The influence of benzoate anion substituents on the crystal packing and hydrogen-bonding network of 9-aminoacridinium salts

Article abstract of DOI:10.1016/j.tet.2011.02.083

As a continuation of our recent work, we discuss the crystal structures of a series of salts with the 9-aminoacridinium cation and 3-chlorobenzoate, 4-chlorobenzoate and 3-hydroxybenzoate anions. The crystal structure of [2(C₁₃H₁₁N

Full text of DOI:10.1016/j.tet.2011.02.083

Tetrahedron 67 (2011) 2839e2843
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Tetrahedron
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The influence of benzoate anion substituents on the crystal packing and
hydrogen-bonding network of 9-aminoacridinium salts
*
ꢀ
Artur Sikorski , Damian Trzybinski
ꢀ
ꢀ
Faculty of Chemistry, University of Gdansk, J. Sobieskiego 18, 80-952 Gdansk, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
As a continuation of our recent work, we discuss the crystal structures of a series of salts with the
9-aminoacridinium cation and 3-chlorobenzoate, 4-chlorobenzoate and 3-hydroxybenzoate anions. The
crystal structure of [2(C13H11Nþ2 )$C7H5O3ꢀ$Clꢀ$2(H2O)] is the first of all the known 9-aminoacridinium
salts where mixed salts were obtained. Analysis of the hydrogen bonds in the crystal lattices of the title
compounds shows that the ions are linked via N(amino)eH/O(carboxy) hydrogen bonds forming R22(8)
or R42(16) hydrogen bond ring motifs. In the packing, there are also two kinds of hydrogen bond chain
motif. The first, C24(16), in which 9-AA cations, a Clꢀ anion and a water molecule are interlinked, and the
second, C(7), in which aromatic carboxylic acid anions are connected directly. We also observed the
influence of the different anions on the packing of the acridine skeletons in the crystal lattice.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 11 December 2010
Received in revised form 10 February 2011
Accepted 28 February 2011
Available online 5 March 2011
Keywords:
Crystal structure
Mixed salts
9-Aminoacridine
Hydrogen bonds
pep stacking
Crystal engineering
1. Introduction
9-AA cation and 3-chlorobenzoate anions in the asymmetric unit
(Fig. 1S, Table 1S, Supplementary data). In the packing of the mol-
Having interesting antibacterial, antiprion, antitumor, and anti-
inflammatory properties,1 9-aminoacridine (9-AA) derivatives are
a group of amine bases capable of interacting with organic acids.
The synthesis of these compounds and the analysis of the in-
teractions between them are very useful in view of their impor-
tance in a wide range of different biological systems.2
In our investigations of new structural aspects of 9-amino-
acridinium derivatives and as a continuation of our recent work,3 we
had intended to obtain its 3-chlorobenzoate (1), 4-chlorobenzoate (2),
and 3-hydroxybenzoate (3) salts. To our surprise, however, compound
3 crystallized in the form of mixed salts: 2(C13H11Nþ2 )$C7H5O3ꢀ$Clꢀ$2
(H2O), representaninterestingobjectofresearchinthecontextofdrug
therapy4 and crystal engineering.5 In this paper we report on the
synthesis and X-ray characterization of these compounds.
ecules in 1, the crystal structure is stabilized via NeH/O and
CeH/O hydrogen bonds and stacking interactions (Tables 2S
pep
and 3S, Supplementary data). Analysis of the hydrogen bonds in the
structure of 1 has shown that the inversely oriented cations and
anions form a tetramer; these ions are linked via N(amino)eH/O
(carboxy) hydrogen bonds in the crystal lattice and form an R22(8)
hydrogen bond ring motif (Fig. 1a).6
In this motif amino groups from the cations and one O atom
from the carboxy group in the anions participate in the hydrogen
bonds. Additionally, the O(carboxy) atoms engaged in the forma-
tion of this motif also take part in weak C(acridine)eH/O(carboxy)
hydrogen bonds that stabilize the tetramers. The tetramers in 1 are
linked through an N(acridine)eH/O(carboxy) hydrogen bond,
where the O atom is not involved in the formation of the R22(8)
hydrogen bond ring motif (Fig. 1a). Analysis of the
pep interactions
in 1 shows that the adjacent acridine skeletons are linked via
p
-
2. Results and discussion
stacking interactions in the AB arrangement to form a two-fold
helical arrangement (Fig. 1b), in which the overlapping mode of
neighboring cations shows that the adjacent acridine skeletons are
rotated in-plane with respect to one another by approximately
135ꢁ. All the aromatic rings from the acridine skeletons participate
2.1. 9-Aminoacridinium 3-chlorobenzoate (1)
Single-crystal X-ray diffraction measurements show that com-
pound 1 crystallizes in the monoclinic P21/c space group with the
in pep interactions, forming a zigzag motif with centroid/centroid
ꢁ
ꢁ
distances from 3.552 to 4.069 A and a distance of 3.380 A between
the mean planes of the neighboring acridine skeleton. Analysis of
* Corresponding author. Tel.: þ48 58 523 5425; fax: þ48 58 523 54 72; e-mail
the pep interactions between the aromatic rings in the acid anions
address: art@chem.univ.gda.pl (A. Sikorski).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.083

