Synthesis, characterization and antimicrobial properties of some mixed ligand complexes of Zn(II) dithiocarbamate with different N-donor ligands

Article abstract of DOI:10.1016/j.ica.2016.03.033

In this study, adducts of Zn(II) dithiocarbamates containing different N-donor ligands (pyridine, 2,2′-bipyridine and 1,10-phenanthroline) have been synthesized. The parent dithiocarbamate complex comprise N-methyl-N-phenyl dithiocarbamate (L¹) and N-ethyl-N-phenyl dithiocarbamate (L²), and the adducts are represented as [ZnL¹L²py], [ZnL¹L²bpy], and [ZnL¹L²phen] (where py = pyridine, bpy = 2,2′-bipyridine, and phen = 1,10-phenanthroline). All the compounds have been characterized by elemental analysis and spectroscopic techniques (IR and NMR). In addition, the crystal structure of [ZnL¹L²bpy] complex is also reported. The structure indicates that the two dithiocarbamate ligands are disordered in 0.67:0.33 ratio and alternatively bond as monodentate and bidentate ligands. The bipyridine acts as a bidentate ligand, and gives the structure around the Zn atom a distorted square pyramidal geometry. In order to evaluate their antimicrobial properties, the precursor complex and the adducts were screened against six pathogenic bacteria strains and two fungi organisms. The antimicrobial activities of the complexes were in the order [ZnL¹L²] > [ZnL¹L²py] > [ZnL¹L²bpy] > [ZnL¹L²phen]. The precursor complex, ZnL¹L², showed the lowest MIC and is considered as the complex with most antimicrobial activity against the selected microorganisms.

Full text of DOI:10.1016/j.ica.2016.03.033

Accepted Manuscript
Synthesis, characterization and antimicrobial properties of some mixed ligand
complexes of Zn(II) dithiocarbamate with different N-donor ligands
Damian C. Onwudiwe, Yvonne B. Nthwane, Anthony C. Ekennia, Eric Hosten
PII:
S0020-1693(16)30136-0
http://dx.doi.org/10.1016/j.ica.2016.03.033
ICA 16968
DOI:
Reference:
To appear in:
Inorganica Chimica Acta
Received Date:
Revised Date:
Accepted Date:
18 February 2016
23 March 2016
24 March 2016
Please cite this article as: D.C. Onwudiwe, Y.B. Nthwane, A.C. Ekennia, E. Hosten, Synthesis, characterization and
antimicrobial properties of some mixed ligand complexes of Zn(II) dithiocarbamate with different N-donor ligands,
Inorganica Chimica Acta (2016), doi: http://dx.doi.org/10.1016/j.ica.2016.03.033
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Synthesis, characterization and antimicrobial properties of some mixed
ligand complexes of Zn(II) dithiocarbamate with different N-donor ligands
1
Damian C. Onwudiwe , Yvonne B. Nthwane , Anthony C. Ekennia , Eric Hosten
,2
1,2
3
4
∗
1
Material Science Innovation and Modelling (MaSIM) Research Focus Area, Faculty of
Agriculture, Science and Technology, North-West University (Mafikeng Campus), Private Bag
X2046, Mmabatho, South-Africa.
2
Department of Chemistry, School of Mathematical and Physical Sciences Faculty of
Agriculture, Science and Technology, North-West University (Mafikeng Campus), Private Bag
X2046, Mmabatho 2735, South Africa.
3
Department of Chemistry, Federal University Ndufu-Alike Ikwo (FUNAI), P.M.B 1010,
Abakaliki, Ebonyi State, Nigeria.
4
Department of Chemistry, Nelson Mandela Metropolitan University, P.O Box 77000, Port
Elizabeth 6031, South Africa
*
Corresponding author
Email: Damian.Onwudiwe@nwu.ac.za
Tel: +27 18 389 2545
Fax: +27 18 389-2420
1

Abstract
In this study, adducts of Zn(II) dithiocarbamates containing different N-donor ligands
(pyridine, 2,2’-bipyridine and 1,10-phenanthroline) have been synthesized. The parent
1
dithiocarbamate complex comprise N-methyl-N-phenyl dithiocarbamate (L ) and N-ethyl-N-
2
phenyl dithiocarbamate (L ), and the adducts are represented as [ZnL L py], [ZnL L bpy],
1 2
1 2
1
and [ZnL L phen] (where py = pyridine, bpy = 2, 2’-bipyridine, and phen = 1, 10-
2
phenanthroline). All the compounds have been characterized by elemental analysis and
1
2
spectroscopic techniques (IR and NMR). In addition, the crystal structure of [ZnL L bpy]
complex is also reported. The structure indicates that the two dithiocarbamate ligands are
disordered in 0.67:0.33 ratio and alternatively bond as monodentate and bidentate ligands.
The bipyridine acts as a bidentate ligand, and gives the structure around the Zn atom a
distorted square pyramidal geometry. In order to evaluate their antimicrobial properties,
the precursor complex and the adducts were screened against six pathogenic bacteria
strains and two fungi organisms. The antimicrobial activities of the complexes were in the
1
2
1 2
1 2
1 2
1 2
order [ZnL L ] ˃ [ZnL L py] ˃ [ZnL L bpy] ˃ [ZnL L phen]. The precursor complex, ZnL L ,
showed the lowest MIC and is considered as the complex with most antimicrobial activity
against the selected microorganisms.
Keywords: Zn(II); adducts; X-ray crystal structure; antimicrobial properties.
2

