Synthesis, spectroscopic, thermal Studies, antimicrobial activities and crystal structures of Co(II), Ni(II), Cu(II) and Zn(II)-orotate complexes with 2-methylimidazole

Article abstract of DOI:10.1016/j.poly.2009.06.052

The 2-methylimidazole complexes of Co(II), Ni(II), Cu(II) and Zn(II) orotates, mer-[Co(HOr)(H₂O)₂(2-meim)₂] (1), mer-[Ni(HOr)(H₂O)₂(2-meim)₂] (2), [Cu(HOr)(H₂O)₂(2-mei

Full text of DOI:10.1016/j.poly.2009.06.052

Polyhedron 28 (2009) 3087–3093
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis, spectroscopic, thermal Studies, antimicrobial activities
and crystal structures of Co(II), Ni(II), Cu(II) and Zn(II)-orotate complexes
with 2-methylimidazole
b
c
Hakan Erer a, Okan Zafer Yeßsilel a, , Cihan Darcan , Orhan Büyükgüngör
*
a Eskißsehir Osmangazi University, Faculty of Arts and Sciences, Department of Chemistry, 26480 Eskißsehir, Turkey
b Dumlupınar University, Faculty of Arts and Sciences, Department of Biology, 43010 Kütahya, Turkey
c Ondokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139 Samsun, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
The 2-methylimidazole complexes of Co(II), Ni(II), Cu(II) and Zn(II) orotates, mer-[Co(HOr)(H2O)2(2-
meim)2] (1), mer-[Ni(HOr)(H2O)2(2-meim)2] (2), [Cu(HOr)(H2O)2(2-meim)] (3) and [Zn(HOr)(H2O)2(2-
meim)] (4), were synthesized and characterized by elemental analysis, spectral (UV–Vis and FT-IR)
methods, thermal analysis (TG, DTG and DTA), magnetic susceptibility, antimicrobial activity studies
and single crystal X-ray diffraction technique. The complexes 1 and 2 have distorted octahedral geome-
tries with two monodentate 2-methylimidazole and one bidentate orotate and two aqua ligands. The
complexes 3 and 4 have distorted square pyramidal and trigonal bipyramidal geometry, respectively,
with one 2-methylimidazole, bidentate orotate and aqua ligands. The orotate coordinated to the metal(II)
ions through deprotonated nitrogen atom of pyrimidine ring and oxygen atom of carboxylate group as a
bidentate ligand. The antimicrobial activities of 1 and 4 were found to be more active gram (+) than gram
(ꢀ) and 4 could be use for treatment Staphylococcus aureus.
Received 5 May 2009
Accepted 19 June 2009
Available online 27 June 2009
Keywords:
Orotate complexes
2-Methylimidazole complexes
Antimicrobial activity
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
substituents have been screened as therapeutic agents for cancer
[7–12].
Supramolecular compounds have received much attention in
coordination chemistry because of novel structural topologies
and potential applications [1–3]. The non-covalent forces include
Besides its important biological role, the mono- and dianion of
orotic acid (H2Orꢀ and HOr2ꢀ) are potentially polydentate ligands.
It may coordinate through two nitrogen atoms of the pyrimidine
ring, two carbonyl oxygen atoms and carboxyl group [13–44]. It
was found that, in neutral or slightly acidic environment, it coordi-
nates through the carboxylate group [25–27] while in basic sur-
roundings it coordinates through the carboxylate and the adjacent
hydrogen bonds and
pꢁ ꢁ ꢁp interactions have been used extensively
in the development of supramolecular chemistry. In the construc-
tion of new supramolecular complexes based the pyrimidine car-
boxylate ligands are of special interest, because they can be
regarded not only as hydrogen bonding acceptors but also as
hydrogen bonding donors, depending upon the number of deproto-
nated groups [4]. In the present work, we selected the potentially
interesting orotic acid (1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidine-
carboxylic acid, vitamin B13, H3Or) that is a member of pyrimidine
carboxylates. It is a useful tool for constructing crystalline architec-
tures because of its proton donating and accepting capabilities for
nitrogen atom [17]. In the mer-[Mn(l-HOr)(H2O)(2-meim)2]n [16],
[Ni(HOr)(H2O)3], [M(HOr)bipy(H2O)] (M = Mn(II), Co(II)) [17], [Co
(HOr)(OH)(H2O)(NH3)]n and [Ni(HOr)(OH)(H2O)2(NH3)]n complexes
[28], the orotate anion acts as a bridging ligand between the metal
ions forming one-dimensional polymeric chains, its coordination
sites being the carboxylate and the nitrogen atom of pyrimidine ring
and carbonyl oxygen atom. In the polymeric [Cu(HOr)(H2O)2]n [29]
and [Cu(HOr)(ba)2]n [30] complex, molecules form chains in a way
that the carboxylate group acts as a bridge between metal ions
and the orotato-group being tridentate.
Recently, we have reported the synthesis and structures of oro-
tate complexes of K(I) [15], Mn(II) [5,16], Co(II) [18,19,31–33],
Ni(II) [19,34–39], Cu(II) [18,38–43], Zn(II) [44] and Cd(II) [20,45]
with different aromatic amines.
hydrogen bonds and
p p interactions [4,5].
ꢁ ꢁ ꢁ
Metal orotates are also widely applied in medicine and they
have been used e.g. as uricosurica (for enhanced excretion of uric
acid) and for electrolyte substitution (in heart and liver protection)
[6]. Platinum, palladium and nickel orotates with wide variety of
In the present paper, we describe the syntheses, spectroscopic
(IR and UV–Vis), thermal studies (TG, DTG, DTA), antimicrobial
* Corresponding author. Tel.: +90 2222393750; fax: +90 2222393578.
E-mail address: yesilel@ogu.edu.tr (O.Z. Yesßilel).
0277-5387/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2009.06.052

3088
H. Erer et al. / Polyhedron 28 (2009) 3087–3093
of Medicine) were used for the antimicrobial assays. Antimicrobial
O
C
activity tests were carried out using the broth dilution method as
described by the NCCSL standards [50]. All stock solutions of the
orotic acid and the complexes were prepared in dimethylsulfoxide
(DMSO, Merck) according to the needed concentrations for
experiments.
