Synthesis, characterization and antibacterial activity of the transition metal complexes of (1-formylferrocene)-3,5-dibenzyloxybenzoyl hydrazone

Article abstract of DOI:10.1080/15533170701316742

A new chelating ligand, (1-formylferrocene)-3,5-dibenzyloxybenzoyl hydrazone (HL) and three transition metal complexes, ML2 [M=Cu(II), Ni(II), Zn(II)], have been synthesized and characterized on the basis of elemental analyses, molar conductivity, IR and 1H NMR spectra. The structure of the prepared complexes is suggested. The antibacterial activities of the prepared compounds have been evaluated. The ligand (HL) and its complexes showed selective antibacterial acitivity against S. aureus.

Full text of DOI:10.1080/15533170701316742

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Synthesis, Characterization and Antibacterial
Activity of the Transition Metal Complexes of
(1‐formylferrocene)‐3,5‐dibenzyloxybenzoyl hydrazone
Ling Zhang a , Bao-Hua Zhang a & Ning Tang b
a College of Environmental and Chemical Engineering , Shanghai University , Shanghai, P. R.
China
b College of Chemistry and Chemical Engineering , Lanzhou University , Lanzhou, P. R. China
Published online: 09 May 2007.
To cite this article: Ling Zhang , Bao-Hua Zhang & Ning Tang (2007) Synthesis, Characterization and Antibacterial Activity
of the Transition Metal Complexes of (1‐formylferrocene)‐3,5‐dibenzyloxybenzoyl hydrazone, Synthesis and Reactivity in
Inorganic, Metal-Organic, and Nano-Metal Chemistry, 37:4, 263-266
To link to this article: http://dx.doi.org/10.1080/15533170701316742
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Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 37:263–266, 2007
Copyright # 2007 Taylor & Francis Group, LLC
ISSN: 1553-3174 print/1553-3182 online
DOI: 10.1080/15533170701316742
Synthesis, Characterization and Antibacterial Activity of the
Transition Metal Complexes of (1-formylferrocene)-3,5-
dibenzyloxybenzoyl hydrazone
Ling Zhang and Bao-Hua Zhang
College of Environmental and Chemical Engineering, Shanghai University, Shanghai, P. R. China
Ning Tang
College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China
the free chelator.[6] It is assumed that their mode of biological
A new chelating ligand, (1-formylferrocene)-3,5-dibenzyloxy- action is attributed to the formation of stable chelates with tran-
benzoyl hydrazone (HL) and three transition metal complexes,
ML2 [M 5 Cu(II), Ni(II), Zn(II)], have been synthesized and
sition metals present in the cell. Such a process inhibits many
vital enzymatic reactions catalyzed by these transition metal
characterized on the basis of elemental analyses, molar conduc-
tivity, IR and 1H NMR spectra. The structure of the prepared
complexes is suggested. The antibacterial activities of the
ions.[7] The results of our previous studies showed that 3,5-
dibenzyloxybenzoyl hydrazone and its complexes have anti-
prepared compounds have been evaluated. The ligand (HL) and bacterial activities.[8,9]
its complexes showed selective antibacterial acitivity against
S. aureus.
Due to the biological importance of ferrocene group and
acylhydrazones, we synthesized a new ligand, (1-formylferro-
cene) -3, 5-dibenzyloxybenzoyl hydrazone (HL), and prepared
its complexes with nickel(II), copper(II), zinc(II). All of the
compounds synthesized were tested for their antibacterial
activities against E. coli and S. aureus. The test results were
also evaluated. The structure of the ligand is shown as in
Figure 1.
Keywords ferrocene, hydrazone, complexes, synthesis, antibacterial
activity
INTRODUCTION
Ferrocene is either a stable inorganic compound or an
aromatic molecule, to which the encapsulated iron provides
EXPERIMENTAL
attractive optical, structural, and electrochemical properties.[1] Materials
The ferrocene group was introduced into penicillins and cepha-
losphorins as an important moiety changing their antibiotic
activities.[2]
All chemicals used in this work were of analytical
reagent grade. 1-formylferrocene was prepared by a literature
method.[10] 3,5-dibenzyloxybenzoichydrazide was also
prepared according to the literature procedure.[11]
The biological, chemical and industrial versatility of hydra-
zones and their complexes continues to attract considerable
attention.[3,4] Especially, isonicotinhydrazide and its N-isopro- Measurements
pyl acylhydrazone have been used as effective drugs in curing
human tuberculosis in the past few years.[5] The copper salicy-
laldehyde benzoylhydrazone complex is a potent inhibitor of
DNA synthesis and cell growth and is more effective than
The melting points of the compounds were determined on
an X-4 microscopic melting point apparatus (made in China)
and are uncorrected. Elemental analyses were carried out on
a Vario EL elemental analyzer. IR spectra were obtained in
KBr disc on a Nicolet FT-IR 5DX spectrometer in the 4000–
1
400 cm21 region. H NMR spectra (CHCl3-d) were recorded
Received 16 January 2007; accepted 12 February 2007.
Address correspondence to L. Zhang, Department of Chemical
Engineering and Technology, College of Environmental and
Chemical Engineering, Shanghai University, (Jiading Campus),
Shanghai 201800, People’s Republic of China. E-mail:
zhanglinglzu@163.com or jpzhanglzu@tom.com
on a Bruker AC-80A instrument with TMS as an internal
standard. Mass spectra were performed on a VG-7070E spec-
trometer (made in USA, EI at 70eV). All conductivity measure-
ments were performed in DMF with
a
DDS-11A
conductometer (made in Shanghai, China) at 258C.
263