1
.
Introduction
The coordination chemistry of zinc is a subject of current interest due to the increasing
number of hydrolytic enzymes and DNA binding proteins with Zn(II) in their active sites [1-
3
]. The biologically active zinc sites are capable of forming adducts with N, O donor ligands,
executing efficient and kinetically rapid catalytic reactions due to their variability and
flexibility in coordination behaviour [4]. Various synthesized Zinc based compounds have
been reported and were used as potent antibacterial, antifungal, anticancer drugs and also
as imaging agents [5, 6]. One of such compounds is Zinc dithiocarbamate which shows
interesting variations in their reactions with Lewis bases such as phosphines and hard bases
like nitrogenous ligands. The possibility of this reaction is due to the unsaturated
coordination around the zinc atom in the dithiocarbamate complex, leading to the
formation of compounds of higher coordination number either by the addition of one or
two molecules of a Lewis base or by dimerization of the Zn dithiocarbamate [7]. The exact
nature and reaction mechanism of these adducts is still not fully understood despite several
spectroscopic and crystallographic investigations of these compounds. This has prompted
several recent studies aiming to understand the structural features of zinc adducts with
biologically relevant ligands as synthetic analogues [1, 3].
Dithiocarbamate (DTC) group has been found in a number of biologically active molecules as
a pharmacophore [8, 9]. Compounds of dithiocarbamates possess diverse chemical and
medicinal versatility. The first dithiocarbamate compound to attain prominence as an
antifungal drug was tetramethylthiuram disulfide, commonly known as thiram [10]. Another
analogue, Tetraethylthiuram disulfide better known as disulfiram, has been used in the
treatment of alcoholism for more than 50 years [11]. Dithiocarbamates have been used as
3

th
pesticide and fungicide since 20 century, but have also been of interest to medicinal
chemists due to the strongly nucleophilic character and the unique redox properties of the
sulfur atom which make it a key residue for enzyme catalysis, protein folding, and redox
signaling and regulation. Owing to their strong metal-binding capacity, they can also act as
enzyme inhibitors [12].
Adduct formation allow for the increase in coordination number of metal ions in a complex,
while maintaining the same oxidation state [13 – 15]. Often, the chemical and biological
properties of the resulting adducts are entirely different from their precursor metal
complexes [16 – 18]. In order to study the effect of various N-donor atoms (pyridine, 2,2’
bipyridine and 1,10-phenantroline) on mixed dithiocarbamate complexes of zinc (II), we
report herein, the synthesis, characterization and biological evaluation of 2, 2’-bipyridine, 1,
1
0-phenanthroline and pyridine adducts of Zinc (II) mixed ligand complex of N-methyl-N-
1
phenyl dithiocarbamate (L ) and N-ethyl-N-phenyl dithiocarbamate (L ).
2
2
. Experimental
2
.1. General
All reagents and solvents were commercially available high grade materials (Merck/Sigma
Aldrich) and were used as received. The solvents were purified by standard methods [19].
2
.2. Physical measurements
Elemental analysis was performed on an Elementar, Vario EL Cube, set up for CHNS analysis.
Infrared spectra were recorded on a Bruker alpha-P FT-IR spectrometer in the frequency
−1
range 4000 – 500 cm . The NMR spectra were recorded on a 600 MHz Bruker Avance III
4

