Palladium(II) complexes of the thiosemicarbazone and N- ethylthiosemicarbazone of 3-hydroxypyridine-2-carbaldehyde: Synthesis, properties, and X-ray crystal structure

Article abstract of DOI:10.1002/hlca.200690187

Two novel, stable Pd^II complexes, compounds 3 and 4, of two 3-hydroxypyridine-2-carbaldehyde thiosemicarbazones, 1 and 2, resp., were prepared from Li₂PdCl₄. The single-crystal X-ray structure of complex 3 (=[Pd(2)Cl]) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N-, the imine N-, and the thiolato S-atoms. Intermolecular H-bonds, π-π, and CH...π interactions lead to a two-dimensional supramolecular assembly. The electronic, IR, UV/VIS, and NMR spectroscopic data of the two complexes are reported, together with their electrochemical properties. A sophisticated experimental procedure was used to determine the multiple dissociation constants of the ligands 1 and 2 by UV/VIS titration.

Full text of DOI:10.1002/hlca.200690187

Helvetica Chimica Acta – Vol. 89 (2006)
1959
Palladium(II) Complexes of the Thiosemicarbazone and
N-Ethylthiosemicarbazone of 3-Hydroxypyridine-2-carbaldehyde:
Synthesis, Properties, and X-Ray Crystal Structure
by Mavroudis A. Demertzis*, Paras Nath Yadav, and Dimitra Kovala-Demertzi*
Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina,
GR-45110 Ioannina
(phone: +30-32651-98425; fax: +30-32651-98792; e-mail: dkovala@cc.uoi.gr and mdemert@cc.uoi.gr)
Two novel, stable PdII complexes, compounds 3 and 4, of two 3-hydroxypyridine-2-carbaldehyde
thioACTHERUsNG emicarbazones, 1 and 2, resp., were prepared from Li2PdCl4. The single-crystal X-ray structure of
complex 3 (=[Pd(2)Cl]) shows that the ligand monoanion coordinates in a planar conformation to the
metal via the pyridyl N-, the imine N-, and the thiolato S-atoms. Intermolecular H-bonds, p–p, and
CH···p interactions lead to a two-dimensional supramolecular assembly. The electronic, IR, UV/VIS,
and NMR spectroscopic data of the two complexes are reported, together with their electrochemical
properties. A sophisticated experimental procedure was used to determine the multiple dissociation con-
stants of the ligands 1 and 2 by UV/VIS titration.
Introduction. – 3-Hydroxypyridine-2-carbaldehyde thiosemicarbazone (1) is a ribo-
nucleotide reductase inhibitor affecting the enzymeꢀs metal binding site. Compound 1 is
a member of the so-called ꢁa-(N)-heterocyclic carbaldehyde thiosemicarbazonesꢀ
(HCTs) [1], which are the most-potent known inhibitors of ribonucleoside diphosphate
reductase. The reductive conversion of ribonucleotides to their deoxyribonucleotide
counterparts is a particularly critical step in the synthesis of DNA, since deoxyribonu-
cleotides are present in extremely low concentrations in mammalian cells. Corey and
Chiba [2] have argued that an inhibitor of ribonucleotide reductase could be more
effective than an inhibitor of DNA polymerase in blocking DNA synthesis. Thus, it
seems reasonable that a strong inhibitor of ribonucleotide reductase, which is essential
for cellular replication, would be a useful addition to the existing therapeutic anticancer
agents.
Many HCTs have been reported to also exert tumor-inhibiting effects [3]. Early
studies on structure–activity relationships of heterocyclic thiosemicarbazones have sug-
ꢂ 2006 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
gested that antitumor activity directly correlates with their chelating ability [4]. Com-
pounds 1 and 5-hydroxypyridine-2-carbaldehyde thiosemicarbazone have shown high
activity in animal models, but were found to be readily glucuronidated and rapidly
excreted [5]. The combination of 1 with PtII or PdII agents damaging DNA gives rise
to synergistic inhibition of tumor growth by slowing down degradation processes
through shielding of the coordinating metal by bulky ligands, and may lead to improve-
ments in the effectiveness of cancer chemotherapy.
