Synthesis, characterization, and antimicrobial activities of a dinuclear copper(II) complex with bis(2-[(2-hydroxy-ethylimino)-methyl]-4,6-diiodo-phenol)

Article abstract of DOI:10.1080/00958972.2011.552604

A dinuclear copper(II) complex with a newly synthesized tridentate Schiff-base ligand 2-[(2-hydroxy-ethylimino)-methyl]-4,6-diiodo-phenol (HL), of formula [Cu₂L₂Cl₂·C₄H ₈O] (1), was prepared. Both the ligand and the complex were characterized by X-ray crystallography, confirming that the Schiff base is tridentate and its dinuclear copper(II) complex is five-coordinate from one nitrogen and two oxygens from L and two chlorides. The complex was assayed for antibacterial (Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae) activities by the MTT method. Complex 1 exhibited better antimicrobial activity than the ligand.

Full text of DOI:10.1080/00958972.2011.552604

This article was downloaded by: [New York University]
On: 20 May 2015, At: 08:21
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Coordination Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gcoo20
Synthesis, characterization, and
antimicrobial activities of a dinuclear
copper(II) complex with bis(2-[(2-
hydroxy-ethylimino)-methyl]-4,6-
diiodo-phenol)
Xian-Feng Huang a , Yan-Bin Zhang b , Xiao-Liang Wang b , Jian-
Feng Tang b & Ban-Feng Ruan b
a School of Chemistry & Chemical Engineering , Changzhou
University , Changzhou 213164, P.R. China
b State Key Laboratory of Pharmaceutical Biotechnology , Nanjing
University , Nanjing 210093, P.R. China
Published online: 24 Jan 2011.
To cite this article: Xian-Feng Huang , Yan-Bin Zhang , Xiao-Liang Wang , Jian-Feng Tang & Ban-
Feng Ruan (2011) Synthesis, characterization, and antimicrobial activities of a dinuclear copper(II)
complex with bis(2-[(2-hydroxy-ethylimino)-methyl]-4,6-diiodo-phenol), Journal of Coordination
Chemistry, 64:4, 630-636, DOI: 10.1080/00958972.2011.552604
To link to this article: http://dx.doi.org/10.1080/00958972.2011.552604
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,

systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Coordination Chemistry
Vol. 64, No. 4, 20 February 2011, 630–636
Synthesis, characterization, and antimicrobial activities
of a dinuclear copper(II) complex with bis(2-[(2-hydroxy-
ethylimino)-methyl]-4,6-diiodo-phenol)
XIAN-FENG HUANGy, YAN-BIN ZHANGz, XIAO-LIANG WANGz,
JIAN-FENG TANGz and BAN-FENG RUAN*z
ySchool of Chemistry & Chemical Engineering, Changzhou University,
Changzhou 213164, P.R. China
zState Key Laboratory of Pharmaceutical Biotechnology, Nanjing University,
Nanjing 210093, P.R. China
(Received 12 October 2010; in final form 22 November 2010)
A dinuclear copper(II) complex with a newly synthesized tridentate Schiff-base ligand 2-[(2-
hydroxy-ethylimino)-methyl]-4,6-diiodo-phenol (HL), of formula [Cu2L2Cl2 ꢀ C4H8O] (1), was
prepared. Both the ligand and the complex were characterized by X-ray crystallography,
confirming that the Schiff base is tridentate and its dinuclear copper(II) complex is five-
coordinate from one nitrogen and two oxygens from L and two chlorides. The complex was
assayed for antibacterial (Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis,
Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae) activities by the MTT
method. Complex 1 exhibited better antimicrobial activity than the ligand.
Keywords: Schiff-base ligand; Dinuclear copper(II) complex; Antibacterial activity
1. Introduction
Salicylaldehyde Schiff bases and their metal complexes have a wide spectrum of
antimicrobial properties [1–5]. Many researchers have studied the synthesis, character-
ization, and structure–activity relationship (SAR) of Schiff bases [6–9]. Salicylaldehyde
derivatives, with one or more halogens in the aromatic ring, show antibacterial and
antifungal activities [10], suggesting that the complexes of such Schiff bases would
possess potential biological properties [11].
In this article, a new dinuclear copper complex, [Cu2L2Cl2 ꢀ C4H8O] (1), was prepared
from a newly synthesized tridentate Schiff-base ligand 2-[(2-hydroxy-ethylimino)-
methyl]-4,6-diiodo-phenol (HL). This complex was assayed for antibacterial activities
against three Gram-positive bacterial strains (Bacillus subtilis, Staphylococcus aureus,
and Streptococcus faecalis) and three Gram-negative bacterial strains (Escherichia coli,
Pseudomonas aeruginosa, and Enterobacter cloacae) by the MTT method.
*Corresponding author. Email: bf_ruan@163.com
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2011 Taylor & Francis
DOI: 10.1080/00958972.2011.552604

