Synthesis and crystal structures of cobalt(III) and zinc(II) complexes derived from 4-chloro-2-[(2-morpholin-4-ylethylimino)methyl]phenol with urease inhibitory activity

Article abstract of DOI:10.1134/S1070328410030036

A new mononuclear cobalt(III) complex, [CoL₂(N ₃)]₂ · CH₃OH (I), and a new mononuclear zinc(II) complex, [ZnLCl(CH₃OH)] (II) (HL = 4-chloro-2-[(2-morpholin- 4-ylethylimino)methyl]phenol), were prepared and structurally characterized by elemental analyses, infrared spectroscopy, and singlecrystal X-ray diffraction. The crystal of I is monoclinic: space group P2₁/c, a = 18.742(2) A, b = 15.197(2) A, c = 25.646(2) A, β = 125.996(3)°, V = 5909.8(11) A³, Z = 4. The crystal of II is monoclinic: space group P2₁/c, a = 7.257(1) A, b = 24.707(2) A, c = 9.637(1) A, β = 101.557(2)°, V = 1692.9(3) A³, Z = 4. The Co atom in I is in an octahedral coordination, and the Zn atom in II is in a trigonal-bipyramidal coordination. The urease inhibitory test shows that complex I has strong urease inhibitory activity, while complex II has no activity.

Full text of DOI:10.1134/S1070328410030036

ISSN 1070ꢀ3284, Russian Journal of Coordination Chemistry, 2010, Vol. 36, No. 3, pp. 177–182. © Pleiades Publishing, Ltd., 2010.
Synthesis and Crystal Structures of Cobalt(III) and Zinc(II)
Complexes Derived from 4ꢀChloroꢀ2ꢀ[(2ꢀMorpholinꢀ4ꢀ
ylethylimino)methyl]phenol with Urease Inhibitory Activity1
C. Y. Wang
Department of Chemistry, Huzhou University, Huzhou 313000, P.R. China
Eꢀmail: chenyi _wang@163.com
Received August 6, 2009
Abstract
zinc(II) complex, [ZnLCl(CH3OH)] (II) (HL = 4ꢀchloroꢀ2ꢀ[(2ꢀmorpholinꢀ4ꢀylethylimino)methyl]pheꢀ
nol), were prepared and structurally characterized by elemental analyses, infrared spectroscopy, and singleꢀ
crystal Xꢀray diffraction. The crystal of is monoclinic: space group 21/ = 18.742(2) = 15.197(2)
= 25.646(2) = 125.996(3) = 4. The crystal of II is monoclinic: space group
= 5909.8(11) Å3
21/ = 7.257(1) = 24.707(2) = 9.637(1) = 101.557(2) = 4. The Co
= 1692.9(3) Å3
atom in is in an octahedral coordination, and the Zn atom in II is in a trigonalꢀbipyramidal coordination.
—A new mononuclear cobalt(III) complex, [CoL2(N3)]2
⋅
CH3OH (I), and a new mononuclear
I
P
c
,
a
Å,
b
Å,
c
P
Å,
β
°
,
V
, Z
c,
a
Å,
b
Å,
c
Å,
β
°
,
V
, Z
I
The urease inhibitory test shows that complex
activity.
I
has strong urease inhibitory activity, while complex II has no
DOI: 10.1134/S1070328410030036
1
INTRODUCTION
pared and structurally characterized. The urease
inhibitory activities of the complexes were deterꢀ
mined.
Cobalt and zinc complexes with Schiff bases have
been attracted much attention in coordination chemꢀ
istry and bioinorganic chemistry due to their versatile
structures and biological properties [1–6]. Ureases are
an important class of enzymes involved in the degradaꢀ
tive processing of urea [7–9]. They are ubiquitous in
nature and directly associated with the formation of
infection stones and contribute to the pathogenesis of
pyelonephritis, urolithiasis, ammonia encephalopaꢀ
thy, hepatic coma, and urinary catheter encrustation.
