Synthesis, biological and computational study of new Schiff base hydrazones bearing 3-(4-pyridine)-5-mercapto-1,2,4-triazole moiety

Article abstract of DOI:10.1016/j.saa.2008.05.003

A series of new Schiff base hydrazones (compounds 1-16) were synthesized by condensation reaction of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole with various aldehydes and/or dialdehydes. The structure of the prepared compounds was confirmed by means of ¹H NMR, ¹³C NMR, UV-vis, IR and elemental analyses. The all prepared compounds were assayed for antibacterial (Escherichia coli and Staphylococcus aureus) and antifungal (Candida albicans) activities by disc diffusion method. The results indicate that all tested compounds did not show any antibacterial activity against E. coli, as gram negative bacteria, and antifungal activity against C. albicans. But the compounds 2, 3, 4, 6 and 8 containing 4-Cl, 4-Me, 4-MeO, 2,4-di-Cl and 2-OH substituted phenyl moiety, respectively, showed good inhibition against S. aureus as compare to standard drugs. The structure of all biologically active compounds has also been theoretically studied by ab initio Hartree-Fock (HF) methods.

Full text of DOI:10.1016/j.saa.2008.05.003

Spectrochimica Acta Part A 71 (2008) 1474–1480
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Synthesis, biological and computational study of new Schiff base hydrazones
bearing 3-(4-pyridine)-5-mercapto-1,2,4-triazole moiety
Hamid Khanmohammadia,∗, Mohammad H. Abnosib, Ali Hosseinzadeha, Malihe Erfantalaba
a Department of Chemistry, Arak University, Arak 38156, Iran
b Department of Biology, Arak University, Arak 38156, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of new Schiff base hydrazones (compounds 1–16) were synthesized by condensation reaction of
4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole with various aldehydes and/or dialdehydes. The struc-
ture of the prepared compounds was confirmed by means of 1H NMR, 13 C NMR, UV–vis, IR and elemental
analyses. The all prepared compounds were assayed for antibacterial (Escherichia coli and Staphylococcus
aureus) and antifungal (Candida albicans) activities by disc diffusion method. The results indicate that all
tested compounds did not show any antibacterial activity against E. coli, as gram negative bacteria, and
antifungal activity against C. albicans. But the compounds 2, 3, 4, 6 and 8 containing 4-Cl, 4-Me, 4-MeO,
2,4-di-Cl and 2-OH substituted phenyl moiety, respectively, showed good inhibition against S. aureus as
compare to standard drugs. The structure of all biologically active compounds has also been theoretically
studied by ab initio Hartree–Fock (HF) methods.
Received 11 November 2007
Received in revised form 5 May 2008
Accepted 7 May 2008
Keywords:
1,2,4-Triazole
Schiff base
Hydrazones
Antibacterial
Antifungal
Ab initio
© 2008 Elsevier B.V. All rights reserved.
1. Introduction
We report here the synthesis and characterization of new
Schiff base hydrazones by condensation reaction of 4-amino-3-(4-
Schiff base hydrazone ligands containing 1,2,4-triazole nucleus
have attracted great and growing interest in chemistry and biology
for many years due to their facile synthesis and wide applications
[1–5]. 1,2,4-Triazole containing compounds have been shown to
exhibit a variety of interesting biological actions, including antibac-
terial [5–7], anticonvulsant [8], antimicrobial [9,10], anticancer [11],
antitubercular [12] and antifungal [13] activities. These diversified
applications are at least in part a consequence of the numerous
approaches that are available for the insertion of specific function-
alities into the 1,2,4-triazole nucleus. The alterations in chemical
structure of substituted 1,2,4-triazoles strongly change their activ-
ities and affect their interaction with cells and tissues, thereby
leading to different biological effects [5,14,15].
Prior to this work other groups report the synthesis, and
characterization of phenyl and dichlorofluorophenyl containing
1,2,4-triazoles-based Schiff base hydrazones to study their antimi-
crobial activities [5,15–17]. Pyridine containing hydrazones have
also been found to show antibacterial activity [18]. To our knowl-
edge, no examples of pyridine containing 1,2,4-triazoles-based
Schiff base hydrazones were reported.
pyridine)-5-mercapto-1,2,4-triazole with various aldehydes and/or
dialdehydes (Fig. 1). The choice of these ligands was motivated by
two objectives: (i) to provide new hydrazone ligands and (ii) to
enrich the biological study of Schiff base hydrazones containing
1,2,4-triazole and pyridine moieties. All newly synthesized com-
pounds have been characterized by spectroscopic methods (1H
1
NMR, 13C { H} NMR, UV–vis and IR) as well as microanalysis, and
were screened for the antibacterial and antifungal activity against
Escherichia coli (E. coli), Staphylococcus (S.) aureus, and Candidia albi-
cans (C.A.). From the ant microbial screening data the compounds
2, 3, 4, 6 and 8 with 4-Cl, 4-Me, 4-MeO, 2,4-di-Cl and 2-OH sub-
stituents, were found to have good inhibition against S. aureus. We
have also carried out a full minimization of the structure of all
biologically active compounds using ab initio Hartree–Fock (HF)
method.