For the broth dilution method, cultures were grown in 5 mL
nutrient broth (Merck) at 37 °C for 18 h in an orbital shaker incu-
bator shaking at 175 rpm. These cultures were used as starter cul-
tures. Initial bacterial concentrations (approximately 5 ꢂ 105 cfu/
mL) were estimated for the cultures at 600 nm by matching with
0.5 McFarland turbidity standards. Nutrient broth containing
microorganisms were transferred 1 mL in test tubes and made
OH
(6)
(1)
H
(5)
N
N
(2)
(4)
(3)
O
N
H
O
CH3
N
H
H3Or
2-meim
Scheme 1. Structures of the ligands: H3Or = orotic acid; 2-meim = 2-
methylimidazole.
activities and crystal structures of the orotate complexes of Co(II),
Ni(II), Cu(II) and Zn(II) with 2-methylimidazole ligand (Scheme 1).
twofold serial dilution in nutrient broth from 3000 to 23.4 lg/
mL. The compounds were tested in twofold serial dilution; eventu-
ally the ranges were narrowed to define more exact values. Growth
inhibition was determined by measuring MICs, defined as the low-
est concentration in which microbial growth was prevented. As
indicated by the lack of turbidity or colour change after 24 h of
incubation at 37 °C, represents the mean of at least three determi-
nations. The solvents were also tested for antimicrobial activity.
Standard antibiotics (chloramphenicol, oflaxacin, rifampicin, cefur-
oxime, tetracycline, nystatin) were also tested by disc diffusion
method for the cultures at an optical density at 600 nm by match-
ing with 0.5 McFarland turbidity standards (approximately
106 cfu/mL). Test strains were spread on solid nutrient agar sur-
faces using a sterile glass rod. Standard antibiotic discs were placed
on the agar surface and were incubated 37 °C for 24 h.
2. Experimental
2.1. Preparation of the complexes
A solution of orotic acid monohydrate (0.871 g, 5 mmol) in
water (50 mL) was added dropwise with stirring at 80 °C to a solu-
tion of Co(CH3COO)2ꢁ4H2O (1.25 g, 5 mmol) (1) or Ni(CH3-
COO)2ꢁ4H2O (1.24 g, 5 mmol) (2) or Cu(CH3COO)2ꢁH2O (1.00 g,
5 mmol) (3) or Zn(CH3COO)2ꢁ2H2O (1.09 g, 5 mmol) (4) in distilled
water (25 mL). The solutions immediately became suspensions and
were stirred for 4 h at 60 °C. Then 2-methylimidazole (1.65 g,
20 mmol) for all in water (10 mL) was added dropwise to these
suspensions. The clear solutions that formed were stirred for 2 h
at 60 °C and then cooled to room temperature. The reddish for
(1), green for (2), light blue for (3), colorless for (4) crystals that
formed were filtered and washed with 10 mL of water and dried
in air.
3. Results and discussion
The Co(II), Ni(II) and Cu(II) complexes exhibit magnetic moment
values of 4.66, 2.54 and 1.26 BM which corresponds to three, two
and one unpaired electrons, respectively, which are consistent
with a weak field octahedral geometry as expected. The Zn(II) com-
plex is diamagnetic. All the complexes comprise broad composite
2.2. Materials and measurements
All chemicals used were analytical reagents and were commer-
cially purchased. IR spectra were obtained with a Perkin Elmer 100
FT-IR spectrometer using KBr pellets in the 4000–400 cmꢀ1 range.
The UV–Vis spectra were obtained for an aqueous solution of the
complex (10ꢀ3 M) with a Shimadzu UV-3150 spectrometer in the
range 900–190 nm. Magnetic susceptibility measurements at room
temperature were performed using a Sherwood Scientific MXI
model Gouy magnetic balance. A Perkin Elmer Diamond TG/DTA
Thermal Analyzer was used to record simultaneous TG, DTG and
DTA curves in static air atmosphere at a heating rate of 10 °C minꢀ1
in the temperature range of 30–1000 °C for 1 and 30–700 °C for 2–
4 using platinum crucibles.
*
*
intraligand
bands in the UV region, being due to
p
?
p
and n ?
p
transitions of HOr and 2-meim ligands. The kmax value of the
absorption band in the spectrum of 1 is 499 nm. This value was as-
signed to the following d–d transitions, 4T1g ? 4T2g
. The
4T1g ? 4A2g and 4T1g ? 4T1g(P) transitions were not observed
which are shift to the UV and IR regions, respectively. The UV–
Vis spectrum for 2 exhibits three d–d absorption transitions at
888, 638 and 390 nm which support the octahedral geometry.
These values were assigned to 3A2g ? 3T2g
,
3A2g ? 3T1g
,
3A2g ? 3T1g (P), respectively. The UV–Vis spectrum for 3 exhibits
a broad d–d absorption transition centered at 707 nm. This value
was assigned to a1 ? b1 transition. The colourless Zn(II) complex
does not show d–d bands as expected.
2.3. Crystallographic analyses
Data collection was performed on a STOE IPDS II image plate
The strong and broad absorption bands of m(OH) vibrations of
H2O in complexes are observed between 3402 and 3361 cmꢀ1. IR
spectra of the complexes exhibit a medium intensity and broad
band in the 3272–3178 cmꢀ1 region which can be attributed to
the N–H stretching vibration. The relatively weak two close bands
detector using Mo Ka radiation (k = 0.71073 Å). Data collections:
Stoe X-AREA [46]. Cell refinement: Stoe X-AREA [46]. Data reduc-
tion: Stoe X-RED [46]. The structure was solved by direct-methods
using SIR97 [47] and anisotropic displacement parameters were
applied to non-hydrogen atoms in a full-matrix least-squares
refinement based on F2 using SHELXL-97 [48]. Molecular drawings
were obtained using ORTEP-III [49].
