A nimesulide derivative with potential anti-inflammatory activity: Synthesis, X-ray powder structure analysis and DFT study

Article abstract of DOI:10.1016/j.molstruc.2010.03.075

A nimesulide derivative, N-[4-(2,5-dioxo-2,5-dihydropyrrol-1-yl)-2-phenoxyphenyl]methanesulfonamide (2), was synthesized and its crystal structure has been determined from X-ray powder diffraction data following direct-space global optimization technique and refined by the Rietveld method. The molecular geometry and electronic structure of the title compound were calculated at the DFT level using the hybrid exchange-correlation functional, BLYP. The optimized molecular geometry of 2 corresponds closely to that obtained from the X-ray structure analysis. Intermolecular N-H···O and C-H···O hydrogen bonds in 2 form one-dimensional polymeric chains of R₂²(8) rings propagating along the [1 0 0] direction. Further linking between parallel chains via C-H···π (arene) hydrogen bonds generates a two-dimensional supramolecular assembly in the (1 1 0) plane. The title compound exhibits potential anti-inflammatory activity and can induce 64% edema inhibition in rat paws.

Full text of DOI:10.1016/j.molstruc.2010.03.075

Journal of Molecular Structure 975 (2010) 40–46
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
A nimesulide derivative with potential anti-inflammatory activity: Synthesis,
X-ray powder structure analysis and DFT study
Abir Bhattacharya a, Kavitha Kankanala b,c, Sarbani Pal c, Alok K. Mukherjee a,
*
a Department of Physics, Jadavpur University, Jadavpur, Kolkata 700032, India
b JNT University, Kukatpally, Hyderabad 500072, India
c Department of Chemistry, PG Campus, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A nimesulide derivative, N-[4-(2,5-dioxo-2,5-dihydropyrrol-1-yl)-2-phenoxyphenyl]methanesulfonam-
ide (2), was synthesized and its crystal structure has been determined from X-ray powder diffraction data
following direct-space global optimization technique and refined by the Rietveld method. The molecular
geometry and electronic structure of the title compound were calculated at the DFT level using the hybrid
exchange–correlation functional, BLYP. The optimized molecular geometry of 2 corresponds closely to
that obtained from the X-ray structure analysis. Intermolecular N–HÁÁÁO and C–HÁÁÁO hydrogen bonds
in 2 form one-dimensional polymeric chains of R22(8) rings propagating along the [1 0 0] direction. Further
Received 12 March 2010
Received in revised form 25 March 2010
Accepted 25 March 2010
Available online 3 April 2010
Keywords:
Powder XRD
DFT calculation
Ab-initio structure solution
Supramolecular structure
HOMO–LUMO
linking between parallel chains via C–HÁÁÁ
p (arene) hydrogen bonds generates a two-dimensional supra-
molecular assembly in the (1 1 0) plane. The title compound exhibits potential anti-inflammatory activity
and can induce 64% edema inhibition in rat paws.
Ó 2010 Elsevier B.V. All rights reserved.
Anti-inflammatory activity
1. Introduction
Although single-crystal X-ray diffractometry is undoubtedly
the most widely used technique for atomic level structural char-
Nimesulide, N-(4-nitro-2-phenoxyphenyl) methanesulfonam-
ide (1), belonging to sulfonamide class of non-steroidal anti-
inflammatory drug (NSAID) is a prototype of relatively selective
cyclooxygenase-2 (COX-2) inhibitor [1]. In addition to good anti-
inflammatory, analgesic and anti-pyretic activities expected of an
NSAID, 1 is also effective in a wide range of disorders, which
include various arthritic conditions, gynaecological and urological
problems, post-surgical and cancer pain, and vascular diseases
[2]. Several structural modifications of nimesulide aimed at
enhancing the anti-inflammatory activity and reducing its toxicity
have been reported in the literature [3,4]. It has been observed that
incorporating an electron withdrawing group in the form of a con-
formationally restricted cyclic ketone or lactone in place of nitro
group in 1 often exhibits better COX-2 inhibiting property and
improved oral bioavailability [5]. X-ray structure analysis and
molecular dynamics simulation of COX-2 complexes of these
nimesulide analogues indicate an extensive network of hydrogen
bonds at the enzyme active site [6,7]. In this respect, a knowledge
of crystal structures of inhibitor molecules is of fundamental
importance for understanding the structure–activity correlation.
acterization of organic compounds and metal complexes, an
intrinsic limitation of this approach is the requirement to grow
single crystals of appropriate size and quality that make them
amenable to structure analysis. In such cases, X-ray powder dif-
fraction can be used as a viable alternative for structure elucida-
tion. With the recent developments in direct-space approaches
for structure solution [8–11], crystal structure analysis of organic
molecular solids can nowadays be accomplished from X-ray pow-
der diffraction data, although significant challenges may arise
when the molecule possesses considerable flexibility or there
are multiple molecules in the asymmetric unit. Crystal structures
of several molecular compounds have been determined from
laboratory X-ray powder diffraction data using the direct-space
approaches [12–14].
