Hindawi Publishing Corporation

Bioinorganic Chemistry and Applications

Volume 2008, Article ID 647873, 8 pages
doi:10.1155/2008/647873

Research Article
The First Metal Complexes of
4,6-diamino-1-hydro-5-hydroxy-pyrimidine-2-thione:
Preparation, Physical and Spectroscopic Studies, and
Preliminary Antimicrobial Properties

Sahar I. Mostafa,1 Constantina Papatriantafyllopoulou,2 Spyros P. Perlepes,2 and Nick Hadjiliadis3

1 Chemistry Department, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt
2 Department of Chemistry, University of Patras, 265 04 Patras, Greece
3 Laboratory of Inorganic and General Chemistry, Department of Chemistry,

University of Ioannina, 451 10 Ioannina, Greece

Correspondence should be addressed to Nick Hadjiliadis, [email protected]

Received 2 June 2008; Revised 10 October 2008; Accepted 14 December 2008

Recommended by Ian Butler

The new complexes [M2 O5 L2 (H2 O)2 ] · H2 O (M = Mo, 1; M = W, 2), [RuL2 (H2 O)2 ] · H2 O (3), [ML3 ] · xH2 O (M =
Rh, x = 2, 4; M = Ir, x = 1, 5), [RhL2 (PPh3 )2 ](ClO4 ) · 2H2 O (6), [PdL2 ] · 2H2 O (7), [PdL(phen)]Cl · H2 O (8),
[ReOL2 (PPh3 )]Cl (9) and [UO2 L2 ] (10) are reported, where LH is 4,6-diamino-1-hydro-5-hydroxy-pyrimidine-2-thione. The
complexes were characterized by elemental analyses, physical techniques (molar conductivity, room-temperature magnetic
susceptibility), and spectroscopic (IR, Raman, UV/VIS/ligand field, NMR, mass) methods. The ligand L− is in its thione
form and behaves as a bidentate chelate with the deprotonated (hydroxyl) oxygen and the nitrogen of one amino group
as donor atoms. Oxobridged dinuclear (1, 2) and various mononuclear (3–10) structures are assigned for the complexes in
the solid state. The metal ion coordination geometries are octahedral (1–6, 9, 10) or square planar (7, 8). The free ligand
LH and complexes 1, 4, 7, and 8 were assayed in vitro for antimicrobial activity against two bacterial and two fungal
cultures.

Copyright © 2008 Sahar I. Mostafa et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

1. INTRODUCTION both hydroxy and amino substituents on the pyrimidine ring

is completely unkown.
2-Mercaptopyrimidine nucleotides have been detected in We now describe here the preparation and charac-
Escherichia Coli sRNA and yeast tRNA; it has been found that terization of the first metal complexes of 4,6-diamino-5-
they inhibit the synthesis of tRNA, thus acting as antitumour hydroxy-2-mercaptopyrimidine (LH, Scheme 2). We also
and antithyroid agents [1]. A similar inhibitory effect has report the antimicrobial activity of the free ligand and four
been observed for pyrimidine-2-thione (I in Scheme 1) representative complexes against two bacteria and two fungi.
and its derivatives, which also show pronounced in vitro This work can be considered as a continuation of our interest
bacteriostatic activity [1]. Metal complexes of pyrimidine- on the coordination chemistry of derivatized pyrimidines
2-thione or its pyrimidine-2-thiol tautomeric form [1, 2] [7].
and its amino [2, 3] or hydroxy [4–6] derivatives have
been prepared and studied (for representative ligands see 2. EXPERIMENTS
Scheme 1). Such complexes exhibit rich structural chemistry,
and interesting thermal, magnetic, sorptive, and biological All reagents were purchased from Merck and Alfa/Aesar.
properties. However, the coordination chemistry of ligands Na2 [IrCl6 ] is commercially available. [PdCl2 (phen)] was pre-
based on the 2-mercaptopyrimidine moiety and containing pared by the reaction of K2 [PdCl4 ] and 1,10-phenanthroline
2 Bioinorganic Chemistry and Applications

NH2 NH2

N N N

N S N SH H2N N S

H H
I II III
OH

N N

N OH N

IV V

Scheme 1: Structural formulae of pyrimidine-2-thione (I), and some of its amino (II, III) and hydroxy (IV, V) derivatives shown in one of
their tautomeric forms.

