Synthesis, structure, and biological evaluation of three Cu(II) and Ni(II) (E)-3-(3,4-dimethoxyphenyl)acrylate complexes with organic diamines as potential urease inhibitors

Article abstract of DOI:10.1080/00958972.2013.821198

Three new complexes (1-3) have been synthesized and characterized by X-ray single crystal determination and evaluated for inhibitory activity on jack bean urease. All the complexes contained a new cinnamic acid derivative as the ligand (C1₁H1₂O₄), (E)-3-(3,4-dimethoxyphenyl)acrylic acid, and crystallized in monoclinic C2/c space group. Complex 1 (C1 ₁H1₁O₄)₄(C₃N ₂H₈)₂Cu₂ (C₃N ₂H₈ = 1,2-diaminopropane) was obtained with a = 20.488(2), b = 19.596(2), c = 15.2500(13), β = 93.502(2)°, V = 6111.2(10) A³, Z = 4, R₁ = 0.0616, and wR₂ = 0.2059. Complex 2 (C1₁H1₁O₄)₄(C ₃N₂H₈)₂Cu₂ (C ₃N₂H₈=1,3-diaminopropane) was obtained with a = 20.2494(12), b = 19.5732(12), c = 14.8940(8), β = 96.884(2)°, V = 5860.6(6) A³, Z = 4, R₁ = 0.0409, and wR₂ = 0.1107. Complex 3 (C1₁H1₁O₄) ₂(C₂N₂H₆)₂Ni ₂·H₂O (C₂N₂H₆ = ethylenediamine) was obtained with a = 28.359(2), b = 6.5422(5), c = 16.8587(14), β = 101.359(2)°, V = 3066.5(4) A³, Z = 4, R₁ = 0.0422, and wR₂ = 0.1190. It was found that copper(II) complexes 1 [IC5₀ = 4.71 M] and 2 [IC5₀ = 3.15 M] showed strong inhibitory activity against jack bean urease compared with acetohydroxamic acid [IC5₀ = 10.01 M] as a positive reference. Unfortunately, 3 exhibited no inhibitory activity. 102013

Full text of DOI:10.1080/00958972.2013.821198

Journal of Coordination Chemistry, 2013
Vol. 66, No. 17, 2980–2991, http://dx.doi.org/10.1080/00958972.2013.821198
Synthesis, structure, and biological evaluation of three Cu(II)
and Ni(II) (E)-3-(3,4-dimethoxyphenyl)acrylate complexes
with organic diamines as potential urease inhibitors
HUI ZHU, ZI-ZHEN WANG, BING QI, TAO HUANG and HAI-LIANG ZHU*
School of Life Sciences, Shandong University of Technology, Zibo, People’s Republic of
China
(Received 27 September 2012; in final form 29 May 2013)
Three new complexes (1–3) have been synthesized and characterized by X-ray single crystal
determination and evaluated for inhibitory activity on jack bean urease. All the complexes contained a
new cinnamic acid derivative as the ligand (C11H12O4), (E)-3-(3,4-dimethoxyphenyl)acrylic
acid, and crystallized in monoclinic C2/c space group. Complex 1 (C11H11O4)4(C3N2H8)2Cu2
(C3N2H8 = 1,2-diaminopropane) was obtained with a = 20.488(2), b = 19.596(2), c = 15.2500(13),
β = 93.502(2)°, V = 6111.2(10) Å3, Z = 4, R1 = 0.0616, and wR2 = 0.2059. Complex
2
(C11H11O4)4(C3N2H8)2Cu2 (C3N2H8=1,3-diaminopropane) was obtained with a = 20.2494(12),
b = 19.5732(12), c = 14.8940(8), β = 96.884(2)°, V= 5860.6(6) Å3, Z = 4, R1 = 0.0409, and
wR2 = 0.1107. Complex 3 (C11H11O4)2(C2N2H6)2Ni2·H2O (C2N2H6 = ethylenediamine) was obtained
with a = 28.359(2), b = 6.5422(5), c = 16.8587(14), β = 101.359(2)°, V = 3066.5(4) Å3, Z = 4,
R1 = 0.0422, and wR2 = 0.1190. It was found that copper(II) complexes 1 [IC50 = 4.71 μM] and 2
[IC50 = 3.15 μM] showed strong inhibitory activity against jack bean urease compared with
acetohydroxamic acid [IC50 = 10.01 μM] as a positive reference. Unfortunately, 3 exhibited no inhibi-
tory activity.
Keywords: Cinnamic acid ligand; Transition metal complexes; Crystal structures; Urease inhibitors
1. Introduction
Transition metals have biological activity for many biochemical processes [1]. Commonly
used transition metals include nickel, copper, cobalt, zinc, etc. Copper and nickel act as
cofactors in some important enzymatic and organ functions, resulting in increased activities
of these enzymes. Cinnamic acid is a derivative of phenylalanine. In nature, cinnamic acid
derivatives are important metabolic building blocks in the production of lignins for higher
plants [2]. A derivative of cinnamic acid is an important pharmaceutical for high blood
pressure and stroke prevention and possesses antitumour activity [3], even showing
antibacterial, antitubercular, antifungal [4–7], and antiglycation activities [8]. Functional
activity may be optimized by combining transition metals with organic acids. Biological
activity of metal complexes is a focus and been reported many times [9–11]. Urease is
an important enzyme, causing many human diseases [12] and affecting soil nitrogen
*Corresponding author. Email: hailiang_zhu@163.com
Ó 2013 Taylor & Francis