Dinuclear copper(II)
631
2. Experimental
2.1. Materials and instruments
All chemicals were reagent grade and used as received. The 3,5-diiodosalicylalidene was
synthesized with salicylaldehyde, KI, and KIO3 [12]. Carbon, hydrogen, and nitrogen
assays were carried out with a CHN–O-Rapid instrument and were within ꢁ0.4% of
the theoretical values. Infrared (IR) spectra were recorded on a Nicolet 470 FT-IR
spectrophotometer using KBr discs from 4000 to 400 cmꢂ1. UV spectra were recorded
1
on a U-3000 Spectrophotometer. H NMR spectra were recorded on a Bruker AV 400
spectrometer with TMS as internal standard. Solid-state fluorescence spectra were
obtained using an F-2500 fluorescence spectrophotometer.
2.2. Synthesis of HL
3,5-Diiodosalicylalidene (0.374 g, 1 mmol) and 2-aminoethanol (0.061 g, 1 mmol) were
dissolved in ethanol (15 mL) and refluxed for 1 h. Excess ethanol was removed under
reduced pressure to afford yellow solid. Single crystals of the title compound were
obtained by evaporating slowly in EtOAc/ethyl ether. Yield 86%, m.p.: 171–173ꢃC. UV
(ꢀ nm): 433.5; 257.0. IR data (cmꢂ1, KBr): 3264.7(m), 2877.1(m), 1645.4(s), 1481.9(s),
1424.7(m), 1232.4(m), 1199.9(s), 1133.4(s), 1076.3(s), 1027.5(m), þ1014.4(m), 918.0(m),
867.7(m), 697.1(m). MS (ESI): 418.98 (C9H10I2NOþ2 , [M þ H] ). Anal. Calcd for
C9H9I2NO2 (%): C, 25.92; H, 2.18; N, 3.36. Found (%): C, 25.95; H, 2.19; N, 3.34.
1H NMR (CDCl3) ꢁ (ppm): 14.706 (s, 1H), 8.178 (s, 1H), 8.054 (d, J ¼ 2.0 Hz, 1H),
7.523 (d, J ¼ 2.0 Hz, 1H), 3.929 (d, J ¼ 9.7 Hz, 2H), 3.780 (d, J ¼ 10.1 Hz, 2H).
.
2.3. Synthesis of [Cu2L2Cl2 C4H8O] (1)
HL (0.208 g, 0.5 mmol) with CuCl2 ꢀ 2H2O (0.085 g, 0.5 mmol) was dissolved in
tetrahydrofuran (THF) (6 mL) and stirred at room temperature for 10 min to give a
clear solution. After standing for 5–7 days, the precipitate was separated by filtration,
washed with methanol three times, and dried. Single crystals of the title complex were
obtained by evaporating slowly in methanol/ethyl ether. Yield 81%, m.p.: 228–229ꢃC.
UV (ꢀ nm): 386.5; 258.0. IR data (cmꢂ1, KBr): 3134.4(m), 2917.2(m), 1627.0(s),
1431.2(m), 1405.0(m), 1229.6(m), 1150.8(s), 1070.0(m), 1029.3(m), 879.0(m),þ752.1(m),
681.3(m). MS (MALDI-TOF): 1104.02 (C22H25I4N2O5Cl2Cuþ2 , [M þ H] ). Anal.
Calcd for C22H24I4N2O5Cl2Cu2 (%): C, 23.98; H, 2.20; N, 2.54. Found (%): C,
23.95; H, 2.19; N, 2.51.
2.4. Crystal structure determination and refinement
The crystallographic data for HL and 1 were collected on a Bruker Smart 1000 CCD
˚
area detector diffractometer equipped with Mo-Ka (ꢀ ¼ 0.71073 A) radiation using
!-scan mode. Empirical absorption correction was applied to the data. The structures
were solved by direct methods and refined by full-matrix least-squares on F2. All non-
hydrogen atoms were located from the trial structure and then refined anisotropically.
All hydrogens were generated in idealized positions. All calculations were performed

