Self-activated DNA cleavage and nitric oxide reactivity studies on mononuclear copper complexes derived from tetradentate ligands

Article abstract of DOI:10.1016/j.inoche.2011.09.038

Two new tetradentate ligands Timpy (1,2-bis((E)-(2-phenyl-2-(pyridine-2-yl) hydrozono)methyl)benzene) and Gimpy ((1Z,2Z)-1,2-bis(2-phenyl-2-(pyridine-2-yl) hydrozono)ethane) were synthesized and characterized. Mononuclear complexes [Cu(Timpy)(ClO₄)](ClO₄) (1) and [Cu(Gimpy)](ClO ₄)₂ (2) were synthesized and characterized by IR, UV-visible and conductivity measurements. The molecular structure of [Cu(Timpy)(ClO₄)](ClO₄) (1) was determined by single crystal X-ray diffraction and structural index parameter (τ = 0.4725) supported distorted square planar geometry at the metal centre. Electrochemical studies for 1 and 2 were investigated. Two-fold applications of these complexes were examined. First, self-activated DNA cleavage activity of complexes 1 and 2 and mechanism of nuclease activity. Second, the complexes were utilized as fluorescence probe for the detection of nitric oxide in solution.

Full text of DOI:10.1016/j.inoche.2011.09.038

Inorganic Chemistry Communications 15 (2012) 56–60
Contents lists available at SciVerse ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Self-activated DNA cleavage and nitric oxide reactivity studies on mononuclear
copper complexes derived from tetradentate ligands
⁎
Kaushik Ghosh , Pramod Kumar, Varun Mohan, Udai P. Singh
Department of Chemistry, Indian Institute of Technology, Roorkee, Roorkee-247667, Uttarakhand, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Two new tetradentate ligands Timpy (1,2-bis((E)-(2-phenyl-2-(pyridine-2-yl)hydrozono)methyl)benzene)
and Gimpy ((1Z,2Z)-1,2-bis(2-phenyl-2-(pyridine-2-yl)hydrozono)ethane) were synthesized and character-
ized. Mononuclear complexes [Cu(Timpy)(ClO4)](ClO4) (1) and [Cu(Gimpy)](ClO4)2 (2) were synthesized and
characterized by IR, UV–visible and conductivity measurements. The molecular structure of [Cu(Timpy)(ClO4)]
(ClO4) (1) was determined by single crystal X-ray diffraction and structural index parameter (τ=0.4725)
supported distorted square planar geometry at the metal centre. Electrochemical studies for 1 and 2 were inves-
tigated. Two-fold applications of these complexes were examined. First, self-activated DNA cleavage activity of
complexes 1 and 2 and mechanism of nuclease activity. Second, the complexes were utilized as fluorescence
probe for the detection of nitric oxide in solution.
Received 12 August 2011
Accepted 23 September 2011
Available online 4 October 2011
Keywords:
Copper complexes
Crystal structure
Electrochemistry
Nuclease activity
Self-activation
NO reactivity
© 2011 Elsevier B.V. All rights reserved.
There has been considerable interest in the recent years for design
and synthesis of DNA cleaving reagents for their applications in biotech-
nology and medicine [1,2]. Discovery of cisplatin followed by platinum
metal based anti-tumor drugs are important for their use as chemother-
apeutic agents. However, platinum based drugs exhibit some serious
side effects and toxicity [3,4]. Hence there are continuous quest for the
metal based drug that could be used for cancer treatment and few ruthe-
nium based anticancer drugs are in clinical trial [5]. Transition metal ions
show diverse structural features, variable oxidation and spin states and
redox properties in different complexes and these properties could be
exploited to discover novel artificial nucleases. Among the first row
transition elements, copper has got special interest in this regard since
the discovery of first chemical nuclease by Sigman and coworkers [6].
Copper is one of the essential elements in biology and there are several
metalloproteins which need copper for their activity [4]. Biologically
relevant copper has high affinity for the nucleobases and copper com-
plexes possess biologically accessible redox properties [7].
