Synthesis and antibacterial activity of copper(I) complexes with bisbenzoylthiourea

Article abstract of DOI:10.14233/ajchem.2014.15897

Two copper(I) complexes, [Cu(L)]ClO4 (1) and [Cu(L)Cl]?C2H5OH (2), have been synthesized by the reaction of copper(II) perchlorate hexahydrate and copper(II) chloride dihydrate with N,N'-(1,2-dimethylene)bisbenzoylthiourea (L), respectively and characteri

Full text of DOI:10.14233/ajchem.2014.15897

Asian Journal of Chemistry; Vol. 26, No. 1 (2014), 277-279
http://dx.doi.org/10.14233/ajchem.2014.15897
Synthesis and Antibacterial Activity of Copper(I) Complexes with Bisbenzoylthiourea
*
*
MENG-MENG ZHAO, XIU-YAN DONG , GANG LI and XIAO-QIN YANG
School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, P.R. China
*Corresponding authors: E-mail: dxy568@163.com
Received: 11 June 2013;
Accepted: 23 July 2013;
Published online: 26 December 2013;
AJC-14523
Two copper(I) complexes, [Cu(L)]ClO4 (1) and [Cu(L)Cl]·C2H5OH (2), have been synthesized by the reaction of copper(II) perchlorate
hexahydrate and copper(II) chloride dihydrate with N,N'-(1,2-dimethylene)bisbenzoylthiourea (L), respectively and characterized by
elemental analyses as well as IR spectra and TG-DTA analyses. Antibacterial activity assays exhibit MIC50 values of the two copper(I)
complexes comparable to standard drugs for both Gram-positive and Gram-negative bacteria, both of them show stronger antibacterial
activity.
Keywords: Bisbenzoylthiourea, Complex, Synthesis, Antibacterial activity.
FT-IR spectrophotometer using KBr pellets. TG-DTA analyses
were carried out at a heating rate of 5 °C/min on a ZRY-1P
INTRODUCTION
Benzoylthiourea and its derivatives are particular interest
because of their versatility towards different metal ions either
as a neutral ligand or as a deprotonated ligand through the
N,S atoms1-3. Furthermore, benzoylthioureas and their comp-
lexes have demonstrated significant biological activity and new
examples are being tested for their antitumor, antimicrobial
and antiviral activities of the metal complexes differ from those
of either the ligand or the metal ion itself and increased and/or
decreased biological activities are reported for several transition
metal complexes such as copper(II) and nickel(II)4-13. In many
cases concerning synthesis of copper(I) complexes, the irrever-
sible Cu(II)/Cu(I) redox system was observed14-16. In this paper,
two copper(I) complexes with N, N'-(1,2-dimethylene)-
bisbenzoylthiourea (L) have been synthesized and character-
ized by elemental analyses, IR spectra and TG-DTA analyses.
The interactions of the two copper(I) complexes and antimi-
crobial activities were studied.
1
thermoanalyzer. The H NMR spectra were recorded on a
Mercury-400BB spectrometer at room temperature using
DMSO-d6 as solvent. Melting points was measured by the use
of a microscopic melting point apparatus made in Beijing Taike
Instrument Limited Company and the thermometer was
uncorrected. The microbiology stains were obtained from
China Center of Industrial Culture Collection, including 4
species of Gram-nzegative bacteria (Salmonella typhimurium
CCTCCM91098, Escherichia coliACCC11864, Pseudomonas
aeruginosa NKCCMRNK10.PAO1∆rhlI and Shigella flexneri
CICC21534) and two Gram-positive bacteria (Staphylococcus
aureusACCC01331 and Mycobacterium tuberculosisCVCC343),
Streptomycin and Ampicillin were served as standard anti-
bacterial agents, respectively. The absorbance was measured
using Synergy HT BioTekR USA microplate reader.
General procedure: Benzoyl chloride was treated with
ammonium thiocyanate under the condition of solid-liquid
phase transfer catalysis using PEG-400 as the catalyst to give
the benzoyl isothiocyanate, without isolation, the obtained
benzoyl isothiocyanate was treated with ethanediamine to
afford the ligand (L) in good yield17,18. Synthetic route to N,
N'-(1,2-dimethylene)bisbenzoylthiourea is shown in Scheme-
I. Two synthesized copper(I) complexes have been charac-
terized by elemental analyses as well as IR spectroscopy and
EXPERIMENTAL
Benzoyl chloride, ethanediamine and polyethylene glycol-
400 were purchased and used without further purification. The
other reagents and solvents were analytical grade reagents from
Tianjin Chemical Reagent Factory. Elemental analyses for Cu
was detected by an IRIS ER/S·WP-1 ICP atomic emission
spectrometer. C, H and N analyses were carried out with a
GmbHVariuoELV3.00 automatic elemental analyzer. IR spec-
tra in the range 4000-400 cm-1 were recorded on aVERTEX70
TG-DTA analyses (Tables-1 and 2)19,20
.
Synthesis of N,N'-(1,2-dimethylene)bisbenzoylthiourea
(L): 1.41 g (0.01 mol) of benzoyl chloride was reacted with

