme II). The
crystal structure of three different forms with DABCO and one with caffeine are
reported herein and, as observed in most of the crystal forms previously reported, they
confirm the ability of ASA to interact via O-H···N and/or N-H···O hydrogen bonds.
Scheme II ASA, DABCO, and caffeine
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In this work, we also underline the fact that different forms could be synthesized
by slightly modifying the crystallization conditions. This concept is extremely important
in the synthesis of the DABCO new forms, where the evaporation area of the
crystallization vessels proved to be crucial.
Three new forms [HDABCO]+2⋅[C6H3NH2OH(COO)]-2⋅DABCO⋅7H2O (1),
[HDABCO]+⋅[C6H3NH2OH(COO)]-⋅2H2O (2) and [HDABCO]+⋅[C6H3NH2OH(COO)]-
⋅DABCO⋅H2O (3), were obtained with ASA and DABCO upon distinct evaporating
conditions. Scheme III reports the chemical formulae of the compounds under
discussion. It is noteworthy that in compound 1 and 3 DABCO participates both as
counterion and neutral coformer, while 2 is a salt.33 The synthetic pathways to
selectively obtain ASA:DABCO multicomponent crystal forms are not straightforward
and are not easy to rationalize. While liquid-assisted grinding lead34, 35 to the formation
of 1, traditional crystallization by slow solvent evaporation results in mixtures of the
three forms (1-3). The prevalence of one form over the others obtained by solution
techniques is highly dependent on the evaporation area of the crystallization vessel, with
the crystalline form characterized by the lowest water content being favoured by wider
evaporation areas. Slurries also resulted in mixtures of the three forms. Even though the
different forms have different formulae, the ratio between [HDABCO]+ and
[C6H3NH2OH(COO)]- is the same, the difference arising from the presence of neutral
DABCO and by the hydration degree. All attempts to influence the composition by
changing the reagents ratio were unsuccessful, and mixtures were the recurrent result.
The structural and thermal characterization of these forms (1-3) will be presented and
discussed.
With caffeine, a new hydrate (4) was obtained by solution methods but it was not
possible to determine its crystal structure, and an anhydrous cocrystal (5) is obtained by
recrystallization of the hydrate in methanol, even though in very low yields for this
method. The crystal structure of the anhydrous form 5 was determined,
[C6H3NH2OH(COOH)].[C8H10N4O2], and its structural and thermal characterization are
also discussed herein.
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Scheme III Representation of 1, 2, 3 and 5.
Crystal structure analysis for 1, 2 and 3
The
asymmetric
2 ⋅DABCO ⋅7H 2 O
(1)
unit
of
consists
the
of
salt
two
[HDABCO]+2⋅[C6H3NH2OH(COO)]ASA,
three
DABCO
and
seven
crystallographically independent water molecules. Both ASA moieties are
deprotonated ([C6H3NH2OH(COO)] - [C-O distances are 1.251(4) and 1.267(5) Å;
1.236(5) and 1.294(4) Å in the two anions, respectively]), while of the three
DABCO molecules two are protonated, i.e. they are [HDABCO]+ cations, as
confirmed by the location of the hydrogen atom next to the nitrogen of cationic
nature, and the third is neutral.
The crystallographically independent [C6H3NH2OH(COO)]- anions still maintain
the intramolecular bond, now reinforced by charge assistance [O(H)···OCOO- 2.528(5)
and 2.480(6) Å]. One of the anions connects with three water molecules, while the
second anion links with a fourth water molecule [N(H)anion···OW 2.690(5) Å] and one of
the [HDABCO]+ cations [N(H)anion···N+cation 3.005(6) Å and N+(H)cation···O-COO2.690(5) Å] (see Figure 2.a). The neutral DABCO and one of the cations interact one
with the other [N+(H)cation···NDABCO 2.647(5) Å] and with water molecules, thus forming
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hydrogen bonded zig-zag chains (Figure 2.b). The interaction of these chains with the
motifs previously described is established via a water molecule, giving rise to an
extended hydrogen bonded network (Figure 2.c).
a
b
Figure 2 Crystal packing of 1 (a) hydrogen bonded zig-zag chains formed by
[HDABCO]+ cations (yellow and violet), neutral DABCO (red), ASA anions (blue and
light green) and water molecules (dark green and white); (b) overall packing in a view
along b.
This form was never obtained as a single phase in any of the experiments carried
out and most frequently appears concomitantly with 2 (Figure S1).
The asymmetric unit of [HDABCO]+⋅[C6H3NH2OH(COO)] -⋅2H2O, 2 consists of
two [C6H3NH2OH(COO)]- anions, two [HDABCO]+ cations and four water
molecules. The salt nature of this form was assessed by the C-O distances in the
[C6H3NH2OH(COO)] - anions (1.247(14) and 1.278(14); 1.252(10) and 1.292(9) Å)
and the proton location from the electron density map on the [HDABCO]+ cations.