In earlier work, we investigated the PdII complexes formed with 2-acetylpyridine N-
ethylthiosemicarbazone (HAc4Et) against Leukemia P388 cells. A high correlation
between potency for SCE induction, effectiveness in cell-division delay (P<0.01) in
normal human lymphocytes, both in vitro and in vivo, established antitumor activity
in mice. These complexes were less cytotoxic and mostly more effective than the parent
ligand, HAc4Et, acting synergistically [6]. The PtII complexes of HAc4Et were also
found to exhibit cytotoxic potency in the very low micromolar range, being able to over-
come the cisplatin resistance of A2780/Cp8 cells [7]. These complexes may be endowed
with important anticancer properties since they elicit IC50 values in the same concentra-
tion range as the clinically used drug cis-DDP; moreover, they display cytotoxic activ-
ities in tumor lines resistant to cis-DDP.
In the present work, we have prepared and investigated the PdII complexes 3 and 4
of ligands 1 and 2, respectively, to investigate whether these compounds act synergisti-
cally, the ultimate goal being to correlate chemical structure with biological activity
[6–10]. This work is an extension of previously studied PdII and PtII complexes of thio-
ACHTREUNGsemicarbazones with potentially interesting biological activities [8–11].
Results and Discussion. – 1 .Ligand Dissociation Constants. Both compound 1 and
its Et congener 2, designated here as H2A , possess two protic functions, NH and OH, as
CTHREUNG
well as a pyridine N-atom susceptible to single protonation. Therefore, in aqueous sol-
ution, three independent conjugate acid–base pairs may be present. The dissociation
constants were determined by UV/VIS titration, as described elsewhere [12], the anal-
ysis being based on Eqns. 1–3. The resulting pKa values and details of the calibration
curves are collected in Table 1, and selected titration curves are shown in Fig. 1.
1
Ka1
eo ¼ AH A
þ
ðAH Aþ À AoÞ½H3OþŠ
(1)
(2)
(3)
2
3
Ao À AHAÀ
eo ¼ AH A À Ka2
½H3OþŠ
2
1
Ka3
eo ¼ AA2À
þ
ðAHAÀ À AoÞ½H3OþŠ
2. Synthesis. Compounds 1 and 2 were synthesized by means of the Heinert–Martell
reaction (Scheme) [13]. The corresponding PdII complexes 3 and 4 were prepared by
reacting lithium tetrachloropalladate (Li2PdCl4) – prepared in situ from PdCl2 and
LiCl – with the appropriate ligand in MeOH solution in a molar ratio of 1:1. For details,
see the Exper. Part.

Helvetica Chimica Acta – Vol. 89 (2006)
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Table 1. Analytical Parameters of the UV/VIS-Titration Graphs for the Determination of the Acid–Base
Properties of Ligands 1 and 2
a
Ligand
RSD of slope [%]
Confidence limit of slope
n
R
lobs [nm]
pKa )
1
1.56
À1.69
6.45
2.214.37”1
À0.83
6.42
3.27”103 Æ1.21 102
À4.60”10À8 Æ1.68”10À9
1.13”1012 Æ2.31”10 11
9
15
5
10
10
4
0.9991376
0.9982
0.9938
0.9980
0.9978
0.9945
3.51
Æ0.02
376
384
376
376
385
7.34Æ0.02
12.05Æ0.09
3.64Æ0.02
7.25Æ0.01
11.91Æ0.10
3
2
0
Æ2.22”102
À5.61”10 À8 Æ1.08”10À9
8.42”1011 Æ1.72”1011
a) Three values per ligand are given (pK
aACHTERU(NG 1)–pKaACHRTEU(GN 3)) in the order of acidity.
Fig. 1. UV/VIS Titration curves of the ligand 1 at a) pH 1.56–5.48 (H
3A
+/H
G
pair) and b) pH
6.61–9.05 (H2A
CTHREUNG
/HA– pair). For details, see Exper. Part.
3. Structural Characterization. Complex 4 was recrystallized from MeCN to furnish
orange prisms suitable for single-crystal X-ray analysis (Figs. 2–4). Selected inter-

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme
Fig. 2. X-Ray crystal structure of the PdII complex 4
ACHTREUNGatomic distances and bond angles are collected in Table 2. Anionic 2 acts as a tridentate
ligand coordinating to the PdII center through the pyridyl N-atom, N(1), the azome-
thine N-atom, N(2), and the thiolato S-atom. The ligand shows a (Z,E,Z)-configuration
for these three donor centers, respectively. The SÀC bond distance is consistent with an
increased single-bond character, and both thioamide C=N distances indicate increased
double-bond character. The ligand is basically planar, as indicated by the dihedral angle
between the mean planes of the pyridyl ring and the chelate ring PdÀSÀCÀNÀN, as
well as between the mean planes of the pyridyl ring and PdÀNÀCÀCÀN, with values
of 3.5(3) and 2.3(4)8, respectively.
