Spectroscopic characterization of novel d-amino acid-Schiff bases and their Cr(III) and Ni(II) complexes as antimicrobial agents

Article abstract of DOI:10.1007/s00044-012-0039-5

The aim of this work was to investigate the antibacterial and antifungal activities of novel d-amino acid-Schiff bases including fluorine atom and their Cr(III) and Ni(II) complexes. All these substances have been examined for antibacterial activity against pathogenic strains Listeria monocytogenes 4b ATCC19115, Staphylococcus aureus ATCC25923, Escherichia coli ATCC1280, Salmonella typhi H NCTC 901.8394, Brucella abortus (A.99, UK-1995) RSKK03026, Staphylococcus epidermis sp., Micrococus luteus ATCC9341, and Shigella dysenteria typ 10 NCTC 9351, and antifungal activity against Candida albicans Y-1200-NIH, Tokyo. The antimicrobial test results of these amino acid-Schiff base complexes exhibited better activity than some known antibiotics. In particular, diamagnetic Ni(II) complexes were more potent bactericides than all of the substances synthesized.

Full text of DOI:10.1007/s00044-012-0039-5

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2013) 22:580–587
DOI 10.1007/s00044-012-0039-5
ORIGINAL RESEARCH
Spectroscopic characterization of novel D-amino acid-Schiff bases
and their Cr(III) and Ni(II) complexes as antimicrobial agents
¨
•
•
•
˘
Nurs¸en Sarı Nihat Pis¸kin Hatice Ogu¨tcu¨
Nurdan Kurnaz
Received: 9 January 2012 / Accepted: 21 March 2012 / Published online: 15 April 2012
Ó Springer Science+Business Media, LLC 2012
Abstract The aim of this work was to investigate the
antibacterial and antifungal activities of novel D-amino
acid-Schiff bases including fluorine atom and their Cr(III)
and Ni(II) complexes. All these substances have been
examined for antibacterial activity against pathogenic
strains Listeria monocytogenes 4b ATCC19115, Staphylo-
coccus aureus ATCC25923, Escherichia coli ATCC1280,
Salmonella typhi H NCTC 901.8394, Brucella abortus
(A.99, UK-1995) RSKK03026, Staphylococcus epidermis
sp., Micrococus luteus ATCC9341, and Shigella dysenteria
typ 10 NCTC 9351, and antifungal activity against Candida
albicans Y-1200-NIH, Tokyo. The antimicrobial test
results of these amino acid-Schiff base complexes exhib-
ited better activity than some known antibiotics. In par-
ticular, diamagnetic Ni(II) complexes were more potent
bactericides than all of the substances synthesized.
Introduction
Schiff bases appear to be important intermediates in a
number of enzymatic reactions involving enzyme interac-
tion with an amino or a carbonyl group of a substrate. In
bioinorganic chemistry, the interest in the Schiff base
complexes derives from their ability to provide synthetic
models for metal-containing sites in metalloproteins and to
contribute to developments in medicinal chemistry. Thus,
Schiff bases and their complexes have a variety of appli-
cations in biological, clinical, and analytical fields (Eglof
et al., 2009; Ellis et al., 1997). Recently, there has been
considerable interest in the chemistry of amino acid-Schiff
base compounds due to their potential in nuclear medicine
applications (Abram and Alberto, 2006; Gharagozlou and
Boghaei, 2008).
However, the drug resistances against antibacterial agents
may pose a problem in their use with medical purpose (Singh
et al., 2006). The problem could be overcome by the prep-
aration of metal complexes, by a process of chelation with
the coordination of transition metal ions. It is well known that
N and O atoms play a key role in the coordination of metals.
Amino acid-Schiff bases have N and O atoms as their basic
elements. Schiff base derivatives containing donor atom can
act as good chelating agents for the transition of metal ions
(Avaji et al., 2008; Takeuchi et al., 1999; Sari et al., 2008).
Amino acid-Schiff base metal complexes have found wide
applications in corrosion inhibitors (Negm and Zaki, 2009),
tumor radio-imaging agents (Wang et al., 2005), and phar-
macologically active compounds (Wang et al., 2007).
However, no studies have been carried out on Schiff bases
and their metal complexes derived from amino acid-Schiff
bases including fluorine. This study aimed to fill in this gap.
