An analysis of spectroscopic, computational and biological activity studies of L-shaped sulfamoylbenzoic acid derivatives: A third order nonlinear optical material

Article abstract of DOI:10.1016/j.molstruc.2020.128070

The current article focuses mainly on investigation of structural, reactivity, topology studies, and third order nonlinear optical properties of the synthesized 2-(benzylamino)-4-chloro-5-sulfamoylbenzoic acid (BACSBA) with the aid of spectroscopic techniques and computational methods. The structure in the solid state was obtained unambiguously by SCXRD study that revealed that BACSBA has L-shaped structure stabilized by N–H?O intramolecular hydrogen bond. Further, the two dimensional sheet like architecture formation by linking of molecules via O–H?O and N–H?O hydrogen bonds, were visualized both qualitatively and quantitatively by Hirshfeld surface analysis. Also, a topological analysis made through Quantum Theory of Atoms In Molecules (QTAIM) highlights the observations N–H?O bonds on solid state. The quantum chemical calculation was performed at DFT/6–311++G (d,p) level of basis set. The analysis of each vibrational wave number was performed with the help of potential energy distribution (PED) using VEDA4 software and correlation with experimental data shows good concurrence. The reactive sites have been predicted and visualized by molecular electrostatic surface potential (MESP) and Fukui function calculation, together with hydrogen bond dissociation energy (H-BDE) for the BACSBA compound. Frontier molecular orbitals (FMO), global reactivity parameters, natural bond orbital analysis (NBO), localized orbital locator (LOL) and electron localization function (ELF) properties have also been studied for the titled compound. The super molecule (SM) approach with 372,680 atoms at the DFT/CAM-B3LYP/6–311++G (d,p) level was used for calculating the nonlinear optical properties of the crystal. The electrical parameters such as total dipole moment, average linear polarizability and average second IDRI hyperpolarizability were calculated. In addition, the linear refractive index and the nonlinear third order macroscopic susceptibility of the crystal was estimated as a function of the frequency of the applied electric field. The value of third order nonlinear susceptibility for the BACSBA crystal at 532 nm was found to be 45.57 times greatest than the experimentally measured result of organic crystal (2E)-1-(3-bromophenyl)-3-[4 (methylsulfanyl)phenyl]prop-2-en-1-one (3Br4MSP) demonstrating that BACSBA crystal could be a good potential candidate for nonlinear optical applications. In addition, the thermal stability was studied showing that the crystal as potential optical devices at temperature up to 234 °C. Furthermore, preliminary studies revealed that BACSBA compound displayed promising antifungal and antioxidant activities compared with the standard drugs.

Full text of DOI:10.1016/j.molstruc.2020.128070

Journal Pre-proof
An analysis of spectroscopic, computational and biological activity studies of L-
shaped sulfamoylbenzoic acid derivatives: A third order nonlinear optical material
Krishna Murthy Potla, Nuthalapati Poojith, Francisco A.P. Osório, Clodoaldo
Valverde, Sampath Chinnam, P.A. Suchetan, Suneetha Vankayalapati
PII:
S0022-2860(20)30395-1
DOI:
https://doi.org/10.1016/j.molstruc.2020.128070
MOLSTR 128070
Reference:
To appear in: Journal of Molecular Structure
Received Date: 13 February 2020
Revised Date: 12 March 2020
Accepted Date: 13 March 2020
Please cite this article as: K.M. Potla, N. Poojith, F.A.P. Osório, C. Valverde, S. Chinnam, P.A.
Suchetan, S. Vankayalapati, An analysis of spectroscopic, computational and biological activity studies
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Credit Author Statement:
Title of the manuscript: An analysis of spectroscopic, computational and biological activity
studies of L-shaped sulfamoylbenzoic acid derivatives: A third order nonlinear optical
material
Krishna Murthy Potla: Design, synthesis, crystallization, perform computational calculation,
interpretation of results and writing draft.
Nuthalapati Poojith: Performed bioactivity studies.
Francisco A. P. Osório: Nonlinear Optical properties calculation.
Clodoaldo Valverde: Nonlinear Optical properties calculation.
Sampath Chinnam: Spectral analysis, interpretation of results & English polishing.
P.A. Suchetan: Single crystal X-ray diffraction data analysis.
Suneetha Vankayalapati: Computational calculations, literature collection and writing draft.

An analysis of spectroscopic, computational and biological activity studies of L-shaped
sulfamoylbenzoic acid derivatives: A third order nonlinear optical material
a
b
c,d
Krishna Murthy Potla *, Nuthalapati Poojith , Francisco A. P. Osório ,
e,f
g
h
a,i
Clodoaldo Valverde , Sampath Chinnam **, P.A. Suchetan , Suneetha Vankayalapati
a
Department of Chemistry, Bapatla Engineering College (Autonomous), Acharya Nagarjuna
University Post Graduate Research Centre, Bapatla-522 102, A.P., India.
b
Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research,
Ramachandra Nagar, Porur, Chennai, 600 116, India.
c
Instituto de Física, Universidade Federal de Goiás, 74.690-900, Goiânia, GO, Brazil.
d
Pontifícia Universidade Católica de Goiás, 74605-100, Goiânia, GO, Brazil.
e
Laboratório de Modelagem Molecular Aplicada e Simulação (LaMMAS), Campus de
Ciências Exatas e Tecnológicas, Universidade Estadual de Goiás, 75001-970, Anápolis, GO,
Brazil.
f
Universidade Paulista, 74845-090, Goiânia, GO, Brazil.
g
Department of Chemistry, B.M.S. College of Engineering, Bull Temple Road, Bengaluru,
Karnataka 560019, India.
h
Department of Studies and Research in Chemistry, University College of Science, Tumkur
University, Tumkur-572 103, Karnataka, India.
i
Department of Chemistry, Bapatla College of Arts and Sciences, Baptla-522 101, A.P.,
India.
*Corresponding author: krishnamurthypotla@gmail.com
*
* Co-corresponding author: sampathchinnam@gmail.com
Abstract
The current article focuses mainly on investigation of structural, reactivity, topology studies,
and third order nonlinear optical properties of the synthesized 2-(benzylamino)-4-chloro-5-
sulfamoylbenzoic acid (BACSBA) with the aid of spectroscopic techniques and
computational methods. The structure in the solid state was obtained unambiguously by
SCXRD study that revealed that BACSBA has L-shaped structure stabilized by N-H...O
intramolecular hydrogen bond. Further, the two dimensional sheet like architecture formation
by linking of molecules via O-H...O and N-H...O hydrogen bonds, were visualized both
qualitatively and quantitatively by Hirshfeld surface analysis. Also, a topological analysis
made through Quantum Theory of Atoms In Molecules (QTAIM) highlights the observations
N-H...O bonds on solid state. The quantum chemical calculation was performed at DFT/6-

