Synthesis and Structures of Copper(II) and Nickel(II) Complexes Derived from 2-Methyl-6-[(2-Morpholin-4-ylethylimino)Methyl]Phenol with Antimicrobial Activity

Article abstract of DOI:10.1080/15533174.2013.802340

A new Schiff base compound, 2-methyl-6-[(2-morpholin-4-ylethylimino)methyl] phenol (HL), derived from 3-methylsalicylaldehyde and 2-morpholin-4- ylethylamine, and its copper(II) and nickel(II) complexes [CuL(N₃)] (1) and [NiL(NCS)] (2), have been prepared and characterized by elemental analyses, IR, and single crystal X-ray crystallographic determination. The crystal of (1) is triclinic: space group Pl, a = 8.9887(7), b = 9.4007(7), c = 10.2218(8) A, α = 79.9600(10), β = 64.1580(10), γ = 87.7490(10)^o, V = 764.81(10) A³, Z = 2. The crystal of (2) is monoclinic: space group P₂₁/n, a = 10.1249(5), b = 13.2789(7), c = 12.2445(7) A, β = 103.6490(10)°, V = 1602.60(15) A³, Z = 4. The Schiff base ligand coordinates to the metal atoms through phenolate O and imine N atoms. The effect of the complexes on the antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans was studied. Copyright

Full text of DOI:10.1080/15533174.2013.802340

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Synthesis and Structures of Copper(II) and Nickel(II)
Complexes Derived from 2-Methyl-6-[(2-Morpholin-4-
ylethylimino)Methyl]Phenol with Antimicrobial Activity
Ling-Wei Xuea, Yun-Xiao Fenga & Cai-Xia Zhangb
a College of Chemistry and Chemical Engineering, Pingdingshan University, Pingdingshan,
Henan, P. R. China
b Coal Chemical Industry Branch of Shenhua Ningxia Coal Group, Yinchuan Ningxia, P. R.
China
Accepted author version posted online: 20 Sep 2013.Published online: 02 Jun 2014.
To cite this article: Ling-Wei Xue, Yun-Xiao Feng & Cai-Xia Zhang (2014) Synthesis and Structures of Copper(II) and Nickel(II)
Complexes Derived from 2-Methyl-6-[(2-Morpholin-4-ylethylimino)Methyl]Phenol with Antimicrobial Activity, Synthesis and
Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 44:10, 1541-1544, DOI: 10.1080/15533174.2013.802340
To link to this article: http://dx.doi.org/10.1080/15533174.2013.802340
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 44:1541–1544, 2014
Copyright Ó Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2013.802340
Synthesis and Structures of Copper(II) and Nickel(II) Complexes Derived
from 2-Methyl-6-[(2-Morpholin-4-ylethylimino)Methyl]Phenol
with Antimicrobial Activity
Ling-Wei Xue,1 Yun-Xiao Feng,1 and Cai-Xia Zhang2
1 College of Chemistry and Chemical Engineering, Pingdingshan University, Pingdingshan Henan, P. R. China
2 Coal Chemical Industry Branch of Shenhua Ningxia Coal Group, Yinchuan Ningxia, P. R. China
EXPERIMENTAL
A new Schiff base compound, 2-methyl-6-[(2-morpholin-
4-ylethylimino)methyl]phenol
Materials and Methods
(HL),
derived
from
3-
methylsalicylaldehyde and 2-morpholin-4-ylethylamine, and its
copper(II) and nickel(II) complexes [CuL(N3)] (1) and [NiL
(NCS)] (2), have been prepared and characterized by elemental
analyses, IR, and single crystal X-ray crystallographic
3-Methylsalicylaldehyde and 2-morpholin-4-ylethylamine
were purchased from Fluka. Other reagents and solvents were
analytical grade and used without further purification. Elemen-
tal (C, H, and N) analyses were made on a Perkin-Elmer
Model 240B automatic analyzer. Copper and nickel analyses
were carried out by EDTA titration. IR spectra were recorded
on an IR-408 Shimadzu 568 spectrophotometer. X-ray diffrac-
tion was carried out on a Bruker SMART 1000 CCD area
diffractometer.
determination. The crystal of (1) is triclinic: space group P1, a D
ꢀ
8.9887(7), b D 9.4007(7), c D 10.2218(8) A, a D 79.9600(10), b D
ꢀ
64.1580(10), g D 87.7490(10)o, V D 764.81(10) A3, Z D 2. The crys-
tal of (2) is monoclinic: space group P21/n, a D 10.1249(5), b D
ꢀ
13.2789(7), c D 12.2445(7) A, b D 103.6490(10)o, V D 1602.60(15)
ꢀ
A3, Z D 4. The Schiff base ligand coordinates to the metal atoms
through phenolate O and imine N atoms. The effect of the com-
plexes on the antimicrobial activity against Staphylococcus
aureus, Escherichia coli, and Candida albicans was studied.
Caution! Although the samples we prepared never exploded
during handling, azide metal complexes are potentially explo-
sive: only a small amount of material should be prepared and
it should be handled with care.
Keywords Antimicrobial activity, copper complex, crystal struc-
ture, nickel complex, Schiff base
Synthesis of HL
The Schiff base ligand HL was prepared by the condensa-
tion of equimolar quantities of 3-methylsalicylaldehyde
(0.136 g, 1 mmol) with 2-morpholin-4-ylethylamine (0.130 g,
1 mmol) in methanol (30 mL) at ambient temperature for 1 h.
Then the methanol was evaporated by distillation, yielding a
yellow gummy product of the Schiff base. Analysis: Calcd.
(%) for C14H20N2O2: C 66.72, H 8.12, N 11.28. Found (%):
C 67.53, H 8.22, N 11.41.
INTRODUCTION
Schiff bases are widely used as interesting ligands for
the preparation of versatile complexes with various metal
salts.[1–3] In recent years, transition metal complexes derived
from Schiff bases have attracted remarkable attention due to
their interesting biological activities, such as antifungal, anti-
bacterial, and antitumor.[4–6] It has been shown that Schiff
base complexes derived from salicylaldehyde and its deriva-
tives with primary amines, bearing the N2O, N2S, NO2, or
NSO donor sets, have potential biological activities.[6–8] In the
present work, the preparation, characterization, and antimicro-
bial activity of two new copper(II) and nickel(II) complexes
derived from the Schiff base ligand 2-methyl-6-[(2-morpholin-
4-ylethylimino)methyl]phenol (HL; Scheme 1) are reported.
Synthesis of Complex [CuL(N3)] (1)
The Schiff base HL (0.124 g, 0.5 mmol) was dissolved in
methanol (20 mL), to which was added with stirring a metha-
nol solution (10 mL) of Cu(NO3)2 Á 3H2O (0.121 g, 0.5 mmol)
and an aqueous solution (2 mL) of NaN3 (0.033 g, 0.5 mmol).
The mixture was stirred for 1 h at ambient temperature to give
a blue solution. Block-shaped single crystals suitable for
X-ray diffraction were formed by slow evaporation of the solu-
tion in air for about a week. The yield was 45% (based on HL).
Characteristic IR spectra (n, cm¡1): 2051 v.s (N3), 1632 s
Received 12 April 2013; accepted 29 April 2013.
Address correspondence to Ling-Wei Xue, College of Chemistry
and Chemical Engineering, Pingdingshan University, Pingdingshan
Henan 467000, P.R. China. E-mail: pdsuchemistry@163.com
1541