Once again the intramolecular bonds in [C6H3NH2OH(COO)]- anions are
maintained [O-HOH···O-COO- 2.537(7) and 2.504(10) Å]. Wavy chains of alternating
anions and water molecules are shown in Figure 3.a. The second independent anion
interacts via hydrogen bonds with water molecules and one of the two independent
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cations [N+(H)cation···O-COO- 2.626(8) Å] (Figure 3.b). [HDABCO]+ cations are at close
distance [N+(H)cation···N+cation 2.754(9) Å] and one of them is hydrogen bonded to a
water molecule [O(H)W ···N+cation 2.805(9) Å], giving rise to [C6H3NH2OH(COO)]- –
water – [HDABCO]+ – [HDABCO]+ – [C6H3NH2OH(COO)]- chains (Figure 3.c).
a
b
c
Figure 3 Crystal packing of 2 in views along b: (a) showing the wavy chains formed by
one of the ASA anions (blue) and water (orange); (b) depicting the hydrogen bonding
between one of the ASA anions (green) with a water molecule (dark green) and their
contacts with both DABCO cations (yellow and red), giving rise to chains (c) showing
the overall packing, where the interaction between both type of chains is established by
water molecules (light blue and pink).
Form 2 was possible to obtain as a single phase (Figure S2) when crystallization
vessels with a medium evaporation area, such as beakers, were used.
The asymmetric unit of [HDABCO]+⋅[C6H3NH2OH(COO)]-⋅DABCO⋅H2O 3
consists of one ASA anion, one [HDABCO]+ cation, one neutral DABCO and one water
molecule. The anionic nature of ASA was determined by the C-O distances in the
carboxylate moiety (1.253(2) and 1.282(2) Å) and the cationic nature of one DABCO
was assessed by the proton location from the electron density map.
In
this
system,
as
observed
in
the
previously
described
structures,
-
[C6H3NH2OH(COO)] anions maintain the intramolecular interaction [O-HOH···O-COO2.459(2) Å]. The only intermolecular interactions in which [C6H3NH2OH(COO)]8
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anions are involved is established through the amine and carboxylate moieties [NHASA···O-COO- 2.932(3) Å]. These interactions along with three hydrogen bonds with the
water molecules [N-HASA···OW 2.935(2) Å, O-HW···O-COO- 2.795(3) Å and OHW···OOH 2.815(3) Å] give rise to sheets in the bc plane (Figure 4.a). DABCO
molecules form isolated dimers through N+-HDABCO···NDABCO hydrogen-bonds [N+HDABCO···NDABCO 2.721(3) Å] and pack in between the [C6H3NH2OH(COO)]- anionswater sheets (Figure 4.b).
a
b
Figure 4 Crystal packing of 3 in views (a) along a showing the sheets formed by ASA
and water in the bc plane; (b) along b showing the alternated layers of
[C6H3NH2OH(COO)]- - water sheets and DABCO dimers. (colour code: light blue –
[HDABCO]+ cation; dark blue – DABCO molecule; purple – [C6H3NH2OH(COO)]anion; green – water)
This form is obtained as the only bulk product (Figure S3) if crystallization
vessels with a large evaporation area are used.
Thermal behaviour of the crystalline forms 1-3
DSC, TGA and HSM studies were performed on crystalline forms 1-3 to assess
their thermal stability. The thermal analysis is not straightforward, like it would be
expected as these crystal forms are highly hydrated. In all the three forms water is
released before melting, but in none of them this process is carried out in a single step
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and therefore several thermal events with corresponding water loss are detected below
150°C. The melting point of the three forms is similar and occurs at approximately 163165°C.
For 1, which contains seven water molecules, several sequential events are
detected indicating that the water loss slowly starts at approximately 50°C and is more
intense above 119°C. The melting peak is detected at 165.2°C and is followed by
decomposition (Figure S4). This data is also supported by HSM observations (Figure 5).
Figure 5 HSM for 1, showing the melting and decomposition at 162°C.
The two water molecules per formula unit in crystalline 2 leave the structure
between 50 and 110°C, and the melting, followed by decomposition, is detected at
164.8°C (Figures 6 and S5).
Figure 6 HSM for 2, showing the water release between 50 and 110°C (images at 87
and 105 °C) and the melting and decomposition (image at 170°C).
Crystalline 3 contains only one water molecule per asymmetric unit, and this is
lost in the 60-120°C range. Melting is detected at 165.4°C and is once again followed
by decomposition (Figures 7 and S6).
Figure 7 HSM for 3 showing the water release between 60 and 120°C (images at 80
and 102°C) and the melting and decomposition (image at 166°C).
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Crystal structure analysis for 5
The preparation of new ASA-caffeine cocrystals was attempted by both solution and
grinding. By neat-grinding and LAG, only a mixture of both starting materials is
obtained. In solution, a new compound (4) is always formed, but no single crystals
suitable for X-ray diffraction could be grown. To ascertain that we were working with a
new form we further checked the diffraction data against all the reported polymorphs
and hydrates of caffeine (Figure S7). Several recrystallization attempts using different
solvents (acetone, ethanol, methanol, acetonitrile, water), as well as different
crystallization temperatures (RT and low temperature), were carried out. Single crystals
suitable for diffraction experiments could only be obtained from methanol, which
permitted
the
characterization
of
the
anhydrous
cocrystal
[C6H3NH2OH(COOH)]·[C8H10N4O2], 5.
