Mixed-ligand palladium(II) complexes with amino acids, cytosine, and adenine

Article abstract of DOI:10.1134/S0036023607100166

pH titration shows that 1 : 1 : 1 mixed-ligand complexes are formed in the systems palladium(II)-Cyt-Glu-H₂O (loggB = 19.73) and palladium(II)-Cyt-Lys-H₂O (logβ = 16.20). Complexes Pd(C ₅H₅N₅)(C₅

Full text of DOI:10.1134/S0036023607100166

ISSN 0036-0236, Russian Journal of Inorganic Chemistry, 2007, Vol. 52, No. 10, pp. 1567–1569. © Pleiades Publishing, Inc., 2007.
Original Russian Text © A.K. Molodkin, N.Ya. Esina, M.V. Tachaev, M.N. Kurasova, 2007, published in Zhurnal Neorganicheskoi Khimii, 2007, Vol. 52, No. 10, pp. 1669–1671.
COORDINATION
COMPOUNDS
Mixed-Ligand Palladium(II) Complexes
with Amino Acids, Cytosine, and Adenine
A. K. Molodkin, N. Ya. Esina, M. V. Tachaev, and M. N. Kurasova
Russian University of Peoples’Friendship, ul. Miklukho-Maklaya 6, Moscow, 117198 Russia
Received February 16, 2007
Abstract—pH titration shows that 1 : 1 : 1 mixed-ligand complexes are formed in the systems palla-
dium(II)−Cyt–Glu–ç2é ( logβ = 19.73) and palladium(II)–Cyt–Lys–ç2é ( logβ = 16.20). Com-
plexes Pd(C5H5N5)(C5H8NO4)Cl, Pd(C5H5N5)(C6H13N2O2)Cl, Pd(C4H5N3O)(C6H13N2O2)Cl, and
Pd(C4H5N3O)(C5H8NO4)Cl are synthesized and characterized by chemical analysis, X-ray powder diffraction,
and thermogravimetry. The coordination mode of amino acids, cytosine, and adenine to the palladium(II) ion
is determined.
DOI: 10.1134/S0036023607100166
Complexes of the platinum-group metals have been 9.08, and ä3 = 10.54; and for Glu, pK1 = 2.31, ä2 =
actively studied with the goal of preparing new antitu-
mor medicines. The use of platinum(II)-based medi-
cines is limited by side reactions. Therefore, the atten-
tion of researchers has been focused on palladium(II)
compounds, which are far less toxic [1–6].
4.46, and ä3 = 9.72; we also used the stability con-
stants of binary complexes calculated by the Bjerrum
technique [13].
System
logK1
logK2
logK3
Mixed-ligand complexes of transition metals are
mediators of bioreactions in living organisms and inter-
mediates of technological processes.
Mixed-ligand complexes of palladium(II) with
amino acids, purine bases, and pyrimidine bases were
studied in [7–9].
We studied the interaction of palladium(II) with
adenine (C5H5N5, Ade), cytosine (C4H5N3O, Cyt), glu-
tamic acid (C5H9NO4, Glu), and lysine (C6H14N2O2, Lys).
Pd(II)–Cyt–H2O
10.70
8.52
6.30
8.60
6.85
5.50
Pd(II)–Glu–H O
5.84
2
Pd(II)–Lys–H2O
The titration curves for the Pd(II)–Cyt–Glu–ç2é
and Pd(II)–Cyt–Lys–ç2é systems lie below the
titration curves for amino acids and the pyrimidine
base. The stability constants of mixed-ligand com-
plexes are as follows: logβ (Pd(II)–Cyt–Glu) = 19.73
and logβ (Pd(II)–Cyt–Lys) = 16.20.
Potentiometric titration. pH titration showed that
1 : 1 : 1 mixed-ligand complexes are formed in the palla-
dium(II)–Cyt–Glu–ç2é and palladium(II)–Cyt–Lys–ç2é
systems. The reagents used were 0.01 M solutions of
H2PdCl4, which was synthesized as described in [10],
and 0.01 M solutions of cytosine, lysine, and glutamic
acid. An ionic strength was adjusted at 0.1 mol/L with
a 1 M KNO3 solution. The experiments were carried out
at +(0–21)°ë over a wide pH range. The titrant used
was a 0.1 KOH solution. The starting volume of the
titrated solutions was 50 mL.