264
L. ZHANG, B.-H. ZHANG, AND N. TANG
the cup-plate method.[12] The zone of the growth inhibition
of the bacteria, produced by the diffusion of the compounds
from the cup into the surrounding medium, was measured
after 24 hours. Chloromycetin (a trademark used for an
antibiotic preparation of chloramphenicol) was used as a
standard.
RESULTS AND DISCUSSION
FIG. 1. The structure of the ligand.
The elemental analyses and some physical properties of the
ligand and its complexes are given in Table 1. The analytical
results show that the composition of five complexes corre-
sponds to ML2 [M ¼ Ni(II), Cu(II), Zn(II)].
Preparation of the Ligand (HL)
To an ethanol solution (30 mL) of 3, 5-dibenzyloxybenzoi-
chydrazide (3.48 g, 10 mmol), an ethanol solution (15 mL) of
1-formylferrocene (1.23 g, 10 mmol) was added with stirring
at room temperature. Then the mixture was refluxed in an oil
bath for 4 hours. After cooling to room temperature, the
precipitated solid was filtered, washed with ethanol and
recrystallized from anhydrous ethanol to give the ligand (HL)
in a yield of 45% (2.36 g), m. p. 198–1998C. 1H NMR
(CHCl3-d, 80 MHz) d: 10.05 (1H, s, NH), 7.90 (1H, s, CH),
7.41ꢀ 6.90 (m, ArH), 5.09 (4H, s, -OCH2), 4.31 (5H, s,
C5H5), 4.83 ꢀ 4.64 (4H, m, C5H4). MS (FAB) m/z (%):
544.3 (Mþ).
The ligand is soluble in common organic solvents, such as
ethanol, methanol, acetone and chloroform. The complexes
are insoluble in water, partly soluble in chloroform, and are
easily soluble in DMF and DMSO. The low molar conductance
2
(5.71–11.35 S cm mol21) of the complexes suggests that
.
they are non-electrolytes in DMSO solution.[13]
IR Spectra
The IR spectral data of the compounds and their tentative
assignments are shown in Table 2. It can be seen that the
characteristic absorption peaks in the IR spectra of all of the
complexes are similar, which indicate that the complexes
have similar structures. The bonding of the ligand to the
metal ions was investigated by comparing the infrared
spectra of the free ligand with its metal complexes. The follow-
ing conclusions in this regard can be drawn: (i) The IR spectra
show that the n(C55O) band at 1642 cm21 and the n(NH) band
at 3193 cm21 in the spectra of the ligand were absent in the
complexes. These suggest the bonding of the ligand through
the enolate oxygen in the enol form of the hydrazone
group.[14] (ii) The IR spectra indicate that the n(C55N) bands
in the spectra of the ligand at 1588 cm21 due to the azomethine
linkage were shifted towards lower frequency by 41–58 cm21
in the complexes, indicating that the ligand coordinates to the
Preparation of the Complexes
.
A solution of M(OAc)2 4H2O (0.2 mmol) [M ¼ Ni(II),
Cu(II), Zn(II)] in methanol (10 mL) was added dropwise
with stirring to a solution of the ligand (0.0916 g, 0.2 mmol)
in ethanol. The reaction mixture was refluxed in an oil
bath for 4 hours, then cooled and filtered. The filter cake
was washed three times with water and anhydrous
ethanol, and finally dried in vacuo at room temperature over
three days.
Testing of the Antibacterial Activity
All of the compounds synthesized were tested for their anti- metal ions via the azomethine nitrogen.[15] (iii) Bonding
bacterial activities against E. coli and S. aureus at a concen- through the azomethine nitrogen[16] is also indicated from the
tration of 100 mg/mL in the nutrient agar media employing shift of n (N-N) to higher frequencies by 14–16 cm21
.
TABLE 1
Elemental analysis data and physical properties of the compounds
Found (Calcd.) (%)
Lm
2
(S cm mol
21 a
)
.
Compound (formula)
HL (C32Fe H28N2O3)2
Ni L2 (C64FeH56NiN4O6)2 Brown
Color
Yield (%)
C
H
N
Red brown
52
63
80
72
70.71(70.59)
67.40(67.13)
66.64(66.72)
66.78(66.81)
5.52(5.15)
4.95(4.72)
4.48(4.69)
4.82(4.70)
4.93(5.15)
5.04(4.90)
5.10(4.86)
4.58(4.87)
5.71
11.35
6.82
Zn L2 (C64FeH56N4O6Zn)
Cu L2 (C64CuFeH56N4O6)
Yellow brown
Brown
aFor the molar conductance, the concentration of the solution (in DMSO) was about 1023 mol/dm3.