Novel amino acid-Schiff bases derivatives were investigated
to find out the antibacterial properties of Schiff bases and
Keywords Schiff bases ꢀ Antimicrobial activity ꢀ
Fluorine atom ꢀ Ni(II) complex ꢀ Cr(III) complex ꢀ
Diamagnetic
N. Sarı (&) ꢀ N. Pis¸kin ꢀ N. Kurnaz
Department of Chemistry, Faculty of Science,
Gazi University, 06500 Tenikoklullar, Ankara, Turkey
e-mail: nursens@gazi.edu.tr
¨
H. Ogu¨tcu¨
˘
Department of Biology, Faculty of Arts and Science,
Ahi Evran University, Kırs¸ehir, Turkey
N. Kurnaz
Department of Chemistry, Faculty of Science,
Kırklareli University, Kırklareli, Turkey
123

Med Chem Res (2013) 22:580–587
581
O
5-Fluoro-3-chloro-2-hydroxybenzaldehyde-D-glycine
O
F
CH
F
CH=N-CH-C-OH
CH3OH, H2O
N2, reflux
H2N-CH-C-OH
+
Y
O
A solution of 3-chloro-5-fluoro-2-hydroxbenzaldehyde
0.44 g (2.5 9 10-3 mol) in MeOH (10 ml) was added drop
wise to the 4 ml hot aqueous solution of the D-glycine
0.19 g (2.5 9 10-3 mol) and heated under reflux for 4 h in
nitrogen atmosphere. After cooling, the mixture was fil-
tered and allowed to stand. On standing for a further 6 days
in nitrogen atmosphere, the solid crude formed was col-
lected by filtration, dried in desiccators over CaCl2. Yields:
56.
OH
Y
OH
X
X
Y
X
5-fluoro-3-chloro-2-hydroxybenzaldehyde-D-glycine
5-fluoro-3-chloro-2-hydroxybenzaldehyde-D-alanine
5-fluoro-2-hydroxybenzaldehyde-D-glycine
-H, -Cl
-CH3, -Cl
-H,
-H
5-fluoro-2-hydroxybenzaldehyde-D-alanine
-CH3, -H
Scheme 1 Structure of amino acid-Schiff bases
5-Fluoro-2-hydroxybenzaldehyde-D-alanine
their complexes (Scheme 1). Amino acid-Schiff base
derivatives were synthesized by condensation methods. And
then, Cr(III) and Ni(II) complexes were synthesis by tem-
plate methods.
A solution of 5-fluoro-2-hydroxy benzaldehyde 0.35 g
(2.5 9 10-3 mol) in MeOH (10 ml) was added drop wise
to the 4 ml hot aqueous solution of the D-glycine 0.19 g
(2.5 9 10-3 mol) and heated under reflux for 4 h in
nitrogen atmosphere. After cooling, the mixture was fil-
tered and allowed to stand. On standing for a further 4 days
in nitrogen atmosphere, the solid crude formed was col-
lected by filtration, dried in desiccators over CaCl2. Yields:
68.
Chemicals and methods
5-Fluoro-2-hydroxy benzaldehyde, 3-chloro-5-fluoro-2-
hydroxbenzaldehyde, D-glycine, D-alanine, Ni(II) chloride,
and Cr(III) chloride were provided by Sigma-Aldrich
5-Fluoro-3-chloro-2-hydroxybenzaldehyde-D-alanine
1
Company. H and 13C NMR spectra of the Schiff bases
were recorded using
a
Bruker DPX-300 MHz and
A solution of 3-chloro-5-fluoro-2-hydroxbenzaldehyde
0.44 g (2.5 9 10-3 mol) in MeOH (10 ml) was added drop
wise to the 4 ml hot aqueous solution of the D-alanine
0.22 g (2.5 9 10-3 mol) and heated under reflux for 4 h in
nitrogen atmosphere. After cooling, the mixture was fil-
tered and allowed to stand. On standing for a further 4 days
in nitrogen atmosphere, the solid crude formed was col-
lected by filtration, washed with a small volume of ethanol
and dioxan, and then, finally crystallized from methanol,
dried in desiccators over CaCl2. Yields: 58.
100 MHz using TMS as an internal standard and CDCl3 as
solvent. FTIR spectra in the 4000–400 cm-1 range were
measured using KBr disks on a Mattson 1000 FTIR spec-
trophotometer. Carbon, hydrogen, and nitrogen content
were obtained using LECO-9320 analyzer. Conductivity
measurements were carried out at 20 °C in 10-3 M DMSO
using a Siemens WPA CM 35 apparatus. The room tem-
perature magnetic moments were measured using MK-1
model Gouy Balance of Christison Scientific Equipment
Ltd. Metal contents were determined using a Philips PU
9285 atomic absorption instrument. Mass spectra were
General synthesis of complexes
recorded on
spectrometer.