1542
L.-W. XUE ET AL.
(0.038 g, 0.5 mmol). The yield was 64%. Characteristic IR spec-
O
tra (n, cm¡1): 2107 v.s (NCS), 1632 s (CH D N). Analysis:
Calcd. (%) for C15H19N3NiO2S: C 49.48, H 5.26, N 11.54, Ni
16.12. Found (%): C 49.61, H 5.37, N 11.39, Ni 16.27.
N
N
X-Ray Diffraction
OH
Data were collected from selected crystals mounted on
glass fibers. The data for the two complexes were processed
with SAINT[9] and corrected for absorption using
SADABS.[10] Semiempirical absorption corrections were
applied with c scans.[11] The structures were solved by direct
methods using the SHELXS-97 program and refined by full-
matrix least-squares techniques on F2 using anisotropic dis-
placement parameters.[12] Hydrogen atoms were placed at the
calculated positions. Idealized H atoms were refined with iso-
tropic displacement parameters set to 1.2 (1.5 for methyl
SCH. 1. HL.
(CH D N). Analysis: Calcd. (%) for C14H19CuN5O2: C 47.65,
H 5.43, N 19.85, Cu 18.01. Found (%): C 47.51, H 5.54, N
19.77, Cu 18.20.
Synthesis of Complex [NiL(NCS)] (2)
Complex (2) was prepared by a similar method as that groups) times the equivalent isotropic U values of the parent
described for (1), with Cu(NO3)2 Á 3H2O replaced by Ni(NO3)2 Á carbon and nitrogen atoms. The crystallographic data for the
6H2O (0.145 g, 0.5 mmol), and NaN3 replaced by NH4NCS complexes are listed in Table 1.
TABLE 1
Crystal and structure refinement data for the complexes
(1)
(2)
Habit, color
Block, blue
352.9
298(2)
Block, red
364.1
298(2)
Formula weight
Temperature (K)
Crystal size (mm)
0.19 £ 0.18 £ 0.18
MoKa (0.71073)
Triclinic
0.23 £ 0.22 £ 0.17
MoKa (0.71073)
Monoclinic
P21/n
ꢀ
Radiation, λ (A)
Crystal system
Space group
P1
Unit cell dimensions:
a (A)
ꢀ
8.9887(7)
9.4007(7)
10.1429(5)
13.2789(7)
12.2445(7)
ꢀ
b (A)
ꢀ
c (A)
10.2218(8)
79.9600(10)
a (deg)
b (deg)
g (deg)
64.1580(10)
87.7490(10)
764.81(10)
103.6490(10)
ꢀ
V (A3)
1602.60(15)
4
1.509
Z
2
1.532
r
calcd (mg cm¡3
)
F(000)
Absorption coefficient (mm¡1
366
1.442
2.20–25.50
760
1.350
2.30–25.50
)
u range for data collection (deg)
Index ranges
Reflections collected
¡9 ꢀ h ꢀ 10, ¡9 ꢀ k ꢀ 11, ¡12 ꢀ l ꢀ 11
¡12 ꢀ h ꢀ 7, ¡16 ꢀ k ꢀ 15, ¡14 ꢀ l ꢀ 14
4063
2826
8193
2992
Independent reflections
Data (I > 2s(I))/parameters
Final R indices (I > 2s(I))
R indices (all data)
2513/200
0.0302
0.0738
2610/200
0.0261
0.0636
Goodness-of-fit
Drmax, Drmin (e A¡3
1.027
0.608, ¡0.225
1.044
0.489, ¡0.297
ꢀ
)

