Structural elucidation, Hirshfeld surface analysis and quantum mechanical study of para-nitro benzylidene methyl arjunolate

Article abstract of DOI:10.1016/j.molstruc.2011.06.003

A benzylidene derivative of arjunolic acid, namely, para-nitro benzylidene methyl arjunolate (3) have been synthesized and characterized by X-ray structural studies and the electronic structure was calculated at the DFT level with a detailed analysis of Hirshfeld surface and fingerprint plot facilitating a comparison of intermolecular interactions. The crystal packing of (3) exhibits intermolecular O-H...O and C-H...O hydrogen bonds forming linear chains propagating parallel to [1 0 0] and [0 1 0] directions, respectively, which are further linked through C-H...π (arene) bonds to generate two-dimensional framework. Investigation of intermolecular interactions and crystal packing via Hirshfeld surface analysis reveals that more than two-thirds of the close contacts are associated with weak interactions. Hirshfeld surface analysis for visually analyzing intermolecular interactions in crystal structures employing molecular surface contours and 2D fingerprint plots have been used to examine molecular shapes. The large HOMO-LUMO energy gap indicates a high kinetic stability for the title compound (3).

Full text of DOI:10.1016/j.molstruc.2011.06.003

Journal of Molecular Structure 1000 (2011) 120–126
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Structural elucidation, Hirshfeld surface analysis and quantum mechanical study
of para-nitro benzylidene methyl arjunolate
Saikat Kumar Seth a,b, Gopal Chandra Maity c, Tanusree Kar a,
⇑
a Department of Materials Science, Indian Association for the Cultivation of Science, Kolkata, West-Bengal 700 032, India
b Department of Physics, M.G. Mahavidyalaya, Bhupatinagar, Midnapore (East), West-Bengal 721 425, India
c Department of Chemistry, Abhedananda Mahavidyalaya, Sainthia, Birbhum, West-Bengal, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A benzylidene derivative of arjunolic acid, namely, para-nitro benzylidene methyl arjunolate (3) have
been synthesized and characterized by X-ray structural studies and the electronic structure was
calculated at the DFT level with a detailed analysis of Hirshfeld surface and fingerprint plot facilitating
Received 8 March 2011
Received in revised form 1 June 2011
Accepted 3 June 2011
a
comparison of intermolecular interactions. The crystal packing of (3) exhibits intermolecular
O–Hꢀ ꢀ ꢀO and C–Hꢀ ꢀ ꢀO hydrogen bonds forming linear chains propagating parallel to [1 0 0] and [0 1 0]
directions, respectively, which are further linked through C–Hꢀ ꢀ ꢀ (arene) bonds to generate two-dimen-
Available online 13 June 2011
p
Keywords:
sional framework. Investigation of intermolecular interactions and crystal packing via Hirshfeld surface
analysis reveals that more than two-thirds of the close contacts are associated with weak interactions.
Hirshfeld surface analysis for visually analyzing intermolecular interactions in crystal structures employ-
ing molecular surface contours and 2D fingerprint plots have been used to examine molecular shapes.
The large HOMO–LUMO energy gap indicates a high kinetic stability for the title compound (3).
Ó 2011 Elsevier B.V. All rights reserved.
Arjunolic acid derivative
Crystal structure
Hirshfeld surface
Fingerprint plot
DFT studies
HOMO–LUMO energies
1. Introduction
Molecular self-assembly through weak non-covalent forces is the
hallmark of biological systems. Among a number of non-covalent
Arjunolic acid, a terpenoid, is the major component of the
extracts of the heavy wood of Teminalia arjuna [1] in the form of
a colorless crystalline solid and belongs to the family of combreta-
ceae and is an important medicinal plant found in India [2,3].
Medicinal activities of arjunolic acid and other extraneous constit-
uents of T. arjuna have been reported [4,5]. Clinical investigation of
T. arjuna displayed the benefit in the treatment of coronary artery
disease, heart failures and it has also been found to have antibac-
terial and antimutagenic properties [6]. The extract of the plant
have antibacterial activity against periodontopathic bacteria [7].
Terminalia has also been prescribed as an antidysenteric antimi-
crobial agent and useful in the last phase of AIDS [8]. The arjunolic
acid having a rigid lypophilic backbone offers a great opportunity
for the construction of molecular receptors, supramolecular archi-
tectures, and functional nanomaterials [9].
forces such as hydrogen bonding [10], C–Hꢀ ꢀ ꢀ
p
[11] and
p
ꢀ ꢀ ꢀ
p
[12] interactions, hydrogen bonding and C–Hꢀ ꢀ ꢀ
p interactions have
been widely utilized in directing molecular self-assembly for the
construction of various supramolecular architectures.
Investigation of the structural stability of compounds by both
experimental techniques and theoretical methods is of great inter-
est. With the development of computational methods, theoretical
modeling of drug design, functional material design, has become
possible [13]. In recent years, density functional theory (DFT) has
been favourite in theoretical modeling. Literature search shows
that the DFT has a great accuracy in reproducing the experimental
values of in geometry, dipole moment, vibrational frequency, etc.
[14–18]. During our ongoing phytochemical investigations on this
plant, we have isolated the title derivative of arjunolic acid and to
investigate the molecular structure, the possibilities for intra- and
intermolecular hydrogen bonding in the solid state, the X-ray
structure analysis was undertaken along with the DFT calculations
to investigate the molecular geometry and electronic structure.