3
NMR spectrometers at room temperature in CDCl . The electronic spectra of the metal
complexes were recorded on a Perkin-Elmer λ20 UV-VIS spectrophotometer in chloroform.
Room temperature magnetic moments and molar conductance measurements were
recorded on Sherwood susceptibility balance MSB Mark 1 and Hanna conductivity model
H19991300 meters respectively.
2
.3. Chemistry
1
.3.1. Synthesis of ligands and precursor complex [ZnL L ]
2
2
The ligands, ammonium N-methyl-N-phenyl dithiocarbamate and ammonium N-ethyl-N-
phenyl dithiocarbamate, were prepared according to a previously described method with
slight modification [20]. Briefly, the respective aniline (0.05 mol) was introduced into a
round bottom flask containing cold 15 mL ammonia solution (0.05 mol) placed inside an ice
bath. After stirring for 5 min, 3 mL carbon disulphide, CS2, (0.05 mol) was added to the
mixture. The mixture was stirred for 5 - 6 h and filtered by suction. The precipitate obtained
was rinsed with ice-cold ethanol and stored under a very low temperature. The precursor
complex was prepared as reported earlier [21]. In brief, a 20 mL aqueous solution of freshly
prepared ammonium N–methyl–N–phenyldithiocarbamate (1.00 g, 0.005 mol) was added to
a 20 mL aqueous solution of ammonium N–ethyl–N–phenyldithiocarbamate (1.07 g, 0.005
2
mol). The solution was stirred for approximately 2 min. Then, ZnCl (2.22 g, 0.005 mol)
dissolved in 20 mL water was added to the mixture and stirred for 1 h. The solid product
obtained was rinsed thrice with 30 mL distilled water.
5

2
.3.2. Synthesis of (2, 2’-bipyridyl)(N, N–methyl phenyl–N, N–ethyl phenyl
1
dithiocarbamato)zinc(II) [ZnL L bpy]
2
1
2
A 15 mL hot chloroform solution of [ZnL L ] (0.44 g, 0.001 mol) was added into a round-
bottom flask containing 20 mL hot ethanol solution of 2,2’-bipyridine (0.156 g, 0.001 mol).
The resulting yellow solution was refluxed for 1 h, then concentrated to about 15 mL and
filtered. The pale yellow solids which separated out from the solution were filtered after 24
h and dried in the desiccator. Single crystals suitable for X-ray analysis were obtained from
slow evaporation of dichloromethane-methanol solvent mixture. (Yield: 0.52 g, 87%; Anal.
Calc. for C27
26 4 4
H N S Zn (600.16): C, 54.03; H, 4.37; N, 9.34; S, 21.37. Found: C, 54.12; H, 4.32;
N, 9.51; S, 21.35%
2
.3.3. Synthesis of (1, 10-phenanthroline)(N, N–methyl phenyl–N, N–ethyl phenyl
1
dithiocarbamato)zinc(II) [ZnL L phen]
2
1
2
1 2
The procedure for the synthesis of [ZnL L phen] is the same as [ZnL L bpy] except that
chloroform was used in place of ethanol. A 15 mL hot chloroform solution of 1,10
phenanthroline (0.2 g, 0.001 mol) was added into a hot 35 mL chloroform solution of
1
2
[
ZnL L ] (0.44 g, 0.001 g). The mixture was refluxed for 1 h, then concentrated to about 20
mL. The pale yellow solids which separated out from the solution were filtered after 24 h
and dried in a desiccator. (Yield: 0.45 g, 72%; Anal. Calc. for C29 Zn (624.18): C, 55.80;
H, 4.19; N, 8.98; S, 20.55. Found: C, 55.75; H, 4.22; N, 8.98; S, 20.54%
26 4 4
H N S
6

2
.3.4. Synthesis of (pyridyl)(N, N–methyl phenyl–N, N–ethyl phenyl dithiocarbamato)zinc(II)
1
2
[
2
ZnL L py].
1
The adduct [ZnL L py] was prepared following an earlier reported method [22]. About 0.4 g
2
1
ZnL L ] was dissolved in 20 mL pyridine solution, and the solution was refluxed for 3 h at a
2
[
temperature between 80 and 85 °C. The reaction gave a clear solution, and shortly
afterwards some white precipitate began to form. After the reaction, the pyridine solution
was filtered off and the precipitates obtained were rinsed with water followed by ethanol
and recrystallized from hot chloroform. (Yield: 0.174 g, 75%; Anal. Calc. for C22
23 3 4
H N S Zn
(523.08): C, 50.52; H, 4.43; N, 8.03; S, 24.52. Found: C, 51.01; H, 4.42; N, 8.10; S, 22.42%.
2
.4. X-ray crystallography
1
2
Diffraction data for [ZnL L bpy] was recorded at 200 K using a Bruker Kappa Apex II
diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 Å). APEXII was
used for data collection and SAINT for cell refinement and data reduction [23]. The
structures were solved by direct methods using SHELXS-2014 [24], and refined by least-
squares procedures using SHELXL-2014 [25] with SHELXLE [26] as a graphical interface. All
non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were calculated
in idealized geometrical positions. The H atoms of the alkyl groups were allowed to rotate
with a fixed angle around the C–C bond to best fit the experimental electron density (HFIX
1
37 in the SHELX program suite [25], with Uiso(H) set to 1.5Ueq(C). Data were corrected for
absorption effects by the numerical methods using SADABS [23]. Reflections obscured by
the beam stop were omitted from the refinement.
7

