Short Articles
DNA Interactions and Cytotoxicity
of the Aryls-Vertexed Zinc(II)
Thiosemicarbazone Complex
Rajamuthy Vikneswaran,1 Naser Eltaher Eltayeb,2
Subramaniam Ramesh,*1 and Rosiyah Yahya3
Figure 1. An ORTEP view of [Zn(Httsc-N-Ph)2] with 50%
ellipsoidal probability, showing the atom numbering
scheme.
1Centre for Ionics University of Malaya, Faculty of Science,
University of Malaya, Lembah Pantai,
50603 Kuala Lumpur, Malaysia
2Department of Chemistry, Sciences and Arts College -
Rabigh, King Abdulaziz University, Rabigh, Saudi Arabia
ligands has been synthesized and studied for DNA binding,
nuclease activity and cytotoxicity. The molecular structure of
[Zn(Httsc-N-Ph)2] along with atom numbering scheme is given
in Figure 1. [Zn(Httsc-N-Ph)2] presents a tetrahedral geom-
etry, which is distorted around the zinc atom, with the basal
plane occupied by the S(1), S(1A), N(1), and N(1A) atoms
of two ligands. The distortion from tetrahedral geometry is
evident from the bond angles S(1)-Zn(1)-N(1) 86.04(3)°,
S(1)-Zn(1)-S(1A) 144.33(2)°, S(1)-Zn(1)-N(1A) 115.79(3)°,
S(1A)-Zn1-N1 115.79(3)°, N(1)-Zn(1)-N(1A) 106.64(4)
(10)°, S(1A)-Zn(1)-N(1A) 86.04(3)° and bond lengths Zn(1)-
S(1) 2.2878(3) ¡, Zn(1)-N(1) 2.0395(10) ¡, Zn(1)-S(1A)
2.2878(3) ¡ and Zn(1)-N(1A) 2.0395(10) ¡.
3Department of Chemistry, Faculty of Science, University of
Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia
E-mail: rameshtsubra@gmail.com
Received: March 11, 2015; Accepted: May 14, 2015;
Web Released: May 25, 2015
A
new mononuclear zinc complex of N-phenyl-
substituted thiophene thiosemicarbazone ligand [Zn(Httsc-
N-Ph)2] was synthesized and characterized, and investigated
as nuclease mimic. As compared to carboplatin, a much
greater activity against HeLa cells is exhibited by [Zn(Httsc-
N-Ph)2] which binds to DNA through an intercalation
mechanism.
The DNA binding properties of [Zn(Httsc-N-Ph)2] were
studied by UV, fluorescence spectroscopy and viscosity mea-
surements. The absorption spectra of [Zn(Httsc-N-Ph)2] in the
absence and presence of CT-DNA at various concentrations
are given in Figure 2a. In the UV region, [Zn(Httsc-N-Ph)2]
exhibits an intense absorption band around 333 nm which
is attributed to the intraligand transition of the coordinated
thiosemicarbazonato ligands. When concentration of CT-DNA
was increased, red-shift of 5 nm together with hypochromism
was noticed. This implies that there occurs a binding inter-
action between the CT-DNA and [Zn(Httsc-N-Ph)2]. The
intrinsic binding constant (Kb) for [Zn(Httsc-N-Ph)2] is 5.72 ©
Several different biological characteristics are demonstrated
by thiosemicarbazones and these characteristics are largely
dependent on the parent ketone or aldehyde and greater activity
is seen if they are heterocyclic aromatic systems.1,2 Clinicians
make use of numerous thiosemicarbazones including triapine
or marboran even though different concerns have been raised
related to their mechanism of action.3,4 Still, it has been estab-
lished that mode of action of heterocyclic thiosemicarbazones
involves inhibition of an essential enzyme i.e. ribonucleotide
reductase which is required for synthesis of DNA precursors.5
Besides showing biologically activity, these Schiff bases prove
to be potent coordinating agents and their interaction with
metals results in formation of stable complexes.6 Studies indi-
cate that effectiveness and action of organic therapeutic agents
can be accelerated if they contain metal ions in the form of
complexes.7-9 Researchers have been recently attracted to the
exploration of interactions between nucleic acids and transi-
tion-metal complexes as findings of these investigations can be
helpful in developing innovative reagents for medicine and
biotechnology.10 Owing to its bioavailability, hard Lewis acid
characteristics, low toxicity and redox inertness, zinc ion is
known as one of the most suitable metal ion for research
studies based on DNA.11,12 For that reason, in this communi-
cation a zinc(II) complex whose coordination sphere is occu-
pied by the N-phenyl-substituted thiophene thiosemicarbazone
¹1
104 M (determined by regression analysis).13 This value of
binding constant shows that [Zn(Httsc-N-Ph)2] binds with DNA
moderately. To investigate the interaction mode between [Zn-
(Httsc-N-Ph)2] and CT-DNA, ethidium bromide (EB) fluores-
cence displacement experiments were carried out. As shown
in Figure 2b, a prominent reduction trend was noticed in the
fluorescence intensity of EB bound to the DNA at 584 nm with
increasing concentration of the [Zn(Httsc-N-Ph)2]. The reduc-
tion in fluorescence occurs because some EB molecules were
discharged from the EB-DNA system following an exchange
with the complex. This observation is usually attributed to
intercalation. Viscosity measurements were carried out to fur-
ther verify the interaction of the metal complexes with DNA.
Alterations in the relative viscosity can be used as an indicator
for differentiating electrostatic and intercalative DNA binding.
It has been established that viscosity of the DNA solution in-
creases considerably when a ligand intercalates into the DNA.
This is because the distance between the base pairs increases at
the site of intercalation which in turn results in an increase in
© 2015 The Chemical Society of Japan
Vikneswaran, Rajamuthy