3
11++G (d,p) level of basis set. The analysis of each vibrational wave number was performed
with the help of potential energy distribution (PED) using VEDA4 software and correlation
with experimental data shows good concurrence. The reactive sites have been predicted and
visualized by molecular electrostatic surface potential (MESP) and Fukui function
calculation, together with hydrogen bond dissociation energy (H-BDE) for the BACSBA
compound. Frontier molecular orbitals (FMO), global reactivity parameters, natural bond
orbital analysis (NBO), localized orbital locator (LOL) and electron localization function
(ELF) properties have also been studied for the titled compound. The super molecule (SM)
approach with 372,680 atoms at the DFT/CAM-B3LYP/6-311++G(d,p) level was used for
calculating the nonlinear optical properties of the crystal. The electrical parameters such as
total dipole moment, average linear polarizability and average second IDRI
hyperpolarizability were calculated. In addition, the linear refractive index and the nonlinear
third order macroscopic susceptibility of the crystal was estimated as a function of the
frequency of the applied electric field. The value of third order nonlinear susceptibility for the
BACSBA crystal at 532 nm was found to be 45.57 times greatest than the experimentally
measured result of organic crystal (2E)-1-(3-bromophenyl)-3-[4(methylsulfanyl)phenyl]prop-
2
-en-1-one (3Br4MSP) demonstrating that BACSBA crystal could be a good potential
candidate for nonlinear optical applications. In addition, the thermal stability was studied
showing that the crystal as potential optical devices at temperature up to 234°C. Furthermore,
preliminary studies revealed that BACSBA compound displayed promising antifungal and
antioxidant activities compared with the standard drugs.
Keywords: NLO properties; reactivity analysis; SCXRD studies; biological activity; BDE
calculations; sulfamoylbenzoic acid.
1
. Introduction
The search for organic crystal that can be used as nonlinear optical (NLO) materials has
been immensely increased in the last decade, motivated by the ease of manipulation and
versatile synthetic route and by the presence of high non-linearity of these compounds [1,2].
Organic crystals have gained much importance for application in the photonic area [3,4], as
well as in spectroscopy [5, 6], frequency modulators [7] and data transmission [8].
Sulfonamides (sulfa drugs) are the versatile and novel pharmacophores prevalent in nearly
2
00 drugs. Sulfonamide compounds have extensive applications in agricultural and
pharmaceutical [9-12], nonlinear optical [13] and analytical [14], owing to their unique
physicochemical and biological properties. Among a large variety of sulfonamide
compounds, chlorosulfonamide moieties have great potential applications in medicinal

chemistry. Some of the chlorosulfonamide drugs used in medicine includes furosemide(1),
fenquizone(2), metolazone(3), azosemide(4), chlorothiazide(5), hydrochlorothiazide(6) (as
diuretics) and diclofenamide(7) (as carbonic anhydrase inhibitor) (Figure 1).
Lamotte et al. reported the crystal structure of furosemide [15]. Jagadeesh et al. disclosed the
ploymorphic forms of furosemide through single crystal X-ray diffraction studies [16].
Detailed investigation of X-ray structure and vibrational spectral analysis of furosemide was
carried out by Bolukbasi et al. [17]. Florence, et al. performed the structure elucidation of
hydrochlorothiazide by X-ray powder diffraction method [18]. Hernández et al. studied the
conformational analysis of hydrochlorothiazide by theoretical studies [19].
Hydrochlorothiazide N,N-dimethylformamide solvate crystal structure was reported by
Johnston et al. [20]. Fernandes et al. reported the solvate structure of chlorothiazide N,N-
dimethylformamide [21]. Boopathi et al. investigated molecular structure, vibrational analysis
and MEP studies of diuretic drug metolazone theoretically [22]. Porchelvi et al. reported
spectroscopic and computational studies of 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiazine-
7
sulphonamide1,1-dioxide (6CDBSD) [23]. Kavitha et al. reported the synthesis,
spectroscopic characterization and reactivity parameter analysis of 4-chloro-3-
sulfamoylbenzoic acid with antibacterial activity studies [24]. Rahman et al. performed the
diuretic and anti-hypertensive studies on synthesized quinazoline derivatives [25].
Thirumalaiselvam et al. measured the Third-order nonlinear optical susceptibility of 4-methyl
benzene sulfonamide single crystal by using Z-scan technique [13].
Keeping in view of the above observations, we have investigated the spectroscopic studies
(SCXRD, FT-IR, FT-Raman), Hirshfeld surface analysis, QTAIM studies, computational
characterizations (optimization, vibrational analysis, HOMO-LUMO analysis, MESP, Fukui
calculation, ELF, LOL, BDE and H-BDE studies) of the synthesized 2-(benzylamino)-4-
chloro-5-sulfamoylbenzoic acid (BACSBA). Moreover, the NLO properties of the
sulfonamide BACSBA crystal was studied via the density functional theory (DFT) with the
functional CAM-B3LYP and 6-311++G(d,p) basis set. The total dipole moment, the average
linear polarizability and the average second hyperpolarizability were calculated as a function
of the applied electric field frequency. From the values of these electric parameters, the
dynamic linear refractive index and the dynamic third order nonlinear susceptibility was
determined, and its value compared with experimental data available in the literature from Z-
scan experiments. In continuation to our earlier reported works [24, 26, 27], we herein
disclose nonlinear optical properties and computational as biologically potent sulfonamides
and sulfonyl moieties.

2
. Experimental
2
.1. General
The chemicals, reagents and solvents were procured from commercial source and used
directly without further purification. FT-Raman spectrum was recorded for the solid sample
-
1
-1
in the range 50-4000 cm with resolution 2 cm by using Nd:YAG 1064 nm laser source on
BRUKER RFS 27: Stand alone FT-Raman Spectrometer (Figure S1). FT-IR spectrum was
-1
recorded for the solid sample (which is dispersed in KBr) in the range 4000-450 cm with
-1
resolution 1 cm on Perkin Elmer Spectrum1 FT-IR instrument with Spectrum one: FT-IR
Spectrometer model (Figure S2). TG-DTA spectrum was recorded using EXSTAR TG/DTA
SII 6300 instrument.
2
.2. Synthesis of 2-(benzylamino)-4-chloro-5-sulfamoylbenzoic acid
1
-Phenylmethanamine (0.19 mL, 1.77mmol) was taken into a 50 mL round-bottomed flask
and dissolved in tetrahydrofuran (THF) as a solvent (10 mL). To this, triethylamine (0.29 mL,
.07 mmol) was added at room temperature. Subsequently, 2,4-dichloro-5-sulfamoylbenzoic
2
acid (0.4 g, 1.48 mmol) was added drop-wise and then refluxed for 12h. The reaction mixture
was evaporated under reduced pressure and acidified with 6N HCl solution. The resulting
solid was dissolved in ethyl acetate (10 mL) and washed with brine solution (3 mL). The
organic layer was concentrated under reduced pressure to afford 2-(benzylamino)-4-chloro-5-
sulfamoylbenzoic acid as off-white solid (0.33g, yield: 65%) (Scheme-1). Suitable crystals
were grown for SCXRD studies in methanol at ambient temperature by using slow
evaporation crystal growth technique.
2
.3. X-ray crystallography
A colourless, needle shaped single crystal of the BACSBA compound, with dimensions of
.25mm×0.22mm×0.18 mm was selected and mounted on a Bruker APEX-II CCD
0
diffractometer with monochromated MoKα radiation (λ = 0.71073 Ǻ) at 296(2) K. The data
was processed with SAINT and corrected for absorption using SADABS [28]. The structure
was solved by the direct method using the program SHELXT and refined by using the
2
program SHELXS-97 [29] by full-matrix least squares technique on F using anisotropic
displacement parameters for all non-hydrogen atoms. The carbon bound hydrogen atoms
were positioned with idealized geometry using a riding model with C–H = 0.93–0.97 Å. H
atoms were refined with isotropic displacement parameters (set to 1.2 times of the U of the
eq
parent atom). The oxygen and amino nitrogen bound H-atoms were also positioned
geometrically using a riding model with O-H = 0.82 Å and N-H= 0.86 Å. The hydrogen
atoms of the –NH group were located from the difference Fourier map and were refined
2

