Isostructural polymorphs: Qualitative insights from energy frameworks

Article abstract of DOI:10.1039/c6ce01501h

Three isostructural polymorphs with two-dimensional and three-dimensional similarities are demonstrated quantitatively from similarity relationship analysis. The similarity dimensions are then visualized and correlated in a novel way via qualitative analy

Full text of DOI:10.1039/c6ce01501h

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Journal Name
ARTICLE
Isostructural Polymorphs: Qualitative Insights from Energy
Frameworks
Kunal Kumar Jha,a Sanjay Dutta,a Vijay Kumarb and Parthapratim Munshi*a
Received 00th January 20xx,
Accepted 00th January 20xx
Three isostructural polymorphs with two dimensional and three dimensional similarities are demonstrated quantitatively
from similarity relationship analysis. The similarity dimensions are then visualized and correlated in a novel way via
qualitative analysis using ‘energy frameworks’. Two of the three polymorphs with three dimensional similarities exhibiting
alike physical properties are having almost equi-energetic crystal structures while the most stable third polymorph exhibits
distinct properties. Thereby structure-property correlations are derived, both quantitatively and qualitatively.
DOI: 10.1039/x0xx00000x
www.rsc.org/
similarity among crystal structures and polymorphs. While the
former can be identified from molecular packing analysis, the
latter approach helps quantifying the similarity relationship
Introduction
Isostructurality and polymorphism, despite being two
contradictory phenomena, exist together in crystal structures.
While the occurrence of similar crystal structures of different
compounds refers to isostructurality,1 the phenomena of
existence of at least two different crystal structures of a same
compound refers to polymorphism.2 Recently, Bernstein and
his co-workers have reviewed the history of polymorphism
phenomena and its facts and concluded upon systematic
screening that the occurrence of polymorphs in molecular
crystals is frequent.3 Based on their database analysis and also
experiments Fabian and Kalman have demonstrated the
existence of isostructural polymorphs in molecular crystals and
their similarity dimensions.4 While one- and two-dimensional
(1D and 2D, respectively) isostructurality4c in polymorphic
systems has been discovered in several occasions,5 three-
dimensional (3D) similarities among polymorphs are rare.6
Occasionally identifying very similar yet different structures as
polymorphs might become difficult. In the context of
borderline cases of similarity and dissimilarity in polymorphic
structures, Desiraju questioned “when it is a matter of
chemical common sense or quantitative crystallographic
indicators, which criterion prevails?”7 Both, concept of
between crystal structures. Energetics of polymorphs and
especially of the isostructural ones are often nearly equal and
characterizations of such structures warrants careful
investigation.10 While quantification of intermolecular
interaction energies using Gavezzotti’s PIXEL method11 is quite
popular, Spackman has recently introduced the concept of
‘energy frameworks’12 – a novel graphical representation of
the magnitude of interaction energies. ‘Energy frameworks’,
which provides qualitative picture of 3D-topology of the
predominant interactions in molecular crystals, pertains to the
various properties of crystals as well.
In this paper we present three polymorphs of (Z)-3-(3,4-
dimethoxyphenyl)-2-(4-nitrophenyl)acrylonitrile (Scheme I),
here after called m-MeO-CMONS
 the meta-methoxy
derivative of CMONS;13 a well-known NLO material,14 which
also exists in polymorphic forms. Moreover, CMONS and its
derivatives, similar to the one studied here, are known to
serve as anti-cancer and anti-microbial agents.15 In the present
study, crystallization of freshly synthesized m-MeO-CMONS
(See ESI) from its slow evaporation in various solvents often
resulted in the original form (P1)
16 and on some occasions two
more new forms (P2 and P3) were discovered (Table S1, ESI).