NH2 NH2 with an integration sphere. 1 H NMR studies were performed

HO 4 4 on a Varian Gemini WM-200 spectrometer. 31 P{1 H} NMR
5 3 HO 5
N
3 spectra were recorded with a Varian Mercury equipment
N
[ref. 85% H3 PO4 (ext.)] . Mass spectra were recorded on a
6 2 6 2 Matson 5988 MS spectrometer. Conductivity measurements
H2N N1 S H 2N N SH were carried out at room temperature on a YSI, model 32
1
H
conductivity bridge using 10−3 M solutions. Room tempera-
ture magnetic susceptibility measurements were performed
Thione form Thiol form using a Johnson Matthey magnetic balance standardized
with HgCo(NCS)4 ; diamagnetic corrections were estimated
Scheme 2: 4,6-diamino-5-hydroxy-2-mercaptopyrimidine (LH). using Pascal’s constants.

2.1. Preparation of the complexes

in H2 O/EtOH. [ReOCl3 (PPh3 )2 ] was synthesized as pre- [Mo2 O5 L2 (H2 O)2 ] · H2 O (1)
viously reported [8]. DMSO used in conductivity mea-
surements was dried over molecular sieves. The DMSO- An aqueous solution (5 cm3 ) of (NH4 )2 [MoO4 ] (0.24 g,
d6 protons (NMR) were referenced using TMS. Warning: 1.0 mmol) was added to a solution of LH (0.16 g, 1.0 mmol)
perchlorate salts are potentially explosive; such compounds in EtOH (25 cm3 ). The obtained slurry was heated and the
should be used in small quantities and treated with utmost resulting orange solution was refluxed for 4 hours, during
care at all times. Elemental analyses (C, H, N, S) were which time an orange precipitate is formed. The solid was
performed by the University of Ioannina (Greece) Micro- collected by filtration, washed with ethanol (2 cm3 ) and
analytical Unit with an EA 1108 Carlo-Erba analyzer. The diethyl ether (2 × 5 cm3 ) and dried in vacuo. The yield was
water content of the complexes was also confirmed by 35% (based on the metal). Elemental analytical calculation
TG/DTG measurements performed on a Shimadzu Thermo- for C8 H16 N8 O10 S2 Mo: C, 15.00; H, 2.50; N, 17.50; S, 10.00%
gravimetric Analyzer TGA-50. IR spectra were recorded on found that C, 14.98; H, 2.82; N, 17.51; S, 9.87%; ΛM (DMSO):
a Matson 5000 FT-IR spectrometer with samples prepared 3 S cm2 mol−1 .
as KBr pellets. Far-IR spectra were recorded on a Bruker IFS
113 v FT spectrometer with samples prepared as polyethylene [W2 O5 L2 (H2 O)2 ] · H2 O (2)
pellets. FT Raman data were collected on a Bruker IFS
66 v interferometer with an FRA 106 Raman module, a Using (NH4 )2 [WO4 ] and following exactly the same proce-
CW Nd: YAG laser source, and a liquid nitrogen-cooled dure as that described for complex 1, a bright yellow material
Ge detector. Solution electronic spectra were recorded using was isolated. The yield was 50% (based on the metal).
a Unicam UV2−100 spectrophotometer. Solid-state (diffuse Elemental analytical calculation for C8 H16 N8 O10 S2 W: C,
reflectance, DRS) electronic spectra in the 300–800 nm range 11.77; H, 1.96; N, 13.73; S, 7.85% found that C, 11.62; H,
were recorded on a Varian Cary 3 spectrometer equipped 1.90; N, 13.77; S, 7.95%; ΛM (DMSO): 2 S cm2 mol−1 .
Sahar I. Mostafa et al. 3

[RuL2 (H2 O)2 ] · H2 O (3) [PdL(phen)]Cl · H2 O (8)

