Synthesis, crystal structure, and urease inhibition of [N'-(3,5-dibromo-2- hydroxybenzylidene)isonicotinohydrazido]-(benzohydroxamato)oxovanadium(V)

Article abstract of DOI:10.1134/S1070328414070082

A new oxovanadium(V) complex [VOL(BZH)] was prepared by the reaction of [VO(Acac)₂] (Acac = acetylacetonate) with N'-(3,5-dibromo-2- hydroxybenzylidene)isonicotinohydrazide (H₂L) and benzohydroxamic acid (HBZH) in methanol. Crystal and molecular structure of the complex was determined by elemental analysis, infrared spectra and single crystal X-ray diffraction. The complex crystallizes in the monoclinic space group P2 ₁/c, with unit cell dimensions a = 11.424(1), b = 12.012(1), c = 19.565(2) A, β = 93.487(3)°, V = 2679.8(4) A³, Z = 4, GOOF = 1.152, R ₁ = 0.0593, and wR ₂ = 0.1942. The V atom is in octahedral coordination. Thermal stability and the inhibition of urease of the complex were studied.

Full text of DOI:10.1134/S1070328414070082

ISSN 1070ꢀ3284, Russian Journal of Coordination Chemistry, 2014, Vol. 40, No. 7, pp. 505–509. © Pleiades Publishing, Ltd., 2014.
Synthesis, Crystal Structure, and Urease Inhibition
of [N'ꢀ(3,5ꢀDibromoꢀ2ꢀHydroxybenzylidene)isonicotinohydrazido]ꢀ
(Benzohydroxamato)oxovanadium(V)1
G. H. Shenga, Z. Youb, *, and H. L. Zhua, **
aSchool of Life Sciences, Shandong University of Technology, ZiBo, 255049 P.R. China
bDepartment of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029 P.R. China
*eꢀmail: youzhonglu@lnnu.edu.cn*; hailiang_zhu@163.com**
Received December 21, 2013
Abstract—A new oxovanadium(V) complex [VOL(BZH)] was prepared by the reaction of [VO(Acac)2]
(Acac = acetylacetonate) with N'ꢀ(3,5ꢀdibromoꢀ2ꢀhydroxybenzylidene)isonicotinohydrazide (H2L) and
benzohydroxamic acid (HBZH) in methanol. Crystal and molecular structure of the complex was deterꢀ
mined by elemental analysis, infrared spectra and single crystal Xꢀray diffraction. The complex crystallizes in
the monoclinic space group
P
21/
Z
c
, with unit cell dimensions
a
= 11.424(1),
b
= 12.012(1),
c
= 19.565(2) Å,
β
=
93.487(3)
°
,
V
= 2679.8(4) Å3,
= 4, GOOF = 1.152, 1 = 0.0593, and wR2 = 0.1942. The V atom is in octaꢀ
R
hedral coordination. Thermal stability and the inhibition of urease of the complex were studied.
DOI: 10.1134/S1070328414070082
1
INTRODUCTION
EXPERIMENTAL
Urease has important negative effects on human,
Materials and measurements. Commercially availꢀ
able 3,5ꢀdibromosalicylaldehyde, isonicotinohyꢀ
drazide and benzohydroxamic acid were purchased
from Aldrich and used without further purification.
Other solvents and reagents were made in China and
used as received. C, H, and N elemental analyses were
performed with a PerkinElmer elemental analyser.
Infrared spectra were recorded on a Nicolet AVATAR
360 spectrometer as KBr pellets in the 4000–400 cm–1
region. Thermal stability analysis was performed on a
PerkinElmer Pyris Diamond TGꢀDTA thermal analyꢀ
ses system.
stockbreeding, and agriculture [1–4]. Control of the
activity of urease through the use of inhibitors could
counteract these negative effects. Metal complexes
have been proved to be a kind of versatile enzyme
inhibitors [5]. Among versatile metal complexes, those
derived from hydrazones have been received particular
attention in biological and medicinal chemistry [6–9].