Investigation of literature revealed that oxidative DNA cleavage
reaction by copper complexes are mediated by reactive oxygen spe-
cies produced via oxidation of CuII to CuIII by oxidizing agents and
reduction of CuII to CuI by reducing agents [7–13]. Alternatively, a
transient metal bound species formulated as [CuOH]2+ [CuOOH]+
and [CuO]+ are also reported to be responsible for DNA strand scis-
sion [8,9,14]. However, addition of such oxidising or reducing agents
is not useful for in vivo applications of such complexes in metallo-
pharmaceutical research [15], hence it would be of interest to find a
self-activated system that would not require any type of activation
to generate reactive species for DNA cleavage activity. Reedijk and
coworkers reported [15,16] copper complexes derived from ligand
pbt and [CuII(pyramol)(Cl)] which exhibited self-activated DNA
cleavage. There are also few reports of such type of nuclease activity
by Tonde et al. [17], Li et al. [18], Kellett et al. [19] and Sissi et al.
[20]. Recently we have reported mononuclear copper(II) complex
[Cu(Pyimpy)(Cl)(ClO4)] afforded cleavage of pBR322 plasmid DNA
via self-activation and investigation of mechanism indicated the pos-
sible role of reactive oxygen species in DNA cleavage [21].
Herein we report two new copper complexes derived from ligands
Timpy and Gimpy as shown in Scheme 1 and their self-activated nucle-
ase activity. The new ligands were characterized by UV–visible, IR, NMR
and fluorescence spectral studies. Copper complexes [Cu(Timpy)
(ClO4)](ClO4) (1) and [Cu(Gimpy)](ClO4)2 (2) were synthesized and
characterized by spectroscopic studies. Molecular structure of complex
[Cu(Timpy)(ClO4)](ClO4) (1) was determined by single crystal X-ray
diffraction. Stabilization of copper (II) centre was examined by electro-
chemical studies. Nuclease activity with plasmid pBR322 DNA was
investigated and results of our mechanistic studies will be scrutinized
in this report.
Interestingly, it has been found out during spectroscopic characteri-
zation that the new ligands reported in this communication exhibited
fluorescence emission. During characterization of copper complexes
we found out the quenching of fluorescence emission of the ligands.
These data prompted us to study fluorescence based nitric oxide sens-
ing by copper complexes. There has been considerable current interest
in the fluorescence-based detection of nitric oxide (NO) [22,23], which
is a diatomic radical species and is involved in variety of biological pro-
cesses namely vasodilatation, immune response, neurotransmission,
⁎
Corresponding author. Tel.: +91 1332 285547; fax: +91 1332 273560.
E-mail address: ghoshfcy@iitr.ernet.in (K. Ghosh).
1387-7003/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2011.09.038

K. Ghosh et al. / Inorganic Chemistry Communications 15 (2012) 56–60
57
H
H
N
N
N
N
N
N
N
N
N
N
N
N
Timpy
Gimpy
Scheme 1. Schematic drawing of ligands.
apoptosis etc. in different cells and tissues [24]. Reduction of Cu(II) to Cu
(I) by NO is important for biological activity of several enzymes namely
cytochrome c oxidase, laccase etc. [25]. Interestingly, this reduction
generates a diamagnetic metal centre (Cu(I), d10) [26] and helps the de-
tection of NO in solution by fluorescence spectral studies [22]. Hence we
report here two novel copper complexes which are not only important
for self-activated DNA cleavage but also are useful for fluorescence-
based detection of nitric oxide.
Fig. 1. Ball and stick representation of [Cu(Timpy)(ClO4)](ClO4) (1) showing the atom
numbering scheme. Perchlorate anion is omitted for clarity. Selected bond lengths (Å)
and angles (˚): Cu(1)−N(1) 1.944(3), Cu(1)−N(3) 1.987(3), Cu(1)−N(4) 1.964(3), Cu
(1)−N(5) 1.975(3), Cu(1)−O(1) 2.321(3), N(1)−Cu(1)−N(3) 79.91(14), N(1)−Cu
(1)−N(4) 177.23(14), N(1)−Cu(1)−N(5) 99.58(14), N(1)−Cu(1)−O(1) 90.05(14),
N(3)−Cu(1)−N(4) 99.48(14), N(3)−Cu(1)−N(5) 148.91(13), N(4)−Cu(1)−N(5)
82.34(14), N(3)−Cu(1)−O(1) 99.96(13), N(4)−Cu(1)−O(1) 87.39(13), N(5)−Cu
(1)−O(1) 111.13(15).