Solid RuCl3 · 3H2 O (0.12 g, 0.46 mmol) was added to a To a stirred yellow slurry of [PdCl2 (phen)] (0.18 g,
solution of NaO2 CMe (0.62 g, 7.5 mmol) in water (30 cm3 ). 0.5 mmol) in a methanol/benzene solvent mixture (15 cm3 ,
Solid LH (0.24 g, 1.5 mmol) was then added and the resultant 3:2 v/v) was added a solution of KOH (0.055 g, 1.0 mmol)
reaction mixture was refluxed for 12 hours. The deep brown in methanol (15 cm3 ). Solid LH (0.08 g, 0.5 mmol) was
solid formed was collected by filtration while the reaction added to the reaction mixture which soon dissolved. The
mixture was hot, washed with hot water, and dried in vacuo. solution was filtered and stirred for 48 hours at room
The yield was 30% (based on the metal). Elemental analytical temperature. During this time, a brown precipitate formed
calculation for C8 H16 N8 O5 S2 Ru: C, 20.46; H, 3.41;N, 23.88; which was collected by filtration, washed with water (1 cm3 )
S,13.64% found that C, 20.32; H, 3.05; N, 23.57; S, 13.21%; and methanol (2 × 3 cm3 ), and dried in air. The yield was
ΛM (DMSO): 1 S cm2 mol−1 . 40% (based on the ligand). Elemental analytical calcula-
tion for C8 H14 N8 O4 S2 Pd: C, 21.03; H, 3.07; N, 24.54; S,
[RhL3 ] · 2H2 O (4) 14.02% found that C, 21.23; H, 3.22; N, 24.85; S, 14.21%;
ΛM (DMSO): 77 S cm2 mol−1 .
Using RhCl3 · 3H2 O and following the same procedure as
that described for complex 3, a reddish brown material was [ReOL2 (PPh3 )] Cl (9)
isolated. The yield was 60% (based on the metal). Elemental
analytical calculation for C12 H19 N12 O5 S3 Rh: C, 23.61; H, To a stirred slurry of [ReOCl3 (PPh3 )2 ] (0.25 g, 0.2 mmol) in
3.12; N, 27.55; S, 15.74% found that C, 23.73; H, 3.11; N, ethanol (30 cm3 ) was added solid LH (0.057 g, 0.4 mmol).
26.36; S, 14.98%; ΛM (DMSO): 6 S cm2 mol−1 . The solid soon dissolved and stirred at 40◦ C for 5 hours.
The brown solution deposited a brown microcrystalline
[IrL3 ] · H2 O (5) solid which was collected by filtration, washed with ethanol
(3 × 3 cm3 ), and dried in vacuo. The yield was 65%
Using Na2 [IrCl6 ] and following the same procedure as that (based on the metal). Elemental analytical calculation for
described for complex 3, a yellow solid was isolated. The C26 CIH25 N8 O3 S2 Re: C, 38.34; H, 3.07; N, 13.76; S, 7.86%
yield was 25% (based on the metal). Elemental analytical found that C, 38.37; H, 3.11; N, 13.87; S, 7.98%; ΛM (DMSO):
calculation for C12 H17 N12 O4 S3 Ir: C, 21.14; H, 2.50; N, 24.66; 46 S cm2 mol−1 .
S, 14.09% found that C, 21.33; H, 2.64; N, 24.75; S, 13.85%;
ΛM (DMSO): 5 S cm2 mol−1 . [UO2 L2 ] (10)

