Synthesis and characterization of novel sulfonamides derivatives and their antimicrobial, antioxidant and cytotoxicity evaluation

Article abstract of DOI:10.4314/bcse.v31i3.13

Five novel sulfonamides derivatives HR5-HR8 and HR14 were synthesized by sulfonylation of primary or secondary amine in the presence of base through nucleophilic substitution reaction. Structural elucidation was carried out through FT-IR, UV, ¹

Full text of DOI:10.4314/bcse.v31i3.13

Bull. Chem. Soc. Ethiop. 2017, 31(3), 491-498.
2017 Chemical Society of Ethiopia and The Authors
DOI: http://dx.doi.org/10.4314/bcse.v31i3.13
ISSN 1011-3924
Printed in Ethiopia

SYNTHESIS AND CHARACTERIZATION OF NOVEL SULFONAMIDES
DERIVATIVES AND THEIR ANTIMICROBIAL, ANTIOXIDANT AND
CYTOTOXICITY EVALUATION
1
*
1
2
3
1
Hajira Rehman , Dr. Abdul Qadir , Zulfiqar Ali , Shahid Nazir , Asmat Zahra and Tanzeela
4
Gulab Shahzady
1
Department of Chemistry, University of the Punjab, Lahore, Pakistan
2
Department of Basic Sciences & Humanities, University of Engineering and Technology
Lahore KSK Campus, Pakistan
Department of Chemistry, Comsat Institute of Information & Technology Riawind road
3
Lahore, Pakistan
4
Department of Chemistry, Lahore Garrison University, DHA phase VI Lahore, Pakistan
(
Received February 20, 2016; Revised December 16, 2017; Accepted December 21, 2017)
ABSTRACT. Five novel sulfonamides derivatives HR5-HR8 and HR14 were synthesized by sulfonylation of
primary or secondary amine in the presence of base through nucleophilic substitution reaction. Structural
1
elucidation was carried out through FT-IR, UV, H NMR, MS and elemental analysis. Prepared compounds were
evaluated against pathogenic strains of bacteria (S. aureus and E. coli) and fungi (A. flavous and A. nyger). Results
were compared against standard antifungal and bacterial drug already available in market (isoconazole and
sulfmethoxazole). It was found that compound HR14 showed good activity with MIC 1.5 µg/mL and 2.0 µg/mL
for S. aurues and E. coli, respectively. While HR5 showed best antifungal activity with zone of inhibition
2
7.2+0.12 mm (MIC: 5.25 µg/mL) and 18.1+0.12 mm (MIC: 12.5 µg/mL) against A. flavous and A. nyger,
respectively. Synthesized compounds were also tested for their in vitro antioxidant activity by using DDPH.
Amongst all compounds HR5 was found to have potential activity with 15.60% antioxidant activity at 6 mM
concentration.
KEY WORDS: Sulfonamide, DPPH, AntiMICrobial activity
INTRODUCTION
Sulfonamides drugs have been used as preventive agents in chemotherapy against various
diseases [1]. More than 30 drugs having sulfa drug as a functional group are in clinical use, such
as antibacterial [2], antifungal [3], antiprotozoal [4], anti-inflammatory [5], and translational
initiation inhibitors [6]. More recent use of sulfonamides are as an anticancer agent [7], antiviral
HIV [8], and in Alzheimer’s disease [9]. They are used effectively for the treatment of
ulcerative colitis [10], urinary, intestinal and ophthalMIC infections and also for obesity [11].
Beside their vital role in human medicine they are also showing their promising importance in
field of veterinary and agricultural sciences. Due to presence of SO
2
NH− group most important
role of sulfonamide in medicinal field is as an antibacterial agent. Synthesis of bacterial DNA
and RNA requires tetrahydrofolate as a co-factor, which is inhibited by sulfonamides, so
production of new DNA and RNA dropped from lack of tetrahydrofolate which eventually
decayed bacteria. Newer sulfonamides and their derivatives has obtained great attention in
pharmaceutical field in order to compete life threatening issues caused by drug resistant strains
of bacteria, i.e. Methicillin resistance as they have unusual ability of acclimatization against
stress caused by antibiotics [12]. Disease causing organisms become much resistant when
treated medically with routine antibiotic drug molecule, with appearance of additional species as
per mutation, conjugation, transduction or transformation. So synthesis of new sulfonamides and
_
*
_________
Corresponding author. E-mail: aries_cute8@hotmail.com
This work is licensed under the Creative Commons Attribution 4.0 International License

492
Hajira Rehman et al.