The novel chiral para-nitro benzylidene methyl arjunolate deriva-
tive (3) of arjunolic acid has the potential to be used as a structural
framework for molecular recognition in supramolecular chemistry.
An investigation of close intermolecular contacts between the
molecules via Hirshfeld surface analysis is also presented in order
to quantify the interactions within the crystal structure.
The properties of crystalline material strongly depend on how
the constituent components are organized with respect to one
another and a control over this organization directly provides a
handle over the functional properties of the material. Crystals are
assembled in spontaneous process called self-assembly that
proceeds through
a series of molecular recognition events.
⇑
Corresponding author. Tel./fax: +91 33 2473 2805.
E-mail address: mstk@iacs.res.in (T. Kar).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.06.003

S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
121
2.3. Crystallographic analysis
2. Experimental
Single crystal of compound (3) was obtained by slow evapora-
2.1. Materials and measurements
tion. Data collection was carried out at 150(2) K using a Bruker
APEX–II CCD diffractometer with MoK
a radiation (k = 0.71073 Å).
All chemicals were of analytical grade and used without further
purification. Elemental analyses (C, H and N) were performed on a
Perkin–Elmer 2400 elemental analyzer. IR spectrums were
recorded on a Perkin-Elmer L120-00 FT-IR spectrophotometer with
the sample prepared as a KBr pellet. All NMR spectra were recorded
at 300 K on a Bruker DRX-300 spectrometer operating at the fre-
quencies of 300.0 MHz (1H), 75.0 MHz (13C). The spectra were mea-
sured in CDCl3 solution and the sample concentrations ranged from
40 to 70 mg per 0.4 mL of solvent, in a 5 mm sample tube.
The structure of (3) was solved by direct methods (SHELXS 97)
[19] and refined by the full-matrix least-square technique on F2
(SHELXL97) [20]. All calculations were carried out using WinGX
system Ver-1.64 [21] and PLATON [22]. The hydroxyl hydrogen
position has been determined from difference Fourier map and
treated as riding whereas all other hydrogen atoms were placed
at their geometrically idealized positions. More details of crystal
data and relevant refinement parameters are given in Table 1.
2.4. Computational details
2.2. Preparation of para-nitro benzylidene methyl arjunolate
The isolated molecule DFT calculations were performed using
DMol3 code [23] in the framework of a generalized-gradient approx-
imation (GGA) [24]. The starting atomic coordinates were taken
from the final X-ray refinement cycle. The geometry of the mole-
cules was fully optimized using the hybrid exchange–correlation
Methyl arjunolate (0.5 g, 0.994 m mol) was taken in a dry R.B
flask (10 mL) and dissolved in dry benzene (6 mL). Then the reac-
tion mixture was successively treated with 4-nitro benzaldehyde
(0.183 g, 0.364 m mol), catalytic amount of perchloric acid
(0.04 mL, 70% solution) (Scheme 1). The reaction mixture was
stirred magnetically at room temperature for 2 h. Then the crude
product was diluted with chloroform (90 mL). The organic layer
was washed with 5% sodium bicarbonate (3 ꢁ 20 mL), brine
(3 ꢁ 20 mL) and finally dried over anhydrous sodium sulphate. Vol-
atiles were removed under reduced pressure to give a foamy mate-
rial. The crude product was purified by column chromatography
(Si-gel, 100–200 mesh) using 10% ethyl acetate/chloroform mixture
as an eluent to afford a foamy solid (0.0542 g) in 80% yield. The
product was then dissolved in propanol, heated at ꢂ50 °C for an
hour with continuous stirring. The solution was then cooled to
room temperature and left unperturbed for the slow evaporation
of the solvent. After 2 weeks, colorless needle-like single crystals
suitable for X-ray analysis were obtained. Analysis found: C,
71.80%; H, 8.45%; N, 2.21% Calculated for C38H53NO7: C, 71.78%;
H, 8.40%; N, 2.20%; m.p. 321 °C; MRMS (ESI): m/z calcd. 635.638
found 636. 6340 (M + H+). FTIR: mmax (cmꢃ1) 3590, 3518, 2945,
2864, 1713, 1606, 1521, 1458, 1434, 1386, 1344, 1263, 1205,
1170, 1120, 1081, 1027, 852, 748, 702, 671. 1H NMR (300 MHZ,
CDCl3) d: 8.26 (d, J = 5.1, 2H), 7.72 (d, J = 5.4, 2H), 5.63 (s, 1H),
5.32 (app. t, 1H), 3.95 (d, J = 7.2, 1H), 3.92 (d, J = 7.2, 1H), 3.65 (s,
3H), 3.5(d, J = 10.3, 1H), 3.33 (d, J = 10.0, 1H), 2.90 (dd, J1 = 13.9,
J2 = 3.9, 1H), 2.45 (s, 1H), 2.13–0.9 (m, 20H terpenoid proton),
1.23 (s, 3H), 1.18 (s, 3H), 1.09 (s, 3H), 0.96 (s, 3H), 0.94 (s, 3H),
0.75 (s, 3H). 13C NMR (75 MHZ, CDCl3) d: 178.3, 148.4, 144.7,
143.9, 127.6, 123.6, 101.1, 90.6, 79.0, 65.3, 51.5, 47.8, 46.8, 46.7,
46.0, 41.8, 41.3, 39.5, 38.2, 37.1, 34.0, 33.2, 32.5, 32.1, 30.8, 27.8,
26.1, 24.3, 23.7,23.4, 23.1, 21.3, 17.9, 17.8, 17.0, 14.5. Rf = 0.36
Table 1
Crystal data and structure refinement for the title compound.