freely. The ORTEP diagram of the compound is given in Figure 2 and the packing of
molecules in the crystal lattice is shown in Figure 3. The crystallographic data and refinement
parameters are summarized in Table 1. Geometric parameters for hydrogen bonds (A°)
operating in the crystal structure Table 2.
2
.4. Computational details
Quantum chemical calculations (optimization, vibrational frequencies, Frontier molecular
orbitals (FMO), Natural bond orbital (NBO), molecular electrostatic surface potential
(MESP) and bond dissociation energy (BDE) calculations) have been performed by
employing density functional theory (DFT) at B3LYP/6-311++G (d,p) [30] method using the
Gaussian09 software [31]. The assignments and analysis of each vibrational wave numbers
were performed by using the potential energy distribution (PED) analysis using VEDA4
program [32]. A scaling factor of 0.9613 [33] had to be utilized to acquire an impressive
better concurrence with the experimental data. Electron Localization Function (ELF) and
Localized Orbital Function (LOL) studies were used in examining the chemical bonding
between atoms of the titled compound employing Multiwfn 3.4.1 program [34].
The super molecule method (SM) was used for simulating the polarization effect of the
crystalline environment around the asymmetric unit [35]. The SM is an iterative process that
considers the atoms of the surrounding molecules to the asymmetric unit as point charge. The
iterative process starts with the determination of the electrical charge of each atom of the
asymmetric unit in vacuum, by adjusting the molecular electrostatic potential (CHELPG) at
DFT/CAM-B3LYP/6-311++G (d,p) level. Then, in the position of each corresponding atom
in the generated unit cells, the atoms were replaced by their partial atomic charge obtained
previously. Later, the total dipole moment (ꢀ) were determined and in the sequence the new
atomic charges of the atoms of the asymmetric unit were calculated and the process was
repeated until the convergence of the total dipole moment was reached [26, 36, 37] (Figure
4
). Here, a bulk with 10,648 molecules totalling 372,680 atoms was built.
The SM approach has been implemented in several works for the calculation of the electric
parameters as the Hyper-Rayleigh first hyperpolarizability and the third order nonlinear
susceptibility and the obtained theoretical results were close to the experimental results for
some organic crystal [35, 38, 39].
The dynamic average linear polarizability (〈ꢀ(−ꢁ; ꢁ)〉) and the average second
hyperpolarizability associated corresponding to the dc-Kerr effect (ꢂꢃ(−ꢁ; ꢁ, 0,0)ꢄ) were
calculated using the expressions:

1
3
〈
ꢀ(−ꢁ; ꢁ)〉 =
ꢅ ꢀ (−ꢁ; ꢁ),
ꢆꢇꢈ,ꢉ,ꢊ
ꢆꢆ
(1)
ꢋ
ꢋ
ꢂꢃ(−ꢁ; ꢁ, 0,0)ꢄ = ꢍꢃ
+ ꢃꢉꢉꢉꢉ + ꢃꢊꢊꢊꢊꢎ + ꢏꢃꢈꢈꢉꢉ + ꢃꢉꢉꢈꢈ + ꢃꢈꢈꢊꢊ +
ꢋꢌ
ꢈꢈꢈꢈ
ꢌ
(2)
ꢃꢊꢊꢈꢈ + ꢃꢉꢉꢊꢊ + ꢃꢊꢊꢉꢉ + 4ꢍꢃꢉꢈꢉꢈ + ꢃꢊꢈꢊꢈ + ꢃꢊꢉꢊꢉꢎꢐ.
The linear refractive index (ꢑ(ꢁ)) was calculated using the Clausius-Mossotti equation given
by,
ꢒ
ꢑ(ꢁ) − 1
4ꢔ
ꢓ=ꢓ
〈ꢀ(−ꢁ; ꢁ)〉,
(3)
ꢒ
ꢑ(ꢁ) + 2
3ꢓꢕꢖꢗ
where ꢕ is the unit cell volume.
ꢖꢗ
(ꢙ)
The third order nonlinear susceptibility (ꢘ (−ꢁ; ꢁ, ꢁ, −ꢁ))ꢓof the BACSBA crystal can be
written as
ꢑꢒ(ꢁ) + 2 ꢜ ꢝꢓ
(ꢙ)
ꢘ (−ꢁ; ꢁ, ꢁ, −ꢁ) =ꢓꢚ
ꢛ
〈γ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉
(4)
3
ꢞꢟꢓꢕꢖꢗ
In equation (4), the average second hyperpolarizability of the intensity dependent refractive
index (IDRI) were calculated using the following approximation,
〈
ꢃ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉 ≅ 2〈ꢃ(−ꢁ; ꢁ, 0,0)〉 − 〈ꢃ(0; 0,0,0)〉.
(5)
All the numerical calculations were performed using the Gaussian 09 package and converted
into electrostatic units (esu).
2
.5. QTAIM Analysis
Topological analysis was carried out en route QTAIM methodology at the theoretical level
DFT/B3LYP/6-311++G(d,p) [30] coupled in the Gaussian09 package and by Multiwfn
software [34]. Based on the generated wave function, the QTAIM methodology was
performed [40- 42]. In accordance with the mechanical quantum concepts the observable
properties are present in the electron density [ρ(r)], which can be used with the gradient
vector [∇ρ(r)] as a fundamental condition for establishing molecular topology [43, 44].
2
.6. Biological activity studies
The antifungal activity of the synthesized compound BACSBA was determined against A.
Niger (MTCC-1881), F. oxysporum (MTCC-1755) and A. foetidus (NCIM-505) by using
agar disc-diffusion method [45,46]. The antioxidant activity of the synthesized compound
BACSBA was determined by 1,1'-diphenyl-2-picrylhydrazyl (DPPH) [47] and Nitric oxide
(NO) methods [48].
3
. Results & discussion