278 Zhao et al.
Asian J. Chem.
S
HN CH2CH2 NH
S
O
O
O
NH4SCN
NH
NH2CH2CH2NH2/CH2Cl2
r.t.
PEG-400/CH2Cl2 , r.t.
N=C=S
Cl
HN
O
Scheme-I: Synthetic route to N,N'-(1, 2-dimethylene)bisbenzoylthiourea (L)
1.15 g (0.015 mol) of ammonium thiocyanate in 25 mL of
CH2Cl2 under solid-liquid phase transfer catalysis conditions,
using 0.18 g of 3 % polyethylene glycol-400 as the catalyst,
to give the benzoyl isothiocyanate after stirring for 1 h at the
room temperature, a white pricipatate was formed and the white
solution turned to yellow, filtered and washed with CH2Cl2,
which was reacted with a CH2Cl2 (15 mL) solution of 0.27 g
(0.0045 mol) of ethanediamine at the room temperature, after
stirring for 2.5 h. The solid isolated was separated from the
liquid phase by filtration, washed successively with CH2Cl2
and H2O, respectively, the product was dried under reduced
pressure and purified with recrystallization from DMF to obtain
the title compound. The product was dried under reduced
pressure and purified with recrystallization from DMF to yield
318.95 mg of colourless crystalline solid. Yield 82.3 %. m.p.
487-488 K. 1H NMR (400 MHz, DMSO-d6, ppm) 3.98 (t, 4H,
CH2); 7.36-7.98 (m, 10H, C6H5); 10.95 (s, 2H, NH); 11.31 (s,
2H, NH).
of the culture was strictly maintained between 0.12-0.19 at
540 nm. The total volume in each well was kept to 200 µL.
The incubation was done at 37 °C for 16-24 h with lid on the
microplate. The absorbance was measured at 540 nm, before
and after incubation and the difference was noted as an index
of bacterial growth. The percent inhibition was calculated using
the formula:
Inhibition (%) = 100 × (X-Y)/X
where X is absorbance in control with bacterial culture andY
is absorbance in test sample. Results are mean of triplicate (n
= 3, mean sem). Streptomycin and Ampicilin were taken as
standard drugs. Minimum inhibitory concentration (MIC) was
measured with suitable dilutions and results were calculated
using EZF it 5 Perrella Scientific Inc. Amherst USA software
and data expressed as MIC50.
RESULTS AND DISCUSSION
The colour, yields and elemental analytical results of the
synthesized bisbenzoyl-thiourea L and its copper(I) complexes
are presented in Table-1. The copper(I) complexes 1 and 2 are
yellow and green solid, respectively, stable in air and soluble
in chloroform, DMF and DMSO, insoluble in methanol, ethanol,
dichloromethane, ether, acetone, acetonitrile, benzene and n-
hexane. The analytical results of the copper(I) complexes 1
and 2 are given in Table-1. Their compositions agree with the
formula [Cu(L)](ClO4)2 for the complex 1 and [Cu(L)Cl]·C2H5OH
for the complex 2.
Synthesis of copper(I) complex (1): To an DMF solution
(5 mL) of the ligand (L) (193.2 mg, 0.50 mmol) was added an
DMF solution (5 mL) of Cu(ClO4)2·6H2O (203.8 mg, 0.55
mol). After the solution had been refluxed for 1 h, the mixture
was fltered, washed successively with DMF and diethyl ether
respectively, the product was dried under reduced pressure to
obtain 92.5 mg of grass green crystalline solid.Yield: 28.5 %.
Synthesis of copper(I) complex 2:A solution of CuCl2·2H2O
(22.2 mg, 0.13 mmol) in DMF/ethanol (1:1) (10 mL) was added
dropwise to a solution of the ligand (L) (96.8 mg, 0.25 mmol)
in DMF (3 mL) at room temperature. a yellow pricipatate was
formed immediately. After stirring for 1 h, the mixture was
fltered, washed with DMF and diethyl ether, respectively. The
product was dried in vacuo and obtained 23.7 mg of yellow
solid. Yield: 33.5 %.
The molar conductance of the complex 1 at 20 °C in 10-3
mol/L DMF solution is 80.4 S cm2 mol-1, indicating that the
complex 1 is 1:1 electrolyte and the molar conductance of the
complex 2 at 20 °C in 10-3 mol/L DMF solution is 13.7 S cm2
mol-1, indicating that the complex 2 is non-electrolyte22.
IR spectra: The important FT-IR spectra data for L and
its corresponding copper(I) complexes are given in Table-2.
The IR spectra of the copper(I) complexes show two bands at
3215 and 3431 cm-1, due to NH stretchings. Because C=O
groups are locked into the hydrogen bonds, the carbonyl
stretching bands appears at 1676 cm-1. A strong band at 1172
cm-1 is assigned as the thionyl group, which has a shift of 4 cm-1
to high wavenumber compared with 1168 cm-1 in free ligand L.
This indicates coordination of the thionyl group with Cu(I) ion.
In the range below 1000 cm-1, two bands at 590 and 406 cm-1
Antimicrobial activities: Antibacterial activities were
performed in sterile 96-wells microplates under aseptic envi-
ronments21. The method is based on the principle that micro-
bial cell number increases as the microbial growth proceeds
in the log phase of growth which results in increased absorbance
of broth medium. The organisms were maintained on stock
culture agar. The test samples with suitable solvent and dilution
were pipetted into wells (20 µg/well). Overnight maintained
fresh bacterial cultures after suitable dilution with fresh nutrient
broth were poured into wells (180 µL). The initial absorbance
are attributed to Cu-S and Cu-Cl vibrations, respectively16,23
.
TABLE-1
COLOUR, YIELDS AND ANALYTICALDATA OF LAND ITS COPPER(I) COMPLEXES
Elemental analysis (%): Found (calcd.)
Comp.
Colour
Yield (%)
m.f. (m.w.)
C
H
N
Cu
–
L
Colourless
Yellow
Green
82.3
28.5
33.5
C18H18N4O2S2 (386.5)
C18H18ClCuN4O6S2 (549.5)
C20H24ClCuN4O3S2 (531.6)
55.90 (55.94)
39.61 (39.34)
45.36 (45.19)
4.59 (4.69)
3.25 (3.30)
4.37 (4.55)
14.28 (14.50)
[Cu(L)]ClO4
10.13 (10.20) 11.79 (11.56)
10.28 (10.54) 12.21 (11.95)
[Cu(L)Cl]·C2H5OH