In recent years, vanadium complexes have been
reported to have interesting biological activities such
as normalizing the high blood glucose levels and acting
as models of haloperoxidases [10–12]. It is notable
that Ara and coꢀworkers reported that some binuclear
vanadium(IV) complexes possess interesting urease
inhibitory activities [13]. Aslam and coꢀworkers
reported that the Schiff bases of hydrazone type also
possess urease inhibitory activities [14]. Recently, our
research group has reported a few vanadium comꢀ
plexes with urease inhibitory activities [15, 16]. In
order to explore more potent urease inhibitors, in the
present paper, a new oxovanadium(V) complex
[VOL(BZH)] (H2L = N'ꢀ(3,5ꢀdibromoꢀ2ꢀhydroxyꢀ
Synthesis of H2L. 3,5ꢀDibromosalicylaldehyde
(1.0 mmol, 0.28 g) and isonicotinohydrazide
(1.0 mmol, 0.14 g) were dissolved in methanol
(30 mL) with stirring. The mixture was stirred for
about 30 min at room temperature to give a clear soluꢀ
tion. The solvent was evaporated to give colorless crysꢀ
talline products. The yield was 87%.
For C13H9N3O2Br2
benzylidene)isonicotinohydrazide, HBZH = benzoꢀ anal. calcd., %: C, 39.1;
hydroxamic acid, has been presented.
H, 2.3;
H, 2.2;
N, 10.5.
N, 10.4.
Found, %:
C, 39.3;
N
H
Synthesis of [VOL(BZH)]. A methanolic solution
(10 mL) of [VO(Acac)2] (0.1 mmol, 26.5 mg) was
added to a methanolic solution (10 mL) of H2L
(0.1 mmol, 39.9 mg) and benzohydroxamic acid
(0.1 mmol, 13.7 mg) with stirring. The mixture was
stirred for 30 min at room temperature to give a deep
brown solution. The resulting solution was allowed to
Br
N
N
O
OH
(H2L)
Br
1
The article is published in the original.
505

506
SHENG et al.
Table 1. Crystallographic data and refinement parameters
for the complex
placed in idealized positions and constrained to ride
on their parent atoms. The crystallographic data for
the complexes are summarized in Table 1. Selected
bond lengths and angles are given in Table 2.
Parameter
Value
M
600.1
Supplementary material for structure of complex
[VOL(BZH)] has been deposited with the Cambridge
Crystallographic Data Centre (no. 978239;
Crystal color, habit
Crystal size, mm
Crystal system
Brown, block
0.20
Monoclinic
21/
×
0.20 0.17
×
deposit@ccdc.cam.ac.uk
cam.ac.uk).
or
http://www.ccdc.
Space group
P
c
Urease inhibitory activity assay. Helicobacter pylori
(ATCC 43504; American Type Culture Collection,
Manassas, VA) was grown in brucella broth suppleꢀ
mented with 10% heatꢀinactivated horse serum for
Unit cell parameters:
a
, Å
, Å
11.424(1)
12.012(1)
19.565(2)
93.487(3)
2679.8(4)
4
b
24 h at 37 C under microaerobic condition (5% O2,
°
c
, Å
10% CO2, and 85% N2). The method of preparation of
Helicobacter pylori urease by Mao was followed [20].
β
V
Z
, deg
, Å3
Briefly, broth cultures (50 mL, 2.0
×
108 CFU mL–1)
were centrifuged (5000 , 4 C) to collect the bacteria,
g
°
and after washing twice with phosphateꢀbuffered
ρcalcd, g cm–3
1.487
saline (pH 7.4), the Helicobacter pylori precipitation
was stored at –80 C. While the Helicobacter pylori was
°
Temperature, K
298(2)
returned to room temperature and mixed with 3 mL of
distilled water and protease inhibitors, sonication was
μ
, mm–1
3.385
F
(000)
1176
performed for 60 s. Following centrifugation (15000
g,
Number of unique data
Number of observed data (
Number of parameters
Number of restraints
4981
4
°
C), the supernatant was desalted through Sephaꢀ
dexGꢀ25 column (PDꢀ10 columns, AmershamꢀPharꢀ
macia Biotech, Uppsala, Sweden). The resultant
crude urease solution was added to an equal volume of
I
> 2
σ
(
I
))
3428
292
1
glycerol and stored at 4
ment. The mixture, containing 25
bacter pylori urease and 25 L of the test compound,
°
C until used in the experiꢀ
R1
,
,
wR2
(
I
> 2
σ(I
))
0.0593, 0.1942
0.0922, 0.2171
1.152
μ
L (4 U) of Helicoꢀ
μ
R1
wR2 (all data)
was preꢀincubated for 3 h at room temperature in a 96ꢀ
well assay plate. Urease activity was determined by
measuring ammonia production by the indophenol
method.