at 2752–2964 cmꢀ1 are due to the
m(CH) vibrations. The strong and
broad bands appeared in the 1653–1623 and 1488–1382 cmꢀ1 re-
gions in all complexes are ascribed to the asymmetric and sym-
metric stretching vibrations of the coordinated carboxylate
groups of the orotate ligand, respectively. Similar absorption val-
ues have already been reported earlier for Ni(II) and Co(II)-orotate
complexes with imidazole and its derivatives [16,19,33,51] and the
positions of these bands have been well described in recently re-
ports [52]. Separation between asymmetric and symmetric
stretching frequencies for complexes range from 167 to 141 cmꢀ1
is in agreement with monodentate coordination mode for the
2.4. Antimicrobial activity studies
Escherichia coli W3110, Pseudomonas aeruginosa ATCC 27853,
Staphylococcus aureus ATCC 6535, Bacillus cereus ATCC 7064, Can-
dida albicans ATCC 10231 and clinical isolate (Methicillin Resistant
S. aureus (MRSA) – Orthopedy Exuda, Pseudomonas aeruginosa –
urology–urine isolates, from Ondokuz Mayıs University, Faculty

H. Erer et al. / Polyhedron 28 (2009) 3087–3093
3089
Table 1
IR data of the complexes.a
Assignmenta
Co(II)b
1
2
3
4
m
m
m
m
m
m
m
(OH)
3544s
3255m
3207m
3087–2971w
1639s
1620s
1483m
1427w; 1373m
522w; 466w
3402s, br
3266m
–
3092sh–2925m
1642s
1623s
1486m
1398m, 1382m
595w, 481m
3361s, br
3268m
3199sh
3104sh–2930m
1651s
1628s
1488s
1399s, 1382m
576m, 487m
3400s
–
NHmeim
NHHOr
CH
3272m
3204w
3120sh, 2925w
1653s
3254sh
3178br
2930w
1651s, br
1628s
1484m
1392s
583m, 481m
C@Oacid
+
m
m
C@C
C
(2)@O
C
(6)@O +
1626s
C@N
1485m
1399vs
593m
dNH
M–O; M–N
a
Abbreviations: sh, shoulder; w, weak; m, medium; s, strong; vs, very strong; br, broad.
[Co(HOr)(H2O)(4-meim)3] [19].
b
carboxylate group. In IR spectra of the complexes,
m
(OHacid) band at
between 288 and 458 °C orotate ligand is abruptly burnt
(DTA = 423 °C). The total mass loss of all decomposition process
is 77.61% (calc. 76.29%) suggest that CuO is the end product.
2500 cmꢀ1 in the orotic acid completely disappeared and a new
carboxylate band
m(COO) appeared between 1488 and
1382 cmꢀ1, respectively, indicating that the carboxylate group par-
ticipates in the coordination with the metal ions by deprotonation
(Table 1).
3.2. Crystal structures
Details of crystal data, data collection, structure solution and
refinement are given in Table 2. The molecular structures of 1
and 2 with the atom-numbering scheme are shown in Fig. 1. Se-
lected bond lengths and angles together with the hydrogen bond-
ing geometry are collected in Table 3. The structures of 1 and 2
consist of the mer-[M(HOr)2(H2O)2(2-meim)2] (M = Co(II) and
Ni(II)) molecules. Both metal ions are coordinated bidentate oro-
tate ligand thought oxygen atom of carboxylate group and nitrogen
atom of pyrimidine ring, two aqua ligands and two 2-methylimid-
azole ligands. The basal plane of the distorted octahedral is formed
by N1, O4, O5 and O6 atoms. The Co–O (average 2.108 (1) Å), Ni–O
(average 2.071 (1) Å) and Co–N1 (2.138 (1) Å), Ni–N1 (2.087 (1) Å)
bond distances are longer than previously reported values ([Co-
(HOr)(H2O)4]ꢁ2.5H2O [47], [Co(HOr)(en)2](H2Or)ꢁ5H2O [18] and
mer-[Ni(HOr)(H2O)2(ata)2] [43]). However these bond distances
are similar to the corresponding values found in reported [Co-
(HOr)(H2O)3]n, [Ni(HOr)(H2O)3]n [23] and [Ni(HOr)(bipy)] [53]. Dis-
torted octahedral geometry is completed with two nitrogen atoms
by monodentate coordination of two 2-meim ligands (Co1–N3/
N5 = 2.164(2)/2.158(2) and Ni1–N3/N5 = 2.127 (2)/2.123 (2) Å).
The crystal packing of 1 and 2 are stabilized through strong in-
tra- and intermolecular hydrogen bonding interactions (Fig. 2a).
Each HOr ligand is doubly hydrogen bonded forming DA:AD dimer
between the O1, N2 of HOr and the O4 atom of carboxylate group
and aqua ligand (O5) [N2ꢁ ꢁ ꢁO4 = 2.896 (2) for 1, 2.882 (2) for 2 and
O5ꢁ ꢁ ꢁO1 = 2.757 (2) for 1, 2.736 (2) for 2] with a pattern R22ð8Þ in
3.1. Thermal analyses
3.1.1. [Co(HOr)(H2O)2(2-meim)2] (1) and [Zn(HOr)(H2O)2(2-meim)]
(4)
The thermal behaviour of 1 and 4 are quite similar and they
show a three stage mass loss (Supplementary Figs. S1 and S2).
The first stage between 37 and 199 °C for 1, 33 and 212 °C for 4 cor-
responds to the endothermic elimination of two aqua ligands with
an experimental mass loss of 9.06% and 11.19% (calc. mass loss
8.71% and 10.66%). The removal of 2-meim ligands occurs in the
second stage between 199 and 391 °C for 1, 212 and 373 °C for 4
with an experimental mass loss of 40.54% and 23.49% respectively
(calc. mass loss 39.73% and 24.32%). In the last stage, a strong exo-
thermic peak on the DTA curve (DTAmax = 423 and 529 °C, respec-
tively) is associated with decomposition and burning of the orotate
ligands. The overall experimental mass losses, 82.92% for 1 and
75.18% for 4, are in agreement with this stoichiometry. The ther-
mal decomposition products were identified as CoO or ZnO (calc.
81.85% and 75.88%).