The tetradentate ligands Timpy and Gimpy were synthesized by
reacting phthaladehyde and glyoxal with 2-(1-phenylhydrazinyl)pyri-
dine respectively and characterized by elemental analysis, IR, UV–visible,
and 1H and 13C NMR spectroscopic studies. Reaction of Cu(ClO4)2∙2H2O
with tetradentate ligands Timpy and Gimpy in dichloromethane solution
afforded the complexes [Cu(Timpy)(ClO4)](ClO4) (1) and [Cu(Gimpy)]
(ClO4)2 (2). Details of the synthesis of ligands, copper complexes and
their spectra are shown in supporting information. In IR spectra of cop-
per complexes, shifting of azomethine (−HC=N–) stretching frequency
of the ligands indicated the ligation of azomethine nitrogen to metal cen-
tre [13, 21]. The splitting of the band near 1099 cm−1 and 1047 cm−1 in
IR spectrum of complex 1 showed the coordinated perchlorate ion to the
copper centre (Fig. S5) however, complex 2 has uncoordinated perchlo-
rate ions (Fig. S6) [13]. In UV–visible spectra, the intense electronic
bands observed between 361 and 445 nm for complexes 1 and 2 were
due to ligand to metal charge transfer [27]. Both the complexes 1 and 2
showed absorption bands~650 nm (ε=280 M−1 cm−1) and ~660 nm
(ε=150 M−1 cm−1) due to d-d transitions [26]. Magnetic moment
measurements at room temperature gave rise to one-electron paramag-
netic metal centre for both the complexes [16]. The molar conductivity
measurement of complexes 1 and 2 in DMF solution (ca. 10–3 M)
were found to be 132 and 136 Ω–1cm2mol–1 respectively at 25 °C indi-
cating bi-univalent electrolytic behaviors [28]. The ESI-MS spectra of
less than the angles N3−Cu1−N4 and N1−Cu1−N5 (99.47° and
99.57°). The distortion at the metal was also supported by the angles
(N3−Cu1−N5) and (N1−Cu1−N4) which are found to be 148.89°
and 177.24° respectively.
Non-covalent interactions in crystalline state are important in supra-
molecular chemistry and crystal engineering [31]. Crystal structure of 1
revealed that perchlorate ions in the crystal lattice were involved in sev-
eral types of hydrogen bonding (distances of 2.302 Å–2.692 Å) interac-
tion with aryl, imine, pyridine hydrogens (Fig. S8) [13,21]. The phenyl
ring of phthalaldehyde moiety of one molecule exhibited π–π interaction
with the same phenyl ring of the other molecule in the crystal lattice and
the distance was calculated to be near 3.92 Å (Fig. S9) [15]. However
distance between two closest carbon atoms of the phenyl rings involved
in π–π interaction was found to be 3.38 Å.
The redox behavior of both Cu(II) complexes 1 and 2 was investi-
gated by cyclic voltammetry at a glassy carbon electrode using Ag/
AgCl reference electrode. The voltammograms for complexes 1 and
2 are shown in Fig. 2. Complexes 1 and 2 exhibited irreversible
cathodic peaks near +0.075 V and +0.205 V vs Ag/AgCl respectively
complex
1
showed that [Cu(Timpy)]2+ (100%) and [Cu(Timpy)
(ClO4)]+ (15%) were present in the solution (Fig. S7). These data clearly
expressed that coordinated perchlorate ion in 1 got detached from the
metal centre and 1 and 2 possess similar behavior in solution although
for complex 1 we found metal coordinated perchlorate ion in IR and in
X-ray crystal structure (vide infra).