Empirical formula
Formula weight
C38H53NO7
635.81
Temperature
150(2) K
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
Orthorhombic, P212121
a = 9.5259(7) Å
b = 17.5146(13) Å
c = 20.0556(15) Å
3346.1(4) Å3
Volume
Z, calculated density
Absorption coefficient
F(0 0 0)
4, 1.262 Mg/m3
0.086 mmꢃ1
1376
Crystal size
h range for data collection
Limiting indices
Reflections collected/unique
Completeness to h
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
0.19 ꢁ 0.16 ꢁ 0.14 mm
1.54–25.00°
ꢃ11 6 h 6 11, ꢃ20 6 k 6 20, ꢃ23 6 l 6 23
31539/5897 [R(int) = 0.0473]
100.0%
Semi-empirical from equivalents
0.98 and 0.98
Full-matrix least-squares on F2
5897/0/425
1.042
Final R indices [I > 2
R indices (all data)
Weighting scheme
r
(I)]
R1 = 0.0338, wR2 = 0.0848
R1 = 0.0379, wR2 = 0.0871
w = 1/{r
2(F2o ) + (0.0466P)2 + 0.3577P}
where P = (F2o + 2Fc2)/3
0.0(1)
Absolute structure parameter
Extinction coefficient
Largest diff. peak and hole
0.0031(5)
(60%
chloroform/
petroleum
ether);
[a
]
D
298 = +35.8868
0.25 and ꢃ0.14 e Åꢃ3
(c = 0.19 gm/100 ml, CHCl3).
2
Scheme 1. (i) CH2N2/ether, (ii) 4-nitrobenzaldehyde, 70% cat.HClO4, dry benzene.

122
S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
Table 2
functional BLYP [25,26] with a double numeric plus polarization
(DNP) basis set. The electronic structures were calculated at the
same level.
Selected bond lengths (Å), bond angles and torsion angles (°) determined by X-ray
diffraction and DFT calculations.
X-ray
DFT
MOGUL(mean)
Bond lengths
O(1)–C(7)
O(1)–C(10)
O(2)–C(7)
1.413(2)
1.432
1.459
1.432
1.455
1.582
1.598
1.560
1.580
1.629
1.548
1.343
1.548
1.565
1.560
1.572
1.42(1)
1.43(2)
1.41(1)
1.43(1)
1.56(1)
1.56(1)
1.54(1)
1.56(1)
1.58(1)
1.53(1)
1.33(2)
1.53(1)
1.54(1)
1.54(1)
1.54(1)
3. Results and discussion
1.440(2)
1.409(2)
1.443(2)
1.561(2)
1.575(2)
1.551(2)
1.564(2)
1.598(2)
1.538(2)
1.327(2)
1.537(2)
1.555(2)
1.540(2)
1.557(2)
3.1. Structural description
O(2)–C(8)
C(13)–C(14)
C(13)–C(18)
C(16)–C(17)
C(17)–C(18)
C(17)–C(22)
C(18)–C(19)
C(20)–C(21)
C(21)–C(22)
C(25)–C(26)
C(26)–C(27)
C(25)–C(30)
The molecular view [27] of (3) with atom numbering scheme is
shown in Fig. 1. The molecular moiety consists of six fused
six-membered rings A–F and one benzene rings P (Fig. 1). All the
fused rings have trans fusion except one cis fusion between ring
E and F. However, as one of the common atoms between rings D
and E is on a double bond, the arrangement between these two
rings actually indicates that the C(35) methyl group is trans to
the C(36) one. The hydroxyl group is in equatorial position, all
methyl groups on rings A–E are substituted axially. The C–O
bond-distances lying in the normal range are similar to those
found in the analogous structures [28,29]. Some of the bond
lengths in (3) are found to be longer than the normal values and
some angles are also widened due to steric overcrowding of axial
methyl groups. Moreover, the cis fusion between rings E and F
may be responsible for the unusually large C–C bond lengths
1.575(2) Å and 1.598(2) Å for C(13)–C(18) and C(17)–C(22),
respectively. However these values are comparable with the
corresponding values observed for molecules containing the arjun-
olic acid skeleton [30]. The bond-lengths and angles which have
large values compare to the corresponding values of the average
molecular skeleton are listed in Table 2. The bond-length/angles
agree well with the mean values of relevant bond distances
obtained with MOGUL [31] from searches based on related molec-
ular fragments run on the CSD [32]. The two methyl groups at atom
C28 are in almost antiperiplanar and gauche orientations with
respect to the C28–C29 bond [C33–C28–C29–C30 = ꢃ175.16(16)°
and C34–C28–C29–C30 = 65.3(2)°]. The extended conformations
of O = C–O–CH3 is established by the torsion angle ꢃ176.58(15)°.
