Difluorovanadium(IV) dicarboxylates: Coordination behavior and biological activity

Article abstract of DOI:10.1134/S1070328407080052

Different vanadium(IV) complexes of general formula VF₂L ₂ have been synthesized, where L are various nonsteroidal antiinflammatory drugs. The complexes are characterized by elemental analysis, UV-visible, and infrared spectroscopy.

Full text of DOI:10.1134/S1070328407080052

ISSN 1070-3284, Russian Journal of Coordination Chemistry, 2007, Vol. 33, No. 8, pp. 576–581. © Pleiades Publishing, Ltd., 2007.
Difluorovanadium(IV) Dicarboxylates: Coordination Behavior
and Biological Activity1
R. Ashrafa, S. Shahzadia, S. Alia, M. H. Bhattib, S. Yaquba, and F. Ahmadc
a Department of Chemistry, Quaid-i-Azam University, 45320-Islamabad, Pakistan
b Department of Chemistry, Allama Iqbal Open University, H / 8 Islamabad, Pakistan
c NESCOM, Islamabad, Pakistan
E-mail: drsa54@yahoo.com
Received June 20, 2006
Abstract—Different vanadium(IV) complexes of general formula VF2L2 have been synthesized, where L are
various nonsteroidal antiinflammatory drugs. The complexes are characterized by elemental analysis, UV-vis-
ible, and infrared spectroscopy. The metal contents estimated by the ICP-AES method in the synthesized com-
plexes are in good agreement with their calculated values and spectroscopic data proposed the octahedral ge-
ometry for the reported complexes. Conductance measurements show the nonelectrolytic nature of complexes.
Biological screening tests against different bacteria and fungi show significant antibacterial and antifungal ac-
tivity for all the complexes.
DOI: 10.1134/S1070328407080052
1
Recently, vanadium and its compounds came to in their biological activity as compared to its parent
focus in many areas including the medical and biologi- ligand [7]. The vanadium complexes have potential
cal sciences due to their discovered biochemical activ- antitumor activity. The vanadium complexes are also
ity [1, 2]. Vanadium in its oxidation state +4 is able to used as anti diabetic and anticarcinogenic agents.
interact with metal ion binders of biological system Among the complexes of vanadium in the oxidation
containing negatively charged oxygen donors, such as state +4, and mostly the oxovanadium complexes with
phenolates, phosphates, and carboxylates [3, 4].
NSAIDS were reported and found to be successful
antidiabetic agents, and show other biological activities
[8]. In the present investigation, we describe the synthe-
sis and characterization of some new complexes of
vanadium(IV) with NSAIDs taking vanadium(IV) fluo-
ride as a precursor. Moreover, the antibacterial and anti-
fungal activity of these complexes were also checked.
Nonsteroidal anti-inflammatory drugs (NSAIDS)
are medications having pain relieving, as well as, the
effect of reducing inflammation when used over a
period of time. The major clinical application is their
action as anti-inflammatory agents in muscle skeletal
diseases [5]. It is well known that most of anti-inflam-
matory drugs are carboxylic acids in which the carbox-
ylate group is available for metal ligand interaction [6].
Mefenamic acid (2-[(2,3-dimethylphenyl)amino]ben-
zoic acid), ketoprofen (2-(3-benzoylphenyl)propionoic
acid), flurbiprofen (2-(2-fluro-4-biphenyl)propanoic
acid), pefloxacin (l-ethyl-6-fluoro-1,4-dihydro-7-(4-
methyl-1-piperazinyl)-4-oxo-3-quinoline), ibuprofen
(2-(4-isobutylphenyl)propanoic acid), cetrizine dihy-
drogenchloride (2-[4-[(4-chlorophenyl)phenylmethyl]-
1-piperazinyl]ethoxy acetic acid), diclofenac acid
(2-[(2,6-dichlorophenylamino)phenyl]ethanoic acid),
and warfarin acid (4-oxo-3-(oxo-1-phenylbutyl)2H-1-
benzopyran-2-one) are different nonsteroidal antiin-
flammatory drugs. Several transition metal complexes
with NSAIDS have extensively been studied. Vanadium
forms complexes with NSAIDS that are more effective
EXPERIMENTAL
Materials and instrumentation. All the reagents
and solvents were commercially available (highest
grade) and used without further purification. Vanadium
tetrafluoride was purchased from Aldrich. Mefenamic
acid was kindly supplied by the Ferozsons Laboratories
Ltd. (Nowshera, Pakistan), while diclofenac sodium
was given by Wilson Pharmaceuticals (Islamabad).
Pefloxacin, cetrizine dihydrogenchloride and warfarin
sodium were kindly supplied by Shaigan Pharmaceuti-
cals (Pvt.) (Rawalpindi). Flurbiprofen was donated by
Upjohn Pakistan (Pvt.) Ltd. (Islamabad). Ketoprofen
and ibuprofen were supplied by Werrick Pharmaceuti-
cals (Islamabad).
Melting points were determined in a capillary tube
on an electrothermal melting point apparatus (model
1
The article was submitted by the authors in English.
576