Synthesis of complexes. Mixed-ligand complexes
Pd(Cyt)(Glu–)Cl and Pd(Cyt)(Lys–)Cl were synthe-
sized by mixing 0.01 M solutions of the reagents in the
1 : 1 : 1 (mol/mol) ratio. The solution was concentrated
to a viscous mass on a water bath; then, it was repeat-
edly treated with ethanol and acetone until a green-
brown precipitate appeared. The precipitate was fil-
tered, rinsed with acetone and ether, dried to constant
weight, and then analyzed.
We failed to determine stability constants for palla-
dium(II) complexes with adenine by potentiometric
titration because of the low solubility of the complexes.
Because palladium(II) forms sparingly soluble com-
pounds with adenine, complexes Pd(Ade)(Lys–)Cl and
SCOGS software was used to calculate the stability Pd(Ade)(Glu–)Cl were prepared by a different proce-
constants of mixed-ligand complexes [11]. The ioniza- dure, as follows. A 1 : 1 mixture of 0.01 M solutions of
tion constants of ligands used in the calculations were H2PdCl4 and lysine was concentrated to one-third its
determined by titrating amino acid and cytosine solu-
tions with 0.1 M HCl and KOH as in [12]: for Cyt,
pK1 = 4.32 and ä2 = 11.56; for Lys, pK1 = 2.35, ä2 =
initial volume on a water bath, then an equimolar
amount of a hot adenine solution was added. A pre-
cipitate was filtered, rinsed with an acetone + ethanol
1567

1568
MOLODKIN et al.
Results of chemical analysis of complexes
Found/calcd., %
Compound
Mr
Pd
N
C
H
Pd(C4H5N3O)(C5H8NO4)Cl (I)
Pd(C4H5N3O)(C6H13N2O2)Cl (II)
Pd(C5H5N5)(C6H13N2O2)Cl (III)
Pd(C5H5N5)(C5H8NO4)Cl (IV)
398.2
399.1
422.0
422.2
26.85/26.72
26.75/26.66
25.10/25.21
25.10/25.20
14.10/14.06
17.60/17.54
23.50/23.22
19.80/19.90
27.05/27.12
30.02/30.07
31.82/31.28
28.35/28.42
3.15/3.26
4.42/4.51
4.45/4.26
3.15/3.08
(1 : 2) mixture, and then stored in a desiccator until dium(II), because the band shifts relative to the uncom-
plexed ligand (1704 cm–1 in cytosine). The changed fre-
quencies of the stretching vibrations of the pyrimidine
ring (1621, 1510, 1464, and 1393 cm–1 in complexes
against 1601, 1504, 1472, and 1363 cm–1 in pure
cytosine) confirms that the ligand interacts with the
metal. Apparently, the heterocyclic N3 atom interacts
with the metal: the in-ring C=N stretching vibrations in
the complex appear at 1669 cm–1, and in uncomplexed
cytosine at 1633 cm–1. The bending frequencies of the
pyrimidine hydrogen atoms experience some shift:
1256 cm–1 (1240 cm–1) and 969 cm–1 (996 cm–1). The
Pd–N vibrations appear about 422 cm–1.
water was completely removed.
The compounds were identified and their formulas
determined by chemical analysis, thermogravimetry,
X-ray powder diffraction, and IR spectroscopy.
Palladium was determined gravimetrically [14].
Carbon, nitrogen and hydrogen were determined by
combustion and the absorption of the products on a
Carlo Erba CHNS-O EA 1108 Elemental Analyzer
[15]. The results of chemical analyses are tabulated.
X-ray powder diffraction (DRON-2, monochro-
matic CuKα radiation, 1/4 deg/min) implies that all
compounds were individual.
