Synthesis, structure, and urease inhibitory activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic acid

Article abstract of DOI:10.1080/00958972.2016.1213819

[Co^III(L₁)₂·H₂O]NO₃ (1), [Mn^II(L₁)₂·H₂O] (2), and [Zn^II(L₁)₂·H₂O] (3) with a hydrazone derived from protocatechu

Full text of DOI:10.1080/00958972.2016.1213819

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Synthesis, structure and urease inhibitory
activities of Co(III), Mn(II) and Zn(II) complexes with
hydrazone derived from protocatechuic acid
Cun-Fang Wang, Zhi-Jian Chen, Ke-Dong Zhao, Xiang-Fei Chen, Chun-Yang
Zhang, Gui-Hua Sheng & Hai-Liang Zhu
To cite this article: Cun-Fang Wang, Zhi-Jian Chen, Ke-Dong Zhao, Xiang-Fei Chen, Chun-Yang
Zhang, Gui-Hua Sheng & Hai-Liang Zhu (2016): Synthesis, structure and urease inhibitory
activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic
acid, Journal of Coordination Chemistry, DOI: 10.1080/00958972.2016.1213819
To link to this article: http://dx.doi.org/10.1080/00958972.2016.1213819
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Date: 24 July 2016, At: 04:56

Publisher: Taylor & Francis
Journal: Journal of Coordination Chemistry
DOI: http://dx.doi.org/10.1080/00958972.2016.1213819
Synthesis, structure and urease inhibitory activities of Co(III), Mn(II) and Zn(II)
complexes with hydrazone derived from protocatechuic acid
#
#
CUN-FANG WANG , ZHI-JIAN CHEN , KE-DONG ZHAO, XIANG-FEI CHEN, CHUN-YANG ZHANG,
GUI-HUA SHENG* and HAI-LIANG ZHU*
School of Life Sciences, Shandong University of Technology, ZiBo 255049, PR China
III
II
II
[
Co (L
1
)
2
·H
2
O]NO
3
(1), [Mn (L
1
)
2
·H
2
O] (2) and [Zn (L
1 2 2
) ·H O] (3) with a hydrazone derived
from protocatechuic acid (HL = C H N O ) were designed, synthesized and characterized by
1
15 13
3
3
C, H, N elemental analyses, single crystal X-ray diffraction and IR spectra, which revealed that
the three complexes are similar structures. Docking study has been done. The urease inhibitory
activities of the three complexes were tested. Complexes 1 and 3 showed strong inhibitory
activity against jack bean urease with IC50 values of 45.9 and 11.64 μM. Complex 2 had no
obvious inhibitory activity to urease; the IC was > 50 μM.
5
0
Keywords: Complex; Hydrazone; Urease inhibitors; Protocatechuic acid; Molecular docking
1
. Introduction
Urease is widely found in organisms such as plants, algae, bacteria and fungi [1, 2]. Urease (urea
amidohydrolase; E.C.3.5.1.5) is a nickel-containing metalloenzyme that rapidly catalyzes the
hydrolysis of urea to form ammonia and carbamate [3]. The reaction catalyzed by urease may
cause an accumulation of ammonia and accompanying pH elevation, which has negative
*
Corresponding authors. Email: sgh76@126.com (Gui-hua Sheng); hailiang_zhu@163.com (Hai-liang Zhu)
These authors contributed equally to this paper.
#
1