20
10
0
Molecular structure of mononuclear copper complex [Cu(Timpy)
(ClO4)](ClO4) (1) is depicted in Fig. 1 and the matrix parameters are
described in Table S1. The stereochemistry around metal centre is
described as distorted square pyramidal considering structural index
parameters τ=0.4725 shown in supporting information (The percent-
age of trigonal distortion from square-pyramidal geometry is described
by the parameter defined as [(α-β)/60]×100, where α and β are the an-
gles between the donor atoms forming the plane in a square pyramidal
geometry) [29]. Two pyridine nitrogens and two imine nitrogens gener-
ated equatorial plane and the perchlorate oxygen occupied the axial
positions. The Cu–NPy and Cu–Nim distances were consistent with the
reported values [13,30]. The axial Cu–OClO3 distance 2.32 Å is consistent
with the value reported by Palaniandavar and coworkers [10]. The cop-
per centre is 0.245 Å above the plane generated by the N1, N3, N4 and
N5 donors. Two pyridine rings and two imines are in the same plane
whereas the phenyl ring is roughly perpendicular (78.47° and 87.57°)
to the ligand binding plane. The two imine donors with copper form a
seven membered ring which generated the distortion in the molecule.
The angles N1−Cu1−N3 and N4−Cu1−N5 (79.91° and 82.36°) are
-10
-0.5
0.0
0.5
1.0
V vs Ag/AgCl
Fig. 2. Cyclic voltammograms of a 10−3 M solution of 1 (solid) and 2 (dotted) in
dichloromethane in presence of 0.1 M TBAP as a supporting electrolyte, glassy-carbon
as a working electrode; scan rate 0.1 V/s.

58
K. Ghosh et al. / Inorganic Chemistry Communications 15 (2012) 56–60
100
and are possibly due to Cu(II)/Cu(I) couple [13,21]. These complexes
also exhibited an anodic peak at +0.798 V and +0.837 V for 1 and 2
respectively and these anodic peaks probably satisfy the condition
for DNA cleavage via self-activation exhibited by complexes 1 and 2
[15,21] (vide infra).
SC
NC
LC
80
60
40
20
0
We investigated the nuclease activity of the complexes 1 and 2. The
cleavage of supercoiled (SC) pBR322 DNA by 1 and 2 and formation of
nicked (NC) and linear (LC) DNA were studied by several gel electropho-
resis experiments in Tris-boric acid–EDTA buffer (TBE). The nuclease
activity of 1 and 2 was observed in absence of any oxidizing or reducing
agents and the amount of NC DNA was found to be increased with the
concentration of 1 and 2 (10–100 μM) without the formation of LC
form of DNA (Fig. 3). The enhancement of DNA cleavage activity was ob-
served due to variation of incubation time. For complete conversion of
SC form to NC and LC form, 6 h incubation was enough (Fig. S10).
In another experiment, we investigated the cleavage activity of ligands
Timpy and Gimpy in presence of metal salts such as Cu(ClO4)2∙6H2O, Mn
(ClO4)2∙6H2O, Zn(ClO4)2∙6H2O and CoCl2 (metal-ligand ratio 1:1) and we
found out that Cu(ClO4)2∙6H2O exhibited the nuclease activity in pres-
ence of both the ligands (Fig. S11). The ligand Timpy and Gimpy showed
negligible nuclease activity (Fig. 3). DNA cleavages were also performed
aerobically in the presence of oxidizing or reducing agent. Complexes 1
and 2 showed complete conversion of SC form into NC and LC form of
pBR322 DNA in the presence of H2O2 and 2–mercaptoethanol (BME)
(Fig. 4). In presence of H2O2 complex 1 and 2 afforded similar nuclease ac-
tivity (Fig. 4, lanes 4,7) however, in the presence of 2-mercaptoethanol,
complex 2 showed higher nuclease as compared to 1 (Fig. 4, lanes 5,8).
Hence we found out the enhancement of DNA cleavage activity in pres-
ence of H2O2 and 2-mercaptoethanol (BME).