2. Experimental
2.1. General information
All chemicals and solvents were of reagent grade and pur-
chased commercially. 4-Amino-3-(4-pyridyl)-5-mercapto-1,2,4-
triazole [19], 4-methyl-2,6-diformylphenol [20], 4-methoxy-2,6-
diformylphenol [20], 4-chloro-2,6-diformylphenol [21] and 4-
bromo-2,6-diformylphenol [21] have been prepared and purified
∗
Corresponding author. Tel.: +98 861 2777401; fax: +98 861 4173406.
E-mail address: h-khanmohammadi@araku.ac.ir (H. Khanmohammadi).
1386-1425/$ – see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2008.05.003

H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
1475
Fig. 1. The synthesized hydrazones.
according to the method reported in the literature. 1H and 13C
2.2. Procedure for biological activity study
1
{ H}NMR spectra were obtained with a Bruker Avance 300 MHz
All newly prepared hydrazones were screened for their activity
against E. coli, S. aureus, and C.A. strains by disc diffusion method
as gram negative, gram positive and fungal organisms, respectively.
Themuller hinton agarandsubro dextrose agarwere used to culture
bacteria and fungal, respectively. The culture media was poured
into sterile plates and microorganisms were introduced onto the
spectrometer. Electronic spectral measurements were carried
out using PerkinElmer Lamda spectrophotometer in the range
200–900 nm. Elemental analyses were performed on an Elemen-
tar Vario EL III elemental analyzer. Infrared spectra were recorded
as pressed KBr discs, using a Unicom Galaxy Series FTIR 5000 spec-
trophotometer (4000–400 cm−1).

1476
H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
surface of agar plates individually. The blank sterile discs measuring
6.4 mm in diameter were soaked in a known concentration of the
test compounds. Then the soaked discs were implanted on the sur-
face of the plates. A blank disc was soaked in the solvent (DMSO) and
implanted as negative control on each plate along with the standard
drugs. The plates were incubated at 37 ◦C (24 h) and 27 ◦C (48 h)
for bacterial and fungal strain, respectively. The inhibition zones
were measured and compared with the controls. Zone of inhibition
values are given in Table 3.
protons, J = 7.47 Hz), 8.19 (d, 2H, p-nitrophenyl protons, J = 7.47 Hz)
1
and 7.96 (d, 2H, pyridine protons, J = 4.59 Hz). 13C { H} NMR (d6-
DMSO, ppm): ı 164.0, 163.3, 150.2, 149.8, 147.0, 138.1, 134.1, 130.4,
124.8 and 122.9. ꢀmax (nm) (ε (M−1 cm−1)): 290 (12,300), 348 (105)
in DMSO.
2.3.2. Compound 2
1H NMR (d6-DMSO, ppm): ı 14.85 (s, 1H, NH/SH), 9.86 (s,
1H, N CH), 9.02 (d, 2H, pyridine protons, J = 6.38 Hz), 8.41 (d,
2H, pyridine protons, J = 6.38 Hz), 7.99 (d, 2H, p-chlorophenyl
2.3. General procedure for the synthesis of Schiff base hydrazones
protons, J = 8.49 Hz) and 7.65 (d, 2H, p-chlorophenyl pro-
1
tons, J = 8.49 Hz). 13C { H} NMR (d6-DMSO, ppm):
ı 166.0,
To a suspension of 4-amino-3-(4-pyridyl)-5-mercapto-1,2,4-
triazole (1 mmol) in ethanol (25 ml), an equimolar amount of
aldehyde (1 and/or 2 mmol) in ethanol (20 ml), was added. The
suspension was heated until clear solution was obtained. Then few
drops of concentrated sulfuric acid were added as catalyst. The solu-
tion was refluxed for 3–4 h. Then solvent was evaporated under
reduced pressure and the crude product was washed with water
and crystallized from ethanol–DMF (1:2). The characterization data
of synthesized compounds are given in Tables 1 and 2.
163.9, 145.4, 144.7, 139.7, 138.4, 131.2, 131.0, 129.9 and
124.8. ꢀmax (nm) (ε (M−1 cm−1)): 284 (11,400), 330 (100) in
DMSO.