The asymmetric unit of 5 consists on one ASA and one caffeine molecules, without any
proton transfer, and therefore this form corresponds to a cocrystal. Once again the
intramolecular interaction [O-HOH···OCOOH 2.605(7) Å] is maintained in ASA. Each
ASA moiety interacts with three different caffeine molecules via hydrogen bonds [OHCOOH···NCAF 2.702(8) Å, N-HASA···OC=O,CAF 2.927(8) and 2.975(8) Å], giving rise to a
3D crystal packing with alternated ASA and caffeine molecules (Figure 8.a), in which
similar molecules do not interact directly among them. In this crystal structure the
crystal packing is further reinforced by π··· π interactions (Figures 8.b and 8.c).
a
b
c
Figure 8 Crystal packing of 5, depicting (a) the ASA (blue) ˗ caffeine (green)
alternated arrangement, (b) π··· π distances, in Å, between aromatic rings centers of
ASA and caffeine molecules, and (c) π··· π interactions between ASA (blue) and
caffeine (green) molecules in a view along the a axis.
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Thermal behaviour of crystalline 4
DSC data for the compound initially obtained with ASA and caffeine, 4, (Figure
S8) reveals two endothermic peaks: the first one corresponding to a 7% mass loss in the
TGA, the second to melting followed by decomposition, overlapping with a small
exothermic peak. The mass loss between 50 and 70°C suggests that this form is likely to
be a solvate. As the same form is obtained with different solvents, this is most probably
a hydrate: the 7% mass loss would therefore correspond to the loss of 1.5 water
molecules per formula unit, i.e. crystalline 4 should be a sesquihydrated 1:1 cocrystal.
Figure S-9 shows VT-XRPD measurements on crystalline 4. A change in the diffraction
pattern is indeed detected in the diffractogram collected at 80°C, in agreement with the
results from DSC and TGA. The new pattern does not change, but for small shifts due
to temperature variations, when the sample is cooled down to room temperature.
Similarities can be found with the pattern calculated for crystalline 5 on the basis of
single crystal data (Figure S-9); unfortunately, in spite of numerous attempts at
recrystallizing the dehydrated product or at determining the structure from powder data,
we have not been able, so far, to characterize it.
CONCLUSIONS
The discovery of new solid forms of old drugs is an important research field not
only in modern solid-state and materials chemistry, but also in the pharmaceutical field.
These new forms include polymorphs, solvates, salts, and cocrystals, all of them with
distinct structural and physicochemical properties, which may be very useful to
overcome several issues (such as stability, solubility and bioavailability) of the drug
forms currently used.36-58
The tendency of ASA to form solvates and molecular salts had already been
proven and this is reinforced in this study. We have also demonstrated herein the
importance of reaction conditions to yield different forms with a single co-former.
Based on a Cambridge Structural Database23 survey, we have investigated the
possibility of forming new crystal forms between ASA and cyclic lone-pair containing
heterocycles such as DABCO. These coformers carry nitrogen atoms that can act as
proton acceptors or hydrogen bonding acceptors thus being able to be engaged in
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extended hydrogen bonded networks, suitable for the study of synthon competition and
cooperation established in this type of structures. Carboxylic acids are known for their
potential in the formation of hydrogen bonds and their predisposition to form dimeric
carboxyl···carboxyl homosynthons that generate self-complemented hydrogen-bonding
interactions in their crystal structures.59,
60
But in the presence of N-containing
heterocyclic moieties, the homosynthon is commonly disrupted by the robust OHCOOH···Npyridine heterosynthon that is preferentially shaped in the resultant
multicomponent crystal form (cocrystal, salt, molecular salt, solvate).61, 62
The ASA molecule is sufficiently acidic to transfer the carboxylic proton to
DABCO molecules,31 as expected based on the ∆pka rule and by analyzing studies of
similar structures with other salicylic acid derivatives and these co-formers.15, 63-66
The strong homomeric carboxylic acid synthon observed in ASA cannot occur in
the molecular salts studied herein due to the proton transfer from the API carboxylic
group to the amine moiety of the co-former. This disruption gives rise to charge-assisted
N+-Hcation···O-COO- supramolecular interactions, originating different ring and chain
synthons in the molecular salts studied.
On the other hand, in the anhydrous form of caffeine there is no proton transfer
and this form corresponds to a cocrystal. In this case, the strong homomeric carboxylic
acid synthon observed in ASA is also disrupted, but the charge-assisted interactions
previously mentioned are replaced by O-HCOOH···NCAF and N-HASA···OC=O,CAF
hydrogen bonds, with π··· π further reinforcing the crystal packing. The N-HASA···OOH
interaction is maintained in two of the crystal structures discussed herein.
Experimental
All reagents were purchased from Sigma and used without further purification.
SYNTHESIS OF MULTICOMPONENT CRYSTAL FORMS
Solution synthesis of [HDABCO]+2⋅[C6H3NH2OH(COO)] -2⋅DABCO⋅7H2O (1): A
solution was prepared in a flask with ASA (0.0339 g, 0.2214 mmol) and DABCO
(0.05059 g, 0.4502 mmol) and dissolved in 5 mL of ethanol. The solution was heated at
boiling temperature for 5 minutes and left to crystallize at room temperature. Crystals
were formed after 2 days.
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Solution synthesis of [HDABCO]+⋅[C6H3NH2OH(COO)]-⋅2H2O (2): A solution
was prepared in a beaker with ASA (0.0406 g, 0.2651 mmol) and DABCO (0.0302 g,
0.2692 mmol) and dissolved in 5 mL of ethanol. The solution was heated at boiling
temperature for 5 minutes and left to crystallize at room temperature, but covered with
parafilm. Crystals were formed after 2 days.