[RhL2 (PPh3 )2 ](ClO4 ) · 2H2 O (6) Solid LH (0.08 g, 0.5 mmol) was added to a stirred solution
of [UO2 (NO3 )2 ] · 6H2 O (0.25 g, 0.5 mmol) in methanol
A hot ethanolic solution (20 cm3 ) of LH (0.25 g, 1.6 mmol) (10 cm3 ). The solid soon dissolved. The resultant yellow
was added to a solution of RhCl3 · 3H2 O (0.21 g, 0.8 mmol) solution was filtered and refluxed for 4 hours, during which
in 6 M HClO4 (15 cm3 ). The resultant orange solution was time a red microcrystalline solid was precipitated. The
refluxed for 4 hours and to this was added a solution of product was collected by filtration, washed with methanol
PPh3 (0.43 g, 1.6 mmol) in hot ethanol (15 cm3 ). The new (5 cm3 ) and diethyl ether (2 × 5 cm3 ), and dried in vacuo.
solution was refluxed for a further 3 hours and filtered, and The yield was 55% (based on the metal). Elemental analytical
its volume decreased in vacuo to give a red-brown solid. The calculation for C8 H10 N8 O4 S2 U: C,16.44; H, 1.71; N, 19.18;
solid was collected by filtration, washed with hot water (2 S, 10.96% found that C, 16.35; H, 2.02; N, 18.98; S, 10.86%;
x 2 mL) and hot ethanol (2 x 3 cm3 ), and dried in vacuo. ΛM (DMSO): 11 S cm2 mol−1 .
The yield was 25% (based on the metal). Elemental analytical
calculation for C44 CIH44 N8 O8 S2 P2 Rh: C, 49.05; H, 4.09; N, 2.2. Antimicrobial activity
10.41; S, 3.30% found that C, 48.79; H, 4.09; N, 10.44; S,
3.46%; ΛM (DMSO): 48 S cm2 mol−1 . The bacterial strains (S. aureus and P. aeruginosa) were grown
in Nutrient agar slants and the fungal strains (A. niger and
[PdL2 ] · 2H2 O (7) C. albicans) were grown in Sabouraud dextrose agar slants.
The viable bacterial cells were swabbed onto Nutrient agar
To a stirred slurry of LH (0.16 g, 1.0 mmol) in methanol plates, while the fungal spores onto Sabouraud dextrose agar
(15 cm3 ) was added an aqueous solution (15 cm3 ) of plates. The free ligand and complexes 1, 4, 7 were dissolved
K2 [PdCl4 ] (0.16 g, 0.5 mmol). The resulting suspension was in DMSO, while complex 8 was dissolved in H2 O with 10, 20,
stirred at 40◦ C for 60 hours and the brown solid formed 50, and 100 mg/mL concentrations. The blank was DMSO in
was collected by filtration, washed with water (5 × 3 cm3 ) saline buffer. The bacterial and fungal plates were incubated
and cold methanol (2 × 5 cm3 ), and dried in air. The for 36 and 72 hours, respectively, and the activity of the
yield (based on the metal) was 50%. Elemental analytical compounds was estimated by measuring the diameter of
calculation for C8 H14 N8 O4 S2 Pd: C,21.03; H, 3.07; N, 24.54; the inhibition zone (the affected zone by the compounds)
S, 14.02% found that C, 21.23; H, 3.22; N, 24.85; S, 14.21%; around the respective zone (the normal place in the agar).
ΛM (DMSO): 9 S cm2 mol−1 . The incubation temperature was 27 ± 0.5◦ C.
4 Bioinorganic Chemistry and Applications