3
.1. Crystal structure analysis
The molecule was L-shaped with the dihedral angle between the two aromatic rings being
o
7
5.70(1) . The carboxylic acid group and the attached aromatic ring were in the same plane
with the torsions C20-C21-C31-O4 and C20-C21-C31-O5 having values of 0.7(3) and -
o
1
78.89(18) respectively. The –COOH group has syn conformation with the O-H and C=O
bonds oriented in the same direction. The molecular conformation was stabilized by an
intramolecular N19-H33…O4 hydrogen bond that closes into an S(6) motif.
2
In the crystal structure, the molecules were connected into inversion related R (8) dimers via
2
O5-H32…O4 hydrogen bonds. These dimers were linked to the adjacent dimers via a pair of
2
N24-H35...O3 hydrogen bonds forming another R (8) motif. The result of these two
2
2
alternating R (8) dimers was a one dimensional ribbon like architecture. The adjacent
2
ribbons were further interconnected via N24-H34...O3 hydrogen bonded C4 chains that
propagates along b axis to form a two dimensional sheet along ab plane.
3
.2. QTAIM studies
Figure S3 shows the presence of bond critical point (BCP) for BACSBA compound
interactions. The observables of each BCP is shown in Table 3 [where [ρ(r)] was electron
ꢒ
density, [ꢠ ꢡ(ꢢ)] was the Laplacian of electron density; V(r) is the potential energy density;
H(r) and G(r) are the electronic energy density and Lagrangian kinetic energy respectively.
ꢒ
For hydrogen bonds, ꢠ ꢡ(ꢢ) is positive and ρ(r) is small and the character of interaction can
ꢒ
be measured by the indicators: (1) ꢠ ꢡ(ꢢ)< 0 and H(r) < 0 ; strong interactions with covalent
ꢒ
ꢒ
character, (2) ꢠ ꢡ(ꢢ)> 0 and H(r) < 0 ; medium strength and (3) ꢠ ꢡ(ꢢ)> 0 and H(r) > 0 ;
ꢒ
weak interactions with electrostatic character (4) ꢠ ꢡ(ꢢ)< 0, ꢡ(ꢢ) > 0.20ꢓꢣ. ꢤ., H(r) < 0 and
|
ꢕ(ꢢ)| > ꢥ(ꢢ) interactions with covalent character [49].
The electrostatic hydrogen bonds were confirmed by the small values of ρ(r) and the positive
values H(r).
ꢒ
Since Laplacian of electron density is positive i.e., ꢠ ꢡ(ꢢ) > 0, the electron density is less
than 0.10 a.u. (ρ(r) < 0.10 a.u.) and electronic energy density is positive (H(r) > 0).The
interactions N19–H33...O4, O5–H32...O4, and N24–H34...O3 in Table 3 were closed-shell
interactions and interaction N24–H35...O3 is covalent.
3
.3. Hirshfeld surface analysis
The Hirshfeld surface [50-52] and associated finger print analysis [53-55] were done with the
aid of a powerful graphical tool CrystalExplorer3.1 program [56], which take
crystallographic information file as an input file. The Hirshfeld surfaces and finger print plots

of the titled compound are depicted in Figure 5. The surfaces have been mapped over
dnorm(1), shape index (2), curvedness (3) and fragment path (4) in the range of -0.7398 –
1
.7522 Å, -1.00 – 1.00 Å, -4.00 – 0.400 and 0.00 – 14.00 Å, respectively (Figure 5). The
mapped dnorm surfaces of the title compound shows three interactions: the first interaction
between the hydrogen atom of the acid group (H3O) with the oxygen atom (O4) of the acid
group, labelled as ‘a’ and ‘a'’, which was envisaged as bright red regions. The second and
third interactions between hydrogen atoms (H2N1 and H1N1) of sulfonamide group with the
oxygen atom (O1) of sulfonamide group labelled as ‘b’ and ‘b'’, ‘c’ and ‘c'’, which was
envisaged as faint red regions. The decomposition analysis of fingerprint plots reflects that
O...H/H...O (33%) interactions give the major contribution towards Hirshfeld surface and are
visualized as two distinct spikes with almost equal length. The upper spike labelled as ‘1’
corresponds to the donor spike (hydrogen atom in acid group interacting with oxygen atom of
the acid group and hydrogen atoms in sulfonamide group interacting with oxygen atom of the
sulfonamide group), the lower spike labelled as ‘2’ being an acceptor spike (oxygen atom of
the acid group interacting with hydrogen atom of acid group and oxygen atom of the
sulfonamide group interacting with hydrogen atoms of sulfonamide groups). The second
major contribution from H...H (27%) interactions appear in the middle of the scattered points
in the two-dimensional fingerprint maps. The remaining contributions were mostly due to
H...C (16%), H...Cl (12.1%), O...C (3.5), C...Cl (2.9%), C...C (2.4%), H...N (2.2), O...N
(0.4%) and O...O (0.3%).
3
.4. Optimization of geometry
The geometry optimization of BACSBA compound (Figure S4) was performed by using DFT
conjugation with B3LYP/6-311++G(d,p) basis set. Optimized structure of the titled
compound has ground state energy -1810.37965193 a.u. and possess C1 point group.
Selected geometrical parameters, viz. bond lengths (Å), bond angles (º) and torsional angles
(
º) of BACSBA compound were outlined in Table 4.
The C-C bond lengths (DFT/XRD) of phenyl rings were in the range of 1.379-1.430/1.368-
.426 Å (PhI) and 1.393-1.397/1.35-1.39 Å (PhII) and for the benzene ring, the C-C bond
1
length was 1.3993 Å [57]. The bond length of C20-N19 was 1.35620/1.346 Å (DFT/XRD),
which was much shorter than the single bond C-N length 1.49 Å [58] and thereby supporting
the presence of some character of a conjugation or double bond [59]. For the carboxylic
group, the bond lengths were (DFT/XRD) C31-O4 = 1.22146/1.232 Å, C31-O5 =
1
.35789/1.307 Å, O5-H32 = 0.96831/0.81 Å. The literature data for the similar derivatives
were 1.20772/1.252 Å, 1.35213/1.273 Å, 0.96872/0.8185 Å [24], 1.201/1.208 Å, 1.359/1.304