a Micro Mass-UK Platform II mass
Cr(III) and Ni(II) complexes of Schiff bases resulting from
the condensation of 1 mol of aldeyhde with 1 mol of D-
amino acid has been isolated by metal template reaction. A
sample of CrCl3ꢀ6H2O and NiCl2ꢀ6H2O (for Cr(III) and
Ni(II); 0.67 and 0.59 g, respectively, 2.5 9 10-3 mol) was
dissolved in methanol (25 ml). To the solution, amino acid
(D-glycine 0.19 g, D-alanine 0.22 g; 2.5 9 10-3 mol) and
aldehyde (5-fluoro-2-hydroxy benzaldehyde 0.35 g,
3-chloro-5-fluoro-2-hydroxbenzaldehyde 0.44 g; 2.5 9
10-3 mol) in methanol (25 ml) was added, immediately
giving a colored solution. The resulting solution was stirred
for ca. 5 h in nitrogen atmosphere, filtered, and allowed to
stand. On standing for a further 10–20 days, the solid com-
plexes formed was collected by filtration, washed with a
5-Fluoro-2-hydroxybenzaldehyde-D-glycine
A solution of 5-fluoro-2-hydroxy benzaldehyde 0.35 g
(2.5 9 10-3 mol) in MeOH (10 ml) was added drop wise
to the 4 ml hot aqueous solution of the D-glycine 0.19 g
(2.5 9 10-3 mol) and heated under reflux for 4 h in
nitrogen atmosphere. After cooling, the mixture was fil-
tered and allowed to stand. On standing for a further 4 days
in nitrogen atmosphere, the solid crude formed was col-
lected by filtration, dried in desiccators over CaCl2. Yields:
52.
123

582
Med Chem Res (2013) 22:580–587
small volume of ethanol and acetone, and then, dried in a
desiccator over CaCl2. Yields: 61–73.
ampicillin (preventing the growth of gram-negative bac-
teria), nystatin (binding to sterols in the fungal cellular
membrane, altering the permeability, and allowing leakage
of the cellular contents), kanamycin (used in molecular
biology as agent to isolate bacteria), sulfamethoxazol
(bacteriostatic antibacterial agent that interferes with folic
acid synthesis in susceptible bacteria), amoxycillin (b-lac-
tam antibiotic used to treat bacterial infections caused by
susceptible microorganisms), Sulbactam.
Detection of antimicrobial activity
The bacterial subcultures chosen were Listeria monocytog-
enes 4b ATCC19115, Staphylococcus aureus ATCC25923,
Escherichia coli ATCC1280, Salmonella typhi H NCTC-
901.8394, Brucella abortus (A.99, UK-1995) RSKK03026,
Staphylococcus epidermis sp., Micrococus luteus ATCC
9341, and Shigella dysenteria type 10 NCTC 9351. An
antifungal susceptibility test was used by Candida albicans
Y-1200-NIH, Tokyo.
Results and dissociations
Analytical data and some of the physical properties of the Schiff
bases and their complexes are summarized in Table 1. The
complexes are only soluble in DMF and DMSO, but insoluble
in organic solvents like CCl4 and benzene. Molar conductance
values of the Cr(III) and Ni(II) complexes were found to be ca.7
lS/cm in 10-3 M DMF solutions, indicatingthe 1:1 electrolytic
nature of the compounds. This state indicated the nonelectro-
lytic behavior for Cr(III) and Ni(II) complexes (Altundas et al.,
2010). The results obtained showed that the structure of com-
plexes is the ML complexes according to the LC-mass spec-
troscopy of [M-3H2O]? 253 (m/z: %11.2), [M-3H2O]? 267
(m/z: %9.8), [M-H2O]? 287.6 (m/z: %18.2), [M-H2O]? 301.6
(m/z: %11.2), [M-2H2O]? 281.7 (m/z: %11.2), [M-2H2O]?
295.7 (m/z: %11.2), [M-2H2O]?317.1 (m/z: %11.2), and [M-
2H2O]? 330.1 (m/z: %11.2); for [Ni(5F-Gly)(H2O)3], [Ni(5F-
Ala)(H2O)3], [Ni(5F-3Cl-Gly)(H2O)], [Ni(5F-3Cl-Ala)(H2O)],
[Cr(5F-Gly)Cl(H2O)2], [Cr(5F-Ala)Cl(H2O)2], [Cr(5F-3Cl-
Gly)Cl(H2O)2], and [Cr(5F-3Cl-Ala)lCl(H2O)2], respectively.
