Synthesis, crystal structure, and biological property of a novel dinuclear copper(II) complex

Article abstract of DOI:10.1080/15533174.2014.963238

The reaction of 2-acetylpyridine, cyclohexylamine and copper(II) perchlorate in methanol resulted in the dinuclear copper(II) complex [Cu₂L₂]·2ClO₄, where L is the monoanionic form of 1-methoxy-1,3-dipyridin-2-ylbutane-1,3

Full text of DOI:10.1080/15533174.2014.963238

This article was downloaded by: [ECU Libraries]
On: 24 April 2015, At: 12:58
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
Synthesis and Reactivity in Inorganic, Metal-Organic,
and Nano-Metal Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsrt20
Synthesis, Crystal Structure and Biological Property of
a Novel Dinuclear Copper(II) Complex
Chao Lia, Xu-Feng Menga, Wei-Ning Lia, Xin Zhoua & Jing-Jun Maa
a College of Sciences, Agricultural University of Hebei, Baoding 071001, P. R. China
Accepted author version posted online: 18 Feb 2015.
Click for updates
To cite this article: Chao Li, Xu-Feng Meng, Wei-Ning Li, Xin Zhou & Jing-Jun Ma (2015): Synthesis, Crystal Structure and
Biological Property of a Novel Dinuclear Copper(II) Complex, Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-
Metal Chemistry, DOI: 10.1080/15533174.2014.963238
To link to this article: http://dx.doi.org/10.1080/15533174.2014.963238
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service
to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting,
typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of
the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the
content, and all legal disclaimers that apply to the journal relate to this version also.
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

ACCEPTED MANUSCRIPT
Synthesis, Crystal Structure and Biological Property of a Novel Dinuclear Copper(II)
Complex
Chao Li, Xu-Feng Meng, Wei-Ning Li, Xin Zhou, Jing-Jun Ma*
College of Sciences, Agricultural University of Hebei, Baoding 071001, P. R. China
* Corresponding author. Email address: majingjun71@126.com
Abstract
The reaction of 2-acetylpyridine, cyclohexylamine and copper(II) perchlorate in methanol
resulted in the dinuclear copper(II) complex [Cu2L2]·2ClO4, where L is the monoanionic form of
1-methoxy-1,3-dipyridin-2-ylbutane-1,3-diol. The complex was characterized by elemental
analysis and IR spectroscopic method in the solid state. Single crystal X-ray analysis was
performed, which indicated that the complex possesses a crystallographic inversion center
symmetry. The Cu atom in the complex is in a square pyramidal geometry. Thermal behavior
and biological property on the bacteria strains B. subtilis, E. coli, and S. aureus of the complex
were studied.
Keywords
Copper complex, dinuclear complex, crystal structure, thermal behavior,
antibacterial activity.
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
Transition metal complexes with various organic ligands have been reported to possess
interesting biological properties, such as bacterial, antifungal and antitumor activities.[1-4] In
general, the complexation of organic ligands with most transition metal atoms influences their
antibacterial activities.[5-7] In recent years, copper complexes have been extensively used in
antibacterial agents.[8-10] At this point of view and in continuation of work on the study of metal
complexes, herein we report a novel dinuclear copper complex, [Cu2L2]·2ClO4, where L is the
monoanionic form of 1-methoxy-1,3-dipyridin-2-ylbutane-1,3-diol.
EXPERIMENTAL
Materials and Methods
2-Acetylpyridine and cyclohexylamine were purchased from Merck and Fluka, and used as
received. Copper perchlorate was prepared by the reaction of basic cupric carbonate with
perchloric acid in aqueous solution. All other chemicals and solvents used in this work are of
analytical grade available commercially and used without further purification. Elemental
analyses (carbon, hydrogen and nitrogen) of the complex were obtained from a Carlo ERBA
Model EA 1108 analyzer. Infrared spectrum was performed by using a KBr pellet on a Jasco-
5300 FT-IR spectrophotometer. Solution electrical conductivity was measured with a DDS-11A
conductivity meter.