Solution synthesis of [HDABCO]+⋅[C6H3NH2OH(COO)]-⋅DABCO⋅H2O (3): A
solution was prepared in a crystallization vessel with a very wide evaporation area with
ASA (0.0340 g, 0.2220 mmol) and DABCO (0.0432 g, 0.3851 mmol) and dissolved in
4.3 mL of ethanol. The solution was heated at boiling temperature for 5 minutes and left
to crystallize at room temperature. Crystals were formed over night.
Synthesis of 1-3 by slurry: Two preparations were attempted. ASA and DABCO
in two different stoichiometric ratios (3:2 and 1:2) were suspended in ethanol and stirred
in a closed vessel for six days. In both cases the final bulk consists of a mixture of the
three forms previously obtained by solution technique but other forms different, in each
case, are additionally present. No crystals suitable for single crystal X-ray diffraction of
a new form were obtained from the recrystallization of these experiments.
Solution synthesis of the ASA·caffeine cocrystal (4): equimolar amounts of ASA
and caffeine were dissolved in water/ethanol solutions that were left to crystallize at
room temperature. Powder formed after 3 days and was identified by XRPD as a
powder pattern distinct from any form of the starting materials. Alternatively, similar
solution was left at 5°C for crystallization and a similar result was obtained. Both
acetone and acetonitrile, as well as just water, were tested as solvents and once again the
new powder pattern was obtained. The same result was obtained by joining two
different solutions: an ASA solution in ethanol and a caffeine solution in acetonitrile,
and leave them to crystallize at room temperature.
Despite the many recrystallization attempts carried out using different techniques,
single crystals suitable for SCXRD were never obtained.
Whenever higher percentage of ASA was used in the preparations, this reagent
was detected in the final XRPD analysis, along with form 4, showing that changes in the
starting ratio of the reagents do not affect the final form obtained.
Synthesis of the ASA·caffeine cocrystal (4) by mechanochemistry: equimolar
amounts of ASA and caffeine were manually ground in an agate mortar for 30 minutes.
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No conversion into new forms was detected by XRPD data. Reaction occurred by
adding a few drops of solvent (water, ethanol or acetone) before grinding the mixture.
Crystal growth of [C6H3NH2OH(COOH)]·[C8H10N4O2] (5) from solution:
equimolar quantities of ASA and caffeine were dissolved in methanol and were left to
crystallize at 5°C. After 5 days a couple of crystals suitable for single crystal X-ray
diffraction were formed. However, the majority of the obtained material was powder. Its
XRPD diffraction analysis showed that the majority of the obtained material
corresponded to the hydrated form 4.
CHARACTERIZATION
Single crystal X-ray diffraction (SCXRD)
Data collection was carried out in an Oxford X’Calibur S CCD diffractometer
equipped with a graphite monochromator (Mo-Kα radiation, λ = 0.71073Å) at room
temperature and in a Bruker AXS-KAPPA APEX II diffractometer with graphitemonochromated radiation (Mo-Kα radiation, λ = 0.71073 Å) at 150 K. Refinement
details are listed in the Table II. All non-hydrogen atoms were refined anisotropically.
HOH atoms were added in calculated positions. HNH atoms were located from difference
Fourier maps and refined. HCH and HOH atoms were added in calculated positions and
refined riding on their respective C and O atoms. SHELX-9767 was used for all structure
solutions and refinements on F2. Crystal data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44)1223-336-033; or email: deposit@ccdc.cam.ac.uk). CCDC numbers 1561330-1561333.
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Table II Crystallographic details for 1-3 and 5
1
2
3
Mr
2(C7H6NO3).2(C6H13N2).
C6H12N2.7(H2O)
768.91
C7H6NO3.C6H13N2
. 2(H2O)
301.34
C7H6NO3.C6H13N2.C6H12N2
C7H7NO3.C8H10N4O2
. H2O
395.5
347.33
T/K
150
150
150
293
Morphology, colour
Plate, brownish
Block, brownish
Plate, brownish
Prism, colourless
Crystal size / mm
0.10x0.08x0.03
0.08x0.05x0.05
0.17x0.16x0.10
0.12x0.11x0.09
Crystal system
Orthorhombic
Monoclinic
Monoclinic
Orthorhombic
Space group
Pca21
Cc
P21/n
P212121
a/Å
15.5430(15)
16.277(2)
11.3830(5)
7.5118(5)
b/Å
9.0140(8)
8.8488(11)
14.245(6)
7.8571(5)
c/Å
27.676(3)
21.007(2)
12.4480(5)
27.0495(19)
β/°
90
95.57(4)
91.908(2)
90
V / Å3
3877.5(6)
3011.4(6)
2017.3(9)
1596.49(18)
Z
4
8
4
4
d / mg.cm-3
1.317
1.329
1.302
1.445
µ / mm-1
0.102
0.102
0.093
0.111
θ min / °
1.47
2.68
2.17
3.5302
θ max / °
26.39
25.42
25.92
20.4550
25038/4052
5636/2681
22018/3925
6891/3673
Chemical formula
Reflections
collected/unique
Rint
5
0.0900
0.0439
0.0745
0.0373
GoF
1.019
1.024
1.015
1.053
Threshold expression
> 2σ(I)
> 2σ(I)
> 2σ(I)
> 2σ(I)
R1 (obsd)
wR2 (all)
0.0527
0.0611
0.0463
0.0871
0.1506
0.1873
0.1204
0.1885
X-Ray Powder diffraction (XRPD) and variable-temperature X-Ray Powder
diffraction (XRPD-VT)
X-ray powder diffraction data were collected with a Panalytical X’Pert Pro and in
a D8 Advance Bruker AXS θ-2θ diffractometer, with a copper radiation source (Cu Kα,
λ=1.5406 Å) and a secondary monochromator, operated at 40 kV and 40 mA
Hot-stage microscopy (HSM)
Hot Stage experiments were carried out using a Linkam TMS94 device connected
to a Linkam LTS350 platinum plate.
