DNA-binding, antioxidant activity and solid-state fluorescence studies of copper(II), zinc(II) and nickel(II) complexes with a Schiff base derived from 2-oxo-quinoline-3-carbaldehyde

Article abstract of DOI:10.1007/s11243-011-9494-y

A Schiff base derived from 2-oxo-quinoline-3-carbaldehyde-4-aminophenazone and its Cu(II), Zn(II) and Ni(II) complexes were synthesized. The molecular structures of the Zn(II) and Ni(II) complexes were determined by X-ray crystal diffraction. The DNA-bind

Full text of DOI:10.1007/s11243-011-9494-y

Transition Met Chem (2011) 36:489–498
DOI 10.1007/s11243-011-9494-y
DNA-binding, antioxidant activity and solid-state fluorescence
studies of copper(II), zinc(II) and nickel(II) complexes
with a Schiff base derived from 2-oxo-quinoline-3-carbaldehyde
•
Zeng-Chen Liu Zheng-Yin Yang Tian-Rong Li
•
•
•
Bao-Dui Wang Yong Li Ming-Fang Wang
•
Received: 19 January 2011 / Accepted: 18 April 2011 / Published online: 6 May 2011
ꢀ Springer Science+Business Media B.V. 2011
Abstract A Schiff base derived from 2-oxo-quinoline-3-
carbaldehyde-4-aminophenazone and its Cu(II), Zn(II) and
Ni(II) complexes were synthesized. The molecular struc-
tures of the Zn(II) and Ni(II) complexes were determined
by X-ray crystal diffraction. The DNA-binding modes of
the compounds were investigated by spectroscopic meth-
ods, viscosity measurements and ethidium bromide-DNA
displacement experiments. The experimental evidence
indicated the compounds interact with calf thymus DNA
through intercalation. Additionally, the compounds exhib-
ited potential antioxidant properties in in vitro studies, and
the Cu(II) complex was the most effective. The solid-state
fluorescence properties of the Zn(II) complex were studied.
small molecules such as quinoline, flavone and coumarin [5,
6]. The non-covalent interactive modes, which include
intercalation, groove binding and electrostatic binding, are
important in the biological activity of many drugs and the
mechanisms by which DNA replication is inhibited in can-
cer cells. Biological activities such as antitumor, antima-
larial and antibacterial activities are all relevant to the
binding modes of DNA to drugs [7, 8]. Hence, studies on
interactive modes of transition metal complexes with DNA
can provide us with new insights, not only for the design of
drugs but also to develop highly sensitive diagnostic agents.
Quinoline derivatives have attracted much attention
during the last decades due to their potential application as
antibacterial drugs that effectively inhibit DNA replication
[9, 10]. It has been reported that some transition metal
complexes with quinoline derivatives exhibit excellent
DNA-binding and biological activities [11, 12]. Many
Schiff base complexes have been investigated extensively
owing to the good coordination properties of such ligands
and attractive biological activities of the complexes
[13–19]. In this paper, the synthesis, characterization and
DNA-binding activities of new transition metal complexes
(Cu, Zn, Ni) with quinoline-2-one-3-carbaldehyde-4-ami-
nophenazone Schiff base are presented. The structures of
the Zn(II) and Ni(II) complexes have been characterized by
X-ray crystallography. The DNA-binding activities have
been investigated by UV–Vis spectroscopic titration, fluo-
rescence spectra and viscosity measurements. Furthermore,
the intrinsic binding constants have been determined by
fluorescence titration. As reported in previous papers, some
transition metal complexes exhibit potential antioxidant
activities [20–23]. Since free radicals such as hydroxyl
are relevant to many diseases such as Alzheimers and
Parkinsons [24], the investigation into hydroxyl radical
scavenging by metal complexes is of interest.