2
.5. Antimicrobial studies
Antibacterial and antifungal activities were carried out using disc diffusion method [26].
Petri plates were prepared with 20 mL of sterile Mueller–Hinton agar (MHA). The test
cultures were swabbed on the top of the solidified media and allowed to dry for 15 min.
Specific amount (25 μL from the 500 μg/mL) of the compound was introduced into each
disc. The loaded discs were placed on the surface of the medium and left for 30 min at room
temperature for compound diffusion. Negative control was DMSO. The plates were
o
o
incubated for 24 h at 37 C for bacteria and for 48 h at 30 C for fungi. Zones of inhibition
were recorded in millimetres and the experiment was repeated twice. The bacteria strains
were Escherichia coli, Klebsilla oxytoca, Bacillus cereus, Psuedomonas aureginosa, salmonila
typhi and Staphylococcus aureus. While the fungi organisms were Aspergillus flavus and
Fasiparium oxysporium.
2
.5.1. Minimum inhibitory concentration (MIC)
Minimum inhibitory concentration studies of the complexes were performed according to
the standard method for bacteria [26] and fungi [27]. Different concentrations (200, 100, 50
and 10 μg/mL) of the compounds were dissolved in DMSO (2 %) and used. They were added
to each medium in 96-well plates. An inoculum of 100 μL from each well was inoculated.
Fluconazole as an antifungal agent and Streptomycin as antibacterial agent were included in
o
the assays as positive controls. For fungi, the plates were incubated for 48 – 72 h at 30 C
o
and 24 h at 37 C for the bacteria. The MIC for fungi was defined as the lowest sample
concentration, showing no visible fungal growth after incubation time. 5 μL of tested broth
was placed on the sterile MHA plates for bacteria and incubated at respective temperature.
8

The MIC for bacteria was determined as the lowest concentration of the compound
inhibiting the visual growth of the test cultures on the agar plate.
3
. Results and Discussion
3
.1. Synthesis
The reactions of mixed ligand complex of Zn(II) containing different N-alkyl-N-phenyl
dithiocarbamate with 2,2’-bipyridine, 1,10-phenanthroline, and pyridine at elevated
temperature afforded four monomeric adducts. The reaction involving 2,2’-bipyridine and
1
,10-phenanthroline were conducted in chloroform/ethanol solvent media, but in the
reaction involving the pyridine, the pyridine acted both as the Lewis base and also the
solvent medium. During the reaction, the precursor complex first dissolved in the solvent
and the central metal utilises its outer d-orbital to form an adduct with the N-donor ligands
1
22]. While [ZnL L bpy] and [ZnL L phen] appeared as bright yellow solution, the [ZnL L py]
2
1 2
1 2
[
precipitated out from the pyridine as a white product upon the adduct formation. All the
compounds are soluble in dichloromethane, tetrahydrofuran, and DMSO. The schematic
representation of the reaction routes are presented in scheme 1.
3
.2. FTIR studies
In general, the IR spectra of dithiocarbamate compounds show three main regions of
interest: the region primarily associated with ʋ(C―N) of NCS which appears in the range of
580 - 1450 cm , the 1060 - 940 cm region which is attributed to the asymmetric ʋ(C―S)
2
-1
-1
1
-1
of CSS, and the 420 - 250 cm region which is assigned to ʋ(M―S) bond [28-30]. The
9

-
1
thioureide peaks were observed in the region of 1454 – 1490 cm . The position of the bands
indicates a partial double bond character in the CN bond of S C–NR . The stretching
frequencies of single (C―N) bond appears in the range 1250 – 1360 cm , while doubly
2
2
−1
−1
bonded carbon and nitrogen (C=N) is expected around 1640 –1690 cm [31]. The single and
-1
strong peaks at 969 – 984 cm are attributed to C=S stretch of a symmetrically bound
1
dithiocarbamate [32]. The spectra of [ZnL L bpy] showed two other peaks at 1025 and 1007
2
-
1
-1
cm in addition to the observed peak at 969 cm . This indicates the presence of two
different binding fashion. The occurrence of a single peak is indicative of bidentate
coordination of the dithio ligand, while for a monodentate unsymmetrically coordination of
the ligand to the central metal, a doublet is observed [32].
3
3
.3. NMR studies
1
.3.1. H-NMR
1
The H-NMR chemical shifts (ppm) of the complexes are presented in Table 1. All the
complexes displayed peaks in the range 7.49 – 7.34 ppm and 7.33 – 7.14 ppm, which are
ascribed to the aromatic rings from the N-ethyl-N-phenyl dithiocarbamate and N-methyl-N-
phenyl dithiocarbamate groups respectively. The methyl group and the methylene group of
the ethyl substituents resonated between 1.18 – 1.27 ppm as triplet, and between 4.18 –
4
–
.24 ppm as quartet respectively in all the complexes. A sharp singlet observed around 3.67
3.75 ppm is ascribed to the methyl group linked directly to the N atoms contained in the
dithiocarbamate moiety, while the peaks due to the protons of the pyridine molecule in
1
2
[
ZnL L py] appeared between 9.00 – 7.48 ppm. The downfield shift of the peaks associated
with the protons of the ethyl and methyl groups in these compounds relative to position of
1
0