their derivatives have got more attention from researchers for its application in the field of
medicine sciences and medical chemistry. In the present study five sulfonamide derivatives have
been synthesized by the reaction of p-toluene sulfonyl chloride with NH group containing drugs
2
such as ceftriaxone, cefepime, nicotinamide (vitamin B), cefadroxil, and nimsulide, respectively
and their biological activities were evaluated by using bacterial and fungal strains such as
Escherichia coli, Aspergillum niger and Aspergillum flavus.
EXPERIMENTAL
1
6
H NMR spectra were conducted on Bruker 400 MHz spectrometer in DMSO-d with
tetramethylsilane as internal standard. MS data was recorded on Finnigan MAT 112 mass
spectrometer. Elemental analysis was performed by using Perkin Elmer elemental analyzer.
Melting points were taken on Gallenhamp MP Apparatus MP70. Infrared spectra were recorded
-
1
on Cary 630 Agilent FT-IRin the range between 4000-600 cm . Absorption spectra were
recorded by PGT90+ UV-Vis spectrophotometer.
General procedure
In this work efficient method based on Hinsberg test was used for preparation of sulphonamides,
i.e. sulfonylation of primary or secondary amine in presence of base resulting in nucleophilic
attack by amine. For sulfonylationtosyl chlorides were used [13] and base were used for
neutralization of generated HCl, i.e. pyridine in synthesis of sulfonylmethylamide [14]. In the
present work base sodium carbonate was used for neutralization of HCl. It was a one pot
reaction, amine containing drug (0.001 M) in water was stirred and pH was noted, then
equimolar sulfonyl chloride was added and mixture was allowed to stirrer for 2 hours and pH
was monitored. Precipitates were separated by filtration and were purified by preparatory thin
layer chromatography.
Synthesis of (6R,7R)-7-((Z)-2-(methoxyimino)-2-(2-(4-methylphenylsulfonamido)thiazol-4-
yl)acetamido)-3-(((2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thio)methyl)-8-
methylene-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (HR5)
Title compound HR5 was prepared by above mentioned general procedure and was purified by
-
1
using mobile phase DCM:EtOH, 50:50 with 83% yield. UV-Vis, λmax: 270 nm. FT-IR (cm ):
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Synthesis and characterization of novel sulfonamides derivatives
493
1
3
178.19 (S=O str), 1037.18 (C−N str), 1633.80 (C=O), 846.97 (C−S str), 945.04 (S−N str),
1
395.40 (−OH). H NMR (400 MHZ, DMSO-d
6.5, −CHNHCO), 8.11 (1H, s, −CONHNCH ), 7.39-7.47 (2H, d, m, ArH), 7.22 (1H, s,
, δ): 11.22 (1H, s, −COOH), 8.36-8.47 (1H, d, J
6
=
−
=
−
3
CHS−), 7.05-7.11 (2H, m, ArH), 5.68-5.76 (1H, d, J = 6.3, −CHNHCO−), 5.47-5.50 (1H, d, J
1.2, −CHH=CH−), 5.12-5.23 (1H, d, J = 6.2, −NCHS−), 4.70-4.73 (1H, d, J = 1.1,
CHH=CH−), 4.56 (2H, s,−CH
.56 (1H, d, J = 6.5,−CHHS−), 3.31 (3H, s, −NCH
3H, s, −ArCH ); MS (m/z, ESI): calcd. for C26
06.0210615. Anal. calcd. For C26 : C, 42.36; H, 3.4; N, 15.81; O, 20.32; S, 18.10.
2
2 3
SC=N−), 4.15 (1H, s, −NHSO −), 3.92 (3H, s, −OCH ), 3.47-
3
(
7
3
), 3.08-3.17 (1H, d, J = 6.3,−CHHS−), 2.49
H N O S [M+H] 706.0210312; found
26 8 8 4
+
3
26 8 8 4
H N O S
Found: C, 42.16; H, 3.46; N, 15.84; O, 20.17; S, 18.13.
