FULL PAPER
DOI: 10.1002/ejic.201200054
Design and Synthesis of a Functional Derivative of the Triazinium Cation and
Its Rhodium Complex that Shows Photoinduced DNA Cleavage Activity and
Photocytotoxicity
Pradip Ghosh,
[a]
Mominul Sinan,
[a]
Debojyoti Lahiri,
[b]
Sovan Roy,
[b]
and
Sreebrata Goswami*
[a]
Keywords: Medicinal chemistry / Photodynamic therapy / DNA cleavage / Rhodium / Photochemistry
The design and synthesis of an intensely blue rhodium(III)
complex [3]
+
of a new N,N-donor ligand, 8-(quinolin-8-yl-
amino)pyrido[2,1-c][1,2,4]benzotriazin-11-ium, [2]
+
, which
contains a planar pendant triazinium arm, is described.
Structural characterization for [3]
+
was carried out by using
various spectroscopic techniques and single-crystal X-ray
crystallography. The organometallic rhodium(III) compound
shows a ligand-based reversible reduction at –0.65 V. The
electrochemically reduced compound displays a single-line
EPR spectrum that signifies the formation of ligand-based
free radicals. Compound [3]
+
shows a binding propensity to
calf thymus DNA to give a K
app
value of 6.05 10
5
M
–1
. The
parent triazinium salt, pyrido[2,1-c][1,2,4]benzotriazin-11-
Introduction
The design of molecules that can efficiently show pho-
tonuclease activity upon exposure to long-wavelength light
is a current subject of interest in the development of new
drugs for photodynamic therapy (PDT) applications.
[1–5]
In
the PDT process, the tumor cells are selectively damaged
by irradiating the affected area, whereas the unexposed
healthy cells remain unaffected. In the presence of oxygen,
the photoactivation of the PDT drugs generates reactive
species (singlet oxygen, superoxide, hydroxyl radicals) and
causes damage of the tissues.
[6–9]
These systems suffer major
drawbacks because their activity is dependent on the supply
of oxygen into the cells and consequently these become in-
effective under hypoxic cellular conditions. Therefore, the
development of photosensitizers that absorb low-energy
light and can function even in the absence of molecular
oxygen is of interest.
[a] Department of Inorganic Chemistry, Indian Association for the
Cultivation of Science,
Kolkata 700032, India
E-mail: icsg@iacs.res.in
[b] Department of Inorganic and Physical Chemistry, Indian
Institute of Science,
Bangalore 560012, India
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201200054.
Eur. J. Inorg. Chem. 2012, 4719–4727 © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4719
ium [1]
+
and the ligand salt [2]
+
exhibit photoinduced cleav-
age of DNA in UV-A light, whereas the reference Rh complex
[3]
+
photocleaves DNA with red light (647.1 nm). The com-
pounds show photonuclease activities under both aerobic
and anaerobic conditions. Mechanistic investigations under
aerobic conditions with several inhibitors indicate the forma-
tion of hydroxyl radicals by means of a photoredox pathway.
Under anaerobic conditions, it is believed that a photoin-
duced oxidation of DNA mechanism is operative. Compound
[3]
+
exhibits photocytotoxicity in HeLa cervical cancer cells
to give IC
50
values of (12 0.9) μM in UV-A light at 365 nm
and (31.4 1.1) μM in the dark.
It is now known that photoactive and electroactive cen-
ters in the drug molecules are essential prerequisites
[10]
for
DNA cleavage. Accordingly, transition-metal complexes of-
fer potential advantages over the more common organic-
based compounds for the photocleavage of DNA due to
their tunable coordination environments, accessible redox
states, and versatile spectral properties.
[11]
Metal complexes
that have ligands like dipyridyl[3,2-a:2',3'-c]phenazine,
phenanthroline, and bipyridine with appended photoactive
aromatic hydrocarbon groups
[10,12–14]
such as naphthalene,
anthracene, and pyrene have been explored for photonucle-
ase studies in recent years. Moreover, several monometallic
rhodium(III) as well as dirhodium(II) complexes have also
been reported to show DNA photocleavage as well as pho-
tocytoxicity.
[15–21]
Herein we disclose the new rhodium(III)
complex [3]
+
of an N,N-chelate [2]
+
. The ligand salt [2]ClO
4
was obtained following C–N bond fusion
[22–28]
between a
triazinium salt and 8-aminoquinoline. The reference ligand
salt is red (λ
max
= 490 nm), whereas the rhodium complex
[3]ClO
4
is intense blue and absorbs in the low-energy region
of visible light. The two new compounds, [2]ClO
4
and
[3]ClO
4
, were characterized by different spectroscopic tech-
niques. We also report here the results of our studies of
DNA interactions with the ligand [2]ClO
4
and the rhodi-
um(III) complex. Their photonuclease activities have been
compared with the parent triazinium salt. The significant
results of this study include a shift of the irradiating wave-