2.3.3. Compound 3
1H NMR (d6-DMSO, ppm): ı 14.47 (s, 1H, NH/SH), 9.63 (s, 1H,
N
CH), 8.75 (d, 2H, pyridine protons, J = 4.58 Hz), 7.87 (d, 2H, pyri-
dine protons, J = 4.58 Hz), 7.82 (d, 2H, p-methylphenyl protons,
J = 7.77 Hz), 7.40 (d, 2H, p-methylphenyl proton, J = 7.77 Hz) and
1
2.41 (s, 3H, methyl protons). 13C { H} NMR (d6-DMSO, ppm): ı
167.8, 163.3, 150.8, 146.9, 144.0, 133.2, 130.4, 129.5, 129.4, 122.2
and 21.8. ꢀmax (nm) (ε (M−1 cm−1)): 290 (12,100), 345 (102) in
DMSO.
2.3.1. Compound 1
1H NMR (d6-DMSO, ppm): ı 14.67 (s, 1H, NH/SH), 10.10 (s, 1H,
N
CH), 8.82 (br, 2H, pyridine protons), 8.38 (d, 2H, p-nitrophenyl
Table 1
The characterization data of the prepared compounds
Compound
Color
Molecular formula
mp (◦C)
Yield (%)
Analysis (%) [found (calculated)]
C
H
N
S
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Orange
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
C14 H10 N6O2S
C14 H10 N5ClS
C15 H13 N5S
270–72
220–22
228–31
207–10
>300
188–90
205–08
197–99
265a
85
73
67
65
58
76
81
83
70
70
52
88
71
64
79
78
51.43 (51.55)
53.36 (53.28)
60.85 (61.04)
57.70 (57.90)
47.85 (48.03)
48.21 (48.03)
48.18 (48.03)
56.70 (56.59)
55.24 (55.07)
55.18 (55.07)
64.32 (64.57)
54.39 (54.57)
53.61 (53.72)
52.31 (52.10)
49.30 (49.41)
45.39 (45.62)
3.18 (3.07)
3.32 (3.17)
4.54 (4.40)
4.29 (4.18)
2.64 (2.57)
2.81 (2.57)
2.63 (2.57)
3.94 (3.70)
4.07 (3.97)
4.11 (3.97)
6.77 (6.59)
3.42 (3.30)
3.32 (3.50)
3.64 (3.39)
3.11 (2.80)
2.62 (2.59)
25.89 (25.75)
22.45 (22.18)
23.90 (23.72)
22.73 (22.50)
20.24 (20.00)
20.32 (20.00)
20.24 (20.00)
23.74 (23.56)
21.62 (21.40)
21.32 (21.40)
17.38 (17.10)
29.11 (28.91)
27.47 (27.22)
26.57 (26.40)
26.42 (26.18)
24.33 (24.17)
9.66 (9.81)
9.95 (10.14)
10.51 (10.84)
10.12 (10.28)
9.28 (9.14)
9.22 (9.14)
9.23 (9.14)
10.49 (10.77)
9.81 (9.78)
9.93 (9.78)
C
C
C
C
C
C
C
C
15 H13 N5OS
14 H9N5Cl2S
14 H9N5Cl2S
14 H9N5Cl2S
14 H11 N5OS
15 H13 N5O2S
15 H13 N5O2S
22H27N5OS
240–42
270a
7.71 (7.82)
C22H16 N10 S2
>300
13.41 (13.22)
12.64 (12.45)
12.31 (12.07)
12.28 (11.97)
11.28 (11.05)
C23H18 N10 OS2
C23H18 N10 O2S2
C22H15 N10 ClOS2
195–97
260a
>300
265–67
C
22H15 N10 BrOS2
a
At this temperature the compound has been decomposed.
Table 2
Tentative assignments of some selected IRa frequencies (cm−1) of the prepared compounds
Compound
ꢁ(C N–N)
ꢁ(Ar–H)
ꢁ(C N/C C)
ꢁ(C N)py
ꢁ(N–N)
ꢁ(NO2)
ꢁ(C–Cl)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1520
1507
1547
1560
1553
1507
1507
1532
1533
1510
1570
1535
1550
1520
1557
1532
3152
3084
3110
3085
3124
3088
3174
3090
3100
3143
3123
3130
3136
3110
3124
3110
1632, 1607, 1483
1638, 1611, 1468
1642, 1610, 1466
1638, 1603, 1499
1640, 1605, 1472
1642, 1606, 1464
1640, 1610, 1466
1640, 1607, 1458
1638, 1605, 1485
1636, 1603, 1473
1653, 1607, 1479
1649, 1609, 1489
1661, 1611, 1462
1661, 1607, 1462
1647, 1609, 1462
1642, 1609, 1429
1582
1594
1582
1573
1576
1580
1580
1578
1574
1570
1577
1580
1574
1574
1572
1578
1105
1173
1176
1180
1184
1173
1199
1182
1169
1172
1169
1207
1224
1214
1223
1217
1520, 1342
–
772
–
–
785, 756
787, 754
783, 764
–
–
–
–
–
–
–
768
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
a
In KBr discs.