Cu(II) and Ni(II) Complexes
2981
fertilization and ammonia volatilization and root damage [13]. It is important to find an
excellent inhibitor.
In view of the biological importance of transition metal complexes, we designed a new
cinnamic acid derivative, the (E)-3-(3,4-dimethoxyphenyl)acrylic acid, and synthesized
new complexes with the cinnamic acid derivative as ligand. In this paper, we synthesized
and evaluated the structure and biological activities.
2. Results and discussion
2.1. Synthesis
Cinnamic acid (E)-3-(3,4-dimethoxyphenyl)acrylic acid (C11H12O4) was prepared by
reaction of malonic acid and veratraldehyde in a solution of absolute ethanol in 70–80%
yield. Each new complex was synthesized by (E)-3-(3,4-dimethoxyphenyl)acrylic acid and
copper sulfate pentahydrate and nickel sulfate heptahydrate in 50–60% yield. We obtained
three complexes in different solvents by the cinnamic acid metal salts and different
Table 1. Crystal data and refinement parameters for 1–3.
Complex
1
2
3
CCDC deposit no.
876276
899450
899449
Molecular formula
Molecular weight
C50H60N4O16Cu2
1154.17
C50H64N4O16Cu2
1228.25
C26H34N4O8Ni
643.31
Temperature (K)
296
293
296
Radiation λ
Crystal system
Space group
Mo Kα (0.71073 Å)
Monoclinic
C2/c
Mo Kα (0.71073 Å)
Monoclinic
C2/c
Mo Kα (0.71073 Å)
Monoclinic
C2/c
a/Å
b/Å
c/Å
β/°
20.488(2)
19.596(2)
15.2500(13)
93.502(2)
6111.2(10)
4
20.2494(12)
19.5732(12)
14.8940(8)
96.884(2)
5860.6(6)
4
28.359(2)
6.5422(5)
16.8587(14)
101.359(2)
3066.5(4)
4
V/Å3
Z
Dcalc (g cmꢀ3
)
1.255
1.392
1.393
Crystal size (mm)
Crystal color
0.21 ꢁ 0.23 ꢁ 0.27
0.22 ꢁ 0.23 ꢁ 0.28
0.20 ꢁ 0.23 ꢁ 0.25
Blue
Blue
Blue
Abs. coefficient (mmꢀ1
)
0.779
0.771
5.743
Abs. correction Tmin and
Tmax
0.8172 and 0.8534
0.8130 and 0.8486
0.3278 and 0.3930
F (0 0 0)
2416
2584
1360
Reflections collected/unique
5985/22,482 [Rint = 0.037] 6070/29,729 [Rint = 0.024] 2852/15,414
[Rint = 0.020]
Range/indices (h, k, l)
ꢀ24, 25; ꢀ24, 24; ꢀ18,
ꢀ25, 23; ꢀ24, 24; ꢀ18,
ꢀ34, 34; ꢀ7, 7; ꢀ20,
18
18
20
h limit (°)
No. of observed data,
2.1–26.0
4148
2.5–26.5
5136
2.46–25.50
2695
I > 2σ(I)
No. of restraints
Goodness of fit on F2
Largest diff. peak/hole
5985
1.056
0.99/ꢀ0.42
6070
1.096
0.66/ꢀ0.34
2852
1.051
0.54/ꢀ0.52
(e Åꢀ3
)
R1, wR2 [I P 2σ(I)]a
R1, wR2 (all data)a
0.0616, 0.2059
0.0960, 0.2257
0.0409, 0.1107
0.0506, 0.1172
0.0422, 0.1190
0.0441, 0.1216
aR1 = Fo – Fc/Fo, wR2 = [Σw(Fo2 – Fc2)/Σw(Fo2)2]1/2
.