1
2
3
4
5
6
7
8
Fig. 4. Gel electrophoresis patterns and the proportions of DNA for different form of
pBR322 DNA (40 ng) by complexes and (100 μM) in the presence of H2O2
(200 μM) and BME (200 μM) after 2 h incubation at 37 °C. Key: lane 1, DNA control;
lane 2, DNA+Cu(ClO4)2∙2H2O (100 μM); lane 3, DNA+1; lane 4, DNA+1+H2O2;
lane 5, DNA+1+BME; lane 6, DNA+2; lane 7, DNA+2+H2O2; lane 8, DNA+2+BME.
1
2
nuclease activity could be diagnosed by monitoring the quenching of
DNA cleavage in the presence of radical scavengers in solution [7–13].
The hydroxyl radical scavengers like DMSO, ethanol and urea did not
show the inhibition of nuclease activity (Fig. 5, lanes 3–5 and lanes
10–12). These results suggested that hydroxyl radicals may not be in-
volved in the cleavage process for both the complexes 1 and 2. Addition
of singlet oxygen scavengers like NaN3 and L−histidine (Fig. 5, lanes
6,7 and lanes 13,14) showed inhibition of nuclease activity. So these re-
sults suggested that 1O2 or any other singlet oxygen-like entity may
participate in the DNA strand scission [13,21,32]. Probable participation
of hydrogen peroxide was also included due to inhibition of nuclease
activity upon addition of catalase (Fig. 5, lane 8,15). On the basis of
Investigation of the mechanism becomes very much important
when copper complexes exhibited nuclease activity in absence of any
external reagent. There are several reports in the literature where
such type of activity was described; however, following reports [7–13]
will be of our interest at this point. In few reports, authors explained
such type of DNA cleavage activity via hydrolytic pathway because
nuclease activity was not inhibited by radical scavengers. Later on reli-
gation experiment was examined to confirm hydrolytic cleavage. If
nuclease activity was inhibited by the presence of radical scavengers
we could speculate the possible role of reactive oxygen species (ROS)
in nuclease activity. Involvement of reactive oxygen species (hydroxyl
radical, superoxide ion, singlet oxygen and hydrogen peroxide) in
100
SC
NC
100
NC
SC
80
60
40
20
80
60
40
20
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Fig. 5. Gel electrophoresis patterns and the proportions of DNA for different forms of
pBR322 DNA (40 ng) by complexes 1 and 2 (100 μM) in the presence or absence of rad-
ical scavengers after 2 h of incubation at 37 °C. lane 1, DNA; lane 2, DNA+1; lanes 3–8,
DNA+1+DMSO (20 mM), urea (20 mM), ethanol (20 mM), NaN3 (20 mM), L-
histidine (20 mM), catalase (10 U) respectively; lane 9, DNA+2; lanes 10–15, DNA+
2+DMSO (20 mM), urea (20 mM), ethanol (20 mM), NaN3 (20 mM), L-histidine
(20 mM), catalase (10 U) respectively.
Fig. 3. Gel electrophoresis patterns and the proportions of DNA for different form of
pBR322 DNA (40 ng) by complexes 1 and 2 after 2 h incubation at 37 °C. Key: lane 1,
DNA control; lane 2, DNA+Gimpy; lane 3, DNA+Timpy; lanes 4–9, DNA+1=10,
25, 40, 50, 75, 100 μM respectively; lanes 10–15, DNA+2=10, 25, 40, 50, 75,
100 μM respectively.

K. Ghosh et al. / Inorganic Chemistry Communications 15 (2012) 56–60
59
above observations we predict that complex 1 and 2 generated reactive
oxygen species (ROS) (most probably singlet oxygen and hydrogen per-
oxide) which were responsible for nuclease activity. Hence we report
that 1 and 2 are another novel examples by which nuclease activity hap-
pened via self-activation.