Interestingly, all three crystal forms exhibit distinct cell
parameters belonging to the space group P1 with two
“supramolecular
arrangements of intermolecular interactions in crystals and
“supramolecular which implies spatial
construct”,9
synthon”,8
which
implies
spatial
crystallographically independent molecules in the asymmetric
unit, Z’ = 2 (Table 1 and Fig. 1). This scenario is extremely rare
and to the best of our knowledge there are only two more
such cases reported in the Cambridge Structural Database;17
Ref codes: MELFIT03/04/06 and SOBPEE/01/02. The former
one, aripiprazole drug, exists in nine polymorphic forms and is
the most polymorphic drug published to date. m-MeO-CMONS
being the third one in this series and having biological
importance of its analogs we have performed thorough
arrangement of molecules in crystals, are used to identify the
a.Chemical and Biological Crystallography Laboratory, Department of Chemistry,
School of Natural Science, Shiv Nadar University, Tehsil Dadri, Uttar Pradesh-
201314, India. E-mail: parthapratim.munshi@snu.edu.in
b.Department of Chemistry, Central University of Gujarat, Gandhinagar, Gujarat-
382030
† Electronic Supplementary Information (ESI) available: Details of experimental
and computational methods, Characterization techniques: single-crystal and
powder X-ray diffraction, DSC, HSM, energy calculations. CCDC 1456630, CCDC
1456631 and CCDC 1456632. See DOI: 10.1039/x0xx00000x
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characterizations of its polymorphs and correlated their Crystallography
View Article Online
DOI: 10.1039/C6CE01501H
properties with their respective structures, in a novel way.
Single crystal X-ray diffraction data were collected using D8
Venture
I
S
microfocus dual sources Bruker APEX3
N
diffractometer equipped with PHOTON 100 CMOS detector
and Oxford cryogenic system. Monochromatic Mo Kα radiation
(λ=0.71073 Å) was used for the data collection using phi (ϕ)
and omega (ω) scan strategy. All three data sets were collected
at 100(2) K using exposure time per frame of 7s for P1, 17s for
P2 and 4s for P3 and keeping the crystal to detector distance
at 40mm. The cell measurement, data collection, integration,
scaling and absorption correction was done using APEX3
software.18 The data was processed using SAINT19 and an
absorption correction was applied using SADABS20 integrated
in APEX3. The structure was solved using SHELX21 program and
refined using XSHELL program, both implemented in APEX3.
Same strategy was adopted for solution and refinement of all
three forms. The non-H atoms were located in successive
difference Fourier syntheses and refined with anisotropic
thermal parameters. All the hydrogen atoms were placed at
calculated positions and refined using a riding model with
appropriate HFIX commands. The program Mercury22 was used
for molecular packing analysis. The detailed crystallographic
data has been summarized in Table 1.
MeO
C
NO2
MeO
Scheme
I:
Chemical
diagram
of
(Z)-3-(3,4-dimethoxyphenyl)-2-(4-
nitrophenyl)acrylonitrile
Experimental Section
Synthesis
m-MeO-CMONS
[(Z)-3-(3,4-dimethoxy
phenyl)-2-(4-
nitrophenyl)acrylonitrile] was synthesized by condensation of
4-nitrophenylacetonitrile and 3,4-dimethoxybenzaldehyde in
ethanol at 70°C for three hours in the presence of piperidine as
basic catalyst as reported earlier (Scheme S1).16
Characterizations
Infrared spectra (FT-IR) of the solid samples were recorded on
a Thermo Scientific Nicolet iS5 spectrophotometer equipped
with iD5-ATR accessory, in the range of 4000 – 400 cm-1.
Samples were prepared by crushing the respective crystal
forms. 1 mg of sample was used to perform the experiment
after taking into account of the background due to air media.
1H NMR spectroscopy study was carried out using Bruker
AVHDN 400 spectrometer. UV-Vis experiment was performed
using Thermo Scientific Evolution 201 spectrophotometer.