3. RESULTS AND DISCUSSION 6, 8, and 9 behave as 1 : 1 electrolytes, supporting their

ionic formulation [10]. All the complexes are diamagnetic,
3.1. Synthetic comments and physical as expected [9]. It should be mentioned at this point
characterization 3+
that the π bonding in the {ReV = O} unit of 9 causes
The preparative reactions for selected complexes can be sufficient splitting of the t2g (in Oh ) set (5dxz , 5d yz 
represented by the stoichiometric equations (1)–(7); no 5dxy ) that diamagnetism occurs through the configuration
attempts were made to optimize the yields, (5dxy )2 .
Complexes 1–10 are microcrystalline or powder-like,
2(NH4 )2 [MO4 ] + 2LH stable in the normal laboratory atmosphere, and solu-
EtOH/H2 O
ble only in DMF and DMSO. We had hoped to struc-
−−−−−−→ [M2 O5 L2 (H2 O)2 ] + 4NH3 + H2 O (1) turally characterized one or two complexes by single-
T
crystal X-ray crystallography (working mainly with DMF or
M = Mo(1), W(2), DMF/MeCN), but were thwarted on numerous occasions
RhCl3 · 3H2 O + 3LH+3NaO2 CMe by twinning problems or lack of single crystals. Thus, the
characterization of the complexes is based on spectroscopic
H2 O
(2) methods.
−−→ [RhL3 ](4) + 3NaCl + 3MeCO2 H + 3H2 O,
T
RhCl3 · 3H2 O + 2LH+2PPh2 + HCIO4 3.2. Electronic spectra
EtOH/H2 O
(3)
−−−−−−→ [RhL2 (PPh3 )2 ](ClO4 )(6) + 3HCl + 3H2 O, The band at 335 nm in the DRS spectrum of 1 is assigned to
T
an O2− → MoVI p–d LMCT transition and is characteristic
K2 [PdCl4 ] + 2LH of the {MoO2 }2+ moiety [11] in octahedral complexes.
(4) The transition appears at 337 nm as a shoulder in solution
MeOH/H2 O
−−−−−−−→ [PdL2 ](7) + 2KCl + 2HCl, (DMSO). The DRS spectrum of 3 is indicative of its low-
[PdCl2 (phen)] + LH + KOH spin octahedral structure. The ground term is 1 A1g and the
(5) two spin-allowed transitions to 1 T1g and 1 T2g are observed at
MeOH/benzene
−−−−−−−−−→ [PdL(phen)]Cl(8) + KCl + H2 O, 565 and 420 nm, respectively [12]; the corresponding bands
in DMSO are at 560 and 430 nm. The DRS spectra of the
[ReOCl3 (PPh3 )2 ] + 2LH
Rh(III) complexes 4 and 6 both exhibit bands at ∼470 and
(6) ∼380 nm; the spectra resemble those of other six-coordinate
EtOH
−−−→ [ReOl2 (PPh3 )2 ]Cl(9) + 2HCl + PPh3 ,
Rh(III) compounds and the bands are assigned as transitions
[UO2 (NO3 )2 ] · 6H2 O + 2LH from the 1 A1g ground state to the 1 T1g and 1 T2g upper states
(7) in octahedral symmetry in decreasing order of wavelength
MeOH
−−−−→ [UO2 L2 ](10) + 2HNO3 + 6H2 O. [12]. The lower wavelength band may also have a charge-
T
transfer character. Both complexes exhibit an additional
The metal is reduced (RuIII → RuII , IrIV → IrIII ) band in the blue region of the spectrum (∼520 nm) which
during the preparation of complexes 3 and 5 although is responsible for their red-brown colors; a possible origin
the reactions are performed in air. The redox reaction of this band is the singlet-triplet, spin-forbidden transition
1A
1g → T2g [12]. The spectrum of the Ir(III) complex 5
3
may be facilitated by the reducing character of LH, the
products from the oxidation of the ligand remaining in the shows two bands at 380 and 335 nm, which have a similar
solution. Thus, LH possibly plays two roles in the reactions, interpretation; the 1 A1g → 3 T2g transition is not observed.
that is, the role of the ligand and that of the reducing A weak shoulder in the spectrum of 9 is assigned to the
3 T (F) → 3 T transition in a d2 octahedral environment,
agent. It is well known that Ru(III) can undergo reduction 1g 2g
2− while an intense band at 375 nm most probably has an
reactions and that the [IrIV Cl6 ] ion is a convenient one-
electron oxidant [9]. The use of a base (KOH) in the LMCT origin [12]. The ligand-field spectra of 7 and 8 are
preparation of 8 is necessary to obtain the complex in pure typical of a square planar environment around pdII with
form; otherwise, the produced aqueous HCl decomposes the a mixed N,O-ligation; the bands at 480, 375, and 330 nm
compound. are assigned [12] to the 1 A1g → 1 A2g ,1 A1g → 1 Eg , and
1A
1g → B1g transitions, respectively, under D4h symmetry.
1
Complexes 1–5, 7 and 10 are nonelectrolytes in DMSO
[10]. Complexes 7 and 10 exhibit slightly increased molar The spectra in DMSO exhibit only two bands at 480 and
conductivity values in DMSO. Since DMSO is a good donor 330 nm.
solvent, this may be due to the partial displacement of
one L− ligand by two DMSO molecules. Assuming an 3.3. NMR studies
equilibrium between the neutral and the resulting cationic
complex, this displacement changes the electrolyte type of Diagnostic 1 H NMR assignments (in DMSO-d6 ) for repre-
the compound explaining the increased ΛM value [10]. From sentative complexes are presented in Table 1. The study was
the molar conductivities in DMSO (complexes 6 and 9) based on comparison with the data obtained for diamagnetic
and DMF (complex 8), it is concluded that compounds complexes with similar ligands [7, 13, 14]. In all the spectra
Sahar I. Mostafa et al. 5