Synthesis of [Cu2L2]·2ClO4
2-Acetylpyridine (0.01 mol, 1.21 g) and cyclohexylamine (0.01 mol, 0.99 g) were reacted in
methanol (15 mL) at room temperature for 30 min. Then, copper perchlorate (0.01 mol, 3.88 g)
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
and NH4BF4 (0.01 mol, 1.05 g) in methanol (10 mL) were added slowly to the above stirred
solution. The final mixture was stirred at room temperature for another 30 min to give a blue
solution. The solution was filtered to remove some microdirty, and left to slow evaporate in air.
A few days later, small block-shaped single crystals were obtained. Yield: 2.75 g (63%). Anal.
Calcd. for C15H17ClCuN2O7 (%): C, 41.29; H, 3.93; N, 6.42. Found: C, 41.13; H, 4.02; N, 6.55.
IR data (cm-1, KBr): 3391, 1609, 1571, 1491, 1474, 1445, 1376, 1218, 1097, 863, 783, 757, 623,
553, 525, 479, 429, 345.
X-ray Crystallography
A well-shaped X-ray quality crystal of the complex was pick up under a microscope and
investigated in a diffraction experiment at 298(2) K on a Bruker Apex II diffractometer with
monochromated Mo Kα radiation (λ = 0.71073 Å) obtained from a graded multilayer X-ray
optics. The structure was solved by direct method with SHELXS-97,[11] and refined with full-
matrix least-squares techniques on F2 with SHELXL-97.[11] The C- and O-bonded hydrogen
atoms were calculated in an idealized geometry, riding on their parent atoms, with distances
restrained to 0.93–0.97 Å for C–H and 0.93 Å for O–H. The perchlorate anion is disordered over
two sites with occupancies of 0.64(2) and 0.36(2). The crystal data and refinement parameters
are listed in Table 1.
Antibacterial Assay
The antibacterial activities were tested against B. subtilis, E. coli, and S. aureus using Mueller-
Hinton medium. The MICs (minimum inhibitory concentrations) of the test compounds were
determined by a colorimetric method using the dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl tetrazolium bromide]. A stock solution of the synthesized compound (50 μg mL-1) in
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
DMSO was prepared and quantities of the test compounds were incorporated in specified
quantity of sterilized liquid Mueller-Hinton medium. A specified quantity of the medium
containing the compound was poured into microtitration plates. A suspension of the
microorganism was prepared to contain approximately 105 cfu mL-1 and applied to microtitration
plates with serially diluted compounds in DMSO to be tested and incubated at 37 °C for 24 h.
After the MICs were visually determined on each of the microtitration plates, 50 μL of PBS
(phosphate buffered saline 0.01 mol L-1, 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 of MTT/mL was added to each well.
Incubation was continued at room temperature for 4-5 h. The content of each well was removed
and 100 μL of isopropanol containing 5% 1 mol L-1 HCl was added to extract the dye. After 12 h
of incubation at room temperature, the optical density (OD) was measured with a microplate
reader at 550 nm. The antibiotics kanamycin and penicillin were used as standard drugs. The
observed MIC values are given in Table 3.