Differential Scanning Calorimetry (DSC)
Calorimetric measurements were performed using a Perkin-Elmer Diamond.
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Thermogravimetric Analysis (TGA)
TGA analysis was performed with a Perkin-Elmer TGA-7.
Acknowledgements: Authors acknowledge Fundação para a Ciência e a Tecnologia for funding
(PEst-OE/QUI/UI0100/2013, PTDC/CTM-BPC/122447/2010, RECI/QEQ-QIN/0189/2012 and
SFRH/BPD/78854/2011)
Supporting information: Supporting information is available containing information
on powder X-ray diffraction, TGA and DSC data.
REFERENCES:
(1)
Verreck, G.; Decorte, A.; Heymans, K.; Adriaensen, J.; Liu, D.; Tomasko, D.; Arien, A.;
Peeters, J.; Van den Mooter, G.; Brewster, M. E., Hot stage extrusion of p-amino salicylic acid
with EC using CO2 as a temporary plasticizer. Int. J. Pharm. 2006, 327, 45-50.
(2)
Odonnell, L. J. D.; Arvind, A. S.; Hoang, P.; Cameron, D.; Talbot, I. C.; Jewell, D. P.;
Lennardjones, J. E.; Farthing, M. J. G., Double-blind, controlled trial of 4-aminosalicylic acid and
presnisolone enemas in distal ulcerative-colitis. Gut 1992, 33, 947-949.
(3)
Schreiber, S.; Howaldt, S.; Raedler, A., Oral 4-aminosalicylic acid versus 5aminosalicylic acid slow-release tablets - double-blind, controlled pilot-study in the
maintenance treatment of Crohns ileocolitis. Gut 1994, 35, 1081-1085.
(4)
Bailey, M. A.; Ingram, M. J.; Naughton, D. P.; Rutt, K. J.; Dodd, H. T., Aminosalicylic acid
conjugates of EDTA as potential anti-inflammatory pro-drugs: synthesis, copper chelation and
superoxide dismutase-like activities. Transition Met. Chem. 2008, 33, 195-202.
(5)
Beeken, W.; Howard, D.; Bigelow, J.; Trainer, T.; Roy, M.; Thayer, W.; Wild, G.,
Controlled trial of 4-ASA in ulcerative colitis. Dig. Dis. Sci. 1997, 42, 354-358.
(6)
Zhao, Z. B.; Zheng, H. X.; Wei, Y. G.; Liu, J., Synthesis of azo derivatives of 4aminosalicylic acid. Chin. Chem. Lett. 2007, 18, 639-642.
(7)
Sheng, S. F.; Zheng, H. X.; Liu, J.; Zhao, Z. B., Synthesis of phenol-class azo derivatives of
4-aminosalicylic acid. Chin. Chem. Lett. 2008, 19, 419-422.
(8)
Lahiani-Skiba, M.; Youm, I.; Bounoure, F.; Skiba, M., Improvement in the water
solubility and stability of 4ASA by the use of cyclodextrins. J. Inclusion Phenom. Macrocyclic
Chem. 2011, 69, 327-331.
(9)
Xu, D. Y.; Li, G. J.; Liao, Z. F.; Chen, X. D., Synthesis and characterization of a novel pHsensitive complex for drug release. J. Wuhan Univ. Technol.-Mater. Sci. Ed. 2010, 25, 24-27.
(10)
Xu, D. Y.; Zhao, M. M.; Ren, J. Y.; Li, G. J.; Liao, Z. F., Investigation of interactions in 4aminosalicylic acid/polysaccharide in aqueous media. Food Res. Int. 2010, 43, 2077-2080.
(11)
Chen, H. L.; Cheng, H. C.; Liu, Y. J.; Liu, S. Y.; Wu, W. T., Konjac acts as a natural laxative
by increasing stool bulk and improving colonic ecology in healthy adults. Nutr. 2006, 22, 11121119.
(12)
Bertinotti, F.; Giacomello, G.; Liquori, A. M., Crystal and molecular structure of paraaminosalicylic acid. Acta Crystallogr. 1954, 7, 808-812.
(13)
Lin, C. T.; Siew, P. Y.; Byrn, S. R., Solid-state dehydrochlorination and decarboxylation
reactions. 1. Reactions of para-aminosalicylic acid hydrochoride and para-aminosalicylic acid,
and revised crystal structure of para-aminosalicylic acid. J. Chem. Soc.-Perkin Trans. 2 1978,
957-962.
(14)
Cherukuvada, S.; Bolla, G.; Sikligar, K.; Nangia, A., 4-Aminosalicylic Acid Adducts. Cryst.
Growth Des. 2013, 13, 1551-1557.
17
ACS Paragon Plus Environment
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
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18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Page 18 of 21
(15)
Smith, G.; Hartono, A. W.; Wermuth, U. D.; Healy, P. C.; White, J. M.; Rae, A. D., 5nitrosalicylic acid and its proton-transfer compounds with aliphatic Lewis bases. Aust. J. Chem.
