Synthesis, characterization, and biological study of some biologically potent schiff base transition metal complexes

Article abstract of DOI:10.1134/S107032840809008X

The synthesis and characterization of a Schiff base derived from aniline and salicylaldehyde and its Co(II), Mn(II), and Zn(II) complexes is reported; several physical tools, in particular, elemental analysis, infrared and NMR techniques were used to investigate the chemical structure of the reported complexes. The ligand is found to be bound to the metal atom through the oxygen atom of the hydroxyl group, which is also supported by spectroscopic techniques. The results obtained by FT-IR and NMR showed that the Schiff base-transition metal complexes have octa hedral geometry. Biological screening of the complexes reveals that the Schiff base-transition metal complexes show significant activity against all microorganisms.

Full text of DOI:10.1134/S107032840809008X

ISSN 1070-3284, Russian Journal of Coordination Chemistry, 2008, Vol. 34, No. 9, pp. 678–682. © Pleiades Publishing, Ltd., 2008.
Synthesis, Characterization, and Biological Study of Some
Biologically Potent Schiff Base Transition Metal Complexes1
W. Rehmana, F. Samana, and I. Ahmadb
a Department of chemistry, Hazara University, Mansehra, Pakistan
b Department of Physics, Louisiana State University USA
E-mail: sono_waj@yahoo.com
Recieved August 25, 2007
Abstract—The synthesis and characterization of a Schiff base derived from aniline and salicylaldehyde and its
Co(II), Mn(II), and Zn(II) complexes is reported; several physical tools, in particular, elemental analysis, infra-
red and NMR techniques were used to investigate the chemical structure of the reported complexes. The ligand
is found to be bound to the metal atom through the oxygen atom of the hydroxyl group, which is also supported
by spectroscopic techniques. The results obtained by FT-IR and NMR showed that the Schiff base-transition
metal complexes have octa hedral geometry. Biological screening of the complexes reveals that the Schiff base-
transition metal complexes show significant activity against all microorganisms.
DOI: 10.1134/S107032840809008X
1
INTRODUCTION
and determined biological activities of a Schiff base
derived from aniline and salicylaldehyde and its various
transition metal complexes and results of this study are
reported herein.
The preparation and study of inorganic compounds
containing biologically important ligands is made eas-
ier, because certain metal ions are active in many bio-
logical processes; species of low molecular weight are,
hence, sought that reproduce, as far as possible, the
structural properties and the reactivity of naturally
occurring complexes of these ions in such processes.
The fact that copper together with magnesium, cal-
cium, iron, zinc, chromium, vanadium, and manganese
are essential metallic elements and display great bio-
logical activity when associated with certain metal–
protein complexes, participating in oxygen transport,
electronic transfer reactions, or the storage of ions [1]
has created massive interest in the study of systems
containing these metals [2].
Schiff base ligands are considered “privileged
ligands” because of their easiness of preparation and
their use as flourogenic agent, pesticides and herbicidal
agents [3], blocking agents, and in catalysis [4]. Schiff
bases derived from salicylaldehydes are well known as
polydentate ligands [5]. Coordinating in deprotonated
or neutral forms. Several adducts of non-transition,
early transition, and f-metals with such bases acting
neutral ligands [5, 6] have been studied. Comparatively,
there is little information [7, 8] about the capacity of the
d (5–10) elements of the first transition series to form
similar compounds. Previously a number of biologi-
cally important metal complexes have been by reported
our group [9–15]. In order to broaden the scale of inves-
tigations on the Schiff base transition metal complexes,
we have now synthesized, structurally characterized,
EXPERIMENTAL
All chemicals used in this work were reagent grade
(RDH/Aldrich/Fluke/Merck), including cobalt(II)
chloride hexahydrate, Manganese(II) chloride tetrahy-
drate, Zinc acetate dihydrate, DMSO, salicylaldehyde,
aniline, methanol, chloroform, acetone and DMF. The
melting points were measured on a Reichert thermom-
eter (Gallen Kamp Co.). Elemental analyses (C, H, N)
were performed on a Carlo Erba 1106 elemental ana-
lyzer. The amount of metal was measured on an ARL
3580 inductively coupled plasma / optical emission
spectrometry (ICP/OESO) instrument. The IR spectra
were recorded using KBr discs (4000 400 cm–1 on a
1
Shimadzu 8300 FT-IR spectrophotometer. The H and
13C NMR spectra were recorded on a multinuclear FT
NMR 300 MHz JEOL instrument using TMS as an
internal standard.