The ligands and the complexes were tested for their
antimicrobial activity by the well-diffusion method. Each
ligand and complex was kept dry at room temperature and
dissolved (0.25 lg/ml) in DMF. DMF was used as solvent
and also for control. It was found to have no antimicrobial
activity against any of the tested organisms. 1% (v/v) of
24-h broth culture containing 106 CFU/ml was placed in
sterile Petri dishes. Mueller-Hinton Agar (MHA) (15 ml)
kept at 45 °C was then poured into the Petri dishes and
allowed to solidify. Then 6-mm diameter wells were pun-
ched carefully using a sterile cork borer and were entirely
filled with the test solutions. The plates were incubated for
24 h at 37 °C. On completion of the incubation period, the
mean value obtained for the three holes was used to cal-
culate the zone of growth inhibition of each sample. Bac-
terial and fungal subcultures were tested for resistance to
six antibiotics (produced by Oxoid Lt., Basingstoke, UK):
Table 1 Analytical and physical data for amino acid-Schiff bases and their Ni (II) and Cr(III) complexes
Compound
Empirical formula
(formula weight, g)
m.p. (°C), lB Elemental analysis, found (calcd) %
Electrolyte
C
H
N
M
lS/cm
Type
[5F-Gly]
C9H8NO3F (196.6)
82–83, –
85–87, –
92–94, –
96–97, –
229, 2.88
250[, 2.84
115a, D
53.61 (54.93) 4.98 (4.06) 8.28 (7.12)
53.79 (56.98) 4.73 (4.74) 7.21 (6.64)
47.13 (46.75) 3.31 (3.03) 6.41 (6.06)
49.37 (48.97) 3.19 (3.67) 6.12 (5.71)
–
–
–
–
KCl 14.38 1:1
H2O 2.21 ne
DMF 0.27 ne
[5F-Ala]
C
10H10NO3F (210.6)
C9H7NO3FCl (231)
10H9NO3FCl (245)
[5F-3Cl-Gly]
[5F-3Cl-Ala]
[Ni(5F-Gly)(H2O)3]
[Ni(5F-Ala)(H2O)3]
C
C9H12NO6FNi (307,7)
C10H14NO6FNi (321,7)
34.75 (35.09) 3.77 (3.89) 4.33 (4.54) 18.52 (19.07) 6.23
36.61 (37.30) 4.82 (4.35) 4.78 (4.36) 17.30 (18.24) 6.67
35.11 (35.34) 4.55 (4.35) 5.01 (4.58) 19.37 (19.20) 7.03
38.03 (37.54) 2.49 (2.81) 4.71 (4.38) 17.78 (18.36) 7.22
33.47 (33.99) 3.56 (3.14) 4.61 (4.40) 15.22 (16.33) 7.28
35.63 (36.17) 3.21 (3.61) 4.31 (4.22) 15.21 (15.64) 7.32
30.11 (30.58) 2.27 (2.83) 3.51 (3.96) 14.72 (14.69) 7.47
ne
ne
ne
ne
ne
ne
ne
[Ni(5F-3Cl-Gly)(H2O)] C9H7NO4FClNi (305.6)
[Ni(5F-3Cl-Ala)(H2O)] C10H9NO4FClNi (319.6)
[Cr(5F-Gly)Cl(H2O)2] C9H10NO5FClCr (317.7)
122, D
103, 4.08
[Cr(5F-Ala)Cl(H2O)2] C10H12NO5FClCr (331.7) 112, 3.97
[Cr(5F-3Cl-
Gly)Cl(H2O)2]
C9H10NO5FCl2Cr (353.1) 114, 4.10
[Cr(5F-3Cl-
Ala)lCl(H2O)2]
C10H11NO5FCl2Cr (366.1) 119, 3.81
32.46 (32.77) 3.42 (3.00) 3.37 (3.82) 15.87 (14.17) 7.52
ne
D diamagnetic, ne nonelectrolitic
a
Decomposition temperature
123

Med Chem Res (2013) 22:580–587
583
Table 2 summarizes the main IR and UV–visible bands
of the Schiff bases and their complexes. IR bands of
water molecules are coordinated to the metal ion
(Scheme 2). The appearance of new bands in the 503–560
and 405–411 cm-1 regions are due to m(M–O) and m(M–N),
respectively (Altundas et al., 2010).