DIFLUOROVANADIUM(IV) DICARBOXYLATES
577
Sanyo Gallen Kamp MPD-350 BM 3.5) and were in 25 ml of methanol was added into the reaction flask
uncorrected. UV-visible spectra were recorded on a
UV-visible spectrophotometer (Shimadzu, model
TCC-240A). Infrared spectra were recorded in a range
of 4000–400 cm–1 as KBr pellets and as thin film on a
Bio-Red Elmer 16 FPC FTIR spectrophotometer. Con-
ductance measurements were made using an EC meter
(model Cyber Scan 500).
dropwise with constant stirring. The reaction mixture
had pH 3. The resulting mixture was refluxed for 2 h
and kept overnight with stirring at room temperature.
The solvent was removed on a rotary apparatus under
reduced pressure. The solid product was recrystallized
in a methanol-n-hexane (1 : 1) mixture. The general
chemical reaction is given below:
General procedure for the synthesis of the vana-
dium(IV) complexes. Method 1. A solution of a drug
(2 mmol) in 50 ml of methanol was prepared and placed
in a 250-ml two-necked round-bottom flask equipped
with a water condenser, a magnetic stirrer, and a hot
(i) Dry methanol;
VF4 + 2RCOOH
V(RCOO)2F2,
(ii) Reflux for 2 h;
(iii) Overnight stirring
plate. Then, vanadium tetrafluoride (1 mmol) dissolved where R = R1−R6.
O
C
CH
NH
CH3
H3C
CH3
(R1)
(R2)
H3C
N
C2H5
N
F
N
CH
CH3
F
O
(R3)
(R4)
H3C
H3C
CH CH2
CH
CH3
(R5)
Cl
CH
N
N CH2 CH2 O CH2
(R6)
Method 2. Ligands in the form of sodium salt were method mentioned above. The general chemical reac-
tions are given below:
converted to the corresponding acid by dissolving them
in distilled water, and concentrated HCl was added
dropwise. White precipitates obtained were washed
with distilled water, in dried air, and checked for the
HClconc
HClconc
RCOONa + H2O
RCOOH + NaCl,
ROH + NaCl,
RNa + H2O
melting point. The complexes were synthesized by the where R = R7, R8.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 33 No. 8 2007