situ reacted with copper complexes and afforded greenish-yellow and
yellow colored solution respectively for 1 and 2, which indicated the
formation of new copper complexes. The d–d transitions for complexes
1 and 2 were found to appear at 650 nm and 660 nm respectively. On
passing the nitric oxide by layering, these bands disappeared due to for-
mation of some copper nitrosyl complexes (Fig. S12 and S13) [26]. The
paramagnetic copper complexes 1 and 2 derived from ligands Timpy
and Gimpy did not show any fluorescence; however, the in situ gener-
ated new nitrosyl copper complexes exhibited fluorescence in dichlor-
omethane solution and spectra are shown in Fig. 7. The UV–visible
and fluorescence data support the formation of copper complex con-
taining {Cu-NO}10[22] moiety according to Enemark and Feltham nota-
tion [35]. However we would like to mention that IR spectra of 1 and 2
afforded peaks at 1739 cm−1 and 1744 cm−1 respectively (shown in
Fig. S14 and S15 respectively). These two peaks are consistent with
the data reported by Fujisawa et al. [36] where copper complex, [Cu
(L3)(NO)](ClO4), containing {Cu-NO}11 moiety was derived from neu-
tral ligand. Investigation of literature revealed that NO has the tendency
to reduce the copper centre [25] during its reactivity with copper com-
plexes. In fact in few cases we observed dissociation of the ligand from
the metal complexes [26]. Hence coordination of NO to the metal centre
could afford {Cu-NO}10 species, on the other hand reduction of Cu(II)
centre followed by NO coordination may lead to the formation of {Cu-
NO}11 species. At this point it is difficult to predict which particular spe-
cies and/or both are formed in the solution however our data indicate the
formation of copper nitrosyl complexes. Hence such metal complexes
could be used for detection of NO in solution and insight into this work
is under progress.
The ligands Timpy and Gimpy afforded fluorescence emission spectra
near 440 nm upon excitation at 370 nm (i.e. λex =370 nm). Effect of sol-
vent on the emission bands of Timpy and Gimpy was displayed in Fig. 6.
Both the ligands showed the three humped emission curves near 415,
435 and 460 nm when methanol and ethanol were used as solvent.
However, in more polar solvents like in acetonitrile and water, Timpy
and Gimpy exhibited a broad band in the range 440–490 nm. A similar
change was observed in the emission spectra of Timpy and Gimpy on
going from toluene to dichloromethane. The fluorescence property of
ligand is expected to be quenched on coordination to the paramagnetic
center [33] hence the coordination of copper centre in these ligand
frames completely quenched the fluorescence. As an alternative, the
reduction of Cu(II) to Cu(I) by nitric oxide can offer a methodology for
diamagnetic species formation and the recovery of the fluorescence
property [22,23].
The reactivity of nitric oxide with both the copper complexes 1 and 2
was investigated in dichloromethane solution at room temperature.
Nitric oxide was generated in situ by acid nitrite solution [34] which
was layered on dichloromethane solution of 1 and 2 (details are de-
scribed in the supporting information). NO molecules generated in
Timpy
a
Acetonitrile
300
Dichloromethane
Dimethyl formamide
Ethanol
80
60
Water
200
100
0
Toluene
Methanol
40
20
0
400
500
600
Wavelength (nm)
400
420
440
460
480
500
Wavelength (nm)
Gimpy
100
80
60
40
20
0
b
200
100
0
Acetonitrile
Dimethyl formamide
Water
Methanol
Dichloromethane
Ethanol
Toluene
400
420
440
460
480
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
Fig. 7. Fluorescence spectra of complexes 1 and 2 (dotted lines ⋅⋅⋅⋅) (100 μM) in
dichloromethane. After passing NO five scans for each complex (solid lines −−−)
within 10 min at 298 K (λex =370 nm).
Fig. 6. Fluorescence emission spectra of ligands Timpy and Gimpy in different solvent
(λex =370 nm).

60
K. Ghosh et al. / Inorganic Chemistry Communications 15 (2012) 56–60
[3] C.X. Zhang, S.J. Lippard, Current Opinion in Chemical Biology 7 (2003) 481.
In conclusion, mononuclear copper(II) complex [Cu(Timpy)(ClO4)]
[4] I. Bertini, H.B. Gray, S.J. Lippard, J.S. Valentine, Bioinorganic Chemistry; University
Science Books, Viva Books Private Limited, South Asian Edition, New Delhi, 2004.