RESULTS AND DISCUSSION
Synthesis and Characterization
Massa and coworkers reported a mononuclear copper(II) complex with the Schiff base ligand
derived from pyridine-2-carbaldehyde with cyclohexylamine.[12] In the present work, we used 2-
acetylpyridine and cyclohexylamine as the starting material, to form a Schiff base ligand
cyclohexyl-(1-pyridin-2-ylethylidene)amine. The Schiff base ligand was further reacted with
copper perchlorate in the presence of NH4BF4. To our surprise, the ligand transferred to 1-
methoxy-1,3-dipyridin-2-ylbutane-1,3-diol during the reaction and crystallization. The complex
was obtained as single crystals, stable in air and soluble in polar organic solvents such as ethanol,
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
methanol, DMF, and DMSO. Elemental analyses of the complex are consistent with the general
molecular formula proposed by single crystal X-ray determination. The molar conductivity of the
complex in absolute methanolic solution confirms the 1:1 electrically nature.[13]
Description of the Crystal Structure of the Complex
Figure 1 gives the ORTEP diagram with atomic labeling scheme of the complex. Selected
bond lengths and angles are given in Table 2. The complex possesses a crystallographic
inversion center symmetry, and the asymmetric unit of the complex contains a dinuclear copper
complex cation and two disordered perchlorate anions. The Cu···Cu distance is 2.985(1) Å. In
the complex cation, two of the monoanionic four-dentate ligands wrap the Cu atoms with
coordination of two pyridine nitrogen atoms and two oxygen atoms in a distorted square
pyramidal coordination, which is proved by the τ reference (τ = 0.24).[14] One phenolic hydroxyl
is deprotonated on complexation, and acts as a bridging group, while the other one is kept in
neutral. The distortion of the square pyramidal coordination mainly comes from the tensile force
of the four-membered chelate ring Cu1-O6-Cu1A-O6A and five-membered chelate rings Cu1-
N2-C1-C6-O7 and Cu1-N3A-C10A-C9A-O6A. The apical O7 atom forms coordinate bond
angles in the range of 76.0(1)-108.5(2)° with the basal donor atoms N2, N3, O6 and O6A. The
two trans angles in the basal plane of the square pyramidal coordination differ by 8.0(2) and
22.5(2)° from the ideal values. The coordinate bond values are with normal ranges as compared
to other similar copper(II) complexes.[15-18]
The molecular packing structure of the complex is shown in Figure 2. The perchlorate anions
are linked to the complex cations through intermolecular O7–H7D···O1 hydrogen bonds [O7–
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
H7D = 0.93 Å, H7D···O1#1 = 2.28 Å, O7···O1#1 = 2.89(1) Å, O7–H7D···O1#1 = 123°; symmetry
code for #1: 1 – x, – y, 1 – z].
Thermal Behavior
Thermogravimetric analysis of the complex was carried out in the temperature range 50–800
°C at a heating rate of 10 °C min-1. The TG curve of the complex is given following degradation
scheme (Figure 3). The complex decomposes from 180 °C to 520 °C. The final residue is CuO.
The observed residue of 16.5% is close to the calculated value of 18.0%.
Antibacterial Activity
From Table 3, the copper complex has medium activity against E. coli, and strong activities
against B. subtilis and S. aureus. Especially for S. aureus, the complex has even stronger activity
than the reference drugs Penicillin and Kanamycin. The complex has stronger activity against E.
coli than Penicillin, but weaker than Kanamycin. As for B. subtilis, the activity of the complex is
slightly weaker than the two reference drugs.
CONCLUSIONS
A novel dinuclear copper(II) complex was synthesized by the reaction of 2-acetylpyridine,
cyclohexylamine, copper perchlorate and NH4BF4 in methanol at room temperature. The ligand
underwent an interesting transformation. The reaction mechanism may be further studied by
organic and catalytic researchers. The complex has effective antibacterial activities on the strains
B. subtilis, E. coli, and S. aureus.
ACKNOWLEDGMENTS
The authors are grateful to Hebei Key Laboratory of Bioinorganic Chemistry and College of
Sciences of Agricultural University of Hebei for financial support.
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
SUPPLEMENTARY MATERIAL
CCDC 980234 contains the supplementary crystallographic data for the complex. The data can
be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44)
1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
1. Siddiqi, Z.A.; Khalid, M.; Kumar, S.; Shahid, M.; Noor, S. Antimicrobial and SOD activities
of novel transition metal complexes of pyridine-2,6-dicarboxylic acid containing 4-picoline
as auxiliary ligand. Eur. J. Med. Chem. 2010, 45, 264-269.
