Metal based sulfanilamides: A note on their synthesis, spectral characterization, and antimicrobial activity

Article abstract of DOI:10.1134/S107036321708031X

Objectives of the current study were synthesis, spectral characterization and biological screening of sulfanilamide derived Schiff bases and their metal based compounds. Sulfanilamide Schiff bases (L¹–L³) were synthesized by condensation of 4-aminobenzenesulfanilamide with 1-(furan-2-yl)ethanone, 1-(thiophene-2-yl)-ethanone, and 1-acetylindoline-2,3-dione. The ligands were used for preparation of their Co(II), Ni(II), Cu(II), and Zn(II) complexes by using metals chlorides in metal: ligand (1: 2) molar ratio. All metal chelates had octahedral geometry with bidentate ligands. The ligands and their metal complexes were characterized by physical, spectral and analytical data, and screened for in-vitro antibacterial activity against six bacterial pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Bacillus subtilis) and for in vitro antifungal activity against six fungal pathogens (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glabrata). The results of antimicrobial studies revealed that the ligands activity was significantly increased upon chelation.

Full text of DOI:10.1134/S107036321708031X

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 8, pp. 1834–1842. © Pleiades Publishing, Ltd., 2017.
Metal Based Sulfanilamides: A Note on Their Synthesis,
Spectral Characterization, and Antimicrobial Activity1
S. Rania, S. H. Sumrrab*, and Z. H. Chohanc
a Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800 Pakistan
b Department of Chemistry, University of Gujrat, Gujrat, 50700 Pakistan
*e-mail: sajjadchemist@gmail.com
c Department of Chemistry, University of Sargodha, Bhakkar Campus, Sargodha, Pakistan
Received April 14, 2017
Abstract—Objectives of the current study were synthesis, spectral characterization and biological screening of
sulfanilamide derived Schiff bases and their metal based compounds. Sulfanilamide Schiff bases (L1–L3) were
synthesized by condensation of 4-aminobenzenesulfanilamide with 1-(furan-2-yl)ethanone, 1-(thiophene-2-yl)-
ethanone, and 1-acetylindoline-2,3-dione. The ligands were used for preparation of their Co(II), Ni(II), Cu(II),
and Zn(II) complexes by using metals chlorides in metal : ligand (1 : 2) molar ratio. All metal chelates had
octahedral geometry with bidentate ligands. The ligands and their metal complexes were characterized by
physical, spectral and analytical data, and screened for in-vitro antibacterial activity against six bacterial
pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus
aureus, and Bacillus subtilis) and for in vitro antifungal activity against six fungal pathogens (Trichophyton
longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glabrata).
The results of antimicrobial studies revealed that the ligands activity was significantly increased upon
chelation.
Keywords: sulfanilamides, metal(II) chelates, antimicrobial activity
DOI: 10.1134/S107036321708031X
INTRODUCTION
4-[1-(thiophene-2-yl)ethylideneamino]benzenesulfanil-
amide (L2), and (Z)-4-[1-acetyl-2-oxoindolin-3-ylidene-
amino]benzenesulfanilamide (L3) (Scheme 1). In order
to determine the effect of chelation, Co(II), Cu(II),
Ni(II), and Zn(II) metal complexes 1–12 (Scheme 2) of
these compounds that could be considered as a novel
class of metal based potential antibacterial drugs. All
the prepared compounds were screened for their
bactericidal/fungicidal activity against some bacterial/
fungal strains as reported herein.
Sulfanilamide drugs have been used as potential
chemotherapeutic agents [1, 2]. The mode of their
action is hindering the synthesis of folic acid in
bacteria [3] causing death of cells. From the time of
discovery, sulfa drugs [4–6] attracted a remarkable
attention as antiviral [7], antibacterial [8], anti-
inflammatory [9], antifungal [10] and anticancer [11]
agents. Usually biologically active compounds,
including sulfa drugs, demonstrate enhanced activity
upon chelation with metals [12, 13]. Isatin derived
compounds are also known to display a wide range of
biological [14, 15] and pharmacological activities
[16–18]. Versatile medicinal importance of sulfanil-
amides and potential bioactivity of isatins, furanyl and
thioenyl compounds, gave us a good reason for
combining both types of molecules by synthesizing
3 novel Schiff base derivatives of sulfanilamide, 4-[1-
(furan-2-yl)ethylideneamino]benzenesulfanilamide (L1),
RESULTS AND DISCUSSION
Schiff base ligands L1–L3 were synthesized in the
reaction of 4-aminobenzenesulfanilamide with 1-(furan-
2-yl)ethanone/1-(thiophene-2-yl)ethanone/1-acetylindo-
line-2,3-dione in an equimolar ratio (Scheme 1). The
ligands were colored air and moisture stable com-
pounds soluble in DMSO and DMF at room tem-
perature and in methanol and ethanol upon heating.