578
ASHRAF et al.
Table 1. The elemental analysis data and some physical properties of the vanadium(IV) complexes
Contents (calcd/found), %
Mol. Yield,
ΩM ,
Compound Empirical formula
M.p., °C
weight
%
Ohm–1 cm2 mol–1
C
H
N
V**
I
VF2C30H28O4N2
VF2C32H26O6
VF4C30H24O4
VF4C34H38O6N6
VF2C26H34O4
569
595
575
753
499
70
72
75
76
80
82
75
77
226–8
*
0.049
0.045
0.015
0.262
0.052
0.082
0.199
0.043
63.2/63.4 4.9/4.7 4.9/5.0 8.95/8.63
64.5/64.1 4.3/4.8
II
III
IV
V
94–6
224–6
86–8
142–6
162–6
170
62.6/62.1 4.1/4.6
8.60/8.37
54.1/53.9 5.0/5.8 11.1/11.7 6.78/6.39
62.5/62.9 6.8/6.1
10.20/10.41
VI
VII
VIII
VF2C42H52O6N4Cl6 1010
VF2C28H20O4N2Cl4 679
49.9/50.4 5.1/4.8 5.5/5.9
49.4/49.8 2.9/3.1 4.1/4.5 8.38/8.53
64.8/64.1 4.2/4.9 7.25/7.99
VF2C38H30O8
703
Notes: * Gel-like state.
** The estimation of vanadium was done by using atomic emission spectroscopy (ICP−AES).
it is generally a shoulder, so that its maximum position
is known with least accuracy [11]. All other bands
above 30000 cm–1 are charge-transfer in origin.
Cl
Cl
CH2
NH
The assignments of electronic absorption spectral
bands of the vanadium(IV) complexes were a matter of
controversy [12, 13]. According to ordering of the
energy levels (Ballhausen and Gray scheme), band I in
a range of 11737–13003 cm–1 results from the B2
(R7)
O
O
O
E transition. Band II in a range of 16556–17730 cm–1
CH3CO CH2 CH
C6H5
is assigned to the B2
B1 transition, and band III in a
range of 25062–28490 cm–1 is attributed to the B2
transition. The shift of the B2 E and B2
A1
B1
(R8)
bands to the red and blue regions, respectively, com-
pared with that of VF4, agrees with carboxylate coordi-
nation to the metal center [14, 15]. Other bands above
30000 cm–1 are charge-transfer in origin.
RESULTS AND DISCUSSION
Infrared spectroscopy. The most important fea-
tures of the infrared spectra of the complexes and cor-
responding free ligands are shown in Table 3. The pres-
ence of various ring vibrations and C–H absorption
makes the spectra fairly complicated for complete
assignments of individual bands. The important absorp-
tion frequencies are ν(O–H), ν(N–H), ν(C=O),
νas(COO), νs(COO), ν(V–O), and ν(V–F). The values
assigned to these bands are in accordance with the val-
ues reported in literature [16, 17]. The complexation of
vanadium(IV) fluoride with the ligands is confirmed by
the disappearance of the ν(O–H) band in the spectra of
the complexes occurring at 3440–3405 cm–1, which is
characteristic of carboxylic acids. The complexation of
Physical properties. The reaction of vanadium(IV)
fluoride with nonsteroidal antiinflammatory drugs in
dry methanol at pH 3 resulted in the formation of com-
plexes of general formula VF2L2 (where L are L1–L8 in
complexes I–VIII, respectively). The synthesized com-
plexes were in the crystalline solid/gel-like state, green-
colored, and fairly stable at room temperature. They
show good solubility in common organic solvents. The
molar conductance values of all the synthesized com-
plexes determined in methanol at room temperature
suggest the nonelectrolytic nature of the complexes.
The elemental analysis data and some physical proper-
ties of vanadium(IV) complexes are given in Table 1.
The UV-visible spectra for all the synthesized vanadium with an oxygen donor ligand is also con-
complexes were recorded in methanol and are shown in firmed by the appearance of the ν(V–O) band in the
Table 2. The vanadium(IV) complexes generally range 595–504 cm–1. The ν(V–F) band appeared in the
exhibit three bands due to d–d transitions. These bands range 484–400 cm–1. The ν(COO) stretching vibrations
are not well developed. It seems more probable that the are important to predict the bonding mode of the ligand.
first two transitions lie under the envelope of the band I The peak for ν(COO) in the region 1741–1630 cm–1 for
[9]. Band III is not observed but is thought to be buried carboxylic acids was shifted to lower-frequency side
beneath the low-energy tail of the strongly intense showing complexation. The lowering of νas(COO) and
charge-transfer band [10], and when it is observed that rise of νs(COO) for the carboxylate group show the
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 33 No. 8 2007