Schiff bases in the 1663–1667 cm-1, 3110–3125 cm-1
,
2798–2864/2446–2467 cm-1 regions are characteristic of
m(CH=N), m(OH), and m(CH)arom/alif, respectively (Sarı and
Gu¨rkan, 2004). The bands in the 1621–1638 cm-1 and
1579–1590 cm-1 regions may, respectively, ascribe to
mCOO-(asym) and mCOO-(sym) vibrations (Sarı and Gu¨rkan,
2004). The electronic spectra of the Schiff bases in DMF
show bands ca. 340 nm are attributed to the azomethine
chromospheres n ? p* transition (Sari et al., 2003). The
bands at higher energies (272–343 nm) are associated with
the benzene p ? p* and r ? r* transition (Sari et al.,
2003; Silverstein et al., 1981). The 1H-NMR and 13C-NMR
data of the Schiff bases are presented in Table 3. In gen-
eral, the duplets, quartet, or triplets observed at
7.10–7.85 ppm are assigned to aldehyde ring protons. The
singlet at 8.27–8.41 ppm and 9.95–9.99 ppm are assigned
to imine and aromatic hydroxyl protons, respectively. The
protons of –CH3, –CH2, and –CH of amino acid group in
the Schiff bases are also observed as expected. The 13C-
NMR spectra data of the Schiff bases (Table 3) are also in
accordance with the proposed structures.
Since all Cr(III) complexes and octahedral Ni(II) com-
plexes are paramagnetic, the 1H-NMR spectra could not be
1
obtained. H-NMR spectra of [Ni(5F-3Cl-Gly)(H2O)] and
[Ni(5F-3Cl-Gly)(H2O)] complexes were obtained due to the
diamagnetic properties. The diamagnetic Ni(II) complexes
exhibit signals in the range of 8.42–8.43 ppm due to
–CH=N protons. These signals are observed in the lower
field than ligands. The signals (1H-NMR and IR spectra) of
Ni(II) complexes are different from those of the corre-
sponding ligands, suggesting the coordination through
oxygen atoms in a phenol ring and azomethine groups. The
ligands showed signals at 9.95–9.99 ppm, but the com-
plexes do not contain OH signals as the ligands can coor-
dinate Ni(II) ions with deprotonated phenolic oxygen
(Table 3). More detailed information about the structure of
the ligands and their Ni(II) complexes were provided by the
13C-NMR spectra data. 13C-NMR spectra of the ligands
were assigned by comparison with those of their Ni(II)
complexes. The signals of carbon atoms, which neighbor to
an –OH group, were different. This can be attributed to the
coordination of the phenolic oxygen atom (Altundas et al.,
2010) (Table 3). C9 and C4 carbon atoms in the free Schiff
bases showed a significant shift after complexation. Fur-
thermore, doublets observed at 192.70–192.64 ppm and
192.71–192.68 ppm due to complexion, are assigned to
carbon of –COOH. This case may be due to the coordination
of the ligand to the metal atom by the azomethine nitrogen
and phenolic oxygen. Paramagnetic [Ni(5F-Gly)(H2O)3]
and [Ni(5F-Ala)(H2O)3] complexes show three d–d bands in
The azomethine and carboxylate bands in the IR spectra
of the complexes appear in the range 1683–1691,
1651–1658, and 1549–1561 cm-1, somewhat different
than observed for the free ligands. These indicate that the
azomethine nitrogen and the oxygen of the carboxylate
group are coordinated to metal ion. The IR spectra of all
complexes exhibit characteristic bands of coordination
water at ca. 3450, 885, and 774 cm-1 assigned to m(OH),
qr(OH), and qW(OH2) vibrations, respectively (Sarı and
Gu¨rkan, 2004). These observations clearly suggest that the