Synthesis of (6R,7R)-7-((Z)-2-(methoxyimino)-2-(2-(4-methylphenylsulfonamido)thiazol-4-yl)
acetamido)-3-((1-methylpyrrolidin-1-ium-1-yl)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-
ene-2-carboxylate (HR6)
Designated compound HR6 was prepared by following the general procedure mentioned earlier
and was purified by using mobile phase DCM:EtOH, 40:60. Compound was obtained with a
-
1
good yield, 85%. λmax 280 nm. FT-IR (cm ): 1158.15 (S=O str), 1045.15 (C–Nstr), 1649.55
1
(
–N–C=O), 825.38 (C−S str), 930.60 (S−N str), 3378.15 (−OH). H NMR (400 MHZ,
DMSO-d
, δ): 8.01-8.03 (1H, d, J = 6.1, −CHNHCO−), 7.62-7.65 (2H, d, J = 8.3, −ArH), 7.44
1H, s, −C=CHS−), 7.32-7.35 (2H, d, J = 8.2, −ArH), 5.52-5.58 (1H, d, J = 6.3, −NHCHCO−),
6
(
5
.08-5.10 (1H, d, J = 5.9, −SCHNCO−), 4.28 (1H, s, −NHSO
NCH ), 3.61 (1H, s, −CH NCH ), 3.37-3.48 (4H, t, J = 7.5, CH
.29 (1H, d, J = 6.5,−CHHS−), 3.07-3.14 (1H, d, J = 6.4,−CHHS−), 2.49 (3H, s, −ArCH
.60 (4H, Q, J = 6.9, CH NCH CH CH −); MS (m/z, ESI): calcd. for C H N O S [M+H]
2
−), 4.01 (3H, s, −OCH
NCH CH −), 3.20-
), 1.44-
3
), 3.81
(
2H, s, −CH
2
3
2
3
3
2
2
3
1
6
3
+
3
2
2
2
26 30
6
7 3
30 6 7 3
34.1094327; found 634.0923741. Anal. calcd. for C26H N O S : C, 49.20; H, 4.76; N, 13.24;
O, 17.64; S, 15.5. Found: C, 49.35; H, 4.75; N, 13.23; O, 17.63; S, 15.16.
Synthesis of N-tosylnicotinamide (HR7)
Following above mentioned procedure labeled compound HR7 was purified by using mobile
-1
phase DCM:EtOH, 60:40 having 76% yield. λmax 285 nm. FT-IR (cm ): 1150.35 (S=O str),
1
1
055.12 (C−N str), 1641.45 (C=O), 815.32 (C−S str), 930.16 (S−N str), 3388.12 (−OH). H
NMR (400 MHZ, DMSO-d
, δ): 9.24 (1H, s, −ArH), 8.84-8.88 (1H, d, J = 8.3, −ArH), 8.51-8.54
1H, d, J = 8.2, −ArH), 8.15 (1H, s, −NHSO −), 7.95-7.97 (2H, d, J = 8.1, −ArH), 7.68-7.71
1H, t, J = 6.4, −ArH), 7.40-7.42 (2H, d, J = 8.2, −ArH), 2.33 (3H, s, −ArCH
). MS (m/z, ESI):
6
(
(
2
3
+
calcd. For
C
13
H
12
N
2
O
3
S
[M+H] 276.5352716; found 276.573781. Anal. calcd. For
Bull. Chem. Soc. Ethiop. 2017, 31(3)

494
Hajira Rehman et al.
C H N O S: C, 56.51; H, 4.38; N, 10.14; O, 17.37; S, 11.60. Found: C, 56.35; H, 4.41; N,
1
3
12
2
3
1
0.8; O,17.43; S, 11.56.