The ligands acted as bidentate and reacted readily with
Co(II), Cu(II), Ni(II), and Zn(II) chlorides in ethanol to
form the corresponding metal(II) complexes (Scheme 2).
1 The text was submitted by the authors in English.
1834

METAL BASED SULFANILAMIDES
1835
Scheme 1. Synthesis of Schiff base ligands L1–L3.
O
H2N S
O
O
H2N S
O
R
R'
C(R)(R')
ethanol
+
NH2
N
refluxing
O
L1−L3
Substituted carbonyls
4-Aminobenzenesulfanilamide
H3C
O
N
(L1),
(L3).
O
(L2),
R = CH3, R' =
R = CH3, R' =
R = CH3, R' =
O
S
Scheme 2. Proposed structure of metal(II) complexes 1–12.
H3C
O
X
H2N
S
N
O
M
H2O
OH2
Cl2
O
S
N
NH2
X
O
CH3
1−4 (L1); X = O, 5−8 (L2); X = S.
O
N
CH3
N
O
O
S
H2N
M
Cl2
H2O
H3C
OH2
O
O
S
O
N
NH2
O
N
O
9−12 of (L3).
Attempts to produce large crystals of ligands and their
metal complexes were unsuccessful.
and a new band appeared at 1640–1658 cm–1 due to
azomethine (C=N) linkage [19]. Other characteristic
bands [20] also supported formation of the cor-
responding product. Comparison of the IR spectra of
the ligands and their metal(II) complexes 1–12
justified coordination of the ligands to the metals
bidentately. Azomethine ν(C=N) vibrations of all
metal complexes were shifted to lower frequency by
All complexes were microcrystalline compounds
soluble in DMSO and DMF.
IR spectra. In IR spectra (Table 2) of all syn-
thesized Schiff base ligands one NH2 band of sulfanil-
amide and C=O band of ketone moiety disappeared
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 8 2017

1836
RANI et al.
Table 1. Physical measurements and analytical data of metal(II) complexes 1–12
Calculated (found), %
Comp.
no.
Yield,
%
Metal(II) complex
[Co(L1)2(H2O)2]Cl2
Mw
Formula
mp, °C
C
H
N
M
1
2
3
4
5
6
7
8
9
66 694.47 C24H28N4O8S2Cl2Co 312–314
68 694.23 C24H28N4O8S2Cl2Ni 317–318
74 699.08 C24H28N4O8S2Cl2Cu 325–326
71 700.95 C24H28N4O8S2Cl2Zn 234–235
69 726.60 C24H28N4O6S4Cl2Co 309–311
68 726.36 C24H28N4O6S4Cl2Ni 333–334
70 731.21 C24H28N4O6S4Cl2Cu 307–309
69 733.08 C24H28N4O6S4Cl2Zn 239–240
71 852.58 C32H30N6O10S6Cl2Co 231–232
74 852.34 C32H30N6O10S6Cl2Ni 217–218
76 857.20 32H30N6O10S6Cl2Cu 237–238
74 859.06 C32H30N6O10S6Cl2Zn 242–243
41.51
4.06
8.07
8.49
(8.46)
(41.45)
(4.02)
(8.03)
[Ni(L1)2(H2O)2]Cl2
[Cu(L1)2(H2O)2]Cl2
[Zn(L1)2(H2O)2]Cl2
[Co(L2)2(H2O)2]Cl2
[Ni(L2)2(H2O)2]Cl2
[Cu(L2)2(H2O)2]Cl2
[Zn(L2)2(H2O)2]Cl2
[Co(L3)2(H2O)2]Cl2
41.52
(41.47)
4.07
(4.04)
8.07
(8.04)
8.45
