Zn(II) and Pd(II) complexes of thiosemicarbazone-S-alkyl esters derived from 2/3-formylpyridine

Article abstract of DOI:10.1081/SIM-120035948

Representative S-methyl/ethyl-4-H/phenylthiosemicarbazones and their Zn(II) and Pd(II) complexes were synthesized. Characterization of the 1:1 complexes, [Zn(L)Cl₂], [Pd(L)Cl₂], and [Pd(L)Cl]Cl, was accomplished by means of elemental

Full text of DOI:10.1081/SIM-120035948

SYNTHESIS AND REACTIVITY IN INORGANIC AND METAL-ORGANIC CHEMISTRY
Vol. 34, No. 4, pp. 653–665, 2004
Zn(II) and Pd(II) Complexes of
Thiosemicarbazone-S-alkyl Esters
Derived from 2/3-Formylpyridine
˙
¨
*
Irfan Kızılcıklı, Bahri Ulku¨seven, Yasemin Das¸demir,
and Barbaros Akkurt
Department of Chemistry, Engineering Faculty, Istanbul University,
Avcilar, Istanbul, Turkey
ABSTRACT
Representative S-methyl/ethyl-4-H/phenylthiosemicarbazones and their
Zn(II) and Pd(II) complexes were synthesized. Characterization of
the 1 : 1 complexes, [Zn(L)Cl2], [Pd(L)Cl2], and [Pd(L)Cl]Cl, was
accomplished by means of elemental analyses, IR and 1H NMR spectra.
The multidentate S-alkyl thiosemicarbazones coordinate as mono-, bi-,
or tridentate ligands depending on the types of the alkyl moiety and
metal ion.
Key Words: Polydentate thiosemicarbazones; Zn(II) and Pd(II) com-
plexes.
¨
*
Correspondence: Bahri Ulku¨seven, Department of Chemistry, Engineering Faculty,
Istanbul University, 34850-Avcilar, Istanbul, Turkey; E-mail: bahseven@istanbul.
edu.tr.
653
DOI: 10.1081/SIM-120035948
0094-5714 (Print); 1532-2440 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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INTRODUCTION
Thiosemicarbazones and their derivatives have been of great importance
because of their biological activities. In additon to the bacteriostatic and
fungistatic activities of thiosemicarbazone derivatives, the antiviral and anti-
tumor activities of this class of compounds have become very popular in
recent years.[1–9] Thiosemicarbazones that have a nitrogen or another hetero-
atom at the a-position, along with S-alkyl esters of thiosemicarbazones,
have outstanding selective biological activities when compared with others
in the same class. In the last decade, when the antitumor activity of metal com-
plexes of these compounds was discovered, the structural analysis of thiosemi-
carbazones in metal complexes has been an important topic.[10–12]
Thiosemicarbazones coordinate to metal ions through the azomethine
nitrogen and sulfur atoms. In addition, the coordination behavior is enhanced
by the presence of a heteropolar atom in the ring, which is also likely to be
coordinated to the metal ion and, therefore, a tridentate function is gener-
ated.[13] Pd(II) and Zn(II) complexes of biologically active tridentate thio-
semicarbazones, like the complexes of 2-acetylpyridine and 2-formylpyridine
thiosemicarbazone derivatives, have been studied intensively.[14–20,22]
The thiosemicarbazone ligands outlined in Fig. 1 were synthesized and
some of the structural properties of their Zn(II) and Pd(II) complexes were
investigated. Characterization of the compounds was accomplished by melting
points, molar conductivities, elemental analyses, IR and 1H NMR spectra.
RESULTS AND DISCUSSION
Synthesis and Some Physical Properties of the Compounds
It can be said that because the isolation of pure formylpyridine-S-alkyl-
thiosemicarbazones without the hydrohalide form is generally not possible,
they are thought to be solids with low melting points (Table 1). These
compounds could be obtained only as oily, viscous liquids in solution. The
hydrohalide forms of the ligands are bright yellow in color, while they are
pale yellow in the free ligand form. The melting points of the hydrohalides
were found to be in the 160–170 8C range, whereas the unique ligand L3,
which we were able to isolate in the free ligand form, has a melting point
of 62–63 8C. The zinc complexes are bright yellow while the palladium
complexes are brown.
The interaction of the ligands L (L ¼ L1–6) with metal salts in 1 : 1 molar
ratio in ethanol yielded stable solid complexes corresponding to the general
formulae [M(L)Cl2] and [M(L)Cl]Cl.