1543
SYNTHESIS AND STRUCTURES OF Cu(II) AND Ni(II) COMPLEXES
RESULTS AND DISCUSSION
The Schiff base ligand HL was prepared by the condensa-
tion of equimolar quantities of 3-methylsalicylaldehyde with
2-morpholin-4-ylethylamine in methanol at ambient tempera-
ture. The Schiff base prepared in this way is formed in a nearly
quantitative yield and is of high purity. The copper and nickel
complexes are stable at room temperature in the solid state
and soluble in common organic solvents, such as methanol,
ethanol, chloroform, and acetonitrile. The results of elemental
analyses are in accord with the composition suggested for the
ligand and complexes.
IR Spectra
In the IR spectra of both complexes, the strong bands
observed at 1632 cm¡1 are assigned to the azomethine group
vibration. The strong absorption band at 2051 cm¡1 for (1) is
assigned to the vibration of the terminal coordinated azide
ligand. The strong absorption band at 2107 cm¡1 for (2) is
assigned to the vibration of the terminal coordinated thiocya-
nate ligand.
FIG. 2. Perspective view of complex (2) with 30% probability thermal
ellipsoids.
(2)o]. The CuÀÀO and CuÀÀN bonds in (1) are longer than the
NiÀÀO and NiÀÀN bonds in (2). All the bond values are com-
parable with those observed in other similar copper(II)[13–15]
and nickel(II) complexes.[16–18]
Crystal Structure Description
The molecular structures of complexes (1) and (2) are
shown in Figures 1 and 2, respectively. Selected bond distan-
ces and angles are listed in Table 2.
Antimicrobial Activity
Qualitative determination of antimicrobial activity was
done using the disk diffusion method.[19,20] The results are
summarized in Table 3. A comparative study of minimum
inhibitory concentration (MIC) values of the Schiff base HL
and the two complexes indicate that the complexes have better
activity than the free Schiff base ligand. Generally, this is
caused by the greater lipophilic nature of the complexes than
the ligand. Such increased activity of the metal chelates can be
Complex (1) is an azide coordinated mononuclear copper
(II) compound, while complex (2) is a thiocyanate coordinated
mononuclear nickel(II) compound. In both complexes, the
metal atoms are four-coordinated in a square-planar geometry,
with one phenolic O, one imine N, one amine N atoms of the
Schiff base ligand, and one N atom of the azide or thiocyanate
ligand. As expected, the morpholin rings in the complexes are
in chair conformation. The azide and thiocyanate ligands are
approximately linear and show bent coordination mode with
the metal atoms [(1) N3-N4-N5/Cu1-N3-N4 D 177.0(3)o/
125.0(2)o; (2) N3-C15-S1/Ni1-N3-C15 D 178.2(2)o/167.9
ꢀTABLE 2
Selected bond lengths (A) and angles (ꢀ) for the complexes
(1)
Bond lengths
Cu(1)–O(1)
Cu(1)–N(2)
Bond angles
1.896(2)
2.090(2)
Cu(1)–N(1)
Cu(1)–N(3)
1.919(2)
1.931(2)
O(1)–Cu(1)–N(1) 93.67(8) O(1)–Cu(1)–N(3) 93.32(8)
N(1)–Cu(1)–N(3) 166.48(10) O(1)–Cu(1)–N(2) 164.84(8)
N(1)–Cu(1)–N(2) 84.74(8) N(3)–Cu(1)–N(2) 91.46(8)
(2)
Bondlengths
Ni(1)–O(1)
Ni(1)–N(2)
Bondangles
1.8284(14)
1.9754(16)
Ni(1)–N(1)
Ni(1)–N(3)
1.8415(16)
1.8740(18)
O(1)–Ni(1)–N(1) 94.22(7) O(1)–Ni(1)–N(3) 86.09(7)
N(1)–Ni(1)–N(3) 177.20(8) O(1)–Ni(1)–N(2) 177.81(6)
N(1)–Ni(1)–N(2) 86.75(7) N(3)–Ni(1)–N(2) 93.04(7)
FIG. 1. Perspective view of complex (1) with 30% probability thermal
ellipsoids.