(8.41)
41.23
(41.37)
4.04
(4.00)
8.01
(7.96)
9.09
(9.05)
41.12
(41.08)
4.03
(3.98)
7.99
(7.96)
9.33
(9.30)
39.67
(39.62)
3.88
(3.85)
7.71
(7.67)
8.11
(8.08)
39.69
(39.65)
3.89
(3.85)
7.71
(7.68)
8.08
(8.04)
39.42
(39.36)
3.86
(3.83)
7.66
(7.62)
8.69
(8.66)
39.32
(39.28)
3.95
(3.91)
7.64
(7.61)
8.92
(8.89)
45.08
(45.02)
3.55
(3.51)
9.86
(9.82)
6.91
(6.88)
10 [Ni(L3)2(H2O)2]Cl2
11 [Cu(L3)2(H2O)2]Cl2
12 [Zn(L3)2(H2O)2]Cl2
45.09
(45.04)
3.55
(3.52)
9.86
(9.81)
6.89
(6.85)
44.84
(44.78)
3.53
(3.50)
9.80
(9.76)
7.41
(7.37)
44.74
3.52
9.78
7.61
(44.69)
(3.47)
(9.75)
(7.58)
8 to15 cm–1 in the region of 1625–1650 cm–1 indicating
coordination [21] of the C=N group with the Metal(II)
ions. The new low-frequency weaker bands that
appeared in the spectra of the metal complexes at 3477–
3488, 546–555, 460–468, and 434–445 cm–1 were
assigned to ν(H2O), ν(M–N), ν(M–S), and ν(M–O),
thus confirming the coordination [22] of metal atoms
with ligands via furanyl-O, thienyl-S, isatin-O, and
azomethine-N linkages. Position and intensities of
ν(C–O) stretching of furanyl moiety, ν(C–S) of thienyl
ring and ν(C=O) of isatin were shifted in IR spectra of
the complexes supporting the above groups
involvement in coordination/chelation [23].
provided evidence for condensation of only one amino
group of sulfanilamide. Coordination of the amino
protons was evident by downfield shifting of all proton
signals of Zn(II) complexes which was attributed to
attraction of electronic density by Zn(II) metal. All
other protons underwent downfield shift by 0.5–
1.2 ppm due to increased conjugation upon
coordination with Zn(II). Thus, the number of protons
calculated from the integration curves [25] and CHN
analysis data were in good agreement with the
proposed structures.
13C NMR spectra. Downfield shifting of the methyl
and azomethine groups carbons in the spectra of Zn(II)
complexes indicated electrons density interaction with
Zn(II) ion. All carbon atoms of aromatic/
heteroaromatic rings experienced the influence of
chelation.
1H NMR spectra. 1H NMR spectra of sulfonilamide
derivatives L1–L3 and their diamagnetic Zn(II)
complexes demonstrated [24] distinctive amino (NH2)
protons signals at 9.14–9.25 ppm as a singlet which
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METAL BASED SULFANILAMIDES
1837
Table 2. Conductivity, magnetic and spectral data of metal(II) complexes 1–12
Comp.
no.