Samples were prepared by dissolving 1 mg of respective
crystals in 10 ml of ethyl acetate. The clear solutions obtained
were tested by UV-Vis spectroscopy. Powder X-ray diffraction
Table 1 Single crystal X-ray diffraction data and the refinement parameters
Polymorphs
Formula
P116
P2
P3
C17 H14 N2 O4
C17 H14 N2 O4
C17 H14 N2 O4
Crystal size (mm)
0.089 x 0.177
x 0.183
0.052 x 0.151
x 0.218
0.102 x 0.260
x 0.397
Formula weight
Space group
a(Å)
310.30
310.30
310.30
P1
P1
P1
10.2321(4)
11.9576(5)
12.2700(5)
91.0010(10)
99.5610(10)
100.1880(10)
1455.36(10)
4; 2
8.6636(4)
11.9452(6)
14.3305(7)
100.527(2)
90.917(2)
95.640(2)
1450.15(12)
4; 2
7.6956(2)
12.3234(4)
15.6647(5)
82.0790(10)
86.3800(10)
84.4590(10)
1462.66(8)
4; 2
b(Å)
c(Å)
(PXRD) patterns were recorded on a Rigaku Ultima IV α(°)
diffractometer using Cu Kα radiation. The powder samples
were prepared after grinding the respective polymorphic
crystal forms. Differential scanning calorimetry (DSC)
measurements on all three polymorphic crystals and also on
bulk sample were carried out using Mettler Toledo DSC1
model under nitrogen gas (40 ml/min) atmosphere. Hot stage
microscopy (HSM) studies on three crystal forms were carried
out using Leica polarizing microscope MZ75 equipped with
heating stage P350. Leica IM 50 software was used for image
grabbing and monitoring the sample temperatures.
β(°)
γ(°)
Volume (Å3)
Z; Z’
Density (g cm-3)
F(000)
1.416
1.421
1.409
648
648
648
 (mm-1)
Tmin ; Tmax
R(merge)
0.103
0.103
0.102
0.913, 0.959
0.0428
0.884, 0.986
0.0575
0.923, 0.973
0.0518
Measured reflections 28719
38022
42858
Crystallization
Unique reflections
5536
5517
5556
A range of HPLC grade solvents and their combinations at
room temperature (22-25°C) and low temperature (3-6°C)
were used for the crystallization of m-MeO-CMONS via slow
evaporation method. The solvents, crystallization conditions
and the outcome of the crystallization experiments are listed
in Table S1. The crystal morphologies as captured using
Olympus SZX10 Polarized Microscope equipped with digital
camera are shown in Fig. S4.
No. of parameters
420
420
420
R(F2)
0.0405
0.0942
1.038
0.28
0.0628
0.1390
1.106
0.62
0.0457
0.1047
1.053
0.48
Rw(F2)
S
Δρmax (e Å-3)
Δρmin (e Å-3)
-0.21
-0.270
-0.24
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Crystal14 calculation
Computational Section
Hirshfeld surface analysis
View Article Online
Crystal14 program27 was used to calculatDeOlaI:t1t0ic.1e03e9n/Cer6gCyE0a1t50th1He
B97D/6-31G** level of theory and using crystal geometries
after setting the HB distances to 1.083Å, as used above. Same
scale factor of 1.0 as used for the calculations using
CrystalExplorer is also used here. The dispersion factor was
taken into account by inserting GRIMME keyword in the third
block of input file, calculates a London-type pairwise empirical
correction to the energy as proposed by Grimme.28 The lattice
energies were then calculated based on the following
expression.
The package CrystalExplorer 3.123 was used to perform the
Hirshfeld surface analysis on each of the symmetry
independent molecules of all three forms. The analysis was
carried out based on their respective crystal geometries. The
corresponding 2D fingerprint plots were also generated using
CrystalExplorer 3.1.
XPac analysis
Elatt = Ecryst/Z
 Emol
The similarity relationship among the polymorphs and their
dimension of similarity was analysed using the XPac 2.0
Where Ecryst is the energy of the crystal, Z is the number of
molecules in the unit cell and Emol is the energy of a single
molecule in the lattice.
The energy term Ecryst was calculated based on the periodic
calculation on the crystal lattice and the term Emol was
obtained by performing calculation on two molecules
extracted from the crystal lattice, as here in all three cases
there are two molecules in the asymmetric unit.
program.9 The crystal geometries of form P1
, P2 and P3, as
obtained from single-crystal X-ray diffraction experiment were
used for this purpose. Structure fragments were defined based
on the best figure of merit and lowest filter.