632
X.-F. Huang et al.
with SHELXL-97 programs. Other relevant parameters of the crystal structure are
listed in table 1.
2.5. Antimicrobial activity
The antibacterial activity of the synthesized complex was tested against B. subtilis,
S. aureus, S. faecalis, P. aeruginosa, E. coli, and E. cloacae using MTT medium. The
minimum inhibitory concentrations (MICs) of the test complexes were determined by a
colorimetric method using the dye MTT [13]. A stock solution of the synthesized
complex (50 mg mLꢂ1) in DMSO was prepared and quantities of the test complexes were
incorporated in a specified quantity of sterilized liquid medium. A specified quantity of
the medium containing the complex was poured into microtitration plates. Suspension
of the microorganism was prepared to contain 105 cfu mLꢂ1 and applied to
microtitration plates with serially diluted complexes in DMSO and incubated at 37ꢃC
for 24 h. After the MICs were visually determined on each of the microtitration plates,
50 mL of phosphate buffered saline (PBS 0.01 mol Lꢂ1, pH 7.4: Na2HPO4 ꢀ 12H2O 2.9 g,
KH2PO4 0.2 g, NaCl 8.0 g, KCl 0.2 g, distilled water 1000 mL) containing 2 mg mLꢂ1 of
MTT was added to each well. Incubation was continued at room temperature for 4–5 h.
The content of each well was removed and 100 mL of isopropanol containing 5%
1 mol Lꢂ1 HCl was added to extract the dye. After 12 h of incubation at room
Table 1. Crystallographic and experimental data for HL and 1.
HL
1
Empirical formula
Formula weight
Temperature (K)
Crystal system
Space group
C9H9I2NO2
416.97
298(2)
Monoclinic
P2(1)/c
C22H24Cl2Cu2I4N2O5
1102.01
298(2)
Monoclinic
C2/c
ꢃ
˚
Unit cell dimensions (A, )
a
b
c
ꢂ
ꢃ
ꢄ
16.0265(17)
8.6930(11)
8.4063(10)
90
102.0010(10)
90
1145.6(2), 4
2.418
5.466
27.886(3)
8.6890(12)
26.598(2)
90
105.521(2)
90
6233.1(12), 8
2.349
5.533
3
˚
Volume (A ), Z
Calculated density (g cmꢂ3
)
Absorption coefficient ꢅ (mmꢂ1
F(000)
)
768
4112
Max. and min. transmission
Data/restraints/parameters
ꢆ range for data collection (ꢃ)
Limiting indices
0.2369 and 0.1748
2017/0/128
2.60–25.02
ꢂ19 ꢄ h ꢄ 15;
ꢂ10 ꢄ k ꢄ 8;
ꢂ10 ꢄ l ꢄ 9
5542/2017
0.0314
0.0270
0.0580
0.854 and ꢂ0.646
0.3065 and 0.1765
5486/0/344
1.58–25.01
ꢂ33 ꢄ h ꢄ 18;
ꢂ10 ꢄ k ꢄ 9;
ꢂ30 ꢄ l ꢄ 31
15,157/5486
0.0487
0.0486
0.1175
1.542 and ꢂ1.277
Reflections collected/unique
Rint
Ra (I 4 2ꢇ(I ))
wRb (I 4 2ꢇ(I ))
(Dꢈ)max, (Dꢈ)min (e A
ꢂ3
˚
)
P
P
P
P
aR ¼ ||Fo| ꢂ |Fc|| |Fo||; bwR ¼ [ [wðFo2 ꢂ Fc2Þ ]/ [wðFo2Þ ]]1/2
.
2
2