High concentration of ammonia arising from these
reactions, as well as accompanying pH elevation, has
important implications in medicine and agriculture
[10, 11]. Therefore, urease inhibitors have recently
been attracted much attention as potential new antiꢀ
ulcer drugs. A recent research indicated that the Schiff
base complexes had potent urease inhibitory activity
[12]. Schiff bases derived from the condensation of
salicylaldehyde and its derivatives with primary
amines represent an important class of chelating
ligands, the metal complexes of which have been
widely studied. However, no complexes with the
Schiff base 4ꢀchloroꢀ2ꢀ[(2ꢀmorpholinꢀ4ꢀylethꢀ
ylimino)methyl]phenol (HL) have been reported. In
this paper, a new mononuclear cobalt(III) complex,
O
Cl
N
N
OH
(HL)
EXPERIMENTAL
Materials and measurements. All chemicals and
reagents used for the preparation of the ligands and
complexes were commercial products (Lancaster) and
used without further purification. Jack bean urease
was obtained from SigmaꢀAldrich Co. (St. Louis, MO,
USA). C, H, and N analyses were performed with a
PerkinElmer 2400 series II analyzer. The infrared
spectra (KBr pellet) were recorded using a FTS165
BioꢀRad FTIR spectrophotometer in the range 4000–
400 cm–1
.
Synthesis of HL. A methanolic solution (10 ml) of 2ꢀ
morpholinꢀ4ꢀylethylamine (130.2 mg) was added with
stirring to a methanolic solution (20 ml) of 5ꢀchlorosaliꢀ
cylaldehyde (1.0 mmol, 156.6 mg). The mixture was
stirred at reflux for 30 min to give a yellow solution. The
solution was evaporated to give a yellow powder, which
[CoL2(N3)]2
zinc(II) complex, [ZnLCl(CH3OH)] (II
⋅
CH3OH (
I
)
, and a new mononuclear
), were preꢀ
1
The article is published in the original.
177

178
WANG
Table 1. Crystallographic parameters and summary of data colꢀ
three times with cold methanol, and dried in air. The yield
was 37% based on HL.
lection and refinement for the complexes
I
and II
Value
For C53H68Cl4Co2N14O9
Parameter
anal. calcd., %: C, 48.8;
Found, %: C, 48.3;
H, 5.3;
H, 5.5;
N, 15.0.
N, 15.3.
I
II
M
1304.9
400.6
Synthesis of [ZnLCl(CH3OH)] (II). A methanolic soꢀ
lution (10 ml) of HL (0.1 mmol, 26.8 mg) was added with
stirring to a methanolic solution (5 ml) of ZnCl2 (0.1 mmol,
13.6 mg). The mixture was stirred for 30 min at room temꢀ
perature and filtered. Upon keeping the filtrate in air for a
few days, colorless blockꢀshaped crystals of II, suitable for
Xꢀray singleꢀcrystal diffraction, were formed on the bottom
of the vessel. The crystals were collected by filtration,
washed three times with cold methanol, and dried in air.
The yield was 62% based on HL.
Crystal shape/color
Crystal size, mm
Crystal system
Space group
Block/red
Block/colorless
0.20 0.20
Monoclinic
21/
0.18
Monoclinic
21/
×
0.17
×
0.15 0.23
×
×
P
c
P
c
a
, Å
, Å
, Å
, deg
, Å3
18.742(2)
15.197(2)
25.646(2)
125.996(3)
5909.8(11)
4
7.257(1)
24.707(2)
9.637(1)
101.557(2)
1692.9(3)
4
b
c
For C14H20Cl2N2O3Zn
β
anal. calcd., %: C, 42.0;
Found, %: C, 41.5;
H, 5.0;
H, 5.1;
N, 7.0.
N, 6.7.
V
Z
Crystal structure determination. A suitable single
crystal of each complex was mounted on a glass fiber.
The diffraction experiments were carried out on a
Bruker AXS SMART CCD diffractometer. The proꢀ
gram SMART was used for collecting frames of data,
indexing reflections, and determination of lattice
parameters [13]. SAINT was used for integration of
the intensity of reflections and scaling [13], SADABS
was used for absorption correction [14], and
SHELXTL was applied for space group and structure
determination and leastꢀsquares refinements on F2
[15]. All nonꢀhydrogen atoms were refined anisotropiꢀ
μMo, mm–1
0.809
1.778
Tmin
0.868
0.685
Tmax
0.888
0.717
Reflections/parameters
Independent reflections
12699/741
6278
3666/203
3151
F
(000)
Goodnessꢀofꢀfit on F2
R1 wR2 ))*
R1 wR2 (all data)*
2712
824
1.019
1.044
cally. The H(3A) atom attached to O(3) in II was
,
(I
≥
2σ
(
I
0.0551, 0.1295
0.1347, 0.1849
0.0298, 0.0749
0.0366, 0.0780
located from a difference Fourier map and refined isoꢀ
tropically with O–H distance restrained to 0.85(1) Å.