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A. Sikorski, D. Trzybinski / Tetrahedron 67 (2011) 2839e2843
2840
ꢁ
in 1 shows that the shortest centroid/centroid distance is 5.475 A,
which indicates that -stacking interactions are absent. In the su-
p
pramolecular architecture of 1, there are columns forming separate
layers (Fig. 1c).
2.2. 9-Aminoacridinium 3-chlorobenzoate (2)
Compound 2 forms triclinic crystals (P-1 space group) with the
9-AA cation, 4-chlorobenzoate anion and water molecule in the
asymmetric unit (Fig. 2S, Table 1S, Supplementary data). The crystal
structure of 2 is stabilized by NeH/O and OeH/O hydrogen
bonds and
pep interactions (Tables 4S and 5S, Supplementary
data). Analysis of the hydrogen bonds in the structure of 2 shows
that the ions form tetramers and produce an R42(16) hydrogen bond
ring motif (Fig. 2a). In this motif, the cations and anions are linked
via N(amino)eH/O(carboxy) hydrogen bonds in the crystal lattice;
in contrast to 1, however, both O atoms from the carboxy group are
involved in the formation of the hydrogen bond ring motif. In the
crystal lattice of 2, the tetramers are linked through an N
(acridine)eH/O(water) and O(water)eH/O(carboxy) hydrogen
bond (Fig. 2a). Incidentally, it is interesting to note that the tetra-
mers are not stabilized through C(acridine)eH/O(carboxy) hy-
drogen bonds, as was observed in other structures from this group
of compounds (e.g., compound 1). Analysis of the
in 2 shows that the ‘head-to-tail’ oriented neighboring acridine
skeletons in 2 interact through -stacking interactions in an ABA
arrangement forming columns (Fig. 2b). In this arrangement, the
interactions with centroid/centroid distances from 3.417 to
pep interactions
p
pep
ꢁ
ꢁ
3.824 A and a distance of 3.346 A between the mean planes of the
neighboring acridine skeleton form a zigzag motif, as in 1. In the
overlapping mode of the neighboring acridine skeletons, adjacent
cations are alternately shifted along the longest axis of the acridine
ꢁ
skeletons for a distance of w1.2 A. Analysis of
pep interactions
between the aromatic rings in the acid anions in 2 shows that the
ꢁ
shortest centroid/centroid distance is 3.820 A (Fig. 2c). This in-
dicates that
p-stacking interactions between the benzene rings
from the acid anions are observed. In the supramolecular archi-
tecture of 2, there are chains of R42(16) hydrogen bond ring motifs
forming columns in a staircase motif. These columns are interlinked
via
pep interactions between the aromatic rings in the anions
(Fig. 2c).
2.3. 9-Aminoacridinium 3-hydroxybenzoate (3)
Compound 3 crystallizes in the triclinic P-1 space group. The
asymmetric unit of 3 consists of two 9-AA cations, 3-hydrox-
ybenzoate and chlorate anions as well as two water molecules
(Fig. 3S, Table 1S, Supplementary data). This structure is the first of
all the known 9-aminoacridinium salts where mixed salts were
obtained.7 It is worth attention that the average deviations from
ꢁ
planarity of the acridine skeleton are 0.015(2) and 0.027(2) A, and
the angle between the mean planes of the right- and left-hand
halves of the acridine skeleton is equal to 1.5 and 3.7ꢁ in cations A
and B, respectively. This shows above all that the presence of an
aromatic carboxylic acid anion clearly influences the planarity of
the acridine skeleton, which adopts the butterfly conformation,8
especially in the case of cation B.
The crystal structure of 3 is stabilized by NeH/O, NeH/Cl,
OeH/O, OeH/Cl, CeH/O, and CeH/Cl hydrogen bonds as well
as pep stacking (Tables 6S and 7S, Supplementary data). Analysis of
thehydrogenbonds in 3 showsthat theions do notform tetramers in
the crystal lattices, but produce two nearly perpendicularly aligned
kinds of hydrogen bond chain motif. In the first, a C24(16) hydrogen
bond chain motif, both A and B 9-aminoacridinium cations are
linked via N(acridine)eH/Cl/HeN(amino) hydrogen bonds bi-
furcated on the chloride cation and N(acridine)eH/O/HeN
Fig. 1. Network of the intermolecular interactions in 1: R22(8) hydrogen bond ring motif
(a),
pep interactions (b) and crystal packing (c).