Introduction
Ever since the discovery of cis-platin as an anticancer agent,
investigation into the interactions of transition metal
complexes with DNA has been pursued, because of their
utility as DNA footprinting agents, structural probes,
sequence-specific cleavage agents and potential antitumor
drugs [1–4]. We have focused on the DNA-binding prop-
erties of metal complexes derived from biologically active
Z.-C. Liu ꢀ Z.-Y. Yang (&) ꢀ T.-R. Li ꢀ B.-D. Wang ꢀ Y. Li ꢀ
M.-F. Wang
College of Chemistry and Chemical Engineering and State Key
Laboratory of Applied Organic Chemistry, Lanzhou University,
730000 Lanzhou, People’s Republic of China
e-mail: yangzy@lzu.edu.cn
Z.-C. Liu ꢀ Z.-Y. Yang ꢀ T.-R. Li ꢀ B.-D. Wang ꢀ Y. Li ꢀ
M.-F. Wang
Key Laboratory of Nonferrous Metal Chemistry and Resources
Utilization of Gansu Province, Lanzhou University,
730000 Lanzhou, People’s Republic of China
123

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Transition Met Chem (2011) 36:489–498
The Zn(II) complex, which emits Kelly fluorescence
stirred under reflux for 12 h, where upon a white precipi-
tate separated out. The precipitate was filtrated off and
washed with ethanol. Recrystallization from DMF/H2O
(V:V = 1:1) gave the ligand HL, which was dried under
under UV light, exhibits excellent solid-state luminescence
properties, as reported in this paper.
1
vacuum. Yield, 1.16 g, 85%. m.p: 307–309 ꢁC. H–NMR
Experimental
(DMSO-d6 400 MHz): d 11.95 (1H, s, –N1–H), d 9.75 (1H,
s, –CH=N), d 8.54 (1H, s, –C4–H), d 7.83–7.81 (1H, J = 8,
0
0
0
Calf thymus DNA (CT-DNA) and EB (Ethidium bromide)
were purchased from Sigma. The CT-DNA was dissolved
in double distilled deionized water. The concentrations of
DNA were determined using the molar extinction coeffi-
cient of 6,600 M-1 cm-1. Acetanilide was purchased from
Guang Fu Chemical Co, Tianjin, China. All materials
and solvents were of analytical reagent grade quality and
were used without further purification. All spectroscopic
measurements were taken in Tris–HCl buffer (pH = 7.2)
containing 5 mM tris [Tris (hydroxymethyl)-amino meth-
ane] and 50 mM NaCl.
1H-NMR spectra were recorded on a Varian VR300-
MHz spectrometer with TMS as an internal standard.
Melting points were determined on a Beijing XT4-100X
microscopic melting point apparatus. ESI-MS spectra were
recorded on an Esquire 6000 mass spectrograph. UV–Vis
spectra were recorded on a Perkin-Elmer Lambda-35 UV–
Vis spectrophotometer. Fluorescence spectra were obtained
on a Shimadzu RF-5301 spectrophotometer at room tem-
perature. Molar conductivity measurements were taken
with a DDS-11C type conductivity bridge using 1.0 9
10-3 mol/L solutions in ethanol at 25 ꢁC. IR spectra were
recorded on a Thermo Mattson FTIR instrument using KBr
discs in the 4,000–400 cm-1 region.
d, –C8–H), d 7.55–7.50 (3H,0 overlap, –C10 ,14 ,12 –H), d
0
7.39–7.36 (3H, overlap, –C11 ,13 ,6–H), d 7.33–7.31 (1H,
J = 8, d, –C5–H), d 7.22–7.18 (1H, J0 = 16, m, –C7–H), d
0
3.30 (3H, s, –C7 –H), d 3.20 (3H, s, –C5 –H). IR (KBr) cm-1
:
m (C=O)2-oxo-quinoline 1,654, m (C=O)4-aminophenazone 1,652, m
(C=N) 1,622.