1544
L.-W. XUE ET AL.
TABLE 3
MIC values (mg/mL) for antimicrobial activities of the tested
compounds
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derived from paeonol. Transition Met. Chem. 2009, 34, 499–505.
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methoxyphenol. Molecules 2009, 14, 1747–1754.
Staphylococcus
aureus
Escherichia
coli
Candida
albicans
Compound
HL
(1)
>512
8.0
64
256
2.0
>512
64
128
(2)
Tetracycline
64
2.27
0.35
>1024
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Q.; Zhu, M. L. Ternary oxovanadium(IV) complexes of ONO-donor
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polarity of the metal atoms will be reduced to a greater extent
due to the overlap of the ligand orbital and partial sharing of
positive charge of the metal atoms with donor atoms. Further,
it increases the delocalization of p electrons over the whole
chelate ring and enhances the lipophilicity of the complexes.
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complexes into the lipid membrane and blocks the metal bind-
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cal studies on the new symmetric Schiff base derived from 2,6-diformyl-
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€
of Area Detector Data; University of Gottingen: Gottingen, Germany,
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greater antibacterial and antifungi activities against Staphylo-
coccus aureus, Escherichia coli, and Candida albicans, when
compared to the free Schiff base HL and the nickel complex
(2). For Escherichia coli, complex (1) has stronger activity
than the control drug Tetracycline. But for Staphylococcus
aureus and Candida albicans, complex (1) shows weaker
activity than Tetracycline. Further work needs to be carried
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€
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characterization, X-ray structure and magnetic study of the azido adducts
of tridentate (NNO) Schiff base copper(II) complexes. Polyhedron 2011,
25, 2191–2197.
FUNDING
This research was supported by the National Sciences
Foundation of China (Nos. 20676057 and 20877036) and Top-
class foundation of Pingdingshan University (No. 2008010).
16. Mondal, N.; Mitra, S.; Gramilich, V.; Ghodsi, S.O.; Malik, K. M. A. Syn-
thesis, characterization and crystal structures of some four coordinated
nickel(II) complexes with tridentate Schiff base ligands. Polyhedron
2001, 20, 135–141.
SUPPLEMENTAL MATERIAL
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B.; Grech, E.; Wozniak, K. On the different coordination of NiII, ZnII and
CdII cations in their model Schiff base complexes—Single crystal X-ray
and solid state NMR studies. Polyhedron 2012, 31, 241–248.
18. Sun, Y.-X. Two different structures controlled by small secondary
ligands:{4-chloro-2-[2-(dimethylamino)ethyliminomethyl]phenolato}thi-
ocyanatonickel(II) and catena-poly[[{4-chloro-2-[2-(dimethylamino)eth-
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C62, m109–m110.
CCDC-926175 (1) and 926176 (2) contain the supplemen-
tary crystallographic data for this paper. The data can be
obtained free of charge at http://www.ccdc.cam.ac.uk/const/
retrieving.html or from the Cambridge Crystallographic Data
Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK;
fax: C44(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk.
19. Barry, A. In Antibiotics in Laboratory Medicine, Lorian Victor, Ed., Wil-
liams and Wilkins: Baltimore, MD, 1991, p. 1.
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