H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
1477
2.3.4. Compound 4
161.0, 150.7, 146.8, 133.4, 129.5, 122.4, 111.6, 107.8, 101.3 and 55.9.
1H NMR (d6-DMSO, ppm): ı 14.76 (s, 1H, NH/SH), 9.69 (s, 1H,
ꢀmax (nm) (ε (M−1 cm−1)): 275 (12,000), 330 (82) in DMSO.
N
CH), 8.96 (d, 2H, pyridine protons, J = 4.29 Hz), 8.32 (d, 2H, pyri-
dine protons, J = 4.29 Hz), 7.84 (d, 2H, p-methoxyphenyl protons),
7.40 (d, 1H, p-methoxyphenyl proton) and 2.41 (s, 3H, methoxy
2.3.11. Compound 11
1H NMR (d6-DMSO, ppm): ı 14.51 (br, 1H, NH/SH), 10.68 (s, 1H,
OH), 9.64 (s, 1H, N CH), 8.75 (br, 2H, pyridine protons), 7.79 (d,
2H, pyridine protons, J = 4.47 Hz), 7.51 (s, 1H, phenyl proton), 7.45
(s, 1H, phenyl proton), 1.39 (s, 9H, t-Bu protons) and 1.29 (s, 9H,
1
protons). 13C { H} NMR (d6-DMSO, ppm): ı 167.7, 163.8, 145.6,
144.2, 138.8, 130.4, 130.1, 129.5, 129.4, 124.3 and 61.7. ꢀmax (nm)
(ε (M−1 cm−1)): 281 (11,700), 338 (98) in DMSO.
1
t-Bu protons). 13C { H} NMR (d6-DMSO, ppm): ı 172.1, 163.8, 156.7,
150.8, 146.9, 142.1, 137.3, 133.0, 128.4, 127.7, 122.4, 116.6, 35.2, 34.4,
31.6 and 29.7. ꢀmax (nm) (ε (M−1 cm−1)): 270 (10,700), 328 (92) in
DMSO.
2.3.5. Compound 5
1H NMR (d6-DMSO, ppm): ı 14.56 (s, 1H, NH/SH), 9.85 (s, 1H,
N
CH), 8.76 (br, 2H, pyridine protons), 8.18 (d, 1H, dichlorophenyl
proton, J = 1.53 Hz) and 7.91 (m, 4H, dichlorophenyl and pyridine
1
protons). 13C { H} NMR (d6-DMSO, ppm): ı 164.5, 163.3, 150.7,
2.3.12. Compound 12
1H NMR (d6-DMSO, ppm): ı 14.72 (s, 2H, NH/SH), 10.00 (s, 2H,
147.1, 136.0, 133.1, 132.9, 132.7, 132.1, 130.9, 128.9 and 122.4. ꢀmax
(nm) (ε (M−1cm−1)): 274 (10,800), 340 (89) in DMSO.
N
CH), 8.90 (d, 4H, pyridine protons, J = 4.47 Hz) and 8.15 (m, 8H,
pyridine and terphataldehyde protons). 13C { H} NMR (d6-DMSO,
ppm): ı 165.6, 163.6, 148.0, 146.4, 136.2, 136.0, 130.0 and 123.6.
ꢀmax (nm) (ε (M−1 cm−1)): 264 (11,300), 313 (94), 342 (75) in DMSO.
1
2.3.6. Compound 6
1H NMR (d6-DMSO, ppm): ı 14.55 (s, 1H, NH/SH), 10.55 (s,
1H, N CH), 9.02 (d, 2H, pyridine protons, J = 6.60 Hz), 8.36 (d,
2H, pyridine protons, J = 6.60 Hz), 8.16 (d, 1H, dichlorophenyl pro-
ton, J = 8.52 Hz), 7.89 (d, 1H, dichlorophenyl proton, J = 1.92 Hz) and
2.3.13. Compound 13
1H NMR (d6-DMSO, ppm): ı 14.75 (s, 2H, NH/SH), 11.24 (br, 1H,
OH), 10.11 (s, 2H, N CH), 8.96 (d, 4H, pyridine protons, J = 5.46 Hz),
8.28 (d, 4H, pyridine protons, J = 5.46 Hz), 8.05 (s, 2H, phenol pro-
7.61 (dd, 1H, dichlorophenyl proton, J = 6.60 Hz and J = 1.92 Hz). 13
C
1
{ H} NMR (d6-DMSO, ppm): ı 163.6, 159.9, 145.2, 144.5, 139.1,
138.8, 136.7, 130.4, 129.6, 129.0, 128.9 and 124.9. ꢀmax (nm) (ε
(M−1 cm−1)): 271 (12,100), 345 (102) in DMSO.
tons) and 2.36 (s, 3H, methyl protons). 13C { H} NMR (d6-DMSO,
1
ppm): ı 163.6, 163.0 and 158.5, 154.2, 151.2, 146.9, 133.0, 132.4,
121.8, 120.3 and 22.6. ꢀmax (nm) (ε (M−1 cm−1)): 269 (12,100), 310
(94), 356 (68) in DMSO.