Preparation of the complexes
HL (0.2 mmol, 0.0716 g) and Cu(II) nitrate (0.2 mmol,
0.0483 g) were added to ethanol (10 mL). After stirring for
5 min, the mixture was filtered to remove insoluble residues
and then stirred under reflux for 10 h. The resulting green
precipitate (yield: 0.096 g, 85%) of the Cu(II) complex was
filtered off, washed several times with ethanol and dried for
24 h under vacuum. Anal. Calcd for C21H20N6O9Cu (%): C,
44.7; H, 3.6; N, 14.9. Found (%): C, 45.7; H, 3.6; N, 14.5. ESI-
MS (CH3OH, m/z): 439.2, IR (KBr) cm-1: m (C=O)2-oxo-quinoline
-
1,642, m (C=O)4-aminophenazone 1,639, m (C=N) 1,615, m (NO3
1,384.
)
The Zn(II) and Ni(II) complexes were prepared by the
same method as for the Cu(II) complex. Zn(II) com-
plex: Yield, 80%, Colour yellow, Anal. Calcd for
C21H24N5O11Zn (%): C, 41.9; H, 4.0; N, 13.9. Found
(%): C, 41.7; H, 4.0; N, 13.5. IR (KBr) cm-1
:
Synthesis of the ligand
m (C=O)2-oxo-quinoline 1,642, m (C=O)4-aminophenazone 1,638,
m (C=N) 1,614, m (NO3-) 1,383. Ni(II) complex: Yield,
75%, Colour green. Anal. Calcd for C21H24N5O11Ni (%):
C, 42.4; H, 4.1; N, 14.1. Found (%): C, 42.6; H, 3.9; N,
As shown in Scheme 1, 2-oxo-quinoline-3-carbaldehyde
was prepared according to the literature [25, 26]. An ethanol
solution (10 mL) of 4-aminophenazone (0.71 g, 3.5 mmol)
was added to an ethanol solution (10 mL) of 2-oxo-quino-
line-3-carbaldehyde (0.6 g, 3.5 mmol). The mixture was
14.1. IR (KBr) cm-1
: m (C=O)2-oxo-quinoline 1,644,
-
m (C=O)4-aminophenazone 1,639, m (C=N) 1,615, m (NO3
1,384.
)
Scheme 1 Synthesis of ligand
(2-oxo-quinoline-3-
carbaldehyde-4-
H
N
CH3
CHO
CHO
POCl3
DMF
70%HAc
aminophenazone Schiff base)
O
N
H
O
N
Cl
5'
4'
N
1'
4
N
5
7'
N
H2N
3'
6'
8'
3
6
7
N
O
2'
HL
N
10'
2
9'
15'
C2H5OH(reflux)
11'
12'
N
O
O
1
8
16'
H
14'
13'
123

Transition Met Chem (2011) 36:489–498
X-ray crystallography
491
r. All experiments were conducted at 20 ꢁC in a buffer
containing 5 mM Tris–HCl (pH = 7.2) and 50 mM NaCl.
The viscosity measurements were obtained using an
Ubbelohde viscometer in a water bath maintained at
298.0 ( 0.1) K. The DNA concentration was kept constant
(5 lM), and the concentration of test compound was
gradually increased (0.5–3.5 lM). The solution’s flow time
through the capillary was determined to the nearest 0.02 s
using a stopwatch. Each sample was measured three times,
and then an average flow was calculated. Data were ana-
lysed as (g/g0)1/3 versus the ratio of the concentration of the
compound to CT-DNA, where g is the viscosity of CT-
DNA in the presence of the compound, and g0 is the vis-
cosity of CT-DNA alone. Viscosities were calculated from
the observed flow times of solutions containing CT-DNA
corrected for the flow time of buffer alone (t0), g = t-t0.
Ethidium bromide experiments were conducted by
adding solutions of the compounds to the Tris–HCl buffer
containing EB-DNA. The change in fluorescence intensity
was recorded using excitation and emission wavelengths of
521 and 587 nm, respectively.
A yellow crystal of the Zn(II) complex was mounted on a
Bruker Smart-1000 CCD diffractometer with graphite-
˚
monochromated Mo-ka radiation (k = 0.71073A) at 296(2) K.