implications in medicine and agriculture [4-9]. Urease is regarded as a virulent factor in human
and animal infections of the urinary and gastrointestinal tracts. This enzyme may cause chronic
gastritis, duodenal ulcer, gastric ulcer, gastric cancer, etc. [10, 11]. Urease is in Helicobacter
pylori, which is now accepted as a major cause of peptic ulcers. H. pylori is characterized by
very high urease activity which may act as a virulence or survival factor. Urease inhibitors could
counteract these negative effects through control of the activity of urease, so urease inhibitors
have very important status in the treatment of infections caused by urease producing bacteria
[12]. Because of the low efficiency and negative side effects of the presently reported inhibitors,
it is necessary to search for new urease inhibitors [13]. Transition metals have biological activity
in many biochemical processes [14]. They act as cofactors in some important enzymatic and
organ functions, resulting in increased activities of these enzymes [15]. Hydrazones, bearing
–
C(O)–NH–N=CH– groups, are a special kind of Schiff bases, which are of particular interest in
coordination chemistry and biological applications. In this paper, we report the synthesis of a
hydrazone derived from protocatechuic acid and synthesized three new metal complexes with the
hydrazone derivative as ligands. The structure and urease inhibitory activities of these complexes
were evaluated.
2
2
. Experimental
.1. Material and methods
All solvents were of reagent grade and purchased commercially unless otherwise stated. All
chemicals were also commercially available and used without purification. Elemental analyses
for C, N and H were performed on a Perkin-Elmer 240 C elemental analyzer.
2
.2. Synthesis of hydrazone ligand based on protocatechuic acid
The protocatechuic acid derivative (HL ) was synthesized with protocatechuic acid,
1
1
,2-dibromoethane, hydrazine hydrate and pyridine-2-carboxaldehyde (scheme 1). The synthesis
steps include esterification, cyclization, hydrazine solution and condensation. Three complexes
2

1
were synthesized by reactions of HL with the corresponding metal salts (scheme 2) in different
organic solvents.
2
.3. Synthesis of complexes
The three complexes were prepared by similar method. A methanol solution (0.5 mL) of
Co(NO ·6H O (0.05 mmol, 0.015 g) was added to an ethanol solution (4.0 mL) of HL
0.10 mmol, 0.028 g) for 1. A methanol solution (0.5 mL) of MnCl ·4H O (0.05 mmol, 0.009 g)
was added to 6.0 mL mixed solvent solution (ethanol:acetone:acetonitrile = 1:1:1) of HL1
0.10 mmol, 0.028 g) for 2. The solutions were left for 5 days at room temperature and red
3
)
2
2
1
(
2
2
(
block-shaped single crystals of 1 and 2 suitable for the structure determination were obtained at
the bottom of the vessel on slow evaporation of the solvent. Complex 3 was obtained with
3 2 2
similar procedure as for 2 by using Zn(NO ) ·6H O (0.05 mmol, 0.015 g) instead of
MnCl ·4H O. Complex 3 was yellow needle-shaped single crystals. Crystals of complexes were
2
2
isolated by filtration and washed with ethanol and then dried in air. For 1, yield 78%. Anal. Calc.
for C H CoN O : C, 51.22; H, 3.73; N, 13.94%. Found: C, 51.31; H, 3.74; N, 13.89%. For 2,
3
0
26
7
10
yield 76%. Anal. Calc. for C30
.12; N, 13.20%. For 3, yield 72%. Anal. Calc. for C30
Found: C, 55.71; H, 4.05; N, 12.92%.
H
26MnN
6
O
7
: C, 56.52; H, 4.11; N, 13.18%. Found: C, 56.39; H;
4
26 6 7
H N O
Zn: C, 55.61; H, 4.04; N, 12.97%.
2
.4. X-ray crystallography
Single-crystal X-ray diffraction data for 1, 2 and 3 were collected using a Bruker SMART
APEX-II CCD area detector equipped with graphite-monochromated Mo-Kα radiation (λ =
0
.71073 Å) at 291 K. Absorption correction was applied by SADABS [16]. Empirical absorption
corrections were applied based on equivalent reflections. The structures of 1, 2 and 3 were solved
2
by direct methods and refined by full-matrix least-squares on F using Bruker’s SHELXS-97
crystallographic software package [17]. All of the atoms were refined anisotropically except
hydrogen. Hydrogens bound to N or O were first found in the Fourier map and then fixed at their
3