ΩM,
μeff,
λm, nm
IR spectrum, cm–1
Ω–1 cm2 mol–1 BMa
1
2
141.2
139.2
4.7
3.3
2.1
7296, 17498, 20508, 3485 (H2O), 1635 (C=N), 1111 (C–O), 554 (M–N), 432 (M–O)
29373
10409, 15695, 26538, 3480 (H2O), 1632 (C=N), 1113 (C–O), 550 (M–N), 432 (M–O)
29996
3
4
5
140.7
138.4
139.3
14984, 19184,30357 3483 (H2O), 1636 (C=N), 1110 (C–O), 548 (M–N), 432 (M–O)
Dia 28985
3481 (H2O), 1632 (C=N), 1114 (C–O), 551 (M–N), 432 (M–O)
4.6
3.1
2.1
7410, 17454, 20586, 3488 (H2O), 1625 (C=N), 870 (C–S), 546 (M–N), 468 (M–S)
29325
6
135.4
10394, 15710, 26456, 3480 (H2O), 1628 (C=N), 868 (C–S), 551 (M–N), 465 (M–S)
29875
7
8
9
140.5
139.7
142.0
14995, 19162, 30375 3486 (H2O), 1630 (C=N), 871 (C–S), 549 (M–N), 460 (M–S)
Dia 28935
3483 (H2O), 1631 (C=N), 874 (C–S), 554 (M–N), 467 (M–S)
4.8
3.3
2.4
7409, 17451, 20589, 3477 (NH2), 1712 (C=O), 1645 (C=N), 555 (M–N), 436 (M–O)
29321
10
137.5
10398, 15709, 26457, 3485 (H2O), 1715 (C=O), 1646 (C=N), 550 (M–N), 433 (M–O)
29878
11
12
139.1
140.2
15013, 19166, 30379 3483 (H2O), 1710 (C=O), 1650 (C=N), 545 (M–N), 430 (M–O)
Dia 28939
3480 (H2O), 1711 (C=O), 1648 (C=N), 551 (M–N), 435 (M–O)
a Dia is diamagnetic.
Molar conductance and magnetic measurements.
Molar conductance measurements of the metal(II)
complexes (DMF) were in the range of 135.4–
142 Ω–1 cm2 mol–1 thus indicating [26] the electrolytic
(2 : 1) nature of the complexes. Magnetic moments of
the Co(II) complexes (Table 2) were observed in the
range of 4.6–4.8 BM indicating those as high-spin
three unpaired electrons in an octahedral environment.
Ni(II) complexes were likely to have an octahedral
[27] geometry as well. The magnetic moments of 2.1–
2.4 BM for Cu(II) complexes indicated one unpaired
electron per Cu(II) ion for the d9-system typical for
octahedral [28] geometry. All Zn(II) complexes were
measured to be diamagnetic [29].
ligand charge transfer. Electronic spectral data of the
Ni(II) complexes demonstrated [31] bands in the
regions of 10394–10409, 15695–15710, and 26456–
26538 cm–1 that were assigned to transitions, 3A2g (F) →
3T2g (F), A2g (F) → T1g (F) and A2g (F) → T2g (P)
respectively, suggesting their octahedral geometry.
Also a strong band due to metal to ligand charge
transfer appeared at 29875–29996 cm–1. The spectra of
the Cu(II) complexes demonstrated two week bands at
14984–15013, 19162–19182 cm–1 that could be
assigned to the transitions 2B1g → 2A1g and 2B1g → 2Eg
respectively, and their octahedral geometry [32]. A
high intensity band at 30357-30379 cm–1 was assigned
to the metal → ligand charge transfer. The Zn(II)
complexes being diamagnetic demonstrated only d–d
transitions and a strong band of high intensity at 28935–
28985 cm–1 due to metal → ligand charge transfer [33].
3
3
3
3
Electronic spectra. Electronic spectra of Co(II)
complexes generally displayed [30] three low to high
transition intensity bands at 7296–7410, 17451–17498,
4
4
and 20508–20589 cm–1 due to T14g (F) → T2g (F),
Biological studies. Antibacterial screening. Sulfonil-
amide derived Schiff bases L1–L3 and their Metal(II)
complexes 1–12 have been screened for in vitro
antibacterial activity against Escherichia coli, Shigella
4T1g (F) → A2g (F) and T1g (F) → T2g (P) transitions
in an octahedral environment. A high intensity band at
29321–29373 cm–1 was attributed to the metal →
4
4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 8 2017

1838
RANI et al.
Table 3. Antibacterial activity of ligands L1–L3 and metal(II) complexes 1–12a
Zone of inhibition, mm
g–
g+
Comp. no.
