Synthesis, spectroscopy and X-ray crystal structures of some zinc(II) and cadmium(II) complexes of the 2-pyridinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazates

Article abstract of DOI:10.1016/j.poly.2014.02.016

The Schiff bases formed by condensation of S-methyl- and S-benzyldithiocarbazate with 2-pyridinecarboxaldehyde react with zinc(II) and cadmium(II) acetates to form stable metal complexes of general formulas, [Zn(NNS)(CH₃COO)]₂ and [M(NNS)₂] (M = Zn ²⁺, Cd²⁺; NNS^- = anionic forms of the 2-pyridinecarboxaldenhdye Schiff bases of S-methyl- and S-benzyldithiocarbazate, respectively) which have been characterized by a variety of physico-chemical techniques and X-ray crystallographic structure analysis. The complexes, [Zn(NNS)(CH₃COO)]₂ are acetate anion-bridged centrosymmetric dimers in which each of the Schiff bases is coordinated to the zinc(II) ions as a uninegatively charged NNS tridentate chelating agent coordinating via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. The acetate anion acts as a bridging bidentate ligand coordinating with the two zinc atoms in a syn-syn manner. Each zinc(II) ion in the dimer adopts an approximately square-pyramidal geometry. The bis-ligand complexes, [M(NNS)₂] (M = Zn²⁺, Cd²⁺) have distorted octahedral structures in which the two anionic Schiff bases are coordinated to the metal ions meridionally as NNS tridentate chelating agents via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. Both the mono- and bis-ligand zinc(II) complexes exhibit strong cytotoxic activity against the HELA (human cervical cancer) cell lines. Some of these compounds exhibit stronger cytotoxicity against HELA than the commercially important anticancer drug, Tamoxifen.

Full text of DOI:10.1016/j.poly.2014.02.016

Polyhedron 74 (2014) 16–23
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis, spectroscopy and X-ray crystal structures of some zinc(II)
and cadmium(II) complexes of the 2-pyridinecarboxaldehyde Schiff
bases of S-methyl- and S-benzyldithiocarbazates
Aminul Huq Mirza a,1, Malai Haniti S.A. Hamid a, Sazwani Aripin a, Mohammad Rezaul Karim b,
Md. Arifuzzaman b, Mohammad Akbar Ali a, , Paul V. Bernhardt c
⇑
a Faculty of Science, Universiti Brunei Darussalam, Jalan Tungku Link, BE 1410, Brunei Darussalam
b Department of Chemistry, Tennessee State University, TN 37209-1561, USA
c School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
The Schiff bases formed by condensation of S-methyl- and S-benzyldithiocarbazate with 2-pyridinecar-
boxaldehyde react with zinc(II) and cadmium(II) acetates to form stable metal complexes of general
formulas, [Zn(NNS)(CH3COO)]2 and [M(NNS)2] (M = Zn2+, Cd2+; NNSꢀ = anionic forms of the 2-pyridine-
carboxaldenhdye Schiff bases of S-methyl- and S-benzyldithiocarbazate, respectively) which have been
characterized by a variety of physico-chemical techniques and X-ray crystallographic structure analysis.
The complexes, [Zn(NNS)(CH3COO)]2 are acetate anion-bridged centrosymmetric dimers in which each of
the Schiff bases is coordinated to the zinc(II) ions as a uninegatively charged NNS tridentate chelating
agent coordinating via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur
atom. The acetate anion acts as a bridging bidentate ligand coordinating with the two zinc atoms in a
syn–syn manner. Each zinc(II) ion in the dimer adopts an approximately square-pyramidal geometry.
The bis-ligand complexes, [M(NNS)2] (M = Zn2+, Cd2+) have distorted octahedral structures in which
the two anionic Schiff bases are coordinated to the metal ions meridionally as NNS tridentate chelating
agents via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom.
Both the mono- and bis-ligand zinc(II) complexes exhibit strong cytotoxic activity against the HELA
(human cervical cancer) cell lines. Some of these compounds exhibit stronger cytotoxicity against HELA
than the commercially important anticancer drug, Tamoxifen.
Received 24 December 2013
Accepted 11 February 2014
Available online 28 February 2014
Keywords:
Zinc(II) and cadmium(II) complexes of Schiff
bases
2-Pyridinecarboxaldehyde Schiff bases of
S-methyl- and S-benzyldithiocarbazates
Acetate-bridged dimer
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
structurally characterized. It not only exhibits the same anti-cancer
activity as the metal-free chelating agent but also enhances the
Schiff bases derived from S-alkyl/aryl esters of dithiocarbazic
acid and their metal complexes have been extensively studied [1]
because of their interesting physical and chemical properties [2]
and potentially useful biological activities [3]. Tridentate NNS do-
visualization of the uptake and distribution of Triapine by cancer
cells [5]. The cellular distribution of Triapine and its zinc(II) com-
plex has been studied by fluorescence microscopy in living SW
480 cells (human Colon carcinoma) [5].
nor Schiff bases derived from
a
-N-heterocyclic carboxaldehydes
Since complexes of the zinc(II) ion are involved in a large num-
ber of important biological processes [6] and the chemical similar-
ity of cadmium(II) with that of zinc(II) suggests that the former
may displace the latter from metalloenzymes containing zinc(II)
at the active sites, a thorough study of the coordination chemistry
of these metal ions with sulfur-nitrogen chelating agents would be
worthwhile. Although, cadmium is known to be extremely toxic to
mammals and is generally viewed as an environmental problem
not used by nature in any way, a recent study [7] reporting the
characterization of a previously unknown metalloenzyme from
the marine diatom Thalassiosira weissflogii shows that this
and S-alkyl/aryl dithiocarbazates are analogs of the experimental
anticancer drug, Triapine (3-aminopyridine-2-carboxaldehyde thi-
osemicarbazone; Fig. 1) that has entered several Phase I and Phase
II clinical trials as a potent anti-cancer chemotherapeutic agent [4].
The zinc(II) complex of Triapine has recently been synthesized and
⇑
Corresponding author.
E-mail address: palonkuri@yahoo.com (M.A. Ali).
Tel.: +88 01720118782; fax: +673 2 461502.
1
http://dx.doi.org/10.1016/j.poly.2014.02.016
0277-5387/Ó 2014 Elsevier Ltd. All rights reserved.

A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
17
2.4. Preparation of the ligands
N
S
N
These ligands were prepared following literature methods
[9,13] as detailed below.