Synthesis of (6R,7R)-7-((R)-2-(4-hydroxyphenyl)-2-(4-methylphenylsulfonamido)acetamido)-3-
methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid (HR8)
By following general procedure labeled compound HR8 was purified by using mobile phase
-
1
DCM:EtOH, 80:20 having 87% yield. λmax 275 nm. FT-IR (cm ): 1160.35 (S=O str), 1053.12
1
(
C−N str), 1647.45 (C=O), 816.32 (C−S str), 940.16 (S−N str), 3368.12 (−OH). H NMR (400
MHZ, DMSO-d , δ): 9.48 (1H, s,−COOH), 8.01-8.03 (1H, d, J = 6.1, −CHNHCO), 7.25-7.29
6
(
1H, d, J = 6.2, −CHNHSO
C=CHS−), 6.03 (1H, s, −ArOH), 5.57 -5.72 (1H, t, J = 7.1, −CHNHCO−), 5.06 (1H,
s,−NCHCOOH), 4.84-4.86 (1H, d, J = 6.4, −CHN(S)), 4.78-4.82 (1H, d, J = 6.3, −NHCHAr),
.31 (3H, s, −ArCH ), 2.49 (3H, s, CH CH=CH−); MS (m/z, ESI): calcd. For C H N O S
7 2
2
), 6.98-7.17 (4H, m, −ArH), 6.72-6.85 (4H, m, −ArH), 6.27 (1H, s,
−
3
3
3
23 23
3
+
[
M+H] 517.5342617; found 517.5783681. Anal. calcd. For C23
23 3 7 2
H N O S : C, 53.37; H, 4.48; N,
8
.12; O, 21.64; S, 12.39. Found: C, 53.35; H, 4.46; N, 8.14; O, 21.63; S, 12.36.
Synthesis of 4-methyl-N-(methylsulfonyl)-N-(4-nitro-2-phenoxyphenyl)benzenesulfonamide
HR14)
(
Labeled compound HR14 was synthesized by adopting above procedure in yield 56% and was
-
1
purified by using mobile phase DCM: EtOH, 40:60.λmax290. FT-IR (cm ):1154.28 (S=O str),
1
1
079.40 (C−N str), 1595.70 (C=O), 805.16 (C−S str), 975.07 (S−N str), 3761.15 (−OH). H
NMR (400 MHZ, DMSO-d
, δ): 7.69-7.72 (4H, m, −ArH ), 7.39-7.43 (4H, m, −ArH ), 7.12-7.14
3H, d, J = 8.1, −ArH), 6.72-6.74 (2H, d, J = 8.2, −ArH), 2.94 (3H, s, CH SO −), 2.35 (3H, s,
6
(
−
3
2
+
3 18 2 7 2
ArCH ); MS (m/z, ESI): calcd. for C20H N O S [M+H] 462.0362647; found 462.753910.
Anal. calcd. for C H N O S : C, 51.94; H, 3.92; N, 6.06; O, 24.22; S, 13.87. Found: C, 51.65;
2
0
18
2
7 2
H, 3.86; N, 6.10; O, 24.23; S, 13.76.
Antioxidant activity
DPPH radical scavenging assay. Using DDPH in vitro antioxidant activity of synthesized
compounds was evaluated by a reported method [15]. All compounds were run in triplicate in
2
order to produce precision of results. Trolox was used for standard curve. Using R value
relative concentrations of compounds were determined, and scavenging %, directly representing
antioxidant activity, was determined using formula: Inhibition % = (1-sample530/blank530) × 100.
The results are given in Table 1.
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Synthesis and characterization of novel sulfonamides derivatives
495
Table 1. Antioxidant activity of sulfonamide derivatives HR5-HR8 and HR14.
%
mM
antioxidant activity
Compound
4
6 mM
12.87
15.60.
15.19
15.06
14.17
13.07
Trolox
HR5
HR6
HR7
HR8
1.53
1.52
1.47
1.48
1.26
1.22
HR14
Biological activity
Antibacterial activity. Growth media used was Luria-Bertain broth as it is highly efficient in
bacterial growth [16]. Media was prepared using 4.0 g of tryptone, 2.0 g of yeast extract and 4.0
g of sodium chloride in 400 mL distilled water. Value of pH of media was maintained at 7.0.
o
Above mentioned media was autoclaved at 125 C for 30 min. Sample solutions were prepared
in 5-50 µg concentration range. Three test tubes were labeled for each bacterial strain, i.e. S.
aureus and E. coli. 2 mL of LB Broth and 20 µL of bacterial strain were added in above
sterilized tubes. After that stocks of 5, 10, and 20 µL containing 5, 12.5, and 50 µg were added
o
in them. Then these tubes were incubated at 37 C for 72 hours. After this OD of each medium
and control medium were taken at 600 nm. Graph was plotted between concentration and OD of
compounds showing a comparative study for synthesized compounds (Table 2).