ideal positions. Detailed crystallographic data are summarized in table 1. Selected bond lengths
and angles are listed in table 2. Hydrogen bond geometrical parameters are shown in table 3.
2
.5. 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 reported [18, 19]. The assay
mixture, containing 25 μL (10 kU/L) of jack bean urease and 25 μL of the tested samples
(complexes, parent ligands and metal salts) of various concentrations (dissolved in solution of
DMSO:H O=1:1 (v/v)), was preincubated for one hour at 37 °C in a 96-well assay plate. After
2
preincubation, 200 μL of 100 mM HEPES (N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulfonic
acid]) buffer pH=6.8 containing 500 mM urea and 0.002% phenol red was added and incubated
at 37 °C [20]. The reaction time was measured by a 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 [21].
2
.6. Docking study
Molecular docking of 1, 2 and 3 with the active site of jack bean urease (3LA4) was performed
by the AUTODOCK 4.2 program suite. The structures of complexes in docking protocol were
used as crystal structures. The graphical user interface AutoDockTools was used to install the
enzymes; all hydrogens were added at every inhibitor enzyme interaction, Gasteiger charges
were calculated and non-polar hydrogens were merged to carbons. The Ni initial parameters are
set as r = 1.170 Å, q = +2.0, and van der Waals well depth of 0.100 kcal/mol. The 3D structures
of ligand molecules were saved in Mol2 format with the assistance of the program MERCURY.
The partial charges of Mol2 file were further modified by using the ADT package so that the
charges of the non-polar hydrogens would be assigned to the atom to which hydrogen is attached
[22]. The resulting file was saved as pdbqt file. The docking input files were generated by
AutoDockTools program. A grid box size of 60×60×60 pointing in x, y and z directions were
4

built. The maps were centered on the Ni842 atom in the catalytic site of the protein in all
docking.
3
3
. Results and discussion
.1. Synthesis
1
HL was synthesized by esterification, cyclization, hydrazine solution and condensation. Three
complexes were obtained by coordination of HL
1
with Co(II), Mn(II) and Zn(II) salts. HL
1
,
1
white powder, yield: 72%, mp: 112-113 °C. H NMR (400 MHz, DMSO) δ: 4.22-4.31 (m, 4H),
6
1
1
.98-7.02 (m, 1H), 7.40-7.50 (m, 3H), 7.85-7.98 (m, 2H), 8.44-8.61 (m, 2H), 11.93-11.96 (m,
1
3
H), C NMR (400 MHz, DMSO) δ: 39.81, 49.07, 64.67, 117.36, 120.36, 121.82, 124.81,
26.25, 137.34, 143.51, 147.20, 148.03, 149.93, 153.75, 162.99.
3
.2. Crystal structure description
Solid structures of 1, 2 and 3 were determined by single-crystal X-ray diffraction, showing that
the three complexes are similar mononuclear structures. Crystal structures of 1, 2 and 3 are
shown in figures 1-4. The detailed crystallographic data are summarized in table 1. Selected
bond lengths and angles are listed in table 2. Hydrogen bond geometrical parameters are shown
in table 3.
III
3
.2.1. Description of 1. As shown in figure 1, [Co (L ) ·H O]NO (1) crystallizes in triclinic
1
2
2
3
space group P-1. Each molecule consists of one cobalt ion, two hydrazone ligands (HL
1
), a free
water molecule and a free nitrate. Each cobalt(III) is six-coordinate with four nitrogens and two
oxygens of two ligands. The coordination geometry around Co is octahedral. In each complex,
the hydrazone ligand is tridentate with the enolate O, imino N and pyridine N occupying a
meridional plane. In the crystal, the O10-H10E from free water and O8 from free nitrate
participate in the formation of an intermolecular hydrogen bond. The O10-H10B from free water
and O7 from free nitrate participate in formation of an intramolecular hydrogen bond. The
5