The intensity data were collected by the x scan mode
within 2.32 \ h \ 28.49ꢁ for hkl (-11 B h B 12,
-14 B k B 13, -17 B l B 17) in the Triclinic crystal
system. The positions and anisotropic thermal parameters
of all non-hydrogen atoms were refined on F2 by full-
matrix least-squares techniques with the SHELX-97 pro-
gram package (G. M. Sheldrick, Bruker AXS, Madison,
WI, 2001). Absorption corrections were employed using
semi-empirical methods from equivalents.
A green crystal of the Ni(II) complex was measured on a
Bruker Smart-1000 CCD diffractometer with graphite-
˚
monochromated Mo-ka radiation (k = 0.71073A) at 296(2) K.
The intensity data were collected by the x scan mode
within 2.31 \ h \ 28.40ꢁ for hkl (-11 B h B 11, -14 B
k B 14, -17 B l B 17) in the Triclinic crystal system. The
positions and anisotropic thermal parameters of all non-
hydrogen atoms were refined on F2 by full-matrix least-
squares techniques with the SHELX-97 program package.
Absorption corrections were employed using semi-empir-
ical methods from equivalents.
Hydroxyl radical scavenger measurements
Hydroxyl radicals in aqueous media were generated using
the Fenton system [28, 29]. Solutions of the test complexes
were prepared with double distilled water. The 5 mL
assay mixture contained the following reagents: safranin
(11.4 lM), EDTA-Fe(II) (40 lM), H2O2 (1.76 mM), the
test complex (1–6 lM) and a phosphate buffer (67 lM,
pH = 7.4). The assay mixtures were incubated at 30 ꢁC for
10 min in a water bath. The absorbance was then measured
at 520 nm. All the tests were run in triplicate and are
expressed as the mean and standard deviation (SD) [30].
The scavenging ratio is defined as
DNA-binding study methods
UV–Vis absorption titration experiments were performed
by maintaining a constant concentration of the compounds
(10 lM) and gradually increasing the concentration of CT-
DNA. The compounds were dissolved in a mixed solvent of
1% methanol and 99% Tris–HCl buffer. The reference
solution was the corresponding Tris–HCl buffer solution.
When measuring the absorption spectra, equal amounts of
CT-DNA were added to both the compound and reference
solutions to eliminate the absorbance of CT-DNA itself.
The sample solution was scanned in the range 200–500 nm.
For the fluorescence spectroscopic titrations, fixed
amounts of the compounds (10 lM) were titrated with
increasing amounts of CT-DNA. The samples were excited
at 375 nm, and the fluorescence emission intensity was
monitored at 501 nm. K values were determined using the
following equation [27];
Scavenging ratio ð%Þ ¼ ½ðAi ꢁ A0Þ=ðAc ꢁ A0Þꢂ ꢃ 100
where Ai = absorbance in the presence of the test com-
pound; A0 = absorbance of the blank in the absence of the
test compound; Ac = absorbance in the absence of the
tested compound, EDTA-Fe(II) and H2O2.
Solid-state fluorescence experiments were performed at
roomtemperature with a slitwidth of1.5 nmfor both entrance
and exit slits. The excitation wavelength was 393 nm, and the
emission wavelength was 513 nm for all compounds.
r=Cf ¼ Kð1 ꢁ nrÞ
where r = Cb/[DNA], Cf = Ct [(F-F0)/(Fmax-F0)], and
Cb and Ct are the concentrations of free compound and total
compound, respectively. F is the observed fluorescence
emission intensity at a given DNA concentration, F0 is the
intensity in the absence of DNA and Fmax is the fluores-
cence intensity of the totally bound compound. Binding
data were analysed using a Scatchard plot of (r/Cf) versus
Results and discussion
Characterization and structures of the complexes
The free ligand and its two complexes are soluble in eth-
anol, methanol, DMF and DMSO, but insoluble in water or
123

492
Transition Met Chem (2011) 36:489–498
diethyl ether. They are all air stable. Crystals of the Zn(II)
and Ni(II) complexes were obtained by evaporating methanol
solutions. The formulation of the Cu(II) complex was
established by its molar conductivity, elemental analyses,
ESI-MS spectra and IR data.