3.1.2. [Ni(HOr)(H2O)2(2-meim)2] (2)
The complex 2 shows three stages decomposition process (Sup-
plementary Fig. S3). Although the complex is containing aqua li-
gands, it is stable up to 151 °C. In the first stage, complex 2 starts
to lose aqua ligands between 151 and 225 °C with an experimental
mass loss of 8.71% (calc. mass loss 9.73%). The second stage is re-
lated to the release of two imidazole ligands by giving endothermic
effect (found = 41.11, calc. = 39.74%). This type of behaviour of
Etter’s notation [54]. There are also
pꢁ ꢁ ꢁp interaction between
the symmetry related 2-meim rings [CgA = N(3)–C(6)–C(7)–N(4)–
C(8) and CgB = N(5)–C(10)–C(11)–N(6)–C(12), CgA–CgAi = 3.8251
(i = ꢀx, ꢀy, ꢀz) and CgB–CgBi = 3.9814 Å, i = 1 ꢀ x, 1 ꢀ y, ꢀz)
(Fig. 2b).
methylimidazole ligands in the mer-[Mn(l-HOr)(H2O)(2-meim)2]n
[16] and [Ni(HOr)(H2O)(4-meim)3] [19] complexes have been re-
ported earlier. In the last extremely exothermic stage between
398 and 474 °C orotate ligand is abruptly burnt (DTA = 454 °C).
The total mass loss of all decomposition process is 82.82% (calc.
81.88%) suggest that NiO is the end product.
In pentacoordinated systems, the actual geometry of the com-
plex can be described by a structural index parameter
ꢀ b/60°, where and b are the two largest angles (
Thus, the geometric parameter is applicable to pentacoordinated
structures as an index of the degree of trigonality, within the struc-
tural continuum between trigonal bipyramidal ( = 1) and square
values of 0.20 for
0.60 for
distorted square
s
such that
s
=
a
a
a
> b).
s
3.1.3. [Cu(HOr)(H2O)2(2-meim)] (3)
s
The complex 3 shows four stages decomposition process (Sup-
plementary Fig. S4). In the first stage, the complex starts to lose
one aqua ligand between 37 and 160 °C with an experimental mass
loss of 5.65% (calc. 5.36%). The second stage is related to the release
of other aqua ligand by giving endothermic effect (found = 6.22,
calc. = 5.36 %). The third stage in the temperature range of 246–
288 °C related to release of 2-meim ligand (found 23.42, calc.
24.45%, DTAmax = 267 °C). In the last extremely exothermic stage
pyramidal (
= (169.81 ꢀ 158.00)/60 = 0.20]
= (164.91 ꢀ 128.77)/60 = 0.60], indicating
s
= 0). The complex 3 and 4 have
s
3
[s
and
4
[s
a
bipyramidal and trigonal bipyramidal geometries, respectively
(Fig. 3). The M ion in [M(HOr)(H2O)2(2-meim)] (M = Cu(II) and
Zn(II)) is coordinated by a bidentate HOr ligand, two coordinated
water molecules and one 2-meim ligand [Cu1–N1 = 1.992(2),
Cu1–O4 = 2.073(1), Zn1–O4 = 2.083 (2) and Zn1–N1 = 2.066 (2) Å]

3090
H. Erer et al. / Polyhedron 28 (2009) 3087–3093
Table 2
Crystallographic data and structure refinement parameters for the complexes.
Complexes
1
2
3
4
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C13H18N6O6Co
413.26
monoclinic
P21/c
8.3165 (4)
14.1580 (4)
15.3992 (7)
90
102.478 (4)
90
C13H18N6O6Ni
413.04
monoclinic
P21/c
8.2609 (5)
14.1719 (6)
15.3190 (9)
90
102.791 (5)
90
C9H12N4O6Cu
335.77
C9H12N4O6Zn
337.60
triclinic
triclinic
ꢀ
ꢀ
P1
P1
7.5760 (6)
8.1422 (6)
11.5213 (9)
69.657 (6)
85.372 (6)
77.057 (6)
649.43 (9)
2
7.1751 (5)
8.2451 (6)
11.9655 (8)
73.759 (6)
87.218 (6)
71.923 (5)
645.51 (8)
2
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
1770.35 (13)
4
1.01
1748.93 (17)
4
1.15
Z
l
(mmꢀ1
)
1.71
1.717
1.94
1.737
Dcalc (Mg mꢀ3
)
1.551
1.569
Crystal size (mm)
h Range (°)
0.35 ꢂ 0.30 ꢂ 0.23
1.98–26.5
14 984
3679
0.025
0.028, 0.079
1.04
0.27; ꢀ0.40
0.58 ꢂ 0.49 ꢂ 0.41
1.98–26.5
13 938
3633
0.041
0.028, 0.080
1.07
0.29; ꢀ0.30
0.46 ꢂ 0.33 ꢂ 0.25
1.89–26.5
7124
2677
0.046
0.030, 0.079
1.09
0.57; ꢀ0.56
0.37 ꢂ 0.28 ꢂ 0.14
2.71–26.5
6765
2668
0.047
0.034, 0.091
1.05
0.45; ꢀ0.62
Measured reflections
Independent reflections
Rint
R[F2 > 2
r
(F2)], wR(F2)
Goodness-of-fit on F2
qmin (e Åꢀ3
D
qmax
,
D
)
Table 3
Selected bond distances (Å), angles (°) and hydrogen bonding geometries (Å, °) for 1
and 2.