2005, 58, 47-52.
(16)
Garcia, H. C.; Cunha, R. T.; Diniz, R.; de Oliveira, L. F. C., From molecular to coordination
complex: Two new supramolecular networks involving 4,4 '-bipy, aminosalicylic acid and Co(II)
ions. J. Mol. Struct. 2011, 991, 136-142.
(17)
Goswami, P. K.; Thaimattam, R.; Ramanan, A., Multiple Crystal Forms of pAminosalicylic Acid: Salts, Salt Co-Crystal Hydrate, Co-Crystals, and Co-Crystal Polymorphs.
Cryst. Growth Des. 2013, 13, 360-366.
(18)
Garcia, H. C.; Diniz, R.; de Oliveira, L. F. C., An interesting pseudo-honeycomb
supramolecular arrangement obtained from the interaction between 4-aminosalicylic acid,
trans-1,2-bis(4-pyridyl)ethylene and transition metal ions. Cryst. Eng. Comm. 2012, 14, 18121818.
(19)
Sarcevica, I.; Orola, L.; Belyakov, S.; Veidis, M. V., Spontaneous cocrystal hydrate
formation in the solid state: crystal structure aspects and kinetics. New J. Chem. 2013, 37,
2978-2982.
(20)
Grobelny, P.; Mukherjee, A.; Desiraju, G. R., Drug-drug co-crystals: Temperaturedependent proton mobility in the molecular complex of isoniazid with 4-aminosalicylic acid.
Cryst. Eng. Comm. 2011, 13, 4358-4364.
(21)
Caira, M. R., Molecular complexes of sulfonamides. 2. 1/1 Complexes between drug
molecules - sulfadimidine acetylsalicylic acid and sulfadimidine-4-aminosalicylic acid. J.
Crystallogr. Spectrosc. Res. 1992, 22, 193-200.
(22)
Connelly, P. R.; Morissette, S.; Tauber, M.; Morisette, S. Co-crystal, useful e.g. for
treating hepatitis C virus infection and molecular modeling to identify other possible co-crystal
forms, comprises vertex hepatitis C virus protease inhibitor, salicylic acid, aminosalicylic acid or
oxalic acid. WO2007098270-A2; US2007212683-A1; WO2007098270-A3; EP1991229-A2;
AU2007217355-A1; IN200803511-P2; CN101489557-A; JP2009529006-W, 2008.
(23)
Allen, F. H., The Cambridge Structural Database: a quarter of a million crystal
structures and rising. Acta Crystallogr. Sect. B: Struct. Sci. 2002, 58, 380-388.
(24)
Andre, V.; Braga, D.; Grepioni, F.; Duarte, M., Crystal Forms of the Antibiotic 4Aminosalicylic Acid: Solvates and Molecular Salts with Dioxane, Morpholine, and Piperazine.
Cryst. Growth Des. 2009, 9, 5108-5116.
(25)
Andre, V.; Duarte, M. T.; Braga, D.; Grepioni, F., Polymorphic Ammonium Salts of the
Antibiotic 4-Aminosalicylic Acid. Cryst. Growth Des. 2012, 12, 3082-3090.
(26)
Seaton, C. C.; Blagden, N.; Munshi, T.; Scowen, I. J., Creation of Ternary
Multicomponent Crystals by Exploitation of Charge-Transfer Interactions. Chem. - Eur. J. 2013,
19, 10663-10671.
(27)
Drozd, K. V.; Manin, A. N.; Churakov, A. V.; Perlovich, G. L., Drug-drug cocrystals of
antituberculous 4-aminosalicylic acid: Screening, crystal structures, thermochemical and
solubility studies. Eur. J. Pharm. Sci. 2017, 99, 228-239.
(28)
Drozd, K. V.; Manin, A. N.; Churakov, A. V.; Perlovich, G. L., Novel drug-drug cocrystals
of carbamazepine with para-aminosalicylic acid: screening, crystal structures and comparative
study of carbamazepine cocrystal formation thermodynamics. Cryst. Eng. Comm. 2017, 19,
4273-4286.
(29)
Braga, D.; Maini, L.; de Sanctis, G.; Rubini, K.; Grepioni, F.; Chierotti, M. R.; Gobetto, R.,
Mechanochemical preparation of hydrogen-bonded adducts between the diamine 1,4diazabicyclo [2.2.2] octane and dicarboxylic acids of variable chain length: An x-ray diffraction
and solid-state NMR study. Chem. - Eur. J. 2003, 9, 5538-5548.
(30)
Braga, D.; Grepioni, F., Making crystals from crystals: a green route to crystal
engineering and polymorphism. Chem. Comm. 2005, 3635-3645.
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(31)
Sarma, B.; Nath, N. K.; Bhogala, B. R.; Nangia, A., Synthon Competition and
Cooperation in Molecular Salts of Hydroxybenzoic Acids and Aminopyridines. Cryst. Growth
Des. 2009, 9, 1546-1557.
(32)
Andre, V.; Braga, D.; Grepioni, F.; Duarte, M. T., Crystal Forms of the Antibiotic 4Aminosalicylic Acid: Solvates and Molecular Salts with Dioxane, Morpholine, and Piperazine.
