Transition metal(II) complexes of vitamin B13 with monodentate orotate(1-) ligands

Article abstract of DOI:10.1016/j.molstruc.2005.12.030

The formation of bisorotate(1-) complexes of the type [M(C₅H₃N₂O₄)₂(H₂O)₄]·nH₂O (M=Co, Ni, Zn and n=2, 4) was achieved by the reaction of ammonium orotate with the corresponding M(II) ions. The crystal structure of [Co(C₅H₃N₂O₄)₂(H₂O)₄]·2H₂O was determined by single crystal X-ray diffraction analysis. Each Co(II) ion in the monomeric Co(C₅H₃N₂O₄)₂(H₂O)₄ units adapts a slightly distorted octahedral geometry comprised of two monodentate orotate anions and four H₂O ligands. Columnar packing of pyrimidine rings along the c axis leads to the formation of layers that propagate parallel to the b axis and the adjacent layers are linked by hydrogen bonds forming a 3D lattice. Complexes of nickel and zinc were assumed to contain monodentate bound orotate ligands as well on the basis of physical and spectroscopic data.

Full text of DOI:10.1016/j.molstruc.2005.12.030

Journal of Molecular Structure 789 (2006) 147–151
www.elsevier.com/locate/molstruc
Transition metal(II) complexes of vitamin B13 with monodentate
orotate(1K) ligands
a
Dursun Ali K o¨ se , Birg u¨ l Z u¨ mreoglu-Karan
a, b
*
, Onur S¸ ahin , Orhan B u¨ y u¨ kg u¨ ng o¨ r
b
a
Department of Chemistry, Hacettepe University, Beytepe Campus, 06532 Ankara, Turkey
Faculty of Arts and Sciences, Department of Physics, Ondokuz Mayıs University, Samsun, Turkey
b
Received 16 November 2005; accepted 20 December 2005
Available online 20 February 2006
Abstract
The formation of bisorotate(1K) complexes of the type [M(C H N O ) (H O) ]$nH O (MZCo, Ni, Zn and nZ2, 4) was achieved by the
5
3
2
4 2
2
4
2
reaction of ammonium orotate with the corresponding M(II) ions. The crystal structure of [Co(C
5 3 2 4 2 2 4 2
H N O ) (H O) ]$2H O was determined by
single crystal X-ray diffraction analysis. Each Co(II) ion in the monomeric Co(C H N O ) (H O) units adapts a slightly distorted octahedral
4
5
3
2
4 2
2
2
geometry comprised of two monodentate orotate anions and four H O ligands. Columnar packing of pyrimidine rings along the c axis leads to the
formation of layers that propagate parallel to the b axis and the adjacent layers are linked by hydrogen bonds forming a 3D lattice. Complexes of
nickel and zinc were assumed to contain monodentate bound orotate ligands as well on the basis of physical and spectroscopic data.
q 2006 Elsevier B.V. All rights reserved.
Keywords: Vitamin B13; Orotic Acid; Orotate Complexes; Monodentate coordination
1
. Introduction
The crystal structures of mononuclear Ni [7,8], Mg [9], Co
10], Zn [11] complexes have been described where orotate
[
dianions (HOr)
2
K
Orotic acid (Vitamin B13, uracil carboxylic acid,
C H N O ) plays a key role in the biosynthesis of pyrimidine
act as bidentate ligands. In polymeric
K
2
complexes, (HOr) acts as a polydentate ligand and bridges
the metal ions forming 1D-polymeric chains with Ca [12], Cd
[13], Mn [5], Cu [14], Ni [15,16] or 2D-layer structures in
mixed metal complexes where the layers are interconnected
with hydrogen bonds to form the final network structures [17].
Relatively little information is available regarding the
5
4 2 4
bases of nucleic acids [1]. Some metal compounds of the acid
itself and derivatives have successful applications in curing
syndromes related with metal ion deficiencies [2] and
promising applications as therapeutic agents for cancer [3].
The biocoordination chemistry of vitamin B13 therefore
demands a better understanding regarding its interactions
with metal ions.
1
K
compounds with orotate monoanion, (H Or) . Crystal studies
2
with Mg [18], Zn [19] and Ni [20] have showed that aquated
1
metal cations interact with the (H Or) counter ions through
K
2
The orotic acid molecule (H Or) has a multidentate nature
3
hydrogen bonds. In these isotopic compounds, the orotate
monoanion does not enter the inner coordination sphere of the
metal. Here we report the synthesis and characterization of
complexes of the type [M(H Or) (H O) ]$nH O (MZCo(1),
Ni(2), Zn(3) and nZ2, 4) where bis-coordinated orotate
monoanions bind monodentately.
(
Fig. 1). The most potential coordination sites in the pH range
of 5–9 are the carboxylic oxygen and the adjacent pyrimidine
nitrogen atom (N1), for the formation of a stable chelate ring.
In very alkaline solutions, deprotonation occurs from (N1) and
coordination through the other sites becomes available as well
due to the existence of different tautomeric forms [4–6 and the
references therein]. The literature lists several reports on
mononuclear and polynuclear orotato complexes.
2
2
2
4
2
2. Experimental
2.1. Synthesis
*
Corresponding author. Tel.: C90 312 2977951; fax: C90 312 2992163.
E-mail address: bkaran@hacettepe.edu.tr (B. Z u¨ mreoglu-Karan).
Because of the low solubility of orotic acid in water and also
the difficulty in controlling the extent of ionization in alkaline
medium, the ammonium salt was used in all experiments as the
source of the orotate monoanion. Ammonium orotate
0
022-2860/$ - see front matter q 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2005.12.030