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Figure 1. Structures of the ligands.
Typical complexation reactions are given below.
L ꢀ HI þ ZnCl2 ꢁ! ½Zn(L)Cl2ꢂ þ HI
L ꢀ HI þ Li2½PdCl4ꢂ ꢁ! ½Pd(L)Cl2ꢂ þ 2LiCl þ HI
L ꢀ HI þ Li2½PdCl4ꢂ ꢁ! ½Pd(L)Cl]Cl þ 2LiCl þ HI
Hydroiodide salts of the ligands have poor solubilities in chlorinated
organic hydrocarbons such as dichloromethane, but are very soluble in
polar solvents like DMF or DMSO. The solubilities of the free ligands in
non-polar solvents are greater than their hydroiodide salts. The complexes
are very easily soluble in DMF and DMSO while their solubilities in ethyl
alcohol are negligible.
According to molar conductivities of the metal complexes of 2- and
3-pyridyl-derived ligands, it can be said that they fall into two groups.
Molar conductivities in DMSO of the Pd(II) complexes of L1, L2, L3, and
L4 range from 20 to 35 V21 cm2 mol21, in contrast, the Zn complexes have
relatively low conductivities of about 7 V21 cm2 mol21. The complexes
[Pd(L5)Cl2] and [Pd(L6)Cl2] have very low molar conductivities of about
1–3 V21 cm2 mol21
.
IR Spectra
IR spectra were obtained on KBr disks in the 4000–400 cm21 range. In
the IR spectra of the HI salts of the ligands (except L3), the bands in the
3350–3180 cm21 region are assigned to n(NH2) vibrations. The 4-phenyl
derivatives (L3 and L4) have only one band at ca. 3180–3210 cm21, as
expected. There are complicated bands in the IR spectra of the ligands in
the 1660–1550 cm21 range, which may be attributed to d(NH) deformation

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and n(C55N) vibrations belonging to azomethine, thioamide, and the pyridine
ring. In some spectra, it is also possible to observe those three bands separ-
ately. The stretching bands n(C–H) at 2915 + 10 cm21 and n(C–S) at
650–715 cm21 are present in the spectra.
The spectra of the Zn(II) complexes show some negligible shifts com-
pared to the ligands. Besides, it is thought that both of the n(NH2) bands in
Zn(L5)Cl2 at 3368 and 3268 cm21 are split into two bands.
In the spectra of the Pd(II) complexes of the ligands, one resonance was
observed at either lower or higher frequency with respect to the n(C55N)
bands in the spectra. The spectra of the Pd(II) complexes with L1 and L2 do
not contain the n(NH2) band system. However, the Pd(II) complexes of L5
and L6 give bands at 3425–3370 cm21, attributable to n(NH2) vibrations.
1H NMR Spectra
The 1H NMR spectra of HI salts of the ligands (except L3) were found to
be as expected (Table 2). The proton of HI in the ligands was observed at
12.0–14.0 ppm. The characteristic chemical shifts belong to the protons Hd
(d, J ¼ 4.8–5.0 Hz) for L1, L2, L3, and L4 and He for L5 and L6. These protons
were observed at 8.50–9.12 ppm due to the effect of the pyridine nitrogen. The
proton Ha of the pyridine ring in all of the ligands (d, J ¼ 4.6–4.8) shows
nearly the same chemical shift as the azomethine proton Hf. Both protons
were observed either in a broad singlet or within a non-split peak since they
are in the same system because of conjugation.
The cis–trans isomerism of methyl and ethyl groups as to the double
bond in the N255C moiety can be clearly distinguished in the spectra of L4
and L5. From the integral values of the peaks belonging to the isomers, a
40 : 60 ratio of the cis and trans structures was determined. There are also
cis and trans isomers of the alkyl moiety in [Zn(L1)Cl2], [Pd(L1)Cl]Cl,
[Pd(L3)Cl2], [Pd(L4)Cl2], and [Pd(L6)Cl2], with ratios between 40 : 60 and
30 : 70.
In the ZnCl2 complexes of L1 and L3, the chemical shift of the proton Hd
(d, J ¼ 4.2 Hz) changes upfield by ca. 0.2 ppm. This might show that the pyri-
dine nitrogen is coordinated to Zn(II) ion with a d10 system. The proton Hf in
the azomethine group shifts in a similar manner and, therefore, it can be con-
cluded that the Zn(II) ion coordinates through the pyridine and the azomethine
nitrogens.
In the spectra of [Zn(L5)Cl2], there is not a significant difference in the
chemical shifts of the protons He and Hf compared with the free ligand. How-
ever, the amide protons in the complex [Zn(L5)Cl2] were observed at 9.06 ppm
by shifting ca. 0.45 ppm to lower frequency.