Within the crystal, complex 4 is arranged in a head-to-tail fashion with a neighbor-
ing complex to form dimeric substructures stabilized by strong double p–p interactions
via Pd(1)ÀSÀC(7)ÀN(3)ÀN(2) {Cg(1)} ! Pd(1)ÀN(2)ÀC(6)ÀC(5)ÀN(1) {Cg(2)}, the
rings Cg(1) and Cg(2) facing each other at a typical stacking distance of 3.601(5) Š (Fig.
4, Table 3). The dimers are also connected by CH–p interactions. Atom HÀC(8) is
directed towards the symmetry-related (2Àx, Ày, 2Àz) pyridyl ring, with a distance
of 3.531(11) Š (Table 3). Thereby, one molecule of H2O participates in H-bonding.
Strong intermolecular H-bonding occurs between the O(2)-atom of H2O and HÀ
O(1) (2Àx, 1 /2+y, 5/2Àz) [O(1)···O(2), 2.645(11) Š; O(1)···H, 1.86 Š; O(2)···HÀ

Helvetica Chimica Acta – Vol. 89 (2006)
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Table 2. Selected Interatomic Distances (in Š) and Angles (in 8) for 4. The following symmetry trans-
formations were used to generate equivalent atoms: #1: (Àx+1, y+1/2, Àz+3/2); #2: (Àx+1, yÀ1/2,
Àz+3/2).
Pd(1)ÀN(2)
Pd(1)ÀN(1)
Pd(1)ÀS
1.933(8)
2.039(7)
2.236(3)
2.317(2)
1.739(8)
1.339(11)
1.387(11)
1.289(12)
1.330(11)
1.371(10)
1.315(10)
1.334(12)
1.473(11)
N(2)ÀPd(1)ÀN(1)
N(2)ÀPd(1)ÀS
81.3(3)
85.0(3)
166.3(2)
179.2(3)
98.2(2)
N(1)ÀPd(1)ÀS
Pd(1)ÀCl
N(2)ÀPd(1)ÀCl
N(1)ÀPd(1)ÀCl
SÀPd(1)ÀCl
SÀC(7)
N(3)ÀC(7)
N(3)ÀN(2)
N(2)ÀC(6)
N(1)ÀC(1)
N(1)ÀC(5)
O(1)ÀC(4)
N(4)ÀC(7)
N(4)ÀC(8)
95.51(9)
95.5(3)
C(7)ÀSÀPd(1)
C(7)ÀN(3)ÀN(2)
C(6)ÀN(2)ÀN(3)
C(6)ÀN(2)ÀPd(1)
N(3)ÀN(2)ÀPd(1)
C(1)ÀN(1)ÀC(5)
C(1)ÀN(1)ÀPd(1)
C(5)ÀN(1)ÀPd(1)
110.7(7)
119.0(7)
117.0(7)
123.9(6)
116.7(8)
132.1(6)
111.2(6)
Table 3. p–p and CH–p Interactions for 4. Cg(1), Cg(2), and Cg(3) refer to the centroids
Pd(1)ÀSÀC(7)ÀN(3)ÀN(2), Pd(1)ÀN(2)ÀC(6)ÀC(5)ÀN(1), and N(1)ÀC(1)ÀC(2)ÀC(3)ÀC(4)ÀC(5), resp.
p–p Interactions
(Cg(I) ! Cg(J))
Distance between ring Angle b between ring Cg(I)ÀPerpa) Cg(J)ÀPerpb)
centroids [Š]
centroids [8]
[Š]
[Š]
Cg(1) ! Cg(1)i c)
Cg(1) ! Cg(2)i
Cg(2) ! Cg(1)i
3.933(4)
3.601(5)
3.601(5)
24.98
10.59
10.59
3.565
3.551
3.540
3.565
3.540
3.551
CHÀp Interactions
C(8)ÀH(8B) ! Cg(3)ii
H···Cg [Š]
2.73
CÀH···Cg [8]
C···Cg [Š]
3.531 (11)
140.0
a) Cg(I)ÀPerp is the perpendicular distance of Cg(I) on ring J and b) Cg(J)ÀPerp is the perpendicular dis-
tance of Cg(J) on ring I. c) Symmetry transformations: i =(1Àx, Ày, 2Àz); ii =(2Àx, Ày, 2Àz).