Table 1 Crystal data and structure refinement of Zn(II) and Ni(II)
complexes
ZnL
NiL
Formula
C21H24N6O11Zn
601.85
C21H24N6O11Ni
595.15
FW
The molar conductivity of the Cu(II) complex in
methanol is 196 S m2 mol-1, which is in the range
expected for a 1:2 electrolyte. The elemental analysis
suggests the empirical formula CuꢀHLꢀ(NO3)2ꢀ H2O, and this
is supported by the electrospray ionization (ESI) mass
spectrum (m/z: 439.2), which can be assigned to the ion
[Cu.HL.H2O]? (M–2NO3-).
Crystal colour
Crystal size(mm)
Crystal system
Space group
Yellow
Green
0.35 9 0.32 9 0.29
Triclinic
0.34 9 0.31 9 0.29
Triclinic
P-1
P-1
˚
a (A)
9.011 (6)
8.9514 (17)
10.924 (2)
13.163 (2)
81.253 (2)
78.334 (2)
82.422 (2)
1,239.0 (4)
2
˚
b (A)
10.926 (8)
13.289 (9)
80.948 (9)
78.757 (8)
82.467 (8)
1,260.4 (15)
2
˚
c (A)
The IR spectra of the free ligand and Cu(II) complex were
compared. The IR spectrum of the free ligand shows bands at
1,654 and 1,652 cm-1, which are attributed to the stretching
a (ꢁ)
b (ꢁ)
c (ꢁ)
vibrations m (C=O)2-oxo-quinoline and m (C=O)4-aminophenazone
,
3
˚
V (A )
respectively. These have been replaced by bands at 1,642 and
1,639 cm-1 in the spectrum of the Cu(II) complex. A band at
1,604 cm-1 for the free ligand is assigned to the m (C=N)
stretch, which shifts to 1,595 cm-1 upon coordination of the
nitrogen atom to copper. Additionally, an intense band asso-
ciated with the asymmetric stretching of nitrate is observed at
1,384 cm-1, establishing that the Cu(II) complex contains
free nitrate (C2v). All these results suggest that the formula of
the Cu(II) complex is [Cu.HL.H2O].(NO3)2. The IR spectra of
the Ni(II) and Zn(II) complexes are consistent with that of the
Cu(II) complex.
Z
Dcalc (g/cm3)
Abs coeff (mm-1
F (000)
1.586
1.595
)
1.046
0.856
620.0
616
hmin and max(deg)
2.32–28.49
3,249/6,379
[R(int) = 0.0510]
R1 = 0.0651
wR2 = 0.1503
R1 = 0.1201,
wR2 = 0.1790
2.31–28.40
4,578/6,221
[R(int) = 0.0235]
R1 = 0.0387
wR2 = 0.0922
R1 = 0.0545,
wR2 = 0.1004
Reflections collected
Unique
Final R indices
[I [2 sigma(I)]
R indices (all data)
Crystal structures of the Zn(II) and Ni(II) complexes
The crystallographic data for the Zn(II) complex are given
in Table 1. An ORTEP representation of the complex,
including the atom numbering scheme, is shown in Fig. 1,
and selected bond lengths and angles are listed in Table 2.
The complex is mononuclear, and the coordination of the
ligand to Zn(II) results in the formation of both five-
membered (ZnOCCN) and six-membered (ZnNCCCO)
chelate rings. The coordination configuration of Zn(II) with
N3O1O2O4O6O7 shows a classic six-membered ring. There
are also one water molecule and nitrate, which do not take
part in coordination, within the crystal lattice. The asym-
metric unit cell consists of two crystallographically inde-
pendent molecules of the Zn(II) complex.
DNA-binding mode and affinity
The binding modes of compounds to CT-DNA are classi-
cally characterized through electronic absorption titrations.