Bond lengths (Å)
Complex 1
N1–Co1
N3–Co1
N5–Co1
O4–Co1
Co1–O5
Co1–O6
Complex 2
N1–Ni1
N3–Ni1
N5–Ni1
O4–Ni1
Ni1–O5
Ni1–O6
2.138 (1)
2.164 (2)
2.158 (2)
2.104 (1)
2.105 (1)
2.114 (1)
2.0874 (13)
2.1272 (15)
2.1233 (15)
2.062 (1)
2.070 (1)
2.081 (1)
Angles (°)
O4–Co1–O5
O4–Co1–O6
O5–Co1–O6
O4–Co1–N1
O5–Co1–N1
O6–Co1–N1
O4–Co1–N5
O5–Co1–N5
O6–Co1–N5
N1–Co1–N5
O4–Co1–N3
O5–Co1–N3
O6–Co1–N3
N1–Co1–N3
N5–Co1–N3
92.42 (5)
171.52 (5)
95.83 (5)
79.18 (5)
170.23 (5)
92.76 (5)
87.98 (5)
88.50 (6)
90.28 (6)
96.11 (6)
90.88 (5)
88.54 (6)
91.28 (6)
86.63 (5)
176.78 (6)
O4–Ni1–O5
O4–Ni1–O6
O5–Ni1–O6
O4–Ni1–N1
O5–Ni1–N1
O6–Ni1–N1
O4–Ni1–N5
O5–Ni1–N5
O6–Ni1–N5
N1–Ni1–N5
O4–Ni1–N3
O5–Ni1–N3
O6–Ni1–N3
N1–Ni1–N3
N5–Ni1–N3
91.95 (5)
173.61 (5)
93.98 (5)
80.55 (5)
171.01 (5)
93.74 (5)
88.09 (5)
88.86 (6)
89.65 (6)
95.79 (5)
90.98 (5)
88.24 (6)
91.59 (6)
86.95 (5)
176.92 (5)
D–Hꢁ ꢁ ꢁA
Hꢁ ꢁ ꢁA (Å)
Dꢁ ꢁ ꢁA (Å)
D–Hꢁ ꢁ ꢁA (ꢁ)
Complex 1
Fig. 1. Ortep III view of 1 and 2 with the atom-numbering scheme (M = Co1 and
N2–H2ꢁ ꢁ ꢁO4i
N6–H6Cꢁ ꢁ ꢁO2ii
N4–H4ꢁ ꢁ ꢁO3iii
O6–H6Bꢁ ꢁ ꢁO1
O5–H5Bꢁ ꢁ ꢁO2iv
O5–H5Aꢁ ꢁ ꢁO1v
O6–H6Aꢁ ꢁ ꢁO3vi
2.04
2.10
2.03
1.939 (16)
1.858 (17)
1.899 (16)
1.888 (17)
2.8960 (18)
2.906 (2)
2.843 (2)
2.7373 (19)
2.6689 (18)
2.7572 (19)
2.7065 (18)
177
156
157
156 (2)
166 (2)
175 (2)
169 (2)
Ni1).
(Table 4). These distances are found to be similar to those of previ-
ously reported complexes [7,18,41,55]. The dihedral angle between
the pyrimidine and imidazole rings is 67.65 Å for 3 and 66.79 for 4.
The C5–O4 bond distance (1.260 Å for 3 and 1.251 Å for 4) is longer
than C5–O3 bond distance (1.240 Å for 3 and 1.241 Å for 4) in HOr
ligand due to the coordination of M(II) ion.
The presence of aqua ligands and carboxyl or carbonyl groups
make extensive hydrogen bonding interactions in complexes 3
and 4, which are listed in Table 4. Each of the HOr ligand is doubly
hydrogen bonded to corresponding ligands of a neighbouring HOr
ligand, forming DA:AD dimer [N2ꢁ ꢁ ꢁO2i = 2.830 (2) for 3 and 2.897
(3) Å for 4, N2–H2ꢁ ꢁ ꢁO2i = 172 for 3 and 170° for 4, (i) ꢀx + 2, ꢀy,
z + 1 for 3 and x + 2, ꢀy, ꢀz + 1 for 4]. These arrangement gives rise
Complex 2
N2–H2ꢁ ꢁ ꢁO4i
N6–H6Cꢁ ꢁ ꢁO2ii
N4–H4ꢁ ꢁ ꢁO3iii
O6–H6Bꢁ ꢁ ꢁO1
O5–H5Bꢁ ꢁ ꢁO2iv
O5–H5Aꢁ ꢁ ꢁO1v
O6–H6Aꢁ ꢁ ꢁO3vi
2.02
2.09
2.02
1.938 (16)
1.851 (17)
1.935 (16)
1.906 (18)
2.8818 (19)
2.900 (2)
2.830 (2)
2.7358 (18)
2.6661 (18)
2.7730 (19)
2.7150 (17)
177
156
156
155 (2)
166 (2)
176 (2)
165 (2)
Symmetry codes: (i) x, ꢀy + 1/2, z + 1/2; (ii) ꢀx + 1, yꢀ1/2, ꢀz + 3/2; (iii) ꢀx + 1,
ꢀy + 1, ꢀz + 1; (iv) xꢀ1, ꢀy + 1/2, zꢀ1/2; (v) x, ꢀy + 1/2, zꢀ1/2; (vi) xꢀ1, y, z for 1
and 2.

H. Erer et al. / Polyhedron 28 (2009) 3087–3093
3091
Fig. 3. Ortep III view of 3 and 4 with the atom-numbering scheme (M = Cu1 and
Zn1).
Table 4
Selected bond distances (Å), angles (°) and hydrogen bonding geometries (Å, °) for 3
and 4.