Goodness of fit on F2
Largest difference peak/hole,
e
Å–3
1.187/–0.529
stand in air for a few days. Brown blockꢀshaped crysꢀ
tals suitable for Xꢀray single crystal diffraction were
formed at the bottom of the vessel. The isolated prodꢀ
ucts were washed three times with cold methanol and
dried in air. The yield was 37%.
RESULTS AND DISCUSSION
Replacement of two acetylacetonate ligands in
[VO(Acac)2] by hydrazone and benzohydroxamate
ligands in methanol resulted in the formation of the
complex. The complex is soluble in DMF, DMSO,
methanol, ethanol, and acetonitrile. Molar conducꢀ
tance of the complex at a concentration of 10–4 mol/L
For C20H13N4O5Br2V
anal. calcd., %: C, 40.0;
Found, %: C, 39.8;
H, 2.2;
H, 2.3;
N, 9.3
is 30
[21].
Ω
–1 cm2 mol–1, indicating it is a nonꢀelectrolyte
N, 9.5.
Xꢀray crystallography. Diffraction intensities for
the complex were collected at 298(2) K using a Bruker scheme of the complex is shown in Fig. 1. The V atom
D8 VENTURE PHOTON diffractometer with Mo in the complex is in octahedral coordination with the
= 0.71073 Å). The collected data were three donor atoms of the hydrazone ligand and the
The molecular structure and atom numbering
K
α
radiation (
λ
reduced using the SAINT program [17], and multiꢀ hydroxyl O atom of the benzohydroxamate ligand
scan absorption corrections were performed using the defining the equatorial plane, and with one oxo
SADABS program [18]. The structure was solved by O atom and the carbonyl O atom of the benzohydroxꢀ
direct method and refined against F2 by fullꢀmatrix amate ligand occupying the axial positions. The disꢀ
leastꢀsquares method using the SHELXTL [19]. All of tance between atoms V(1) and O(5) is 1.59 Å, indicatꢀ
the nonꢀhydrogen atoms were refined anisotropically. ing it is a typical V=O double bond. The V(1)–O(3)
The amino H atom was located from a difference Fouꢀ bond in the complex is significantly longer than the
rier map and refined isotropically, with N–H distance remaining coordinate bonds, yet, it is not uncommon
restrained to 0.90(1) Å. The remaining H atoms were for such complexes [22, 23]. The coordinate bond
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 40
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2014

SYNTHESIS, CRYSTAL STRUCTURE, AND UREASE INHIBITION
507
Table 2. Selected bond distances (Å) and angles (deg) for
the complex
lengths in the complex are comparable to those
observed in the mononuclear oxovanadium(V) comꢀ
plexes with octahedral coordination [22–26]. The
angular distortion in the octahedral environment
around V comes from the fiveꢀ and sixꢀmembered
chelate rings taken by the hydrazone ligand. For the
same reason, the trans angles significantly deviate
Bond
d
, Å
Bond
d, Å
V(1)–O(1)
V(1)–O(3)
V(1)–O(5)
1.885(4) V(1)–O(2)
2.184(5) V(1)–O(4)
1.591(5) V(1)–N(1)
1.966(4)
1.845(4)
2.091(5)
from the ideal values of 180
dral coordination can be observed from the coordinate
bond angles, ranging from 75.2(2) to 102.8(2) for the
perpendicular angles and from 156.4(2) to 172.2(2)
°
. Distortion of the octaheꢀ
Angle
ω
, deg
Angle
ω
, deg
°
°
O(5)V(1)O(4)
O(4)V(1)O(1)
O(4)V(1)O(2)
O(5)V(1)N(1)
O(1)V(1)N(1)
O(5)V(1)O(3)
O(1)V(1)O(3)
N(1)V(1)O(3)
96.2(2) O(5)V(1)O(1)
100.7(2) O(5)V(1)O(2)
95.6(2) O(1)V(1)O(2)
102.8(2) O(4)V(1)N(1)
83.8(2) O(2)V(1)N(1)
172.2(2) O(4)V(1)O(3)
84.0(2) O(2)V(1)O(3)
84.6(2)
98.9(2)
96.2(2)
156.4(2)
159.5(2)
75.2(2)
76.1(2)
83.4(2)
°
°
for the diagonal angles. The displacement of the
Vatom from the equatorial plane is 0.280(1) Å. The
formation of the coordinate bonds with the V atom,
together with the delocalization of the ligand, leads to
the planarity of the hydrazone moiety. The dihedral
angle between the C(1)–C(6) benzene ring and the
V(1)–N(1)–N(2)–C(8)–O(2) chelate ring is 5.3(2)
The dihedral angle between the benzene ring and the
pyridine ring of the hydrazone ligand is 19.0(3) . The
°
.