Dinuclear copper(II)
633
temperature, the optical density (OD) was measured with a microplate reader at
570 nm. The observed MICs are presented in table 2.
3. Results and discussion
IR spectra of the complexes (KBr pellets) display an intense absorption at ca
1617–1629 cmꢂ1 attributable to the ꢉ(C¼N)imine stretching frequency. This band shifts ca
17–29 cmꢂ1 to lower wavenumbers compared to 1645 cmꢂ1, attributable to ꢉ(C¼O)imine
of C9H9I2NO2. UV spectra of the complexes display an intense absorption at
257–258 nm (ꢊ ! ꢊ*) and 380–406 nm (n ! ꢊ*).
HL crystallizes in monoclinic with space group P2(1)/c. As shown in figure 1, the
two iodines are on the benzene ring. The I(1)–C(4), I(2)–C(6), N(1)–C(1), N(1)–C(8),
O(1)–C(3), and O(2)–C(9) bonds are 2.093(4), 2.092(4), 1.302(5), 1.453(5), 1.281(5), and
˚
1.406(5) A, respectively. The bond angles of N(1)–C(1)–C(2), C(1)–N(1)–C(8), and
N(1)–C(8)–C(9) are 123.3(4)ꢃ, 122.9(4)ꢃ, 112.3(4)ꢃ, respectively.
Table 2. MICs of the synthetic complex.
MICs (mg mLꢂ1
)
Gram positive
Gram negative
Compounds
B. subtilis
S. aureus
S. faecalis
P. aeruginosa
E. coli
E. cloacae
1
HL
Penicillin
Kanamycin
3.125
6.25
1.562
0.39
6.25
12.5
1.562
1.562
6.25
25
1.562
3.125
12.5
12.5
6.25
3.125
3.125
6.25
6.25
6.25
12.5
3.125
1.562
3.125
Figure 1. Crystal structure of HL showing 30% probability displacement ellipsoids (all hydrogens have been
omitted for clarity).

634
X.-F. Huang et al.
The molecular structure of 1 is shown in figure 2 and the selected bond lengths and
angles are given in table 3. Compound 1 is dinuclear with two unique copper(II) ions in
the asymmetric unit. Both Cu(II)s adopt a distorted trigonal bipyramidal geometry
coordinated by one nitrogen and two oxygens from HL and two chlorides. The distance
Figure 2. Crystal structure of 1 showing 30% probability displacement ellipsoids (all hydrogens have been
omitted for clarity).
ꢃ
˚
Table 3. Selected bond lengths (A) and angles ( ) of HL and 1.
HL
C1–N1
C9–O2
C4–I1
1.301
1.406
2.093
C8–N1
C3–O1
C6–I2
1.454
1.282
2.091
O2–C9–C8
C2–C3–O1
C3–C4–I1
C5–C6–I2
113.3
C8–N1–C1
C4–C3–O1
C5–C4–I1
C7–C6–I2
122.9
122.0
117.9
119.3
122.3
119.3
121.2
1
Cu1–O1
Cu1–N1
Cu1–Cl2
Cu2–O4
Cu2–Cl1
1.921
Cu1–O2
Cu1–Cl1
Cu2–O3
Cu2–N2
Cu2–Cl2
1.985
1.944
2.732
2.031
2.799
2.271
1.892
1.935
2.256
O1–Cu1–N1
O1–Cu1–Cl2
O2–Cu1–N1
O2–Cu1–Cl2
O3–Cu2–N2
O3–Cu2–Cl2
O4–Cu2–N2
Cu1–Cl1–Cu2
93.8
O1–Cu1–Cl1
O1–Cu1–O2
O2–Cu1–Cl1
Cl1–Cu1–Cl2
O3–Cu2–Cl1
O3–Cu2–O4
Cl1–Cu2–Cl2
Cu1–Cl2–Cu2
92.6
94.7
81.1
94.0
92.6
92.4
81.9
85.8
170.0
91.9
92.4
103.7
172.4
90.9
87.7

Dinuclear copper(II)
635
Figure 3. (a) The packing structure of 1 along the a-axis, (b) the packing structure of 1 along the b-axis, and
(c) the packing structure of 1 along the c-axis. All hydrogens and THF have been omitted for clarity.