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d

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An interesting result from the H NMR spectra is that only the methyl
1
esters form complexes with ZnCl2. The unexpected degree of magnitude of
steric hindrance from the ethyl group might have prevented the reaction of
L2, L4, and L6 with Zn(II) ion.
The split of n(NH2) bands in the IR spectra of [Zn(L5)Cl2] confirms the
structure. Taking the changeable character of amide protons into account, it
was concluded that Zn(II) is coordinated only via the thioamide moiety of
L5 since the pyridine nitrogen is farther removed in the molecule.
1
A fundamental change appears for pyridine ring protons in the H NMR
spectra of the Pd(II) complexes with L1, L2, L3, and L4, especially the proton
Hd (d, J ¼ 5.0–6.8 Hz). For example, the proton Hd of L1 at 8.34 ppm clearly
splits into two doublets (J ¼ 5.1 Hz) at 8.47 and 8.84 ppm with complexation.
This splitting occurs in a similar manner for the spectra of the Pd(II) com-
plexes with L2, L3, and L4. In addition, the proton Hc (d, J ¼ 6.2–7.4) in
[Pd(L3)Cl2] and [Pd(L4)Cl2] also gives a similar splitting. The new doublets
are due to cis and trans isomers of the protons Hc and Hd. Because the
Pd(II) ion is coordinated through the pyridine nitrogen, Pd(II) and (N55C)py
are in same coordination plane. The bonding can be compared with a p-accep-
tor ligand (ethylene derivatives, for example). Although the nitrogen atom of
the 3-pyridine ring is more distant, the change of the chemical shift of the pro-
ton Ha by 0.35 ppm downfield indicates the coordination of the palladium ion
with the ring nitrogen.
The resonances of the proton Hf in all of the Pd(II) complexes except for
[Pd(L4)Cl2] are shifted upfield when compared with the free ligand, indicating
that this region (at least the azomethine nitrogen) is always involved in the
coordination.
In the 1H NMR spectra, the amide protons on N4 of the Pd(II) complexes
with L1 and L2 were not observed clearly, because of both the tautomerism on
the thioamide groups and the proton N4H, which may be more acidic due to
the coordination of the N4 atom. However, the amide protons of L3, L4, L5,
and L6 in the complexes appear between 8.97 and 10.28 ppm. Therefore, the
general formulae of the Pd(II) complexes with L1 and L2 should be written
as [Pd(L)Cl)]Cl. This formulation is also confirmed by the relatively higher
conductance values of these complexes. For the Pd(II) complexes of L1 and
L2, the IR and 1H NMR data suggest dual five-membered chelate rings
(Fig. 2). The other Pd(II) complexes give a single five-membered chelate
ring with the azomethine and the pyridine nitrogens (Fig. 3).
The broad proton N4H signal of L5 appears as three peaks at 10.15, 9.92, and
9.65 ppm in the spectra of [Pd(L5)Cl2] and [Pd(L6)Cl2] due to the cis/trans
position of the amide protons relative to the double bonds (CH55N1) and (N255C).
In the complexes of L5 and L6, the Pd(II) ion comes close to the ring due to
coordination with the N3 nitrogen, and then the amide group rotates freely.