Bond lengths (Å)
Complex 3
N1–Cu1
N3–Cu1
O4–Cu1
Cu1–O6
Cu1–O5
Complex 4
N1–Zn1
N3–Zn1
O4–Zn1
Zn1–O5
Zn1–O6
1.992 (2)
1.961 (2)
1.973 (2)
1.994 (2)
2.204 (2)
2.066 (2)
2.008 (3)
2.083 (2)
1.988 (2)
2.071 (2)
Angles (°)
N3–Cu1–O4
N3–Cu1–N1
O4–Cu1–N1
N3–Cu1–O6
O4–Cu1–O6
N1–Cu1–O6
N3–Cu1–O5
O4–Cu1–O5
N1–Cu1–O5
O6–Cu1–O5
90.81 (7)
169.81 (7)
81.50 (6)
92.51 (7)
158.00 (9)
92.20 (7)
94.21 (7)
103.90 (7)
94.13 (7)
97.54 (8)
O5–Zn1–N3
O5–Zn1–N1
N3–Zn1–N1
O5–Zn1–O6
N3–Zn1–O6
N1–Zn1–O6
O5–Zn1–O4
N3–Zn1–O4
N1–Zn1–O4
O6–Zn1–O4
112.7 (1)
128.8 (1)
117.97 (9)
88.22 (9)
97.98 (10)
91.96 (8)
87.61 (9)
97.01 (9)
79.44 (8)
164.91 (9)
D–Hꢁ ꢁ ꢁA
Hꢁ ꢁ ꢁA (Å)
Dꢁ ꢁ ꢁA (Å)
D–Hꢁ ꢁ ꢁA (°)
Complex 3
N2–H2ꢁ ꢁ ꢁO2i
N4–H4ꢁ ꢁ ꢁO3ii
N4–H4ꢁ ꢁ ꢁO4ii
O5–H5Aꢁ ꢁ ꢁO1iii
O5–H5Bꢁ ꢁ ꢁO2iv
O6–H6Aꢁ ꢁ ꢁO1
O6–H6Bꢁ ꢁ ꢁO3v
1.98
2.02
2.61
1.961 (19)
1.965 (18)
1.83 (2)
1.884 (19)
2.830 (2)
2.870 (3)
3.194 (2)
2.798 (2)
2.783 (2)
2.633 (3)
2.715 (2)
172
169
126
171 (3)
170 (4)
157 (3)
168 (4)
Complex 4
N2–H2ꢁ ꢁ ꢁO2i
N4–H4ꢁ ꢁ ꢁO3ii
O6–H6Bꢁ ꢁ ꢁO3iii
O5–H5Bꢁ ꢁ ꢁO1iv
O5–H5Aꢁ ꢁ ꢁO2v
O6–H6Aꢁ ꢁ ꢁO1
2.05
1.98
1.86 (2)
1.89 (2)
1.89 (2)
1.83 (2)
2.897 (3)
2.822 (3)
2.680 (3)
2.686 (3)
2.706 (3)
2.634 (3)
170
166
179 (4)
165 (5)
175 (5)
162 (4)
Fig. 2. Part of the crystal structure of 1 and 2, showing the formation of hydrogen
bonding [2-meim ligands are omitted] (a) and
omitted] (b).
pꢁ ꢁ ꢁp interaction [H atoms are
Symmetry codes: (i) x, ꢀy + 1/2, z + 1/2; (ii) ꢀx + 1, y ꢀ 1/2, ꢀz + 3/2; (iii) ꢀx + 1,
ꢀy + 1, ꢀz + 1; (iv) xꢀ1, ꢀy + 1/2, zꢀ1/2; (v) x, ꢀy + 1/2, zꢀ1/2; (vi) xꢀ1, y, z for 3
and (i) ꢀx + 2, ꢀy, ꢀz + 1; (ii) ꢀx, ꢀy + 1, ꢀz; (iii) ꢀx + 1, ꢀy + 1, ꢀz + 1; (iv) ꢀx + 1,
ꢀy, ꢀz + 1; (v) x, y + 1, z for 4.
to eight membered rings that can be described as R22ð8Þ [54]
(Fig. 4). These intermolecular hydrogen bonding interactions are
very important in the construction of the crystal edifice of com-
plexes 3 and 4. Similar orotate complexes containing double
hydrogen bonding interactions were reported [41–45]. In addition,
and 3.895 Å for 4 (i = ꢀx, 2 ꢀ y, ꢀz). All of these intermolecular
interactions give three-dimensional framework results (Fig. 5).
the layers are interlinked together into a network by
p
ꢁ ꢁ ꢁ
p
interac-
3.3. Antimicrobial activities
tions between both pyrimidine rings of orotate ligand [CgA = N(1)–
C(1)–N(2)–C(2)–C(3)–C(4)] (CgAꢁ ꢁ ꢁCgAi) is 3.863 Å for 3 (i = 1 ꢀ x,
1 ꢀ y, z) and 4.011 Å for 4 (i = 1 ꢀ x, ꢀy, 1 ꢀ z) and imidazole rings
[CgB = N(3)–C(6)–C(7)–N(4)–C(8)], the contact distance of two
adjacent aromatic rings (CgBꢁ ꢁ ꢁCgBi) is 3.763 for 3 (ꢀx, 2 ꢀ y, ꢀz)
The complexes were tested for their in vitro antimicrobial activ-
ities against two Gram-positive bacteria (S. aureus and B. cereus),
two Gram-negative bacteria (E. coli and P. aeruginosa), one fungi
C. albicans and two clinical isolate (MRSA and P. aeruginosa). For

3092
H. Erer et al. / Polyhedron 28 (2009) 3087–3093
Fig. 4. The
pꢁ ꢁ ꢁp and hydrogen bonding interactions of 3 and 4.
ied microorganism were approximately 1000
lg/mL exception B.
cereus (750 g/mL). The antimicrobial activities of 5 and 8 are high-
l
er than the orotic acid, 6 and 7 on the all tested microorganisms.
While MIC values of 6 according to orotic acid was decreased at
E. coli (from 1375 to 750
mL), C. albicans (from 2000 to 750
creased P. aeruginosa (from 1000 to 1500
750 to 1000 g/mL), MRSA (from 1000 to 1800
late P. aeruginosa (from 1000 to 1250 g/mL). Compared to the oro-
l
g/mL), S. aureus (from 1000 to 750
g/mL), its activity was in-
g/mL), B. cereus (from
g/mL) clinical iso-
lg/
l
l
l
l
l
tic acid, the MICs of 7 did not approximately change effective dose
on microorganism. Complex 8 had the highest activity on wild type
microorganisms between complexes.
The MICs of new complex 1 for strains, gram (ꢀ) wild type
E. coli, P. aeruginosa, and clinic isolate P. aeruginosa were 800, 700
and 1000
eus and clinic strain MRSA were inhibited more effectively at 400,
400, 250 g/mL. For 2, the growth of all the strains with exception
MRSA were inhibited at approximately concentration of 1100–
1300 g/mL of the complex, while the MICs for MRSA was
900 g/mL. 3 had much the same MIC values for all the strains.
lg/mL respectively, while the growth of S. aureus, B. cer-
l
l
l
As can clearly be seen from Table 5, the effective dose of 1–4 were,
almost without exception, superior to that of metal orotic acid li-
gands 5–8 across all of the bacterial and the fungal strains studied,
except for 4 at S. aureus and MRSA. As a result, antimicrobial activ-
ities were decreased with to be synthesized from 5–8 ligands to 1–
4. Complex 4 is more effective at both wild type and clinic strain S.
aureus in comparison to 8 and orotic acids.