Escherichia Pseudomonas Salmonella Shigella Staphylococcus Bacillus Statistical
Average
coli
16
12
18
20
17
19
18
16
15
14
17
24
26
23
25
28
aeruginosa
typhi
12
13
20
15
14
16
17
16
19
17
16
23
26
21
24
29
flexneri
aureus
subtilis
analysis
1.97
1.63
2.23
2.16
3.43
1.63
2.16
1.51
2.94
2.50
1.72
1.63
1.64
1.86
1.63
1.17
L1
L2
L3
1
14
15
16
18
19
17
16
18
21
20
19
22
23
20
24
27
16
13
17
14.67
13.67
19.17
18.33
18.17
18.33
18.33
17.33
18.33
16.67
17.83
23.33
24.50
22.67
24.33
28.17
14
16
12
21
18
22
19
17
21
2
22
15
22
3
20
18
20
4
21
17
21
5
19
19
16
6
18
22
15
7
16
19
14
8
16
20
19
9
25
21
25
10
11
12
22
25
25
25
23
24
24
22
27
Standard drug
(Imipenem)b
28
27
30
Average activity of ligand L1–L3 = 15.84 mm, average activity of of 1–12 = 18.71 mm; weaker = 0–10 mm, moderate = 10–15 mm,
a
b
significant is above 16 mm.
flexneri, Pseudomonas aeruginosa, Salmonella typhi,
Staphylococcus aureus, and Bacillus subtilis bacterial
strains according to the standard procedure (Table 3)
and were compared with those of the standard drug
imipenum. Ligand (L1) exhibited significant (16–
17 mm) activity against Escherichia coli, Salmonella
typhi ,and Bacillus subtilis bacterial strains. The
remaining strains demonstrated moderate (12–14 mm)
activity. Likewise, ligand (L2) possessed overall
moderate (12–15 mm) activity against all strains
except Staphylococcus aureus (16 mm). But the ligand
L3 demonstrated significant (16–22 mm) activity
against all bacterial strains. The metal complexes 3–5
and 8–12 displayed exceptional (16–26 mm) activity
against all strains. Overall, it was concluded that metal
complexes demonstrated higher activity against one or
more bacterial strains that support our earlier results
[34]. The Ni(II) complex 10 of L3 was found to have
the highest antibacterial activity.
Antifungal studies. Antifungal screening of all
synthesized compounds was carried out against
Trichophyton longifusus, Candida albicans, Aspergillus
flavus, Microsporum canis, Fusarium solani, and
Candida glabrata fungal strains (Table 4) according to
the common protocol. It is noteworthy that the metal
complexes 1 and 2 demonstrated high (55–65%)
activity against all strains, except Trichophyton
longifusus and Fusarium solani. The metal complexes
9–12 exhibited overall significant 56–77% activity
against all fungal strains. The accumulated data (Table 4)
indicated that the ligand L3 demonstrated the overall
highest antifungal activity among all ligands. The
Zn(II) complex 9 of L3 was determined to be the most
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METAL BASED SULFANILAMIDES
1839
Table 4. Antifungal activity of ligands L1–L3 and metal(II) complexes 1–12
Percent of inhibition, mm
Trichophyton Candida Aspergillus Microsporum Fusarium Candida Statistical
Comp. no.
Average
longifusus
albicans
35.0
46.0
57.0
55.0
60.0
46.0
43.0
58.0
61.0
56.0
62.0
74.0
70.0
69.0
62.0
110.8
flavus
56
0
canis
solani
28.00
26.00
43.00
41.00
50.00
45.00
37.00
39.00
44.00
41.00
40.00
58.00
58.00
63.00
56.00
73.25
glabrata analysis
L1
L2
L3
0
40
39.0
49.0
52.0
56.0
59.0
62.0
58.0
57.0
66.0
59.0
60.0
77.0
67.0
71.0
70.0
110.8
18.61
21.05
4.85
33.00
35.17
49.50
51.67
55.50
53.33
50.33
48.67
52.33
52.00
49.50
65.17
63.00
65.50
61.00
–
59
31.0
49.0
59.0
57.0
58.0
60.0
43.0
40.0
52.0
46.0
60.0
62.0
66.0
59.0
98.4
46
50
65
71
69
65
21
37
35
18
62
65
60
58
20
1
34
11.72
11.71
11.34
12.06
18.38
13.46
12.36
19.10
8.16
2
36
3
40
4
39
5
74
6
66
7
69
8
71
9
60
10
56
5.37
11
64
4.04
12
61
4.90
Standard drugsb, µg/mL
70
–
a
Average activity of ligands L1–L3 = 37.33%; average activity of 1–12 = 58.01%. b Standard drugs (MIC µg/mL); miconazole
(Trichophyton longifusus, Candida albicans, Microsporum canis, Fusarium solani, Candida glabrata) and amphotericin B (Aspergillus
flavus); weaker = 0–33%, moderate = 34–54%, significant = 55–100%.