The molecular moiety of ring P lies exactly in the same plane with
the substituted NO2 group. The atoms O6 and O7 have the largest
deviation in opposite direction [O(6): ꢃ0.1778(22) Å and O(7):
+0.17420(19) Å] from the least square mean plane through the
atoms of the phenyl ring. The H atom at C(26) and the COOCH3
group at C(25) are in b-positions. The non bonded distances
between C atoms of diaxial methyl groups C(36)ꢀ ꢀ ꢀC(37) and
C(37)ꢀ ꢀ ꢀC(38) are 3.226(3) and 3.213(4) Å, respectively.
Bond angles
C(7)–O(1)–C(10)
C(7)–O(2)–C(8)
108.62(13)
111.39(13)
113.12(13)
107.53(13)
114.72(12)
115.21(13)
116.29(13)
114.57(14)
110.36(13)
112.82(13)
115.35(13)
111.72(13)
112.41(14)
109.31(14)
111.34(14)
107.43(16)
114.34(15)
109.26
112.33
114.24
109.03
114.96
115.63
115.64
114.75
110.40
113.76
114.99
112.86
111.56
109.32
111.53
108.36
111.83
110(1)
110(1)
115(2)
111(1)
114(2)
116(1)
114(1)
113(2)
110(1)
113(1)
114(2)
112(1)
112(1)
110(1)
111(1)
109(1)
112(1)
C(9)–C(10)–C(11)
C(10)–C(11)–C(12)
C(11)–C(12)–C(13)
C(9)–C(14)–C(13)
C(9)–C(14)–C(15)
C(15)–C(16)–C(17)
C(16)–C(17)–C(22)
C(13)–C(18)–C(19)
C(22)–C(23)–C(24)
C(21)–C(26)–C(25)
C(21)–C(26)–C(27)
C(24)–C(25)–C(26)
C(24)–C(25)–C(30)
C(33)–C(28)–C(34)
O(5)–C(31)–C(25)
Torsion angles
C(33)–C(28)–C(29)–C(30)
C(34)–C(28)–C(29)–C(30)
C(25)–C(31)–O(5)–C(32)
O(4)–C(31)–O(5)–C(32)
C(24)–C(25)–C(26)–C(27)
ꢃ175.2(2)
65.3(2)
ꢃ173.06
67.31
–
–
ꢃ176.6(2)
175.12
ꢃ0.60
ꢃ176.58
5.91
–
5.9(2)
ꢃ76.0(2)
ꢃ77.29
two fused ring C and E assumes a distorted chair conformation,
with C14 and C24 atoms displaced from the corresponding ring
plane by ꢃ0.299(2) and ꢃ0.272(2) Å respectively. These conforma-
tional properties are very much similar to the arjunolic acid
skeleton [30].
The crystal packing in (3) is stabilized by a combination of inter-
Two fused six membered rings A and B of arjunolic acid skele-
ton are individually almost planar with small [10.47(5)°] dihedral
angle between them. Both the rings assumes a chair conformation,
the ring puckering parameters [33] are given in Table 3. Another
fused six member ring F of the steroid skeleton also adopts a chair
conformation. Ring D is in a slightly distorted sofa conformation
due to the flattening caused by the C20 = C21 double bond. The rest
molecular O–HꢀꢀꢀO, C–Hꢀ ꢀ ꢀO and C–Hꢀ ꢀ ꢀ
p (arene) hydrogen bonds
(Table 4). The hydroxyl oxygen atom O(3) in the molecule at
(x, y, z) acts as a donor to carbonyl oxygen atom O(4) in the mole-
cule at (ꢃ1/2 + x, 3/2 ꢃ y, 1 ꢃ z). Also the methyl carbon atom C(32)
of COOMe group in the molecule at (x, y, z) acting as donor to the
hydroxyl oxygen atom O(3) in the molecule at (1/2 + x, 3/2 ꢃ y,
Fig. 1. ORTEP view and atom numbering scheme of the title compound with displacement ellipsoid at the 30% probability.

S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
123
Table 3
Ring puckering parameters (Å, °) for (3).
Ring
q2
q3
QT
U2
h
Conformation
A(O1/C7/O2/C8/C9/C10)
B(C9–C14)
C(C13–C18)
D(C17–C22)
E(C21–C26)
0.032(1)
0.096(2)
0.138(2)
0.409(2)
0.153(2)
0.062(2)
ꢃ0.586(2)
ꢃ0.574(2)
ꢃ0.565(2)
0.347(2)
0.587(2)
0.582(2)
0.582(2)
0.536(2)
0.494(2)
0.545(2)
–
–
3.15(14)
Chair
Chair
Distorted chair
Distorted Sofa
Distorted chair
Chair
170.45(14)
166.23(18)
49.70(16)
161.99(20)
173.44(20)
ꢃ122.55(69)
8.89(22)
40.01(66)
–
ꢃ0.470(2)
F(C25–C30)
ꢃ0.542(2)
Table 4
Hydrogen bonding geometry of the title compound (Å, °).