Table 2 Specific FTIR and UV-GB spectra data of amino acid-Schiff bases and their Ni (II) and Cr(III) complexes
Compound
tOH, tCH=N
tCH(alif)/tCH(arom) tCOOH (asim)
/
t
kmax (e)
Ni–O/Ni–N)
tCOOH (sim)
[5F-Gly]
3125, 1664 2466, 2305/2798 1628/1587
3110, 1667 2467, 2310/2861 1621/1590
3114, 1665 2468, 2308/2855 1632/1584
3120, 1663 2467, 2310/2864 1638/1579
3425, 1689 2767, 2606/3104 1651/1559
–
–
–
–
294 (1.267); 343 (0.967); 383 (0.55)
[5F-Ala]
294 (1.981); 318 (3.898); 333 (3.91)
[5F-3Cl-Gly]
[5F-3Cl-Ala]
[Ni(5F-Gly)(H2O)3]
272 (3.97); 314 (4.00); 337 (3.92); 361 (3.91)
277 (3.913); 308 (3.93); 348 (3.95); 373 (3.59)
528/411
288 (2.961); 337 (2.377); 400 (0.281); 641(0.034);
865 (0.031)
[Ni(5F-Ala)(H2O)3]
[Ni(5F-3Cl-Gly)H2O]
3425, 1684 2767, 2606/3107 1654/1556
3489, 1691 2765, 2680/3110 1658/1550
534/410
503/405
284 (2.582); 389 (0.411); 636(0.036); 893 (0.84)
271 (2.449); 313 (3.994); 331 (3.96); 354 (3.938);
448 (0.441)
[Ni(5F-3Cl-Ala)(H2O)]
3498, 1687 2667, 2597/3116 1658/1552
560/413
270 (3.486); 318 (3.872); 335 (3.931); 355 (3.581);
452 (0.514)
[Cr(5F-Gly)Cl(H2O)2]
[Cr(5F-Ala)Cl(H2O)2]
3465, 1691 2765, 2621/3115 1654/1551
3473, 1687 2764, 2629/3112 1651/1549
516/408
521/411
519/412
286 (2.874); 325 (2.078); 358 (0.687); 627(0.566)
283 (2.882); 369 (2.814); 537 (0.703)
[Cr(5F-3Cl-Gly)Cl(H2O)2] 3485, 1683 2769, 2601/3113 1657/1554
271 (3.049); 306 (2.971); 329 (1.621); 571 (0.497)
284 (2.885); 321 (2.870); 335 (1.531); 623 (0.365)
[Cr(5F-3Cl-Ala)Cl(H2O)2] 3475, 1685 2767, 2607/3117 1658/15561 517/409
123

584
Med Chem Res (2013) 22:580–587
123

Med Chem Res (2013) 22:580–587
585
O
C
Scheme 2 Structure of
suggested for studied complexes
M: Cr(III) or Ni(II)
R-CH
N
X: -H or –Cl; R: -H or –CH3
:
O:
Y
CH
Y, Z: H2O, for octahedral Ni(II) / -, for diamagnetic Ni(II)
Y: H2O; Z: -Cl for octahedral Cr(III)
M
OH2
:
O
Z
X
F
Table 4 Antimicrobial activity of studied compounds (0.25 lg/ll) and standard reagents (diameter of zone inhibition (mm))
Microorganisms
Compound
Control
[5F-Gly],
[Ni(5F-Gly)(H2O)3],
[5F-Ala],
[Ni(5F-Ala)(H2O)3],
[5F-3Cl-Gly],
[Ni(5F-3Cl-Gly)H2O],
[5F-3Cl-Ala],
[Ni(5F-3Cl-Ala)H2O],
[Cr(5F-Gly)Cl(H2O)2]
[Cr(5F-Ala)Cl(H2O)2]
[Cr(5F-3Cl-Gly)Cl(H2O)2]
[Cr(5F-3Cl-Ala)Cl(H2O)2]
Gram (?ve)
Sh.dys. typ 10
L. monocytogenes
S. typhi H
Br. abortus
Gram (-ve)
S. aureus
11, –, 8
–, 10.5, –
18, 20, 10
10, 8, 10
11.5, 12.5, –
12.5, 10,7
–
–
–
–
10, 10, 8.5
15, 13.5, 12
11.5, 8.5, 10
6.5, 9, 9
–, 10.5, 13.5
10.5, 13, 11.5
18, 6.5, 11.5
15, 12.5, 11
11.5, 16, 11.5
17.5, 15, 15
7,11.5, 7
6, 11.5, 10
5, 13, 8.5
14, 11.5, 8.5
10, 10, –
18.5, 12.5, 10
12.5, 14, –
16, 17.5, –
–
–
–
–
S. epidermis
M. luteus
6,8.5, 8.5
12, 16.5, 7
15, 12, 21
13, 11.5, 12.5
26.5, 24, 17.5
16,16.5, 8.5
23.5, 31.5, 11
15.5, 19.5, –
E. coli
Yeast
C. albicans
10, 13, 13.5,
12.5, 10.5, 10,
15.5, 20.5, 10.5
15, 20, 10.5
–
Pozitif control
S. aureus
L. monocytogenes
E. coli
S. typhi H
Br. abortus
C. albicans
K30
25
24
30
30
–
15
11
16
22
–
25
18
10
14
–
20
17
11
19
–
–
–
SXT25
AMP10
AMC30
NYS100
SCF
–
–
–
–
–
–
–
20
–
–
–
–
–
12
K30 Kanamycin 30 lg, SXT25 Sulphamethoxazol 25 lg, AMP10 Ampicillin 10 lg, AMC30 Amoxycillin 30 lg, NYS100 Nystatin 100 lg,
SCF Sulbactam (30 lg)
Biological activity of Schiff bases and their complexes
the region 865–893 nm, 636–641 nm, and 389–400 nm.