2.3.7. Compound 7
1H NMR (d6-DMSO, ppm): ı 14.49 (s, 1H, NH/SH), 10.77 (s,
1H, N CH), 8.96 (d, 2H, pyridine protons, J = 6.35 Hz), 8.59 (d, 2H,
pyridine protons, J = 6.35 Hz), 8.26 (d, 2H, dichlorophenyl protons,
2.3.14. Compound 14
1H NMR (d6-DMSO, ppm): ı 14.53 (s, 2H, NH/SH), 10.54 (s, 1H,
OH), 10.06 (s, 2H, N CH), 8.77 (br, 4H, pyridine protons), 8.76 (d,
4H, pyridine protons, J = 4.71 Hz), 7.67 (s, 2H, phenol protons) and
J = 6.57 Hz) and 7.60 (m, 1H, dichlorophenyl proton). 13C { H} NMR
1
(d6-DMSO, ppm): ı 163.4, 159.6, 146.4, 145.5, 138.9, 135.4, 133.9,
130.4, 128.2 and 123.9. ꢀmax (nm) (ε (M−1 cm−1)): 278 (11,800),
340 (95) in DMSO.
3.82 (s, 3H, methoxy protons). 13C { H} NMR (d6-DMSO, ppm): ı
1
163.9, 163.4, 156.2, 154.1, 150.8, 147.1, 133.1, 131.5, 122.5, 121.4 and
56.3. ꢀmax (nm) (ε (M−1 cm−1)): 260 (12,200), 310 (87), 350 (71) in
DMSO.
2.3.8. Compound 8
1H NMR (d6-DMSO, ppm): ı 14.73 (s, 2H, NH/SH), 10.58 (s, 1H,
OH), 10.02 (s, 1H, N CH), 8.98 (d, 2H, pyridine protons, J = 5.85 Hz),
8.36 (d, 2H, pyridine protons, J = 5.85 Hz), 7.92 (d, 1H, phenyl pro-
ton, J = 7.83 Hz), 7.46 (m, 1H, phenyl proton), 6.97 (m, 2H, phenyl
2.3.15. Compound 15
1H NMR (d6-DMSO, ppm): ı 14.56 (s, 2H, NH/SH), 11.18 (br, 1H,
OH), 10.07 (s, 2H, N CH), 8.76 (br, 4H, pyridine protons), 8.11 (s,
2H, phenol protons) and 7.86 (d, 4H, pyridine protons, J = 4.83 Hz).
1
protons). 13C { H} NMR (d6-DMSO, ppm): ı 163.8, 163.7, 159.2,
13C { H} NMR (d6-DMSO, ppm): ı 163.5, 162.9, 158.3, 150.8, 147.2,
1
145.5, 145.2, 139.4, 135.3, 127.5, 124.5, 120.2, 118.5 and 117.2. Dept
135 (d6-DMSO, ppm): ı 163.7, 145.2, 135.3, 127.5, 124.5, 120.2 and
117.2. ꢀmax (nm) (ε (M−1 cm−1)): 278 (12,200), 319 (102), 334 (75)
in DMSO.
133.1, 132.6, 125.2, 122.5 and 122.4. ꢀmax (nm) (ε (M−1 cm−1)): 266
(12,400), 312 (90), 330 (78) in DMSO.
2.3.16. Compound 16
1H NMR (d6-DMSO, ppm): ı 14.55 (s, 2H, NH/SH), 11.23 (br, 1H,
OH), 10.06 (s, 2H, N CH), 8.77 (d, 4H, pyridine protons, J = 4.58 Hz),
8.21 (s, 2H, phenol protons) and 7.85 (d, 4H, pyridine protons,
2.3.9. Compound 9
1H NMR (d6-DMSO, ppm): ı 14.41 (s, 1H, NH/SH), 10.02 (s, 1H,
OH) 9.84 (s, 1H, N CH), 8.75 (br, 2H, pyridine protons), 7.86 (d, 2H,
pyridine protons, J = 5.82 Hz), 7.46 (d, 1H, phenyl proton, J = 7.26 Hz),
7.19 (d, 1H, phenyl proton, J = 7.26 Hz), 6.91 (t, 1H, phenyl proton)
1
J = 4.58 Hz). 13C { H} NMR (d6-DMSO, ppm): ı 163.5, 162.9, 158.2,
150.7, 147.2, 135.5, 133.1, 124.7, 122.7 and 122.5. ꢀmax (nm) (ε
(M−1 cm−1)): 266 (10,900), 315 (97), 332 (81) in DMSO.