intermolecular O10-H10E…O8[x-1/2, -y+1, z] hydrogen bonds and intramolecular
O10-H10B…O7 hydrogen bonds serve as bridges to link free water and free nitrate into 1D
chains along the a axis (figure 2 and table 3).
II
3
.2.2. Description of 2. As shown in figure 3, [Mn (L ) ]·H O (2) is mononuclear. Each
1
2
2
1
molecule consists of one manganese ion, two hydrazone ligand (HL ) anions and a free water.
Each manganese is six-coordinate with four nitrogens and two oxygens of two ligands. The
coordination geometry around each Mn is octahedral. In each crystal, the hydrazone ligand is
tridentate in which the enolate O, imino N and pyridine N occupy a meridional plane.
II
3
.2.3. Description of 3. As shown in figure 4, [Zn (L
1
)
2
]·H
2
O (3) is mononuclear. Each
) anions and a free water. Each zinc
molecule consists of one zinc ion, two hydrazone ligand (HL
1
ion is six-coordinate with four nitrogens and two oxygens of two ligands. The coordination
geometry around each Zn is octahedral. In each complex, the hydrazone is tridentate in which the
enolate O, imino N and pyridine N occupy a meridional plane.
3
.3. IR spectra
IR spectra of 1, 2 and 3 are compared with HL to determine the coordination sites that may be
1
involved. The important IR bands with their tentative assignments are depicted as follows. IR
-1
spectrum of HL shows a medium intensity band at 3211 cm due to intramolecular hydrogen
1
bonding vibrations (N-H). The absence of this band in spectra of 1, 2 and 3 indicates
deprotonation of the imino N, HL
1
turn into L
1
and coordinates to the metal ions. The νC=N
-1
+
absorption is observed at 1657 cm in the K salt of the ligand anion. In 1, 2 and 3, this band
-1
shifted to lower frequency (39-56 cm ), indicating participation of pyridine N in coordination.
6

3
.4. Inhibitory activity against jack bean urease
2
+
2+
2+
The parent ligand HL
1
, Co , Mn , Zn , 1, 2 and 3 were evaluated for inhibitory activity against
jack bean urease according to the literature phenolred method. The results are summarized in
2
+
2+
2+
table 4. The IC value of the ligand and Co , Mn , Zn are >100 μM. Under the same
5
0
conditions, the IC of 1 was 45.9 μM; the IC of 2 was >50 μM, the results of urease test
5
0
50
showed that 2 had no obvious inhibitory activity to urease; the IC50 of 3 was 11.64 μM, showing
that 3 had obvious inhibitory activity to urease.
3
.5. Molecular docking
In order to explain the inhibitory activity of the complexes against urease, molecular docking
study of the complexes in the active sites of urease enzyme from jack bean urease (entry 3LA4
in the Protein Data Bank) were carried out by the AutoDock program.
The optimized cluster (50 occurrences) was ranked by energy level in the best
conformation of the inhibitor-urease modeled structures, where the binding energy of the amino
acid residues with 1, 2 and 3 showed -1.32, 12.47, -2.76 kcal/mol, respectively, and the lowest
intermolecular energy showed -1.47, 12.72, -2.83 kcal/mol, respectively. The results of the
molecular docking study are consistent with the inhibitory activities observed from the jack bean
urease experiment.
The binding mode of 1 and 3 with urease enzyme and the enzyme surface model are
shown in figure 5 and figure 6. The binding models reveal that N4 and N5 of 1 form hydrogen
bonds with the ARG439 and CME592 of the urease with hydrogen-bonding distance of 2.551 Å
1
(N4 complex 1…H –NARG439), 2.856 Å (N5 complex 1…H–OCME592) and 2.106 Å
(N4 complex 1…H–OCME592), respectively. Polar interaction exists between the benzene ring of 1 and
the amino acid (ARG439). In 3, O forms hydrogen bonds with the CME592 and ARG439 of the
1
urease with hydrogen-bonding distance of 2.138 Å (O1 complex 3…H–OCME592). Polar interaction
exists between the benzene ring of 3 and the amino acid (ARG439).
7

4
. Conclusion
In this article, we report the synthesis, structure, inhibitory activity and docking against jack
bean urease of three complexes with hydrazone derived from protocatechuic acid. Single crystal
X-ray diffraction, IR and UV-Vis spectra revealed that the three complexes are similar
mononuclear structures. The IC value for 3 was 11.64 μM while the IC values for 1 and 2
5
0
50
were 45.9 μM and more than 50 μM, respectively. The IC50 values for the metal-free ligand and
2
+
2+
2+
Co , Mn , Zn ions were more than 100 μM [23]. The results showed that 3 had obvious
inhibitory activity against urease and may be used as a urease inhibitor. Detailed investigations
are continuing to study the mechanisms of the inhibitory activity reported here.
Supplementary material
Crystallographic data for the structural analysis have been deposited with the Cambridge
Crystallographic Data Center (CCDC-141575 for 1, -141576 for 2 and -141577 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).
Acknowledgements
We thank the financial support from National Natural Science Foundation of China
(Grant No. 31200090), Scientific Research Foundation for Returned Scholars, Ministry of
Education of China and National College Students' Innovative and Entrepreneurial Training Plan
of China (Grant No. 201410433033).
References
[1]
Z.P. Xiao, T.W. Ma, W.C. Fu, X.C. Peng, A.H. Zhang, H.L. Zhu. Eur. J. Med. Chem., 45,
064 (2010).
5
8