studied, the integration ratio of the signals is consistent with Table 1: Diagnostic1 H NMR (δ, ppm)a spectral data for LH and
the assignments. the representative complexes 1, 3, 4, and 6–8 in DMSO-d6 .
The spectrum of LH exhibits two singlets at δ 6.07 and
Compound –N(1)H– –N(4)H2 /–N(6)H2 –O(5)H
6.18 assigned to the –N(4)H2 /–N(6)H2 (for the numbering
scheme see Scheme 2) amino hydrogens, respectively, and LH 7.43 6.07, 6.18 9.13
two relatively broad singlets at δ 7.43 and 9.13 due to 1 7.57 6.18, 6.55 —
the amide and hydroxyl protons –N(1)H– and –O(5)H, 3 7.49 6.14, 6.47 —
respectively. The appearance of these four peaks is consistent 4 7.44 6.20, 6.49 —
with the exclusive presence of the thione form of LH 6 b 6.11, 6.47 —
(Scheme 2) in solution. The proton of the hydroxyl group 7 7.47 6.17, 6.48 —
is not observed in the spectra of the complexes confirming 8 7.39 6.08, 6.46 —
its deprotonation and coordination to the metal ions. In the a The spectra were run 10–15 min after dissolution.
spectra of 1, 3, 4, and 6–8, the –N(1)H– signal undergoes b Obscured by the signals of the aromatic protons.
a marginal shift to indicate the noninvolvement of this
group in coordination; a relatively large downfield shift
would be expected if coordination had occurred. In the same
spectra, two signals appear for –NH2 protons, as expected. the 3400–3200 cm−1 region; this is apparently due to the
The most pronounced variation in chemical shift is the simultaneous presence of crystal and coordinated water in
downfield shift of one signal. Since more specific assignments these complexes [14]. In the spectra of 4–8, a medium
of these two signals seem impossible, it is difficult to conclude broad absorption indicates the presence of exclusively crystal
which amino nitrogen is coordinated. NMR evidence for (lattice) water.
the presence of thione –thiol tautomerism in the metal The absence of an IR or Raman band at ∼2600 cm−1 in
complexes in solution was not found. the spectrum of free LH suggests that the ligand exists in its
The 1 H NMR spectrum of 4 confirms that the three N,O- thione form (see Scheme 2) [18]. This is corroborated by the
bidentate (vide infra) ligands are equivalent (C3 symmetry), appearance of the medium v(C=S) band at 1177 cm−1 (this
and, therefore, the complex has the fac stereochemistry [15]. vibration appears as a strong peak at 1160 cm−1 in the Raman
The spectrum of 8 is indicative of the presence of one spectrum) and the strong IR v(N–H) band at 2970 cm−1 (this
solution species containing coordinated phen, consisting vibration appears as a medium peak at ∼3000 cm−1 in the
of four resonances [16]. Assignments are as follows (the Raman spectrum); the broadness and low frequency of the
numbers in parentheses are the positions of the protons latter IR band are both indicative of the involvement of the
in the classical numbering scheme of 1,10-phenanthroline; –NH– group in strong hydrogen bonding.
s = singlet, dd=doublet of doublets): 9.15 dd(2H; 2,9), The medium IR band at 3305 cm−1 in the spectrum of
8.53 dd(2H; 4,7), 8.00s(2H; 5,6), and 7.81q(2H; 3,8). Con- free LH is assigned to the v(OH) vibration. This band does
siderable downfield coordination shifts, Δδ(Hl )[Δδ(Hl ) = not appear in the spectra of the complexes indicating depro-
δ(Hl )complex − δ(Hl )free phen ], are observed for all resonances, tonation of the –OH group and suggesting coordination of
their values being 0.16, 0.27, 0.31, and 0.19 for the protons of the resulting, negatively charged oxygen atom. The absence
the positions (2,9), (4,7), (5,6), and (3,8), respectively. These of large systematic shifts of the δ(N–H), δ(NH), v(C=N),
shifts are characteristic of coordinated phen [16]. v(C2 –N1 )/v(C2 –N3 ), and v (C=S) bands in the spectra of
The 31 P{1 H} NMR spectrum of the Re(V) complex 9 in the complexes implies that there is no interaction between
DMSO-d6 consists of a sharp singlet at δ − 16.89, a value the ring nitrogen atoms or the exocyclic sulfur atom and the
which is typical for PPh3 -containing oxorhenium(V) species metal ions. The vas (NH2 ) and vs (NH2 ) bands are doubled
[17]. in the spectra of the complexes. One band for each mode
appears at almost the same wavenumber compared with the
3.4. Vibrational spectra corresponding band in the spectrum of free LH, whereas
the other band of each pair is significantly shifted to lower
Tentative assignments of selected IR ligand bands for wavenumbers. This fact is a strong evidence for the presence
complexes 1–10 and free LH are listed in Table 2. The of one coordinated and one “free” (i.e., uncoordinated)
assignments have been given by studying literature reports amino group per L− in the complexes [7].
[3, 13, 14], comparing the spectrum of LH with the spectra The presence of coordinated PPh3 groups in 6 and 9 is
of the complexes and by performing deuterium isotopic manifested by the strong IR bands at ∼1100 and ∼750 cm−1 ,
substitution experiments in few cases. As a general remark, attributed to the v(P–C) and δ(CCH) vibrations, respectively
we must emphasize that some stretching and deformation [17]; the former band overlaps with the ClO4 − stetching
modes are coupled, so that the proposed assignments should vibration in the spectrum of the Rh(III) complex 6. In the
be regarded as approximate descriptions of the vibrations. spectrum of 8, the bands at 1627, 1591, 1510, 1485, and
In the v(OH)water region, the spectra of complexes 1–3 1423 cm−1 are due to the phen stretching vibrations [16];
show one medium-intensity band at ∼3420 cm−1 attributed these bands are at higher wavenumbers compared with the
to the presence of coordinated water [13]. The same spectra free phen indicating chelation. The bands at 854, 841, 743,
exhibit, in addition to the relatively sharp band of coordi- and 725 cm−1 are assigned to the γ(CH) vibrations of the
nated water, a weaker broad continuous absorption covering coordinated phen [16].
6 Bioinorganic Chemistry and Applications

