Neutral and ionic supramolecular complexes of phenanthridine and some common dicarboxylic acids: Hydrogen bond and melting point considerations

Article abstract of DOI:10.1021/cg200573m

Supramolecular complexes of phenanthridine have been prepared with various dicarboxylic acids. Cocrystallization of phenanthridine with fumaric acid, succinic acid, and isophthalic acid produced neutral cocrystals. Proton transfer from maleic acid and oxalic acid to the phenanthridine moiety results in salts of these two acids. It was found that neutral cocrystals are formed when the ΔpK_a value of the complex is smaller than 2.56, whereas salts are formed when ΔpK_a is greater than 3.66. The crystal structures of supramolecular complexes have been determined. The structure of each compound depends on acid geometry, and the compounds may be described as dimers, trimers, or chains. A comparison of the melting points, hydrogen bonds, and densities of each molecular complex and the corresponding dicarboxylic acid is presented. Utilizing the approximate relative bond strengths of hydrogen bonds, a comparison of the number of hydrogen bonds in the acid and the cocrystal is possible.

Full text of DOI:10.1021/cg200573m

ARTICLE
pubs.acs.org/crystal
Neutral and Ionic Supramolecular Complexes of Phenanthridine and
Some Common Dicarboxylic Acids: Hydrogen Bond and Melting Point
Considerations
Liana Orola,† Mikelis V. Veidis,*,† Ilpo Mutikainen,‡ and Inese Sarcevica†
†Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga, LV-1013, Latvia
‡Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, FIN-00014, Helsinki, Finland
S Supporting Information
b
ABSTRACT: Supramolecular complexes of phenanthridine have
been prepared with various dicarboxylic acids. Cocrystallization of
phenanthridine with fumaric acid, succinic acid, and isophthalic acid
produced neutral cocrystals. Proton transfer from maleic acid and
oxalic acid to the phenanthridine moiety results in salts of these two
acids. It was found that neutral cocrystals are formed when the ΔpKa
value of the complex is smaller than 2.56, whereas salts are formed
when ΔpKa is greater than 3.66. The crystal structures of supramo-
lecular complexes have been determined. The structure of each
compound depends on acid geometry, and the compounds may be
described as dimers, trimers, or chains. A comparison of the melting
points, hydrogen bonds, and densities of each molecular complex and
the corresponding dicarboxylic acid is presented. Utilizing the approximate relative bond strengths of hydrogen bonds, a comparison
of the number of hydrogen bonds in the acid and the cocrystal is possible.
’ INTRODUCTION
from one component to another they cannot be considered
alone. Other factors such as the crystalline environment and
reaction conditions (solvent, temperature, etc.) may also affect
the ionization state of a compound.16
The understanding of intermolecular interactions and the
application of these interactions in the design of new solid-state
assemblies is perhaps the main goal of supramolecular chemistry
and crystal engineering.1,2 In recent years, advances in crystal
engineering have enabled the design and the synthesis of pharma-
ceutical cocrystals as well as salts exhibiting improved physico-
chemical properties.3À5
The utility of N-heterocyclic bases to obtain molecular com-
plexes with dicarboxylic acids is well documented.6À12 Depend-
ing on the solid state interaction between the N-heterocyclic base
and a dicarboxylic acid, a neutral synthon I and II or an ionic
synthon III and IV may be observed (Figure 1).
Structural studies of supramolecular complexes of N-hetero-
cyclic bases and dicarboxylic acids show differences depending
on the number of proton acceptors (nitrogen atoms) in the base
molecule. The alternating chains of base and acid units are
dominant in the crystal structures of the adducts containing a
N-heterocyclic base with two proton acceptors and dicarboxylic
acid.9,10,17À19 N-heterocyclic bases with one proton acceptor
often form supramolecular trimers with dicarboxylic acids.7,11,20
Phenanthridine is chosen as a molecular complex former
because it can participate in hydrogen bonding with donor mole-
cules such as carboxylic acids. Koshima and co-workers have
reported the cocrystallization of phenanthridine with several
monocarboxylic acids: diphenylacetic acid,21 3-indolepropionic
acid,22 9-fluorenecarboxylic acid,23 3-indoleacetic acid,24 and
bis(thien-2-yl)acetic acid.25
A feature of synthons I and III is that both strong OÀH N/
3 3 3
N+ÀH OÀ hydrogen bonds and weak CÀH O interac-
3 3 3
3 3 3
tions are formed. The relatively weak CÀH O interactions can
3 3 3
play a significant role in the stabilization of these synthons.10,13
The occurrence of the OÀH N/N+ÀH OÀ hydrogen
3 3 3
3 3 3
bonds depends on the difference in pKa values between the base
and the acid. According to Johnson and Rumon,14 a pyridineÀ
carboxylic acid system salt would be expected for ΔpKa > 3.75.