[2]
G.M. Cox, J. Mukherjee, G.T. Cole, A. Casadevall, J.R. Perfect. Infect. Immun., 68, 443
2000).
(
[3]
[4]
[5]
[6]
[7]
P.A. Karplus, M.A. Pearson, R.P. Hausinger. Acc. Chem. Res., 30, 330 (1997).
H.L.T. Mobley, M.D. Island, R.P. Hausinger. Microbiol. Rev., 59, 451 (1995).
M. Zaman, J.D. Blennerhassett. Agric. Ecosyst. Environ., 136, 236 (2010).
B. Krajewska, R. Eldik, M. Brindell. J. Biol. Inorg. Chem., 17, 1123 (2012).
Z.L. You, D.H. Shi, J.C. Zhang, Y.P. Ma, C. Wang, K. Li. Inorg. Chim. Acta, 384, 54
(2012).
[
8]
9]
B. Krajewska, R. Eldik, M. Brindell. J. Biol. Inorg. Chem., 17, 1123 (2012).
A. Sanz-Cobena, L. Sánchez-Martín, L. García-Torres, A. Vallejo. Agric. Ecosyst.
Environ., 149, 64 (2012).
[
[
10] S. Ciurli, S. Benini, W.R. Rypniewski, K.S. Wilson, S. Miletti, S. Mangani. Coord. Chem.
Rev., 102, 331 (1990).
[
11] J. Torres, G. Pérez-Pérez, K.J. Goodman, J.C. Atherton, B.D. Gold, P.R. Harris, A.M.
la Garza, J. Guarner, O. Muñoz. Arch. Med. Res., 31, 431 (2000).
12] B. Krajewska. J. Mol. Catal. B. Enzym., 59, 9 (2009).
[
[
[
13] B.J. Marshall. Gastroenterol. Clin. N., 22, 183 (1993).
14] U. Ermler, W. Grabarse, S. Shima, M. Goubeaud, R.K. Thauer. Curr. Opin. Struct. Biol.,
8
, 749 (1998).
[15] S. Burt. Int. J. Food Microbiol., 94, 223 (2004).
[16] G.M. Sheldrick, SADABS Program for Empirical Absorption Correction of Area
Detector, University of Göttingen: Germany (1996).
[
[
[
[
[
17] G.M. Sheldrick. Acta Cryst., A64, 112 (2008).
18] T. Tanaka, M. Kawase, S. Tani. Life Sci., 73, 2985 (2003).
19] C.Y. Wang. J. Coord. Chem., 62, 2860 (2009).
20] W. Zaborska, B. Krajska, Z. Olech. J. Med. Chem., 19, 65 (2004).
21] D.D.V. Slyke, R.M. Archibald. J. Biol. Chem., 154, 623 (1944).
9

[
22] F. Musiani, E. Arnofi, R. Casadio, S. Ciurli. J. Biol. Inorg. Chem., 6, 300 (2001).
23] C.Y. Wang, J.Y. YE, C.Y. Lv, W.Z. Lan, J.B. Zhou. J. Coord. Chem., 62, 2164 (2009).
[
10