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H. Zhu et al.
Table 2. Selected bond distances (Å) and angles (°) for 1–3.
1
Cu1–N1
Cu1–N2
1.991(5)
1.989(4)
Cu1–O2
Cu1–O6
1.950(3)
1.976(3)
Cu1–O6a
2.372(3)
N2–Cu1–O6
O2–Cu1–N2
N1–Cu1–N2
N2–Cu1–O6a
90.21(16)
179.13(15)
84.62(18)
88.01(14)
O2–Cu1–O6
O6–Cu1–N1
O6–Cu1–O6a
89.96(13)
173.15(15)
82.56(11)
2
Cu1–N1
Cu1–N2
Cu1–O5a
N2–Cu1–O5a
O4–Cu1–N1
O4–Cu1–O5
1.985(2)
2.0148(19)
1.9934(16)
85.11(8)
90.69(8)
90.45(7)
Cu1–O4
Cu1–O5
N2–Cu1–O5
N1–Cu1–N2
O4–Cu1–N2
O4–Cu1–O5a
1.9568(17)
2.3568(16)
90.28(7)
95.95(8)
173.25(8)
88.40(7)
3
Ni1–O1
Ni1–N2
O1–Ni1–N2
2.1267(18)
2.094(2)
88.28(8)
Ni1–N1
O1–Ni1–N1
N1–Ni1–N2
2.106(2)
89.91(7)
82.38(9)
diamines in different conditions. The details of the crystallographic data are summarized in
table 1. Selected distances and angles are listed in table 2.
2.2. Discussion
We designed and synthesized a new cinnamic acid, (E)-3-(3,4-dimethoxyphenyl)acrylic
acid. With a series of diamines, new coordination compounds could be synthesized. We
used many combination experiments, but only three crystalline complexes were obtained.
The ligand had two electron-donating groups and the methoxy.
Molecular structure and atomic numbering scheme of 1, 2, and 3 are shown in figures
1–3, respectively. Complexes 1 and 2 contain one molecule in the asymmetric unit, while
the crystal of 3 is composed of one mononuclear unit and two lattice waters. As shown in
table 3, the cinnamic acid ligand has no influence on the activity of jack bean urease.
Under the same conditions, 1 and 2 showed better inhibitory activity with IC50 values of
4.71 and 3.15 μM, respectively. In contrast, 3 showed no urease inhibitory activity. This
indicates that urease inhibitory activities of cinnamic acid metal complexes depend on
more than the organic ligand, including the central ions.
The precipitation of each type of coordination compound was subject to different
environments; solvents used in the synthesis were important. The most suitable solvents
were methanol, ethanol, acetonitrile, and a mixed solution; temperature, pH, and
volatibility also influenced crystal growth [14].
2.3. Crystal structure description
Figures 1–3 give perspective views of the crystal structures of the complexes with the
atomic labels. Single crystal X-ray diffraction reveals that 1 and 2 are binuclear structures.
Each contained a centrosymmetric dinuclear unit with an inversion center at the center of
planar arrangement of Cu and O. On the contrary, 3 was a mononuclear nickel(II)