Bhogala et al.15 propose that for carboxylic acidÀpyridine base
In order to investigate further the relation between the ΔpKa
value and the synthon species formed as a result of the interac-
tions of a one proton acceptor N-heterocyclic base with dicar-
boxylic acids and determine the melting point temperatures and
supramolecular systems when ΔpKa < 0 a neutral OÀH
N
3 3 3
hydrogen bond results, when 0 < ΔpKa < 3.75 the synthons have
an intermediate OÀH N/N+ÀH OÀ hydrogen bond, and
Received: May 5, 2011
3 3 3
3 3 3À
when ΔpKa > 3.75 an ionic N+ÀH O hydrogen bond forms.
Revised:
July 19, 2011
3 3 3
Although ΔpKa values are widely used to predict proton transfer
Published: July 25, 2011
r
2011 American Chemical Society
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Scheme 1. Chemical Structures of Components of Molecular
Complexes
Figure 1. Supramolecular synthons I, II, III, and IV discussed in this
paper. I and III represent neutral and ionic R22(7) synthon. II represents
noncyclic dimer D. IV represents R22(5) synthon.
densities of the obtained cocrystals, we have prepared and deter-
mined the structures of neutral and ionic complexes of phenan-
thridine with the dicarboxylic acids: fumaric acid, maleic acid,
isophthalic acid, succinic acid, and oxalic acid (Scheme 1).
X-ray Powder Diffraction (XRPD). X-ray powder diffraction analysis
was performed using a Bruker AXS D8 Advance powder diffractometer
(Bruker AXS GmbH, Germany) with Cu KR radiation (λ = 1.5418 Å),
40 kV, 40 mA. Data were collected at room temperature with a 0.02ꢀ step
and a scan speed of 1ꢀ/min.
Thermal Analysis. Differential thermal analysis and thermogravi-
metric analysis (DTA/TGA) were performed using Seiko Exstar6000
TG/DTA6300 (Seiko Instruments Inc., Japan) equipment. The samples
(4À7 mg) were heated in open aluminum pans at a rate of 10 ꢀC/min
in air.
’ EXPERIMENTAL SECTION
All chemicals were supplied by Sigma-Aldrich or by other commercial
suppliers.
Synthesis of Supramolecular Complexes. PhenanthridineÀ
Fumaric Acid (2:1) Cocrystal, 1. Cocrystal formed when phenanthridine
and fumaric acid in a 1:1 molar ratio (0.060 g, 0.33 mmol, and 0.039 g,
0.33 mmol, respectively) were dissolved in 5 mL of hot ethanol and
allowed to crystallize.
’ RESULTS AND DISCUSSION
PhenanthridineÀFumaric Acid (4:1.5) Cocrystal, 2. Cocrystal
formed when phenanthridine and fumaric acid in a 2:1 molar ratio
(0.090 g, 0.50 mmol, and 0.029 g, 0.25 mmol, respectively) were
dissolved in 5 mL of hot ethanol and allowed to crystallize.
PhenanthridineÀSuccinic Acid (2:1) Cocrystal, 3. The cocrystals
were obtained upon cocrystallization of phenanthridine (0.090 g,
0.50 mmol) and succinic acid (0.030 g, 0.25 mmol) from hot ethanol
(5 mL).
PhenanthridineÀIsophthalic Acid (1:1) Cocrystal, 4. Phenanthridine
(0.045 g, 0.25 mmol) and isophthalic acid (0.042 g, 0.25 mmol) were
dissolved in 5 mL of hot ethanol. Slow evaporation of the solvent gave
colorless crystals.
Phenanthridinium Maleate, 5. Phenanthridine (0.090 g, 0.50 mmol)
and maleic acid (0.058 g, 0.50 mmol) were dissolved in 5 mL of hot
ethanol. Slow evaporation of the solvent produced colorless crystals.
Phenanthridinium Oxalate, 6. Crystallization of phenanthridine and
oxalic acid in a 2:1 molar ratio resulted in a phenanthridine oxalate with
1:1 stoichiometry. The salt was obtained by dissolving phenanthridine
(0.090 g, 0.50 mmol) and 0.023g (0.25 mmol) oxalic acid in 5 mL of hot
ethanol followed by slow evaporation.