NH
NH2
NH2
2.4.1. Preparation of the 2-pyridinecarboxaldehyde Schiff base of S-
methyldithiocarbazate (Hpysme) (1)
Fig. 1. Triapine.
S-Methyldithiocarbazate (3.0 g, 0.025 mol) dissolved in hot eth-
anol (50 mL) was mixed with a solution of 2-pyridinecarboxalde-
hyde (3.0 g, 0.028 mol) in the same solvent (50 mL). The yellow
product that had instantly formed was then filtered off and recrys-
tallized from a 1:2 mixture of MeCN and MeOH. Yield, 2.00 g
(39%). M.p. 190–195 °C. Anal. Calc. for C8H9N3S2: C, 45.47; H, 4.29;
N, 19.89. Found: C, 45.40; H, 3.99; N, 19.32%. 1H NMR [TMS, CDCl3]
dH: 13.62(br. s, 1H, NH), 8.30(s, 1H, HC@NA), 8.69(d, 1H, py-H),
8.09–7.30(m,3H, py-H), 2.67(s, 3H, –SCH3); 13C NMR [TMS, DMSO-
d6], dC: 199.79(C@S), 152.80(CH@N), 150.28(py-C), 146.90(py-C),
137.50(py-C), 125.37(py-C), 120.48(py-C), 17.31(SCH3).
metalloenzyme specifically uses cadmium to achieve its biological
function.
In view of the less work reported on zinc(II) and cadmium(II)
complexes of tridentate NNS dithiocarbazate ligands and the signif-
icant anticancer activity exhibited by the zinc(II) complex of Tria-
pine, which is structurally related to the 2-pyridinecaboxaldehyde
Schiff bases of S-methyl- and S-benzyldithiocarbazates, we report
here the zinc(II) and cadmium(II) complexes of two NNS tridentate
chelating agents that are structurally related to the experimental
anticancer drug, Triapine.
2.4.2. Preparation of the 2-pyridinecarboxaldehyde Schiff base of
S-benzyldithiocarbazate (Hpysbz)(2)
2. Experimental
S-Benzyldithiocarbazate (0.93 g, 4.7 mmol) dissolved in boiling
absolute ethanol (20 mL) was mixed with a solution of 2-pyridinecar-
boxaldehyde (0.5 g, 4.7 mmol) in the same solvent (10 mL). The
resulting solution was heated under reflux for 1 h and left to stand
to cool to roomtemperature. The yellowsolid that hadformed was fil-
teredoff, washedwith coldethanolanddried invacuo over anhydrous
silica gel. The crude product was recrystallized from ethanol to obtain
pale yellow crystals. Yield, 0.77 g (57%). M.p. 198–202 °C (Lit. [3f],
m.p. 193 °C). Anal. Calc. for C14H13N3S2: C, 58.51; H, 4.56; N, 14.62.
Found: C, 57.58; H, 4.21; N, 14.54%. 1H NMR [DMSO-d6], dH:
13.51(br, s, 1H, NH), 8.25(s, 1H, CH@N), 8.60(d, 1H, py-H),
7.81–7.89(m, 2H, Ar-H and py-H), 7.40–7.43(m, 3H, py-H and Ar-H),
7.23–7.34(m, 3H, py-H), 4.48 (s, 2H, CH2-S); 13C NMR [TMS,
DMSO-d6], dC: 197.50 (C@S), 152.80(CH@N), 150.30(py-C),
147.20(py-C), 137.70(py-C), 137.30(ph-C), 130.00(ph-C), 129.20(ph-
C), 128.00(ph-C), 125.60(py-C), 120.60(py-C), 38.20(SCH2).
2.1. Reagents
Chemicals and solvents used were of analytical reagent grades
and used without any further purification. 2-Pyridinecarboxalde-
hyde and the zinc(II) salts were purchased from the Aldrich Chem-
ical Company and S-methyl- and S-benzyldithiocarbazates were
prepared according to published procedures [8,9].
2.2. Physical measurements
Microanalyses for C, H and N were performed by the Elemen-
tal Analysis Laboratory, National University of Singapore,
Singapore. Molar conductances of ca. 10ꢀ3 M solutions of the
complexes DMSO were measured by means of a CMD400 conduc-
tivity meter. The melting points of the compounds were deter-
mined by a Sem1 Stuart Scientific Melting Point apparatus and
were uncorrected. IR spectra were recorded as KBr discs on a
Perkin-Elmer Spectrum 100 spectrometer. 1H NMR spectra were
2.5. Preparation of the complexes
2.5.1. Preparation of [Zn(pysme)2] (3)
To a solution of zinc(II) acetate dihydrate (0.10 g, 0.47 mmol) in
boiling MeOH (5 mL) was added a solution of Hpysme (1.0 mmol)
in a hot 2:1 mixture of MeOH and MeCN (15 mL). The mixture was
then heated on a steam bath until the volume of the reaction mix-
ture was reduced to about 10 mL. On standing at room tempera-
ture for a week, the reaction mixture deposited crystals of the
complex which were filtered off and recrystallized from a 2:1 mix-
ture of MeCN and MeOH. Yield, 0.13 g (57%). M.p. >300 °C (dec.).
Anal. Calc. for C16H16N6S4Zn: C, 39.54; H, 3.32; N, 17.29. Found:
C, 39.58; H, 3.14; N, 17.04%. 1H NMR [DMSO-d6] dH: 9.00(s, py-
H), 8.01(t, py-H), 7.85(d, py-H), 7.40–7.47(m, py-H), 7.23–7.33(m,
py-H), 3.15(s, SCH3).
recorded on
a Varian 400-NMR spectrometer using either
DMSO-d6 or CDCl3 as solvents and TMS as an internal standard
at Universiti Brunei Darussalam or were run in CDCl3 on a Bruker
Advance, 400 MHz spectrometer in the Department of Chemistry,
Tennessee State University, USA.
2.3. X-ray crystallography
Crystallographic data for compounds 2–8 were collected at
23 °C on an Oxford Diffraction Gemini CCD diffractometer employ-
ing Mo Ka radiation (0.71073 Å) and operating in the x-scan mode.