Å, 0.96749/0.886 Å [60], which shows close agreement with that of the titled compound. The
C8-C11 bond length (DFT/XRD) was 1.74327/1.7295 Å, which are in accordance with
reported values 1.75083/1.720Å [24]. The bond lengths of sulfonamide group were S2-O3 =
1
1
1
1
.45602/1.4448Å, S2-O6 = 1.45595/1.4211Å, S2-N34 = 1.66250/1.5978 Å, C7-S2 =
.81239/1.7565 Å, which were close to the reported values 1.45235/1.4374 Å,
.45598/1.4258 Å, 1.66847/1.5884 Å, 1.82275/ 1.78 Å [24], 1.457/1.435 Å, 1.456/1.423 Å,
.706/1.636 Å, 1.794/1.756 Å(DFT/XRD) [27].
The bond angles around C8 atom were (DFT/XRD) C7-C8-C25 = 121.12101/121.51º, C7-
C8-Cl1 = 121.33440/120.77º, C25-C8-C11 = 117.54416/117.72º and the asymmetry in angles
was due to the presence of electronegative atom C11. At C31 position, the bond angles
(DFT/XRD) were O4-C31-O5 = 120.33229/122.01º, C21-C31-O4 = 125.72039/123.25º,
C21-C31-O5 = 113.94732/114.74º and the asymmetry in these angles confirms the existence
of interactions between acid groups. The bond angles around C7, S2 and N24 positions
(DFT/XRD) were C7-S2-N24, O3-S2-N24, C7-S2-O3, S2-N24-H34, S2-N24-H35
1
1
06.62024/107.80º,
105.76817/105.91º,
107.69232/107.0º,
116.96940/115.0º,
17.02003/115.0º, respectively, which show interaction between O3 atom of SO group, H34
2
and H35 atoms of NH group.
2
3
.5. Vibrational analysis
The C8-C7-C22-C21-C20-C25 and C15-C13-C11-C9-C27-C29 rings were labelled as PhI
and PhII, respectively. The computational (scaled) wave numbers, experimental FT-IR, FT-
Raman bands and assignments are presented in the Table S1.
The carboxylic acid group was characterized by the OH stretch, C=O stretch and OH out-of-
plane deformation, C-O stretch and OH in-plane deformation. For the titled compound, the
-1
OH stretching mode was theoretically observed at 3627 cm with IR intensity 125.4641,
Raman activity 174.4250 and a PED of 100%. Kavitha et al. reported the OH stretching mode
-1
for 4-chloro-3-sulfamoylbenzoic acid at 3623 cm theoretically [24]. The carboxyl group
-1
-
C=O stretching vibrational mode displayed a band at 1681 cm in the IR spectrum, 1682 cm
1
-1
in the Raman spectrum, and theoretically at 1684 cm with IR intensity 457.8412, Raman
-1
activity 103.1175 and a PED of 73 %, as expected in the region 1600-1750 cm [61]. The
-1
-1
bands were observed at 627 cm (IR spectrum), 674, 643, 629 cm (Raman spectrum) and at
-1
6
72, 645, 630 cm (theoretically) were assigned to C=O deformation modes, which was
-1
expected in the region 625±70 cm [62]. Kavitha et al. reported the C=O deformation modes
-1
-1
at 675cm (Raman spectrum) and at 674, 646 cm theoretically [24]. The O-H in-plane
-1
deformation, coupled to the C-O stretching mode is expected in the region 1390±55 cm [61].

-1
For the titled compound, this mode observed at 1346 cm (theoretically), and experimentally
-1
-1
observed at 1343 cm (IR spectrum) and at 1342 cm (Raman spectrum).
The frequency of vibration modes associated with NH group is expected in the regions 3300-
2
-1
-1
-1
-1
3
540 cm (stretching), 1640-1580 cm , 1300-1100 cm and 710-585 cm (deformation
modes), respectively [61-64]. The NH group stretching frequencies were observed at 3368
2
-1
-1
cm in the IR spectrum, 3367 cm in the Raman spectrum and assigned theoretically at 3552
-1
cm with 52.3853 IR intensity, 46.3442 Raman activity and a PED of 50% (asymmetric
-1
-1
stretching mode), and at 3283 cm in the IR spectrum, 3279 cm in the Raman spectrum,
-1
3
421 cm theoretically with 49.4078 IR intensity, 97.9981 Raman activity and a PED of 50%
(
symmetric stretching mode). For a similar derivative, NH group asymmetric stretching
2
-
1
-1
-1
-
bands were observed at 3401 cm (IR spectrum), 3403 cm (Raman spectrum), 3495cm
-1
(
theoretically), and the symmetric stretching mode at 3281 cm (IR spectrum), 3279 cm
1
-1
(
Raman spectrum) and 3383 cm (theoretically) [24]. The observed difference between the
-1
-1
calculated and experimental N-H vibrational values are 184 cm and 185 cm in the IR
-1
-1
spectrum, 185 cm and 142 cm in the Raman spectrum, due to N-H---O interactions in solid
phase. For the BACSBA compound, NH group deformation modes were assigned at 1497,
2
-1
-1
-1
9
90 cm in the IR spectrum, 1497, 991 cm in the Raman spectrum and at 1510, 992 cm
theoretically.
-1
The vibrational modes associated with N-H group was expected in the region 3500-3300 cm
-1
(
stretching modes) and around 1500 cm (deformation modes) [61-66]. In case of the
synthesized compound (BACSBA), the N-H stretching was assigned theoretically at 3389
-1
cm with 172.5639 IR intensity, Raman activity 108.0501 and a PED of 99%. Kuruvilla et al.
-1
reported N-H stretching mode theoretically at 3393 cm [67]. The deformation modes were
-1
-1
assigned at 1416 cm in the IR spectrum, 1558, 1417 cm in the Raman spectrum and at
-1
1
556, 1417 cm theoretically, which was in agreement with reported values [65].
The asymmetric and symmetric stretching vibrational mode of SO group was expected in the
2
-1
-1
region 1330-1295 cm and 1150-1025 cm , respectively [64]. For the titled compound, the
-1
-1
asymmetric modes were observed at 1291 cm in the IR spectrum, 1290 cm in the Raman
-1
-1
spectrum and theoretically at 1292 cm , while the symmetric modes at 1083 cm in the IR
-1
-1
spectrum, 1080 cm in the Raman spectrum and theoretically at 1081 cm . These were in
-1
-1
agreement with reported values of 1284 cm (IR spectrum), 1285 cm (Raman spectrum),
-1
-1
-1
1
286 cm (DFT) (asymmetric) and 1090, 1072 cm (Raman), 1090, 1071 cm (DFT)
(
symmetric) [24]. The deformation modes of SO group were expected in the regions -
2
-1
-1
-1
scissoring 560±40 cm , wagging 500±55 cm and twisting 440±50 cm [61]. In the titled