[5] Y.K. Yan, M. Melchart, A. Habtemariam, P.J. Sadler, Chemical Communications
(2005) 4764.
[6] D.S. Sigman, A. Mazumdar, D.M. Perrin, Chemical Reviews 93 (1993) 2295.
[7] J. Chen, X. Wang, Y. Shao, J. Zhu, Y. Zhu, Y. Li, Q. Xu, Z. Guo, Inorganic Chemistry 46
(2007) 3306.
[8] C. Tu, Y. Shao, N. Gan, Q. Xu, Z. Guo, Inorganic Chemistry 43 (2004) 4761.
[9] J. Tan, B. Wang, L. Zhu, Journal of Biological Inorganic Chemistry 14 (2009) 727.
[10] V. Rajendiran, R. Karthik, M. Palaniandavar, H. Stoeckli-Evans, V.S. Perisami, M.A.
Akbarsha, B.S. Srinag, H. Krishnamurthy, Inorganic Chemistry 46 (2007) 8208.
[11] X. Sheng, X. Guo, X.M. Lu, G.Y. Lu, Y. Shao, F. Liu, Q. Xu, Bioconjugate Chemistry 19
(2008) 490.
(ClO4) (1) and [Cu(Gimpy)](ClO4)2 (2) derived from tetradentate
ligands Timpy and Gimpy respectively were synthesized and character-
ized. Molecular structure of complex 1 determined by X−ray crystal-
lography showed the distorted square planar geometry around the
metal centre and this was supported by structural index parameter.
Redox property of 1 and 2 was investigated and both complexes exhib-
ited two irreversible couples in the cyclic voltammograms.
We have found two-fold applications of complexes 1 and 2. First,
these complexes exhibited nuclease activity in absence of any oxidizing
or reducing agent. Hence these complexes showed DNA cleavage activ-
ity via self-activation and enhancement of activity was found in pres-
ence of oxidizing and reducing agents. The self-activated DNA cleavage
efficiency was dependent both on the complex concentration and on
the time of incubation. Mechanistic investigation implicated possible
role of singlet oxygen and hydrogen peroxide in DNA cleavage activity.
Hence such types of complexes demand their applications in metallo-
pharmaceutical research.
Second, these complexes exhibited fluorescence emission during
their reactivity studies with nitric oxide, although complexes 1 and 2
did not show fluorescence emission. Hence these complexes could be
used for the fluorescence-based detection of nitric oxide in solution.
Details of mechanistic investigation on nuclease activity, biological
activity studies, modification of the ligand frame and applications of
these complexes are currently under progress.
[12] Y. Shao, J. Zhang, C. Tu, C. Dai, Q. Xu, Z. Guo, Journal of Inorganic Biochemistry 99
(2005) 1490.
[13] K. Ghosh, P. Kumar, N. Tyagi, U.P. Singh, V. Aggarwal, M.C. Baratto, European Jour-
nal of Medicinal Chemistry 45 (2010) 3770.
[14] M. Pitie, G. Pratvial, Chemical Reviews 110 (2010) 1018.
[15] P.U. Maheswary, M.V.D. Ster, S. Smulders, S. Barends, G.P. van Wezel, C. Massera,
S. Roy, H.D. Dulk, P. Gamez, J. Reedijk, Inorganic Chemistry 47 (2008) 3719.
[16] P.U. Maheswary, S. Roy, H.D. Dulk, S. Barends, G.P. van Wezel, B. Kozlevčar, P.
Gamez, J. Reedijk, Journal of the American Chemical Society 129 (2006) 710.
[17] S.S. Tonde, A.S. Kumbhar, S.B. Padhye, R.J. Butcher, Journal of Inorganic Biochem-
istry 100 (2006) 51.
[18] K. Li, L.-H. Zhou, J. Zhang, S.-Y. Chen, Z.-W. Zhang, J.-J. Zhang, H.-H. Lin, X.-Q. Yu,
European Journal of Medicinal Chemistry 44 (2009) 1768.