Table 2: Diagnostic ligand IR bands (cm−1 ) for LH and complexes 1–10.

Compound vas (NH2 )a vs (NH2 ) v(N–H) v(C=N), v(C=C) v(C2 –N1 ), v(C2 –N3 ) δ(NH) v(C=S)
LH 3390 3185 2970 1652 1652 1455 1177
1 3377, 3330 3180, 3156 3005 1631 1553 1460 1155
2 3388, 3356 3188, 3160 3000 1633 1556 1465 1170
3 3399, 3343 3180, 3079 3010 1632 1558 1464 1157
4 3400, 3320 3160, 3105 3005 1642 1560 1460 1170
5 3387, 3320 3166, 3110 3010 1635 1556 1455 1177
6 3380, 3357 3170, 3095 3015 1641 1552b 1443b 1176
7 3395, 3357 3164, 3098 3010 1646 1550 1446 1170
8 3397, 3360 3165, 3100 3015 1640 1553 1450 1176
9 3400, 3355 3155, 3105 3012 1639 1555b 1460b 1170
10 3405, 3324 3180, 3100 3010 1641 1558 1462 1164
a Overlapping with the v(OH)water band in the spectra of 1–8.
b Overlapping with phenyl stretching vibrations of the coordinated PPh3 ligands.

Table 3: Diameters (mm) of growth inhibitions zones for the NH2

antibacterial activity of LH and complexes 1, 4, 7, and 8.
O 4
a a 5 3
S. aureus (mg/cm3 ) P. aeruginosa (mg/cm3 ) N
Compound
10 20 50 100 10 20 50 100 M
2
LH 5 11 28 58 4 10 30 55
6
8 13 22 47 99 10 17 41 83 N N S
H2 1
7 10 17 42 86 9 14 39 77
4 8 13 29 49 7 13 30 44 H
1 10 19 43 80 7 13 32 61
a mg/cm3 represents the concentration of the reagent in the gel. Scheme 3: The proposed coordination mode of the anionic ligand
L− in complexes 1–10; M=metal ion.

Table 4: Diameters (mm) of growth inhibition zones for the

antifungal activity of LH and complexes 1, 4, 7, and 8.
a a
A. niger (mg/cm3 ) C. albicans (mg/cm3 )
Compound 896 cm−1 . As expected [19], the symmetric mode is weak
10 20 50 100 10 20 50 100 in the IR spectrum and strong in the Raman spectrum,
LH 5 12 23 44 6 9 34 55 while the opposite applies for the asymmetric mode. The
8 15 21 43 91 13 19 44 89 appearance of two stretching bands is indicative of the
7 10 17 40 79 9 16 38 68 cis configuration [19]. The strong IR band at 745 cm−1
4 0 0 0 0 6 11 21 37 is assigned to the vas (Mo–O–Mo) mode [20], indicating
1 6 15 31 63 7 16 33 68 the presence of a μ-O2− group. The vs (WO2 ), vas (WO2 ),
and vas (W–O–W) bands appear at 945, 922, and 755 cm−1 ,
Nystatinb 17 19 36 65 20 26 42 79
a mg/cm3
respectively, in the IR spectrum of complex 2 [19, 21];
represents the concentration of the reagent in the gel. the vs (WO2 ) and vas (WO2 ) Raman bands are at 940 and
bA currently prescribed antifungal drug.
917 cm−1 , respectively. The vs (WO2 ) and vas (WO2 ) modes
are at higher wavenumbers when compared to those of the
analogous Mo(VI) complex 1, suggesting [21] that the cis-
The vibrational spectra of the inorganic “parts” of WO2 2+ group has some “triple” bond character [21]. In the
complexes 1, 2, 6, 9, and 10 are also diagnostic. The IR spectra of 9, the band attributed to ν (Re=O) appears at 956
spectrum of 6 exhibits a strong band at ∼1100 and a medium (IR) and 968 (Raman) cm−1 [17, 19]. The IR spectrum of the
band at 624 cm−1 due to the v3 (F2 ) and v4 (F2 ) modes of the uranyl complex 10 exhibits only one U=O stretching band,
uncoordinated Td ClO4 − ion [19], respectively, the former that is, vas (UO2 ), at 940 cm−1 (not observed in the Raman
having also v(P–C) character [17]. In the 1000–750 cm−1 spectrum) indicating its linear transdioxo configuration
region, the spectra of 1 and 2 show bands characteristic of the [19]. The vs (UO2 ) mode appears as a strong Raman peak
cis-MO2 2+ units and the {O2 M–O–MO2 }2+ core (M=Mo, at 905 cm−1 , and, as expected, the corresponding IR band
W) [20, 21]. The IR bands at 930 and 912 cm−1 in 1 are is very weak. The bands at 345 and 298 cm−1 in the far-IR
assigned to the vs (MoO2 ) and vas (MoO2 ) modes, respectively spectrum of 7 are assigned to the v(Pd–NH2 ) and v(Pd-
[19, 20]; the corresponding Raman bands appear at 910 and O) vibrations, respectively. The appearance of one band for
Sahar I. Mostafa et al. 7