-1
compound, these modes were observed at 460 and 381cm in the Raman spectrum and
-1
theoretically at 461 and 384 cm .
The stretching vibrational modes of SN group were observed at 789 cm in the IR spectrum,
-1
-
1
-1
7
1
90 cm in the Raman spectrum and theoretically at 794 cm with high IR intensity
14.4742, low Raman activity 9.0882 and a PED of 79% which was in accord with literature
-1
-1
values of 785 cm (Raman spectrum) and 782 cm (DFT) [24].
-1
-1
The vibrational mode observed at 643 cm in the Raman spectrum and calculated at 645 cm
with 44.3873 IR intensity, 12.2815 Raman activity and a PED of 19% was assigned for CS
stretching vibrational mode of BACSBA compound. For the titled compound, CCl stretching
-1
-1
modes were observed at 497 cm (IR spectrum), 499 cm (Raman spectrum) and
-1
-1
theoretically at 504 cm with a PED 20% (DFT), as expected in the region 710-505 cm [61].
For the CH groups, the stretching and deformation (scissoring, wagging, twisting and
2
-1
-1
rocking) modes appear in the range 3050-2935 cm and 1500-800 cm , respectively [61, 62].
-1
The CH modes of the titled compound were assigned at 2943, 2901 cm (IR), 2942, 2903
2
-1
-1
-1
-
cm (Raman), 2943, 2902 cm (DFT) (stretching) and 1432, 1330 cm (IR), 1431, 1329 cm
1
-1
(
Raman), 1436-1334 cm (DFT) (deformation modes), which were in agreement with
reported values [65].
-
The CH stretching modes of the aromatic rings were normally expected above 3000 cm
1
-1
-1
[
61,62]. Here, these modes were displayed at 3105 cm in the IR spectrum, 3102 cm in the
-1
-1
Raman spectrum and at 3106, 3104 cm theoretically for PhI, 3065, 3040, 3030 cm in the
-1
-1
IR spectrum, 3060, 3039 cm in the Raman spectrum and at 3068-3029 cm theoretically for
PhII. For aromatic rings, the CH in-plane and out-of-plane deformations were expected above
-1
and below 1000 cm [61]. In the present case, the modes were assigned as follows: i) for PhI
-1
-1
a) in-plane deformations at 1416, 1222 cm (IR spectrum), 1417, 1221 cm (Raman
-1
-1
spectrum) and 1417, 1222 cm (theoretically), b) out-of-plane deformations at 887, 825 cm
-1
-1
(
IR spectrum), 885, 823 cm (Raman spectrum), 888, 827, 826 cm (theoretically); for PhII
-1
a) in-plane deformations at 1301, 1153, 1137 cm (IR spectrum), 1428, 1381, 1300, 1151,
-1
-1
1
136 cm (Raman spectrum), theoretically in the range 1470-1137 cm , b) out-of-plane
-1
-1
deformations at 949, 725, 689 cm
(IR spectrum), 951, 879, 716, 688 cm
(Raman
-1
spectrum) and theoretically at 967, 952, 881, 716, 688 cm , respectively [61].
-1
The phenyl ring stretching modes were attributed at 1569, 1343, 1287 cm (IR spectrum),
-1
-1
1
571, 1342, 1285 cm (Raman spectrum) and in the range 1572-1289 cm (theoretically) for
-1
-1
PhI and 1584, 1565, 1301 cm (IR spectrum), 1584, 1563, 1300 cm (Raman spectrum) and
-1
in the range 1584-1300 cm (theoretically) for PhII. The ring breathing mode for PhII

-1
(
mono-substituted phenyl ring) assigned at 977 cm in the Raman spectrum and theoretically
-1
at 978 cm has low IR intensity (2.0156), medium Raman activity (24.2603) with a PED of
-1
2
7%. These values were close to the theoretical value of 977 cm reported by Krishna et al.
-1
[
59]. The ring breathing mode was observed at 980 cm in the Raman spectrum and at 982
-1
cm theoretically for PhI.
.6. Frontier molecular orbitals analysis
3
Easy way for the calculation of global reactivity parameters is accounting the energy value
difference between the highest occupied molecular orbital (HOMO) and the lowest
unoccupied molecular orbital (LUMO) of a molecule. The combination of these orbitals
commonly called as frontier molecular orbitals (FMOs) are the outmost orbitals of the
molecules. The energy parameters of HOMO and LUMO are directly associated to electron
donating ability and electron accepting ability of molecule, respectively, and the energy gap
difference between these orbitals plays crucial role to explain reactivity parameters of the
molecules. The energy values of the frontier orbitals were calculated at DFT/B3LYP/6-
3
11G++ (d,p) method.
The depiction associated to spatial distribution of HOMO and LUMO, related energies and
energy gap is summarized in Figure S5. It was observed that the HOMO (MO: 88) was
confirmed over whole molecule other than amine group, chloro group and partially on
methylbenzene ring; while, the LUMO (MO: 89) was localized over whole molecule other
than methyl benzene ring and sulfonamide group. Consequently, computed absorption band
λmax = 327 nm (Figure S6) implies transition between HOMO→LUMO orbitals of the present
investigated compound. The transitions, wavelength, oscillator strengths and CI coefficient
calculated by DFT/B3LYP/6-311G++ (d,p) method are given in Table S2.
The global chemical parameters of title compound are: EHOMO (88) = -6.4280 eV, ELUMO (89)
=
-2.0779 eV, ∆E =4.3501eV, ionization potential (I) = 6.4280 eV, electron affinity (A)
2.0779 eV, electronegativity (χ) = 4.2529 eV, global hardness (η) = 2.1750 eV, chemical
=
softness (ν) = 0.4597 eV, chemical potential (ꢀ) = -4.2529 eV and electrophilicity index (ω) =
.1579 eV [68]. The negative value of the chemical potential indicates that the compound
was stable.
.7. Local reactivity calculations (molecular electrostatic surface potential and Fukui
4
3
function)
The molecular electrostatic surface potential (MESP) is a most commonly used quantum
chemical descriptor for understanding the connection between the structure and chemical
reactivity through visualisation of three-dimensional colour coding based on electron density

[
69-71]. It is a unique and valuable technique for the assessment of chemical and physical
parameters, particularly for pharmaceutically important molecules. Politzer et al. [72] used
MESP to illustrate a variety of chemical processes like chemical reactivity, hydrogen
bonding, etc. In the three-dimensional MESP plot depicted in Figure S7, electron rich regions
(negative potential areas) (for instance, vicinity over un-protonated atoms like oxygen atoms
of sulfonamide group, which are good hydrogen bond acceptors as well as most probable
sites for electrophilic attack) were marked with red colour. On the contrary, the electron poor
regions (positive potential areas) (such as vicinity over protonated atoms like hydrogen atoms
of amines and acid groups, which are good hydrogen bond donors as well as most probable
sites for nucleophic attack) were marked with blue colour. From these observations, it can be
concluded that the SO and NH groups play a crucial role in the chemical and intermolecular
2
2
interactions.
Parr and Yang in 1984 proposed a technique called Fukui function for examining and
analysis of the most reactive sites for electrophilic or nucleophilic reactions in a molecule,
when the number of electrons is altered (either addition or remove). Fukui calculations were
performed by altering the multiplicity and charge. This also helps to examine the molecular
polarizability, electronic structure and electrostatic potential surface [73-76].
Fukui functions can be calculated using the following equations
-
f = q r (N) – q r (N-1) for electrophilic attack
(8)
(9)
r
+
r
f = q r (N+1) – q r (N) for nucleophilic attack
0
r
f = ½[q r (N+1) – q r (N-1) for radical attack
(10)
th
In these equations, qr is the atomic charge at the r atomic site is the anionic (N+1), cationic
N-1) and neutral (N) molecule [77].
(
The local softness is related to Fukui function as follows:
-
sr-fr- = Sf for electrophilic attack
(11)
(12)
(13)
k
+
sr+fr+ = Sf for nucleophilic attack
k
0
sr0 fr0 = Sf for radical attack
k
From the analysis of dual descriptor, the reactive sites (nucleophilic and electrophilic) of the
title compound explained. From the Table 5 values, the reactivity order for nucleophic attack
C8≈C9>C31>C22>O4>C20>O5>Cl1>N24>C27>S2. On other hand, for electrophilic attack
we can observe N19>C7>C25>C21>C15>O3>O6>C29>C13>C11.
3
.8. Chemical Bonding Analysis (Electron Localization Function and Localized Orbital
Function)