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Figure 2. Tentative structures of [Pd(L1)Cl)]Cl and [Pd(L2)Cl)]Cl (R55CH3, C2H5).
With these data in hand, we suggest the tentative structural formulae for
these types of the complexes, as shown in Figs. 2 and 3. In the light of the
above data, it was concluded that thiosemicarbazone-S-alkyl esters derived
from some pyridine carboxaldehydes may exhibit mono-, di-, or tridentate
functions depending on the types of alkyl moieties, the 2- or 3-position of
the pyridine nitrogen, and the metal ion.
EXPERIMENTAL
Chemicals and Apparatus
All chemicals and solvents were reagent grade and purchased from
Merck. IR spectra were recorded (KBr disks) on a Mattson 1000 FTIR spec-
1
trometer. H NMR spectra were obtained on a Bruker AC-200 NMR spec-
trometer (TUBITAK, Turkey). Chemical shifts were expressed in ppm
relative to TMS. The residual DMSO-d6 signal was also used as an internal
reference. Analytical data were obtained with a Carlo Erba 1106 analyzer
and Unicam Solar 929 atomic absorption spectrometer. The molar conduc-
tances of the compounds were measured in DMSO on a WPA CMD750 con-
ductivity meter at 25 + 1 8C. The chloride content was determined by a
Jenway 3040 ion analyzer.
Figure 3. Tentative structures of [Zn(L1)Cl2], [Zn(L3)Cl2], [Pd(L3)Cl2], and
[Pd(L4)Cl2] (M ¼ Zn, Pd; R2 ¼ CH3, C2H5; R3 ¼ H, Ph).

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Synthesis of 2-Formylpyridine-S-methylthiosemicarbazone
(L1) Hydroiodide
Thiosemicarbazide (4.55 g, 50 mmol) and methyl iodide (6.5 mL,
100 mmol) were refluxed in 50 mL ethanol for 2 hr. After the reaction mixture
was cooled to 50–60 8C, 2-formylpyridine (5 mL, 50 mmol) was added
dropwise and stirred for 1 hr. The bright yellow precipitate was collected by
filtration and washed with 5 mL portions of cold ethanol and diethyl ether,
respectively. The final product was dried over CaCl2 for 24 hr in vacuo.
The other ligands were prepared in a similar manner.[21] Melting points,
yields, and some other properties of the ligands are included in Table 1.
Synthesis of Dichloro(2-formylpyridine-
S-methylthiosemicarbazide)zinc(II)
The ligand L1 HI (100 mg, 0.31 mmol) was dissolved in 4 mL ethanol
.
and neutralized with a sufficient amount of aqueous NaHCO3 solution
(10%, w/w). The ligand solution was added to a solution of ZnCl2 (40 mg,
0.29 mmol) in 5 mL ethanol and the reaction mixture was stirred for 1 hr.
The bright yellow precipitate was collected by filtration and washed with
2 mL portions of cold ethanol and diethyl ether, respectively. The final product
was dried over CaCl2 for 24 hr in vacuo.
The Zn(II) complexes with L3 and L5 were prepared in a similar manner
(Table 1). The Zn(II) complexes of L2, L4, and L6 could not be obtained
in sufficient yield and purity. The beige-colored products obtained from the
reaction mixtures do not yield reproducible elemental analysis results.
Although the purity has been improved by recrystallization from various
solvent mixtures, the analytical data are not acceptable values. TLC test
indicates an impurity and the presence of free ligand in all cases.
Synthesis of Chloro(2-formylpyridine-
S-methylthiosemicarbazonato)palladium(II) Chloride
The ligand L1 HI (100 mg, 0.31 mmol) was dissolved in 4 mL ethanol
.
and neutralized with a sufficient amount of aqueous NaHCO3 solution
(10%, w/w). To the ligand solution was added 5 mL of a freshly prepared
Li2[PdCl4] solution (81 mg, 0.31 mmol) and the reaction mixture was
stirred for 2 hr at 50 8C. The brown precipitate was collected by filtration
and washed with 5 mL of cold ethanol. The product was dried over P4O10
for 8 hr in vacuo.

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Reactions of the other ligands with Li2[PdCl4] solution were accom-
plished as mentioned above. Only L3 was obtained in the free ligand form.
ACKNOWLEDGMENT
This study was supported by the Research Fund of Istanbul University,
Project Number 1162/070998.
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