Table 4. Intramolecular H-Bonds for 4. D and A refer to ꢁdonorꢀ and ꢁacceptorꢀ, resp.
DÀH
A
D···A [Š]
H···A [Š]
DÀH···A [8]
O(2)ÀH
N(4)ÀH
O(1)ÀHiv
C(1)ÀH
N(3)
2.822(9)
1.71
2.611
1.86
2.76
163.0
Cliii
O(2)
Sv
)
3.464(8) 73.0
2.645(11)
3.547(10)
a
a
)
161.0
143.0
a) Symmetry transformations: iii =(1Àx, À1/2+y, 3/2Àz) ; iv =(2Àx, 1 /2+y, 5/2Àz) ; v =(1Àx, 1 /2+y,
3/2Àz).
O(1), 1618] and between N(3) and HÀO(2) [N(3)···O(2), 2.822(9) Š; N(3)···H, 1.71
Š; O(2)ÀHÀN(3), 1638] (Table 4). Also, there is an intermolecular H-bond between
the HÀN(4) and the coordinated Cl ligand, and another one between HÀC(1) and

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 3. Intermolecular H-bonds in the crystal structure of 4. Symmetry operations: iii =(1Àx, À1/2+y,
3/2Àz), iv =(2Àx, 1 /2+y, 5/2Àz), v =(1Àx, 1 /2+y, 3/2Àz).
Fig. 4. Crystal packing of 4 viewed along the b-axis of the unit cell

Helvetica Chimica Acta – Vol. 89 (2006)
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the S-atom (Fig. 3, Table 4). These two intermolecular H-bonds connect the monomers,
which results in an infinite two-dimensional network (Fig. 4). Thereby, each complex is
partly hydrophilic at its outer surface, and partly hydrophobic at the interior. Strong
intermolecular H-bonding, p–p, and CH–p interactions help to stabilize the structure.
4. Spectroscopic Properties. 4.1. IR Spectra. The coordination of the azomethine N-
atom to the PdII center was suggested in the IR spectra of complexes 3 and 4, relative to
those of the free ligands, by a shift of the v(C=N) band to lower frequencies, along with
the occurrence of a v(NÀN) band to higher frequency. Furthermore, the presence of a
band at ca. 450–500 cmÀ1 was assigned to n(PdÀN). The thioamide band, which con-
tains considerable v(CS) character, was less intense in the complexes and found at a
lower frequency, suggesting coordination of the metal through sulfur after deprotona-
tion. Coordination of the thiolato S-atom was further indicated by a decrease in the
energy of the thioamide band, as well as by the presence of a band at ca. 400 cmÀ1
assignable to v(PdÀS). As expected, greater energy decreases in the thioamide band
occurred for the anionic form of the ligand owing to the CÀS entity formally becoming
a single bond. The ꢁbreathing motionꢀ of the pyridine ring was shifted to higher fre-
quency upon complexation, which is consistent with coordination of the pyridine N-
atom. An IR band at 1229 or 1221 cmÀ1 for 1 and 2, respectively, was assigned to
n(CÀO). This band was found to be shifted to 1185 and 1197 cmÀ1, respectively, in
the spectra of the corresponding complexes 3 and 4, which indicates that coordination
of the carbonyl O-atom does not occur. The relatively low energy of the n(CÀO) vibra-
tion in the spectra of 1–4 indicated that the carbonyl O-atom is involved in H-bonding
[14].
4.2. NMR Spectra. Peak assignments were based on 2D-NMR data (1H,1H-COSY,
1H,13C-HMQC, 1H,13C-HMBC). In the 1H-NMR spectra of the ligands 1 and 2, HÀN(3)
resonated at ca. d(H) 11.50, indicating that this H-atom is involved in H-bonding
[15][16]. This resonance was absent in the spectra of the corresponding complexes,
which indicated deprotonation of HÀN(3) and, thus, anionic semicarbazone moieties.
In the 1H-NMR spectra of the PdII complexes 3 and 4, both HÀC(1) and the formyl
H-atom HÀC(6) were shifted upon coordination, which indicated variations in the elec-
tron density at positions 1and 6. These two signals were shifted upfield, in accord with
an increased electron density at these sites in the complexes. However, due to p-back-
bonding from PdII to the imine function, an upfield shift of these resonances was
observed. These data indicate that the complexes are formed by ligand deprotonation
followed by metallation, a structural motive that seems to be stable both in the solid
state and in DMSO solution. The C=S resonances of the thiosemicarbazone moieties
in the free ligands resonated at d(C) 177.1–178.4. In the complexes, downfield shifts
were observed, indicating decreased electron density from the thiolato C-atoms
[15][16].