active among all complexes. So, the metal(II)
complexes were characterized by higher activity [35]
than the free ligands.
recorded on a UV-Vis double beam PC scanning spec-
trophotometer UVD-2950 LAMBOED in the range of
250–800 nm. Conductivity meter Jenway model 70
was used for measuring conductivity of metal
complexes using 0.001 molar solutions in DMF at
room temperature. A Stanton SM12/S Gouy balance
was used to measure the magnetic susceptibility of the
metal complexes at room temperature using mercury
acetate ligand as a standard. In vitro antibacterial and
antifungal properties were studied at HEJ Research
Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Pakistan.
EXPERIMENTAL
All chemicals of analytical grade were purchased
from Sigma Aldrich and used without further
purification. Synthesis of ligands was carried out in
purified and dried solvents. Melting points were
measured on a Fischer Scientific apparatus. IR spectra
(KBr discs) were recorded on a 8400 Shimadzu FTIR
Transform Infrared Spectrophotometer. Elemental
analysis was carried out on a Perkin Elmer analyzer
(USA model). 1H and 13C NMR spectra were measured
in DMSO-d6 on a Bruker Spectrospin Avance DPX-
400 spectrometer using TMS as the internal standard.
Electron impact mass spectra (EIMS) were recorded
on a JEOL MSRoute instrument. UV-Vis spectra were
4-[1-(Furan-2-yl)ethylideneamino]benzenesul-
fanilamide (L1). 4-Aminobenzenesulfanilamide
(0.002 M, 0.34g) in ethanol (10 mL) was added to a
stirred solution of 1-(furan-2-yl)ethanone (0.002 M,
0.22 g) in ethanol (10 mL) followed by 2–3 drops of
acetic acid. The reaction mixture was stirred for 4 h
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1840
RANI et al.
with continuous monitoring by TLC. The mixture was
left overnight at room temperature. Precipitate formed
was filtered off, washed with cold ethanol, then with
ether, dried, and recrystallized from a mixture of
ethanol:dichloromethane (1 : 1). Ligands L2 and L3
were synthesized according to the same method. Light
brown solid, yield 62%, mp 220°C. IR spectrum, ν, cm–1:
3364 (NH2), 1648 (C=N), 1317, 1162 (S=O), 1125
from a mixture of hot ethanol: methanol (1 : 1) to get
the corresponding TLC pure compound (Table 1).
1
[Zn(L1)2] (4). H NMR spectrum, δ, ppm: 2.26 s
(3H), 7.08 d.d (1H, J = 4.8, 3.7 Hz), 7.44 d (1H, J =
4.8 Hz), 7.69 d (1H, J = 3.8 Hz), 7.70–7.99 m (4H,
Ph), 9.30 s (2H, SO2NH2). 13C NMR spectrum, δ, ppm:
16.6, 116.0, 122.5, 124.2, 124.9, 127.3, 128.4, 138.0,
141.2, 146.5, 151.8, 156.4, 165.3.
1
(C–O), 935 (S–N), 845 (C–S). H NMR spectrum, δ,
1
[Zn(L2)2] (8). H NMR spectrum, δ, ppm: 2.19 s
ppm: 2.15 s (3H), 7.01 d.d (1H, J = 4.8, 3.7 Hz), 7.35 d
(1H, J = 4.8 Hz), 7.63 d (1H, J = 3.8 Hz), 7.65–7.91 m
(4H, Ph), 9.25 s (2H, SO2NH2). 13C NMR spectrum, δ,
ppm: 15.1, 115.2, 121.9, 123.5, 124.1, 126.8, 127.7,
137.3, 140.6, 145.8, 151.2, 155.6, 163.9. MS (ESI):
[M]+ = 264 (264.30). Found, %: C 54.49; H 5.54; N
10.57. C12H12N2O3S. Calculated, %: C 54.53; H 4.58;
N 10.60.