Presumably, cytosine is coordinated to palla-
dium(II) through its heterocyclic N3 atom and the car-
bonyl oxygen atom (C=O). Lysine and glutamic acid
are presumably bidentate due to their α-NH2 and
Thermogravimetric analysis (MOM derivato-
graph, 20–1000°ë, 10 K/min, Al2O3 reference) showed
that all compounds have identical thermal curves. At
200–500°ë, the melting occurs, which is followed by
decomposition of complexes because of the destruction
and burning up of the organic part of the molecule. The
final thermolysis product is metallic palladium with
minor carbon.
IR spectra (400–4000 cm–1) were recorded as KBr
disks on Specord 75IR and Specord M82 spectropho-
tometers. IR absorption spectra were assigned with ref-
erence to the assignment of the spectra of the reagents
and analogues [16–18].
ëéé– groups.
The spectra of mixed-ligand complexes with ade-
nine differ from the spectra of the uncomplexed
ligands. The differences are in the stretching and bend-
ing vibrations of the purine ring. For example, the C=N
stretching vibrations in the heterocycle shift toward
1706 cm–1 (against 1673 cm–1 in adenine). The C=C
and C–N bending vibrations in the purine ring are
observed at 990–937 and 813–774 cm–1 (cf. 1021 and
The IR spectra of the complexes differ from the 852–871 cm–1 in the pure ligand).
spectra of free ligands, indicating that the ligands are
coordinated to a palladium(II) ion. The similarity
of the spectra of Pd(C4H5N3O)(C5H8NO4)Cl and
Pd(C4H5N3O)(C6H13N2O2)Cl implies the identical
bonding of palladium(II) atoms with amino acids and
cytosine in these complexes.
Some vibrational bands (at 1536, 1184, and 1099 cm–1)
can be assigned to the N–H bending vibrations in the
α-amino group of the amino acid, which apparently
interacts with the metal.
The vibrations at 1634 and 1412 cm–1 are likely due
to the antisymmetrical and symmetrical vibrations of
the ëéé– group of the amino acid, which interacts with
the metal; the bending vibrations of this group appear
at 591 and 535 cm–1.
The vibrations in the purine ring appear at 1617,
1586, 1441, and 1380 cm–1; they experience a shift rel-
ative to the pure ligand (1612, 1510, 1419, 1367 cm–1).
13C NMR spectra of solutions of ligands, either free
or complexed, were recorded with suppression of pro-
ton signals on a high-resolution Fourier-transform
Bruker AC-200 pulsed spectrometer with a working
proton frequency of 200.13 MHz. Chemical shifts were
determined relative to external tetramethylsilane.
Analyzing the spectroscopic data, we observe
changes in the chemical shifts for all 13ë signals from
lysine in compounds II and III relative to the uncom-
plexed ligand. The displacement of the chemical shifts
of signals from the carboxy carbon atom of lysine
(∆δë1 = 2.98 ppm) proves that this carboxy group is
chemically bonded to a palladium(II) ion. The displace-
ment of the chemical shift for signals from the ë3 atom
There is a strong band at 1725 cm–1; it can be
assigned to the stretching vibrations of the C=O group
of cytosine. this group possibly interacts with palla- (∆δë3 = 2.69 ppm) indicates the involvement of the
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 52 No. 10 2007

MIXED-LIGAND PALLADIUM(II) COMPLEXES
1569
4. I. A. Efimenko, N. A. Ivanova, and O. S. Erofeeva, Pro-
ceeding of the 21st Chugaev International Conference
on Coordination Chemistry (Kiev, 2003), p. 72 [in Rus-
sian].
5. O. N. Shishilov, T. A. Stromnova, and A. V. Churakov,
Zh. Neorg. Khim. 51 (4), 626 (2006) [Russ. J. Inorg.
Chem. 51 (4), 574 (2006)].
6. Aydin Tavman, Mustafa Hayvali, Hayati Filik, Emine
Kilic // Zh. Neorg. Khim. 51 (8), 1284 (2006) [Russ. J.
Inorg. Chem. 51 (8), 1198 (2006)].
7. L. F. Krylova and I. S. Kuprov, Zh. Neorg. Khim. 48 (8),
1288 (2003) [Russ. J. Inorg. Chem. 48 (8), 1168 (2003)].