Interaction energy calculation
CrystalExplorer 3.1 was used to evaluate the interaction
energies of all three polymorphs. The energy components
calculated within this procedure are electrostatic, polarization,
dispersion and exchange-repulsion and finally the total
interaction energy. These energy calculations are performed at
the B97D3/6-31G(d,p) level of theory and using crystal
geometries of the respective forms. All the hydrogen bond
(HB) distances were set to the default value of 1.083Å. The
scale factor was also set to the default value of 1.0.24 The
detailed computational procedure of these calculations has
been discussed in ESI. Interaction energies were also
calculated for all three polymorphs using the UNI force field.25
Results and Discussion
Systematic crystallization experiment using various solvents
resulted in two new polymorphic forms of compound m-MeO-
CMONS (Table S1). The best diffraction quality crystals of form
P1 was grown from 1,4-dioxane at low temperature (40C).
While both the forms P2 and P3 were grown from toluene, P2
was achieved from crystallization at room temperature (RT)
but P3 at low temperature. Interestingly, crystal of from P2
was achieved only from the crystallization using toluene at RT.
However, all three polymorphic crystal forms are reproducible
from the respective crystallization conditions as tabulated in
Table S1. In most of the cases, at room temperature, crystals
appeared overnight. However, for low temperature crystals
were obtained in about 2-3 days.
Energy frameworks analysis
Energy frameworks for all three polymorphs have been
constructed based on the interaction energies as discussed
above and the frameworks were visualized using the
CrystalExplorer 3.1. The tube size (scale factor) used in all the
energy frameworks was 10 and the energy threshold (cut off)
value was set to zero.
X-ray diffraction experiments carried out on the best
quality crystals revealed that all three crystal forms belonging
to the space group P1 exhibit Z’ = 2 (Table 1). The structure
has a stilbene like core with cyano (-CN) substitution on C=C
bond having two phenyl ring at the two ends. One of the
phenyl rings has acceptor nitro group (-NO2) while the second
phenyl ring has two donor methoxy groups (-MeO) at the meta
and para position (Scheme I). The orientation of the two
symmetry independent molecules in the asymmetric unit of
the three forms represented with orange and green colour
Lattice energy calculations
The following two approaches were considered for the
calculation of lattice energies of all three polymorphs.
PIXEL calculation
The intermolecular interaction energies in the crystal lattices
were estimated by using PIXEL (version November 2015)
program.11 The molecular electron density required for this
calculations were obtained by using Gaussian0926 upon
generating the input from PIXEL. The electron density
calculations were performed at MP2/6-31G** level of theory
and using their crystal geometries after setting the HB
distances to 1.083Å, as used in CrystalExplorer. The densities
were then used in PIXEL program to calculate the four energy
terms; Coulomb, polarization, dispersion and repulsion.
Thereby the lattice energies of each form were calculated.
codes for molecules
A
and
B, respectively, is depicted in Fig. 1.
In each form the molecules
A
and are aligned anti-parallel to
B
each other forming a dimer via C-H…N interactions of varying
geometry (Table 2). Overlay diagrams of the polymorphs
suggest that the orientation of molecules
distinct from those in forms P2 but almost identical with P3
Distinct orientation of molecules and was also noticed
between the forms P2 and P3 (Fig. S6, ESI). In all three forms
the molecules and in the asymmetric unit exhibit similar
A and B in form P1 is
.
A
B
A
B
conformations. Almost indistinguishable overlay diagram of
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molecules
A and B
(Fig. S7, ESI), the marginal variations in Weak C(sp2)-H···π and H···H interactions are alsoViceownAtrtricibleuOtnilninge
torsion angles about the central C=C bond and the negligible to the stability of the crystal structurDeO. I:31D0.10st3r9u/Cct6uCrEe0s150a1rHe
angle between the overlaying planes (Table S2) clearly justify further stabilized by the π···π interactions between the layers
their conformational similarity.
Distinct molecular arrangements are noticed across the and C-H···
unit cells of the three polymorphic forms (Fig. 2). However, the and among themselves are remarkably similar for the forms
orientation of molecules in form P2 can somewhat be achieved P1 and P3 (Fig. 4). A slightly different interaction picture is
(Fig. S9). Moreover, the 2D layers formed via C-H···N, C-H···
O

interactions between the molecule and molecule
A
B
by applying 2-fold rotational symmetry along b-axis to the noticed in form P2
molecules in form P3. Remarkably, almost identical undulating
.
