International Journal of Chemical and Analytical Science
ISSN: 0976-1206
Research Article
www.ijcas.info
Synthesis, Structural Characterization and Biological Activity of Tri- and
Tetradentate Ligands Containing Manganese(II) Complexes
Ramasamy Elayaperumal1, Periasamy Dharmalingam2*
1Department of Chemistry, J. J. College of Engineering and Technology, Tiruchirappalli, TamilNadu, India.
2Department of Chemistry, Urumu Dhanalakshmi College, Tiruchirappalli, TamilNadu, India.
Manganese (II) metal complexes with pyridine base derived from pyridine-2-aldehyde have been prepared and characterized by
elemental analysis, 1H NMR and UV–Vis spectra and electrochemical measurements. On the basis of these studies, a six
coordinated distorted octahedral environment and a five coordinated distorted trigonal bipyramidal geometry have been
proposed for the Mn(II) ion. The synthesized ligands and their complexs were also screened for its antimicrobial activity against
the test strains (Candida albicans, Escherichia coli, Staphylococcus aureus). The activity data show that the metal complexes are
found to have greater antibacterial and antifungal activity than the parent compounds and respective standards.
Keywords: Manganese(II), pyridine base, antifungal, test strains.
INTRODUCTION
The study of metal complexes of pharmaceutical compounds is
an important and active research area in bioinorganic
chemistry because the synergistic action of the beneficial effects
from the ligand and the activity of the metal can provide
enhanced activity of the drugs.[1–10] Co-ordination compounds
exhibit different characteristic properties which depend on the
metal ion to which they are bound. On the basis of nature of
the metal as well as the type of ligand, these metal complexes
have extensive applications in various fields of human
interest.[11] Chelation or complexation observes more potent
antibacterial effect against some microorganisms than the
respective drug. Manganese chloride causes loss of testicular
germ cells in rats and rabbits [12], and decreased libido and
impotency synthesized were reported in a man occupationally
exposed to manganese. The coordination chemistry of
manganese is dominated by stable Mn(II) and Mn(III) centers
and a mononuclear Mn+2 centers has been established at the
active site of some enzymes that display superoxide dismutase
activity.[13-14] The increasing prevalence of fungal infections,
especially hospital-acquired infections and infections in
immunocompromised patients, has heightened the need for
new anti-fungal treatments. Drug-resistant fungal isolates have
been reported for all known cases of antifungal drugs. Thus,
there is an urgent need to develop new and more effective
antifungal therapies. With the increasing incidence of deep
mycosis in recent years, there has been an increasing emphasis
on screening new and more effective antimicrobial drugs with
low toxicity. So we have evaluated the in vitro antifungal
activity of our complexes against various fungi. We report here
the synthesis and the structural characterization of
manganese(II) complexes with ligands deriving from pyridine2-aldehyde (Scheme 2.1). In addition, the results of their
activities against various fungi are also described.
MATRIALS AND METHODS
The
chemicals
used
include
2-chloromethylpyridine
hydrochloride,
picolylamine,
manganese(II)
chloride
tetrahydrate, sodium triacetoxyborohydride (Aldrich), and
tetrahydrofuran,
dichloromethane,
ethylacetate
and
triethylamine (Merck, India) were used as received.
Microanalyses were performed at Sophisticated Test and
Instrumentation Centre (STIC), Cochin University, Kerala. The
electronic spectra were recorded on an Agilent 8453 diode array
spectrophotometer. 1H NMR spectra were recorded on a Bruker
200 MHz NMR spectrometer. Cyclic voltammetry (CV) and
differential pulse voltammetry (DPV) were performed in a
single compartment cell with a three electrode system using a
EG & G PAR273 potentiostat/Galvanostat equipped with
Pentium-IV computer. EG&GM270 software was used to
acquire the data. The working electrode was Pt sphere (0.2866
cm2), counter electrode was Pt plate and the reference electrode
was a Ag/AgNO3 electrode. The supporting electrolyte was
0.1 M TBAP. Antimicrobial studies were carried out in Gene
Pool Research Centre, Gudalur.
Synthesis of Ligands
Synthesis of N,N,N-tris(pyrid-2-ylmethyl)amine (L1)
This was prepared by a procedure reported previously.[15] To a
mixture of picolylamine (4.5 mmol) and sodium
triacetoxyborohydride (3.75 g, 17.7 mmol) in dichloromethane
(100 mL) was added pyridine-2-carboxaldehyde (1.45 g, 13.5
mmol) and stirred for 18 h. The reaction was quenched with
sodium hydrogencarbonate and extracted with ethylacetate
(3×150 mL). The organic fractions were combined, dried
(Na2SO4), and the solvent was removed under reduced
pressure. The residue was redissolved in tetrahydrofuran (50
mL) and treated with NaH (0.22 g, 9.1 mmol). After the
mixture was stirred for 2 h, the solvent was removed and the
residue was extracted with dichloromethane. The extracts were
combined, and the solvent was evaporated under reduced
pressure to obtain L1 as a pale yellow solid, which is used
without further purification. Yield : 3.45 g (88 %). 1H NMR (200
MHz, CDCl3):  8.48-7.29 (m, 12H), 3.92 (s, 6H).