Other hydrogen atoms were placed in idealized posiꢀ
tions and allowed to ride on the connecting atoms.
The crystallographic data for the complexes are sumꢀ
marized in Table 1. Selected bond lengths and angles
are listed in Table 2. Hydrogen bonds are listed in
Table 3.
,
2
o
2
c
2
2 1/2
2
* R = S||F | – |F ||/S|F |, wR = [Sw(F – F ) /Sw(F ) ]
.
1
o
c
o
2
o
was washed with methanol and dried in air. The yield was
93%.
Atomic coordinates and other structural parameters
of the complexes have been deposited with the Camꢀ
For C13H17ClN2O2
bridge Crystallographic Data Center (nos. 740909 (I)
anal. calcd., %: C, 58.1;
Found, %: C, 58.5;
H, 6.4;
H, 6.3;
N, 10.4.
N, 10.6.
and 740910 (II); deposit@ccdc.cam.ac.uk).
Measurement of urease. The assay mixture conꢀ
taining 25 of jack bean urease and 25 l (100 g) of
μl
μ
μ
Synthesis of [CoL2(N3)]
solution (5 ml) of Co(ClO4)2
was added with stirring to a methanolic solution (10 ml) of
HL (0.1 mmol, 26.8 mg) and sodium azide (0.1 mmol,
6.5 mg). The mixture was stirred for 30 min at room temꢀ
perature and filtered. Upon keeping the filtrate in air for a
few days, red blockꢀshaped crystals of I, suitable for Xꢀray
⋅
⋅
CH3OH (I). A methanolic
6H2O (0.1 mmol, 36.6 mg)
the test compound was preincubated for 0.5 or 3 h at
room temperature in a 96ꢀwell assay plate. After preinꢀ
cubation, 0.2 ml of 100 mM phosphate buffer (pH 6.8)
containing 500 mM urea and 0.002% phenol red were
added and incubated at room temperature. The reacꢀ
tion time was measured by a microplate reader
(570 nm), which was required for enough ammonium
singleꢀcrystal diffraction, were formed on the bottom of carbonate to form to raise the pH of a phosphate buffer
the vessel. The crystals were collected by filtration, washed from 6.8 to 7.7 [16].
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 36
No. 3
2010

SYNTHESIS AND CRYSTAL STRUCTURES
Table 2. Selected bond lengths and bond angles for the
179
RESULTS AND DISCUSSION
complexes
The Schiff base HL was readily synthesized via
Schiff base condensation using equimolar quantities
of 5ꢀchlorosalicylaldehyde with 2ꢀmorpholinꢀ4ꢀ
Bond
d, Å
Bond
d, Å
I
ylethylamine. Complex
I was synthesized by mixing
Co(1)–O(1)
Co(1)–N(1)
Co(1)–N(4)
Co(2)–O(5)
Co(2)–N(8)
Co(2)–N(11)
1.894(3) Co(1)–O(3)
1.958(4) Co(1)–N(3)
2.074(4) Co(1)–N(5)
1.910(3) Co(2)–O(7)
1.953(4) Co(2)–N(10)
2.067(4) Co(2)–N(12)
II
1.880(3)
1.901(4)
1.927(4)
1.888(3)
1.895(4)
1.927(4)
equimolar quantities of HL, NaN3, and Co(ClO4)2
⋅
6H2O in a methanolic solution, yielding an azideꢀ
coordinated octahedral cobalt(III) complex. It is
notable that the Co atom was oxidized during the proꢀ
cess. Complex II was synthesized by a similar proceꢀ
dure as that described for
replaced by ZnCl2, yielding a chlorideꢀcoordinated
I
, but with Co(ClO4)2 6H2O
⋅
trigonal bipyramidal zinc(II) complex.
The Schiff base HL is soluble in DMF, DMSO,
methanol, ethanol, chloroform, and acetonitrile. The
elemental analyses are in good agreement with the
chemical formula proposed for the compound. Both
complexes are stable in air at room temperature. They
are soluble in DMF, DMSO, methanol, ethanol, and
acetonitrile, and insoluble in water.