Data reduction and empirical absorption corrections (multi-scan)
or analytical absorption corrections were performed with Oxford
Diffraction CrysAlisPro software. For compound 1 data were mea-
sured on an Enraf–Nonius CAD4 four circle diffractometer employ-
2.5.2. Preparation of [Zn(pysbz)2] (4)
Zinc(II) nitrate hexahydrate (0.23 g, 0.76 mmol) dissolved in
MeOH (10 mL) was added to a solution of the ligand (0.10 g,
0.35 mmol) in a hot 1:1 mixture of MeOH and MeCN (40 mL).
The resulting dark yellow solution was heated for 2 h on a steam
bath to reduce its volume to about 25 mL. On standing overnight,
the reaction mixture yielded a bright yellow product which was fil-
tered off, washed with cold MeOH and dried in vacuo over anhy-
drous silica gel. Yield: 77.4 mg (23%). M.p. 205–208 °C (dec.).
Anal. Calc. for C28H23N6S4Zn: C, 52.78; H, 3.64; N, 13.19. Found:
C, 52.85; H, 3.67; N, 13.21%. 1H NMR [DMSO-d6] dH: 4.43(s, 4H,
SCH2), 7.24–7.34(m, 6H, py-H + ph-H), 7.40–7.41(m, 6H, py-H),
ing graphite monochromated Mo K
hꢀ2 scan mode. Data reduction and empirical absorption correc-
tions ( -scans) were applied. All structures were solved by direct
a radiation and operating in the
x
w
methods with SHELXS and refined by full-matrix least-squares anal-
ysis with SHELXL-97 [10]. All non-H atoms were refined with aniso-
tropic thermal parameters. Molecular structure diagrams were
produced with ORTEP3 [11]. All calculations were carried out within
the WinGX graphical user interface [12]. Crystal and refinement
data are summarized in Table 1.

18
A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
Table 1
Crystal and refinement data.
1 Hpysme
2 Hpysbz
3
4
5 [Zn(pysme)-
6 [Zn(pysbz)-
7
8
[Zn(pysme)2]
[Zn(pysbz)2]
(OAc)]2
(OAc)]2
[Cd(pysme)2]
[Cd(pysbz)2]
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal class
Space group
Cell dimensions
a (Å)
C8H9N3S2
211.30
293(2)
0.71073
orthorhombic monoclinic
C14H13N3S2
287.39
293(2)
C16H16N6S4Zn C28H24N6S4Zn C20H22N6O4S4Zn2 C32H30N6O4S4Zn2 C16H16N6S4Cd C28H24N6S4Cd
485.96
293(2)
0.71073
triclinic
638.14
293(2)
0.71073
monoclinic
669.42
293(2)
0.71073
monoclinic
P21/n
821.60
293(2)
0.71073
triclinic
532.99
293(2)
685.17
293(2)
0.71073
monoclinic
P21/c
triclinic
ꢀ
ꢀ
ꢀ
ꢀ
P212121
P21/n
P1
P1
P1
P1
5.3172(5)
9.8119(7)
19.846(3)
11.883(1)
6.3782(5)
18.324(2)
8.6883(6)
10.5627(5)
12.9242(7)
67.012(5)
81.833(5)
68.375(5)
1015.0(1), 2
1.590
11.1443(8)
11.6821(7)
13.0943(7)
84.352(4)
70.571(5)
65.576(7)
1462.3(2), 2
1.449
7.6582(8)
19.019(2)
9.1444(8)
8.4403(6)
9.0923(7)
13.2286(9)
72.295(6)
71.904(6)
68.327(7)
875.9(1), 1
1.558
13.3068(5)
10.2310(4)
16.0485(6)
11.1660(6)
11.8837(6)
13.2185(7)
81.920(4)
69.405(5)
65.101(5)
1489.2(1), 2
1.528
b (Å)
c (Å)
a
(°)
b (°)
(°)
Volume (Å3), Z
90.982(7)
110.03(1)
105.137(4)
c
1035.4(2), 4
1.356
0.471
1388.6(2), 4
1.375
0.372
1251.4(2), 2
1.777
2109.1(1), 4
1.679
q
l
(g cmꢀ3
)
(mmꢀ1
)
1.635
1.155
2.292
1.653
1.445
1.042
h range (°)
F(000)
2.05–24.96
440
3.38–25.00
600
3.05–25.00
496
3.08–25.00
656
3.01–24.99
680
2.81–24.98
420
3.05–25.00
1064
3.09–25.00
692
Reflection collected
Independent reflections
1566
1403
4900
2439
6663
3568
9933
5143
4476
2201
5570
3070
9712
5242
11121
3705
Rint = 0.0322
Rindices (all data) (R1, wR2) 0.1318,
Rint = 0.0489
0.1119,
0.0460
Rint = 0.0325
0.0638,
0.0508
Rint = 0.0305
0.0728,
0.0559
Rint = 0.0352
0.0585, 0.0931
Rint = 0.0291
0.0706, 0.0515
Rint = 0.0305
0.0432,
0.0558
Rint = 0.0309
0.0503,
0.0458
0.0885
Rindices [observed data]
(R1, wR2)
0.0393,
0.0693
1403/0/119
0.0414,
0.0401
2439/0/172
0.0343,
0.0482
3568/0/244
0.0360,
0.0519
5143/0/352
0.0410, 0.0834
2201/0/165
0.0350, 0.0482
3070/0/217
0.0278,
0.0534
3705/0/244
0.0301,
0.0345
5242/0/352
Data/restraints/
parameters
Goodness of fit on F2
Residual extrema (e Åꢀ3
CCDC
0.983
0.729
0.785
0.767
1.006
0.785
0.903
0.842
)
0.189, ꢀ0.215 0.215, ꢀ0.159 0.482, ꢀ0.309 0.31, ꢀ0.31
0.462, ꢀ0.386
0.497, ꢀ0.349
0.418, ꢀ0.425 0.312, ꢀ0.331
977546 977457 977548 977549
977550
977551
977552 977553
7.83–7.87(m, 4H, py-H and ph-H), 8.01(t, 2H, py-H), 9.00(s, 2H,
CH@N).
8.12(t, 1H, py-H), 7.98–8.03(m, 2H, ph-H), 7.83–7.86(m, 2H, py-
H + ph-H), 7.64–7.68(m, 1H, ph-H), 7.38–7.47(m, 5H, ph-H),
7.21–7.33(m, 5H, py-H), 4.41(d, 4H, SCH2), 1.75(s, 6H, CH3).