148
D.A. K o¨ se et al. / Journal of Molecular Structure 789 (2006) 147–151
Table 1
Crystal data of [Co(H Or)
2
2
(H
2
O)
]$2H O and structure refinement
4 2
Empirical formula
Formula weight
Temperature (K)
C
10
H
18CoN
4 14
O
477.21
296
˚
Wavelength (A)
0.71073
Monoclinic
Crystal system
Space group
1
P2 /c
Unit cell dimensions
˚
a (A)
˚
b (A)
9.7205(8)
12.4541(7)
7.1266(6)
96.520(6)
857.17(11)
2
Fig. 1. Orotic acid.
˚
c (A)
monohydrate (m.p.Z350.5 8C) was prepared from anhydrous
orotic acid (Fluka) according to the procedure described by
Solbakk [21]. To a solution of M(NO ) $nH O (Aldrich), a
b
3
˚
Volume (A )
Z
3
2
2
K3
Calculated density (mg/m
Absorption coefficient (mm
F(000)
)
1.849
warm solution of NH H Or$H O was added in a 1:2 molar
4
K1
2
2
)
1.090
ratio. The precipitates obtained in about 3 weeks at room
temperature were separated by filtration and dried in a
desiccator. The yields were found around 65% based on the
metal. The compounds have low solubility in water and in
common organic solvents. The Co compound dissolves better
upon gentle heating.
490
Crystal size (mm)
0.320!0.213!0.080
2.11–15.99
q range for data collection
Index ranges
K11!h!11, K15!k!15, K8!l!8
1681
Independent reflection
Measurement reflection
Absorption correction
Refinement method
11,630
Integration
2
Found: C, 25.53; H, 4.06; N, 11.59. Calc. For
C H N O Co: C, 25.16; H, 3.77; N, 11.74. Found: C,
Full-matrix least-squares on F
2
Goodness-of-fit on F
1.144
1
0 8 4 10
Final R indices [IO2s(I)]
R indices (all data)
R
R
1
Z0.047
Z0.051
2
5.59; H, 4.03; N, 11.59. Calc. For C H N O Ni: C, 25.16;
10 8 4 10
1
H, 3.77; N, 11.74. Found: C, 23.48; H, 4.72; N, 10.78. Calc. For
C H N O Zn: C, 23.12; H, 4.24; N, 10.79.
K3
˚
1.72 and K0.51 e A
Largest diff. peak and hole
1
0 8 4 10
Geometric calculations were performed on Platon [27].
Selected geometric parameters and hydrogen-bonding geome-
try parameters are listed in Table 2.
2
.2. Characterization
Carbon, hydrogen and nitrogen analyses were performed
using a LECO CHNS 932 instrument. FTIR spectra were
recorded in KBr matrix on a MATTSON 1000 FTIR
spectrophotometer. Thermal gravimetric analyses were per-
3
. Results and discussion
K1
The compounds were found to be pure and formulated as
Co(C H N O ) (H O) $2H O (1), Ni(C H N O ) (H O) $2-
H O (2) and Zn(C H N O ) (H O) $4H O (3) based on micro-
4
formed in flowing nitrogen atmosphere (10 mL min ) using a
Schimadzu DTG-60 instrument.
5
3
2
4 2
2
4
2
5
3
2
4 2
2
4
2
5
3
2
4 2
2
2
analytical, spectroscopic and thermo-analytical results.
2
.3. Crystallography
3.1. FTIR spectra
The green crystals of the Ni complex were found to be
of twin nature and those of the Zn complex gradually
transformed amorphous as noted previously for Mg- and Zn-
bis[orotate(1K)] phases [19]. A red single crystal of the cobalt
complex, [Co(H Or) (H O) ]$2H O, suitable for data collec-
tion was mounted on a glass fiber and data collection was
performed on a STOE IPDS II diffractometer with graphite
monochromated Mo Ka radiation at 296 K. Details of crystal
data, data collection and refinement are given in Table 1.
The FTIR spectra of the compounds exhibited characteristic
features in the OH, ketone/carboxylate and NH regions. The
spectrum of the Zn compound differed slightly from those of
the Co and Ni compounds due to the presence of a higher
amount of lattice water leading to different hydrogen bonding
interactions with the coordinated water and orotate anions. The
assignments proposed were discussed considering previous
assignments for similar molecules (Table 3).
2
2
2
4
2
The structure was solved by direct methods using SHELXS-
2
7 [22] and refined by full-matrix least-squares methods on F
9
Table 2
˚
Selected geometric parameters (A, 8)
using SHELXL-97 [23] from within the WINGX [24,25]
suitable of software. All non-hydrogen atoms were refined with
anisotropic parameters. Hydrogen atoms bonded to carbon and
O1–Co1
O2–Co1
O3–Co1
2.090(3)
2.133(3)
2.063(2)
˚
nitrogen were placed in calculated positions (C–HZ0.93 A
˚
H1B/O7
1.87(2)
and N–HZ0.86 A) and refined using riding model with UZ
O3–Co1–O1
O3–Co1–O2
O1–Co1–O2
85.09(11)
90.92(11)
92.95(12)
1
.2 U of the parent atom for CH and NH. The H atoms of water
˚
were refined with fixed O–HZ0.83 A (UZ1.5 U of the parent
atom). Molecular drawing was obtained using ORTEP-III [26].