Synthesis of ligand. Aniline (50 mmol) in a mixture of
chloroform–benzene was taken in a two neck flask
equipped with a reflux condenser and a thermometer. To
this mixture salicylaldehyde (50 mmol) was added drop-
wise with constant stirring. This reaction mixture was re-
fluxed for 3 h; water formed during the reaction was re-
moved by using a Dean Stalk funnel, excess of the solvent
was removed under reduced pressure. The yellow solid
1
The text was submitted by the authors in English.
678

SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL STUDY
679
product thus obtained was then recrystallized from chloro- C(3) 128.0, C(4) 116.3, C(5) 133.5, C(6) 114.1, C(8)
form. Yield was 88%; mp = 47°C.
179.7, C(11) 119.6, C(12) 127.5, C(1): 126.4, C(14) 128.0,
C(15) 121.9.
For C13H11NO (M = 197)
III: yield was 82%; orange red; mp = 71°C.
anal. calcd, (%): C, 79.19; H, 5.587; N, 7.10; O, 19.09.
Found, (%):
C, 79.13; H, 5.50; N, 6.90; O, 18.80.
For C26H24O2N2Mn (M = 451)
anal. calcd, (%): C, 69.18; H, 5.32; N, 6.20; Mn, 12.30.
IR (ν, cm–1): 3600 s ν(OH), 1500 ν(CO), 1600 m ν(C=N);
1H NMR(CDCl3): H(3): 7.1 m. (1H, 1CH), H(4) 6.6 m.
(1H, 1CH), H(6) 6.8 m. (1H, 1CH), H(7) 12.2 s. (1H,
1OH), H(8) 9.1 s. (1H, 1CH), H(11) 7.3 m. (1H, 1CH),
H(12) 7.5 m. ([1H, 1CH), H(13) 7.2 m. (1H, 1CH), H(14)
Found, (%):
C, 69.13; H, 5.25; N, 5.98; Mn, 11.90.
IR (KBr cm–1): 3400 w ν(C–H), 1500 s ν(CO), 1600 m
1
ν(C=N), 650 sh ν(Mn–O), 500 s ν(Mn
N); H
13
7.8 m. (1H, 1CH); C NMR(CDCl3) C(1) 158.5, C(2)
NMR(CDCl3): H(3) 7.0 m. (2H, 2CH), H(4) 6.5 m. (2H,
2CH), H(6) 7.1 m. (2H,2CH), H(8) 8.8 s. (2H, 2CH),
H(11) 6.9 m. (2H, 2CH), H(12) 7.7 m. (2H, 2CH), H(13)
7.1 m. (2H, 2CH), H(14) 7.4 m. (2H, 2CH), Hα 12.1 s.
(2H, 2OH); 13C NMR (CDCl3) C(1) 170.9, C(2) 119.0,
C(3) 128.2, C(4) 114.8, C(5) 131.9, C(6) 111.9, C(8)
175.2, C(11) 119.0, C(12) 125.5, C(13) 128.1, C(14)
127.8, C(15) 122.1.
115.8, C(3) 129.9, C(4) 116.6, C(5) 133.4, C(6) 114.2,
C(8) 172.5, C(11) 119.7, C(12) 127.2, C(13) 126.5, C(14)
128.9, C(15) 121.9.
Synthesis of complexes metals with schiff baces
(M = Co (I), Zn (II), and Mn (III). To a three neck
flask equipped with a reflux condenser and a thermom-
eter a methanolic solution of the ligand (10 mmol). To
this a hot methanolic solution of metal salt (5 mmol)
was added with constant stirring. This mixture was
refluxed for 3 h; excess of the solvent was removed
under vacuum. The solid product was formed, which
Antifungal activity. The dilution plate method [16]
was used for isolation of fungi. Selected and isolated
fungi were maintained on potato dextrose agar plates at
was recrystallized from methanol–acetone for Co, 4°C for further experimental work. The antifungal
methanol for Zn, and chloroform for Mn.
I: yield was 76%; light pink; mp = 214°C.
activities of the ligands, mixed ligand complexes, metal
nitrates, fungicides (bavistin and emcarb), and the con-
trol DMSO (dimethyl sulfoxide) were screened using
the plate poison technique [17]. Seven day-old cultures
of Aspergillus niger, Fusarium oxysporum, and
Aspergillus flavus were used as test organisms. A stock
solution of 500 g/ml was made by dissolving 50 mg of
each compound in DMSO (100 ml). The sterilized
medium with the added stock solution was poured into
90 mm sterile petri plates and allowed to solidify. They
were inoculated with a 5-mm actively growing myce-
lial disc and incubated at 27°C for 72 h. After 72 h of
inoculation, the percent reduction in the radial growth
diameter over the control was calculated. The growth
was compared with dimethylsulfoxide as the control.