Table 2. Determination of MIC µg/mL synthesized products against bacterial strains.
S. No.
Name of compound
S. aureus
E. coli
5
8.5
4.0
3.0
1
2
3
4
5
6
HR5
HR6
HR7
HR8
HR14
2
6.5
3
2.5
1.5
0.2
2.0
0.04
Sulfmethoxazole
Antifungal activity. Antifungal activity of compounds was evaluated by performing well
diffusion test [17-21] using PDA (potato dextrose agar). A 24 h yeast culture of PDA was used
to prepare inoculum. Sterile saline solution (0.85%) was used for making suspension.
Spectrophotometer was used to adjust turbidity of above suspension at 600 nm for getting final
concentration matching with 0.5 McFarland standard. Agar medium was autoclaved for 30 min
o
o
at 120 C then cooled at 50 C and inoculated with 1ml of above suspension having absorbance
.5 McFarland. This inoculated medium were then poured into all assay plates 9cm in diameter
and were allowed to cool down until solidified. Upon solidification, equidistance four wells
mm in diameter were cut out of agar 6 µL of medium was added into these wells having
0
6
o
synthesized compounds. These plates were than incubated at 27 C for 48 h. MIC values in
µg/mL and zone of inhibition in mm were calculated for each compound, comparing it with
standard antifungal isoconazol (ISC) in concentration 1.0 µg/mL in each plate as +ve control.
Results are given in Table 3 and 4.
Cytotoxicity test. In vitro, cytotoxicity test was performed using Vero cell line. Assay was based
on protocol described by Borenfreund and Puerner (1984). 10% FBS (Fetal Bovine Serum)
containing Trypsin enzymes were used for cell growth in 96-well plates for 24 hours. After that
1
00 µL of each sample and standard was loaded in above plate. MIC values were determined by
comparison to doxorubicin hydrochloride as a reference drug. Two fold dilutions of test
Bull. Chem. Soc. Ethiop. 2017, 31(3)

496
Hajira Rehman et al.
compounds and doxorubicin were prepared in ethanol (1 mL). Each dilute was finally added to
-
1
media at room temperature giving a final concentration of 100, 50, 12.5 µg mL .This loaded
o
plate was incubated for 48 hours at 37 C, then natural red dye 10 µL (40%) was introduced in
all wells and incubated at same temperature for 4 hours. Then plate was washed two times with
PBS and finally one time with acidified ethanol. Absorbance was recorded at 540 nm in a
MICrotitre plate reader spectrophotometer. Activity of each well was found using given formula
and is presented in Table 5. Cytotoxicity of sample = (1-Experimental well abs/ abs of negative
control) x100.
Table 3. Determination of MIC µg/mL products against fungal strains.
S. No.
Name of compound
HR5
A. flavous
5.25
8.50
12.5
50.0
A. nyger
12.5
14.5
30.0
65.5
1
2
3
4
5
6
HR6
HR7
HR8
HR14
7.50
0.50
13.0
0.76
Isoconazole
Table 4. Diameter of zone of inhibition (mm±SD).
S. No.
Name of compound
HR5
A. flavous
27.2±0.12
26.5±0.30
18.9±0.11
12.4±0.22
25.5±0.10
30
A. nyger
18.1±0.12
16.3±0.33
14.9±0.22
10.6±0.10
17.1±0.11
29.5
1
2
3
4
5
6
HR6
HR7
HR8
HR14
Isoconazole
Table 5. Cytotoxicity values of sulfonamide derivatives.