3
First band is assigned for 3A2g(F) ? T2g(F)(t1), the second
3
band for 3A2g(F) ? T1g(F)(t2), and third band 3A2g(F) ?
The ligands and their complexes were screened for anti-
microbial activity in DMF solvent as a control substance.
The compounds were tested with the same concentrations
in DMF solution (0.25 lg/ll). All the synthesized com-
pounds and antibiotic exhibited varying degree of inhibi-
tory effects on the growth of different tested strains
(Table 4). All the compounds were active against
L. monocytogenes, Br. abortus, M. luteus, and C. albicans.
Br. abortus is a gram-negative bacterium that causes pre-
mature abortion of a cattle fetus. What makes this bacte-
rium so dangerous is that it can be transferred from an
animal to a human host (Sari et al., 2006). In humans, this
3T2g(P)(t3) transition. The UV-spectrum of Chromium (III)
complexes shows three bands in the regions 537–627 nm,
329–369 nm, and 283–306 nm. The peak ca. 550, 350, and
4
4
290 nm corresponds to the 4A2g ? T2g, 4A2g ? T1g (F),
and 4A2g ? T1g (P) electronic transition, respectively. The
4
magnetic measurements for Cr(III) and two Ni(II) (for
[Ni(5F-Gly)(H2O)3] and [Ni(5F-Ala)(H2O)3]) complexes
showed three and two unpaired electrons, and the magnetic
moment values 4.10–3.81 BM and 2.84–2.88 BM, respec-
tively, for Cr(III) and paramagnetic Ni(II) ion suggesting
consistency with their octahedral environment.
123

586
Med Chem Res (2013) 22:580–587
disease causes both acute and chronic symptoms, but can
be treated with antibiotics. This research indicates that
amino acid-Schiff bases and their Ni(II) and Cr(III) com-
plexes are active against Br. abortus (Table 4). All the
synthesized compounds showed moderate activity against
L.monocytogenes except [5F-3Cl-Ala]. [5F-Ala] and its
Cr(III) complexes were inactive in S.typhi H, whereas [5F-
Gly] and their complexes were active gram (-ve), [5F-3Cl-
Gly] and their complexes were active gram (?ve). In
general, the metal complexes are more potent bactericides
than the ligand. This enhancement in activity may be
explained on the basis of chelation theory (Altundas et al.,
2010). Chelation reduces the polarity of the metal ion.
Hence, a complex has lipophilic character, and increases
the interaction between metal ion and the lipid is favored.
This lead to the breakdown of the permeability barrier of
the cell, resulting in interference with the normal cellular
processes (Murukan and Mohanan, 2007). As seen in
Table 4, diamagnetic Ni(II) complexes showed a signifi-
cant activity against gram (?ve) and gram (-ve)
(Scheme 3). The investigated compound’s antimicrobial
activity values in this research were higher than that
reported for other amino acid-Schiff base derivatives (Sa-
kiyan et al., 2004; Sari et al., 2003). The main difference in
the amino acid-Schiff base derivatives reported in this
paper is the presence of the fluorine atom. The other amino
acid-Schiff base derivatives included substituted benzyl,
pyridine, or naphtha groups. Coordination structure of
complexes plays an important role in their biological
activity mechanisms. The results show that the diamagnetic
Ni(II) complexes are more active against the tested yeast
and as compared to the paramagnetic Ni(II) complexes.
Diamagnetic Ni(II) complexes have square planer structure
(D4h). Square planer structure may be reducing the polarity
of the metal ion due to the strong overlap in between the
dx2-y2 orbital of metal ion and donor orbital of the ligand.
Thus, the lipophilic character of the central metal atom is
enhanced, which results in a higher capability to penetrate
the microorganisms through the lipid layer of the cell
membrane.
Furthermore, the antibacterial activity of these com-
pounds was also compared with seven commercial antibi-
otics, namely Kanamycin, Sulfamethoxazol, Ampicillin,
Ciprofloxacin, Amoxycillin, Sulbactam, and Nystatin. It
was seen that the synthesized compounds were effective as
the antibiotics mentioned.
Conclusions
In this paper, new amino acid-Schiff base derivatives were
synthesized by the condensation of 5-fluoro-2-hydroxy
benzaldehyde,
3-chloro-5-fluoro-2-hydroxbenzaldehyde
with D-glycine, D-alanine. And then, Ni(II) and Cr(III)
complexes were prepared by the template method. The
structures of the prepared compound were confirmed by
1
elemental analysis, IR H and 13C NMR spectral analysis.