For C26H24O2N2Co (M = 455)
anal. calcd, (%): C, 68.57; H, 5.27; N, 6.15; Co, 19.09.
Found, (%):
C, 68.51; H, 5.23; N, 6.11; Co, 18.80.
IR (ν, cm–1): 3400 w ν(C–H), 1600 s ν(CO), 1100 m
1
ν(C=N), 538 s ν(Co–O), 500 sh ν(Co
N); H
NMR(CDCl3): H(3) 7.0 m. (2H, 2CH), H(4) 6.9 m. (2H,
2CH), H(6) 7.2 m. (2H,2CH]), H(8) 8.8 s. (2H, 2CH),
H(11) 7.5 m. (2H, 2CH), H(12) 7.8 m. (2H, 2CH), H(13)
7.6 m. (2H, 2CH), H(14) 7.3 m. (2H, 2CH), Hα 10.5 s.
13
(2H, 2OH); C NMR (CDCl3) C(1) 169.3, C(2) 115.1,
C(3) 129.2, C(4) 116.1, C(5) 133.2, C(6) 114.5, C(8)
177.5, C(11) 119.3, C(12) 127.0, C(13) 126.1, C(14)
128.2, C(15) 121.6.
Antibacterial activity. The antibacterial activities
were determined by using the agar well-diffusion
method [18]. The wells were dug in the media with a
sterile borer and eight-hour-old bacterial inoculums
containing ca. 104–106 co-lony-forming units (CFU)/ml
was spread on the surface of the nutrient agar using a
sterile cotton swab. The recommended concentration of
the test sample (2 mg/ml in DMSO) was introduced
into the respective wells. Other wells containing
DMSO and the reference antibacterial drug served as
negative and positive controls, respectively. The plates
were incubated immediately at 37°C for 20 h. The
activity was determined by measuring the diameter of
the inhibition zone (in mm) showing complete inhibi-
tion. Growth inhibition was calculated with reference
to the positive control.
II: yield was 73%, colorless; mp = 288°C.
For C26H24O2N2Zn (M = 461)
anal. calcd, (%): C, 67.68; H, 5.20; N, 6.07; Zn, 20.63.
Found, (%):
C, 67.61; H, 5.16; N, 5.97; Zn, 19.544.
IR (ν, cm–1): 3500 w ν(C–H); 1600 s ν(CO); 1100 m
1
ν(C=N), 650 w ν(Zn–O), 500 sh ν(Zn
N); H
NMR(CDCl3): H(3) 7.2 m. (2H, 2CH), H(4) 6.7 m. (2H,
2CH), H(6) 7.0 m. (2H,2CH]), H(8) 9.2 s. (2H, 2CH),
H(11) 7.1 m. (2H, 2CH), H(12) 7.9 m. (2H, 2CH), H(13)
7.5 m. (2H, 2CH), H(14) 7.6 m. (2H, 2CH), Hα 11.7 s.
13
(2H, 2OH); C NMR(CDCl3) C(1) 168.9, C(2) 117.3,
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 9 2008

680
REHMAN et al.
Table 1. Antifungal activity results for the ligand and com-
CH=N group and a multiplet were observed at 6.6 to
7.8 ppm for the aromatic protons, these peaks are
slightly shifted in the spectra of complexes, the results
obtained are quite comparable with the reported date
[21–24].
plexes
% Inhibition
Compound
(growth diameter in mm)
The mode of bonding suggested above has also been
confirmed by the 13C NMR spectral data. In the
13C NMR spectra of the complexes, the resonance of
the carbon attached to the hydroxyl group in the ligand
is observed at 158.5 ppm, which after complexation
shifted to 168.9–170.9 ppm, suggesting the coordina-
tion of the ligand through this oxygen, to the central
metal atom [25]. The azomethine (C=N) carbon is
deshielded on complexation, and a signal appears in the
172.5–179.7 ppm range. This deshielding provides sup-
port that the azomethine nitrogen also involves in the
complexation [25].
A. niger F. oxysporum A. flavus
Bavistin*
(00)100
(00)100
(21)29
(12)15
(22)28
(22)24
(00)100
(00)100
(28)33
(12)12
(17)22
(26)29
(25)27
(00)100
(00)100
(32)40
(15)16
(21)25
(31)34
(31)37
Emcarb*
DMSO (control)
Ligand
Cobalt complex
Zinc complex
The structure of the Schiff base and proposed struc-
ture of cobalt, zinc and manganese complexes is given
below:
Manganese complex (18)20
* Conventional fungicides.