2. Tumer, M.; Koksal, H.; Sener, M.K.; Serin, S. Antimicrobial activity studies of the binuclear
metal complexes derived from tridentate Schiff base ligands. Transition Met. Chem. 1999,
24, 414-420.
3. Singh, D.P.; Kumar, K.; Sharma, C. Antimicrobial active macrocyclic complexes of Cr(III),
Mn(III) and Fe(III) with their spectroscopic approach. Eur. J Med. Chem. 2009, 44, 3299-
3304.
4. Patil, S.; Claffey, J.; Deally, A.; Hogan, M.; Gleeson, B.; Mendez, L.M.M.; Muller-Bunz, H.;
Paradisi, F.; Tacke, M. Synthesis, cytotoxicity and antibacterial studies of p-methoxybenzyl-
substituted and benzyl-substituted N-heterocyclic carbene–silver complexes. Eur. J. Inorg.
Chem. 2010, 1020-1031.
5. Singh, N.P.; Srivastava, A.N. Synthesis, characterization and antimicrobial studies of novel
binuclear transition metal complexes of Schiff base derived from 1-amino-5-methyl-2,6-
pyrimidine-dione and 2,3-butanedione. Asian J. Chem. 2013, 25, 533-537.
6. Shaabani, B.; Khandar, A.A.; Dusek, M.; Pojarova, M.; Mahmoudi, F. Synthesis, crystal
structure, antimicrobial activity and electrochemistry study of chromium(III) and copper(II)
complexes based on semicarbazone Schiff base and azide ligands. Inorg. Chim. Acta 2013,
394, 563-568.
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
7. Singh, K.; Kumar, Y.; Puri, P.; Kumar, M.; Sharma, C. Cobalt, nickel, copper and zinc
complexes with 1,3-diphenyl-1H-pyrazole-4-carboxaldehyde Schiff bases: Antimicrobial,
spectroscopic, thermal and fluorescence studies. Eur. J. Med. Chem. 2012, 52, 313-321.
8. Liu, Z.-C.; Wang, B.-D.; Yang, Z.-Y.; Li, Y.; Qin, D.-D.; Li, T.-R. Synthesis, crystal
structure, DNA interaction and antioxidant activities of two novel water-soluble Cu(2þ)
complexes derivated from 2-oxo-quinoline-3-carbaldehyde Schiff-bases. Eur. J. Med. Chem.
2009, 44, 4477-4484.
9. Dhanaraj, C.J.; Nair, M.S. Synthesis, characterization, and antimicrobial studies of some
Schiff-base metal(II) complexes. J. Coord. Chem. 2009, 62, 4018-4028.
10. Valent, A.; Milnik, M.; Hudecova, D.; Dudova, B.; Kivekas, R.; Sundberg, M.R. Copper(II)
salicylideneglycinate complexes as potential antimicrobial agents. Inorg. Chim. Acta 2002,
340, 15-20.
11. Sheldrick, G.M. A short history of SHELX. Acta Crystallogr. 2008, A64, 112-122.
12. Massa, W.; Dehghanpour, S.; Jahani, K. Structure-dependent spectroscopic and redox
properties of copper(I) complexes with bidentate iminopyridine ligands. Inorg. Chim. Acta
2009, 362, 2872-2878.
13. Geary, W.J. Use of conductivity measurements in organic solvents for characterisation of
coordination compounds. Coord. Chem. Rev. 1971, 7, 81-122.
14. Addison, A.W.; Rao, T.N.; Reedijk, J.; van Rijn, J.; Verschoor, G.C. Synthesis, structure, and
spectroscopic properties of copper(II) compounds containing nitrogen–sulphur donor ligands;
the crystal and molecular structure of aqua[1,7-bis(N-methylbenzimidazol-2-yl)-2,6-
dithiaheptane]copper(II) perchlorate. J. Chem. Soc., Dalton Trans. 1984, 7, 1349-1356.