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A. Sikorski, D. Trzybinski / Tetrahedron 67 (2011) 2839e2843
2841
packing, these chains are linked by N(amino)eH/O(carboxy), N
(amino)eH/O(water), O(water)eH/O(carboxy), O(water)eH/O
(hydroxy), O(water)eH/Cl, and C(benzene)eH/Cl hydrogen
bonds, as shown in Fig 3c. In the crystal lattice of 3, the neighboring
Fig. 2. Network of the intermolecular interactions in 2: R42(16) hydrogen bond ring
motif (a), interactions (b) and the crystal packing (c).
pep
(amino) hydrogen bonds bifurcated on the O atom of the water
molecule (Fig. 3a). In the second, a C(7) hydrogen bond chain motif,
the neighboring 3-hydroxybenzoate anions interact via an O
(hydroxy)eH/O(carboxy) hydrogen bond (Fig. 3b). In the crystal
Fig. 3. Network of the intermolecular interactions in 3: C24(16) hydrogen bond chain
motif (a), C(7) hydrogen bond chain motif (b), connection between C24(16) and C(7)
hydrogen bond chain motifs (c), and crystal packing (d).

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A. Sikorski, D. Trzybinski / Tetrahedron 67 (2011) 2839e2843
2842
acridine skeletons are linked by
rangement forming alternately aligned columns of molecules A and
B (Figs. 3a and 4).
p
e
p
interactions in the ABA ar-
of 3, there are networks of chains forming columns (Fig. 3c). The
presence of chains in the crystal packing is the reason of lack of
-stacking interactions between the aromatic rings in the anions.
p
3. Conclusion
In summary, as a continuation of our recent work, we discuss the
crystal structures of a series of salts with the 9-aminoacridinium
cation and the 3-chlorobenzoate (1), 4-chlorobenzoate (2), and 3-
hydroxybenzoate (3) anions. The structure of 3 is the first of all the
known 9-aminoacridinium salts where mixed salts were obtained.
Conformational analysis of the 9-aminoacridinium skeleton sug-
gests that the aromatic carboxylic acid anions affect the planarity of
the 9-AA skeleton, especially in compound 3, which adopts an evi-
dent butterfly conformation. Analysis of the hydrogen bonds in the
crystal lattices of the title compounds shows that the cations and
anions form tetramers (1 and 2) or chains (3). In the tetramers, the
ions are linked via N(amino)eH/O(carboxy) hydrogen bonds
forming R22(8) (1) or R42(16) (2) hydrogen bond ring motifs. In the
packing of 3, there are two kinds of hydrogen bond chain motif. The
first, C24(16), in which 9-AA cations, a Clꢀ anion and a water molecule
are interlinked, and the second, C(7), in which aromatic carboxylic
acid anions are connected directly. We also observed the influence of
the different anions on the packing of the acridine skeletons in the
crystal lattice. The 9-AA cations are
pep stacked in the AB (1) or ABA
(2 and 3) arrangement to form a two-fold helical arrangement (1) or
columns (2 and 3). Analysis of the
aromatic rings of anions indicates that
p
e
p
p
interactions between the
-stacking interactions are
observed only in the packing of molecules 2.
4. Experimental
4.1. General
The synthesis of compounds 1, 2, and 3 is described in
Supplementary data. Single crystals of 1e3 were grown by slow
evaporation of an ethanol solution.
4.2. Crystal structure determination
Good-quality single-crystal specimens of 1, 2, and 3 were se-
lected for the X-ray diffraction experiments at T¼295(2) K. They