The two dimensional graphical depiction of Localized Orbital Locator (LOL) and Electron
Localization Function (ELF) are shown in Figures S8 and S9. The electron localization
function can be helpful to examine the electron localization in a molecular system [78]. LOL
is also a similar study about the localized electron cloud. The electron localization can be
calculated by applying Pauli repulsion on two like-spin electrons [79]. The bonding,
reactivity and chemical structure can be studied in detail using the data [80]. For ELF, 1
(denotes with red colour) and 0 (denotes with blue colour) are the maximum and minimum
limits [81].
For the examined compound, the maximum Pauli repulsion was indicated with red colour
around hydrogen atoms with single electrons and carbon atoms marked by blue region shows
minimum Pauli repulsion. Covalent regions marked by red colour show high LOL values,
while electron depletion between valence shell and inner shell marked blue coloured areas in
the Figure S8 [82].
3
.9. Natural bond orbital (NBO)
Natural bond orbital (NBO) analysis was done by using NBO 3.1 program [83] actualized in
the Gaussian09 suite at DFT conjugation with B3LYP/6-311++G(d,p) method, which provide
a suitable basis for analysing the hyper conjugative or charge transfer interactions and also
analysis of inter and intermolecular bonding in molecules or systems. The analysis second
order perturbation theory revealed that, the stabilization energy from electron delocalization
over the natural bond orbital or hyperconjugation effect is acquired as
ꢧ ꢩ(ꢆ,ꢪ)ꢫ
ꢨ
ꢦ(ꢒ)
=
(14)
ꢬꢨꢭꢬꢮ
th
th
Here, ꢯ and ꢯ are the energies of i and j NBO, named as the acceptor and donor orbitals,
ꢪ
ꢆ
respectively for a hyperconjugation. ꢰ(ꢱ, ꢲ) and ꢳ are the elements of off-diagonal Fock-
ꢪ
th
th
th
matrix between i and j NBOs and electron population on j orbital, respectively [84,85].
(2)
The enormous estimations of E mirror the presence of more noteworthy interaction between
electron-contributors and electron-acceptors, and the degree of conjugation of the whole
framework.
Second order interactions obtained by the natural bond orbital analysis are tabulated in Table
(2)
(2)
6
and 7. The π-electron delocalization between these bonds were evident from the E (E =
2.53 kcal/mol) values of electron donation from bonding π(C7-C22) orbital to anti-bonding
2
*
*
π (C8-C25) orbital. There was electron delocalization between the π and π orbitals of these
bonds reflected by higher value of stabilization energy. We find large hyper-conjugation
(2)
stabilization (E = 43.80 kcal/mol and 30.76 kcal/mol) due to donation of lone pair of O5

*
*
(
LP(2)) to the π (O4-C31) orbital and O4 (LP(2)) to the σ (O5-C31) orbital, respectively.
This was expected due to resonance effect within the acid group. No significant
hyperconjugation involving NBOs with atomic orbitals from Cl is observed except donation
*
(2)
from a lone pair of Cl (LP(3)) to π (C8-C25) with E = 15.21 kcal/mol, and it comes from
small energy difference and a moderate Fock-matrix element value. There are moderate
stabilization energies due to electron delocalization within the SO NH as shown in the
2
2
Tables 6 and 7. The title compound have ‘push (acid group is capable to push electrons) - pull
chloro group is capable to pull electrons)’ groups at para-position and accordingly, making it
a potential contender for optical application.
.10. Sensitivity towards autoxidation
(
3
Understanding of degradation path and development of a protocol for the removal of organic
pollutants from aquatic media is very essential. Therefore, investigation of lowest H-BDE
values is important for the development of new pharmaceutical drugs. This quantity
calculation allows the assessment of the possibility of a drug candidate to form degradation
products while being stored [86, 87]. Another side was connected to the phase I drug
metabolism, during which the carbon-hydrogen bonds were broken for hydroxylation [88,
8
9]. This underlines the significance of the H-BDE amount to foresee the destiny of the
recently combined medications from both ecological and pharmaceutical angles. However,
the conduction of these types of studies was a rather tedious task [90, 91], but it could be
rationalized and optimized with the of help DFT calculations. Therefore, considering the
importance of calculation of H-BDE values, we have performed the calculations and depicted
the results in Figure 6.
From the environmental angle [92], as per the earlier literature reports, it can be concluded
that the sensitivity towards the autoxidation mechanism was expressed by the H-BDE values
that take esteems in a scope of 70–85 kcal/mol. From the analysis of H-BDE values it can be
concluded that the title compound could not be sensitive towards autoxidation mechanism
due to absence of H-BDE values below 85 kcal/mol. The BDE values have been calculated
for all other single acyclic bonds. The title compound has lowest BDE for S-N bond, with
BDE value of 54.08 kcal/mol reflecting that degradation could start precisely by breaking of
S-N bond.
3
.11. Nonlinear Optical (NLO) properties
Figure 7 shows the DFT/CAM-B3LYP/6-311++G(d,p) graphics for the dynamic average
linear polarizability and for the linear refractive index as a function of the applied electric
field frequency. As it can be seen the 〈ꢀ(−ꢁ; ꢁ)〉 values increases monotonically with the