and 3.86 (s, 3H, methoxy protons). 13C { H} NMR (d6-DMSO, ppm):
1
ı 163.5, 163.3, 150.7, 148.9, 148.8, 147.0, 133.3, 122.4, 120.0, 118.9,
118.6, 116.1 and 56.6. ꢀmax (nm) (ε (M−1 cm−1)): 274 (11,300), 327
(83) in DMSO.
3. Result and discussion
The condensation reaction of 4-amino-3-(4-pyridyl)-5-
mercapto-1,2,4-triazole with substituted aromatic aldehydes
and/or dialdehydes, in the presence of H2SO4 (conc) in ethanol,
gave good yield of the products (Fig. 1). All prepared ligands are
air stable solid and soluble in DMSO at ambient temperature.
The characterization data are given in Tables 1 and 2 and Section
2.
2.3.10. Compound 10
1H NMR (d6-DMSO, ppm): ı 14.37 (s, 1H, NH/SH), 10.61 (s, 1H,
OH), 9.68 (s, 1H, N CH), 8.74 (br, 2H, pyridine protons), 7.85 (d,
2H, pyridine protons, J = 5.07 Hz), 7.81 (s, 1H, phenyl proton), 6.57
(d, 1H, phenyl proton, J = 8.79 Hz), 6.51 (s, 1H, phenyl proton) and
3.80 (s, 3H, methoxy protons). 13C { H} NMR): ı 165.1, 164.3, 163.4,
1

1478
H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
Table 3
Zone inhibition of 1–16
3.1. IR spectra of the compounds 1–16
Positions of some of the prominent bands in the IR spectra of
ligands and their assignments based on extensive data available
for related ligands [5,22,23] are given in Table 2. The IR spectra
of the ligands show broad bands at 2550–2850 cm−1. This band
could be assigned for the intramolecular hydrogen bonding [22].
The IR spectra of all ligands show vibrational bands at 1630–1660,
Compounds
Staphylococcus
aureus (mm)
Escherichia coli
(mm)
Candida
albicans (mm)
1
2
3
4
5
6
–
13
9
9
–
9
–
–
–
–
–
–
–
–
–
–
–
–
1611–1602 and 1140–1130 cm−1 assigned for ꢁs and ꢁas of the C
N
and N–N groups, respectively [5,22].
7
8
9
10
11
12
–
18
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
The IR spectrum of 2 shows strong bonds at 1342 and 1520 cm−1
assigned for the NO2 group [23]. The bands in the IR spectrum of
3–6 at approximately 785 and 760 cm−1 can be assigned to the C–Cl
stretching modes [5].
13
–
–
–
14
15
–
–
–
–
–
–
3.2. NMR spectra of the compounds 1–16
16
DMSO
Standard drugs
–
–
–
–
–
–
1
1H NMR and 13C { H} NMR spectral results, obtained for all
ligands at ambient temperature in d6-DMSO, together with the
hydrogen assignments are presented in Section 2. All ligands show
a slightly broad singlet in the region ıH 14.40–14.75 ppm assigned
to NH/SH proton [5]. The signal at ıH 10.02–11.24 ppm in the 1H
NMR spectra of 8–11 and 13–16 is assigned to the OH proton, as
was confirmed by deuterium exchange when D2O was added to d6-
DMSO solution. The CH N imine proton (protons) exhibit a singlet
resonance in the region ıH 9.60–10.20 ppm. The 1H NMR spectra
of all ligands show a doublet (ıH 8.70–9.02 ppm) and a slightly
broad doublet (ıH 7.97–8.50) assigned to the pyridine protons
(JHa–Hb ≈ 4.50–6.20 Hz). The doublet pattern of ıH 8.70–9.02 ppm
signal is simplified after irradiation of ıH 7.97–8.50 ppm sig-
nal.
Penicillin
33 mm
Gentamicin
18 mm
Nistatin 25 mm
–: indicates bacteria are resistant to the compounds. Zone of inhibition are reported
in mm of diameter. Discs were inoculated with 5 mg of the compounds dissolved in
DMSO.
distribution in the structure, thus hinder the antibacterial activity
of the 9–11.