were mounted with epoxy glue at the tip of glass capillaries Dif-
Fig. 4. Geometry of the
pep interactions in 3.
fraction data were collected on an Oxford Diffraction Gemini R
ꢁ
ULTRA Ruby CCD diffractometer with CuK
a
(
l
¼1.54184 A) (for 1)
ꢁ
In the ABA arrangement of molecules A, all the aromatic rings
from the acridine skeletons participate in interactions, form-
ing a zigzag motif with centroid/centroid distances from 3.573 to
and Mo K
a
(l
¼0.71073 A) (for 2 and 3) radiation. In all cases, lattice
pep
parameters were obtained by least-squares fit to the optimized
setting angles of the collected reflections by means of CrysAlis CCD9
Data were reduced by using CrysAlis RED software with applying
multi-scan absorption corrections (Empirical absorption correction
using spherical harmonics, implemented in SCALE3 ABSPACK
scaling algorithm). The structural resolution procedure was made
using the SHELXS-97 package solving the structures by direct
methods and carrying out refinements by full-matrix least-squares
on F2 using SHELXL-97 program.10 All H-atoms bound with aromatic
C-atoms were placed geometrically and refined using a riding
ꢁ
ꢁ
4.182 A and a distance of 3.450 A between the mean planes of the
neighboring acridine skeleton. In this arrangement, the over-
lapping mode of the neighboring cations shows that they are al-
ꢁ
ternately shifted toward each other for a distance of w1.4 A and
w1.2 A along the shortest and longest axis of the acridine skeletons,
respectively, in the AB sequence and shifted for a distance of w1.4 A
and w1.8 A along the shortest and longest axis of the acridine
ꢁ
ꢁ
ꢁ
skeletons, respectively, in the BA sequence. Molecules of B are also
packed in the ABA arrangement with centroid/centroid distances
ꢁ
model with CeH¼0.93 A and Uiso(H)¼1.2 Ueq(C). All H-atoms
ꢁ
ꢁ
from 3.602 to 4.364 A and a distance of 3.520 A between the mean
planes of the neighboring acridine skeleton. However, there are
differences between the overlapping modes of the neighboring
cations. In the AB sequence, the adjacent cations are alternately
shifted along the longest axis of the acridine skeletons for a dis-
bound with N-atoms were placed geometrically and refined using
ꢁ
a riding model with NeH¼0.86 A and Uiso(H)¼1.5 Ueq(N). The all
amino eNH2 groups were assumed to be planar-trigonal and co-
planar with the mean planes of acridinium skeleton. All H-atoms
from the water molecules were located in a difference Fourier map
and refined freely with Uiso(H)¼1.5 Ueq(O). All interactions dem-
onstrated were found by PLATON program.11
ꢁ
tance of w1.2 A, whereas in the BA sequence, the overlapping mode
of neighboring cations shows that they are alternately shifted along
the shorter axis by a distance of w0.7 A and along the longer axis of
the acridine skeleton by a distance of w2.4 A. In the crystal lattice
ꢁ
Crystallographic data for the structures reported in this paper
have been deposited with the Cambridge Crystallographic Data
ꢁ

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A. Sikorski, D. Trzybinski / Tetrahedron 67 (2011) 2839e2843
2843
Center as supplementary publication no. CCDC-794396 (1), CCDC-
References and notes
794397 (2), and CCDC-794398 (3). Copies of the data can be
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44 1223 336 033; e-mail:
deposit@ccdc.cam.ac.uk).
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