H2 O O O OH2 in the complex. The activity of the Pd(II) complexes 7 and

N
8 is tentatively attributed to their inhibition of the DNA
M O M O N
O O Ru replication (by interacting with enzyme prosthetic groups
N
N O and altering the microbial metabolism) and their ability to
O O OH2
OH2 form hydrogen bonds with the cell wall and cell constituents
[23]. The weaker activity of 4 is noteworthy; the reason for
1, 2 3
this is not clear.
+
O PPh3
N N O N 4. CONCLUSIONS
M' Rh
The M/LH general reaction system fulfilled its promise as a
N
O O O source of interesting complexes. From the overall evidence
PPh3
N presented before, it seems that the ligand L− behaves as
a bidentate chelate in all the prepared complexes with the
6 deprotonated oxygen and most probably the amino nitrogen
4, 5
of the position 6 of the pyrimidine ring being the donor
+ atoms, see Scheme 3. However, the participation of the
O N
O N' amino nitrogen of the position 4 of the ring cannot be ruled
Pd
Pd out. The nonparticipation of the sulfur atom in coordination
N O in complexes 7 and 8 may be seen as unusual given the soft
N N' character of Pd(II) in the context of the HSAB concept.
7 8 The chelate effect (a stable chelating ring with the
participation of the sulfur atom cannot be formed due to
+ the geometry of L− ) seems to govern the thermodynamic
O O
stability of these complexes. The proposed gross schematic
O PPh3 O N
structures for 1–10 are shown in Figure 1. Due to the
Re U
fact that single-crystal, X-ray crystallographic studies are
N N N O
not available, few structural features (e.g., the symmetric
O O
structures of 1–3, 6, 7, and 10) are tentative. The metal
ions adopt octahedral (1–6, 9, 10) or square planar (7, 8)
9 10 stereochemistries.
Figure 1: Schematic structures proposed for the neutral complexes Finally, complexes 1, 4, 7, and 8 are new welcome
1–5, 7, 10 and for the cations of complexes 6, 8, 9. Lattice H2 O additions in the growing family of metal complexes with
molecules and counterions have been omitted for clarity. However, antimicrobial activity.
 
N O and N N represent the ligands L− and phen, respectively. The
The results described in this report represent the initial
N and O donor atoms of L− are the amino nitrogen of the position study of the coordination chemistry of LH and the biological
6 (most probably) and the deprotonated oxygen of the position 5 of activity of its complexes. Further studies with 3d-metal ions
the pyrimidine ring; M=Mo, W; M = Rh, Ir. are in progress.

ACKNOWLEDGMENTS
each mode (B3u and B2u under D2h ) is consistent with a trans
structure [19]. The authors thank Dr. Constantinos Milios (University of
Edinburgh, UK) and Professor H. O. Desseyn (University
of Antwerp, Belgium) for providing them with the 31 P{1 H}
3.5. Antimicrobial activity studies NMR spectrum of 9 and far-IR/Raman spectra of some
complexes.
The free ligand LH and its complexes 1, 4, 7, and 8
were assayed in vitro for antimicrobial activity against two
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