4.3. UV/VIS Spectra. The electronic spectra of complexes 3 and 4 were indicative of
square-planar geometries. In the visible region, three spin-allowed S ! S (d ! d) tran-
sitions can be expected [8]. However, strong charge-transfer (CT) transitions prevented
the observation of all these predicted bands. The very intense band at ca. 25,000–26,000
cmÀ1 in the spectra of the PdII complexes was assigned to the HOMO ! LUMO tran-
sition. The HOMO is a mixed orbital centered on Pd and the two donor atoms, d(Pd)/
p(S)/p(Cl). In contrast, the LUMO is mainly centered on the pyridyl ring. The observed

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Helvetica Chimica Acta – Vol. 89 (2006)
strong bands at 27,000–29,000 cmÀ1 were assigned to intraligand (IL) and CT transi-
tions.
The UV spectrum of complex 3 was also computed by single-point calculations
(ZINDO/1 singly excited interaction configuration) [14][17] based on the X-ray struc-
tural data of the complex.
5. Electrochemical Studies. The cyclic voltammogram (CV) of the ligands 1 and 2 in
DMF solution exhibited an irreversible negative cathodic wave at À1.272 and À1.306
V, respectively. This results from the reduction of the imine and thioamide groups pres-
ent in the thiosemicarbazone moiety, and these values are comparable to those
observed for other thiosemicarbazones [14]. The CVs of the complexes 3 and 4 showed
irreversible reductions at À1.344 and À1.360 V, respectively. The reduction potentials
of 3 and 4 was more negative than that of the corresponding ligands, and a decrease in
the order 1<2<3<4 indicated that the reduction process in the complexes is more dif-
ficult than in the free ligands.
The electrochemical data suggest that the reduction of 1–4 might be regarded as
more or less taking place on the pyridyl ring. The electron transfer from Pt is directed
to the LUMO p* orbital, which is a mixed orbital centered mainly on the pyridine. The
oxidation waves for 1 and 2 were observed at +0.657 and +0.618 V, respectively, and
those for 3 and 4 at +0.339 and +0.295 V, respectively. Oxidation is also associated with
a ligand-based process, and oxidized products are formed. The oxidation potentials of
1–4 increase in the order 1>2>3>4. Thus, reduction of ligands 1 and 2 is more easily
accomplished than in either 3 or 4, while the oxidation processes is more difficult. How-
ever, in the range from +1.5 to À2.5 V, additional peaks were observed.
Experimental Part
General. – Solvents were purified and dried according to standard procedures. UV/VIS Spectra
(including near-IR): JASCO V-570 spectrophotometer; lmax in cmÀ1 (e in l molÀ1 cmÀ1). FT-IR (including
far-IR) Spectra: Nicolet 55XC spectrophotometer, KBr pellets (4000–400 cmÀ1) and nujol mulls dis-
1
persed between polyethylene disks (400–40 cmÀ1). H- and 13C-NMR Spectra: Bruker AMX-400 spec-
trometer, at 250.13 and 62.90 MHz, resp., at ambient temp. in (D6)DMSO; d in ppm rel. to residual sol-
vent signals (d(H) 2.49 and 7.24, resp.). Elemental analyses (C,H,N,S) were performed on a Carlo-Erba
EA-1108 apparatus at the University of Ioannina. Analyses of Pd and Cl were performed in our labora-
tory by gravimetric and potentiometric techniques, resp.
Electrochemical Measurements. All measurements were made with an AUTOLAB PGSTAT30
potentiostat using a Pt microsphere as working electrode, a Pt-wire auxiliary electrode, and an Ag/
AgCl reference electrode in a three-electrode configuration. Ferrocene was added at the end of each
experiment and used as an internal standard. All potentials are reported rel. to the Ag/AgCl reference
electrode and ferrocinium/ferrocene (Fe+/Fc; E1/2 =0.173 V) in DMF at a scan rate 100 mV sÀ1
Et
ments were carried out under N2 atmosphere.
.