2.5.3. Preparation of [Zn(NNS)(CH3COO)]2 (NNS = anionic forms of the
Schiff bases)
2.5.4. Preparation of the [Cd(NNS)2] complexes
2.5.4.1. Preparation of [Cd(pysme)2] (7). Cadmium(II) acetate dihy-
drate (0.1 g, 0.4 mmol) dissolved in boiling MeOH (15 mL) was
added to a solution of 1 (0.2 g, 0.9 mmol) in a 2:1 MeCN:MeOH mix-
ture (50 mL) when the colour of the solution changed from yellow
to light orange. The mixture was then heated for 10 min and left
at room temperature for one week. Orange crystals of the complex
had formed which were filtered off and recrystallized from a 2:1
mixture of MeCN and MeOH. Yield, 0.20 g (94%). M.p. 258–264 °C.
Anal. Calc. for C16H16N6S4Cd: C, 36.05, H, 3.03, N, 15.77. Found: C,
36.06; H, 2.92, N, 15.43%. 1H NMR [CDCl3], dH: 8.56(s, 1H, AHC@N),
7.39–8.10(m, 4H, py-H), 2.66(s, 3H, –SCH3); 13C NMR [DMSO-d6], dC:
2.5.3.1. Preparation of [Zn(pysme)(CH3COO)]2 (5). Zinc(II) acetate
dihydrate (0.20 g, 0.91 mmol) dissolved in MeOH (10 mL) was added
to a solution of the Schiff base, Hpysme (1) (0.20 g,0.95 mmol) in a
hot 3:1 mixture of MeOH and MeCN (20 mL). The mixture was
heated on a water bath for 3 min when a bright yellow compound
formed which was filtered off, washed with cold methanol and dried
in vacuo over anhydrous silica gel. The crude product was recrystal-
lized from a 2:1 mixture of MeCN and MeOH. Yield, 0.219 g (38%).
M.p. 216–218 °C (dec). Anal. Calc. for C20H22N6O4S4 Zn2: C, 35.88;
H, 3.31; N, 12.55; S, 19.16. Found: C, 35.36; H, 3.49; N, 12.52; S,
18.93%. 1H NMR [DMSO-d6], dH: 8.93(s, 1H, CH@NA), 8.71(s, 1H,
CH@N), 8.47(d, 1H, py-H), 8.09–8.14(m, 4H, py-H), 7.92–8.02(m,
4H,py-H), 7.83(d, 2H, py-H), 7.63–7.67(m, 1H, py-H), 7.45–
7.49(m,1H, py-H), 2.50(obscured by solvent peak, SCH3), 1.77(s, 6H,
CH3); 13C NMR [DMSO-d6], dC: 192.32(CS), 176.96(CS), 149.03(CN),
148.12(CN), 147.97(py-C), 147.83(py-C), 147.44(py-C), 147.37(py-
C), 140.64(py-C), 140.13(py-C), 127.42(py-C), 127.31(pyC),
126.96(pyC), 126.65(pyC), 23.04(SCH3), 15.36(CH3), 14.99(CH3).
14.50
(SCH3),
[127.08,127.31,139.90,148.91,147.86](py-C),
149.04(CH@NA), 189.27(CS).
2.5.4.2. Preparation of [Cd(pysbz)2] (8). This compound was pre-
pared in a manner similar to that used for (7). Yield: 0.10 g (86%).
m.pt: 220–230 °C. Anal. Calc. for C28H24N6S4Cd: C, 49.08; H, 3.53;
N, 12.77. Found: C, 49.04; H, 3.30; N, 12.19%. 1H NMR [CDCl3], dH:
4.45(s, 2H, ASCH2A), 7.24–7.48(m, 3H, ph-H), 7.48–7.50(m, 3H,
ph-H), 8.04(t, 1H, py-H), 7.94(d, 1H, py-H), 7.84(d, 1H, py-H),
8.95(s, 1H, CH@N). 13C NMR [DMSO-d6], dC: 188.26(CS),
2.5.3.2. [Zn(pysbz)(CH3COO)]2 (6). Zinc(II) acetate dihydrate (0.04 g,
0.2 mmol) dissolved in MeOH (10 mL) was added to a solution 2
(0.05 g,0.2 mmol) in a hot MeCN (40 mL). The mixture was heated
on a water bath for 30 min. The bright yellow compound that had
formed was filtered off, washed with cold EtOH and dried in vacuo
over anhydrous silica gel. The crude product was recrystallized
from a 2:1 mixture of MeCN and MeOH. Yield, 0.08 g (53%). M.p.
264–268 °C. Anal. Calc. for C32H30N6O4S4Zn2: C, 46.77; H, 3.68; N,
10.23. Found: C, 46.72; H, 3.36; N, 10.25%. 1H NMR [DMSO-d6],
dH: 8.93(s, 1H, CH@N), 8.79(s, 1H, ph-H), 8.48(d, 1H, py-H),
149.71(CH@NA,
[127.35,127.55,138.62,148.68,148.30](py-C),
[140.43,127.89,128.32,129.63](Ph-C).
2.6. Cytotoxicity assay
The cytotoxicity assays were carried out in the Laboratory of
Vaccines and Immunotherapeutics, Institute of Bioscience, Univer-
siti Putra Malaysia, Malaysia.

A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
19
2.6.1. Cell culture
The human cervical cancer (HELA), lymphoblastic leukemia
(HL-60) and breast adenocarcinoma (MDA-HB-231) cell lines were
obtained from the National Cancer Institute, Maryland, USA. The
cells were cultured in RPMI-1640 (Sigma) containing 10% fetal calf
serum and incubated in an atmosphere of 5% CO2 and 100% relative
humidity at 37 °C.
2.6.2. Treatments and sample dilutions
Cells from the cell lines were counted, diluted and inoculated
onto sterile 96-well microtitre plates. The cancer cells were inocu-
lated in a volume of 100 lL per cell at densities of 5000 cells per
well. The microtitre plates containing the cells were preincubated
overnight at 37 °C in an atmosphere of 5% CO2 and 100% relative
humidity to allow stabilization prior to the addition of the com-
pounds. Stock solutions of the compounds (10 mg/mL) were made
in DMSO which were then diluted with the complete medium
ranging from 100 to 0.3 g/mL. Immediately after the preparation
Fig. 3. ORTEP view of of Hpysbz (2) (30% probability ellipsoids shown).
of these diluted samples, 100 lL aliquots of each sample were
added to the appropriate microtitre plates containing cells. The
treated microtitre culture plates were then incubated in an atmo-
sphere of 5% CO2 and 100% relative humidity at 37 °C for 3–4 h.