Table 2: Interaction geometry of C-H…N dimer
and layered molecular packing pattern is noticed across all
three forms while viewed down the particular planes (Fig. 3).
These similar packing patterns indicate that these polymorphs
are isostructural. The presence of acceptor O-atoms in the
nitro and methoxy groups and N-atom in cyano group along
with the weak C(sp2)-H donors forming weak intermolecular
interaction directs the monolayer packing in all three forms.
Forms
Distance (Å)
H2···N2A N2···H2A
Angle (°)
C2-H2…N2A
C2A-H2A…N2
P1
P2
P3
2.693
2.696
2.667
2.457
2.508
2.533
126.36
126.78
123.04
132.50
136.40
129.37
Fig 1 Ellipsoid plots of two symmetry independent molecules in the asymmetric unit drawn at 50% probability level for all three forms. H-atoms are drawn as fixed size spheres.
Colour codes for different atom types as shown in form P1 are same for forms P2 and P3.
Fig. 2 Molecular packing in the unit cell of three forms viewed down the c-axis. The a-axis and b-axis is shown in red and green colors, respectively.
Fig. 3 Similarities in molecular packing diagram across the three polymorphs. Viewed down the (-1 1 0) for P1 and (-1 0 1) for P2 and P3.
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View Article Online
DOI: 10.1039/C6CE01501H
Fig. 4 Monolayer interaction motifs of forms P1, P2 and P3.
Fig. 4 Monolayer interaction motifs of forms P1, P2 and P3 showing the absence (X) and presence () of intermolecular contacts
Fig 5 dnorm mapped on Hirshfeld surfaces of two independent molecules in the asymmetric unit of the three polymorphic forms
Further, in order to visualize and quantify the similarities polymorphic forms are quantified via fingerprint plots30 (Fig.
and differences in intermolecular contacts across three S10, ESI) as generated from Hirshfeld surface analysis and the
polymorphs, we performed Hirshfeld surface analysis29 based resulting histogram is depicted in Fig. 6. Hirshfeld surfaces and
on their crystal geometries. The analysis was done individually the associated fingerprint plots together help quantifying
for the molecules
each form. The contact points as highlighted in the Hirshfeld are noticed for molecule
surface of molecule of each form clearly display the similarity triangle in the fingerprint plot (Fig. S10
of intermolecular interactions generated by molecule of all variations in fingerprint plots for all the six molecules highlight
three polymorphic forms (Fig. 5). Such similarities are also the differences in the crystal environment across the three
evident in the case of molecule of forms P2 and P3, whereas polymorphic forms. The comparison as depicted in Fig. 6
A
and
B
present in the asymmetric unit of intermolecular contacts, conveniently. Shortest O···H contacts
of form P1, labelled with purple
ESI). The subtle
A
B
,
B
A
that of form P1 exhibited slightly different intermolecular reveals that for all the six molecules O···H hydrogen bonding
contacts. However, in each case the variation of strength of and H···H interactions together are associated with nearly 58%
intermolecular interactions can be gauged from the changes in of the surface area. Moreover, the histogram reflects the
area of the red surfaces at the respective contact regions. striking similarities of percentage contributions to the
Further, the similarities/dissimilarities of intermolecular Hirshfeld surface area for the various close intermolecular
contacts in different molecular environment of the three contacts of molecule
B
of all three forms and also for molecule
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A
of the forms P2 and P3, with slight variation of O···H
View Article Online
DOI: 10.1039/C6CE01501H
contacts (27% vs 30%) for P1A.
Fig. 6 Percentage contributions to the Hirshfeld surface area for the various close
intermolecular contacts in molecules A and B of the three polymorphic forms.
Table 2 Comparison of the categorization of the degree of isostructurality among the
three polymorphic forms, obtained using XPac analysis.