D–Hꢀ ꢀ ꢀA
d(D–H)
(Hꢀ ꢀ ꢀA)
d(Dꢀ ꢀ ꢀA)
D–Hꢀ ꢀ ꢀA
Symmetry
O(3)–H(3)ꢀ ꢀ ꢀO(4)
0.82
0.97
0.96
0.93
2.14
2.56
2.55
2.98
2.875(2)
3.506(3)
3.360(2)
3.626
150.0
165.0
142.0
126.0
1/2 + x, 3/2 ꢃ y, 1 ꢃ z
ꢃx, 1/2 + y, 1/2 ꢃ z
1/2 + x, 3/2 ꢃ y, 1 ꢃ z
1/2 + x, 3/2 ꢃ y, 1 ꢃ z
C(8)–H(8A)ꢀ ꢀ ꢀO(7)
C(32)–H(32C)ꢀ ꢀ ꢀO(3)
C(34)–H34Cꢀ ꢀ ꢀCg(1)
Cg(1) is the centroid of the P[C(1)–C(6)] ring.
in the molecule at (ꢃx, 1/2 + y, 1/2 ꢃ z) to generate C(10) hydrogen
bonding motif [34] which is responsible for the formation of infi-
nite 1D chain propagating parallel to [0 1 0] direction (Fig. 3). In
(3), another substructure can also be visualized by considering
the C–Hꢀ ꢀ ꢀ
p (arene) hydrogen bonds where the carbon atoms
C(34) in the molecule at (x, y, z) acts as hydrogen bond donors to
phenyl ring P(C1–C6) in the molecule at (1/2 + x, 3/2 ꢃ y, 1 ꢃ z).
The [1 0 0] and [0 1 0] polymeric chains are further linked through
C–Hꢀ ꢀ ꢀ
p (arene) hydrogen bonds results in a two-dimensional
framework in (3).
3.2. Hirshfeld surface
Molecular Hirshfeld surface [35,36] in the crystal structure is
constructed basing on the electron distribution calculated as the
sum of spherical atom electron densities [37]. The normalized
contact distance (dnorm) based on both de, di and the vdw radii of
the atom, given by Eq. (1) enables identification of the regions of
particular importance to intermolecular interactions [35]. The
combination of de and di in the form of a 2D fingerprint plot [38]
provides summary of intermolecular contacts in the crystal [34].
The Hirshfeld surfaces and fingerprint plots presented here were
generated using CrystalExplorer 2.1 [39].
Fig. 2. The chain along [1 0 0] direction. Hydrogen atoms not involve in hydrogen
bonding has been omitted for the clarity.
1 ꢃ z), together with previous interaction generating secondary
level motif R22(7) [34] which leads to the formation of a one dimen-
sional chain propagating along [1 0 0] direction (Fig. 2). In another
substructure, C(8) atom acts as hydrogen bond donor to O(7) atom
v
dw
v
dw
di ꢃ ri
de ꢃ re
dnorm
¼
þ
ð1Þ
v
dw
vdw
re
ri
Fig. 3. The chain along [0 1 0] direction. Hydrogen atoms not involve in hydrogen bonding has been omitted for the clarity.

124
S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
Fig. 4. Hirshfeld surfaces mapped with (a) dnorm and (b) shape index of (3). The surfaces are shown as transparent to allow visualization of the orientation and conformation of
the functional groups in the molecules.
The Hirshfeld surfaces of (3) are illustrated in Fig. 4 showing
surfaces that have been mapped over dnorm (Fig. 4a) shape index
(Fig. 4b) and curvedness (Fig. S1) (Supplementary). The interaction
between hydroxyl oxygen O–H and hydroxyl and ring oxygen
atoms in (3) (Table 4) can be seen in the Hirshfeld surface as the
bright red areas in Fig. 4a (labeled as 1a). The light red spots are
due to C–Hꢀ ꢀ ꢀO interactions (Fig. 4a) (labeled as 1b and 1c; see
Table 4), and other visible spots on the surface correspond to
Hꢀ ꢀ ꢀH contacts. The Oꢀ ꢀ ꢀH/Hꢀ ꢀ ꢀO intermolecular interactions
appear as distinct spikes in the 2D fingerprint plot (Fig. 5).
Complementary regions are visible in the fingerprint plots where
one molecule act as donor (de > di) and the other as an acceptor
(de < di). The fingerprint plots can be decomposed to highlight par-
ticular atoms pair close contacts [38a]. In (3), there are two sharp
spikes pointing toward the lower left of the plots and are typical
O–Hꢀ ꢀ ꢀO hydrogen bonds. The shortest contact i.e., the minimum
value of (de + di) is around 1.9Å point out the importance of these
interactions. The proportion of Oꢀ ꢀ ꢀH/Hꢀ ꢀ ꢀO interactions compris-
ing 25.1% of the total Hirshfed surfaces for each molecule of (3).
The points in the (di, de) regions of (1.70 Å, 1.18 Å) and (1.18 Å,
1.70 Å) in the fingerprint plots are due to C–Hꢀ ꢀ ꢀO interactions
(Fig. 5). At the top left and bottom right of the fingerprint plot,
there are characteristic ‘‘wings’’ which are identified as a result
is more easily understood using Hirshfeld surface, with the results
further highlighting the power of the technique in mapping out the
interactions.
3.3. Geometry and electronic structure
A superposition of the molecular conformations of (3) as estab-
lished by the quantum mechanical calculations and X-ray studies
show an excellent agreement (Fig. 6a). The largest deviation of
the geometrically optimized bond-lengths/angles from the
corresponding experimental values is 0.04 Å for C–O and 2.51°
for O–C–C for the title compound (3) (Table 2). The small
differences between the calculated and observed geometrical
parameters can be attributed to the fact that the theoretical calcu-
lations were carried out with isolated molecules in the gaseous
phase whereas the experimental values were based on molecules
in the crystalline state. The Mulliken atomic charges were calcu-
lated at BLYP level and illustrated in Table S1 (Supplementary).