Table 1. Crystal and experimental data for 1-3.
1
2
3
Molecular formula
Molecular weight
Temperature (K)
Radiation λ
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (°)
C H CoN O
C H MnN O
C H ZnN O
3
0
26
7
10
30 26
637.51
273
6
7
30 26
647.94
296(2)
6
7
703.51
293(2)
Mo Kα (0.71073 Å)
Orthorhombic
P-1
14.0955(5)
10.7454(4)
19.4690(9)
90
Mo Kα (0.71073 Å) Mo Kα (0.71073 Å)
Monoclinic
Monoclinic
C2/c
C2/c
19.2899(17)
15.3044(14)
12.2217(11)
90
19.5220(10)
15.0220(9)
12.2012(6)
90
β (°)
γ (°)
V (Å )
Z
90.00
115.534(3)
90
116.367(2)
90
90
3
2948.81(2)
4
3255.7(5)
4
3205.9(3)
4
-
3
D (g cm )
1.585
1.301
1.342
c
3
Crystal size (mm )
0.26×0.25×0.19
1448
0.18×0.17×0.16
1316
0.24×0.22×0.20
1336
F(000)
o
θ range ( )
2.38~25.10
2.90~25.07
2.71~25.08
Reflections collected / unique
24944 / 5234
2874 / 2874
2843 / 2843
[R(int) = 0.0254]
[R(int) = 0.0000]
[R(int) = 0.0000]
Reflections obs. I > 2σ(I)
Goodness of fit on F
4656
1839
2067
2
1.018
1.004
1.034
Data / restraints / parameters
5234 / 1 / 434
0.057 / -0.263
0.0357, 0.0810
0.0442, 0.0859
2874 / 193 / 292
0.543 / -0.253
0.0545, 0.1167
0.1047, 0.1300
2843 / 205 / 292
0.507 / -0.495
0.0479, 0.1035
0.0803, 0.1118
-3
Largest diff. peak / hole (e Å )
a
R
1
,wR
2
[I > 2σ(I)]
a
R ,wR (all data)
1
2
a
2
2
2 2 1/2
o
R = F – F /F , wR = [ w(F – Fc )/ w(F ) ]
1
o
c
o
2
o
11

Table 2. Selected distances (Å) and angles (°) for 1-3.
Complex 1
Co(1)-N(1)
1.856(3)
1.899(2)
1.928(3)
176.39(9)
82.49(11)
95.27(11)
83.16(12)
90.15(11)
99.73(11)
165.19(11)
92.34(9)
Co(1)-N(5)
1.857(3)
1.909(2)
1.931(3)
95.06(10)
82.09(11)
90.91(8)
99.45(12)
165.25(11)
82.70(12)
90.39(12)
Co(1)-O(4)
Co(1)-O(1)
Co(1)-N(3)
Co(1)-N(6)
N(1)-Co(1)-N(5)
N(5)-Co(1)-O(4)
N(5)-Co(1)-O(1)
N(1)-Co(1)-N(3)
O(4)-Co(1)-N(3)
N(1)-Co(1)-N(6)
O(4)-Co(1)-N(6)
N(3)-Co(1)-N(6)
N(1)-Co(1)-O(4)
N(1)-Co(1)-O(1)
O(4)-Co(1)-O(1)
N(5)-Co(1)-N(3)
O(1)-Co(1)-N(3)
N(5)-Co(1)-N(6)
O(1)-Co(1)-N(6)
Complex 2 #1-x+1,y,-z+5/2
Mn(1)-O(1)#1
2.130(2)
Mn(1)-O(1)
2.130(2)
2.193(2)
2.289(11)
2.326(9)
120.22(8)
70.99(8)
164.41(12)
94.5(5)
Mn(1)-N(2)
2.193(2)
2.289(11)
2.326(9)
98.17(12)
70.99(8)
120.22(8)
142.0(4)
97.8(4)
Mn(1)-N(2)#1
Mn(1)-N(1)#1
Mn(1)-N(1)
Mn(1)-N(1A)#1
Mn(1)-N(1A)
O(1)#1-Mn(1)-O(1)
O(1)-Mn(1)-N(2)
O(1)-Mn(1)-N(2)#1
O(1)#1-Mn(1)-N(1)#1
N(2)-Mn(1)-N(1)#1
O(1)#1-Mn(1)-N(1)
N(2)-Mn(1)-N(1)
N(1)#1-Mn(1)-N(1)
O(1)-Mn(1)-N(1A)#1
O(1)#1-Mn(1)-N(2)
O(1)#1-Mn(1)-N(2)#1
N(2)-Mn(1)-N(2)#1
O(1)-Mn(1)-N(1)#1
N(2)#1-Mn(1)-N(1)#1
O(1)-Mn(1)-N(1)
N(2)#1-Mn(1)-N(1)
71.6(4)
94.5(5)
142.0(4)
97.8(4)
71.6(4)
97.3(11)
99.7(5)
O(1)#1-Mn(1)-N(1A)#1 142.5(4)
N(2)-Mn(1)-N(1A)#1 96.8(4)
N(1)#1-Mn(1)-N(1A)#1 5.9(10)
O(1)#1-Mn(1)-N(1A) 99.7(5)
N(2)#1-Mn(1)-N(1A)#1 71.5(4)
N(1)-Mn(1)-N(1A)#1 91.4(4)
12