The present paper reports the synthesis, structural character-
ization and anti-inflammatory activity of a nimesulide derivative
(Fig. 1), N-[4-(2,5-dioxo-2,5-dihydropyrrol-1-yl)-2-phenoxyphe-
nyl]methanesulfonamide (2), along with the DFT calculations
to study the molecular geometry and the electronic structure.
Ab-initio crystal structure of
2 has been determined from
laboratory X-ray powder diffraction data using the simulated
annealing technique [15] followed by the Rietveld refinement
[16,17].
* Corresponding author. Tel.: +91 33 24148917; fax: +91 33 24146484.
E-mail address: akm_ju@rediffmail.com (A.K. Mukherjee).
0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.03.075

A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
41
Fig. 1. Chemical diagram of (a) nimesulide (1) and (b) C17H14N2O5S (2).
Fig. 2. Final Rietveld plot of C17H14N2O5S (2). Black crosses: observed pattern, red curve: calculated pattern, blue curve: difference curve, green curve: background. (For
interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
powder of N-[4-(2,5-dioxo-2,5-dihydropyrrol-1-yl)-2-phenoxyphe-
nyl]methanesulfonamide (2) (yield 68%).
2. Experimental and computational methods
Microwave assisted method: a mixture of compound N-(4-ami-
no-2-phenoxy phenyl) methanesulfonamide (278 mg, 1.0 mmol),
maleic anhydride (1.0 mmol) and sodium acetate (100 mg) was
exposed to microwave irradiation in a domestic microwave oven
operating at 2450 MHz. After completion of reaction, the mixture
was diluted with cold water (50 mL), stirred vigorously, filtered
and dried to obtain the desired product 2 (yield 78%). M.P.
2.1. Synthesis
The compound 2 has been synthesized following the method de-
scribed earlier [18]. Anhydrous sodium acetate (100 mg) was added
to a mixture of N-(4-amino-2-phenoxy phenyl) methanesulfonam-
ide (278 mg, 1.0 mmol) and maleic anhydride (1.0 mmol) in glacial
acetic acid (3 mL) and the mixture was allowed to reflux for
10 min. After completion of the reaction, the mixture was poured
into crushed ice (50 g) and stirred. The solid separated was filtered
and dried. The crude product on purification by column chromatog-
raphy and crystallization from methanol yielded microcrystalline
146(2)°C, IR (KBr, m
/cmÀ1); 3478 (–NH), 3239 (–NH), 1708 (–CO),
1725 (–CO), 1507 (Ar C–C), 1492 (Ar C–C), 1336 (–SO), 1322
(–SO), 1262 (–CO), 1161 (–CO). 1H NMR (400 MHz, CDCl3) d 3.0
(s, 3H), 6.80 (s, 2H), 6.88 (d, J = 6.0 Hz, 1H), 6.96 (bs, NH), 7.05

42
A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
(d, J = 9.0 Hz, 2H), 7.12 (dd, J = 12.0 Hz, J = 6.0 Hz, 1H), 7.18
(t, J = 9.0 Hz 1H), 7.40 (t, J = 12.0 Hz, 2H), 7.75 (d, J = 12.0 Hz, 1H);
13C NMR (200 MHz, CDCl3) d 39.7 (CH3), 115.6 (CH), 118.9 (CH),
121.2 (CH), 121.6 (CH), 124.7 (CH), 127.5 (C), 128.2 (C), 130.2
(CH), 134.1 (CH), 147.2 (C), 155.2 (C), 169.0 (CO); mass (m/z) 359
(M+, 100%); elemental analysis : found C 56.90, H 3.96, N 7.97%,
calculated for C17H14N2O5S: C 56.98, H 3.94, N 7.82%.