the protons of allylic methyl and ethyl (1.7 ppm) could be due to the effect of the
electronegativity of the aromatic groups, and also the relative proximity of the alkyl
substituents to the thioureide bond and metal center [22]. The signals due to the 2, 2’-
bipyridine and 1,10-phenanthroline appeared at 9.09, 8.07, 7.95, 7.83 ppm and at 9.62,
9
.52, 8.47, 8.33, 7.82 ppm respectively.
1
.3.2. C-NMR
3
3
1
3
Table 2 contains the C-NMR chemical shifts (ppm) of the complexes. The complexes
exhibit a low field resonance which is associated with the backbone carbon of the
dithiocarbamate [33]. Two distinct peaks were observed at approximately 207.0 and 209.0
ppm. The occurrence of two NCS
methyl/ethyl) on the magnetic equivalence of the two groups of dithiocarbamate. The
ligating group (dithiocarbamate) with higher electronic density would have a more shielded
2
peaks is the consequence of different alkyl substituents
(
–CS
2
carbon [34]. While the methylene carbon of the ethyl group resonated between 53.0 –
5
6.0 ppm and the methyl carbon of the pyridine appeared between 46.0 to 47.0 ppm, the
methyl group of the ethyl substituent was observed at the upfield region between 12.35 to
2.62 ppm. This relatively low resonant frequency is attributed to the distance of the methyl
groups from the deshielding influence of the electronegative nitrogen and the thioureide π-
1
1
2
system [35, 36]. In the aromatic region, signals due to the pyridine molecule of [ZnL L py]
occurred at 149.32, 138.83, and 124.83. The signals due to the carbon atoms of the phenyl
rings appeared between 147.0 to 125.0 ppm. In the Table, these signals have been grouped
into two: peaks due to the aromatic carbons of the N-ethyl unit and peaks due to the N-
1
1

methyl unit. The occurrence of these peaks in different environments is an indication of the
magnetic un-equivalence of the aromatic groups [37].
3
.4. Electronic spectra, magnetic susceptibility and conductance measurement
2
The electronic spectra showed bands at 225 nm, 275 nm, 355 nm, 430 nm (ε =10890 m mol
-
1
1 2
for [ZnL L bpy]; 210 nm, 270 nm, 300 nm, 410 nm (ε = 10243m mol ) for [ZnL L phen]
2
-1
1 2
)
2
and 205 nm, 255 nm, 290 nm, 325 nm, 520nm (ε = 12678 m mol ) for [ZnL L py]. The bands
-1
1 2
around 205 – 290 nm are intra-ligand bands due to n ─ π* transition and those bands
1
0
around 290 ─ 355 nm are also intra-ligand bands due to π ─ π* transitions. For d
complexes, no d-d transitions are expected, however, bands observed in the visible region
1
0
of the complexes are metal to ligand charge transfer (MLCT) bands consistent of a d
system that tailed into the visible region. These results are in agreement with reported
values [7, 38, 39].
Zinc complexes are diamagnetic, thus give a sub-zero magnetic moment [40]. The magnetic
1
2
1 2
1 2
1 2
susceptibility values for [ZnL L phen], [ZnL L bpy], [ZnL L py] and [ZnL L ] are 0.42 BM, 0.32
BM, 0.28 BM and 0.23 BM respectively, and are similar to reported data obtained from
similar complexes [38, 39]. The metal(II) complexes are non-electrolytes in nitromethane as
-1
2
-1
shown by their molar conductivities that are between 32 - 50 ohm cm mol , which are
-1
2
-1
lower than reported value of 60 - 118 ohm cm mol for a 1:1 electrolyte [41].
1
2