H
8a
3
6
8
N
15
12
9
4
5
2
1
10
11
14
13
RESULTS AND DISCUSSION
OH
The reactions for preparing of complexes were
found to be quite facile and were complete within 3 h
of refluxing. The resulting complexes were obtained in
good yield. The complexes were soluble in DMSO. The
elemental analyses obtained are in good agreement
with the calculated one.
7
H
C N
O
α
H2O
M
OH2
IR spectroscopy is a powerful tool for assigning
geometries to the coordination complexes [19–21]. In
the IR spectrum of the ligand, the broad band at OH
(3650 cm–1) is absent in the spectra of the metal com-
plexes showing that the complexation occurs through
phenolic oxygen [9]. The new bands, which are not
present in the spectrum of the Schiff base derived from
aniline and salicylaldehyde, appeared at 500 and
O
N
C
H
where M = Mn, Co, Zn.
750 cm–1 are attributed to ν(M
vibrations. The appearance of ν(M
N) and ν(M–O)
The results of the antifungal studies are presented in
Table 1. The results obtained showed that the mixed-
ligand complexes are more toxic than their parent
ligand against the same microorganisms. The increase
in the antifungal activity of the mixed-ligand com-
plexes may be due to the effect of the metal ion on the
normal cell processes. A possible mode for the toxicity
increase may be considered in light of Tweede’s chela-
tion theory [17]. Chelation considerably reduced the
N) and ν(M–O)
vibrations supports the involvement of the nitrogen and
oxygen atoms in complexation with metal ions under
investigation [20].
A sharp band for ν(C=N) at 1600 cm–1 was shifted
in the spectra of all the synthesized complexes, show-
ing the involvement of methinic nitrogen in complex-
ation [9].
The 1H NMR spectra of the synthesized compounds polarity of the metal ion because of the partial sharing
were recorded in CDCl3. All the protons in the spectra of its positive charge with the donor groups and the
were identified, and the total number of calculated pro- π-electron delocalization over the whole chelate ring.
tons is in good agreement with the proposed structure. Such chelation could enhance the lipophilic character
The spectra of the ligand contain a peak at 12.2 ppm for of the central metal atom, which subsequently favors its
the phenolic proton. This peak is absent in the spectra permeation through the lipid layer of the cell mem-
of all the complexes, which suggests complexation brane. Although there is a sufficient increase in the fun-
through the phenolic oxygen. The singlet peak at gicidal activity of the mixed-ligand complexes as com-
9.1 ppm corresponds to the proton attached to the pared to the free ligand and the control (DMSO), they
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 9 2008

SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL STUDY
Table 2. Antibacterial bioassay results for the ligand and complexes*
681
Micro-organism
Bacillus subtilIs
Ligand
1
2
3
Standard drug**
+
n.a
+++
++
++
+
++
+++
++
++++
++++
++++
++++
++++
++++
Staphylococcus aureus
Escherichia coli
++
+
++
+++
+++
++
++
Schigella flexenari
Pseudomonas aeruginosa
Salmonella typhi
n.a
+
+++
+++
+++
+
n.a
++
* Concentration used 1.0 mg/1.0 ml of DMSO, size of well 6 mm (diameter).
** Standard drug: Imipinem; n.a: no activity; + siginificant activity; ++ low activity; +++ high activity; ++++ maximum activity, 1 —
cobalt complex, 2 — zinc complex, 3 — manganese complex.
cannot attain the effectiveness of the conventional fun- hra, Pakistan is acknowledged for value able discus-
gicides (bavistin and emcarb).
sion.
Bactericidal activities of the ligand and their metal
complexes were tested against various bacteria and are
given in Table 2. It has been suggested that the ligands
with the N- and O-donor systems might have inhibited
enzyme production, since enzymes that require free
hydroxy groups for their activity appeared to the espe-
cially susceptible to deactivation by the ions of the
complexes. The complexes facilitate their diffusion
through the lipid layer of spore membranes to the site
of action ultimately killing them. The variation in the
effectiveness of different biocidal agents against differ-
ent organisms [26] depends on the impermeability of
the cell. The hydrocarbon acts as a lipophilic group [27]
to drive the compound through the semipermeable
membrane of the cell. Chelation reduces the polarity of
the central ion mainly because of the partial sharing of
its positive charge with the donor groups and possible
p-electron delocalization within the whole chelate ring.