When the compounds intercalate with the base pairs of
DNA, the p* orbitals of the intercalated compounds can
couple with the p orbitals of the base pairs, thus decreasing
the p–p* transition energies. On the other hand, the cou-
pling p* orbitals are partially filled by electrons, thus
decreasing the transition probabilities [31]. Therefore,
intercalative interaction can result in both hypochromism
and red shift, as reported previously [32]. As shown in
Fig. 3, the absorption bands of the free ligand and its Cu,
Zn and Ni complexes at 380 nm exhibit hypochromism of
about 50.0, 75.0, 76.5 and 77.8%, respectively, which are
characteristic of intercalation in the presence of CT-DNA
[33]. Hence, high-affinity interactions between CT-DNA
and these compounds are indicated; however, the binding
mode needs to be confirmed by more experiments.
The crystallographic data for the Ni(II) complex are
given in Table 1. An ORTEP representation of the struc-
ture, including the atom numbering scheme, is shown in
Fig. 2 and selected bond lengths and angles are listed in
Table 3. Compared with the Zn(II) complex, the coordi-
nation of the Ni(II) complex shows very similar chelating
rings (octahedral geometry). There are also one non-coor-
dinated water molecule and one nitrate in the crystal lattice.
The asymmetric unit cell contains two crystallographically
independent molecules of the Ni(II) complex.
Fluorescence emission spectroscopy can provide diag-
nostic evidence to distinguish the binding modes of dif-
ferent compounds to DNA [34]. The present compounds
emit weak luminescence in Tris–HCl buffer with a
123

Transition Met Chem (2011) 36:489–498
493
Fig. 1 ORTEP view of [ZnL]
showing the atom numbering of
scheme and 50% thermal
ellipsoids probability for the
non-hydrogen atoms
˚
Table 2 Selected bond lengths (A) and angles (ꢁ) for ZnL
Bond names
Bond lengths
Bond angles
Angle
Zn1–O4
Zn1–N3
Zn1–O7
Zn1–O1
Zn1–O2
Zn1–O6
O2–C22
N3–C11
N3–C12
O4–C1
2.035(3)
2.118(4)
2.057(4)
2.120(4)
2.157(3)
2.178(3)
1.274(5)
1.276(5)
1.396(6)
1.253(5)
1.437(5)
1.355(6)
1.387(5)
1.336(6)
1.393(5)
1.458(6)
1.358(5)
1.354(9)
1.211(6)
1.196(6)
1.268(5)
1.273(5)
1.232(5)
1.231(5)
O4–Zn1–O7
O4–Zn1–N3
O7–Zn1–N3
O4–Zn1–O1
O7–Zn1–O1
N3–Zn1–O1
O4–Zn1–O2
O7–Zn1–O2
N3–Zn1–O2
O1–Zn1–O2
O4–Zn1–O6
O7–Zn1–O6
N3–Zn1–O6
O1–Zn1–O6
O2–Zn1–O6
C22–O2–Zn1
C11–N3–C12
C11–N3–Zn1
C12–N3–Zn1
C1–O4–Zn1
C17–C16–N11
C1–N7–C10
C13–N10–N11
C13–N10-C15
89.97(16)
88.88(13)
177.09(16)
90.57(16)
92.13(18)
90.55(16)
170.93(11)
99.09(15)
82.10(13)
88.55(16)
96.57(14)
85.52(16)
91.96(14)
172.48(15)
84.78(13)
106.0(3)
C16–N11
N7–C1
N7–C10
N10–C13
N10–C11
N10–C15
N11–C22
C19–C20
O9–N12
N12-O8
N12–O11
O6–N9
Fig. 2 ORTEP view of [NiL] showing the atom numbering of
scheme and 50% thermal ellipsoids probability for the non-hydrogen
atoms
125.0(4)
126.3(3)
resulting titration curves. The fluorescence intensity of
these compounds was enhanced dramatically with the
addition of CT-DNA, which clearly indicates that all of the
compounds can insert into the hydrophobic environment
inside the DNA helix. This results in the protection from
the solvent water molecules, leading to enhancement of
the fluorescence intensity [35]. Enhanced fluorescence is
believed to be one of the criteria for intercalative binding
[36, 37]. According to the Scatchard equation, a plot of r/Cf
versus r gives the intrinsic binding constants of the com-
pounds. Thus, CuL (K = 8.74 9 105 M-1) interacts with
108.5(3)
128.5(3)
120.4(4)
126.5(4)
O5–N9
109.5(4)
N9–O3
128.5(4)
maximum at 450 nm. The fluorescence titration spectra of
the compounds with DNA were obtained at constant con-
centrations of the test compounds. Figure 4 displays the
123

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Transition Met Chem (2011) 36:489–498
˚
DNA more strongly than the free ligand (K = 5.34 9
105 M-1), and also the ZnL (K = 6.21 9 105 M-1) and
NiL (K = 7.15 9 105 M-1) complexes. We further char-
acterized the binding to DNA by viscosity studies and
ethidium bromide (EB) competitive experiments.