Phenanthridinium Oxalate Monohydrate, 7. Phenanthridine (0.060
g, 0.33 mmol) and oxalic acid dihydrate (0.042 g, 0.33 mmol), molar
ratio 1:1, were dissolved in 5 mL of hot ethanol. Colorless crystals were
formed upon evaporation of the solvent.
Single Crystal X-ray Diffraction. X-ray diffraction data were measured
using a Nonius Kappa CCD diffractometer (Bruker AXS GmbH,
Germany) with MoÀKR radiation (0.71073 Å). Data were collected
at 173 K. Data reduction was performed with the COLLECT/EVAL26
program. All structures were solved by direct methods using SIR9227 and
SHELXS-8628 as implemented in the program package WinGX.29
Refinement was carried out by full-matrix least-squares method with
the CRYSTALS30 program. All non-hydrogen atoms were refined
anisotropically. The hydrogen atoms were located by the difference
Fourier method. During refinement, hydrogen atoms were refined in the
riding mode. The number of hydrogen bonds was determined by
PLATON31 using the experimental results reported here and the CIF
files for the dicarbocxylic acids available from the CSD.32
Crystallizing phenanthridine with several dicarboxylic acids
neutral and ionic supramolecular complexes have been obtained.
Regardless of an equal number of hydrogen bonding groups in
each component, the observed stoichiometries of the isolated
molecular complexes are different. Compounds 1 and 3 crystal-
lized with a 2:1 ratio of base to acid stoichiometry, while 4À7 had
1:1 stoichiometry. Cocrystallizing phenanthridine with fumaric
acid, the 2:1 complex (1) as well as the 4:1.5 complex (2) was
also obtained. Dissolving starting components in a 1:1 molar
ratio led to the generation of 1, whereas a 2:1 ratio yielded 2.
This cocrystallization experiment was repeated and gave identical
results. The formation of molecular complexes with different
base/acid ratios has been explained by component concentration
changes during solvent evaporation.33
The solid phase of each complex was characterized by XRPD
and DTA/TGA. The XRPD patterns of 1À7 are shown in
Figure 2, but the respective DTA/TGA thermograms are in-
cluded in the Supporting Information.
The crystal and molecular structures of all seven compounds
have been determined by single crystal X-ray diffraction. Crystal-
lographic data are summarized in Table 1. Hydrogen bond para-
meters are listed in Table 2.
PhenanthridineÀFumaric Acid (2:1) Cocrystal, 1. The
cocrystal crystallizes in the monoclinic space group P21/n.
The fumaric acid molecule is located on an inversion center
and links two phenanthridine molecules through OÀH
N
3 3 3
hydrogen bonds, forming centrosymmetric trimers. The angle
between the plane of the carboxylic acid group and the pyridyl
ring plane is 13.6ꢀ. The fumaric acid molecule in the compound
has S-trans/S-trans conformation. The crystal structure along
the a axis shows phenanthridineÀfumaric acidÀphenanthridine
trimer arrangement in which the trimer units pack alongside one
another (Figure 3).
The packing motif of this cocrystal along the a axis is similar to
that of acridineÀfumaric acid complex.11 However, in 1 the angle
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Crystal Growth & Design
ARTICLE
between planes of the carboxylic acid and the acridine molecule is
significantly larger: 60.26ꢀ.
PhenanthridineÀFumaric Acid (4:1.5) Cocrystal, 2. The
compound crystallizes in the triclinic P1 space group. The
asymmetric unit contains four symmetry independent phenan-
thridine molecules (a, b, c, d) and one and one-half symmetry
independent fumaric acid molecules (e, f).
The fumaric molecule f lies on an inversion center. Three
(a, b, c) phenanthridine molecules are oriented perpendicular
to the fourth (d) phenanthridine molecule. The two acid mole-
cules are parallel to each other. The angles between the
carboxylic acid group plane O11, C10, O12 (fumaric acid e
molecule) and the pyridyl ring plane N60, C59, C68, C67, C62,
C61 and between the carboxylic acid group plane O5, C7, O6
(fumaric acid e molecule) and the pyridyl ring plane N32, C33,
C34, C39, C40, C31 are 20.3ꢀ and 38.1ꢀ, respectively. In the
case of the fumaric acid f molecule, which is located on an
inversion center, the angle between the plane of the carboxylic
acid group and pyridyl ring plane is 22.4ꢀ. The fumaric acid
molecules have S-trans/S-trans conformation. In the solid state,
phenanthridine and fumaric acid molecules form a two-layered
structure (Figure 4a).
The first layer consists only of phenanthridine a, b, c molecules
with an -[a-b-b-a-c-c]n- arrangement. In a row of phenanthridine
molecules, three (a, b, c) molecules are oriented in one direction,
but the next three are oriented in the opposite direction as deter-
mined by the packing of these molecules and shown in Figure 4b.