This chelation increases the lipophilic nature of the
central atom, which favors its permeation through the
lipid layer of the membrane. The results revealed that
the ligand has no promising activity against the bacteria
used, while the tin(IV) complexes, especially the triph-
enyltin complex, exhibit excellent activity against all
types of the microorganisms used.
REFERENCES
1. Albertin, G., Bordignon, E., and Orio, A.A., Inorg.
Chem., 1975, vol. 14, p. 1411.
2. Karlin, K.D. and Zubieta, J (Eds), Copper Coordination
Chemistry: Biochemical and Inorganic Perspectives,
New York: Adenine Press, 1983, p. 43.
3. Holm, R.H., Everett, G.W., and Chakravorty, A., Prog.
Inorg. Chem., 1966, vol. 7, p. 83.
4. Kawakami, K., Miya-Uchi, M., and Tanaka, T., J. Inorg.
Nuc. Chem., 1971, vol. 33, p. 3773.
5. Bullock, J.I. and Tajmir-Riahi, H.A., Dalton Trans., 1978,
p. 36.
6. Bamfield, P., J. Chem. Soc., 1967, A, p. 804.
7. Mahmoud, M.R. and El-Haty, M.T., J. Inorg. Nucl.
Chem., 1980, vol. 42, p. 349.
8. Reilley, C.N., Schimid R.W., and Sadek F.A., J. Chem.
Educ., 1959, vol. 36, p. 555.
9. Rehman, W., Baloch, M.K., Badshah, A., and Ali S., J.
Chin. Chem. Soc., 2005, vol. 52, 231.
10. Rehman, W., Badshah, A., Baloch, M.K., et al. J. Chin.
Chem. Soc., 2004, vol. 51, p. 929.
11. Rehman, W., Baloch, M.K., Muhammad, B., et al. Chin.
Sci. Bull., 2004, vol. 49, p. 119.
12. Rehman, W., Baloch, M.K., Badshah, A., et al. Spectro-
chim. Acta A., 2006, vol. 65, p. 689.
13. Rehman, W., Baloch, M.K., and Badshah, A., J. Braz.
Chem. Soc., 2005, vol. 16, p. 827.
ACKNOWLEDGMENTS
14. Rehman, W., Baloch, M.K., Badshah, A., et al. Russ. J.
Coord. Chem., 2005, vol. 31, p. 856.
15. Rehman, W., Baloch, M.K., and Badshah, A., Russ. J.
Inorg. Chem., 2007, vol. 52, p. 140.
One of the authors, Iftikhar Ahmed, is highly grate-
ful to Department of Microbiology, Louisiana State
University, USA for the determination the bioactivities.
Associate Professor A. Christofides (University of
Thessalonki, Greece) is highly obliged for providing 16. Chauhan, J.B., Subramanian, R.B., and Sanyal, P.K., In-
dian J. Environ. Toxicol., 2002, vol. 12, p. 22.
useful research material and Dr. Bakhtiar Muhammad,
Department of Chemistry, Hazara University, Manse-
17. Tweedy, B.G., Phytopatology, 1964, vol. 55, p. 910.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 9 2008

682
REHMAN et al.
18. Rahman, A., Choudhary, M.I., and Thomsen, W.J., Bio- 22. Seeger, D.M., Korzeniewski, C., and Kowalchyk, W., J.
assay Techniques for Drug Development, Amsterdam
(The Netherlands): Harwood Academic Publishers,
2001.
Phys. Chem. 1991, vol. 95, p. 68.
23. Golcu, A., Tumer, M., Demirelli, H., and Wheatley, R,A.,
Inorg. Chim. Acta., 2005, vol. 358, p. 1785.
24. Doine, H., Bull. Chem. Soc. Jpn. 1985, vol. 58, p. 1327.
25. Lewinski, J., Justyniak, I., Zachara, J., and Tratkiewicz, E.,
Organometallics, 2003, vol. 22. p. 4151.
26. Lawrance, P.G., Harold, P.L., and Francis, O.G., Antibi-
otic Chemotheraphy, 1980, vol. 5, p. 1597.
19. Rodriguez-Arguelles, M., Ferrari, M.B., Fava, G.G.
et al. J. Inorg. Biochem. 1997, vol. 66, p. 7.
20. Lima, L., Teixe Ira, L.R., Carneiro, T.G., et al., J. Braz.
Chem. Soc.,1999,vol. 10, p.184.
21. Alderighia, L., Gans P., Ienco, A., et al. Coord. Chem. 27. Rich, S. and Horsfall, J.G., Phytopathology, 1952, vol. 42,
Rev., 1999, vol. 184, p. 311.
p. 457.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 9 2008