3
.5. Description of crystal structures
Details of crystal data and structure refinements are provided in Table 3. Selected bond
lengths and bond angles are shown in Tables 4. The molecular structure of the complex is
shown in Figure 1 while the packing diagram is shown in Figure 2. The structure consists of
mononuclear species in which the central zinc atom is surrounded by two dithiocarbamate
ligands and one bipyridine molecule. The two dithiocarbamate ligands are disordered in
0
.67:0.33 ratio and alternatively bond as monodentate (Figure 1a) and bidentate ligands
(Figure 1b). In the minor disorder state the ligand that was monodentate becomes
bidentate, while the bidentate ligand becomes monodentate. So in both cases only three
out of the four Sulphur atoms of the two dithiocarbamates are coordinated to the zinc
atom. Therefore, at one time in both disordered states there is one long Zn-S distance
showing that there is always one dithiocarbamate ligand that is bidentate, and one
monodentate. To further highlight this, major disorder component (0.666) and minor
disorder component (0.334) have been presented in Table 5. The bipyridine acts as a
bidentate ligand and gives the structure around the Zn atom a distorted square pyramidal
geometry. τ value, which can determine how closely a distorted compound approximates
either a trigonal bipyramidal (tbp) or square pyramidal (sqp) geometry, was calculated using
the formula τ = (β-α)/60, where α(c - e) and β(b - d) are the angles that are opposite each
other in the xy plane [42]. The τ value was obtained as 0.28 and corroborates a distorted
sqp geometry. In a similar reported Zn(II) [43] and Cd(II) [44] adducts involving
dithiocarbamate (homoleptic) and 2,2-bipyridine, monodentate fashion of bonding was
observed in the Zn complex while both dithiocarbamate exhibited a bidentate coordination
in the Cd complex. It is possible that, the Cd atom was able to accommodate all the ligating
atoms due to its larger size. However, while distorted trigonal pyramidal structure was
1
3

reported for the zinc complex, the cadmium atom existed in a highly distorted octahedral
environment. In both complexes [43, 44] no disorder was observed in the alkyl groups
apparently because both dithiocarbamate units contains similar alkyl groups. In the present
1
2
study, the distortion from the regular square pyramidal geometry of [ZnL L bpy] may be due
to the small bite angle of the chelating ligands- dithiocarbamate: S(21)–Zn(1)–S(22), S(33)–
Zn(1)–S(34) and bipyridine: N(11)–Zn(1)–N(12), whose chelate angles (70.99(5), 72.23(9) and
7
4.86(7)°), respectively deviate significantly from the expected 90°. The dithiocarbamate
ligands have a dihedral angle of 58.70 (0.10)˚ and 61.61 (0.06)˚ with the bipyridine ligand.
The methyl and ethyl groups are alternatively disordered on the two dithiocarbamate
ligands in a 0.51:0.49 ratio. There are a number of C—H…S interactions linking the
complexes in the unit cell.
3
.6. Antimicrobial studies
The complexes were assessed for their antimicrobial activity against six bacteria strains and
two fungi organisms at a concentration of 100 μg/mL (Table 6, Figure 3). The complexes
showed moderate to good antimicrobial activity against the Gram negative and Gram
1
2
positive bacteria strains and fungi organisms. On structure activity relationship, the [ZnL L ]
complexes had the best activity against both bacteria and fungi organisms. The
1
2
1 2
antimicrobial activities of the complexes were in the order of [ZnL L ] ˃ [ZnL L py] ˃
1
2
1 2
[
ZnL L bpy] ˃ [ZnL L phen].
In most cases, the mechanism of antimicrobial action of metal complexes has been
attributed to the degree of lipophility of the complexes through the microbial cell wall. The
1
4

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 [45]. The size of a complex could be considered a factor that affects its
Permeability through the microbial cell wall [46]. Arranging the complexes in order of
1
2
1 2
1 2
1 2
increasing molecular weight gives [ZnL L ] ˂ [ZnL L py] ˂ [ZnL L bpy] ˂ [ZnL L phen], which is
in agreement with the order of decreasing antimicrobial activity. Although, the exact
mechanism of antimicrobial activity of our complexes is not fully understood biochemically,
mode of action of antimicrobial agents may include any of the following mechanism: (i)
Interference with the cell wall synthesis, damage as a result of which cell permeability may
be altered (or) they may disorganize the lipoprotein leading to the cell death. (ii) Deactivate
various cellular enzymes, which play a vital role in different metabolic pathways of these
microorganisms. (iii) Denaturation of one or more proteins of the cell, as a result of which
the normal cellular processes are impaired. (iv) Formation of hydrogen bond between the
donor group and the active center of cell constituents, resulting in interference with the
normal cell process [47].
The minimum inhibitory concentration of the complexes is presented in Table 7, and it
shows the lowest concentration of the complexes at which antimicrobial activity were
visible. This was achieved through serial dilution of the stock solution of the complex to
1
2
various concentrations of 75 μg/mL, 50 μg/mL and 25μg/mL. [ZnL L ] showed the lowest
MIC of the test complexes at 25μg/mL and, as such, considered as the complex with most
antimicrobial activity against the selected microorganisms. Generally, the precursor
1
2
complex, [ZnL L ], showed greater antibacterial activity compared to streptomycin against S.
1
5