N+ClOÀ4 (0.1M) was used as supporting electrolyte, with 10À3 M solns. of the complexes. All experi-
4ACHTREUNG
3-Hydroxypyridine-2-carbaldehyde Thiosemicarbazone (1). Commercially available 3-hydroxy-(2-
hydroxymethyl)pyridine hydrochloride was oxidized with MnO2, prepared by heating MnCO3 for 12 h
at 3008, according to [13] to afford 3-hydroxypyridine-2-carbaldehyde in 62% yield as a yellow powder
(m.p. 778). The aldehyde (2 mmol) was then reacted with a soln. of thiosemicarbazide (2 mmol) in
EtOH (6 ml) at 608 for 16 h. Then, the mixture was kept in a refrigerator overnight. The resulting pre-
cipitate was filtered off, washed with cold EtOH, and dried in vacuo over silica gel at 40–508 for 4 h
to afford the title compound. Yield 75%. Bright-yellow powder. M.p. 2098. UV/VIS (DMF): 28,820
(44,100). IR: 3555s, 3451m (n(OH)); 3291m, 3194m (n(NH2, NH)); 1639s (n(C=N)); 1229s (n(CÀO));

Helvetica Chimica Acta – Vol. 89 (2006)
1967
1098s (n(NN)); 827s (n(C=S)). 1H-NMR1): 11.56 (s, HÀN(3)); 8.14 (d, HÀC(1)); 7.24 (m, HÀC(2), HÀ
C(3); 9.67 (s, OH); 8.35 (s, HÀC(6)); 8.04/8.25 (br. s, NH2). 13C-NMR1): 178.4 (C(7)); 153.8 (C(4)); 144.1
(C(6)); 141.3 (C(1)); 137.9 (C(5)); 125.6 (C(2)); 124.5 (C(3)). Anal. calc. for C7H8N4OS (196.04): C 42.8,
H 4.1, N 28.6, S 16.3; found: C 42.6, H 3.9, N 28.2, S 16.0.
3-Hydroxypyridine-2-carbaldehyde N-Ethylthiosemicarbazone (2). A soln. of 3-hydroxypyridine-2-
carbaldehyde (2 mmol) in EtOH (7 ml) was treated with a soln. of N-ethylyhiosemicarbazide (2
mmol) in dist. H2O (3 ml). The mixture was heated at reflux for 2 h, and then left standing in a refriger-
ator overnight. The resulting precipitate was filtered off, washed with cold EtOH, and dried in vacuo over
silica gel at 508 for 4 h. Yield: 80%. Bright-yellow powder. M.p. 2018. UV/VIS (DMF): 28,700 (43,600).
IR: 3298m (n(OH)); 32254m, 3119m (n(NH2, NH)); 1597s (n(C=N)); 1221s (n(CÀO)); 1085s (n(NN));
836m (n(C=S)). 1H-NMR1): 11.53/14.19 (s, HÀN(3)); 9.82 (br. s, OH); 8.48 (t, J=7.5, HÀN(4)); 8.37 (s,
HÀC(6)); 8.12 (d, HÀC(1)); 7.24 (m, HÀC(3), HÀC(2)); 3.56 (q, J=6.9, CH2); 1.12 (t, J=7.1, Me). 13C-
NMR1): 177.3/177.1 (C(7)); 153.66/153.30 (C(4)); 141.3/139.1 (C(1)); 138.16/139.6 (C(5)); 128.15 (C(3));
125.40/143.4 (C(6)); 124.5/126.3 (C(2)); 38.8 (Me); 14.6/14.5 (CH2). Anal. calc. for C9H12N4OS: C 48.2, H
5.4, N 24.9, S 14.3; found: C 48.2, H 5.3, N 24.7, S 14.4.
Chloro(3-hydroxy-2-pyridinecarboxaldehyde Thiosemicarbazonato)palladium(II) ([Pd(1)Cl]; 3). To
lithium tetrachloropalladate (1.2 mmol), prepared in situ from PdCl2 and LiCl, in MeOH (9 ml) was
added a soln. of ligand 1 (1mmol) in MeOH (8 ml). The mixture was stirred for 24 h at r.t., and then
left standing in a refrigerator for 24 h. The resulting orange precipitate was filtered off, washed with
cold MeOH and Et2ACHTREOUNG , and dried in vacuo over silica gel, and then at 708 in vacuo over P4ACHERTUOGN 10 ACHTREfUNG or 2 h.