Zn(1)–O(1)
Zn(1)–N(1)
Zn(1)–Cl(2)
2.070(2) Zn(1)–O(3)
2.017(2) Zn(1)–N(2)
2.219(1)
2.026(2)
2.515(2)
Angle
ω
, deg
Angle
ω
, deg
I
N(1)Zn(1)O(3) 114.3(1)
O(3)Zn(1)O(1) 89.7(1)
O(3)Zn(1)Cl(2) 114.6(1)
N(1)Zn(1)N(2) 76.9(1)
O(1)Zn(1)N(2) 165.7(1)
N(1)Zn(1)O(1)
89.4(1)
In the infrared spectra of the Schiff base HL, the
1
weak and broad absorption band centered at 3350 cm⎯
N(1)Zn(1)Cl(2) 130.3(1)
O(1)Zn(1)Cl(2) 98.5(1)
is assigned to the stretching vibration of the O–H
bond, which absent in the complexes. The strong
absorption band at 1645 cm–1 for HL is assigned to the
O(3)Zn(1)N(2)
92.1(1)
Cl(2)Zn(1)N(2) 93.6(1)
azomethine group,
lower frequencies in the complexes (1627 cm–1 for
and 1623 cm–1 for II). The strong absorption of the
azide group in
is at 2043 cm–1
Figure 1 gives a perspective view of complex
asymmetric unit of consists of two CoL2(N3) complex
ν(C=N) [17], which is shifted to
I
II
O(3)Co(1)O(1)
O(1)Co(1)N(3)
90.0(2)
85.7(2)
O(3)Co(1)N(3)
O(3)Co(1)N(5)
N(3)Co(1)N(5)
O(1)Co(1)N(1)
N(5)Co(1)N(1)
O(1)Co(1)N(4)
N(5)Co(1)N(4)
94.4(2)
91.0(2)
86.7(2)
94.7(2)
92.9(2)
88.6(2)
90.4(2)
I
.
I. The
O(1)Co(1)N(5) 172.4(2)
O(3)Co(1)N(1) 86.2(2)
I
molecules and one methanol molecule of crystallizaꢀ
tion. The methanol molecule is linked to the complex
molecules through the O(9)–H(9)⋅⋅⋅O(5) hydrogen
bond.
In each complex molecule, the Co atom is sixꢀ
coordinated and is best described as having an octaheꢀ
dral coordination. One Schiff base coordinates to the
Co atom through the phenolate O, imine N, and
amine N atoms, and another base coordinates to the
Co atom through the phenolate O and imine N atoms.
The remaining position of the octahedral geometry is
occupied by the N atom of the terminal coordinated
azide group. The three trans angles are ranged from
N(3)Co(1)N(1) 179.3(2)
O(3)Co(1)N(4) 178.6(2)
N(3)Co(1)N(4)
N(1)Co(1)N(4)
O(7)Co(2)O(5)
85.4(2)
94.0(2)
89.8(2)
O(7)Co(2)N(10) 93.2(2)
N(10)Co(2)O(5) 84.7(2)
N(10)Co(2)N(12) 88.5(2)
O(7)Co(2)N(12) 92.8(2)
O(5)Co(2)N(12) 172.8(2)
N(10)Co(2)N(8) 178.6(2)
N(12)Co(2)N(8) 92.4(2)
N(10)Co(2)N(11) 86.3(2)
N(12)Co(2)N(11) 86.3(2)
O(7)Co(2)N(8)
O(5)Co(2)N(8)
85.6(2)
94.4(2)
O(7)Co(2)N(11) 179.0(2)
O(5)Co(2)N(11) 90.9(2)
N(8)Co(2)N(11) 94.9(2)
172.4(2)
°
to 179.3(2)
°
for Co(1) and 172.8(2) to
°
Table 3. The geometric parameters of hydrogen bonds and bond angles for complexes I and II*
Distance, A
Contact D–H⋅⋅⋅
A
Angle D–H⋅⋅⋅A, deg
D–H
H⋅⋅⋅A
D⋅⋅⋅A
I
O(9)–H(9)⋅⋅⋅O(5)
0.82
0.845(10)
2.08
2.889(6)
2.623(2)
172
II
1.782(11)
O(3)–H(3
A)
⋅⋅⋅O(1)i
173(4)
i
* Symmetry code: 2 – x, 1 – y, 1 – z.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 36
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180
WANG
Cl(2)
C(18)
C(19)
N(3)
C(17)
O(9)
C(53)
C(45)
C(14)
Cl(4)
C(44)
C(16)
C(15)
O(3)
Co(1)
C(20)
C(40)
C(46)
C(30)
C(43)
C(42)
C(29)
O(5)
C(21)
O(1)
C(2)
C(3)
C(4)
N(10)
C(41)
O(7)
Cl(3)
C(22)
C(1)
C(31)
C(32)
C(52)
N(7)
C(5)
C(27)
N(6)
Co(2)
N(5)
N(1)
N(14)
C(36)
C(37)
C(9)
C(6)
C(26)
C(10)
N(13)
N(12)
N(4)
Cl(1)
N(11)
C(33)
N(8)
C(51)
C(11)
C(23)
C(8)
N(2)
N(9)
C(49)
C(24)
O(4)
C(34)
O(6)
C(25)
C(39)
C(13)
O(8)
C(50)
O(2)
C(38)
C(12)
Fig. 1. Molecular structure of
I
at 30% ellipsoid. H atoms unrelated to hydrogen bond are omitted.