H
N
H
R
N
C
N
R
N
C
N
H
X
2.6.3. MTT assay
N
C
Cytotoxicity was evaluated using MTT [3-(4,5-dimethylthiazol-
2-yl)-2,5-dimethyltetrazolium bromide] following reports of
Mossman [14]. A 40 lL aliquot of MTT solution (5.0 mg in 1 mL
S
S
H
X
of PBS solution) was added directly to all the appropriate microti-
tre plate wells containing cells. The culture was then incubated for
4 h to allow for MTT to metabolize to formazan. The supernatants
were then pipetted out and 200 mL of DMSO were added to dis-
solve the formazan. The plates were agitated on a plate shaker to
ensure homogeneity of the solution. The optical densities of the
solutions were then read by means of an automated ELISA micro-
plate reader at a test wavelength of 570 nm and a reference wave-
length of 600 nm.
Cytotoxicity is expressed as the minimum concentration of the
compound required to reduce the absorbance of the treated cells
by 50% with reference to the untreated cells (IC50). Tamoxifen
was used as a cytotoxic standard for the HELA and MDA-MB-231
cell lines and Goniothalamin were used for the HL-60 cells.
(a)
(b)
Fig. 4. The thione (a) and the thiol (b) forms of the Schiff bases (R = H, X = SCH3,
SCH2C6H5).
Schiff base adopts a configuration in which the thione sulfur atom,
the azomethine nitrogen atom and the pyridine nitrogen atom are
mutually trans to each other. Here we have identified a different
polymorph of the Schiff base Hpysme and we include the X-ray
structure of this new structure of Hpysme for comparison.
Both the Schiff bases, Hpysme and Hpysbz have the thioamide
functional group (ANHAC(@S)) in their backbones and therefore,
they are capable of exhibiting thione–thiol tautomerism (Fig. 4).
Their IR spectra exhibit the N–H stretching band of the second-
ary amine group at ca. 3100 cmꢀ1 indicating that, in the solid state,
the proton resides on the nitrogen atom (N2) of the hydrazine moi-
3. Results and discussion
ety. The absence of any m
S–H band at ca. 2570 cmꢀ1 in their IR
The synthesis and spectroscopic characterization of the 2-pyri-
dinecarboxaldehyde Schiff base of S-methyldithiocarbazate
(Hpysme; Fig. 2) was previously reported by Akbar Ali et al. [10]
and that of the 2-pyridinecarboxaldehyde Schiff base of S-ben-
zyldithiocarbazate by Akbar Ali and Tarafder [9]. The crystal and
molecular structure of Hpysme has also been reported by Cheng-
Yong et al. in 1999 [15] who reported that, in the solid state, the
spectra is also strong evidence that they remain in their thione
tautomeric forms (Fig. 4a). X-ray crystallographic structural analy-
ses (vide infra) of both the Schiff bases also unequivocally prove
that the thiol form is not present in the solid state (Figs. 2 and
3). The 1H NMR spectrum of the ligand, Hpysme exhibits signals
at 2.67, 8.09–7.30, 8.69, 10.33 and 15.62 ppm, which can be as-
signed to the –SCH3, pyridine, azomethine ACH@N and sec –NH
protons, respectively. The appearance of the –NH proton signal at
15.62 ppm indicates that the proton is attached to the hydrazinic
N atom and that the Schiff base adopts a Z configuration in CDCl3,
since an E configuration is expected to display the –NH proton sig-
nal at a lower ppm value as observed in the spectra of other related
ligands [16].
An examination of the X-ray crystal structures of both Hpysme
and Hpysbz (Figs. 2 and 3) show that the thione sulfur atoms in
these ligands are positioned trans to the azomethine nitrogen atom
and the azomethine nitrogen atom is also trans to the pyridine
nitrogen atom. In these configurations, the Schiff bases are unable
to coordinate to the metal ions as NNS tridentate chelating agents
via the pyridine nitrogen, the azomethine nitrogen and the thiolate
sulfur atoms. However, in solution rotations about the C3–C4 and
Fig. 2. ORTEP view of Hypsme (1) (30% probability ellipsoids shown).

20
A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
Table 2
Selected bond lengths (Å) and bond angles (°).
1 Hpysme
2 Hpysbz
3 [Zn(pysme)2]
4 [Zn(pysbz)2]
5 [Zn(pysme)(OAc)]2
6 [Zn(pysbz)(OAc)]2
7 [Cd(pysme)2]
8 [Cd(pysbz)2]
C1–S1
C1–S2
C1–N1
N1–N2
N2–C3
M–S1
1.642(5)
1.647(3)
1.702(3)
1.693(3)
1.751(3)
1.757(3)
1.325(3)
1.313(3)
1.367(3)
1.379(3)
1.285(3)
1.267(3)
2.464(1)
2.4547(8)
2.114(2)
2.116(2)
2.250(2)
2.272(2)
1.713(2)
1.747(3)
1.740(3)
1.747(3)
1.313(3)
1.313(3)
1.380(3)
1.376(3)
1.276(3)
1.275(3)
2.4533(9)
2.4589(9)
2.125(2)
2.127(2)
2.361(2)
2.238(2)
1.699(4)
1.717(3)
1.718(3)
1.723(3)
1.757(3)
1.755(3)
1.302(4)
1.314(3)
1.379(3)
1.383(3)
1.265(3)
1.277(3)
2.5803(8)
2.5701(8)
2.368(3)
2.357(2)
2.526(2)
2.394(2)
1.720(3)
1.730(3)
1.750(2)
1.746(3)
1.303(3)
1.304(3)
1.391(2)
1.378(3)
1.270(3)
1.269(3)
2.5731(7)
2.5749(9)
2.348(2)
2.350(2)
2.484(2)
2.398(2)
1.749(5)
1.336(6)
1.364(5)
1.272(6)
1.754(2)
1.339(3)
1.376(2)
1.268(3)
1.719(4)
1.291(4)
1.362(4)
1.252(5)
2.375(1)
2.077(3)
2.174(3)
1.753(3)
1.311(3)
1.387(3)
1.276(3)
2.4124(9)
2.105(2)
2.194(2)
M–N2
M–N3
M–O1
M–O2
1.949(3)
1.965(3)
1.990(2)
2.001(2)
S1A–M–S2A
S1A–M–N2A
N2A–M–N2B
N2A–M–N3A
O1–M–S1
O1–M–N2
102.26(3)
78.89(8)
167.5(1)
74.3(1)
101.44(3)
79.38(7)
160.33(9)
72.78(9)
107.06(3)
73.37(6)
149.78(8)
67.32(8)
106.28(3)
74.56(5)
155.77(7)
67.58(7)
103.97(9)
131.4(1)
103.16(6)
109.33(9)
C1–N1 bonds can occur thus enabling the ligands to act as NNS tri-
dentate chelating agents.