1, 4 and 5 have higher activity against Gram-positive than
Gram-negative bacteria. In classifying the antibacterial activity as
Gram-positive or Gram-negative, it would generally be expected
that to be more active against Gram-positive than Gram-negative
bacteria because of outer membrane [55]. The 8 has activity on
both Gram-positive and Gram-negative bacteria at wild type. The
Fig. 5. Packing diagram of 3.
comparison, the orotic acid and its metal complexes ([Co(HOr)-
(H2O)4]ꢁH2O (5) [18], [Ni(HOr)(H2O)4]ꢁH2O (6) [7], [Cu(HOr)-
(H2O)4]ꢁH2O (7) [22] and [Zn(HOr)(H2O)4]ꢁH2O (8) [7]) were tested
for MIC values. The results are presented in Table 5 as minimum
inhibitor concentration (MIC) values (lg/mL) which is the mini-
mum concentration to inhibit the growth of bacteria or fungi.
While orotic acid showed activity at higher concentrations on C.
albicans (2000 lg/mL) and E. coli (1375 lg/mL), MICs of other stud-
Table 5
Minimal inhibitory concentration (MIC) values of the complexes against wild type microorganisms (lg/mL) and clinical isolates.
Complexes
Wild type
Gram (ꢀ)
E. coli
Clinical isolate
Wild type
Eucaryota
C. albicans
Gram (+)
Gram(+)
Gram (ꢀ)
P. aeruginosa
S. aureus
B. cereus
Methicillin resistant S. aureus
P. aeruginosa
H3Or
1375
800
1200
1800
800
500
750
1000
125
1000
700
1300
1500
1500
500
1500
1000
250
1000
400
1100
1800
100
125
750
1500
250
750
400
1000
1500
500
1000
250
900
1500
100
125
1800
1375
500
1000
1000
1100
1600
1300
500
1250
1250
750
2000
1100
1300
1800
1500
250
1000
1000
750
1
2
3
4
5
6
7
8
250
1000
1000
250

H. Erer et al. / Polyhedron 28 (2009) 3087–3093
3093
Table 6
Antimicrobial assays of same antibiotics against wild type and clinical isolates by disc diffusion method (diameter in mm).
Wild type strains
C (30
l
g)
OFX (5
l
g)
RD (2
l
g)
CXM (30
l
g)
TE (30
lg)
N (10 lg)
S. aureus
B. cereus
E. coli
P. aeruginosa
C. albicans
20
23
28
21
–
27
24
30
17
–
27
9
9
18
–
16
–
23
17
–
30
28
27
20
–
–
–
–
–
24
Clinic isolates
MRSA
P. aeroginosa
22
–
–
21
–
–
–
–
13
18
–
–
C: chloramphenicol, OFX: oflaxacin, RD: rifampicin, CXM: cefuroxime, TE: tetracycline, N: nystatin.
[18] H. Icbudak, H. Ölmez, O.Z. Yesilel, F. Arslan, P. Naumov, G. Jovanovski, A.R.
Ibrahim, A. Usman, H.K. Fun, S. Chantrapromma, S.W. Ng, J. Mol. Struct. 657
(2003) 255.
[19] O.Z. Yesßilel, M.S. Soylu, H. Ölmez, O. Büyükgüngör, Polyhedron 25 (2006) 2985.
[20] O.Z. Yesßilel, H. Ölmez, C. Arıcı, Polyhedron 26 (2007) 3669.
[21] A. Karipides, B. Thomas, Acta Crystallogr., Sect. C 42 (1986) 1705.
[22] D. Michalska, K. Hernik, R. Wysokin´ ski, B. Morzyk-Ociepa, A. Pietraszko,
Polyhedron 26 (2007) 4303.
[23] D. Sun, R. Cao, Y. Liang, M. Hong, Y. Zhao, J. Weng, Aust. J. Chem. 55 (2002) 681.
[24] S. Bekiroglu, O. Kristiansson, J. Chem. Soc., Dalton Trans. (2002) 1330.
[25] D.A. Köse, B. Zümreoglu-Karan, O. Sßahin, O. Büyükgüngör, J. Mol. Struct. 789
(2006) 147.
[26] D. Mentzafos, N. Katsaros, A. Terzis, Acta Crystallogr., Sect. C 43 (1987) 1905.
[27] X. Li, Q. Shi, D. Sun, W. Bi, R. Cao, Eur. J. Inorg. Chem. (2004) 2747.
[28] I. Mutikainen, Finn. Chem. Lett. (1985) 193.
presence of metal ions plays an important role at antimicrobial
activity. We think that the disparity at antimicrobial activities be-
tween complexes on the microorganisms is change bond charac-
teristics on target area of metal ions because of identical
molecular structures of 1–8. Orotic acid and metal complexes have
been demonstrated to possess antibacterial and antifungal proper-
ties [43,56].
The results of our study indicate that clinic isolates are more
resistant than wild type microorganism at standard antibiotics (Ta-
ble 6). It is a well-known fact that hospital infections are quite
important for the public healthy and quite resistant against stan-
dard antibiotics. Therefore, there is an urgent demand for new
antibiotics and new classes of chemical formula that will efficiently
inhibit the growth of pathogenic microorganism. In this study, as
part of our efforts into the development of new metal based anti-
microbial complexes, new complex 4 could be a new candidate
for therapy of S. aureus infections and 5 could be candidate for
therapy of candidal infection diseases.
[29] T.T.B. Ha, A.M. Larsonneur-Galibert, P. Castan, J. Jaud, J. Chem. Crystallogr. 29
(1999) 565.
[30] M.S. Soylu, O.Z. Yeßsilel, B. Karabulut, O. Büyükgüngör, Polyhedron 28 (2009)
2487.
[31] O.Z. Yesßilel, F. Tezcan, H. Ölmez, H. Pasßaog˘lu, O. Büyükgüngör, Z. Anorg. Allg.
Chem. 631 (2005) 2497.
_
[32] A. Bulut, H. Içbudak, O.Z. Yesßilel, H. Ölmez, O. Büyükgüngör, Acta Crystallogr.,
Sect. E 59 (2003) m736.
[33] O.Z. Yeßsilel, H. Olmez, C. Arıcı, Acta Crystallogr., Sect. C 63 (2007) m240.
[34] O.Z. Yesßilel, H. Pasßaog˘lu, K. Akdag˘, O. Büyükgüngör, Z. Anorg. Allg. Chem 633
(2007) 1731.