4. Ab initio studies
As we were unable to prepare crystals of prepared compounds
suitable for completely satisfactory X-ray diffraction work, we
chose to assess its structural parameters by undertaking ab ini-
tio molecular orbital calculations using the GAUSSIAN 98 program
[26] on a Pentium-PC computer with a 3600 MHz processor. To
do this the structure of all biological active compounds have been
investigated by ab initio MO calculations at the HF/6-31G* level
of theory. A starting semiempirical structure for the ab initio cal-
culations was optimized using the HyperChem 5.02 program [27].
The validity of each energy minimum structure (Fig. 2) was con-
firmed by performing a frequency analysis. Selected calculated
bond distances and bond angles for 2, 3, 4, 6 and 8 are presented in
Table 4.
3.3. Electronic spectra of the compounds 1–16
Electronic spectra of the prepared hydrazones in DMSO display
main features at 260–295 and 310–360 nm. The intense absorp-
tion band at short wavelengths 260–295 nm may be assigned for
␲–␲* aromatic rings transitions [22]. The weak broad absorp-
tion band at 310–360 nm may be assigned to the n–␲* and
␲–␲* electronic transition associated with the C N linkages
[22].
3.4. Antibacterial and antifungal activities
In this study, we focus our attention on the structural activ-
ity relationships. The investigation of antibacterial screening data
revealed that all tested compounds did not show any antibacterial
activity against E. coli, as gram negative bacteria, and antifun-
gal activity against C.A. (Table 3). But the compounds 2, 3, 4, 6
and 8 containing 4-Cl, 4-Me, 4-MeO, 2,4-di-Cl and 2-OH substi-
tuted phenyl ring, respectively, showed good inhibition against
S. aureus as compare to penicillin zone of inhibition. The anti-S.
aureus activity of compounds 2 and 8 with inhibition zone of 13
and 18 mm, respectively, are better than that of the other com-
pounds.
Table 4
◦
˚
Selected calculated bond lengths (A) and bond angles ( ) for 2, 3, 4, 6 and 8
2
3
4
6
8
Bond lengths
N(1)–N(3)
N(4)–N(7)
N(1)–C(2)
N(3)–C(5)
N(4)–C(5)
N(4)–C(2)
S(10)–C(5)
1.351
1.393
1.275
1.332
1.362
1.378
1.673
1.351
1.394
1.276
1.333
1.362
1.377
1.673
1.352
1.393
1.276
1.332
1.362
1.377
1.672
1.351
1.392
1.275
1.330
1.363
1.383
1.675
1.351
1.391
1.276
1.331
1.360
1.377
1.676
It is interesting to note that the slight structural difference in 5–7
can be observed (Fig. 1), but their antibacterial activity is quite dif-
ferent. The electric property of the compounds has close relations
with biological activity [24,25] and The weak antibacterial activity
of compounds 5 and 7 compared to compound 6 may be explained
by their charge density distribution.
The compound 8 with only OH substitution at ortho position
showed antibacterial activity, where as the same effect was not
observed in 9–11. Though the OH group is present in all of them
but other substitutions, MeO and/or t-Bu, can influence the electron
Bond angles
N(7)–N(4)–C(2)
N(7)–N(4)–C(5)
N(7)–N(4)–C(13)
N(1)–N(3)–C(5)
N(3)–N(1)–C(2)
N(1)–C(2)–N(4)
N(3)–C(5)–N(4)
N(4)–C(5)–S(10)
N(3)–C(5)–S(10)
C(2)–N(4)–C(5)
125.081
124.862
116.683
114.195
104.791
110.245
102.219
130.118
127.657
108.397
125.063
124.980
116.847
114.174
104.725
110.311
102.245
130.222
127.527
108.393
124.875
125.058
117.442
114.147
104.695
110.336
102.268
130.194
127.539
108.386
124.184
125.481
117.354
114.137
104.929
110.079
102.329
130.528
127.085
108.190
124.983
125.177
116.798
114.090
104.763
110.234
102.336
130.445
127.197
108.404

H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
1479
Fig. 2. HF/6-31G* geometry optimized structure of the 2, 3, 4, 6 and 8.
5. Conclusion
References
[1] M.H. Klingele, S. Brooker, Coord. Chem. Rev. 241 (2003) 119.
[2] J.G. Haasnoot, Coord. Chem. Rev. 200–202 (2000) 131.
[3] E. Bermoejo, R. Carballo, A. Castineiras, R. Dominguez, C. Maichle-Mossmer, J.
Strahle, D. West, Polyhedron 18 (1999) 3695.
[4] M.S. Costa, N. Boechat, E.A. Rangel, F.C. Da Silva, A.M.T. De Souza, C.R. Rodrigues,
H.C. Castro, I.N. Junior, M.C.S. Lourenco, S.M.S.V. Wardell, V.F. Ferreira, Bioorg.
Med. Chem. 14 (2006) 8644.