Cu(II) and Ni(II) Complexes
2983
Figure 1. An ORTEP diagram showing the structure of 1 with atom labeling. The thermal ellipsoids are plotted
at 30% probability and hydrogens are omitted for plot clarity.
compound. The structures of two copper crystals were similar, as shown in figures 1 and
2. For 1, the asymmetric unit consists of one copper cation, two (E)-3-(3,4-dimethoxy-
phenyl)acrylic acid molecules and one 1,2-diaminopropane. Two copper(II) were in the
middle of an eight-coordinate distorted monocapped structure. Cu(II) was five-coordinate
with two carboxyl O from two (E)-3-(3,4-dimethoxyphenyl)acrylic acids and two diamine
N from 1,2-diaminopropane. For 2, similar to 1, except using 1,3-diaminopropane instead
of 1,2-diaminopropane. In the crystal structure, for 1, methoxy O8 is a hydrogen-bond
acceptor to N1 of diamine in another molecule at (1 – x, ꢀy, ꢀz). Diamine N1 also is a
donor to methoxy O8 in another molecule at (ꢀx, ꢀy, ꢀz), respectively, forming
intermolecular hydrogen bonds. The molecules are further linked through intermolecular
and intramolecular N–Hꢂ ꢂ ꢂO and O–Hꢂ ꢂ ꢂO hydrogen bonds, forming chains along the
a-axis. For 2, two diamine nitrogens also are hydrogen bond donors to methoxy O1, O7,
and O8 at (ꢀx, ꢀy, 1 – z) and (1/2 + x, ꢀ1/2 + y, z). Diamine nitrogen N2 is a hydrogen
bond donor to methoxy O4 at (1/2 – x, ½ – y, 1 – z), forming intramolecular hydrogen
bonds. The dihedral angle between the two aromatic rings plane in 2 is 46.75(11)°. Single
crystal X-ray diffraction analysis showed that 3 consists of a mononuclear unit and two
lattice H2O as shown in figure 3. Ni is six-coordinate by two carboxyl oxygens of
(E)-3-(3,4-dimethoxyphenyl)acrylic acid and four diamine nitrogens. The H from H2O par-
ticipated in the formation of intermolecular hydrogen bond (table 4). The bond angles sub-
tended at Ni are 82.38(9)–89.91(7)°, indicating a distorted octahedral geometry.
C10–C11 in the complex is slightly twisted. In 1, molecules were mainly connected by
intermolecular hydrogen bond between N from 1,2-diaminopropane and methoxy O from
another molecule (figure 4). Similarly in 2, the primary intermolecular hydrogen bond was

2984
H. Zhu et al.
Figure 2. An ORTEP diagram showing the structure of 2 with atom labeling. The thermal ellipsoids are plotted
at 30% probability and hydrogens are omitted for clarity.
between N from 1,3-diaminopropane and methoxy O from another molecule (figure 5).
Figure 6 showed that in 3, the connection between each molecule was by water.
There were π–π interactions in 1 and 2. These π–π interactions and hydrogen bonds
played roles in the formation, stability, and crystallization of these complexes. The π–π
interactions in 3 were weaker than in the other two complexes.
2.4. IR spectra
The separation between the asymmetric and symmetric carboxylate stretches have been
compared to determine carboxylate binding with metal. In 1–3, the vasðCOOꢀÞ of asym-
metric carboxylates are 1551.7, 1586.0, and 1585.5 cmꢀ1. The vsðCOOꢀÞ of symmetric
carboxylates are 1385.9, 1368.0, and 1376.8 cmꢀ1. The Δ values are 165.8, 218.0, and
208.7 cmꢀ1, respectively. All Δ values are higher than the value for sodium cinnamate
(143 cmꢀ1) [15]. This suggests monodentate coordination of (E)-3-(3,4-dimethoxyphenyl)
acrylic acid in 1–3.
2.5. Inhibitory activity against jack bean urease
As shown in table 3, transition metal ions as enzyme inhibitors exhibit different abilities to
inhibit urease, Cu2+ > Ni2+. This is in accord with inhibitory efficiency of metal ions
toward urease, Cu2+ > Ni2+ > Co2+ > Zn2+, reported in the literature [16, 17]. Compared