°
hydrazone ligand and the benzohydroxamate ligand
are almost perpendicular to each other with a dihedral
angle of 87.7(5) .
The hydrazone ligand showed stretching bands
attributed to C=O, C=N, C–OH, and NH at about
1653, 1619, 1150 and 1223, and 3211 cm–1, respecꢀ
tively. The complex exhibits typical band at 966 cm–1,
assigned to the V=O vibration. The band due to
°
In the crystal structure of the complex, adjacent
two molecules are linked through intermolecular
N(4)–H(4)⋅⋅⋅N(3) hydrogen bonds (N(4)–H(4)
0.90(1), H(4)⋅⋅⋅N(3)i 1.96(5), N(4)⋅⋅⋅N(3)i 2.753(7),
ν
(C=O) was absent in the complex, but new C–O
stretches appeared at 1288 cm–1. This suggests occurꢀ
N(4)–H(4)⋅⋅⋅N(3)i 147(8) (symmetry code: i
x, –1/2 – y,
°
–1/2 +
z), forming dimers (Fig. 2).
rence of ketoꢀimine tautomerization of the ligand durꢀ
C(12)
C(13)
C(5)
C(6)
Br(2)
N(2)
C(7)
C(9)
N(3)
N(1)
C(1)
O(5)
C(4)
C(11)
C(8)
C(10)
C(3)
C(2)
O(2)
O(3)
C(20)
V(1)
O(1)
Br(1)
C(19)
O(4)
N(4)
C(18)
C(17)
C(14)
C(15)
C(16)
Fig. 1. ORTEP plot of the crystal structure of the complex. Displacement ellipsoids of nonꢀhydrogen atoms are drawn at the 30%
probability level.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 40
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508
SHENG et al.
z
y
0
x
Fig. 2. Packing diagram of the complex. Hydrogen bonds are shown as dashed lines.
Weight, %
100
80
60
40
20
0
200
400
600
800
Temperature,
1000
°
C
Fig. 3. DT curve of the complex.
ing complexation. The
ν
(C=N) absorption observed completed at 480 C. The total observed weight loss of
°
at 1619 cm–1 in the free hydrazone ligand shifted to 86.1% is close to the calculated value of 84.8% for the
1601 cm–1 for the complex upon coordination to formation of V2O5 as the final product.
V atom. The weak peaks in the low wave numbers at
The results of the urease inhibition are summarized
495 and 590 cm–1 may be attributed to V–O and V–N
in Table 3. Compared with the reference inhibitor aceꢀ
bonds in the complex.
tohydroxamic acid (AHA), the free hydrazone comꢀ
Differential thermal (DT) analysis was conducted pound and the vanadyl sulfate have very weak interacꢀ
to examine the stability of the complex (Fig. 3). The tions against the urease. The complex at concentration
complex started to decompose at about 70
°
C and of 100
percent inhibition of 73.6 3.5 and with IC50 value of
10.5
mol L–1. It is clear that the activity of the comꢀ
μ
mol L–1 has urease inhibitory activity with
μ
Table 3. Inhibition of urease by the tested materials*
Tested materials Percent inhibition IC50,
mol L–1
10.5
plex is stronger than that of vanadyl sulfate and H2L,
and even near to that of AHA.
μ
In summary, a new oxovanadium(V) complex with
the tridentate hydrazone ligand N'ꢀ(3,5ꢀdibromoꢀ2ꢀ
hydroxybenzylidene)isonicotinohydrazide and the
bidentate ligand benzohydroxamate has been preꢀ
pared and structurally characterized. The complex
may be used as a potential urease inhibitor with the
Complex
H2L
73.6 3.5
10.2 2.1
26.5 1.9
88.2 4.0
Vanadyl sulfate
AHA
220
37.5
–1
IC50 value of 10.5
mol L–1.
μ
* Concentration of the tested material is 100
µ
mol L
.
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SYNTHESIS, CRYSTAL STRUCTURE, AND UREASE INHIBITION
509
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