[5] M.S. Karthikeyan, D.J. Prasad, B. Poojary, K.S. Bhat, B.S. Holla, N.S. Kumari, Bioorg.
Med. Chem. 14 (2006) 7482.
We have synthesized a series of new Schiff base hydrazones con-
taining 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole. Among
the synthesized compounds, Schiff bases with 4-Cl, 4-Me, 4-MeO,
2,4-di-Cl and 2-OH substituents showed good inhibition against
S. aureus. Probably the electric property of these compounds may
be a reason for their biological activity, thus we recommend more
detail studies to understand the possible mechanisms involve in
the inhibition of the growth of S. aureus.
[6] A. Demirbas, C.B. Johansson, N. Duman, A.A. Ikizler, Acta Pol. Pharm. Drug Res.
53 (1996) 117.
¨
¨
[7] N. Ulusoy, O. Ates¸ , O. Ku¨ c¸ u¨ kbasmaci, M. Kiraz, Y. Yeg˘enog˘lu, Monatsh. Chem.
134 (2003) 465.
Acknowledgments
[8] J.L. Kelley, C.S. Koble, R.G. Davis, M.S. McLean, F.E.B. Soroko, R. Cooper, J. Med.
Chem. 38 (1995) 4131.
[9] B.S. Holla, M. Mahalinga, M.S. Karthikeyan, B. Poojary, P.M. Akberali, N.S. Kumari,
We are grateful to the Arak University for financial support of
this work. We kindly thank Mr. M. Falahatchian for his assistance
in Biology Lab.
Eur. J. Med. Chem. 40 (2005) 1173.
¨
[10] U. Salgın-Go¨ks¸ en, N. Go¨khan-Kelekc¸ i, O. Go¨ktas¸ , Y. Ko¨ysal, E. Kılıc¸ , S¸ . Is¸ ık, G.
¨
Aktay, M. Ozalp, Bioorg. Med. Chem. 15 (2007) 5738.

1480
H. Khanmohammadi et al. / Spectrochimica Acta Part A 71 (2008) 1474–1480
¨
[11] B.S. Holla, B. Veerandra, M.K. Shivanada, B. Poojary, Eur. J. Med. Chem. 38 (2003)
759.
[12] S. Joshi, N. Khosla, P. Tiwari, Bioorg. Med. Chem. 12 (2004) 571.
[13] E. Menegola, M.L. Broccia, F. Di Renzo, E. Giavini, Reprod. Toxicol. 15 (2001) 421.
[14] C. Chen, R. Dagnino, C.Q. Huang, J.R. McCarthy, D.E. Grigoriadis, Bioorg. Med.
Chem. Lett. 11 (2001) 3165.
[23] N. Ulusoy, A. Gu¨ rsoy, G. Otu¨ k, Farmaco 56 (2001) 947.
[24] Z. Li-Xia, L. Yi, C. Li-Hua, H. Yan-Jun, Y. Jun, H. Pei-Zhi, Thermochim. Acta 440
(2006) 51.
[25] E.M. Kosower, T. Miyadera, J. Med. Chem. 15 (1972) 307.
[26] M.J. Frich, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
V.G. Zakrazewski, J.A. Montgomery, R.E. Startmann Jr., J.C. Burant, S. Dapprich,
J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Adamo, S. Clifford, J. Ochterski, G.A. Peters-
son, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malik, A.D. Rabuck, K. Raghavachar, J.B.
Foresman, J. Cioslowski, J.V. Ortiz, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.
Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng,
A. Nanyakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen,
M.W. Wong, J.L. Andres, M. Head-Gordon, E.S. Replogle, J.A. Pople, GAUSSIAN
98 (Revision A.3), Gaussian Inc., Pittsburgh, PA, USA, 1998.
[15] D. Demirbas, R. Ugurluoglu, A. Demirbas, Bioorg. Med. Chem. 10 (2002) 3717.
[16] A.A. Abbas, Tetrahedron 60 (2004) 1541.
[17] P.B. Maravalli, T.R. Goudar, Thermochim. Acta 325 (1999) 35.
[18] R.K. Agarwal, R.K. Sarin, Polyhedron 12 (1993) 241.
[19] J.R. Reid, N.D. Heindel, J. Heterocycle Chem. 13 (1976) 925.
[20] N.C. Verani, E. Rentschler, T. Weyhermuller, E. Bill, P. Chaudhuei, J. Chem. Soc.
Dalton Trans. (2000) 151.
[21] F. Ullmann, K. Brittner, Chem. Ber. 42 (1909) 2683.
[22] M. El-Behery, H. El-Twigry, Spectrochim. Acta Part A 66 (2007) 28.
[27] HyperChem, Release 5.02, Hypercube Inc., Gainesville, 1997.