[19] A. Kellett, M. O'Connor, M. McCann, M. McNamara, P. Lynch, G. Rosair, V. McKee, B.
Creaven, M. Walsh, S. McClean, A. Foltyn, D. O'Shea, O. Howe, M. Devereux, Dalton
Transactions 40 (2011) 1024.
[20] C. Sissi, F. Mancin, M. Gatos, M. Palumbo, P. Tecilla, U. Tonellato, Inorganic Chem-
istry 44 (2005) 2310.
[21] K. Ghosh, P. Kumar, N. Tyagi, U.P. Singh, N. Goel, Inorganic Chemistry Communi-
cations 14 (2011) 489.
[22] B. Mondal, P. Kumar, P. Ghosh, A. Kalita, Chemical Communications 47 (2011)
2966.
Acknowledgments
[23] Z.J. Tonzetich, L.E. McQuade, S.J. Lippard, Inorganic Chemistry 49 (2010) 6338.
[24] L.J. Ignarro (Ed.), Nitric oxide: Biology and Pathobiology, Academic Press, San
Diego, CA, 2000.
[25] A.M. Wright, G. Wu, T.W. Hayton, Journal of the American Chemical Society 132
(2010) 14336.
[26] M. Sarma, B. Mondal, Inorganic Chemistry 50 (2011) 3206.
[27] N. Lehnert, U. Cornelissen, F. Neese, T. Ono, Y. Noguchi, K. Okamoto, K. Fujisawa,
Inorganic Chemistry 46 (2007) 3916.
KG is thankful to IIT Roorkee, India for the financial support (Faculty
Initiation grant (Scheme-B) funded by MHRD). PK is thankful to CSIR
and VM is thankful to UGC, India for fellowship. We are thankful to
IITR for the instrumental facilities. UPS is thankful to Instrumental
Centre and IIT Roorkee for the single crystal X-ray facility.
[28] W.J. Geary, Coordination Chemistry Reviews 7 (1971) 81.
[29] K. Ghosh, P. Kumar, N. Tyagi, U.P. Singh, Inorganic Chemistry 49 (2010) 7614.
[30] S.L. Ma, X.X. Sun, S. Gao, C.M. Qi, H.B. Huang, W.X. Zhu, European Journal of Inor-
ganic Chemistry (2007) 846.
[31] G.R. Desiraju, T. Steiner, The Weak Hydrogen Bond in Structural Chemistry and
Biology, Oxford University Press, New York, 1999.
[32] J.L. Garcia-Gimenez, G. Alzuet, M. Gonzalez-Alvarez, A. Castineiras, M. Liu-Gonzalez,
J. Borras, Inorganic Chemistry 46 (2007) 7178.
[33] K. Rurack, J.L. Bricks, B. Schulz, M. Maus, G. Reck, U. Resch-Genger, Journal of the
American Chemical Society 122 (2000) 6171.
Appendix A. Supplementary material
The experimental and crystal structure details are in supporting
information. The CCDC No. for [Cu(Timpy)(ClO4)](ClO4) is 825827.
The data can be obtained free of charge via www.ccdc.cam.ac.uk/
conts/retrieving.html. Supplementary data to this article can be found
online at doi:10.1016/j.inoche.2011.09.038.
[34] K. Ghosh, S. Kumar, R. Kumar, U.P. Singh, N. Goel, Organometallics 30 (2011)
2498.
[35] J.H. Enemark, R.D. Feltham, Coordination Chemistry Reviews 13 (1974) 339.
[36] K. Fujisawa, A. Tateda, Y. Miyashita, K. Okamoto, F. Paulat, V.K.K. Praneeth, A. Merkle,
N. Lehnert, Journal of the American Chemical Society 132 (2008) 1205.
References
[1] F. Mancin, P. Scrimin, P. Tecilla, U. Tonellato, Chemical Communications (2005)
2540.
[2] K.V.D. Schilden, F. Garcia, H. Kooijman, A.L. Spek, J.G. Haasnoot, J. Reedijk, Angewandte
Chemie (International Ed. in English) 43 (2004) 5668.