and Cerny [23] was used for structure solution. The initial molecular
geometry used in FOX was determined by the MOPAC 5.0 program
[24]. Lattice and profile parameters, zero-point and interpolated
background calculated from a previous powder-pattern decomposi-
tion based on the Le Bail algorithm, were introduced into the pro-
gram FOX, while keeping the bond lengths and angles constrained
Elemental analyses (C, H, N) were performed using a Perkin-El-
mer 240 C analyzer. The FTIR spectra (as KBr pellet) were obtained
from a Perkin-Elmer 298 spectrometer. 1H NMR and 13C NMR data
were recorded in a DMSO-d6 solution with a Bruker AV 300 spec-
trometer. Proton chemical shifts (d) are relative to tetramethylsil-
ane (TMS, d = 0.00) as internal standard and expressed in ppm.
Melting point was determined by using a melting point apparatus
and is uncorrected. Mass spectra were recorded on a Jeol JMC-D
300 spectrometer using electron ionization at 70 eV.
2.2. X-ray crystallography
2.2.1. Data collection
X-ray powder diffraction data of 2 were recorded with a Bruker
D8 Advance powder diffractometer using Cu
Ka radiation
(k = 1.5418 Å). The diffraction pattern was scanned with a step size
of 0.02°(2h) and counting time 50 s/step over an angular range of
3.0–100.0° (2h) using the Bragg–Brentano geometry. Partial recol-
lection of data showed no significant evidence of sample degrada-
tion in the X-ray beam.
2.2.2. Structure determination from X-ray powder diffraction data
The powder diffraction pattern was auto-indexed with the pro-
gram NTREOR [19]. The best solution indicated a triclinic unit cell
with a = 8.804(6), b = 16.568(2), c = 5.742(5) Å,
a = 93.13(1), b =
= 89.58(2)° and V = 833.7(2) Å3. The full pattern decom-
Fig. 3. Molecular view of C17H14N2O5S (2) with atom numbering scheme.
Intramolecular C–HÁÁÁO hydrogen bond is shown by the dotted line.
94.24(3),
c
position was performed with EXPO2004 [20] following the Le Bail
algorithm [21] and using a split type pseudo-Voigt peak profile
function [22]. Statistical analysis of X-ray powder data using the
FINDSPACE module of EXPO2004 [20] indicated the most probable
Table 2
Selected geometrical parameters (Å, °) of C17H14N2O5S (2).
ꢀ
space group as P1, which was used for subsequent structure
analysis. The calculated density (Dx = 1.427 g cmÀ3) indicated two
molecules in the unit cell (Z = 2). An ab initio reverse Monte Carlo
structure determination program (FOX) developed by Favre-Nicolin
X-ray
DFT
S1–O2
S1–O3
S1–N2
S1–C13
O1–C5
O1–C7
N1–C3
N2–C6
O4–C14
O5–C17
N1–C14
N1–C17
C14–C15
C15–C16
C16–C17
O2–S1–O3
O2–S1–N2
O2–S1–C13
O3–S1–N2
O3–S1–C13
N2–S1–C13
C5–O1–C7
S1–N2–C6
C14–N1–C17
N1–C17–C16
N1–C14–C15
C6–N2–S1–C13
N2–C6–C5–O1
C6–C5–O1–C7
C4–C5–O1–C7
C5–O1–C7–C8
C2–C3–N1–C14
1.450(1)
1.449(1)
1.669(1)
1.800(1)
1.421(1)
1.420(1)
1.420(1)
1.421(1)
1.250(1)
1.250(1)
1.369(2)
1.369(1)
1.420(1)
1.312(1)
1.420(1)
105.4(2)
120.6(1)
90.9(2)
1.450
1.450
1.669
1.800
1.421
1.420
1.420
1.421
1.250
1.218
1.369
1.369
1.420
1.311
1.420
105.3
120.6
90.9
Table 1
Crystal data and Rietveld refinements parameters of C17H14N2O5S (2).