Polymorphs
Dimensionality
P1 vs P2
2D
P1 vs P3
2D
P2 vs P3
3D
Dissimilarity Index (X)
Stretch Parameter (D)
a (angles, deg)
p (planes, deg)
7.3
0.15
2.0
3.8
0.04
0.8
7.6
0.27
2.8
Fig 7 Energy frameworks corresponding to the total interaction energy in all three
polymorphs with 10 energy scale factor and zero energy threshold. The figures are on
the same spatial scale
6.9
3.7
6.9
Further, XPac9 analysis was performed to quantify the
similarity relationship among these three polymorphic crystal
structures. While such similarities are traditionally interpreted
for whole 3D structures, it is also extended for 2D molecular
layers of the crystal structures.6 The results from XPac analysis
are listed in Table 2. The relevant plots from XPac analysis as
obtained from the program are given in ESI. The values of the
different parameters obtained by comparison among three
polymorphs are well within the isostructurality limits as
discussed by Coles et al. The comparison clearly suggests that
form P1 is two dimensionally similar to the forms P2 and P3
and the highest degree of isostructurality is noticed between
the forms P1 and P3. This supports the striking similarity of the
interaction motifs between the forms P1 and P3 when
examined in a layer, as discussed above (Fig. 4). Further, the
XPac analysis reveals that there is a 3D similarity between the
polymorphs P2 and P3, which has also been realized from the
comparison of structural conformations, 3D molecular packing
and intermolecular contact analysis, demonstrated above. Fig. 8 Energy frameworks corresponding to the different energy components and total
interaction energy in P1, P2 and P3
Although such analysis provides a quantitative measure of the
similarities among the crystal structures it fails to deliver a
similar (Fig. 7). However, a slight variation in the dimension of
the pillars, crossbars and columns between the forms P2 and
P3 is noticed. In the case of form P1, the views down the b-axis
and c-axis look similar to the views down the a-axis and b-axis
of forms P2 and P3, respectively. However, form P1 is found to
show less similarity with forms P2 and P3, along the third
direction. Energy frameworks of form P1 appeared to have
slightly higher degree of similarity with that of form P3 than
form P2. Similarity in electrostatic and dispersion energy-
frameworks, with dispersion energy being the dominating
term, was also noticed among all three polymorphs (Fig. 8,
qualitative picture.
Furthermore, the actuality of isostructurality among these
polymorphic forms is qualitatively validated in a novel way via
‘energy frameworks’,12 constructed using CrystalExplorer.23
The values of interaction energy calculated between the
molecular pairs in each crystal form (Table S3 – S5, ESI) are
used to frame the 3D-topology of major interactions and
thereby the energy frameworks are constructed. A systematic
comparison of the total energy frameworks across three
isostructural polymorphs reveals that forms P2 and P3 are
remarkably similar and that of form P1 is also somewhat
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Figs. S14 – S16, ESI). Indeed, these qualitative pictures of respective peak maximum. The needle shaped crystals
View Article Online
DOI: 10.1039/C6CE01501H
the appeared between 165°C - 185°C for each of the crystal forms
energy
frameworks
strongly
correlate
with
dimensionalities and dissimilarity indices as estimated from as seen in the HSM images are further examined under the X-
XPac analysis (Table 2). Striking similarities of energy- ray. The cell check experiment revealed that this is yet another
frameworks are also noticed in the case of 3D isostructural crystal form with new cell parameters and belongs to once
polymorphs of 3-chloromandelic acid6 (Fig. S17 – S19, ESI) and again in triclinic crystal system.33 Unfortunately, the structure
rather surprisingly, in the case of so-called ‘quasi-isostructural of this new form couldn’t be solved as these crystals diffracted
polymorphs’.31
poorly even at low temperature and using Microfocus X-ray
The molecular pair-wise interaction energies calculated for sources (Mo and Cu). Form P1 is seen to form glassy
the construction of energy frameworks are used to evaluate (amorphous) materials during cooling at around 140°C, which
the net interaction energies in each form. A shell of nearest corresponds to the glass transition peak in DSC at around
neighbouring molecules around each symmetry independent 105°C - 125°C. Forms P2 and P3 are found to behave similarly
molecule, termed residue, is considered for this calculation during the cooling cycle. A semi opaque material is noticed at
(Figs. S11 – S13, ESI). The average neighbouring-shell net around 90°C for form P2, which seems to be corresponding to
interaction energy values (Table S6) for form P1, P2 and P3 are the exothermic peak at around 132°C in the DSC trace and at
-230.6 kJ mol-1, -221.6 kJ mol-1 and -225.4 kJ mol-1, around 80°C for form P3, which seems to be corresponding to
respectively. A similar trend is noticed when energies for the the exothermic peak at around 123°C in the DSC trace. The
intermolecular potential were calculated using the UNI force thermal stabilities of the polymorphs as investigated via DSC
field (Table S7).25 Not surprisingly, the interaction energy and HSM measurements once again suggested that form P1 is
values of these isostructural polymorphs are fairly comparable. slightly different from the 3D isostructural forms P2 and P3
The computation of packing energies25 provided the values of - The slight higher melting point for forms P2 and P3 may be
179.7 kJ mol-1, -178.0 kJ mol-1 and -175.8 kJ mol-1 for forms P1
due to the existence of some stronger pillars (greater
P2 and P3 respectively. Likewise, the lattice energies intermolecular forces) in their energy frameworks than in P1
.