Cryst. Growth Des. 2009, 9, 5108-5116.
(33)
Braga, D.; Chelazzi, L.; Grepioni, F.; Dichiarante, E.; Chierotti, M. R.; Gobetto, R.,
Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a
Combined Structural and Spectroscopic Study. Cryst. Growth Des. 2013, 13, 2564-2572.
(34)
James, S. L.; Adams, C. J.; Bolm, C.; Braga, D.; Collier, P.; Friscic, T.; Grepioni, F.; Harris,
K. D. M.; Hyett, G.; Jones, W.; Krebs, A.; Mack, J.; Maini, L.; Orpen, A. G.; Parkin, I. P.;
Shearouse, W. C.; Steed, J. W.; Waddell, D. C., Mechanochemistry: opportunities for new and
cleaner synthesis. Chem. Soc. Rev. 2012, 41, 413-447.
(35)
Braga, D.; Maini, L.; Grepioni, F., Mechanochemical preparation of co-crystals. Chem.
Soc. Rev. 2013, 42, 7638-7648.
(36)
Aakeroy, C. B.; Fasulo, M. E.; Desper, J., Cocrystal or salt: Does it really matter? Mol.
Pharmaceutics 2007, 4, 317-322.
(37)
Childs, S. L.; Stahly, G. P.; Park, A., The salt-cocrystal continuum: The influence of
crystal structure on ionization state. Mol. Pharmaceutics 2007, 4, 323-338.
(38)
Takata, N.; Shiraki, K.; Takano, R.; Hayashi, Y.; Terada, K., Cocrystal screening of
stanolone and mestanolone using slurry crystallization. Cryst. Growth Des. 2008, 8, 3032-3037.
(39)
Reddy, L. S.; Bethune, S. J.; Kampf, J. W.; Rodriguez-Hornedo, N., Cocrystals and Salts of
Gabapentin: pH Dependent Cocrystal Stability and Solubility. Cryst. Growth Design 2009, 9,
378-385.
(40)
Anderson, K. M.; Probert, M. R.; Whiteley, C. N.; Rowland, A. M.; Goeta, A. E.; Steed, J.
W., Designing Co-Crystals of Pharmaceutically Relevant Compounds That Crystallize with Z ' >
1. Cryst. Growth Des. 2009, 9, 1082-1087.
(41)
Berry, D. J.; Seaton, C. C.; Clegg, W.; Harrington, R. W.; Coles, S. J.; Horton, P. N.;
Hursthouse, M. B.; Storey, R.; Jones, W.; Friscic, T.; Blagden, N., Applying hot-stage microscopy
to co-crystal screening: A study of nicotinamide with seven active pharmaceutical ingredients.
Cryst. Growth Des. 2008, 8, 1697-1712.
(42)
Sun, C. C.; Hou, H., Improving mechanical properties of caffeine and methyl gallate
crystals by cocrystallization. Cryst. Growth Des. 2008, 8, 1575-1579.
(43)
Sreekanth, B. R.; Vishweshwar, P.; Vyas, K., Supramolecular synthon polymorphism in
2:1 co-crystal of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine. Chem. Comm. 2007,
2375-2377.
(44)
Bond, A. D., What is a co-crystal? Cryst. Eng. Comm. 2007, 9, 833-834.
(45)
Rafilovich, M.; Bernstein, J.; Hickey, M. B.; Tauber, M., Benzidine: A co-crystallization
agent for proton acceptors. Cryst. Growth Des. 2007, 7, 1777-1782.
(46)
Zhang, G. G. Z.; Henry, R. F.; Borchardt, T. B.; Lou, X. C., Efficient co-crystal screening
using solution-mediated phase transformation. J. Pharm. Sci. 2007, 96, 990-995.
(47)
Zhou, D. L.; Zhang, G. G. Z.; Law, D.; Grant, D. J. W.; Schmitt, E. A., Physical stability of
amorphous pharmaceuticals: Importance of configurational thermodynamic quantities and
molecular mobility. J. Pharm. Sci. 2002, 91, 1863-1872.
(48)
Jayasankar, A.; Good, D. J.; Rodriguez-Hornedo, N., Mechanisms by which moisture
generates cocrystals. Mol. Pharmaceutics 2007, 4, 360-372.
(49)
Porter, W. W.; Elie, S. C.; Matzger, A. J., Polymorphism in carbamazepine cocrystals.
Cryst. Growth Des. 2008, 8, 14-16.
(50)
Kirchner, M. T.; Das, D.; Boese, R., Cocrystallization with acetylene: Molecular complex
with methanol. Cryst. Growth Des. 2008, 8, 763-765.
19
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Crystal Growth & Design
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51
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53
54
55
56
57
58
59
60
Page 20 of 21
(51)
Trask, A. V.; Motherwell, W. D. S.; Jones, W., Pharmaceutical cocrystallization:
Engineering a remedy for caffeine hydration. Cryst. Growth Des. 2005, 5, 1013-1021.
(52)
Trask, A. V.; Motherwell, W. D. S.; Jones, W., Physical stability enhancement of
theophylline via cocrystallization. Int. J. Pharmaceutics 2006, 320, 114-123.
(53)
Chen, A. M.; Ellison, M. E.; Peresypkin, A.; Wenslow, R. M.; Variankaval, N.; Savarin, C.