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
C17H14N2O5S
358.37
293(2) K
1.5418 Å
Triclinic
P À 1
Unit cell dimensions
a = 8.803(1) Å
b = 16.570(1) Å
c = 5.740(1) Å
a
= 93.138(4)°
b = 94.258 (3)°
c
= 89.562(5)°
111.3(2)
123.6(1)
104.7(1)
113.2(2)
124.6(1)
107.7(1)
107.6(1)
107.8(1)
À106.9(2)
À9.5(2)
111.4
123.7
104.6
113.3
124.5
107.7
107.6
107.8
À107.0
À9.5
Volume
Z
833.7(2) Å3
2
Density (calculated)
2h range for data collection
Step size
Counting time per step
No. of profile data steps
No. of variable parameters
No. of background points
Rp
1.427 g/cm3
3–100°
0.02°
50 s
4981
182
25
0.0523
0.0715
0.1679
130.5(1)
À49.1(2)
162.8(1)
49.6(1)
130.6
À49.1
162.8
49.7
Rwp
RF2
v2
12.9

A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
43
Table 3
GSAS [25]. The lattice parameters, the background coefficients and
profile parameters were refined initially followed by the refinement
of positional coordinates of all non-hydrogen atoms. The atomic
coordinates of 25 non-hydrogen atoms were refined with soft con-
straints on bond lengths and bond angles; planar restraints were ap-
plied on the phenyl rings. The background was described by the
shifted Chebyshev function of first kind with 25 points regularly dis-
tributed over the entire 2h range. A fixed isotropic displacement
parameter of 0.025 Å2 for all non-hydrogen atoms was maintained.
Hydrogen atoms were placed in the calculated positions, and C–H,
N–H and O–H distances restrained. In the final stages of refinement,
preferred orientation correction was applied using the generalized
spherical harmonic (order 10) model. Final Rietveld refinement of
182 parameters (75 atomic coordinates, six lattice parameters, 25
Hydrogen bond geometry (Å, °) in C17H14N2O5S (2).
D–HÁÁÁA
d(D–H) d(HÁÁÁA) d(DÁÁÁA)
<(DHA) Symmetry
transformation
C1–H1–O3
0.96
0.87
0.96
0.96
2.35
2.35
2.60
2.37
2.87
2.990(3) 142
3.166(2) 157
3.428(2) 145
2.973(2) 121
3.554(7) 129
N2–HN2ÁÁÁO2
C13–H13BÁÁÁO3
C16–H16ÁÁÁO5
2 À x, 1 À y, 1 À z
1 À x, 1 À y, 1 À z
1 À x, 1 À y, 1 À z
2 À x, 2 À y, 2 À z
C15–H15ÁÁÁCg(3) 0.96
Cg(3) is the centroids of (C7–C12) phenyl ring.
within 0.10 Å and 5.0°, respectively. The atomic coordinates ob-
tained from the parallel tempering procedure of FOX were used as
the starting model for the Rietveld refinement using the program
Fig. 4. A view of R2(8) rings and formation of two-dimensional framework in C17H14N2O5S (2).
2

44
A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
background points, 10 profile parameters, 65 orientation distribu-
tion function coefficients and one scale factor) converged to
Rp = 0.0523 and Rwp = 0.0715 with excellent agreement between
the observed and the calculated patterns (Fig. 2). Relevant crystallo-
graphic data are summarized in Table 1.
The supramolecular assembly can be readily analyzed in terms of
substructures of lower dimensionality with dimeric unit as the
building block. In 2, a pair of intermolecular N–HÁÁÁO hydrogen
bonds (Table 3) with the sulfonamide N2 atom in the molecule
at (x, y, z) acting as a donor to O2 atom in the molecule at (2 À x,
1 À y, 1 À z) generates a centrosymmetric R22(8) dimeric ring (M)
centered at (1, ½, ½), Fig. 4. Similarly, a pair of intermolecular
C13–H13BÁÁÁO3 hydrogen bonds interconnects two molecules at
(x, y, z) and (1 À x, 1 À y, 1 À z), producing another centrosymmet-
ric R22(8) dimeric ring (N) centered at (1/2, ½, 1/2). The two types of
R22(8) rings are alternately linked into an infinite one-dimensional
MNMNÁÁÁ polymeric chain propagating along the [1 0 0] direction
(Fig. 4). Adjacent one-dimensional chains are further connected
2.3. Computational
The isolated molecule DFT calculation for 2 was performed
using Dmol3 code [26] in the framework of a generalized-gradient
approximation (GGA) [27]. The starting atomic coordinates were
taken from the final X-ray refinement cycle. The geometry of the
molecule was fully optimized using the hybrid exchange–correla-
tion functional BLYP [28,29] and a double numeric plus polariza-
tion (DNP) basis set. The electronic structure was also calculated
at the same level. Geometry optimization was carried out without
any constraint on bond lengths, bond angles or dihedral angles.
via C–HÁÁÁ
p (arene) hydrogen bonds (Table 3). The pyrrole carbon
atom C15 in the molecule at (x, y, z) acts as a donor to the phenyl
ring (C7–C12) in the molecule at (2 À x, 2 À y, 2 À z) to form a two-
dimensional framework in the (1 1 0) plane (Fig. 4).