Diamagnetic Ni(II) complexes showed a significant activ-
ity against gram (?ve) and gram (-ve).
Acknowledgments This work was supported by the Gazi Univer-
sity Research Fund (Project number: 05/2010-03 and 05/2007-02).
References
Abram U, Alberto R (2006) Technetium and rhenium: coordination
chemistry and nuclear medical applications. J Braz Chem Soc
17:1486–1500
¨
Altundas A, Sarı N, Colak N, Ogu¨tcu¨ H (2010) Synthesis and
biological activity of new cycloalkylthiophene-Schiff bases and
their Cr(III) and Zn(II) complexes. Med Chem Res 19:576–588
Avaji PG, Patil SA, Badami S (2008) Synthesis, spectral, thermal,
solid-state DC electrical conductivity and biological studies of
Co(II) complexes with Schiff bases derived from 3-substituted-
4-amino-5-hydrazino-1,2,4-triazole and substituted salicylalde-
hydes. Trans Met Chem (Weinh). 33:275–283
Eglof R, Piotr P, Bogumil B, Franz B (2009) Schiff bases in
biological systems. Curr Org Chem 13:241–249
Ellis G, Chang L, Cogionis B, Daneman D (1997) Incomplete
removal of labile fraction when measuring hemoglobin A1c with
bio-rad variant analyzer. Clin Chem 43:2437–2439
Gharagozlou M, Boghaei DM (2008) Interaction of water-soluble
amino acid Schiff base complexes with bovine serum albumin:
fluorescence and circular dichroism studies. Spectrochim Acta
Mol Biomol Spectros 71:1617–1622
Murukan B, Mohanan K (2007) Synthesis, characterization and
antibacterial properties of some trivalent metal complexes with
[(2-hydroxy-1-naphthaldehyde)-3-isatin] bishydrazone. J Enzym
Inhib Med Chem 22:65–70
Negm NA, Zaki MF (2009) Synthesis and characterization of some
amino acid derived Schiff bases bearing nonionic species as
corrosion inhibitors for carbon steel in 2N HCl. J Disper Sci
Technol 30:649–655
˘ ˘
Sakıyan I, Logoglu E, Sari N, Sakıyan N (2004) Antimicrobial
activities of N-(2-hydroxy-1-naphthalidene)-aminoacid(glycine,
alanine, phenylalanine, histidine, tryptophane) Schiff bases and
their manganese(III) complexes. Biometals 17:115–120
Scheme 3 Imaging of antimicrobial affectivities of Ni(II) complexes
against M. luteus
123

Med Chem Res (2013) 22:580–587
587
Sarı N, Gu¨rkan P (2004) Some novel amino acid-Schiff bases and
their complexes synthesis, characterization, solid state conduc-
tivity behaviors and potentiometric studies. Z Naturforsch B
59(6):692–698
Singh K, Singh DP, Barwa MS, Tyagi P, Mırza Y (2006) Antibac-
terial Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff bases
derived from fluorobenzaldehyde and triazoles. J Enzym Inhib
Med Chem 21:557–562
¨
Sari N, Gu¨rkan P, Cete S, Sakiyan I (2006) Synthesis, potentiometric
and antimicrobial activity studies on DL-Amino Acids-Schiff
Bases and their complexes Russ. J Coord Chem 32(7):511–517
Sarı N, Gu¨rkan P, Arslan S (2003) Synthesis, potentiometric and
antimicrobial activity studies on 2-pyridinilidene-DL-amino
acids and their complexes. Trans Met Chem 28:468–474
Sarı N, Nartop D, Karcı F, Disli A (2008) Novel hydrazone
derivatives and their tetracoordinated metal complexes. Asian J
Chem 20:1975–1985
Takeuchi T, Bottcher A, Quezada CM, Meade TJ, Gray HB (1999)
Inhibition of thermolysin and human a-thrombin by cobalt(III)
Schiff base complexes. Bioorg Med Chem 5:815–819
Wang MZ, Meng ZX, Liu BL, Cai GL, Zhang CL, Wang XY (2005)
Novel tumor chemotherapeutic agents and tumor radio-imaging
agents: potential tumor pharmaceuticals of ternary copper(II)
complexes. Inorg Chem Commun 8:368–371
Wang RM, Mao JJ, Song JF, Huo CX, He YF (2007) Antioxidant
activity of bovine serum albumin binding amino acid Schiff-
bases metal complexes. Chinese Chem Lett 18:1416–1418
Silverstein RM, Bassler GC, Morrill TC (1981) Spectrophotometric
identification of organic compounds, 4th edn. Wiley, New York,
pp 125–130
123