Absorbance
00 50 12.5
% Activity
100 50
Compound
1
12.5
HR5
HR6
HR7
HR8
HR14
0.89 0.90 0.987
0.90 0.94 0.96
0.94 0.98 0.99
0.94 0.97 0.99
0.90 0.94 0.99
0.76 0.89 0.93
44
40
24
24
40
96
40
24
8.0 4.0
12
24
44
5.2
16
4.0
4.0
28
Doxorubicin hydrochloride
RESULT AND DISCUSSION
A series of five sulfonamides were synthesized in aqueous basic media by simple reaction of
five amino group containing drugs; ceftriaxone, cefepime, nicotinamide (vitamin B), cefadroxil
and nimsulide with paratoluenesulphonyl chloride with continuous stirring and details of
reaction conditions are explained in experimental section and synthetic pathway of sulfonamides
is explained in general procedure. The compounds were obtained in good to excellent yield (55–
8
7%). Elemental analysis was performed for the conformation of all the compounds and
measurement of absorption maximum (ꢀmax) provided the justification. The synthesized
−
1
compounds were characterized by FT-IR; the characteristics band at 1148–1155.5ꢀcm of S=O
−
1
−1
−1
stretching and 1048-1055ꢀcm for (C-N) and 813-814ꢀcm (C-S) and 930-958.9ꢀcm (S-N) for
all compounds reveals the formation of sulfonamides. Mass spectral data of all synthesized
24 8 9 4
compounds was obtained by ESI-MS. The molar mass for compound HR5, C25H N O S , was
originated as 708.77(calcd. 708.05). Correspondingly, observed mass for compound HR6,
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Synthesis and characterization of novel sulfonamides derivatives
497
C H N O S , was found as 634.13 (calcd. 634.75) and it proved the formation of the desired
2
6
30
6
7 3
product. The prominent peaks for compounds, HR7 and HR8, were recorded at m/z 122.05 and
+
+
3
63.09 for stable fragments [C H N O] , [C H N O S] , respectively. Observed and calcd
6 6 2 16 17 3 5
molar masses of compounds HR7 and HR8 were found as 276.07 (calcd. 276.31), and 517.10
calcd. 517.57), respectively. The major peak for compound HR14 was noticed at m/z 462.06
and showed good agreement with calculated molecular masses of concerned compound. The
(
1
1
structures of all the compounds were also confirmed by H NMR by dissolving in DMSO. H
NMR spectra of compounds HR5-HR8, all ArCH showed their cheMICal shift values from
1.39 to 21.84 ppm, and found to be very much similar to the literature values. In HR5 and
HR6 two methyl signals, i.e. -NCH and –OCH were also recorded at 38.65, 60.21 ppm and
0.39, 63.99, respectively. The cheMICal shift value of –OCH was observed on downfield side
due to strong electron withdrawing influence of oxygen than nitrogen. In HR7 a
3
2
3
3
5
3
than -NCH
3
prominent peak of methyl (C1) was noticed at 21.39 ppm. In this molecule there are two rings,
one of them is attached with methyl and second ring contains nitrogen. In second ring cheMICal
shift values of C10, C12 were found on downfield side due to electron withdrawing influence of
nitrogen and peaks of C2, C4 were appeared on high field side due to the electron donating
3
effect of –CH group. In HR8 a small peak was noticed at 174.17 ppm due to carbon atom of –
COOH group.
Synthesized compounds were screened for their antibacterial and antifungal activities using
sulfmethoxazole and isoconazol as reference antibacterial and antifungal agents. All developed
compounds showed moderate to good activity for both bacterial and fungal strains but
compound HR14 exhibited excellent activity against the E. coli and S. aureus (MIC 1.5 and
2
1
.0) and compound HR5 showed good activity against A. Flavous and A. Nyger (MIC 5.25 and
2.5). Synthesized compounds were also screened for their antioxidant activity. Compound
HR5 showed excellent and pronounced activity at 4 mM concentration. The MIC values and
zone of inhibitions are presented in Table 1-4. Cytotoxicity evaluation clearly shows that
developed sulfonamides exhibited poor activity than standard drug, i.e. doxorubicin.
Cytotoxicity values are presented in Table 5.
CONCLUSION
Five novel sulfonamides derivatives HR5-HR8 and HR14 were synthesized and evaluated for
their antiMICrobial, antioxidant and cytotoxicity test. Most of the synthesized compounds
showed promising antiMICrobial and antioxidant activity, suggesting a possible clinical
significance of novel compounds. Compound HR14 showed remarkable antiMICrobial results,
but compound HR5 was found to have potential antioxidant activity. However their cytotoxic
effects are not so pronounced.
ACKNOWLEDGEMENTS
Author is highly thankful to HEC of Pakistan for financial support and extremely thankful to
supervisor Dr. Abdul Qadir for his kind guidance. Finally author wishes her sincere gratitude to
Institute of Chemistry, University of Punjab for providing lab facilities.
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