Cu(II) and Ni(II) Complexes
2985
Figure 3. An ORTEP diagram showing the structure of 3 with atom labeling. Thermal ellipsoids are plotted at
30% probability and hydrogens are omitted for clarity.
Table 3. Inhibition of jack bean urease by 1–3, cinnamic acid ligand and metal ions.
Tested materials
IC50 (μM)
Cinnamic acid ligand
Complex 1
>100
4.71
Complex 2
3.15
Complex 3
Acetohydroxamic acid
>100
10.01
with the standard inhibitor acetohydroxamic acid, (E)-3-(3,4-dimethoxyphenyl) acrylate has
no influence on the activity of jack bean urease. Under the same condition, Cu(II)
complexes 1 and 2 showed better inhibitory activity with IC50 of 4.71 and 3.15,
respectively. In contrast, Ni(II) and its (E)-3-(3,4-dimethoxyphenyl) acrylate complex 3
showed no urease inhibitory activities (IC50 > 100 μM).
In conclusion, the urease inhibitory activities revealed that 1 and 2 have significantly
enhanced inhibitory activities compared to parent ligand. Coordination, locking the polar
electronegative atoms in the inner core around the metal and confining the apolar residues in
an external lipophilic envelope, favors diffusion through biomembranes [18]. Factors such as
solubility, conductivity, and dipole moment (influenced by the presence of metal ions) may

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H. Zhu et al.
Table 4. Geometrical parameters for hydrogen bonds.
Hydrogen bonds
D–H (Å)
H···A (Å)
D···A (Å)
D–H···A (°)
Complex 1
N1–H1ꢂ ꢂ ꢂO1#1
0.86
0.86
2.41
2.34
3.236(6)
3.052(6)
162
140
N1–H1Bꢂ ꢂ ꢂO8#2
Complex 2
N1–H1Bꢂ ꢂ ꢂO1#3
N2–H2Aꢂ ꢂ ꢂO7#4
N2–H2Aꢂ ꢂ ꢂO8#4
N2–H2Bꢂ ꢂ ꢂO4#5 (Intra)
0.90
0.90
0.90
0.90
2.37
2.50
2.26
2.36
3.206(3)
3.122(3)
3.089(3)
3.218(3)
155
127
154
159
Complex 3
O6–H6Bꢂ ꢂ ꢂO5#6
O6–H6Aꢂ ꢂ ꢂO5
O5–H5Bꢂ ꢂ ꢂO1#7
0.85
0.85
0.85
2.20
2.19
2.27
2.778(3)
2.778(3)
2.724(3)
125
126
114
#2
#3
Symmetry codes: #11 – x, ꢀy, ꢀz; ꢀx, ꢀy, ꢀz; ꢀx, ꢀy, 1 – z; #41/2 + x, ꢀ1/2 + y, z; #51/2 – x, 1/2 – y, 1 – z;
#6
ꢀx, y, 1/2 – z; #7x, ꢀ1 + y, z.
contribute to the increase in activity [19]. However, 3 showed no urease inhibitory activities;
maybe the performance of the metal, steric, and pharmacokinetic factors may also play roles
in potency of an antiturease agent.
3. Experimental
3.1. Materials and measurements
Unless otherwise stated, all solvents were of reagent grade and purchased
commercially. All chemicals were also commercially available and used without purification.
(E)-3-(3,4-Dimethoxyphenyl)acrylic acid was obtained according to literature method [20].
C, H, O, and N elemental analyses were performed on a Perkin-Elmer 240 C elemental
analyzer. IR spectra were recorded (400–4000 cmꢀ1) on a FT-IR Nicolet 5700 spectrometer.
3.2. Synthesis of (E)-3-(3,4-dimethoxyphenyl)acrylic acid
Malonic acid (0.05 M, 5.30 g) and veratraldehyde (0.05 M, 8.30 g) were added to a solution
of absolute ethyl alcohol with stirring, then piperidine (0.2 mL) was added. The mixture
was stirred and heated under reflux for 8 h. The solution was added in ice-water,
precipitate was obtained and then dissolved in lye. The supernatant was obtained and then
acidification. The white precipitate was separated by filtration, washed three times with
water and dried at 50 °C. Anal. Calcd for C11H12O4: C, 63.45; H, 5.81; N, 30.74%. Found:
C, 63.23; H, 6.02; N, 30.95%.
3.3. Synthesis of Cu[C11H11O4]2 and Ni[C11H11O4]2
(E)-3-(3,4-Dimethoxyphenyl)acrylic acid (10 mM, 2.08 g) dissolved in a solution of sodium
hydroxide (pH was controlled at 7) was added to solution of CuSO4·5H2O (5 mM, 0.81 g)
or NiSO4·7H2O (5 mM, 1.315 g). The precipitates were filtered and dried at 40 °C. Anal.
Calcd for C22H22CuO8: C, 55.29; H, 4.64%. Found: C, 55.45; H, 5.01%. Anal. Calcd for
C22H22NiO8: C, 55.85; H, 4.69%. Found: C, 55.61; H, 4.93%.