Yield: 79%. Orange powder. M.p. 3178 (dec.). UV/VIS (DMF): 28,605 (sh, 39,600), 26,970 (40,900),
25,720 (41,500). IR: 3514w, 3403m (n(OH)); 3310 (br.), 3156 (br.) (n(NH2, NH)); 1626s (n(C=N));
1185s (n(CÀO)); 1045w (n(NN)); 708w (n(C=S)); 499s (n(PdN)); 416m (n(PdS)); 351s (n(PdCl));
1
302m (n(PdNpy)). H-NMR1): 11.52 (s, OH); 8.02 (d, J=7.6, HÀC(1)); 7.82 (br. s, NH2); 7.71( s, HÀ
C(6)); 7.50 (br., HÀC(3), HÀC(2)). 13C-NMR1): 181.97 (C(7)); 153.88 (C(4)); 145.57 (C(6)); 142.75
(C(1)); 139.87 (C(5)); 127.30 (C(2), C(3)). Anal. calc. for C7H7ClN4OPdS: C 24.9, H 2.1, Cl 10.5, N
16.6, Pd 31.6, S 9.5; found: C 25.0, H 2.1, Cl 10.5, N 16.5, Pd 31.5, S 9.6.
Chloro(3-hydroxypyridine-2-carboxaldehyde N-Ethylthiosemicarbazonato)palladium(II) Monohy-
drate ([Pd(2)Cl]·H2O; 4). Prepared as described above for 3, but using ligand 2. Yield 85%. Orange pow-
der. M.p. 2308 (dec.). UV/VIS (DMF): 28,075 (sh, 40,000), 26,740 (sh, 41300), 25,125 (42,200). IR: 3417
(br, n(OH)); 3335w, 3281s (n(NH2, NH)); 1606s (n(C=N)); 1197s (n(CÀO)); 1060w (n(NN)); 757m
1
(n(C=S)); 506m (n(PdN)); 408m (n(PdS)); 335m (n(PdCl)); 296m (n(PdNpy)). H-NMR1): 8.11 (s, HÀ
N(4)); 7.98 (d, HÀC(1)); 7.77 (s, HÀC(6)); 7.44, 7.55 (m, HÀC(3), HÀC(2)); 4.84 (br. s, OH); 3.23 (q,
J=7.8, CH2); 1.07 (t, J=7.1, Me). 13C-NMR1): 178.29 (C(7)); 154.04 (C(4)); 145.51 (C(6)); 143.79
(C(1)); 139.80 (C(5)); 127.76 (C(3)); 127.30 (C(2)); 41.57 (Me); 14.55 (CH2). Anal. calc. for
C9H11ClN4OPdS·H2O: C 28.2, H 3.4, Cl 9.3, N 14.6, Pd 27.8, S 8.4; found: C 28.3, H 3.5, Cl 9.3, N
14.7, Pd 27.3, S 8.4.
X-Ray Crystallography2). Slow evaporation of a MeCN solution of 4 provided an orange prismatic
crystal, which was mounted on a glass fiber and used for data collection. X-ray diffraction data were col-
lected on a Bruker SMART APEX diffractometer with graphite-monochromated MoKa radiation
(l=0.71073 Š). Cell constants and an orientation matrix for data collection were obtained by least-
squares refinement of the diffraction data from 25 reflections in the range 2.128<w<25.008. Data
were collected at 293 K, and corrected for Lorentz and polarization effects. A semi-empirical absorption
correction (w-scans) was made. The structure was solved by direct methods (SHELXS97) [18], and
refined by the full-matrix least-squares method on all F2 data using the WinGX version of the
SHELXL97 software [19]. All H-atoms were located in their calculated positions (CÀH bond length
1
)
)
Trivial atom numbering (see Fig. 2).
2
The crystallographic data of 4 (C9H11ClN4OPdS) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication No. CCDC-293433. Copies of the data can be
obtained, free of charge, at http://www.ccdc.cam.ac.uk/data_request/cif.