3.2. Geometry and electronic structure
2.4. Anti-inflammatory property evaluation
A superposition of molecular conformations of 2 as established
by the quantum mechanical calculations and X-ray structure anal-
ysis shows an excellent agreement (Fig. 5); the largest deviations of
geometrically optimized bond lengths and bond angles from the
corresponding experimental values are 0.032 Å (for O5–C17 bond
distance) and 0.08° (for N2–S1–C13 bond angle) (Table 2). The con-
formation of the sulfonamide group at C6 position and the twist of
the phenyl ring (C7–C12) about the O1–C7 bond as obtained from
the geometry optimized structure are consistent with the X-ray
analysis. The small differences between the calculated and ob-
served geometrical parameters can be attributed to the fact that
the theoretical calculations have been carried out with isolated
molecules in the gaseous phase whereas the experimental values
correspond to molecules in the crystalline state.
Male adult albino Wister rats (100–200 g) were divided into
separate groups of six animals each. The anti-inflammatory activity
of 2 was evaluated following the method described by Winter et al.
[30]. The pedal inflammation in rat paws was induced by sub plan-
tar injection of 0.1 ml carrageenan (0.2%) suspension in gum acacia
into the right hind of the rats. The rat paws thickness was mea-
sured with a vernier calipers before and one hour after the carra-
geenan injection. The compound 2 was injected (100 mg/kg)
intraperitoneally to separate groups of rats one hour after the car-
rageenan injection. The control groups received the vehicle (5%
gum acacia), while diclofenac sodium at a dose of 10 mg/kg was in-
jected to the reference group. The difference between the thickness
of two paws before and one hour after the injection of the test
compound was taken as a measure of edema inhibition.
The net charges of atoms and dipoles, and the molecular orbital
energy of the title compound calculated at the BLYP level are listed
in Table 4. All oxygen and nitrogen atoms in the molecule bear
3. Results and discussion
3.1. Structural description
The molecular view of 2 with atom numbering scheme is shown
in Fig. 3. The essential difference between nimesulide (1) and the
title compound 2 is that the nitro group in 1 is replaced by a dioxo-
pyrrol-1-yl moiety in 2. The sulfonamide group in 2 is bent to-
wards the nitrogen containing heterocyclic ring, C14–C17/N1,
with the S1–N2–C3–N1 torsion angle of 79.1°. The overall molecu-
lar conformation in 2 can be described in terms of the dihedral an-
gle of 84.7(5)° between the oxygen-bridged phenyl rings (C1–C6
and C7–C12), and the orientation of the methanesulfonamide
group, which facilitates intramolecular C–HÁÁÁO hydrogen bonds.
In the nimesulide structure [31], the oxygen-bridged phenyl rings
are inclined to each other by 74.69(8)°. The displacement of the
oxygen atoms of the sulfonamide group prevents any hydrogen
bond inside the COX-2 active site and consequently forms a less
stable enzyme–ligand complex.
A
comparison of C6–N2
[1.420(1) Å] and N2–S1 [1.670(1) Å] bond lengths in 2 (Table 2)
with that of nimesulide [1.409(4) Å and 1.640(2) Å], where the sul-
fonamide group is not deprotonated, indicates that the compounds
2 is in the neutral form; the corresponding C6–N2 and N2–S1 dis-
tances in the zwitterionic form of nimesulide analogue are
1.354(2) Å and 1.609(1) Å, respectively [32]. For the –NHSO2CH3
moiety, the sulfur–oxygen bond distance in 2 [1.450(1) Å] is con-
sistent with S@O distance and is similar to those found in related
compounds [33–35].
Fig. 5. Superposition of molecular conformation as obtained from X-ray structure
analysis (blue) and DFT calculation (red) for C17H14N2O5S (2). (For interpretation of
the references to colour in this figure legend, the reader is referred to the web
version of this article.)
The crystal packing in 2 is stabilized by a combination of inter-
molecular N–HÁÁÁO, C–HÁÁÁO and C–HÁÁÁ
p hydrogen bonds (Table 3).

A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
45
Table 4
Net charge of atoms and dipoles, and the molecular orbital energies of C17H14N2O5S
(2).