A comparison of bond lengths in the hydrazinic side chains of 1
with that in 2 (Table 2) shows that lengths of all the bonds in both
ligands have similar values. The C(1)–N(1), N(1)–N(2) and C(1)–
S(1) bond lengths (Table 2) indicate that there is some
delocalization in the hydrazine side chain.
p-electron
3.1. The structures of the [M(NNS)2] complexes
However, when both Schiff bases are dissolved in an organic
solvent such as methanol or ethanol and solutions of zinc(II) and
cadmium(II) acetate are added to the solutions, they readily
convert to the thiol tautomeric forms, lose the thiol protons and
coordinate with the zinc(II) and cadmium(II) ions in their deproto-
nated thiolate forms. This is unambiguously proven by the X-ray
crystallographic structure determination of the [M(NNS)2] and
[Zn(NNS)(OAc)]2 complexes. The X-ray crystal and molecular
structures of the bis-ligand complexes, [M(NNS)2] (M = Zn2+
,
Cd2+; NNSꢀ = anionic forms of the Schiff bases) are shown in
Figs. 5–8 and selected bond lengths and bond angles are given in
Table 2. The structures show that, in all these complexes, the Schiff
bases are coordinated to the metal ions in their deprotonated thio-
late forms via the pyridine nitrogen, the azomethine nitrogen and
thiolate sulfur atoms. The two NNS ligands are coordinated to the
metal ions meridionally with the two sulfur donor atoms cis and
the two azomethine nitrogen atoms [N2(A) and N2(B)] trans to
each other. The M–S, M–Npy and M–Nazomethine bond lengths (Ta-
ble 3) compare well with that of the bis-ligand zinc(II) [17] and
cadmium(II) complexes [18] of the related tridentate NNS ligands.
A comparison of the Zn–S and Zn–N bond distances in 3 and 4
shows that while the metal–sulfur bond lengths in both complexes
are very close, the two Zn–N bonds, especially the Zn–Npy dis-
tances are different. In both complexes, the Zn–Nimine bond is
shorter than the Zn–Npy bonds. Similar observations have also
been reported in all other bis-ligand six-coordinate zinc(II) com-
plexes of related tridentate NNS donor ligands [17–19]. Another
feature is a more distorted structure of 4 relative to 3, where the
trans N2A–Zn–N2B angle in compound 4 (ꢁ160°) is more distorted
from linearity than in compound 3 (ꢁ167°). Coupled with this the
Fig. 5. ORTEP view of 3 (30% probability ellipsoids).
Fig. 6. ORTEP view of 4 (30% probability ellipsoids).

A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
21
geometry. For example, for an ideal octahedral geometry, the an-
gles N(3b)–M–S(1b) and N(3a)–M–S(1a) should be 180° but they
are actually considerably smaller than this value. Also, for an ideal
six-coordinate octahedral complex, the cis angles, S(1a)–M1–S(1b),
N(3a)–M1–N(3b), N(2a)–M1–S(1b) and N(2b)–M1–N(3b) should
be 90° but they also deviate considerably from this value. The devi-
ations from an ideal octahedral geometry are found to be more
pronounced in the cadmium complexes than in the zinc com-
plexes. Since each ligand has three donor atoms of varying ligand
field strengths [viz. the pyridine nitrogen atom, (N3a), the azome-
thine nitrogen atom (N2a) and the thiolate sulfur atom (S1a)], dis-
tortion from an ideal octahedral geometry is expected. Similar
distorted octahedral structures have also been observed for the
bis-ligand zinc(II) and cadmium(II) complexes of related tridentate
NNS chelating agents [18–20].
3.2. The X-ray crystal structures of 5 and 6
The structures of the two acetato complexes are shown in Figs. 9
and 10 and important bond lengths and angles are given in Table 2.
The structures show that both complexes are interesting centro-
symmetric dimers in which each of the Schiff bases is coordinated
to a single zinc(II) ion via the pyridine nitrogen atom, the azome-
thine nitrogen atom and the thiolate sulfur atom in its deproto-
nated thiolate form Figs. 9 and 10.
Fig. 7. ORTEP view of 7 (30% probability ellipsoids).
The two zinc(II) ions in each complex are also bridged by a pair
of bis-monodentate acetate ligands. This way the zinc(II) ions
adopt a five-coordinate geometry. However, a five-coordinate com-
plex can either adopt a square-pyramidal or a trigonal bipyramidal
geometry. Addison et al. [21] have devised a criterion for assigning
a definitive structure to five-coordinate complexes. The formula,
s
= (b ꢀ
a) /60 where a and b are the two biggest angles, defines
the index of trigonality (distortion from trigonal-bipyramidal or
square-pyramidal geometry) and has been successfully used to dis-
tinguish between a square-pyramidal and a trigonal-bipyramidal
configuration. When
when is 1, the structure is a trigonal-bipyramidal. Using this cri-
terion, the values for 5 and 6 become 0.38 and 0.26, respectively
s is 0, the structure is square-pyramidal but
s
s
indicating that both the zinc(II) ions in each complex adopt a struc-
ture closer to square-pyramidal. The Zn–N and Zn–S bond lengths
(Table 2) in the five coordinate complexes are significantly shorter
than seen in the 6-coordinate bis-dithiocarbazate Schiff base com-
plexes 3 and 4.
Fig. 8. ORTEP view of 8 (30% probability ellipsoids).
The related tridentate thiosemicarbazone, 2-acetylpyridine 4N-
ethylthiosemicarbazone, has also been found to react with zinc(II)
acetate to form an acetate anion-bridged dinuclear zinc(II) com-
plex [22] in which the two acetate anions coordinate with the
two zinc atoms in different modes. One of the acetate anions
bridges the two zinc atoms in a syn–syn fashion similar to that ob-
served in the present complexes, whereas the second acetate anion
acts as a bidentate chelating agent using one of the oxygen atoms
Zn–Npyr are significantly different in 4. This asymmetry is most
probably a result of packing forces as the complex shows expected
C2 symmetry in solution as shown by 1H NMR with both ligands
equivalent. The longer Zn–Npyr bond (to N3A) is evidently a result
of steric repulsion of the adjacent benzyl ring.