Vol. 26, No. 1 (2014)
Synthesis and Antibacterial Activity of Copper(I) Complexes with Bisbenzoylthiourea 279
TABLE-2
IR SPECTRAL DATA AND TG-DTA DATA OF LAND ITS COPPER(I) COMPLEXES
Endothermic
peak (°C)
Exothermic
peak (°C)
Final
product
IR (νmax, cm–1)
Comp.
L
3422, 3234 (NH); 1668 (C=O); 1158 (C=S)
3429, 3275 (NH); 1674 (C=O); 1170 (C=S); 591 (Cu–S)
3431, 3215 (NH); 1676 (C=O); 1172 (C=S); 590 (Cu–S);
406 (Cu–Cl)
215
158
75
289
[Cu(L)]ClO4
302, 346
262, 282
CuO, CuS
CuO, CuS
[Cu(L)Cl]·C2H5OH
TABLE-3
ANTIBACTERIAL ACTIVITIES OF THE COMPLEXS 1 AND 2 (MEAN SEM, n = 3)
Comp.
Antibacterial activity MIC50 (µg/mL)
S. typhi
E. coli
P. aeruginosa
10.61 0.17
11.45 0.15
10.17 0.2
10.26 0.4
S. flexneri
11.8 0.4
No activity
10.55 0.35
9.7 0.25
M. tuberculosis
9.95 0.23
12.8 0.26
11.12 0.33
7.93 0.24
S. aureus
10.55 0.21
11.95 0.31
11.41 0.42
9.79 0.31
[Cu(L)]ClO4
[Cu(L)Cl]·C2H5OH
Ampicillin
10.7 0.21
12.15 0.07
9.31 036
11.18 0.32
10.1 0.27
11.45 0.3
9.28 0.25
9.43 0.27
Streptomycin
8. A. Kumar, Usha and S. Chandra, Synth. React. Inorg. Met. Org. Chem.,
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Antimicrobial activities: In the antibacterial experiment,
the statistic indicated lowest the MIC50 value, highest is the
antibacterial activity. These compounds were active againest
both Gram-positive and Gram-negative bacterial because of
their strong oxidizing property. Compared the two compounds,
[Cu(L)]ClO4 possessed the lower MIC50 value, so it has the
higher antibacterial activity. Both two compounds possessed
MIC50 value close to the standard drugs streptomycin and
ampicillin (Table-3). The concern is compound [Cu(L)]ClO4
has the antitubercular activity close to streptomycin. The results
of this study indicated that these two compounds synthesized
above showed their biological importance and could be
applied in biological medicine industry, especially in the aspect
of antitubercular.
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