The distance between phenanthridine molecule planes is 3.46 Å.
Alternating fumaric acid e and f molecules and phenanthridine d
molecules form the second layer of the crystal structure. Both
layers are connected through OÀH N hydrogen bonds that
3 3 3
involve two fumaric acids and one phenanthridine molecule.
Additional CÀH O hydrogen bonds between oxygen and the
3 3 3
hydrogen atoms of the carboxyl group and phenanthridine d
molecule are also formed.
PhenanthridineÀSuccinic Acid (2:1) Cocrystal, 3. The
cocrystals crystallize in the monoclinic P21/n space group.
The succinic acid molecule is located on an inversion center.
The angle between the plane of the carboxylic acid group and
pyridyl ring plane is 21.5ꢀ. In the solid state, the cocrystal
structure is a centrosymmetric trimer: two molecules of phenan-
thridine are linked by one molecule of succinic acid through
OÀH N hydrogen bonds. Unlike cocrystal 1, the trimers are
3 3 3
placed in a herringbone arrangement when viewed along the a
axis (Figure 5).
Weak CÀH O hydrogen bonds between trimers are
3 3 3
observed and result in planar supramolecular sheets.
PhenanthridineÀIsophthalic Acid (1:1) Cocrystal, 4. The
compound crystallizes in the monoclinic space group Pc.
The angle between the plane of the carboxylic acid group and
the pyridyl ring plane is 42.9ꢀ. Isophthalic acid molecules are
Figure 2. XRPD patterns for complexes of phenanthridine with dicar-
boxylic acids.
Table 1. Crystallographic Data and Structure Refinement Parameters for Supramolecular Complexes 1À7
supramolecular complex
1
2
3
4
5
6
7
chemical formula
C
13H9N
(C13H9N)4
C13H9N
C13H9N
C13H10N+
C13H10N+
C13H10N+
3
3
3
3
3À
À3
À3
(C4H4O4)0.5
(C4H4O4)1.5
(C4H6O4)0.5
C8H6O4
C4H3O4
295.29
C2HO4
269.26
C2HO4 H2O
3
formula weight
237.26
monoclinic
P21/c
890.99
238.27
345.35
287.27
crystal system
triclinic
P1
monoclinic
P21/n
monoclinic
Pc
monoclinic
P21
triclinic
P1
monoclinic
P21/c
space group
a (Å)
3.900(1)
20.070(4)
14.489(3)
90
11.299(2)
13.591(3)
15.293(3)
78.55(3)
75.83(3)
75.89(3)
2184.1(9)
2
4.901(1)
17.210(3)
13.989(3)
90
11.915(2)
3.8719(8)
17.285(4)
90
5.712(1)
8.131(2)
14.943(3)
90
5.584(1)
10.230(2)
10.962(2)
75.17(3)
84.53(3)
86.35(3)
602.1(2)
2
7.557(2)
9.469(2)
18.562(4)
90
b (Å)
c (Å)
R (ꢀ)
β (ꢀ)
γ (ꢀ)
V (Å3)
97.58(3)
90
90.90(3)
90
91.79(3)
90
93.42(3)
90
95.51(3)
90
1124.2(4)
4
1179.8(3)
4
797.1(3)
2
692.8(2)
2
1322.1(5)
4
Z
T (K)
173
173
173
173
173
173
173
reflections collected
independent reflection
observed reflection
threshold expression
R1
13715
2534
39870
15813
2676
11136
1823
12841
1704
9799
23655
3038
9991
2743
1339
5390
1455
1733
1369
1636
1857
>2σ(I)
0.0462
0.1088
0.9876
>1.5σ(I)
0.0656
0.1536
1.0412
>3σ(I)
0.0350
0.0962
1.0653
>0σ(I)
0.0582
0.1120
1.0000
>3σ(I)
0.0320
0.0829
1.0103
>3σ(I)
0.0402
0.1011
1.0248
>2σ(I)
0.0384
0.0772
1.0274
wR2
GOF
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Crystal Growth & Design