(3H), 7.04 d.d (1H, J = 4.8, 3.7 Hz), 7.32 d (1H, J =
4.8 Hz), 7.68 d (1H, J = 3.8 Hz), 7.53–7.94 m (4H,
Ph), 9.19 s (2H, SO2NH2). 13C NMR spectrum, δ, ppm:
15.5, 115.6, 121.9, 124.0, 124.9, 127.0, 128.2, 137.6,
140.9, 145.8, 151.4, 156.1, 164.4.
1
[Zn(L3)2] (12). H NMR spectrum, δ, ppm: 2.16 s
(3H), 7.35–7.65 m (4H, isatin), 7.77–7.99 m (4H, Ph),
9.28 s (2H, SO2NH2). 13C NMR spectrum, δ, ppm:
19.3, 115.8, 12.8, 123.7, 124.7, 126.5, 127.5, 128.4,
129.5, 133.8, 136.9, 139.4, 155.5, 159.6, 165.7, 169.9.
4-[1-(Thiophene-2-yl)ethylideneamino]benzene-
sulfanilamide (L2). Off white solid, yield 68%, mp
215°C. IR spectrum, ν, cm–1: 3369 (NH2), 1640 (C=N),
1321, 1162 (S=O), 930 (S–N), 883 (C–S, thienyl), 840
Antibacterial activity. The agar-well diffusion
method [36] was used for testing toxicity of all newly
synthesized ligands L1–L3 and their metal(II) com-
plexes 1–12 in-vitro against four gram-negative
(E. coli, S. flexneri, P. aeruginosa, S. typhi) and two gram-
positive (S. aureus, B. subtilis) bacterial strains. The
wells (6 mm in diameter) were introduced in the media
with the help of a sterile metallic borer with centers at
least 24 mm apart. Bacterial inoculum after 6–8 h of
growth approximately having 104–106 colony forming
units (CFU)/mL was used. The recommended con-
centration of the test sample (1 mg/mL in DMSO) was
introduced in the respective well. Other wells
supplemented with DMSO and reference antibacterial
drug (imipenem) served as a negative and positive
control, respectively. The plates were incubated at 37°C
for 24 h. Activity was determined by measuring the
diameter of zones which showed complete inhibition
(mm). DMSO demonstrated no activity against any of
the bacterial strains used in this study.
1
(C–S). H NMR spectrum, δ, ppm: 2.06 s (3H), 6.97
d.d (1H, J = 4.8, 3.7 Hz), 7.30 d (1H, J = 4.8 Hz), 7.59
d (1H, J = 3.8 Hz), 7.47–7.81 m (4H, Ph), 9.14 s (2H,
SO2NH2). 13C NMR spectrum, δ, ppm: 14.8, 114.7,
121.3, 123.1, 123.8, 126.5, 127.5, 137.0, 140.1, 145.3,
150.7, 155.3, 163.1; MS (ESI): [M]+ = 280 (280.37).
Found, %: C 51.36: H 4.27; N 9.95. C12H12N2O2S2.
Calculated, %: C 51.41; H 4.31; N 9.99.
4-[1-Acetyl-2-oxoindolin-3-ylideneamino]benzene-
sulfanilamide (L3). Reddish brown solid, yield 65%,
mp 200°C. IR spectrum, ν, cm–1: 3380 (NH2), 1725
(C=O), 1658 (C=N), 1348, 1184 (S=O), 1145 (C-N),
1
931 (S–N), 854 (C–S). H NMR spectrum, δ, ppm:
2.11 s (3H), 7.30–7.55 m (4H, isatin), 7.71–7.89 m
(4H, Ph), 9.22 s (2H, SO2NH2). 13C NMR spectrum, δ,
ppm: 18.7, 115.1, 121.9, 123.0, 123.7, 125.6, 126.8,
127.6, 129.0, 133.2, 136.0, 138.8, 154.7, 158.8, 164.6,
168.3. MS (ESI): [M]+ = 343 (343.35). Found, %: C
55.91; H 3.78; N 12.10. C14H13N3O4S. Calculated, %:
C 55.97; H 3.82; N 12.24.