Atomic charge analysis revealed that charge distributions of fused
ring oxygen atoms and hydroxyl oxygen atom are more negative
than the oxygen atoms of NO2 and ester group. In O3–H3ꢀ ꢀ ꢀO4
hydrogen bond, the charge distributions of O3, H3, and O4 are
ꢃ0.498, 0.252 and -0.441 respectively. In addition, the atomic
charge analysis shows that hydroxyl oxygen atoms behave as
strong donor and also carbonyl oxygen atoms behaves as acceptor.
For understanding electrophilic attack sites and nucleophilic
reactions sites, molecular electrostatic potential (MEP) is very
useful [40–42]. MEP was calculated at the BLYP level and is shown
in Fig. 6b. The red regions and green regions of MEP represent the
net negative and positive charges respectively (Fig. 6b). The red
regions are chiefly over the hydroxyl and nitro oxygen atoms. As
can be seen in Table S1 (Supplementary), hydroxyl oxygen atom
is more negative than the carbonyl oxygen atom. Therefore, the
atomic charge analysis and MEP map confirmed that hydroxyl
oxygen atom is preferred site for electrophilic attack. The total
electronic charge density isosurface of (3) is depicted in Fig. 6c
showing equal distribution of density over the molecular moiety.
of C–Hꢀ ꢀ ꢀ
p interactions [37,38a]. The wings at the top left (di < de)
corresponds to points on the surface around the C–H donor,
whereas that at the bottom right (de > di) corresponds to the sur-
face around the
p acceptor. The decomposition of the fingerprint
plot shows that Cꢀ ꢀ ꢀH/Hꢀ ꢀ ꢀC contacts comprise 8.6% of the total
Hirshfeld surface area for the molecule of (3). They correspond to
all C–Hꢀ ꢀ ꢀC interactions of which C–Hꢀ ꢀ ꢀ
p appear in the fingerprint
plot in a characteristic manner. From Hirshfeld surface, it is clear
that the crystal structure of the title compound (3) do not exhibit
any
p p stacking interaction since there is no evidence of the
ꢀ ꢀ ꢀ
adjacent red and blue triangles on the shape index surface
(Fig. 4b). The curvedness mapped on Hirshfeld surface (Fig. S1)
shows that the largest regions of flat curvedness appear for
compound (3). The nature of the interplay of the title compound

S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
125
Fig. 5. Fingerprint plot of (3): full and resolved into full and resolved into Oꢀ ꢀ ꢀH, Cꢀ ꢀ ꢀH and Hꢀ ꢀ ꢀH contacts showing the percentages of contacts contributed to the total
Hirshfeld surface area of molecule.
Fig. 6. (a) Superposition of molecular conformations obtained from X-ray analysis (red), and DFT calculation (blue) of compound (3). (b) Molecular electrostatic potential map
of (3). (c) Total electronic charge density isosurface of title compound set at 0.15 e Åꢃ3 using DFT method. (d) Charge density of HOMO orbital of the title compound calculated
by DFT method. (e) Charge density of LUMO orbital of the title compound calculated by DFT method. (For interpretation of the references to color in this figure legend, the
reader is referred to the web version of this article.)

126
S.K. Seth et al. / Journal of Molecular Structure 1000 (2011) 120–126
[11] (a) M. Nishio, M. Hirota, Y. Umezawa, The C–Hꢀ ꢀ ꢀ
p Interaction: Evidence,
The Frontier molecular orbitals (FMOs) are very important in
Nature and Consequences, Wiley, VCH: New York, 1998;
(b) K. Biradha, M.J. Zaworotko, J. Am. Chem. Soc. 120 (1998) 6431;
(c) M. Nishio, CrystEngComm 6 (2004) 130;
determining such properties as molecular reactivity and the ability
of a molecule to absorb light. These FBOs is very important for
optical and electric properties [43]. The charge densities for the
HOMO (highest occupied molecular orbital) and LUMO (lowest
unoccupied molecular orbital) in (3) are shown in Fig. 6d and e
respectively. The HOMO–LUMO energy separation has been used
as a simple indicator of kinetic stability [44,45] and could indicate
the reactivity pattern of the molecule [46]. A large HOMO–LUMO
gap (1.993 eV for 3) implies high kinetic stability and low chemical
reactivity, because it is energetically unfavorable to add electron to
a high-lying LUMO, to extract electrons from low-lying HOMO [45].
The orbital energies corresponding to HOMO and LUMO are given
in Table S1 (Supplementary).
(d) M.D.C. Fernandez-Alonso, F.J. Canada, J. Jimenez-Barbero, G. Cuevas, J. Am.
Chem. Soc. 127 (2005) 7379;
(e) D. Braga, S.L. Giaffreda, F. Grepioni, L. Maini, M. Polito, Coord. Chem. Rev.
250 (2006) 1267;
(f) H.J. Schneider, Angew. Chem. Int. Ed. 48 (2009) 3924.