O(1)-Mn(1)-N(1A)
N(2)#1-Mn(1)-N(1A)
N(1)-Mn(1)-N(1A)
142.5(4)
96.8(4)
5.9(10)
N(2)-Mn(1)-N(1A)
71.5(4)
91.4(4)
N(1)#1-Mn(1)-N(1A)
N(1A)#1-Mn(1)-N(1A) 85.6(10)
Complex 3 #1-x,y,-z+1/2
Zn(1)-N(2)
2.072(2)
Zn(1)-N(2)#1
Zn(1)-O(1)
2.072(2)
2.093(2)
2.242(12)
2.247(7)
113.87(8)
74.38(8)
94.72(12)
Zn(1)-O(1)#1
2.093(2)
2.242(12)
2.247(7)
168.53(13)
74.38(8)
113.87(8)
98.4(5)
Zn(1)-N(1A)#1
Zn(1)-N(1A)
Zn(1)-N(1)#1
Zn(1)-N(1)
N(2)-Zn(1)-N(2)#1
N(2)#1-Zn(1)-O(1)#1
N(2)#1-Zn(1)-O(1)
N(2)-Zn(1)-N(1A)#1
O(1)#1-Zn(1)-N(1A)#1
N(2)-Zn(1)-N(1A)
O(1)#1-Zn(1)-N(1A)
N(1A)#1-Zn(1)-N(1A)
N(2)#1-Zn(1)-N(1)#1
O(1)-Zn(1)-N(1)#1
N(1A)-Zn(1)-N(1)#1
N(2)#1-Zn(1)-N(1)
O(1)-Zn(1)-N(1)
N(2)-Zn(1)-O(1)#1
N(2)-Zn(1)-O(1)
O(1)#1-Zn(1)-O(1)
N(2)#1-Zn(1)-N(1A)#1 74.0(5)
147.7(5)
74.0(5)
O(1)-Zn(1)-N(1A)#1
N(2)#1-Zn(1)-N(1A)
O(1)-Zn(1)-N(1A)
N(2)-Zn(1)-N(1)#1
O(1)#1-Zn(1)-N(1)#1
92.0(5)
98.4(5)
147.7(5)
96.3(3)
149.6(3)
92.0(5)
99.0(11)
75.2(3)
96.8(4)
N(1A)#1-Zn(1)-N(1)#1 6.0(9)
93.1(5)
N(2)-Zn(1)-N(1)
75.2(3)
96.8(4)
93.1(5)
87.1(9)
96.3(3)
O(1)#1-Zn(1)-N(1)
N(1A)#1-Zn(1)-N(1)
N(1)#1-Zn(1)-N(1)
149.6(3)
6.0(9)
N(1A)-Zn(1)-N(1)
13

Table 3. Geometrical parameters for hydrogen bonds of 1.
Hydrogen bonds
O10-H10E…O8
O10-H10B…O7
Symmetry code
[ x-1/2, -y+1, z ]
D–H (Å)
0.960
H···A (Å)
2.402
D···A (Å)
3.035
D–H···A (°)
123.19
0.960
2.111
2.899
138.32
14

Table 4. Inhibition of urease by the tested materials.
Tested materials
HL1
IC (μM)
5
0
>100
2
+
Co
>100
2
+
Mn
>100
2
+
Zn
>100
III
Complex 1 : [Co (L ) ·H O]NO
45.9±0.3
>50
1
2
2
3
II
Complex 2 : [Mn (L ) ]·H O
1
2
2
II
Complex 3 : [Zn (L ) ]·H O
11.64±0.4
7.5±0.6
1
2
2
Acetohydroxamic acid
15

1
6

1
7

1
8

1
9

2
0

2
1

2
2

2
3

2
4