DIFLUOROVANADIUM(IV) DICARBOXYLATES
579
204−130 cm–1 and shows that the ligands is bidentate.
The strong bands observed at 1707–1730 cm–1 can be
assigned to ν(C=O) of other than carboxylate group
ligands L2, L4, and L8, which remains practically
unchanged after complexation. The overall IR spectral
evidence suggests that all the ligands act as bidentate
and are coordinated through the carboxylic oxygen
atoms, forming an octahedral structure.
Table 2. UV-visible spectral data for the vanadium(IV) com-
plexes
Absorption bands (ν, cm–1)
Com-
pound
charge-
transfer
bands
band I
band II
band III
2B2
2E
2B2 2B1
2B2 2A1
I
12484
12658
12468
11737
12391
13003
12269
12556
16752
17530
28490
27777
35842
44943
41841
47619
33557
39215
35842
45454
36764
45454
36630
42553
35842
45454
35211
43859
Thermal analyses data confirms the bidentate nature
of ligand in vanadium(IV) complexes in solid state too.
The thermocomposition data can be directly received at
author Saqip Ali–e-mail: drsa54@yahoo.com
II
III
IV
V
Biological activity. All the synthesized complexes
were estimated for their microbial toxicity against a set
of bacterial and fungal strains. The antibacterial activity
of the complexes was tested using the agar well-diffu-
sion method [19], and the results are given in Table 4.
The results show that all the complexes have significant
antibacterial activity.
16778
16750
27777
27777
25510
27777
25062
VI
VII
VIII
17730
16556
The antifungal tests were carried out by using the
agar tube dilution protocol method [20]. The antifun-
gal results of the synthesized complexes are given in
Table 5. All the complexes showed significant antifun-
gal activity against Trichophyton longifusus, Candida
albicans, Fusarium solani and Candida glaberata.
The complexes show moderate activity against Micro-
sporum canis. All the complexes are inactive against
bidentate nature of the ligand in the complexes [18].
The difference ∆ν of νas(COO) and νs(COO) stretching
values for complexes I–VII fall in the range Aspergillus flavus.
Table 3. Infrared spectral data (cm–1) for ligands and their vanadium(IV) complexes
ν(COO)
Compound
ν(O–H)
ν(N–H)
∆ν
ν(V–O)
ν(V–F)
ν(C=O)
asym.
sym.
L1
I
L2
3415
3313
3310
1652
1577
1697
1653
1702
1692
1630
1577
1719
1710
1741
1624
1724
1693
1329
1385
1379
1449
1383
1478
1269
1385
1420
1510
1434
1425
1420
1504
323
192
318
204
319
130
361
192
299
200
307
199
304
189
569
595
575
528
586
510
580
504
475
484
471
463
421
476
400
441
3439
3405
3440
3426
3415
3415
3415
1730
1723
II
L3
III
L4
IV
L5
V
L6
VI
L7
VII
L8
VIII
1717
1715
3324
3324
1707
1707
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 33 No. 8 2007

580
ASHRAF et al.
Table 4. Antibacterial activity data for vanadium(IV) complexes
Zone of inhibition, mm
Name of bacteria*
standard
drug**
I
II
III
IV
V
VI
VII
VIII
Escherichia coli
Bacillus subtilis
Shigella flexenari
Staphylococcus aureus
Pseudomonas aeruginosa
Salmonella typhi
30
28
25
25
10
20
25
24
24
25
20
20
25
24
24
25
20
20
25
30
25
25
25
25
25
25
20
20
20
20
25
25
25
22
20
15
18
15
20
20
20
20
20
20
20
18
22
20
30
33
27
33
24
25
Notes: * Concentration of sample is 3 mg/ml of DMSO.
** Imipenum is 10 µg/disc.
Table 5. Antifungal activity*,** data for the vanadium(IV) complexes
Inhibition, %
Name of fungus
MIC***,
µg/ml
I
II
III
IV
V
VI
VII
VIII
standard drug
Trichophyton longifusus
Candida albicans
Aspergillus flavus
Microsporum canis
Fusarium solani
40
60
0
40
40
0
45
60
0
35
75
0
35
75
0
65
75
0
40
75
0
70
75
0
Miconazole
Miconazole
70
110.8
Amphotericum B 20
60
55
65
0
40
30
65
0
0
0
0
30
50
75
Miconazole
Miconazole
Miconazole
98.4
0
40
60
40
75
50
70
40
75
73.25
110.8
Candida glaberata
60
Notes: * Incubation period 7 days.
** Incubation temp. 27°C.
*** Concentration of sample 200 µg/ml of DMSO.
Symponsium Series 711, Washington: ACS Publishers,
So by interpreting the spectroscopic results, we pro-
posed the octahedral geometry for synthesized com-
plexes I–VIII:
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ACKNOWLEDGMENT
This work was supported by the Higher Education
Commission (Islamabad), project No. 20-130/Acad
(R)/03-415.
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