α-NH2 group in chemical bond with a palladium(II)
ion. Inasmuch as the displacement of the chemical
shifts of signals from the C6 atom of lysine cannot be
evaluated (this signal is under the DMSO signal), the
participation of the ε-amino group of the ligand can be
suggested circumstantially (on the basis of the dis-
placement of the chemical shifts of the C5 signals rela-
tive to uncomplexed lysine). The significant displace-
ment of the chemical shift of the C5 signal from lysine
(∆δ = 2.10 ppm) can signify that the ε-amino group of
the ligand interacts with another palladium ion.
Thus, lysine is coordinated to a metal ion through its
carboxy oxygen atom and the nitrogen atom of the
α-amino group; the ε-amino group of lysine partici-
pates in intermolecular bonds.
8. A. K. Molodkin, N.Ya. Esina, E. K. Gnatik, and D. Ntisi,
Zh. Neorg. Khim. 42 (9), 1502 (1997) [Russ. J. Inorg.
Chem. 42 (9), 1368 (1997)].
9. A. K. Molodkin, N. Ya. Esina, M. N. Kurasova, and
E. E. Khaidarova, Zh. Neorg. Khim. 45 (11), 1823
(2000).
13
The ë-{1H} NMR spectra of complexes III and
IV show that all coordination sites of adenine are
involved in bonding to the metal. The maximum 10. Synthesis of Platinum-Group Metal Complexes metallov,
Ed. by I. I. Chernyaev (Nauka, Moscow, 1964), p. 64 [in
Russian].
11. I. G. Sayce, Talanta 15 (12), 1397 (1968).
12. A. Albert and E. Sergeant, Ionization Constants of Acids
and Bases (Wiley, New York, 1962; Khimiya, Moscow,
1964).
13. J. Bjerrum, Metal Ammine Formation in Aqueous Solu-
tion (Kopenhagen, 1957; Inostrannaya Literature, Mos-
cow, 1961).
changes in the chemical shifts relative to the uncom-
plexed ligand are observed for the C5 and C8 atoms of
adenine (10.08 and 8.27 ppm, respectively); this obser-
vation can indicate that the preferred coordination
mode of adenine to a palladium(II) ion is through the
heterocyclic N7 atom (possibly, because of proton
mobility, through the N9 atom). The amino group of
adenine is presumably hydrogen-bonded to the water
oxygen atom.
14. G. Charlot, Les Methodes de la Chimie Analytique:
Analyse Quantitative Minerale (Masson, Paris, 1961;
Khimiya, Moscow, 1969).
15. V. A. Klimova, in Fundamental Methods of Organic
Microanalysis (Moscow, 1967), p. 104 [in Russian].
With reference to the related literature [19] and
NMR spectroscopic data, we may suggest that adenine
interacts with palladium(II) through its heterocyclic
nitrogen atom (probably, the N7(N9) atom), while
lysine interacts through its carboxy and α-NH2 groups.
16. Y. Inomata, T. Inomata, and T. Moriwaki, Bull. Chem.
Soc. Jpn. 44, 365 (1971).
REFERENCES
17. G. F. Bol’shakov, N. A. Glebovskaya, and Z. G. Kaplan,
in Infrared Spectra and X-ray Diffraction Patterns of
Heteroorganic Compounds (Khimiya, Leningrad, 1967),
p. 168 [in Russian].
18. K. Nakamoto, Infrared Spectra of Inorganic and Coor-
dination Compounds (Wiley, New York, 1963; Mir,
Moscow, 1966).
1. K. B. Yatsimirskii, V. V. Mosin, A. N. Kozachkova, and
I. A. Efimenko, Koord. Khim. 19 (10), 793 (1993).
2. R. Ilavarasi, M. N. S. Rao, and M. R. Udupa, Indian J.
Chem., Sect. A: Inorg., Bio-Inorg., Phys., Theor. Anal.
Chem. 38 (2), 161 (1999).
3. A. K. Molodkin, N. Ya. Esina, and O. I. Andreeva, Zh.
Neorg. Khim. 49 (3), 468 (2004) [Russ. J. Inorg. Chem. 19. A. I. Stetsenko, K. I. Yakovlev, and S. A. D’yachenko,
49 (3), 417 (2004)].
Usp. Khim. 56 (9), 1533 (1987).
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 52 No. 10 2007