D.A. K o¨ se et al. / Journal of Molecular Structure 789 (2006) 147–151
149
Table 3
Some important IR frequencies of orotic acid, ammonium orotate and prepared compounds
a
Or
Assignment
H
3
NH
4
H
2
Or$H
2
O
1
2
3
n(N1–H)
3160 sh
2500 b
1729 vs
3230 sb
–
Unresolved
–
3212 sh
–
3198 sb
–
n(O–H)acid
n(CaO)acid
n(C2aO)
1701 vs
1752 vs
1696 vs
1
741 vs
675 vs
1719 v
1700 vs
1653 v
}
s
n(C4aO)Cn(ring)
n(CaC)
1
}
s
K
nasym(COO
)
–
1636 vs
1480 sh
1430 sh
1365 s
271
1639 vs
1473 m
1407 m
1375 s
262
1641 vs
1475 m
1409 m
1378 s
263
1615 s
1492 m
Unresolved
1380 s
235
Ring
1500–1590
1435 sb
–
d(N1–H)
K
nsym(COO
)
D(n Kn
a
s
)
Abbreviations: b: broad, m: medium, s: strong, sb: strong broad, sh: shoulder, vs: very strong.
a
From Ref. [28].
K1
In the 3500–2500 cm region, the O–H stretching bands of
coordinated water overlapped with the N–H bands of orotate
ions and their involvement in hydrogen bonding produced a
band broadening. The carboxylate group and the nCO stretches
d(N1–H) was observed due to strong hydrogen bonding
between N(1)–H and lattice water molecules.
3.2. Thermogravimetric analysis
of the carbonyl groups exhibited strong bonds in the region
1
K1
750–1700 cm . These strong bands were shifted and
Thermogravimetric analysis of the compounds has been
conducted in the 40–900 8C temperature range under nitrogen
and the results are given in Table 4. The observed mass losses for
the dehydration and decomposition steps agree well with
calculated values. The loss of lattice water and coordinated
water for the cobalt and nickel complexes was observed in an
overlapped pattern below 150 8C. Dehydration of the zinc
complex proceeded in two distinct steps corresponding to
the loss of 6 mol of water at 109 8C, 1 mol of water at 229 8C and
1 mol of water at 302 8C. The difference in the dehydration
behavior of 3 is possibly due to different hydrogen bonding
interactions in a different crystal structure arising from the
presence of a higher amount of lattice water. The anhydrous
forms of 1 and 2 are relatively stable showing a plateau in the
range 200–250 8C while for 3 decomposition immediately starts
following the final dehydration step. The overall weight loss in
the range 250–600 8C corresponds to the loss of organic matter
broadened with respect to free orotic acid. The FTIR spectral
assignments of several transition metal orotate complexes have
been comprehensively discussed by Maistralis et al. [6]. The
authors stated that involvement of N(1) in coordination to the
metal reduces the electron density in the C(2)aO band leading
to a downward shift of related frequencies. No such assignment
was possible in our case and moreover the differences between
the asymmetric and symmetric stretches of the carboxylate
K1
groups of the three complexes, DnO200 cm , suggest a
monodentate binding of the carboxylate group to the metal ion
[29]. Another important band in distinguishing the mono- or
bidentate coordination of the orotate ligand is the n(N1–H) and
dN(1)–H vibrations that are observed around 3200 and
K1
1
430 cm , respectively, in H Or and NH H Or. These
3 4 2
bands disappear in the complexes of orotate(2K) ligands or
change position for many bidentate orotate(1K) complexes due
to the participation of the N(1) atom in coordination [6]. For the
compound [UO (H Or) (H O) $2H O] [30], in which two
in the form of H O, CO/CO and NO/NO in several consecutive
2 2 2
steps to give the metal oxide residue around 600 8C.
3.3. Structural description of complex 1
2
2
2
2
3
2
orotic acid moieties are bonded monodentate through the
carboxylate oxygens, the position of the d(N1–H) remains the
same while n(N1–H) shifts to higher wave numbers with
respect to nonionized orotic acid. The complexes 1, 2 and 3
exhibited a similar shift for n(N1–H) but a downward shift for
The structure of complex 1 was determined by X-ray
crystallography, and a thermal ellipsoid drawing is provided in
Table 4
Thermogravimetric decomposition data
a
Dehydration
Decomposition
Total mass loss (%)
a
DTG peak temperature
8C)
Mass loss (%)
Onset temperature (8C)
DTG peak temperature
(
(8C)
NH
1
4
H
2
Or$H
2
O
114
143
147
109
10 (9.4)
23 (22.6)
23.5 (22.6)
23
y250
y250
y250
y250
273C352
341C470
335C511
359C479
100 (100)
84 (84)
2
79 at 525 8C (85.4)
82 (84)
3
2
3
29
2.7 (28)
}
}
02
2.7
a
Values in parentheses refer to calculated mass losses.