,
,
calculated using PIXEL code32 indicates (Table S8) that form P1 (Figs. 7 & 8).
is the most stable form (-147.3 kJ mol-1) followed by form P2 (-
143.6 kJ mol-1) and form P3 (-143.0 kJ mol-1). Lattice energies
calculated using Crystal1427 program (Table S9) also show a
similar trend; -231.3 kJ mol-1 for P1, -229.1 kJ mol-1 for P2 and -
228.3 kJ mol-1 for P3. Interestingly, the 3D isostructural
polymorphs P2 and P3 are almost equi-energetic and the form
P1, which has 2D similarity with the former forms, appear to
be the energetically most stable form. Therefore, form P1
appears in almost all of the crystallization attempts than the
other forms.
For all three polymorphic forms and also the bulk sample,
the phase and enthalpy changes were monitored via DSC. The
samples were heated at 2°C/min from 25°C to 250°C and
cooled back to 30°C and the cycle repeated again for a second
time. The phase and enthalpy changes occurred in the two
successive heating cycles have been tabulated in Table S10.
The bulk sample as well as all three forms showed similar
trend of phase transitions (Fig. 9). In the first heating cycle,
two phase changes appeared in all the samples; one small
Fig. 9 Traces of DSC for the bulk sample and polymorphs P1, P2 and P3.
exothermic hump and another endothermic melting peak.
While cooling, a single sharp exothermic peak is noticed except
for form P1, in which a broad peak is noticed and so is the case
during second cooling. In the second heating cycle, three
phase changes are noticed; one exothermic peak and two
endothermic peaks. DSC trace of bulk sample looked similar to
that of forms P2 and P3. Further, these phase changes are
visualized via HSM (Fig. S20). In all three forms a crystalline
new phase appeared at around 165°C - 185°C, which may
correspond to the exothermic peak appeared in the DSC traces
around 152°C - 156°C, and finally melted at around 208°C -
220°C. Similar trend in melting point is noticed in their DSC
traces; form P1 has slightly lower melting point (178.10C) than
forms P2 (179.50C) and P3 (179.40C), as recorded from the
The polymorphs were further characterized using PXRD.
The scan rate used for these measurements is 1°/min with
0.02° step in 2. The experimental PXRD patterns of forms P1,
P2 and P3 recorded at room temperature were then compared
with their corresponding simulated PXRD patterns generated
from the respective single-crystal structures of forms P1, P2
and P3 (Fig. 10) also determined at room temperature.34 The
comparison displaying reasonably good agreement between
the observed and predicted patterns justifies the phase purity
of the polymorphic forms. However, for form P2, at around 15°
in 2, the predicted pattern shows two peaks whereas the
observed pattern shows only one peak, which seems to be the
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average of the two predicted peaks. The similar marginal shifts
and discrepancies between the simulated and observed PXRD
pattern are also noticed in a recent study on ‘quasi-
isostructural polymorphs’.31 Observed PXRD patterns of the
three forms are also compared (Figure S20) to highlight the
subtle differences of the phases of these isostructural
polymorphic forms. While variable temperature PXRD studies
on these polymorphs could be useful to probe the effects of
heating and cooling and to check for any thermally-induced
phase transitions the quantitative DSC traces and the
qualitative HSM images as highlighted above certainly serve
these purposes.