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
15. Li, Y.-M.; Zhang, J.-J.; Fu, R.-B.; Xiang, S.-C.; Sheng, T.-L.; Yuan, D.-Q.; Huang, X.-H.;
Wu, X.-T. Three new cubane-like transition metal complexes of di-2-pyridyl ketone in gem-
diol form: Syntheses, crystal structures and properties. Polyhedron 2006, 25, 1618-1624.
16. Telfer, S.G.; Parker, N.D.; Kuroda, R.; Harada, T.; Lefebvre, J.; Leznoff, D.B. Helicates,
boxes, and polymers from simple pyridine-alcohol ligands: the impact of the identity of the
transition metal ion. Inorg. Chem. 2008, 47, 209-218.
17. Boudalis, A.K.; Raptopoulou, C.P.; Psycharis, V.; Abarca, B.; Ballesteros, R.
Ferromagnetism in CuII and CoII complexes derived from metal-assisted solvolysis of di-
4
4
2,6-(2-pyridylcarbonyl)pyridine: Syntheses, structures, and magnetic properties. Eur. J. Inorg.
Chem. 2008, 3796-3781.
18. Georgopoulou, A.N.; Raptopoulou, C.P.; Psycharis, V.; Ballesteros, R.; Abarca, B.; Boudalis,
A.K. Ferromagnetic Cu(II)4, Co(II)4, and Ni(II)6 azido complexes derived from metal-
assisted methanolysis of di-2,6-(2-pyridylcarbonyl)pyridine. Inorg. Chem. 2009, 48, 3167-
3176.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 1. Crystallographic data for the complex
Chemical formula
Formula weight
Crystal system
Space group
Unit cell dimensions
a (Å)
C15H17ClCuN2O7
436.3
Monoclinic
P21/n
10.315(2)
12.416(2)
13.964(2)
97.494(2)
1773.2(6)
4
b (Å)
c (Å)
β (°)
V (Å3)
Z
ρ (g cm-3)
1.634
μ (mm-1)
1.423
Tmin, Tmax
0.7838, 0.7940
9371
Reflections collected
Reflections unique
Reflections observed [I > 2σ(I)]
Parameters
3466
2339
274
Restraints
101
R1, wR2 [I > 2σ(I)]
R1, wR2 (all data)
0.0518, 0.1383
0.0847, 0.1549
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Goodness-of-fit on F2
1.045
Highest peak and deepest hole (e Å-3)
0.667, –0.612
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 2. Selected bond lengths (Å) and angles (°) for the complex
Bond lengths (Å)
Cu1–O6A
1.904(3)
1.973(4)
2.238(3)
Cu1–O6
Cu1–N2
1.948(3)
1.978(4)
Cu1–N3A
Cu1–O7
Bond angles (°)
O6–Cu1–O6A
O6–Cu1–N3A
O6–Cu1–N2
O6–Cu1–O7A
N3–Cu1–O7A
78.43(14)
157.55(15)
93.85(15)
101.24(13)
108.48(15)
O6A–Cu1–N3A
O6–Cu1–N2A
N3–Cu1–N2A
O6–Cu1–O7
81.87(15)
172.04(16)
106.07(17)
85.99(13)
76.04(14)
N2–Cu1–O7
Symmetry code for A: 1 – x, – y, 1 – z.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 3. MIC values (μg mL-1) of the tested compounds
B. subtilis
1.56
E. coli
12.5
S. aureus
0.78
The complex
Penicillin
0.78
>100
6.25
3.13
Kanamycin
0.39
1.56
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 1. Molecular structure of the complex with the atom labeling scheme. All non-hydrogen
atoms are represented at 30% probability thermal ellipsoids. Only the major components of the
disordered perchlorate anions are shown.
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 2. Packing structure of the complex. Hydrogen bonds are shown as thin dashed lines.
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
100
80
60
40
20
0
200
400
600
Temperature (oC)
Figure 3. DT curve of the complex.
17
ACCEPTED MANUSCRIPT