Synthesis of N,N-bis(pyrid-2-ylmethyl)-iso-propylamine (L2)
The above procedure was followed and iso-propylamine was
used to give L2 as viscous pale yellow oil, which is used for
complex preparation without further purification. Yield : 3.04
g (93%). 1H NMR (200 MHz, CDCl3):  8.48-7.29 (m, 8H), 3.88
(s, 4H), 1.87 (m, 1H), 1.05 (d, 6H).
Synthesis of Manganese(II) Complexes [Mn(L1)Cl2] (1)
[Mn(L1)Cl2] was prepared by adding MnCl2.4H2O (0.198 g, 1
mmol) in methanol (10 mL) to a solution of L1 (0.24 g, 1 mmol)
in methanol, stirred for 30 minutes, and then cooled. The white
colored complex was filtered off, washed with cold methanol
Corresponding Author:
Dr. P. Dharmalingam, Associate Professor, Department of Chemistry, Urumu
Tamilnadu, India; e-mail :<drpdharmalingamudc@gmail.com>
Received 11-07-2012; Accepted 01-08-2012
August, 2012
Dhanalakshmi College, Tiruchirappalli-620019,
International Journal of Chemical and Analytical Science, 2012, 3(8), 1496-1499
1496
Elayaperumal and Dharmalingam: Synthesis, Stuctural Characterization and Biological Activity of Tri- and Tetradentate Ligands
Containing Manganese(II) Complexes
and diethylether, and then dried under vacuum. Yield: 0.19 g
(80 %).
[Mn(L2)Cl2] (2)
This was synthesized by using same procedure as described
for the [Mn(L1)Cl2] by reacting MnCl2.4H2O (0.20 g, 1 mmol)
with L2 (0.24 g, 1 mmol). Yield: 0.23 g (63 %).
In vitro anti-microbial screening
Disc diffusion method
All methodology and steps were followed according to CLSI
except for disc content. Concentration of disc content was
roughly estimated by comparing the zone of inhibition values
to that of known antibiotics. An inoculums of 0.5 Mc Farland
standard (108 cfu/mL) was applied on Mueller Hinton Agar (a
depth of 4 mm in a petridish of 100 mm diameter). Maximum
six discs were applied on each plate and they were incubated a
t 350C for 16-18 hours. Zone of inhibition was measured
including the disc diameter (6 mm). Antimicrobial activity was
indicated by the presence of monochromator.
H2N
O
N
+
Na(CH3COO)3BH
N
N
N
N
THF
O
H3C CH3
Na(CH3COO)3BH
NH2
+ HC
3
CH3
THF
N
N
The tripodal/linear tetra- and tridentate ligands L1 and L2 are
expected to impose distorted octahedral geometry and either
distorted square pyramidal or trigonal bipyramidal geometry
respectively around the manganese(II) center. Since the
manganese ion is in +2 oxidation state, the metal complexes of
pyridine-based ligands (L1 and L2) offered high-spin d5 system
as reported in the literature. Conductivity studies in methanol
solution (M, 80-105  -1 cm2 mol-1) suggest that one of the
chloride ions is not coordinated to the metal center.
3.2 Electronic spectra
The complexes shows three bands in the range 213 - 415 nm,
which are assigned as the interelectronic transitions between
* (248 nm for complex 1 and 250 nm for complex 2), n*
(213 nm for complex 1 and 215 nm for complex 2) and d-d
transition (409 nm for complex 1 and 415 nm for complex 2)
respectively.
3.3 Electrochemical measurements
The electrochemical features of the manganese(II) complexes
were investigated in methanol solution by employing cyclic
(CV) and differential pulse voltammetry (DPV) on a stationary
platinum-sphere electrode. The redox potentials of the present
complexes are summarized in Table 2. By comparison to the
electrochemical data given in the literature for similar type of
manganese(II) complexes, the following assignments can be
made for the present system. The present complexes display
one electron redox process around E1/2 = 412 to 585 mV with
Ep = 85-90 mV, corresponding to Mn(II)/Mn(III) redox
couple. Another one around 700-980 mV originating from the
Mn(III)/Mn(IV) redox couple.
N
N
The ligands were reacted with equimolar amount of
MnCl24H2O in methanol to give mononuclear manganese(II)
complexes in good yield.