1
2
aureus, B. cerus, K. oxytoca and E. coli. Similarly [ZnL L py] exhibited greater antibacterial
activity against S. aureus and K. oxytoca. The compounds showed higher antibacterial
activity compared to the positive control against some of the microbes.
Conclusion
We synthesized new heteroleptic complexes by the reaction of mixed ligands
dithiocarbamates complex of zinc with different Lewis bases (pyridine, 2, 2 bipyridine, and 1,
1
0-phenanthroline), with a view of evaluating the antimicrobial properties of these
compounds and relating them to the change in the size of the compounds with respect to
the precursor complex. The synthesized compounds were characterized by elemental
analysis and spectroscopic techniques. The 2,2 bipyridine adducts which was further
characterized by single crystal X-ray diffraction indicated that the Zn atom is in a distorted
square pyramidal geometry, and the methyl and ethyl groups are alternatively disordered
on the two dithiocarbamate ligands. The antimicrobial activities of the complexes were in
1
2
1 2
1 2
1 2
the order [ZnL L ] ˃ [ZnL L py] ˃ [ZnL L bpy] ˃ [ZnL L phen]. The lowest MIC was exhibited
1
2
by [ZnL L ] which is considered as the complex with most antimicrobial activity against the
selected microorganisms.
Supplementary material
CCDC 1452156 contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data Centre via
1
6

www.ccdc.cam.ac.uk/data_request/cif or from the Cambridge Crystallographic Data Centre,
2 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223 336 033; or e mail:
1
deposit@ccdc.cam. ac.uk.
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[
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1
9

(A)
(B)
1
2
Figure 1: Ortep diagram of [ZnL L bpy] showing (a) monodentate and (b) bidentate fashion of the
dithiocarbamate with only the major disordered components shown. Thermal ellipsoids are drawn
at 50% probability level.
2
0

1
2
Figure 2: Packing diagram of [ZnL L bpy] viewed normal to (010). Only the major disorder
components are shown. Thermal ellipsoids are drawn at 50% probability level.
2
1

[ZnL1L2]
[ZnL1L2bpy]
[ZnL1L2phen]
[ZnL1L2py]
Streptomycin
Ketoconazole
3
2
2
1
1
0
5
0
5
0
5
0
Test compounds
Figure 3: A histogram representation of the antimicrobial data of the complexes
2
2

1
Table 1: H-NMR chemical shifts (ppm) of the complexes
Compound
C
6
H
5
–
C
6
H
5
–
CH
3
CH
2
–
CH
3
CH
2
–
CH
3
–
py
bpy
-
phen
-
N(Et)
N(Me)
N(C
6
H
5
)
N(C
6
H
5
)
N(C
6 5
H )
9.00(d)
1
2
[
[
[
ZnL L py]
7.43 –
7.30-
4.18 (q)
4.19 (q)
1.26 (t)
1.18(t)
3.72 (s)
3.67(s)
7.87(t)
7.48(t)
7
.34(m) 7.16 (m)
9
.09(d)
7
.49 –
7.34 –
_
_
8.07(d)
7.95(q)
_
1
2
Zn L L bpy]
7.36(m) 7.14(m)
7
_
.83(q)
9
.62(s)
7
.41 –
7.30 –
4.24(q)
1.23
3.75(s)
9.52(s)
8.47(d)
1
2
Zn L L phen]
7.35(m) 7.15(m)
8
7
.33(d)
.82(d)
2
3

1
Table 2: C-NMR chemical shifts (ppm) of complexes
3
Compound
C
6
H
5
–
C
6
H
5
–
CH
3
CH
2
–
CH
3
–
Py
bpy
phen
N(Et)
46.73
144.58
N(Me)
129.89
128.27
127.42
N(C
6
H
5
)
N(C
6
H
5
)
CS
2
1
149.32
138.83
124.83
1
2
[
ZnL L py]
53.86(CH
12.38(CH
2
3
)
)
46.94
207.96
207.06
-
-
1
29.36
126.82
1
1
47.77
45.46
129.79
127.45
126.34
150.59
149.11
138.53
53.73(CH
12.51(CH
2
3
)
)
47.07
209.40
208.37
_
_
1
2
[
ZnL L bpy]
129.12
125.09
1
49.07
1
47.00
145.03
29.71
129.78
127.82
126.74
53.62(CH
12.62(CH
2
3
)
)
47.10
209.04
207.54
_
_
148.18
138.71
137.41
1
2
[
ZnL L phen]
1
125.13
2
4