frequency from the static values of 31.1 × 10ꢭꢒꢜꢴꢵꢤ to 34.4× 10ꢭꢒꢜꢴꢵꢤ (ω=0.10 a.u.),
presenting a percentage increase of 11%. In the same frequency set the linear refractive index
goes from 1.62 to 1.70.
The obtained value for the static average second hyperpolarizability was 〈ꢃ(0; 0,0,0)〉 =
2
3.11 × 10ꢭꢙꢶꢴꢵꢤ. The dynamic values of the second hyperpolarizabities, corresponding to
the dc-Kerr effect and the IDRI process, increases monotonically with the increase of the
electric field frequency (Figure 8), reaching the values 〈ꢃ(−ꢁ; ꢁ, 0,0)〉 = 39.42 × 10ꢭꢙꢶꢴꢵꢤ
and 〈ꢃ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉 = 55.73 × 10ꢭꢙꢶꢴꢵꢤ at
ω = 0.10ꢓꢣ. ꢤ., respectively. Particularly, the
values of the second hyperpolarizabilities at the frequency of ꢁ = 0.086ꢣ. ꢤ. ( λ=532nm)
were 〈ꢃ(−ꢁ; ꢁ, 0,0)〉 = 33.1× 10ꢭꢙꢶꢴꢵꢤ and 〈ꢃ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉 = 43.1ꢓ × 10ꢭꢙꢶꢴꢵꢤ.
Figure 9 shows the DFT/CAM-B3LYP/6-311++G (d, p) results for the third order nonlinear
susceptibility as function of the applied electric field frequencies for the BACSBA crystal. In
this frequency range, the χꢙ values goes from the static value ꢘ = 48.66 × 10 ꢷ /ꢕ to
ꢙ
ꢭꢒꢒ
ꢒ
ꢒ
ꢘꢙ = 117.2 × 10ꢭꢒꢒꢷ /ꢕ . Table 8 presents some experimental results for organic
materials at 532 nm. It can be observed that the χꢙ value for BACSBA was more than five
times greater than the experimental results presented in the Table 8 [93]. However, the
ꢒ
ꢒ
calculated χꢙ value for BACSBA (90.68ꢓ × 10ꢭꢒꢒꢷ /ꢕ ) was nearly 46 times higher than
ꢒ
ꢒ
the experimental value obtained for (3Br4MSP) [96] (1.99 × 10ꢭꢒꢒꢷ /ꢕ ). Based on these
results, it can be concluded that BACSBA could be investigated for potential use as nonlinear
material.
ꢒ
ꢒ
3
.12. Thermal analysis
Thermo gravimetric-differential thermal analysis (TG-DTA) spectrum (Figure 10) of
o
BACSBA crystal was recorded on EXSTAR TG/DTA SII 6300 instrument up to 650 C with
o
heating rate 5 C/min in a nitrogen environment. The primary weight loss of 1.1% over the
o
o
temperature range of 29 C to 234 C was due to elimination of moisture and other volatile
materials. The BACSBA crystal faces decomposition in three stages, the first from 235°C to
4
5
00°C with major mass loss of 48%. Later, a mass loss of 7 % was observed from 400°C to
00°C, and finally, 44% of mass was lost in the third stage above 650°C. In the TGA graph a
sharp endothermic peak was seen at 238°C which reflect the melting of single crystal or
phase transition temperature. The shape of the peak indicates the good level of crystallinity of
the title compound. From the above thermal analysis, we conclude that the BACSBA crystal
is stable up to 234°C without any measurable decomposition. Hence, it may be stated that the
title compound is stable and could be used as a NLO material up to 234°C.

3
.13. Biological activity studies
(a) Antifungal analysis
The synthesized compound BACSBA was screened for their in vitro antifungal activity. The
antifungal strains A.niger (MTCC-1881), F.oxysporum (MTCC-1755) and A.Foetidus
(
NCIM-505) were used and Ketoconazole was used as a standard drug. Zone of inhibition
ZI) was expressed in mm (Table S3). The titled compound BACSBA exhibited promising
(
antifungal activity against all the fungal strains when compared with the standard drug
Ketoconazole. This could be due to the presence of sulfonamide moiety present on the
benzene ring and other functional groups enhanced the activity.
(b) Antioxidant analysis
Compound BACSBA was evaluated at various concentrations (25, 50, 75, 100 µg/mL) using
Butylatedhydroxytoluene (BHT) and Ascorbic acid as standards in DPPH and NO methods
(Tables S4 and S5). Compound BACSBA displayed significant activity at all the
concentrations in evaluation with the standard drugs. The reason could be the presence of
sulfonamide group and other functional groups which improved the antioxidant activity.
4
. Conclusion
The SCXRD and optimization of geometry results clearly revealed that the titled compound
has an L-shaped structure. Theoretically predicted geometrical parameters and wave numbers
were in accordance with the experimental results. HOMO was confined over whole molecule
other than amine group, chloro group; while, LUMO was confined over whole molecule
other than methyl benzene ring and sulfonamide group. The MESP illustration revealed that
the negative potential was affirmed over deprotonated atoms, possible sites for electrophilic
attack; the positive potential was affirmed over protonated atoms, possible sites for
nucleophilic attack. H-BDE values show that BACSBA molecule was not sensitive towards
the autoxidation. However, the titled compound has very low BDE value i.e., 54.08 kcal/mol
for the S-N bond, which indicates that degradation could start by breaking of the S2-N24
bond. From the thermal analysis, it might be concluded that the titled compound was stable
o
and can be utilized as NLO material up to 234 C. In the current study, we have used the SM
method at DFT/CAM-B3LYP/6-311++G (d,p) level to calculate the electrical parameters
such as total dipole moment (µ), the average linear polarization 〈α(−ω, ω)〉 and the second
average hyperpolarizability IDRI (ꢓ〈ꢃ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉) for the BACSBA crystal. Optical
parameters such as the linear refractive index (ꢑ) and the third order nonlinear macroscopic
ꢙ
susceptibility (ꢘ (−ꢁ; ꢁ, ꢁ, ꢁ)) of crystal structure BACSBA were calculated. The

examined compound presented better values in the third order macroscopic susceptibility
(ꢙ)
than measured experimental results presented in the literature. The ꢘ (−ω; ω, ω, −ω)-value
of the compound was 5.59 to 45.57 times greatest than the results measured experimentally in
the literature. Therefore, the BACSBA crystal has a good suitability for use as a material in
applications involving NLO properties. Also, the synthesized molecule displayed most
promising antifungal and antioxidant activities. The BACSBA compound exhibited
significant antifungal and antioxidant activities compared with the standard drugs.
Furthermore, there could be a scope of exploring this class of scaffolds as new and potent
antifungal and antioxidant agents which will be a prominent application for medicinal
chemists.
Declaration of interests
There was no potential conflict of interest declared by authors.
Acknowledgement
The authors express their grateful thanks to University Grant Commission-Network Resource
Center (UGC-NRC), School of Chemistry, University of Hyderabad for providing
computational support. Authors also thankful to SAIF, Gauhati University and I.I.T. Madras
for the analysis support.
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Figures
Scheme -1: Synthetic scheme for 2-(benzylamino)-4-chloro-5-sulfamoylbenzoic acid
(BACSBA).
Figure 1. Some potent biologically active chlorosulfonamide drug moieties.
Figure 2. ORTEP view of 2-(benzylamino)-4-chloro-5-sulfamoylbenzoic acid (BACSBA)
with thermal ellipsoids drawn at 50% probability.
Figure 3. Packing of molecules in the crystal lattice of BACSBA.
Figure 4. Dipole moment values as function of the iterative steps.
Figure 5. Analysis of 3D-Hirshfeld surfaces and 2D-finger print plots of BACSBA molecule.
Figure 6. H-BDE (violet color) and BDE (green color) values for BACSBA molecule.
Figure 7. Linear polarizability and linear refractive index as function of the electric field
frequencies
Figure 8. Second hyperpolarizabilities 〈ꢃ(−ꢁ; ꢁ, 0,0)〉 and 〈ꢃ(−ꢁ; ꢁ, ꢁ, −ꢁ)〉
(
ꢱꢑꢓꢤꢑꢱꢸꢵꢓꢹꢺꢓ10ꢭꢙꢶꢴꢵꢤ) as function of the electric field frequencies.
Figure 9. Third-order nonlinear susceptibility (10ꢭꢒꢒꢷ /ꢕ ) as function of the frequency.
ꢒ
ꢒ
Figure 10. DTA/TGA graph of BACSBA compound.
Tables
Table 1. Crystal data and structure refinement for BACSBA.
Table 2. Geometric parameters for hydrogen bonds (A, °) operating in the crystal structure of
BACSBA.
Table 3. Topological analysis performed via QTAIM, all data are in a.u.