150
D.A. K o¨ se et al. / Journal of Molecular Structure 789 (2006) 147–151
2 2 2 4 2
Fig. 2. Representative unit in the crystal structure of [Co(H Or) (H O) ]$2H O with atomic numbering.
Fig. 2. Although the crystals were suitable for X-ray analysis,
the overall quality of the crystals was poor.
The compound consists of neutral Co(H Or) (H O) units
4. Conclusion
The complexes described in this article demonstrate the
monofunctional binding property of the orotate ligand.
Physical and spectroscopic data suggest that the metal center
in the cobalt complex is a distorted octahedron formed by the
coordination of the carboxylate oxygens of the orotate ligands
and four aqua ligands. The Ni and Zn complexes could not be
characterized crystallographically because of the unavailability
of suitable crystals. However, based on IR spectroscopy,
compositional and thermal analysis, they were assumed to
contain monodentate bound orotate ligands as well.
2
2
2
4
which are bonded to each other by hydrogen bonds through the
lattice. Each Co atom lies on a crystallographic inversion
center and is coordinated to six oxygens belonging to two
orotate and four aqua ligands. The polyhedron of six oxygen
atoms is a distorted octahedron with two orotate ligands at
˚
.063(2) A, via their carboxylate oxygens, and two H O
2
2
˚
ligands at 2.133(3) A in the equatorial plane. The two axial
˚
ligands at 2.090(3) A are significantly bent by ca. 58 where the
O3–Co–O1 angle is 85.09(11)8 and the O3–Co–O1i is
9
4.91(11)8. Like the molecule in the crystal of free orotic
acid, the orotate ligand occurs in the keto form [31]. The value
of the C2–N1–C5 angle (122.5(3)8) is nearly equal to that in
free orotic acid (122.7(2)8) indicating that N1 is not involved in
complexation with the metal. On the other hand, the
˚
lengthening in the C1–C2 bond (1.522(5) A) and the shortening
˚
in the C1–O3 bond (1.263(4) A) relative to those in the free
5
. Supplementary material
Crystallographic data for 1 have been deposited at the
Cambridge Crystallographic Data Centre, CCDC, with
deposition number 284789.
˚
orotic acid (1.498(4) and 1.306(3) A, respectively) indicate the
Acknowledgements
participation of the carboxylate group in coordination. The
complex contains also crystallization water. Co(II) ions are
arranged in polymeric chains where the lattice water molecules
act as bridges by making strong hydrogen bonds with
This work was supported by the Turkish Scientific and
Technical Research Council through the project TBAG 2236.
The authors wish to acknowledge the Faculty of Arts and
Sciences, Ondokuz Mayıs University, Turkey, for the use of the
Stoe IPDS-II diffractometer (purchased under grant no. F279 of
the University Research Fund).
˚
coordinated water (H1(B)/O(7)Z1.87 A) thus aligning the
molecules in a zigzag fashion forming layers that propagate
parallel to the b axis (Fig. 3). The pyrimidine rings are nearly
planar and pack along the c axis in a columnar mode. There are
also hydrogen bonds in which the pyrimidine ring is a donor
and oxygen from the lattice molecule is an acceptor. The
adjacent layers are linked by hydrogen bonding forming a 3D
lattice.
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