The overall geometry of the bis-ligand complexes can be con-
sidered as distorted octahedral since most of the bond angles devi-
ate considerably from values expected for a regular octahedral
Table 3
0
Comparison of bond lengths (AÅ) in some zinc(II) and cadmium(II) complexes.
Complexa
M–S
M–Npy
M–Nazomethine
Reference
[Zn(pysme)2]
[Zn(pysbz)2]
[Zn(dpksbz)2]
[Zn(pyfN4tsc)2]
2.4635(1), 2.4536(6)
2.4574(8)
2.4199(10)
2.250(2)
2.272(2)
2.307(3)
2.415(2), 2.333(12)
2.114(2)
2.116(2)
2.108(2)
2.071(2), 2.072(19)
2.1160(17), 2.1346(17)
2.526(2), 2.34(2)
2.368(3),2.357(2)
2.2987(19),2.327(2)
This work
This work
[17a]
[18]
[16]
This work
This work
This work
[18]
2.406(1),2.441(1)
[Zn(bpysbz)2]ꢂCH3CN
[Cd(pysme)2]
[Cd(pysbz)2]
2.4403(6), 2.4516(6)
2.5731(7), 2.574(9)
2.5803(8), 2.5701(8)
2.5805(7), 2.5693(8)
2.3188(17), 2.2288(17)
2.484(2), 2.398(2)
2.348(2), 2.3497(19)
2.481(12), 2.5260(19)
[Cd(pyfN4tsc)2]
a
bpysbz = anionic form of the 2-benzoylpyridine Schiff base of S-benzyldithiocarbazate [16]; pyfN4tsc = anionic form of the 2-formylpyrazine-N4-methylthiosemicar-
bazone [18].

22
A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
is consistent with the ligand converting to the iminothiolate form
when it coordinates to the zinc(II) ion. An examination of the bond
distances in the hydrazine side chain of the coordinated ligand
shows that most of the bonds have lengths that are intermediate
between single and double bonds [C(1)–N(1): 1.311(3) Å, C(1)–
S(1): 1.717(3) Å, N(1)–N(2): 1.387(3) Å and N(2)–C(2):
1.276(3) Å] indicating that while coordinating in its iminothiolate
form, the negative charge generated on the thiolate sulfur atom
of the ligand is delocalized in the C–N–N–C–S chain causing the
bond distances to have values that are intermediate between single
and double bonds. Similar observations have also been reported for
other metal complexes of related tridentate dithiocarbazate li-
gands [3c,18,23].
Fig. 9. ORTEP view of 5 (30% probability ellipsoids).
3.3. Characterization of the complexes
All the complexes studied here were stable at ambient temper-
ature and could be kept in a desiccator over anhydrous silica gel
over a long period of time without any sign of decomposition. They
are insoluble in methanol and ethanol but sparingly soluble in
CHCl3 and MeCN. Selected IR bands of the ligands and their zinc(II)
and cadmium(II) complexes, together with their assignments, are
given in Table 5. The assignments shown in the table are based
on those used by Akbar Ali et al. [9,18] for similar compounds.
Bands at ca. 3100, 1580, 1110–1050 and 980 cmꢀ1 in the IR spectra
of the free ligands can be assigned to the
CSS stretching vibrations, respectively. A comparison of these
bands with those of their complexes indicate that the C@N bands
of the free ligands shift to lower wave numbers whereas that of the
N–N bands shift to higher wave numbers (Table 5) indicating
mN–H, mC@N, mN–N and
m
m
m
coordination of the Schiff bases to metal ions via the azomethine
nitrogen atoms. The UV–Vis spectra of the complexes (Table 5)
show absorption bands in the ligands at 409 and 341 nm due to
the n ? p⁄ and
p ?
p⁄ transitions, respectively. There is very little
shifting of these bands after coordination with the metal ions.
3.4. Cytotoxicity
The cytotoxicity data of some of the compounds studied here
are given in Table 6. Interestingly the data indicate that the Schiff
base Hpysme exhibits cytotoxic activity against the HL-60 cell lines
but is non-toxic to HELA or MDA-MB-231 cells. Recently we found
[1c] that Hpysme and Hpysbz are not cytotoxic to SK-N-MC neuro-
epithelioma cells either. By contrast the bis-ligand zinc(II)
complex, [Zn(pysbz)2] and the dimeric acetate-bridged zinc(II)
complexes, [Zn(pysme)(CH3COO)]2 and [Zn(pysbz)(CH3COO)]2
show significant cytotoxic activities against the HELA and HL-60
cell lines. The fact that this contrasts the behavior of the free
ligands suggests that the Zn complex itself is the active form and
indeed the similar activities of the 1:1 and 1:2 Zn:L complexes sug-
gests a common biologically active form of these labile complexes.
These compounds exhibit stronger cytotoxic activities against
these cancer cells than the commercially important anticancer
drug, Tamoxifen, which under similar conditions exhibits cytotox-
Fig. 10. ORTEP view of 6 (30% probability ellipsoids).
as a bridging donor and the other oxygen atom as a non-bridging
donor atom. The two zinc atoms, thus have two different coordina-
tion numbers, one being penta- and the other hexacoordinated.
For the purpose of comparison, zinc(II)-donor atom distances in
the three related dinuclear acetate anion-bridged zinc(II) com-
plexes are given in Table 4. The bond length data show that, de-
spite having different geometries, the zinc-donor atom distances
are similar.
A comparison of bond distances of the free ligands 1 and 2 with
those in complexes 6 and 7 shows that while there is very little
change in the C(3)–N(2) and N(1)–N(2) bond distances, there are
significant changes in the C(1)–N(1) and C(1)–S(1) bond distances.
After coordination with the zinc(II) ion, the ligand’s C(1)–N(1)
bond becomes shorter while the C(1)–S(1) becomes longer. This
icity of 12.8 lg/mL against the HELA cells.