Acknowledgment
View Article Online
We thank Shiv Nadar University foDr OIr:e1s0e.1a0r3c9h/C6fCaEc0il1i5t0ie1sH,
infrastructure and funding and also research fellowship to KKJ
and SD. We are grateful to Prof. Rupamanjari Ghosh for her
kind encouragements and supports. Thanks to Prof. M. A.
Spackman and Prof. D. Jayatilaka for the access to
CrystalExplorer (energy framework analysis). We thank Dr. R.
G. Gonnade for HSM images and Dr. A. Roychoudhury for
certain helps. We are thankful to one of the referees for
providing valuable suggestions to improve this manuscript.
Notes and references
1
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bulk sample
15 M. S. Alam, Y. Nam, D. Lee, Eur. J. Med. Chem., 2013, 69, 790.
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Madison, Wisconsin, USA, 2015.
Being isostructural polymorphs the FT-IR spectra of each
form exhibited identical features (Fig. S1, ESI). Also UV-Vis
spectra of all three polymorphic forms showing λmax value of
384.17 nm (Fig. S2, ESI) fall into the category of ‘yellow
material’,35 which find tremendous applications in dye
industries.36
19 Siemens, SMART system, Siemens Analytical X-ray Instruments Inc.
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20 G. M, Sheldrick , SADABS, Bruker AXS Inc, Madison, WI, 2007.
21 G. M, Sheldrick , Acta Cryst. 2008, A64, 112.
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In summary, unusual polymorphic forms of m-MeO-CMONS
with all three having Z’ = 2 and space group P1 are discovered
23 S. K. Wolff, D. J. Grimwood, J. J. McKinnon, D. Jayatilaka and M. A.
Spackman, Crystal Explorer; University of Western: Perth, Australia,
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to exist as isostructural. Systematic quantitative and
qualitative analyses based on the supramolecular constructs
and the energy frameworks, respectively, revealed their
degree of similarity and dimensions. Thereby structure-
property correlations were derived directly through the
graphical representation of the meaningful energy
frameworks. Similarity/dissimilarity of physical properties
among the polymorphs is well correlated with their respective
similarity dimensions. This novel way of studying polymorphs,
especially the tricky isostructural ones, may expand the scope
of research in crystal engineering and instigate pharmaceutical
industries to perform such analysis systematically yet rapidly.
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33 Cell parameters of the needle shaped crystals as obtained from HSM: a =
3.92 (15) Å, b = 19.10 (18) Å, c = 21. 04 (8) Å, = 71.5 (7)ᵒ, = 85.0 (2)ᵒ
and = 89.8 (2)ᵒ, , V= 1490.00(30) Å3.
34 Cell parameters using single-crystal X-ray diffraction data collected at
room temperature; P1: a = 10.3185 (5) Å, b = 12.0948 (6) Å, c = 12.4088
(6) Å, = 91.276 (2)ᵒ, = 99.834 (2)ᵒ, = 98.874 (2)ᵒ , V= 1505.72(13) Å3;
P2: a = 8.7385 (5) Å, b= 12.0819 (7) Å, c = 14.5627 (8) Å,


= 79.608 (3)ᵒ,
= 89.477 (3)ᵒ, = 83.819 (3) ᵒ, V= 1503.40(15) Å3; P3: a = 7.9476 (6) Å, b
= 12.3304 (8) Å, c = 15.7276 (11) Å,
 = 81.618 (3)ᵒ, = 85.114 (3)ᵒ, =
83.978 (3)ᵒ, V= 1512.55(18) Å3.
35 (a) J. Zyss, Conjugated Polymeric Materials: Opportunities in Electronics,
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(Eds.), Kluwer Academic Publishers, pp 545 – 557, 1990. (b) D. S. Chemla
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1, Academic Press Inc. 1987.
36 A. M. Asiri, Dyes and Pigments, 1999, 42, 209
.
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