[12] (a) C.J. Janiak, Chem. Soc. Dalton Trans. (2000) 3885;
(b) M.J. Packer, M.P. Dauncey, C.A. Hunter, J. Mol. Biol. 295 (2000) 71;
(c) K. Müller-Dethlefs, P. Hobza, Chem. Rev. 100 (2000) 143;
(d) E.A. Mayer, R.K. Castellano, F. Diederich, Angew. Chem. Int. Ed. 42 (2003)
1210;
(e) B.L. Schottel, H.T. Chifotides, M. Shatruk, A. Chouai, L.M. Pérez, J. Bacsa, K.R.
Dunbar, J. Am. Chem. Soc. 128 (2006) 5895;
(f) P. Hobza, H.L. Selzle, E.W. Schlag, Chem. Rev. 94 (1994) 1767;
(g) K.S. Kim, P. Tarakeshwar, J.Y. Lee, Chem. Rev. 100 (2000) 4145;
(h) M.O. Sinnokrot, C.D. Sherrill, J. Phys. Chem. A 110 (2006) 10656;
(i) M. Pitonak, P. Neogrady, J. Rezac, P. Jurecka, M. Urban, P.J. Hobza, Chem.
Theory Comput. 4 (2008) 1829;
4. Conclusion
(j) N.J. Singh, S.K. Min, D.Y. Kim, K.S. Kim, J. Chem. Theory Comput. 5 (2009) 515.
[13] Y. Zhang, Z.J. Guo, X.Z. You, J. Am. Chem. Soc. 123 (2001) 9378.
[14] G. Fitzgerald, J. Andzelm, J. Phys. Chem. 95 (1991) 10531.
[15] T. Ziegler, Pure Appl. Chem. 63 (1991) 873.
[16] J. Andzelm, E. Wimmer, J. Chem. Phys. 96 (1992) 1280.
[17] G.E. Scuseria, J. Chem. Phys. 97 (1992) 7528.
[18] R.M. Dickson, A.D. Becke, J. Chem. Phys. 99 (1993) 3898.
[19] G.M. Sheldrick, SHELXS97: Programs for Crystal Structure Solution, University
of Göttingen, Germany, 1997.
[20] G.M. Sheldrick, SHELXL97: Programs for Crystal Structure Refinement,
University of Göttingen, Germany, 1997.
The molecular conformations of (3) have been established by
single crystal X-ray diffraction and quantum mechanical calcula-
tions. The observed molecular conformation of the title compound
from X-ray analysis agrees well with that obtained from the quan-
tum mechanical calculations. The structural studies shows that the
rings of the steroid skeleton assumes chair and sofa conformations
where all the rings have trans fusion except one ring junction which
is actually in cis fusion. Moreover, the weak interaction (C–Hꢀ ꢀ ꢀ
p
)
[21] L.J. Farrugia, J. Appl. Cryst. 32 (1999) 837.
[22] A.L. Spek, PLATON, A Multipurpose Crystallographic Tool,, Utrecht University,
Utrecht, The Netherlands, 2000.
[23] B. Delley, Phys. Rev. B 66 (2002) 155125.
[24] J.P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 77 (1996) 3865.
[25] A.D. Becke, Phys. Rev. A 38 (1988) 3098.
[26] A.C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[27] L. J. Farrugia, ORTEP III (Version 1.06), Department of Chemistry, University of
Glasgow, Scotland, UK.
[28] S.B. Mahato, A.K. Nandy, P. Luger, M. Weber, J. Chem. Soc. Perkin Trans. 2
(1990) 1445.
plays a crucial role in assembling the molecules into an organized
framework. This paper highlights the usefulness of the Hirshfeld
analysis in understanding the intricacies of interactions occurring
in crystallized solids. The Hirshfeld surface analysis in form of
decomposed fingerprint plots enabled to decode the intermolecular
interaction types present in the title crystal structure.
Appendix A. Supplementary material
[29] M. Parvez, A. Rahman, M.I. Choudhary, S. Zareen, N.M. Akhtar, S. Shujaat, F.N.
Ngounou, Acta Cryst. E 60 (2004) o2130.
[30] A.A. Ajees, K. Balakrishna, Acta Cryst. E 58 (2002) o682.
[31] I.J. Bruno, J.C. Cole, M. Kessler, J. Luo, W.D.S. Motherwell, L.H. Purkis, B.R. Smith,
R. Taylor, R.I. Cooper, S.E. Harris, A.G. Orpen, J. Chem. Inf. Comput. Sci. 44
(2004) 2133.
[32] F.H. Allen, Acta Crystallogr.: Sect. B 58 (2002) 380.
[33] D. Cremer, J.A. Pople, J. Am. Chem. Soc. 97 (1975) 1354.
[34] J. Bernstein, R.E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem. Int. Ed. 34
(1995) 1555.
[35] M.A. Spackman, J.J. McKinnon, CrystEngComm 4 (2002) 378.
[36] (a) J.J. McKinnon, D. Jayatilaka, M.A. Spackman, Chem. Commun. (2007) 3814;
(b) M.A. Spackman, J.J. McKinnon, D. Jayatilaka, CrystEngComm 10 (2008) 377;
(c) M.A. Spackman, D. Jayatilaka, CrystEngComm 11 (2009) 19;
(d) F.L. Hirshfeld, Theor. Chim. Acta 44 (1977) 129;
Crystallographic data (excluding structure factors) for the struc-
tures reported in this article have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation number CCDC 773494 of compound (3). Copies of the data
can be obtained free of charge on application to CCDC, 12 Union
Road, CambridgeCB2 1EZ, UK. Fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.molstruc.2011.06.003.