Acknowledgment
[35] O.Z. Yesßilel, H. Ölmez, I. Uçar, A. Bulut, C. Kazak, Z. Anorg. Allg. Chem. 631
(2005) 3100.
This work was supported by the Eskißsehir Osmangazi Univer-
sity by Project No. 200819042.
[36] O.Z. Yesßilel, K. Akdag˘, H. Pasßaog˘lu, O. Büyükgüngör, Z. Naturforsch. 62b (2007)
818.
[37] I. Ucar, A. Bulut, O.Z. Yesilel, H. Ölmez, O. Büyükgüngör, Acta Crystallogr., Sect.
C 60 (2004) m563.
[38] O.Z. Yesßilel, E. Sßahin, Z. Anorg. Allg. Chem. 633 (2007) 1087.
[39] O.Z. Yesßilel, A. Mutlu, C. Ög˘retir, O. Büyükgüngör, J. Mol. Struct. 889 (2008)
421.
[40] H. Ölmez, H. Içbudak, O.Z. Yesßilel, C. Arıcı, D. Ülkü, Z. Kristollg. 219 (2004) 300.
[41] O.Z. Yesßilel, H. Pasßaog˘lu, K. Akdag˘, O. Büyükgüngör, Polyhedron 26 (2007)
2761.
Appendix A. Supplementary data
_
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.poly.2009.06.052.
[42] O.Z. Yeßsilel, H. Ölmez, H. Içbudak, O. Büyükgüngör, Z. Naturforsch. 60b (2005)
References
1138.
[43] O.Z. Yeßsilel, N. Dege, C. Darcan, O. Büyükgüngör, Z. Naturforsch. 62b (2007)
1590.
[1] C. Janiak, Dalton Trans. (2003) 278.
[44] O.Z. Yesßilel, I. Uçar, A. Bulut, H. Ölmez, O. Büyükgüngör, Z. Naturforsch. 61b
[2] C.N.R. Rao, S. Natarajan, R. Vaidhyanathan, Angew. Chem., Int. Ed. 43 (2004)
1466.
(2006) 147.
[45] O.Z. Yesßilel, H. Pasßaog˘lu, K. Akdag˘, O. Büyükgüngör, Z. Anorg. Allg. Chem. 633
(2007) 1731.
[46] Stoe & Cie, X-AREA (Version 1.18), X-RED32 (Version 1.04), Stoe & Cie,
Darmstadt, Germany, 2002.
[47] A. Altomare, M.C. Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo, A.
Guagliardi, A.G.G. Moliterni, G. Polidori, R. Spagna, J. Appl. Crystallogr. 32
(1999) 115.
[3] L. Jiang, X. Feng, C. Su, X. Chen, T. Lu, Inorg. Chem. 46 (2007) 2637.
[4] S.L. James, D.M.P. Mingos, X. Xu, A.J.P. White, D.J. Williams, J. Chem. Soc.,
Dalton Trans. (1998) 1335.
[5] O.Z. Yesßilel, O. Büyükgüngör, Solid State Sci. 9 (2007) 485.
[6] D. Szeleny, J. Sos, Arzneim.– Forsch. 21 (1991) 777.
[7] M. Sabat, D. Zglinska, B. Jezowska-Trzebiatowska, Acta Crystallogr., Sect. B 36
(1980) 1187.
[48] G.M. Sheldrick, SHELXS97, University of Göttingen, Germany, 1997.
[49] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[50] Clinical and Laboratory Standards Institute, Methods for dilution antimicrobial
susceptibility tests for bacteria that grow aerobically; approved standard, 7th
ed. CLSI document M7–A7. Clinical Laboratory Standards Institute, Wayne, PA,
2006.
[8] A. Karipides, B. Thomas, Acta Crystallogr., Sect. C 42 (1986) 1705.
[9] T. Solin, K. Matsumoto, K. Fuwa, Bull. Chem. Soc. Jpn. 54 (1984) 3731.
[10] P. Castan, E. Colacio-Rodriguez, A.L. Beauchamp, S. Cros, S. Wimmer, J. Inorg.
Biochem. 38 (1990) 225.
[11] J. Leberman, A. Kornberg, E.S. Simms, J. Biol. Chem. 215 (1955) 403.
[12] P. Castan, E. Colacio-Rodriguez, A.L. Beauchamp, S. Cros, S. Wimmer, J. Inorg.
Chem. 38 (1990) 225.
_
[51] O.Z. Yeßsilel, H. Ölmez, H. Içbudak, J. Therm. Anal. Calorim. 89 (2007) 555.
[52] A. Hernanz, F. Billes, I. Bratu, R. Navarro, Biopolymers 57 (2000) 187.
[53] L. Xing, C. Rong, S.D. Fong, H.M. Chun, Chinese J. Struct. Chem. 21 (2002) 374.
[54] M.C. Etter, J.C. MacDonald, J. Bernstein, Acta Crystallogr., Sect. B 46 (1990) 256.
[55] A.R. Mc Cutcheon, S.M. Ellis, R.E.W. Hancock, G.H.N. Towers, J.
Ethnopharmacol. 37 (1992) 213.
[13] A.Q. Wu, F.K. Zheng, X. Liu, G.C. Guo, L.Z. Cai, Z.C. Dong, Y. Takano, J.S. Huang,
Inorg. Chem. Commun. 9 (2006) 347.
[14] C.P. Raptopoulou, V. Tangoulis, V. Psycharis, Inorg. Chem. 39 (2000) 4452.
[15] O.Z. Yesßilel, G. Kaßstasß, O. Büyükgüngör, Inorg. Chem. Commun. 10 (2007) 936.
[16] O.Z. Yesßilel, H. Erer, A. Mutlu, O. Büyükgüngör, Polyhedron 28 (2009) 150.
[17] M.J. Plater, M.R.J. Foreman, J.M.S. Skakle, R.A. Howie, Inorg. Chim. Acta 332
(2002) 135.
[56] P. Ruasmadiedo, J.C. Badagancedo, E.G. Fernandez, D.G. Dellano, C.G. Delos
Reyes Gavilan, J. Food Protect. 59 (1996) 502.