C(8)
C(9)
C(7)
C(6)
C(5)
N(1)
N(2)
C(13)
C(1)
Cl(1)
C(10)
C(11)
Zn(1)
C(12)
C(2)
Cl(2)
C(4)
O(1)
C(3)
O(2)
O(3)
C(14)
Fig. 2. Molecular structure of II at 30% ellipsoid.
179.0(2)
°
for Co(2), and the remaining coordinate
Figure 2 gives a perspective view of complex II. The
bond angles are close to 90 , indicating that the octaꢀ Zn atom is fiveꢀcoordinated and is best described as
°
hedral coordination is slightly distorted. The coordiꢀ having a trigonal bipyramidal coordination. The equaꢀ
nate bond lengths for Co(1) and Co(2) are similar to torial plane of the coordination is defined by one
each other and comparable with the values observed in imine N atom of L, one O atom of the methanol molꢀ
other cobalt(III) complexes with Schiff bases [18–20]. ecule, and one CI atom. The two axial positions are
As expected, the morpholine rings in the complex occupied by one phenolate O atom and one amine N
adopt chair conformations.
atom, respectively. The coordinate bond angles in the
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 36
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2010

SYNTHESIS AND CRYSTAL STRUCTURES
181
x
z
0
y
Fig. 3. Molecular packing diagram of II viewed along the
y
axis. Hydrogen bonds are shown as dashed lines.
equatorial plane are ranged from 114.3(1)
°
to expected, the morpholine ring in the complex adopts
chair conformation.
130.3(1) , and the axial trans bond angle is 165.7(1) ,
°
°
indicating a distorted trigonal bipyramidal coordinaꢀ
tion. The trigonal bipyramidal coordination can furꢀ
In the crystal structure of the complex, adjacent
two molecules are linked through intermolecular
ther be proved by the structural index
which represents the relative amount of trigonality
(square pyramid, = 0; trigonal bipyramid, = 1). The
value for this structure is 0.59, indicating that the
τ
value [21],
O⎯H O hydrogen bonds, forming a dimer, as shown
⋅⋅⋅
in Fig. 3.
τ
τ
The cobalt(III) complex
inhibitory activity with the IC50 value of 27.12
0.73 , which is even stronger than that of the acetoꢀ
I shows strong urease
τ
coordination is severely distorted and best described as
a trigonal bipyramid. The coordinate bond lengths are
typical of and similar to those observed in other
μM
hydroxamic acid (45.37 0.31) coassayed as a standard
reference against the urease. However, zinc(II) comꢀ
zinc(II) complexes with Schiff bases [22–24]. As plex II shows no activity.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 36
No. 3
2010

182
WANG
11. Pearson, M.A., Michel, L.O., Hausinger, R.P., et al., Bioꢀ
chemistry, 1997, vol. 36, no. 26, p. 8164.
ACKNOWLEDGMENTS
This work was supported by the Natural Science
12. Wang, C.ꢀY., Wu, X., Tu, S.ꢀJ., et al., Synth. React. Inorg.
Met.ꢀOrg. NanoꢀMet. Chem., 2009, vol. 39, no. 2, p. 78.
13. SMART & SAINT Software Reference Manuals, Version
6.22, Bruker AXS Analytic Xꢀray Systems Inc., Madison
(WI, USA), 2000.
Foundation of China (project no. 30771696), and the
Natural Science Foundation of Zhejiang Province
(project no. Y407318).
14. Sheldrick, G.M. SADABS
sorption Correction, G ttingen (Germany): Univ. of
ttingen, 2000.
15. Sheldrick, G.M. SHELXTL Reference Manual, Version
5.1, Bruker AXS, Analytic XꢀRay Systems Inc., Madiꢀ
son (WI, USA), 1997.
, Software for Empirical Abꢀ
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