ARTICLE
Table 2. Selected Hydrogen Bond Parameters for Supramolecular Complexes 1À7
supramolecular
complex
dDÀH (Å)
dH 3 3 3 A (Å)
dD 3 3 3 A (Å)
—DÀH A (ꢀ)
symmetry code
3 3 3
1
O1ÀH11 N5
0.85
1.78
2.627(4)
176
3 3 3
2
O1ÀH11 N46
0.84
0.83
0.84
0.93
0.94
1.78
1.80
1.78
2.45
2.42
2.614(6)
2.621(6)
2.617(6)
3.368(6)
3.362(6)
174
170
173
170
179
3 3 3
O5ÀH51 N32
3 3 3
O11ÀH111 N60
3 À x, Ày, 1 À z
À1 + x, y, z
À1 + x, y, z
3 3 3
C24ÀH241 O2
3 3 3
C23ÀH231 O6
3 3 3
3
4
O3ÀH31 N6
0.86
0.94
0.95
1.80
2.53
2.57
2.652(3)
3.359(3)
3.461(3)
175
147
158
À1 + x, y, z
1/2 À x, 1/2 + y, 3/2 À z
À1/2 + x, 3/2 À y, 1/2 + z
3 3 3
C15ÀH151 O1
3 3 3
C17ÀH171 O3
3 3 3
O12ÀH121 N19
1.01
0.86
0.83
0.92
0.94
1.58
1.83
2.58
2.54
2.59
2.579(5)
2.678(5)
3.207(5)
3.294(5)
3.511(5)
173
169
134
140
167
À1 + x, y, z
3 3 3
O1ÀH11 O11
x, 1 À y, 1/2 + z
x, 1 À y, À1/2 + z
1 + x, À1 + y, z
1 + x, Ày, À1/2 + z
3 3 3
C14ÀH141 O3
3 3 3
C20ÀH201 O11
3 3 3
C25ÀH251 O12
3 3 3
5
6
7
N9ÀH91 O1
0.87
0.93
0.94
0.94
0.93
0.85
1.77
2.51
2.36
2.56
2.46
1.61
2.636(3)
3.180(3)
3.292(3)
3.319(3)
3.386(3)
2.453(3)
173
129
175
138
176
168
1 + x, y, z
3 3 3
C14ÀH141 O3
1 + x, y, z
3 3 3
C18ÀH181 O8
À1 + x, À1 + y, z
Àx, À1/2 + y, 1 À z
À1 + x, À1 + y, z
3 3 3
C20ÀH201 O1
3 3 3
C22ÀH221 O8
3 3 3
O7ÀH71 O3 (intra)
3 3 3
N7ÀH71 O6
0.89
0.89
0.87
0.93
0.95
0.87
1.93
2.39
1.61
2.34
2.51
2.50
2.800(3)
2.907(3)
2.474(3)
3.252(3)
3.319(3)
3.258(3)
166
117
171
164
144
146
3 3 3
N7ÀH71 O1
3 3 3
O1ÀH11 O5
À1 + x, y, z
3 3 3
C12ÀH121 O5
1 À x, 2 À y, 2 À z
Àx, 2 À y, 2 À z
À1 + x, y, z
3 3 3
C13ÀH131 O3
3 3 3
O1ÀH11 C4
3 3 3
N8ÀH81 O1
0.92
0.92
0.82
0.82
0.82
0.84
0.94
0.94
1.79
2.51
1.94
2.49
1.90
1.68
2.52
2.56
2.701(3)
3.055(2)
2.723(3)
3.029(3)
2.699(3)
2.522(3)
3.193(3)
3.458(3)
168
118
159
124
166
175
129
161
x, 3/2 À y, À1/2 + z
x, 3/2 À y, À1/2 + z
3 3 3
N8ÀH81 O5
3 3 3
O7ÀH71 O3
3 3 3
O7ÀH71 O6
3 3 3
O7ÀH72 O1
1 À x, À1/2 + y, 3/2 À z
2 À x, 1/2 + y, 3/2 À z
2 À x, 1 À y, 1 À z
3 3 3
O5ÀH51 O7
3 3 3
C9ÀH91 O6
3 3 3
C15ÀH151 O1
1 À x, 1/2 + y, 3/2 À z
3 3 3
held in infinite linear chains by OÀH O hydrogen bonds.
of isophthalic acidÀpyridine solvate,12 chains are formed by the
molecules, with two pyridine moieties hydrogen bonded to
each acid moiety.
3 3 3
Furthermore, each acid molecule interacts with phenanthridine
via an OÀH N hydrogen bond (Figure 6).
3 3 3
Adjacent chains are linked through weak CÀH
O inter-
Phenanthridinium Maleate (2:1), 5. The salt crystallizes in
the monoclinic P21 space group. The angle between the plane of
the carboxylate group and the pyridinium ring plane is 6.7ꢀ. One
phenanthridine moiety interacts with one maleate moiety via
N+ÀH OÀ and CÀH O hydrogen bonds to form dimers
3 3 3
actions between base and acid molecules. The crystal struc-
ture is stabilized by πÀπ interactions of phenanthridine as
well as of isophthalic acids moieties in neighboring chains.