(e) A.D. Martin, K.J. Hartlieb, A.N. Sobolev, C.L. Raston, Cryst. Growth Des. 10
(2010) 5302;
References
(f) B. Chattopadhyay, A.K. Mukherjee, N. Narendra, H.P. Hemantha, V.V.
Sureshbabu, M. Helliwell, M. Mukherjee, Cryst. Growth Des. 10 (2010) 4476;
(g) S. K. Seth, D. Sarkar, T. Kar, CrystEngComm. doi:10.1039/c1ce05037k.;
(h) S. K. Seth, I. Saha, C. Estarellas, A. Frontera, T. Kar, S. Mukhopadhyay, Cryst.
Growth Des. doi:10.1021/cg200506q.
[1] F.E. King, T.J. King, J.M. Ross, J. Chem. Soc. (1954) 3995.
[2] R.N. Chopra, S.L. Nayar, I.C. Chopra, Glossary of Indian Medical Plants, CSIR,
New Delhi, 1956. p. 251.
[3] K.M. Nadkarni, A.K. Nadkarni, Indian Materia Medica, vol. I, Popular Prakashan
Pvt. Ltd., Bombay, 1976. p. 1198.
[4] L.D. Kapoor, Handbook of Ayurvedic Medicinal Plants, CRC Press, Boca Raton,
FL, 1990. p. 319.
[5] A. Bharani, A. Ganguly, K.D. Bhargave, Int. J. Cardiol. 49 (1995) 191.
[6] V.K. Tripathi, B. Singh, R.C. Tripathi, R.K. Upadhyay, V.B. Pandey, Oriental. J.
Chem. 12 (1996) 1.
[37] (a) M.A. Spackman, P.G. Byrom, Chem. Phys. Lett. 267 (1997) 215;
(b) J.J. McKinnon, A.S. Mitchell, M.A. Spackman, Chem. Eur. J. 4 (1998) 2136.
[38] (a) J.J. McKinnon, M.A. Spackman, A.S. Mitchell, Acta Crystallogr., Sect. B 60
(2004) 627;
(b) A.L. Rohl, M. Moret, W. Kaminsky, K. Claborn, J.J. Mckinnon, B. Kahr, Cryst.
Growth Des. 8 (2008) 4517;
(c) A. Parkin, G. Barr, W. Dong, C.J. Gilmore, D. Jayatilaka, J.J. Mckinnon, M.A.
Spackman, C.C. Wilson, CrystEngComm 9 (2007) 648;
(d) F.P.A. Fabbiani, L.T. Byrne, J.J. Mckinnon, M.A. Spackman, CrystEngComm 9
(2007) 728.
[7] E.O. Sote, M. Wilson, Afr. Dent. J. 9 (1995) 15.
[8] J. Koudou, G. Roblot, R. Wylde, Planta Med. 61 (1995) 490.
[9] J. Tamminen, E. Kolehmainen, Molecules 6 (2001) 21.
[10] (a) G.R. Desiraju, T. Steiner, The Weak Hydrogen Bond in Structural Chemistry
and Biology, Oxford University Press, Oxford, 1999;
(b) G.A. Jeffrey, W. Saenger, Hydrogen Bonding in Biological Structures,
Springer, Berlin, 1991;
[39] S.K. Wolff, D.J. Grimwood, J.J. McKinnon, D. Jayatilaka, M.A. Spackman,
CrystalExplorer 2.1, University of Western Australia, Perth, Australia, 2007.
[40] E. Scrocco, J. Tomasi, Adv. Quant. Chem. 11 (1978) 115.
[41] F.J. Luque, J.M. Lopez, M. Orozco, Theor. Chem. Acc. 103 (2000) 343.
[42] N. Okulik, A.H. Jubert, Internet Electron J. Mol. Des. 4 (2005) 17.
[43] I.Fleming,FrontierOrbitalsandOrganicChemicalReactions,Wiley,London,1976.
[44] K.H. Kim, Y.K. Han, J. Jung, Theor. Chem. Acc. 113 (2005) 233.
[45] J. Aihara, J. Phys. Chem. A 103 (1999) 7487.
(c) W.C. Hamilton, J.A. Ibers, Hydrogen Bonding in Solids, Benjamin, New York,
1968;
(d) S. Scheiner, Hydrogen Bonding:
University Press, Oxford, 1997;
A Theoretical Perspective;, Oxford
(e) G.A. Jeffrey, An Introduction to Hydrogen Bonding, Oxford University Press,
Oxford, 1997;
(f) T. Steiner, Angew. Chem. Int. Ed. 41 (2002) 48;
(g) Y.Zhang,Z.Yang,F.Yuan,H.Gu,P.Gao,B.Xu,J.Am.Chem.Soc.126(2004)15028.
[46] (a) B. Chattopadhyay, S. Basu, P. Chakraborty, S.K. Choudhury, A.K. Mukherjee,
M. Mukherjee, J. Mol. Struct. 932 (2009) 90;
(b) S.K. Seth, D.K. Hazra, M. Mukherjee, T. Kar, J. Mol. Struct. 936 (2009) 277.