Antifungal activity. Antifungal activity of all com-
pounds was studied against six fungal strains (T. longifusus,
C. albican, A. flavus, M. canis, F. solani and C. glabrata).
Sabouraud dextrose agar (Oxoid, Hampshire, England)
was seeded with 105 (CFU)/mL fungal spore suspen-
sions and transferred to petri plates. Discs soaked in
20 mL (200 µg/mL in DMSO) of the compounds were
placed at different positions on the agar surface. The
plates were incubated at 32°C for 7 days. The results
Synthesis metal(II) complexes. All metal(II) com-
plexes were prepared according to the standard
procedure. To a metal chloride (5 mmol) in ethanol
(10 mL) upon magnetic refluxing was added ethanol
solution (20 mL) of a ligand (10 mmol). The mixture
was refluxed for 3 h then cooled down to room
temperature. The precipitate was filtered off, washed
with ethanol and diethyl ether, dried, and recrystallized
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METAL BASED SULFANILAMIDES
1841
8. Chohan, Z.-H., Hassan, M.-U., Khan, K.-M., and
Supuran, C.-T., J. Enz. Inhib. Med. Chem., 2005,
vol. 20, p. 183. doi org/10.1080/14756360500043257
9. Supuran, C.-T., Casini, A., and Scozzafava, A., Med.
Res Rev., 2003, vol. 23, p. 535. doi 10.1002/med.10047
10. Chohan, Z.-H. and Naseer, M.-M., Appl. Organomet.
Chem., 2007, vol. 21, p. 728. doi 10.1002/aoc.1279
11. Owa, T. and Nagasu, T., Exp. Opin. Ther. Patents.,
2000, vol. 10, p. 1725. doi org/10.1517/
13543776.10.11.1725
12. Hassan, M.-U., Chohan, Z.-H., Andrea, S., and Supu-
ran, C.-T., J. Enz. Inhib. Med. Chem., 2004, vol. 19,
p. 263. doi org/10.1080/14756360410001689595
13. Idemudia, O.-G., Sadimenko, A.-P., Afolayan, A.-J.,
and Hosten, E.-C., Bioinorg. Chem. Appl., 2015,
vol. 2015, p. 1. doi org/10.1155/2015/717089
14. Mishra, A.-P., Mishra, R., Jain, R., and Gupta, S.,
Mycobiology, 2012, vol. 40, p. 20. doi org/10.5941/
MYCO.2012.40.1.020
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Sci. Trans., 2013, vol. 2, p. 1063. doi 10.7598/
cst2013.527
were recorded as percentage of inhibition and com-
pared with standard drugs miconazole and
amphotericin B.
CONCLUSIONS
The synthesized sulfanilamide Schiff bases acted as
bidentate ligands in coordination with Co(II), Ni(II),
Cu(II), and Zn(II) via azomethine-N, thienyl-S, furanyl-O,
and acetyisatin-N. Physical, spectral and analytical
data confirmed that the Schiff bases had octahedral
geometry in the complexes. Antibacterial and
antifungal activities data of the metal complexes
demonstrated higher biological activity against one or
more bacterial and/or fungal strains than non-chelated
ligands. Probably oxygen of furanyl, sulphur of
thioenyl, nitrogen of azomethine, and isatin were the
sites potentially responsible for the enhancement of
antibacterial and antifungal activities.
ACKNOWLEDGMENTS
16. Hyatt, J.-L., Moak, T., Hatfield, M.-J., Tsurkan, L.,
Edwards, C.-C., Wierdl, M., Danks, M.-K., Wadkins, R.-M.,
and Potter, P.-M., J. Med. Chem., 2007, vol. 50,
p. 1876. doi 10.1021/jm061471k
17. Beauchard, A., Ferandin, Y., Frere, S., Lozach, O.,
Blairvacq, M., Meijer, L., Thiéry, V., and Besson, T.,
Bioorg. Med. Chem., 2006, vol. 14, p. 6434. doi
org/10.1016/j.bmc.2006.05.036
The authors are thankful to HEJ research Institute
of Chemistry, University of Karachi, Pakistan, for
providing their help in measuring NMR and mass
spectra and for the help in carrying out antibacterial
and antifungal bioassays.
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