Table 4
Comparison of bond distances (Å) in dinuclear acetate-bridged zinc(II) complexes of related NNS ligands.
a
5
6
[Zn(Acpy4Nethyltsc)(CH3COO)]2
Zn–S
Zn–Nazomethine
Zn–Npy
2.3754(12)
2.077(3)
2.174(3)
2.4124(9)
2.105(2)
2.194(2)
2.368(5), 2.410(6)
2.09(2), 2.13(2)
2.155(14), 2.21(2)
2.042(13), 1.963(11)
Zn–Oacetate
1.965(3),1.949(3)
1.990(2), 2.001(2)
a
Acpy4Nethyltsc = anionic form of 2-acetylpyridine 4N-ethylthiosemicarbazone; Ref. [22].

A.H. Mirza et al. / Polyhedron 74 (2014) 16–23
23
(b) M. Akbar Ali, A.H. Mirza, C.C. Mei, P.V. Bernhardt, M.R. Karim, Polyhedron
49 (2013) 277;
(c) M.T. Basha, J.D. Chartres, N. Pantara, M. Akbar Ali, A.H. Mirza, D.S.
Kalinowski, D.R. Richardson, P.V. Bernhardt, Dalton Trans. 41 (2012) 6536;
(d) M. Akbar Ali, A.H. Mirza, M.H.S.A. Hamid, N. Aminath, P.V. Bernhardt,
Polyhedron 47 (2012) 79.
Table 5
Selected IRa and UV–Vis absorption bands.
Compound
IR bands (cmꢀ1
(C@N) (N–N)
)
UV abs. bands
(kmax, nm)
m
m
m(CSS)
py ring
vibration
[2] (a) Y. Tian, C. Duan, C. Zhao, X. You, T.C.W. Mak, Z.Y. Zhang, Inorg. Chem. 36
(1997) 1247;
1
2
3
4
5
6
7
8
1584s
1581m
1555br
1574s
1582s
1574m
1586s
1558s
1130s
1108s
1151m
1126w
1085s
1155w
1150s
1151s
870s
998s
633s
632s
638w
638s
630w
638w
633m
633s
404, 393, 378
409, 341
400, 328
408, 340
400, ca.50sh,
337
(b) Z.H. Liu, C.Y. Duan, J. Hu, Inorg. Chem. 38 (1999) 1719;
(c) Z.H. Liu, S.R. Yang, C.Y. Duan, X.Z. You, Chem. Lett. Jpn. 10 (1999) 1063;
(d) Y. Tian, C.Y. Duan, X. You, T.C.W. Mak, Q. Luo, J. Zhou, Transition Met.
Chem. 2 (1998) 17;
(e) Z.A. Abu-Raqabah, G. Davies, M.A. El-Sayed, A. El-Toukhy, S.N. Shaikh, J.
Zubieta, Inorg. Chim. Acta 193 (1992) 43.
1014s
1015m
1014s
1014s
1010s
1005s
409,340, 255
390, 326 432, 335
[3] (a) M. Akbar Ali, A.H. Mirza, R.J. Butcher, M.T.H. Tarafder, Manaf A. Ali, Inorg.
Chim. Acta 320 (2001) 1;
(b) K.A. Crouse, K.-B. Chew, M.T.H. Tarafder, A. Kasbollah, A.M. Ali, B.M. Yamin,
H.-K. Fun, Polyhedron 23 (2004) 61;
a
Band intensities are indicated as: s = strong, br = broad, w = weak, m = medium.
(c) M. Akbar Ali, S.M.M.H. Majumder, R.J. Butcher, J.P. Jasinski, J.M. Jasinski,
Polyhedron 16 (1997) 2749;
(d) M. Das, S.E. Livingstone, Br. J. Cancer 37 (1978) 466;
(e) F.N.-F. Howa, K.A. Crouse, M.I.M. Tahira, M.T.H. Tarafder, A.R. Cowley,
Polyhedron 27 (2008) 3325;
Table 6
Cytotoxic data (IC50 values in l
g/mL)a for the compounds.
(f) M.T.H. Tarafder, A. Kasbollah, K.A. Crouse, A.M. Ali, B.M. Yamin, H.-K. Fun,
Polyhedron 20 (2001) 2363.
[4] F.A. French, E.J. Blanz Jr., J. Med. Chem. 9 (1966) 585.
[5] C.R. Kowoll, R. Trondl, V.B. Arion, M.A. Jakupec, I. Lichtscheidl, B.K. Kepp,
Dalton Trans. 39 (2010) 704.
Compound
HELA
MDA-MB-231
HL-60
Hpysme
Hpysbz
[Zn(pysme)2)(CH3COO)]2
[Zn(pysbz)2]
[Zn(pysbz)(CH3COO)]2
Tamoxifen
inactive
inactive
0.44
0.44
0.57
inactive
12.0
inactive
inactive
15.8
0.25
inactive
0.26
1.32
0.37
–
[6] (a) L.D. Leon-Rodriguez, A.J.M. Lubag Jr, A.D. Sherry, Inorg. Chim. Acta 393
(2012) 12;
(b) C. Andreini, L. Banci, I. Bertini, A. Rosato, J. Proteome Res. 5 (2006) 3173;
(c) E. Tomat, S.J. Lippard, Curr. Opin. Chem. Biol. 14 (2010) 225;
(d) S.L. Kelleher, N.H. McCormick, V. Velasquez, V. Lopez, Adv. Nutr. 2 (2011)
101;
(e) C.F. Mills, Zinc in Human Biology, Springer-Verlag New York, LLC., New
York, 1989.
12.80
–
4.25
–
Goniothalamin
1.50
a
IC50 = Cytotoxic dose at 50%, i.e. the concentration needed to reduce the growth
of cells by 50%. Generally, IC50 < 5.0 g/mL indicates strong cytoxicity; IC50 = 5–10 g/
mL moderately active; IC50 = 10.0–25.0 g/mL, weakly active and IC50 > 25.0 g/mL
means the compound is inactive.
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Since the present zinc(II) complexes exhibit strong cytotoxic
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Appendix A. Supplementary data
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CCDC Nos. 977546–977553 contains the supplementary crys-
tallographic data for Hpysme (1), Hpysbz(2), [Zn(pysme)2] (3),
[Zn(pysbz)2] (4), [Zn(pysme)(OAc)]2 (5) , [Zn(pysbz)(OAc)]2 (6),
[Cd(pysme)2](7) and [Cd(pysbz)2] (8), respectively. These data
can be obtained free of charge via http://www.ccdc.cam.ac.uk/con-
ts/retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-
336-033; or e-mail: deposit@ccdc.cam.ac.uk.
References
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