The distance between the phenanthridine rings is 3.42 Å, but
the distance between acid rings is 3.34 Å. In the crystal structure
3 3 3
(Figure 7).
3 3 3
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Crystal Growth & Design
ARTICLE
Figure 3. Packing motif of 1 along the a axis.
Figure 5. Packing motif of 3 along the a axis.
Figure 6. Formation of extended chains in the crystal structure of 4.
Figure 4. (a) Layered structure of 2 (colored according to symmetry
equivalence) viewed along the b axis. (b) The π-stacking of phenan-
thridine molecules.
Figure 7. Packing motif of 5 along the a axis.
These dimers are further extended through weak CÀH
hydrogen bonds to produce infinite chains (Figure 8).
O
3 3 3
These chains are cross-linked via CÀH O bonds. BaseÀ
oxalate moieties in 6 are arranged in separate layers which are
3 3 3
acid dimer formation is observed in the crystal structure of
acridinium hydrogen maleate11 in which, unlike 5, synthon II is
distorted due to molecular geometry of the acridine molecule. In
connected through weak CÀH O interactions.
3 3 3
Phenanthridinium Oxalate (1:1) Monohydrate, 7. The
compound crystallizes in the monoclinic space group P21/c.
The asymmetric unit of 7 contains one phenanthridinium cation,
one oxalate anion, and one water molecule. The oxalate anion has
an almost planar conformation with the CÀC twist angle of 2.2ꢀ.
Analysis of the CSD32 for oxalate anion geometry in organic
compounds indicates that a twisted or a planar conformation can
be expected. The oxalate anion with two bifurcated hydrogen
bonds is planar due to intermolecular interactions that stabilized
the structure. Similar to the structure of 6, in 7 the oxalate anion
interacts with phenanthridinium cation through asymmetric
the maleate anion of 5, an intramolecular OÀH OÀ hydrogen
3 3 3
bond is also observed as a result of the short distance between the
carboxyl group and carboxylate anion.
Phenanthridinium Oxalate (1:1), 6. The salt crystallizes in
the triclinic P1 space group. The oxalate anion has a twisted
geometry; the CÀC twist angle is 20.7ꢀ. The oxalate anions form
linear chains via OÀH O hydrogen bonds. The anions in a
3 3 3
chain are bound to phenanthridinium cations by asymmetric
bifurcated OÀH N hydrogen bonds (Figure 9).
3 3 3
This mode of bonding between oxalate chains and phenan-
thridinium moieties is similar to previously reported phthalazi-
nium oxalate.34 In the solid state, the phenanthridinium and
bifurcated OÀH N hydrogen bonds and in addition forms
3 3 3
asymmetric bifurcated OÀH O hydrogen bonds with the
3 3 3
water molecule (Figure 10).
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Crystal Growth & Design
ARTICLE
Figure 8. Arrangement of molecules in the crystal structure of 5.
Figure 10. Hydrogen bonding in compound 7.
when simple pyridine derivatives combine with highly oxyge-
nated carboxylic acids.
In the supramolecular complexes, the phenanthridine moiety
does not change and the structures of the compounds 1À7 is
based on acid geometry. Because the linear nature of the fumaric
and the succinic acid molecules, in the solid state centrosym-
metric baseÀacidÀbase trimers formed with phenanthridine. In
the structure of 4, the carboxyl groups of isophthalic acid are
located in the para position, and only one of these is bound by a
hydrogen bond to a phenanthridine moiety. In this instance,
minimal spatial interferences permit hydrogen bonds with other
acid as well as the phenanthridine molecule, and chain formation
in the crystal structure of 4 is preferred. Maleic acid geometry
permits intramolecular hydrogen bonding, and only one carboxyl
group is available for carboxylic acidÀpyridine synthon forma-
tion resulting in phenanthridiniumÀmaleate dimers, 5. The
oxalate ion structure enhances bifurcated bond formation in 6
and 7.
Figure 9. Hydrogen bond formation in 6.
The water molecule connects two anions via OÀH Owater
3 3 3
and OwaterÀH O hydrogen bonds.