SYNTHESIS OF NEW METAL COMPLEX VS. S. AUREUS
265
TABLE 2
IR spectra dataa of the ligand (HL) and its complexes (cm21
)
Compounds
Fc
nNH
nC55O
nC55N
nN-N
HL
3062m, 1454w, 814w
3060m, 1456w, 814w
3063m, 1455w, 814w
3063m, 1454w, 815w
3193m
1642s
1588s
1530s
1531s
1547s
840w
860w
869w
847w
NiL2
CuL2
ZnL2
aw ¼ weak, s ¼ strong, m ¼ medium.
1H NMR Spectra
Since the majority of the coordination compounds are para-
1
magnetic, only the H NMR spectra of the ligand (HL) and
ZnL2 were obtained. The ligand (HL) exhibits signals at d
(ppm) 10.05 (1H, s, NH), 7.90 (1H, s, CH), 7.41–6.90
(m, ArH), 5.09 (4H, s, 2OCH2), 4.83 ꢀ 4.64 (4H, m, C5H4),
4.31 (5H, s, C5H5), while in the ZnL2 complex signals are at
d (ppm) 7.56 (1H, s, CH), 7.44 ꢀ 6.99 (m, ArH), 5.14 (4H, s,
-OCH2), 4.57 (4H, m, C5H4), 4.29 (5H, s, C5H5). The disap-
pearance of the signal at 10.05 (s, NH) in the complex
proves that the hydrazone group coordinates to the metal
ions through enolate form. The downfield shift of the CH
signals suggests bonding of the ligand through the azomethine
1
nitrogen of the hydrazone group. Thus, the H NMR studies
reinforce the conclusions drawn from the IR spectra.
Antibacterial Activity
The antibacterial activity test results of the ligand and its
complexes are shown in Table 3. Preliminary bioassays
indicate that the ligand and its three complexes were active
against S. aureus, although they did not have the effectiveness
against E. coli. It is manifested that the Ni(II), Cu(II) and Zn(II)
complexes showed almost the same antibacterial activity
against S. aureus compared with the ligand, although they
did not reach the effectiveness of the bacteriostatic activity
of chloromycetin taken as standard drug at the concentration
of 100 mg/mL.
FIG. 2. The supposed structure of the complexes.
CONCLUSIONS
The following conclusion can be drawn:
(1) The metal ions are coordinated by the ligand with O
and N donors from the enol oxygen of the hydrazone group
(-N55C-O) and the azomethine (CH55N) group, respectively.
The suggested structure of the complexes is shown in Figure 2.
(2) The ligand and its three complexes showed selective
antibacterial acitivity against S. aureus. The formations of
the complexes have little effect in the antibacterial activity of
the ligand HL.
TABLE 3
Antibacterial activities of the ligand (HL) and its complexes
Compd.
S. aureus
E. coli
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—
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