Cu(II) and Ni(II) Complexes
2987
Figure 4. Molecular packing of 1, viewed along the c axis. Intermolecular hydrogen bonds are shown as dashed
lines.

2988
H. Zhu et al.
Figure 5. Molecular packing of 2, viewed along the c axis. Intermolecular hydrogen bonds are shown as dashed
lines.
3.4. Synthesis of 1
To a MeOH solution of 1,2-diaminopropane (0.5 mM, 0.04 g) was added a MeOH solution
of (E)-3-(3,4-dimethoxyphenyl)acrylic acid copper salt (0.5 mM, 0.24 g). The mixture was
stirred for 10 min at room temperature and filtered. Upon keeping the filtrate in air for
five days, suitable blue, block-shaped single crystals of 1 for structure determination
were obtained by slow evaporation of the solution in air. Anal. Calcd for C25H30CuN2O8:
C, 54.59; H, 5.50; N, 5.09%. Found: C, 54.25; H, 6.01; N, 5.39%. IR (KBr, ν/cmꢀ1):
3302.2 ν(NH, stretching), 1466.0 ν(O–CH3), 1640.5 ν(NH, deformation), 1551.7
νas(COOꢀ), 1424.0 ν(Ar–C=C), 1385.9 νs(COOꢀ), 1139.7 ν(C–N).

Cu(II) and Ni(II) Complexes
2989
Figure 6. Molecular packing of 3, viewed along the c axis. Intermolecular hydrogen bonds are shown as dashed
lines.
3.5. Synthesis of 2
1,3-Diaminopropane (0.5 mM, 0.04 g) was added to a solution of (E)-3-(3,4-dimethoxy-
phenyl)acrylic acid copper salt (0.5 mM, 0.24 g) in a mixed solvent. The mixture was
stirred for 10 min at room temperature and filtered. Keeping the filtrate in air for five days,
suitable blue, block-shaped single crystals of 2 for structure determination were obtained
by slow evaporation of the solution in air. Anal. Calcd for C25H30CuN2O8: C, 54.59; H,
5.50; N, 5.09%. Found: C, 54.27; H, 6.00; N, 5.37%. IR (KBr, ν/cmꢀ1): 3295.6 ν(NH,
stretching), 1464.7 ν(O–CH3), 1640.3 ν(NH, deformation), 1586.0 νas(COOꢀ), 1424.4
ν(Ar–C=C), 1368.0 νs(COOꢀ), 1139.1 ν(C–N).