N
Scheme 2.1. Synthesis of ligands
RESULTS AND DISCUSSION
Table 1: Microanalytical data of ligands and Mn(II) complexes
Ligands
complexes
L1
L2
[Mn(L1)Cl2]
[Mn(L2)Cl2]
Colour
Empirical
formula
C18H18N4
C15H19N3
MnC18H18N4Cl2
MnC15H19N3Cl2
yellow
yellow
White
White
Molecular
weight
290.153
241.158
415.029
366.034
Elemental analysis
C
74.47(74.43)
74.65(74.63)
51.94(51.91)
49.07(49.05)
H
6.26(6.23)
7.94(7.92)
4.36(4.34)
5.22(5.19)
Calculated (found) (%)
N
19.30(19.28)
17.41(17.37)
13.50(13.46)
11.48(11.44)
Table 2: Electrochemical dataa of mononuclear manganese(II) complexes in methanol solution at 25 ± 0.2°C
E1/2
Complex
Epa(mV)
Epc(mV)
Redox process
Ep(mV)
CV(mV)
[Mn(L1)Cl2]
456.5
368.5
88
412.5
[Mn(L2)Cl2]
625.5
538.5
87
582.0
Anti-microbial studies of Mn(II) complexes
Anti-microbial activity of the present complexes were
explored by determining zone of inhibition (Disc Diffusion
Tests) using nystatin/chloramphenicol as reference standard
(Table 3) at 0.25 %, 0.50 % and 1 % concentration. In order to
establish the role of the transition metal center already bound
August, 2012
DPV(mV)
411.5
707.5
585.5
977.5
MnII
MnIII
MnII
MnIII
MnIII
MnIV
MnIII
MnIV
to the ligand on the growth of bacteria, we have initiated a
study on the antimicrobial activity of 1 and 2 against microbes
and the data were compared with the results obtained for the
free non-coordinated ligands L1 and L2. The observed order
of zone of inhibition was Candida albicans > Staphylococcus
aureus > Escherichia coli . The data reveal that the
International Journal of Chemical and Analytical Science, 2012,3(8),1496-1499
1497
Elayaperumal and Dharmalingam: Synthesis, Stuctural Characterization and Biological Activity of Tri- and Tetradentate Ligands
Containing Manganese(II) Complexes
antimicrobial activity of the complexes is superior to that of
the starting materials and standard reference against same
microbes under identical experimental conditions. Out of the
two complexes 1 and 2, the antimicrobial activity of 1 is found
to be more effective than that of 2 because of the presence of
tetradentate ligand which results in greater chelation.
The increased activity of metal chelates can be explained on
the basis of the overtone concept and chelation theory.
According to the overtone concept of cell permeability, the
lipid membrane that surrounds the cell favors the passage of
only lipid-soluble materials in which liposolubility is an
important factor that controls the antimicrobial activity. On
chelation the polarity of the metal ion will be reduced to a
greater extent due to overlap of ligand orbital and partial
sharing of the positive charge of the metal ion with donor
groups. Further it increases the delocalization of π-electrons
over the whole chelate ring and enhances the lipophilicity of
complexes. It is likely that the increased liposolubility of the
ligand upon metal complexation may contribute to its facile
transport into the bacterial cell which blocks the metal
binding sites in enzymes of microorganisms.
Table 3: Antimicrobial activity (Zone of Inhibition) of ligands and Mn(II) complexes
Test compound
L1
L2
[MnL1(Cl)2]
[MnL2(Cl)2]
Standard
(Chloramphenicol)
Antimicrobial activity
E. coli
C. albicans
0.25%
11
8
27
24
0.5%
9
6
32
27
17
1%
8
6
29
25
0.25%
6
5
16
13
0.5%
6
4
19
16
14
S. aureus
1%
8
3
19
17
0.25%
9
6
18
16
0.5%
8
7
24
21
20
1%
8
7
27
25
Values of zone of inhibition [mm, including the diameter of the disk (6 mm)]
These complexes also disturb the respiration process of the
cell and thus block the synthesis of proteins, which restricts
further growth of the organism. This would suggest that
the chelation could facilitate the ability of a complex to
cross a cell membrane[16] and can be explained by Tweedy’s
chelation theory.[17] Chelation considerably reduces the
polarity of the metal ion because of partial sharing of its
positive charge with donor groups and possible π-electron
delocalization over the whole chelate ring. Such a chelation
could enhance the lipophilic character of the central metal
atom, which subsequently favours its permeation through
the lipid layer of the cell membrane. The variation in the
effectiveness of different compounds against different
organisms depends either on the impermeability of the cells
of the microbes or on differences in ribosome of microbial
cells. The enhanced activity of the complexes can also be
explained on the basis of their high solubility (as a result,
water-soluble complexes are readily accumulated in
bacterial and fungal cells, resulting in the activation of
enzymes), fineness of the particles, size of the metal ion and
the presence of bulkier organic moieties.
CONCLUSIONS
The authors thank the Head, Department of Chemistry,
UDC, Trichy for providing Laboratory facilities.
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August, 2012
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Source of support: Nil,
Conflict of interest: None Declared
August, 2012
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