3 3 3
Some Supramolecular Features of 1À7. Pyridine and
carboxylic acid functional groups are known to form robust
intermolecular interactions, and cocrystallizing an N-heterocyclic
base with a carboxylic acid should form synthon I and II or III
and IV depending on the acidity of acid. Molecular complexes of
phenanthridine with dicarboxylic acids are based on either the
Melting Points and ΔpKa of Molecular Complexes. The
neutral cocrystals reported here have higher melting points than
phenanthridine (107.4 ꢀC) but lower melting points than the
individual dicarboxylic acids (Table 3).
neutral synthon II or ionic synthon III and IV. The OÀH
N
3 3 3
hydrogen bond present in synthon I and II is strong and
Phenanthridine and fumaric acid cocrystals with 2:1 and 4:1.5
stoichiometries have different melting points. 1 with a stoichio-
metric ratio 2:1 melts at higher temperature than 2 with a
stoichiometric ratio of 4:1.5. This difference is probably the
result of closer molecular packing in the crystal structures.
Notwithstanding stabilization effects of πÀπ interactions in 2,
the calculated density of 1 is higher than 2. Comparing the
melting points and densities of phenanthridineÀfumaric acid
cocrystal 1 and phenanthridineÀsuccinic acid cocrystal 3, in both
cases a centrosymmetric structure is observed and the cocrystal
with the higher density has the higher melting point. The melting
point of fumaric acid cocrystal (1) is higher than that of the
succinic acid cocrystal (3). Both structures are trimers; however,
the angle between the carboxylic acid plane and the pyridyl ring
plane in trimer 1 is smaller than in trimer 3, and closer packing is
found in 1 resulting in a higher density and higher melting point
of 1. The density of the cocrystals is also either less or slightly
higher that of the dibasic acids, and packing in the solid state may
directional, whereas weak CÀH O interaction cannot form
3 3 3
in all cases. For ring motif R22(7) formation, strong geometrical
complementarity between base and acid molecules is necessary.
Our results show that in cocrystals 1À4 the noncyclic motif D is
formed probably due to relatively large dihedral angles observed
between the carboxylic acid group and pyridyl ring; these angles
range from 13.6 to 42.9ꢀ. In phenanthridinium salt 5, this angle is
6.7ꢀ and an ionic ring motif R22(7) is observed. Other factors such
as conformational flexibility of molecules may also affect synthon
formation. In the compounds 6 and 7 the ionic synthon R22(7)
is absent. The crystal structure of both salts display motif
R21(5) between oxalate anion and phenanthridinium cation.
Interestingly, R22(7) synthon formation takes place generally in
neutral molecular complexes of oxalic acid with N-heterocyclic
bases,9,10,18,34,35 whereas in ionic complexes36,37 the R21(5) syn-
thon is present. Dale and co-workers12 reported poor predict-
ability of the carboxylic acidÀpyridine R22(7) heterosynthon
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Crystal Growth & Design
Table 3. The Number of Hydrogen Bonds, Density, and Melting Point of each Compound 1À6 and Dicarboxylic Acid
ARTICLE
number of
number of
number of weak
strong
total possible
strong
melting
point
number of weak
strong
total possible
strong
melting
point
(ꢀC)38
CÀH
O
OÀH
N
density
dicarboxylic
acid
CÀH
O
OÀH
3 3 3
N
density
3 3 3
3 3 3
3 3 3
38
compd
bonds
(or O) bonds H-bonds (g cmÀ3
)
(ꢀC)
bonds
(or O) bonds H-bonds (g cmÀ3
)
1
2
3
4
5
6
1
3
1
1
1
2
1
1.402
1.355
1.341
1.439
1.416
1.485
164
160
115
150
141
169
fumaric acid
3
3
4
1.635
287
2
2
3
4
4
3.66
1.66
2
succinic acid
isophthalic acid
maleic acid
2
3
2
2
2
1.572
1.526
1.590
1.900
187.9
347
2
2
3.66
2.66
2
2.33
3.33
139
oxalic acid
189.5
also affect the melting point of each compound. Similar correla-
tion between melting points of cocrystals and starting com-
pounds is observed in cocrystals obtained from acridine and
dicarboxylic acids.11
Table 4. pKa and ΔpKa Values for Neutral and Ionic Com-
plexes of Phenanthridine
compound
dicarboxylic acid
pKa
ΔpKa
nature of compound
Intermolecular hydrogen bonding also affects the melting
point of the compound. To compare the number of hydrogen
bonds in the crystal structure, it is important to take into account
the fact that there are relatively weak and relatively strong
1, 2
3
fumaric acid
succinic acid
isophthalic acid
maleic acid
3.02
4.21
3.70
1.92
1.25
2.56
1.37
1.88
3.66
4.33
neutral
neutral
neutral
ionic
4
5
interactions. It has been reported that the CÀH O hydrogen
3 3 3
6
oxalic acid
ionic
bond strength is approximately 25À50% of an OÀH
O
3 3 3
and an OÀH N hydrogen bond.39,40 Assuming that three
3 3 3
form agrees with the melting temperature of 6. XRPD of the
anhydrous form also confirmed that after 2 h dehydration of the
hydrate at 100 ꢀC 6 was obtained. There appears to be no clear
correlation between the melting point and the neutral or ionic
nature of the compound.