Table 3 Selected bond lengths (A) and angles (ꢁ) for NiL
Bond names
Bond lengths
Bond angles
Angle
Ni1–O4
Ni1–N2
Ni1–O5
Ni1–O6
Ni1–O3
Ni1–O2
N2–C21
N2–C10
O2–C12
O4–C1
O3–N5
N3–C12
N1–C1
N1–C9
N5–O8
N5–O7
N3–N4
N4–C11
N4–C20
O10–N6
O9–N6
C9–C8
2.0044(15)
2.0348(16)
2.0447(17)
2.0658(18)
2.0890(16)
2.1272(14)
1.291(2)
1.392(3)
1.265(2)
1.247(2)
1.268(2)
1.364(3)
1.352(3)
1.387(3)
1.227(2)
1.242(2)
1.390(2)
1.341(3)
1.460(3)
1.250(3)
1.207(3)
1.393(3)
1.218(3)
1.397(4)
O4–Ni1–N2
O4–Ni1–O5
N2–Ni1–O5
O4–Ni1–O6
N2–Ni1–O6
O5–Ni1–O6
O4–Ni1–O3
N2–Ni1–O3
O5–Ni1–O3
O6–Ni1–O3
O4–Ni1–O2
N2–Ni1–O2
O5–Ni1–O2
O6–Ni1–O2
O3–Ni1–O2
C21–N2–C10
C21–N2–Ni1
C10–N2–Ni1
C12–O2–Ni1
C1–O4–Ni1
N5–O3–Ni1
O2–C12–N3
O4–C1–N1
O4–C1–C2
91.18(6)
88.19(7)
179.37(7)
89.68(8)
Measurements of DNA viscosity, which is sensitive to
DNA length change, are regarded as the least ambiguous
and the most critical test of binding in solution in the
absence of crystallographic structural data [38, 39]. In
classic intercalation, the DNA helix lengths are separated
to accommodate the ligand, leading to an increase in DNA
viscosity. In contrast, groove binding and electrostatic
modes result in unchanged length of DNA helix and no
alteration in DNA viscosity. Figure 5 shows that the
present compounds cause a significant increase in the vis-
cosity of CT-DNA, which follows the order CuL [
NiL [ ZnL [ L. The results suggest classical intercalation
of the planar ligand. As with the fluorescence experiments,
the Cu(II) complex exhibits higher affinity with CT-DNA
than the other compounds.
90.34(7)
89.64(8)
96.19(7)
93.25(7)
86.83(7)
173.05(7)
174.96(5)
83.88(6)
96.75(6)
89.34(7)
85.14(6)
124.32(17)
126.51(14)
109.04(12)
104.55(12)
127.28(14)
127.98(13)
126.50(18)
117.75(18)
126.42(19)
Ethidium bromide is one of the most sensitive fluores-
cent probes which can bind to DNA through intercalation
[40, 41]. Competitive binding with EB can provide rich
information with regard to the DNA-binding mode. As
shown in Fig. 6, the fluorescence intensity of ethidium
bromide decreases obviously upon addition of the test
compounds. The Kq values for the compounds are
0.71 9 105 M-1 (L), 2.34 9 105 M-1 (CuL), Kq = 1.03
N6–O11
C5–C6
Fig. 3 Absorption spectra of
compounds (10 lM) in the
absence and presence of
increasing amounts of CT-DNA
(2.5, 5, 7.5, 10, 12.5, 15, 17.5,
20, 22.5, 25, 27.5, 30 lM;
subsequent spectra). The arrow
shows the absorbance changes
upon increasing DNA
concentration
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Transition Met Chem (2011) 36:489–498
495
Fig. 4 Emission enhancement spectra of compounds (10 lM) in the
absence and presence of increasing amounts of CT-DNA (2.5, 5, 7.5,
10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30 lM; Arrow shows the
emission intensity changes upon increasing CT-DNA concentration.