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H. Zhu et al.
3.6. Synthesis of 3
Complex 3 was obtained from reaction of ethylenediamine (0.5 mM, 0.04 g) dissolved in
acetonitrile added to ammonia water solution of (E)-3-(3,4-dimethoxyphenyl)acrylic acid
nickel salt (0.5 mM, 0.23 g), stirred at room temperature, and then filtered. Keeping the
filtrate in air for days, single crystals of 3 for structure determination were obtained by
slow evaporation of the solution in air. Anal. Calcd for C13H17NiN2O4: C, 48.19; H, 5.29;
N, 8.65%. Found: C, 47.73; H, 5.36; N, 8.92%. IR (KBr, ν/cmꢀ1): 3351.1 ν(OH, water),
3291.2 ν(NH, stretching), 1462.5 ν(O–CH3), 1638.2 ν(NH, deformation), 1585.5
νas(COOꢀ), 1413.8 ν(Ar–C=C), 1376.8 νs(COOꢀ), 1136.4 ν(C–N).
3.7. Crystal structure determination
X-ray diffraction intensities were collected using a Bruker SMART APEX-II CCD area
detector equipped with graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å) at 298
(2) K. Absorption correction was applied by SADABS [21]. The structure was solved by
direct methods and refined on F2 by full-matrix least-squares using Bruker’s SHELXTL-97
[22]. All nonhydrogen atoms were refined anisotropically. The hydrogens were placed in
calculated positions and constrained to ride on their parent. The details of the crystallo-
graphic data are summarized in table 1. Selected bond lengths and angles are summarized
in table 2. Hydrogen bonds are listed in table 4.
3.8. Measurement of inhibitory activity against jack bean urease
Jack bean urease was purchased from Sigma Aldrich Co. (St. Louis, MO, USA). The
measurement of urease was carried out according to the literature [23, 24]. Generally,
the assay mixture, containing 25 mL of jack bean urease (10 kUꢀ1L) and 25 mL of the
tested complexes of various concentrations [dissolved in the solution of DMSO:
H2O=1 : 1 (v : v)], was preincubated for 1 h at 37 °C in a 96-well assay plate. After pre-
incubation, 0.2 mL of 100 mM HEPES (N-[2-hydroxy-ethyl]piperazine-N’-[2-ethanesulfo-
nic acid]) buffer [25] pH = 6.8 containing 500 mM urea and 0.002% phenol red were
added and incubated at 37 °C. The reaction time was measured by microplate reader
(570 nm), which was required to produce enough ammonium carbonate to raise the pH
of a HEPES buffer from 6.8 to 7.7, the endpoint being determined by the color of
phenol red indicator [26]. The abilities of the ligand, (E)-3-(3,4-dimethoxyphenyl)acrylic
acid, metal ions (M = Cu2+, Ni2+), and complexes 1–3 as inhibitors were studied by the
inhibition rate values of the material (25 mL, 100 mg) tested against jack bean urease
(25 mL, 10 kUꢀ1L) using urea (500 mM) in HEPES buffer (0.2 mL, 100 mM; pH 6.8).
The activities are shown in table 3.
4. Conclusions
The present study describes the preparation of (E)-3-(3,4-dimethoxyphenyl)acrylic acid and
its Ni(II) and Cu(II) complexes. X-ray single crystal determination of the three complexes
showed that three mixed-ligand complexes were synthesized and characterized; they crystal-
lize in monoclinic space group C2/c. The inhibitory activity on jack bean urease indicated

Cu(II) and Ni(II) Complexes
2991
that copper(II) complexes (1 and 2) exhibit stronger activity to inhibit jack bean urease than
3. The trend in this work is in accord with the studies reported earlier. Detailed investigations
are continuing to study the mechanisms of the inhibitory activity reported here.
Supplementary material
Crystallographic data for the structural analysis has been deposited with the Cambridge
Crystallographic Data Center (CCDC 876276 for 1, 899450 for 2 and 899449 for 3). Copy
of this information can be obtained free of charge from The Director, CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (Fax: (+44) 1223-336033; E-mail: deposit@ccdc.cam.ac.
uk or www: http://www.ccdc.cam.ac.uk).
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