G.; Natishan, T. K.; Mathre, D. J.; Dormer, P. G.; Euler, D. H.; Ball, R. G.; Ye, Z. X.; Wang, Y. L.;
Santos, I., Development of a pharmaceutical cocrystal of a monophosphate salt with
phosphoric acid. Chem. Comm. 2007, 419-421.
(54)
Bucar, D. K.; Henry, R. F.; Lou, X. C.; Borchardt, T. B.; Zhang, G. G. Z., A "hidden" cocrystal of caffeine and adipic acid. Chem. Comm. 2007, 525-527.
(55)
Bourne, S. A.; Caira, M. R.; Nassimbeni, L. R.; Shabalala, I., X-ray structural studies and
physicochemical characterization of the 1-butanol, 1-pentanol, and 1,4-dioxane solvates of
succinylsulfathiazole. J. Pharm. Sci. 1994, 83, 887-892.
(56)
Vrcelj, R. M.; Clark, N. I. B.; Kennedy, A. R.; Sheen, D. B.; Shepherd, E. E. A.; Sherwood,
J. N., Two new paracetamol/dioxane solvates - A system exhibiting a reversible solid-state
phase transformation. J. Pharm. Sci. 2003, 92, 2069-2073.
(57)
Hosokawa, T.; Datta, S.; Sheth, A. R.; Brooks, N. R.; Young, V. G.; Grant, D. J. W.,
Isostructurality among five solvates of phenylbutazone. Cryst. Growth Des. 2004, 4, 1195-1201.
(58)
Oswald, I. D. H.; Allan, D. R.; McGregor, P. A.; Motherwell, W. D. S.; Parsons, S.;
Pulham, C. R., The formation of paracetamol (acetaminophen) adducts with hydrogen-bond
acceptors. Acta Crystallogr. Sect. B: Struct. Sci. 2002, 58, 1057-1066.
(59)
Cheney, M. L.; Weyna, D. R.; Shan, N.; Hanna, M.; Wojtas, L.; Zaworotko, M. J.,
Supramolecular Architectures of Meloxicam Carboxylic Acid Cocrystals, a Crystal Engineering
Case Study. Cryst. Growth Des. 2010, 10, 4401-4413.
(60)
Kavuru, P.; Aboarayes, D.; Arora, K. K.; Clarke, H. D.; Kennedy, A.; Marshall, L.; Ong, T.
T.; Perman, J.; Pujari, T.; Wojtas, L.; Zaworotko, M. J., Hierarchy of Supramolecular Synthons:
Persistent Hydrogen Bonds Between Carboxylates and Weakly Acidic Hydroxyl Moieties in
Cocrystals of Zwitterions. Cryst. Growth Des. 2010, 10, 3568-3584.
(61)
Du, M.; Jiang, X. J.; Tan, X.; Zhang, Z. H.; Cai, H., Co-crystallization of a versatile building
block 4-amino-3,5-bis (4-pyridyl)-1,2,4-triazole with R-isophthalic acids (R = -H, -NH2, -SO3H,
and -COOH): polymorphism and substituent effect on structural diversity. Cryst. Eng. Comm.
2009, 11, 454-462.
(62)
Skovsgaard, S.; Bond, A. D., Co-crystallisation of benzoic acid derivatives with Ncontaining bases in solution and by mechanical grinding: stoichiometric variants,
polymorphism and twinning. Cryst. Eng. Comm. 2009, 11, 444-453.
(63)
Kumar, V. S. S.; Kuduva, S. S.; Desiraju, G. R., Pseudopolymorphs of 3,5-dinitrosalicylic
acid. Journal of the Chem. Soc. - Perkin Trans. 2 1999, 1069-1073.
(64)
Kumar, V. S. S.; Nangia, A.; Kirchner, M. T.; Boese, R., Supramolecular synthesis of brick
wall and honeycomb networks from the T-shaped molecule 5-nitrosalicylic acid. New J. Chem.
2003, 27, 224-226.
(65)
Li, Z. H.; Su, K. M., Piperazine-1,4-diium bis(3-carboxy-4-hydroxybenzenesulfonate)
dihydrate. Acta Crystallogr. Sect. E: Struct. Rep. Online 2007, 63, O4744-U5385.
(66)
Wang, K. W.; Pan, Y. J.; Jin, Z. M., Crystal structure of piperazine-1,4-diium
bis(salicylate), (C4H12N2)(C7H5O3)(2). Zeitschrift Fur Kristallographie - New Cryst. Struct.
2002, 217, 435-436.
(67)
Sheldrick, G. M., A short history of SHELX. Acta Crystallogr. Sect. A 2008, 64, 112-122.
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Crystal Growth & Design
For Table of Contents Use Only
Expanding the pool of multicomponent crystal forms of the antibiotic 4aminosalicylic acid: the influence of crystallization conditions
Vânia Andréa*, Oleksii Shemchukb, Fabrizia Grepionib*, Dario Bragab, M. Teresa
Duartea
a
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1,
1049-001 Lisbon, Portugal; bDipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via
Selmi 2, 40126 Bologna, Italy
* vaniandre@tecnico.ulisboa.pt, fabrizia.grepioni@unibo.it
TOC
The discovery of new solid forms of old drugs is an important research field in the
pharmaceutical arena. The tendency of 4-aminosalicylic acid to form multicomponent
crystal forms had already been proven and this is reinforced in this study. We have also
demonstrated herein the importance of reaction conditions to yield different forms with
a single co-former.
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