636
X.-F. Huang et al.
˚
between coppers (3.472 A) is much longer than that in complex [Cu2(dppm)2
L(NO3)(CH3OH)] (L ¼ 2-(9H-carbazol-9-yl)acetic acid), indicating that there is no
weak metal–metal interaction [14]. Furthermore, the complex also contains a THF.
As shown in figure 3, intermolecular H-bonds (O–H ꢀ ꢀ ꢀ O) and weak I ꢀ ꢀ ꢀ I interactions
formed between adjacent molecules generate a 3-D supramolecular network. The
ꢃ
˚
H ꢀ ꢀ ꢀ O distance is 2.686 A and the OH ꢀ ꢀ ꢀ O angle is 138.1 .
Complex 1 was screened for antibacterial activity against three Gram (þ) bacterial
strains (B. subtilis, S. aureus, and S. faecalis) and three Gram (ꢂ) bacterial strains
(E. coli, P. aeruginosa, and E. cloacae) by the MTT method. The MICs of the complex
against six bacterial strains are presented in table 3. Complex 1 exhibits better
antimicrobial activity than HL. The enhanced bactericidal activity on complexation
with copper(II) may be explained by chelation theory, according to which chelation
reduces the polarity of the central metal because of the partial sharing of its positive
charge with the donor groups and possible ꢊ-electron delocalization within the whole
chelate ring [15, 16]. This chelation increases the lipophilic nature of the central atom,
which favors the permeation of the complexes through the lipid layer of the cell
membrane.
Acknowledgments
The work was co-financed by grants from National Natural Science Foundation of
China (Projects 30772627) and from Province Natural Science Foundation of Jiang Su
(Projects 09KJD150005).
References
[1] A. Roth, E.T. Spielberg, W. Plass. Inorg. Chem., 46, 4362 (2007).
[2] L. Shi, H.-M. Ge, S.-H. Tan, H.-Q. Li, Y.-C. Song, H.-L. Zhu, R.-X. Tan. Eur. J. Med. Chem., 42, 558
(2007).
[3] L.-M. Wu, H.-B. Teng, X.-C. Feng, X.-B. Ke, Q.-F. Zhu, J.-T. Su, W.-J. Xu, X.-M. Hu. Cryst. Growth
Des., 7, 1337 (2007).
[4] S.-P. Xu, L. Shi, P.-C. Lv, R.-Q. Fang, H.-L. Zhu. J. Coord. Chem., 62, 2048 (2009).
[5] J.D. Ranford, J.J. Vittal, Y.M. Wang. Inorg. Chem., 37, 1226 (1998).
[6] E.F. Elslager, J. Battaglia, A.A. Phillips, L.M. Werbel. J. Med. Chem., 13, 587 (1970).
[7] P. Prusis, M. Dambrova, V. Andrianov, E. Rozhkov, V. Semenikhina, I. Piskunova, E. Ongwae,
T. Lundstedt, I. Kalvinsh, J.E.S. Wikberg. J. Med. Chem., 47, 3105 (2004).
[8] S. Ren, R. Wang, K. Komatsu, P.B. Krause, Y. Zyrianov, C.E. McKenna, C. Csipke, Z.A. Tokes,
E.J. Lien. J. Med. Chem., 45, 410 (2002).
[9] P.H. Wang, J.G. Keck, E.J. Lien, M.M.C. Lai. J. Med. Chem., 33, 608 (1990).
[10] L.C. Felton, J.H. Brewer. Science, 105, 409 (1947).
[11] E.M. Kosower, T. Miyadera. J. Med. Chem., 15, 307 (1972).
[12] S.-P. Xu, G.-Z. Zhu, R.-Q. Fang, X.-L. Li, H.-L. Zhu. Chin. J. Struct. Chem., 28, 87 (2009).
[13] J. Meletiadis, J.F. Meis, J.W. Mouton, J.P. Donnelly, P.E. Verweij. J. Clin. Microbiol., 38, 2949 (2000).
[14] B.-F. Ruan, R.-T. Hu, Y.-P. Tian, J.-Y. Wu, H.-L. Zhu. J. Coord. Chem., 63, 2999 (2010).
[15] B.G. Tweedy. Phytopathology, 55, 910 (1964).
[16] R.S. Srivastava. Inorg. Chim. Acta, 56, L65 (1981).