CÀH O bonds are energetically equivalent to one full
3 3 3
strength hydrogen bond such as OÀH O (or OÀH N),
3 3 3
3 3 3
it is possible to assign strong hydrogen bonds to the cocrystals
and the respective dicarboxylic acids (total possible strong
H-bonds). The results are presented in Table 3. Using the
assumption regarding the relative strengths of hydrogen bonds
mentioned above, in the nonionic cocrystals studied the number
of possible strong hydrogen bonds in the acids is equal to or
larger than the number of strong hydrogen bonds in the
cocrystal. This would suggest that the formation of fewer
hydrogen bonds in the cocrystal results in a lower melting point
of the cocrystals but a higher melting point of the dibasic acid
having a larger number of possible strong hydrogen bonds.
However, in cocrystals of isonicotinamide with dicarboxylic
acids,40 the cocrystals have higher melting points than the
corresponding individual acids. Possibly supramolecular systems
with a larger number proton donor and acceptor sites for
hydrogen bond formation, as opposed to packing in the unit
cell, are better suited for formation of cocrystals with higher
melting points than the pure dicarboxylic acids. It may be
concluded that both hydrogen bond formation and packing
forces influence the melting point of cocrystals. These are
examples of the influence of structure on physical properties,
and hydrogen bonds and crystal packing do have an impact on
physical properties such as the density and melting point.
Phenanthridine is a relatively basic compound (pKa = 5.58).38
Depending on the acidity of the studied acid, salts or cocrystals
may form. A comparison of the ΔpKa (ΔpKa = pKa base À pKa
acid) values of 1À6 (Table 4) shows that when the value ΔpKa is
less than 2.56 formation of the neutral hydrogen bonded synthon
I takes place.
The formation of the phenanthridine salts occurred when
ΔpKa > 3.66. On the basis of the considerations of Bhogala
et al.,15 when 0 < ΔpKa < 3.75 it is difficult to predict neutral or
ionic hydrogen bond formation in the supramolecular structure.
The ΔpKa values of 1À5 are located in the interval when
cocrystals and/or salts can be expected, but 6 is an ionic complex.
These observations are in good agreement with Brittain’s
method41 for predicting salt formation in aqueous solution by
calculating the percentage of salt formation as a function of pKa
and pKb.
’ CONCLUSIONS
Phenanthridine can form neutral or ionic supramolecular
complexes with dicarboxylic acids depending on the acidity of
The melting points of 5 and 6 are influenced by the ionic
character of these compounds, and hydrogen bonding influence
seems to be reduced. A comparison of melting point of these
salts (Table 3) shows that 5 melts at higher temperature than
phenanthridine and maleic acid, whereas 6 melts at higher
temperature that phenanthridine but lower than oxalic acid.
Compound 7 crystallize as hydrate and DTA/TGA thermogram
indicates a loss of the weight (6.3%) that corresponds to the
theoretical mass of water (6.3%) in a monohydrate. Dehydration
of the compound occurs at 70 and 100 ꢀC, followed by melting of
the anhydrous form. The melting temperature of the anhydrous
the acids. The formation of OÀH N hydrogen bonds in
3 3 3
supramolecular complexes of N-heterocyclic bases and dicar-
boxylic acids is generally predictable, but weak CÀH
O
3 3 3
interactions may be affected by geometrical compatibility be-
tween base and acid molecules, depending on the dihedral angle
between the planes of the carboxylic group and the phenathridine
moiety. As a result of distortion between the carboxylic acid
group and pyridyl ring, the crystal structures of the neutral
cocrystals exhibited a noncyclic dimer motif but not an R22(7)
ring motif. An ionic R22(7) heterosynthon is observed in phenan-
thridinium maleate, whereas phenanthridine salts such as the
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Crystal Growth & Design
ARTICLE
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the acid.
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studied neutral cocrystals is an approximate guide for predicting
melting points. In the studied neutral cocrystals using the
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’ ASSOCIATED CONTENT
S
Supporting Information. DTA/TGA data and X-ray
b
crystallographic information files (CIF) are available. The crystal
structures in this paper have been deposited at the Cambridge
Crystallographic Data Centre with deposition numbers CCDC
816162 (1), 816163 (2), 791362 (3), 816166 (4), 791363 (5),
816165 (6), and 816164 (7). This material is available free of
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: veidis@lu.lv.
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