1968
Helvetica Chimica Acta – Vol. 89 (2006)
Table 5. Crystallographic Data for 4
Empirical formula
Mr [g/mol]
C CHTERUHGN 11ACHRETCUNG lN4AHCTREOUNG PdS
365.13
9A
Crystal system
Space group
Monoclinic
P21/c
Unit-cell dimensions:
a, b, c [Š]
7.2280(10), 13.925(2), 13.246(2)
a, b, g [8]
90, 100.920(10), 90
1309.1(3)
V [Š3]
Z
4
Dcalc [g/cm3]
1.853
m(MoKa) [1/mm]
F(000)
1.780
720
Crystal Size [mm]
Temperature [K]
l [Š]
0.20”0.20”0.30 mm
293(2) K
0.71073
q Range for data collection
Limiting indices
Reflections collected, unique
Absorption correction
Refinement method
Data, restraints, parameters
GoF on F2
2.14–25.008
0<h<8, À1<k<14, À14<l<14
2634, 2238 (Rint =0.0602)
none
Full-matrix least-squares on F2
2238, 0, 174
1.004
Final R [I>2s(I)]
R (all data)
Largest diff. peak and hole
R1=0.0554, wR2=0.1046
R1=0.1151, wR2=0.1247
0.693, À0.821e/A 3
0.93–0.97 Š), and refined using a riding model, except for Ow-H1and Ow-H2, which were located
through Fourier-difference synthesis. Molecular graphics were performed with PLATON 2001[20]. A
summary of the crystal data, experimental details, and refinement results are to be found in Table 5.
Determination of Dissociation Constants. Dist. H2O, obtained from a borosilicate auto-still (BIGASA
À4
Spa, Model BE-115/R), was used throughout. Stock solns. of ca. 1 0 M (concentration not exactly known
[21]) were prepared for each ligand by suspending the appropriate amount of each compound in warm
H2O for some hours, until sufficient dissolution was achieved. Then, the solns. were cooled to r.t., insolu-
ble material being removed by filtration, and finally diluted to the required concentration. From each
stock soln., four working solns. (A–D) of exactly the same, but unknown, ligand concentration (ca.
5”10À5 M) were prepared. Soln. A contained 0.01M KOH and 0.09M KCl, soln. B contained 0.1M HCl
and 0.1M KCl, soln. C contained 0.1M HCl, and soln. D contained 0.1M KOH and 0.1M KCl. During a typ-
ical UV/VIS titration of A with B, C, and D, many samples of nearly 5”10À5 M ligand concentration, hav-
ing different pH values, but constant ionic strengths (m=0.1, see below), were gradually prepared. Their
pH values were measured, and the related absorption spectra were recorded by transferring a portion of
each sample into a UV/VIS cuvette. Specifically, A was titrated within a jacketed vessel against B until
neutralization (pH 7.00). Other amounts of A were again added into the vessel whenever necessary to
correct and obtain a desired pH value. Samples with pH<7.00 were made by adding C in the titrated
soln. of the vessel. Amounts of D were added into the vessel whenever corrections for pH<7.00 were
necessary. It must be emphasized that it was no problem to partly or totally transfer the content of the
cuvette into a vessel, or pouring it elsewhere. Further, soln. A can have different concentrations of
KOH and KCl, provided the sum of them is equal to 0.1M. Soln. B contained various HCl concentrations;

Helvetica Chimica Acta – Vol. 89 (2006)
1969
C, in addition to HCl, may also contain KCl, the sum of their concentrations being 0.1M; finally, D can
only have different concentrations of KOH. All UV/VIS absorption spectra and pH measurements
were made at 258 on a JASCO 590 UV-VIS-NIR spectrophotometer and a Methrom-691 pH meter, resp.
Example: Find the ionic strength of a sample after addition of VB ml of B, which is a M in HCl and
0.1M in KCl, to VA ml of A, containing b M and c M of KOH and KCl, with b+c=0.1, resp. Soln. B contains
a”VB mmol of HCl that react with a”VB mmol of KOH of A and gives a”VB mmol of KCl. After addi-
tion of B to A, the soln. contains (b”VA)À(a”VB) mmol of KOH, but no HCl. The total concentration
ctot of KOH plus KCl in soln. is ctot =(bVA ÀaVB +aVB +cVA +0.1 VB)/(VA +VB)=0.1. The ionic strength
of the soln. (sample) is also 0.1, equal to ctot, since mono-monovalent electrolytes are used. At the equiv-
alence point, the soln. contains only 0.1M of KCl, and below pH 7.00, it contains a total concentration of
HCl+KCl equal to 0.1M. Therefore, the ionic strength of the solution during the titration process is con-
stant and equal to that of the analyte soln. (A).
We thank the NMR center of the University of Ioannina and Dr. V. Exarchou. Dr. R. Vargas is kindly
acknowledged for recording the X-Ray data at the X-ray crystallography center of the University of
Babes-Bolyai University, Cluj-Napoca, Romania.
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Helvetica Chimica Acta – Vol. 89 (2006)
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Received April 7, 2006