Inset: Scatchard plot of the fluorescence titration data of compounds,
KL = 5.34 9 105 M-1. KCuL = 8.74 9 105 M-1. KZnL = 6.21 9 105
M-1. KNiL = 7.15 9 105 M-1
9 105 M-1 (ZnL) and Kq = 1.06 9 105 M-1 (NiL). The
quenching plots illustrate that the quenching of EB bound
to DNA by these compounds is in good agreement with
the linear Stern–Volmer equation and the binding ability
follows the order CuL[ NiL [ ZnL [ L, in agreement
with the fluorescence and viscosity measurements. Further-
more, the quenching constants suggest that the quenching
mode is static rather than dynamic, and the interaction of all
the compounds with DNA should be by intercalation [42].
Antioxidant activity
Figure 7 depicts the inhibitory effect of the compounds on
OH• radicals. The inhibitory activity of the compounds is
marked, and the suppression ratio increases with increasing
concentration of the test compound. The sequence of the
suppression ratio is CuL [ NiL [ ZnL [ L. We compared
the present compounds with the well-known natural
Fig. 5 Effect of increasing amounts of L, CuL, ZnL and NiL on the
relative viscosity of CT-DNA at 25.0 0.1 ꢁC, [DNA] = 5.0 lM
123

496
Transition Met Chem (2011) 36:489–498
Fig. 6 Emission spectra of DNA-EB system (10 lM DNA and
0.33 lM EB), kex = 521 nm, kem = 540–700 nm, in the presence of
(0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 lM)
ligand, CuL, ZnL and NiL. Arrow shows the emission intensity
changes upon increasing compound concentration. Inset: Stern–
Volmer plot of the fluorescence titration of compounds
antioxidants mannitol and vitamin C, using the same
method as reported in a previous paper [43]. The 50%
inhibitory concentration (IC50) value of mannitol is about
9.6 mM. According to the antioxidant experiments, the
IC50 of CuL is 3.08 lM, which implies that CuL exhibits
better scavenging activity than L, ZnL and NiL, as well as
mannitol and vitamin C. We suggest that the mechanism of
action of CuL involves the redox process of Cu(II) [44, 45].
attributed to the increase in the ligand’s conformational
rigidity, thus favouring a more planar and conjugated
structure [46].
Conclusion
In this work, a new 2-oxo-quinoline-3-carbaldehyde Schiff
base ligand and its Cu(II), Zn(II) and Ni(II) complexes
have been synthesized and characterized. The binding
modes of these compounds with CT-DNA have been
studied. The photophysical and viscosity measurements
indicate that the compounds interact with CT-DNA
through intercalative binding modes. In addition, the metal
complexes show higher affinities than the free ligand,
which can be attributed to the more planar structure owing
to upon coordination to the metal. The antioxidant activi-
ties of the compounds were also investigated. CuL exhibits
the most effective scavenging of hydroxyl radical among
these compounds. Finally, the solid-state fluorescence
Solid-state fluorescence spectra
The fluorescence from the free ligand CuL and NiL is
weak; however, the Zn(II) complex exhibits light Kelly
fluorescence (kem = 513 nm). The solid-state fluorescence
emission is readily observed with the naked eye under UV
light, as shown in Fig. 8. The Zn(II) complex is the first
example of a light Kelly fluorescence complex with 2-oxo-
quinoline-3-carbaldehyde-4- aminophenazone Schiff base.
As observed, the coordination of Zn(II) clearly changes
the emission efficiency of the ligand, which can be
123

Transition Met Chem (2011) 36:489–498
497
Acknowledgments This work is supported by the National Natural
Science Foundation of China (20975046).
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