Table 3: Summary of crystal data and structure refinement
1
2
Identification Code
Empirical Formula
Formula weight
Crystal System
Wavelength
Crystal system
Space group
Unit cell dimensions
a (Å)
[ZnL L bpy]
Zn
27 26 4 4
C H N S
600.15
Monoclinic
0.71073 Å
Monoclinic
P21/n
15.5021(9)
9.8197(6)
18.7538(11)
90
b (Å)
c (Å)
α (°)
β (°)
95.021(2)
90
γ (°)
3
V [Å** ]
2843.9(3)
4
Z
3
D(calc) (g/cm** )
1.402
µ(MoKa) (/mm)
F(000)
1.181
1240
Crystal size (mm)
Temperature (K)
Radiation (Å)
θ Min-Max (º)
Dataset
0.18 x 0.41 x 0.42
200
0.71073
1.8 - 28.3
-19:20 ; -13:12 ; -25:24
39253, 7068,
0.016
Tot., Uniq. Data
R(int)
[I > 2.0 sigma(I)]
5561
Nref, Npar
7068, 394
0.0356
R
wR2
0.1007
S
1.05
Max. and Av. Shift/Error
0.00, 0.00
-0.29
3
Min. residual density [e/Å ]
3
Max. residual density [e/Å ]
0.55
2
5

1
Table 4: Selected bond distances and angles for [ZnL L bpy]
2
Bond
distances (Å)
2.4573(17)
2.5753(13)
2.3166(16)
2.217(3)
Bond
angles (˚)
70.99(5)
Zn1– S21
Zn1– S22
Zn1– S31
Zn1– S23
Zn1– S33
Zn1– S34
Zn1– N11
Zn1– N12
S21– C21
S22– C21
S23– C22
S24– C22
S31– C31
S32– C31
S21 – Zn1 – S22
S21 – Zn1 – S31
S21 – Zn1 – N11
S21 – Zn1 – N12
S22 – Zn1 – S31
S22 – Zn1 – N11
S22 – Zn1 – N12
S31 – Zn1 – N11
S31 – Zn1 – N12
S23 – Zn1 – S33
S23 – Zn1 – S34
S23 – Zn1 – N11
S23 – Zn1 – N12
S33 – Zn1 – S34
S33 – Zn1 – N11
S33 – Zn1 – N12
S34 – Zn1 – N11
S34 – Zn1 – N12
N11 – Zn1 – N12
108.39(6)
118.03(7)
86.97(6)
2.543(3)
112.81(5)
95.81(6)
2.424(3)
2.1014(19)
2.2336(19)
1.694(5)
148.76(6)
131.38(6)
94.75(6)
1.702(5)
106.08(10)
135.33(11)
115.22(10)
98.45(10)
72.23(9)
1.719(12)
1.691(11)
1.732(4)
1.692(5)
135.78(9)
84.43(9)
88.30(7)
125.04(8)
74.86(7)
2
6

Table 5: Zn—S distances (Å) in the disordered components showing that in both cases only three
Zn—S bonds are coordinating at one time.
Major disorder component (0.666)
Minor disorder component (0.334)
Zn1—S21
Zn1—S22
Zn1—S31
Zn1—S32
2.4573(17)
2.5753(13)
2.3166(16)
3.2094(18)
Zn1—S23
Zn1—S24
Zn1—S33
Zn1—S34
2.217(3)
3.266(3)
2.543(3)
2.424(3)
2
7

Table 6: Antimicrobial results of the complexes
Complexes
S.aureus B.cerus
P.aureginosa K.oxytoca
E.coli
S.typhi
A.flavus
F.oxysporum
(
[
[
[
[
100 μg/mL)
1
ZnL L ]
2
24±0.7 27±0.0 18±0.7
19±0.0 14±2.1 15±2.1
22±0.0
14±2.1
10±2.1
21±0.7
20±0.7
NS
22±0.7 17±2.1 18±0.7 19±0.0
1
2
ZnL L bpy]
-
-
14±1.4 08±0.7 07±2.1
14±1.4
1
2
ZnL L phen] 13±0.7 12±0.7
-
-
-
-
1
2
ZnL L py]
22±1.4 17±0.7
14±2.1 12±0.7 10±0.7 12±1.4
21±0.7 18±0.0 NS NS
NS NS 21±0.7 23±0.0
Streptomycin 19±0.7 23±0.7 22±1.4
Ketoconazole NS NS NS
Values (in mm) represent the average of two replications and is standard deviation; Streptomycin
antibiotic) was used as positive control for antibacterial screening, Ketoconazole (antifungal) was
used as positive control for antifungal screening, ‘-‘ denotes resistant ‘NS’ denotes not screened.
(
2
8

Table 7: Minimum inhibitory concentration (MIC) of the complexes
Complexes
S.aureus B.cerus P.aureginosa K.oxytoca E.coli S.typhi A.flavus F.oxysporum
1
2
[
[
[
[
ZnL L ]
50
75
50
75
50
50
-
25
25
-
25
50
75
-
75
75
-
1
2
ZnL L bpy]
75
50
1
2
ZnL L phen] 75
75
100
100
25
-
100
50
1
2
ZnL L py]
50
75
-
75
25
NS
50
NS
˂25
75
NS
˂25
Streptomycin ˂25
Ketoconazole NS
Values (in μg/mL)
˂25
NS
˂25
NS
˂25
NS
NS
2
9