S1
N1
N2
O1
O2
O3
O4
O5
C1
C2
C3
C4
0.547
À0.464
À0.355
À0.512
À0.392
À0.391
À0.384
À0.380
À0.082
À0.059
0.206
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
C16
C17
0.152
0.267
À0.076
À0.043
À0.058
À0.044
À0.084
À0.130
0.446
À0.056
À0.056
0.447
À0.096
C5
0.274
Dipole (a.u.)
Binding energy (eV)
2.44
À195.04
EHOMO (eV)
ELUMO (eV)
À5.451
À3.800
Fig. 6. Total electronic charge density isosurface of C17H14N2O5S (2) set at 0.15 eÅÀ3
using DFT method.
Fig. 7. Charge density of (a) HOMO and (b) LUMO orbitals C17H14N2O5S (2)
calculated by DFT method.
negative charges, and the sulfur atom (S1) of methanesulfonamide
group and the carbon atoms of the phenyl and pyrrole rings having
substitutions (C3, C5, C6, C7, C14 and C17) bear positive charges;
the remaining carbon atoms have negative charges. Due to this
charge redistribution, the dipole of the molecule becomes 2.44
a.u. The total electronic charge density isosurface (Fig. 6), set at
0.15 eÅÀ3 for an isolated molecule of compound 2, indicates that
charge density is equally distributed over the entire molecule.
The orbital energy level analysis for 2 at the BLYP level shows
EHOMO (highest occupied molecular orbital) and ELUMO (lowest
unoccupied molecular orbital) values of À5.451 and À3.805 eV,
respectively. The magnitude of the HOMO–LUMO energy separa-
tion could indicate the reactivity pattern of the molecule [36,37].
The charge densities for the HOMO and LUMO in 2 (Fig. 7) indicate
very little charge accumulation on the hydrogen atoms. The HOMO
is located on the C1–C6, C2–C3, C5–C6, C7–C8, C7–C12 and C9–C10
bonds of the phenyl rings as well as on the bridging oxygen atom
(O1) and the nitrogen atoms (N1 and N2) of the molecule. The cor-
responding LUMO population is located mainly on the C14–C15
and C16–C17 bonds of pyrrole ring and two carbonyl oxygen atoms
(O4 and O5). The difference between the orbital energies corre-
sponding to HOMO-1 (À5.947 eV) and HOMO-2 (À6.427 eV) in 2
is much larger than 0.05 eV, which indicates that the HOMO-1
and HOMO-2 energy levels are non-degenerate in 2. Similar con-
clusion can be drawn from the LUMO + 1 and LUMO + 2 orbital en-
ergy calculations.
According to the molecular orbital theory, HOMO and LUMO are
two important factors influencing the bioactivity of a compound.
Preliminary results of anti-inflammatory activity using the rat car-
rageenan paw edema model indicate that compound 2 can induce
64% edema inhibition in rat paws; the corresponding edema inhi-
bition with diclofenac sodium (reference drug) is 66%. The negative
charges in 2, mainly located on the nitrogen and oxygen atoms of
the sulfonamide and dioxopyrrol-1-yl groups, are likely to interact
with the positive parts of the receptor. The positively charged parts

46
A. Bhattacharya et al. / Journal of Molecular Structure 975 (2010) 40–46
of 2, on the contrary, will interact quite easily with the negatively
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The observed molecular conformation of the compound as estab-
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p hydrogen bonds in 2 generate a two-dimensional
supramolecular assembly built with R22(8) rings. The HOMO–LUMO
energy separation (1.65 eV) suggests that the title compound is
likely to be reactive which is in agreement with the anti-inflamma-
tory activity of 2. The edema test indicates that compound 2 can
induce 64% edema inhibition in rat paws. The present study is
promising for revealing the structure at an atomic resolution of
pharmaceutical compounds that cannot be easily obtained as sin-
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5. Supporting information
Crystallographic data for the structure C17H14N2O5S (2) re-
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Crystallographic Data Centre as supplementary publication num-
ber CCDC 768824. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
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Financial support from the University Grants Commission, New
Delhi, and the Department of Science and Technology, Government
of India, New Delhi, through the DRS (SAP-1) and FIST programs for
purchasing the Bruker D8 Advance X-ray powder diffractometer, is
gratefully acknowledged. The authors are grateful to Prof. Monika
Mukherjee, IACS, Kolkata, for helping with the DFT calculations.
AB thanks the University Grants Commission, India, for a research
fellowship.