Preparation, structure, DNA-binding properties, and antioxidant activities of a homodinuclear erbium(III) complex with a pentadentate Schiff base ligand

Article abstract of DOI:10.3184/174751914X13933417974082

An erbium (III) complex of a pentadentate Schiff base ligand [(NO ₃)Er(μ-L)₂Er(NO₃)].2H₂O [H ₂L=bis(N-salicylidene)-3- oxapentane-1,5-diamine] has been synthesised, characterised and its structure confirmed by X-ray crystallography. H₂L and the Er(III) complex both bind to DNA via a groove binding mode, and the Er(III) complex binds to DNA more strongly than H₂L. The complex shows strong scavenging effects for hydroxyl radicals (OH·) and superoxide radicals (O₂-·).

Full text of DOI:10.3184/174751914X13933417974082

JOURNAL OF CHEMICAL RESEARCH 2014
VOL. 38 APRIL, 211–217
RESEARCH PAPER 211
Preparation, structure, DNA-binding properties, and antioxidant activities of
a homodinuclear erbium(III) complex with a pentadentate Schiff base ligand
Huilu Wu*, Guolong Pan, Yuchen Bai, Hua Wang, Jin Kong, Furong Shi, Yanhui Zhang and Xiaoli
Wang
School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, P.R. China
An erbium (III) complex of a pentadentate Schiff base ligand [(NO )Er(µ-L) Er(NO )].2H O [H L=bis(N-salicylidene)-3-
3
2
3
2
2
oxapentane-1,5-diamine] has been synthesised, characterised and its structure confirmed by X-ray crystallography. H L and
2
the Er(III) complex both bind to DNA via a groove binding mode, and the Er(III) complex binds to DNA more strongly than H L.
2
−
·
The complex shows strong scavenging effects for hydroxyl radicals (OH·) and superoxide radicals (O ).
2
Keywords: Schiff base, erbium(III) complex, crystal structure, DNA-binding, antioxidant activity
Many chemicals exert antitumour effects through binding to
DNA, thereby changing the replication of DNA and inhibiting
the growth of the tumour cells. This is the basis of designing new
and more efficient antitumour drugs, and their effectiveness
using KBr pellets. Electronic spectra were taken on Lab-Tech UV
Bluestar and Spectrumlab 722sp spectrophotometers (0.2 nm
spectral resolution). Fluorescence spectra were recorded on a LS-45
1
spectrofluorophotometer. H NMR spectra were obtained with a
1,2
Mercury plus 400 MHz NMR spectrometer with TMS as internal
depends on the mode and affinity of the binding. A number
of metal chelates, as agents for mediation of strand scission
of duplex DNA and as chemotherapeutic agents, have been
standard and CDCl as solvent.
3
All chemicals were of analytical grade. Calf thymus DNA (CT-
DNA), ethidium bromide (EB), nitroblue tetrazolium nitrate (NBT),
3
–5
used as probes of DNA structure in solution. The biological
activities shown by DNA-binder metal complexes are various
and are often related to their specific DNA-binding mechanism,
methionine (MET) and riboflavin (VitB ) were obtained from Sigma-
2
Aldrich Co. (USA) and used without purification. All experiments
involving interaction of the ligand and the complex with CT-DNA
were carried out in a doubly-distilled water buffer containing 5 mM
Tris and 50 mM NaCl adjusted to pH=7.2 with hydrochloric acid. A
solution of CT-DNA gave a ratio of UV absorbance at 260 and 280 nm
of about 1.8–1.9, indicating that the CT-DNA was sufficiently free of
6
,7
ranging from intercalation to covalent and groove binding.
Therefore, an understanding of how these small molecules
bind to DNA will potentially be useful in the design of new
compounds that can recognise specific sites or conformations
8
–10
20
of DNA.
protein. The CT-DNA concentration per nucleotide was determined
Their biological activity and a number of other applications
have resulted in strongly increasing interest in lanthanide
spectrophotometrically by employing an extinction coefficient of
6600 M ·cm at 260 nm.
–1
–1
21
11–14
compounds in the last decade.
One of the most studied
The synthetic route for the ligand precursor H
Scheme 1.
L is shown in
2
applications is the use of lanthanide complexes to address DNA/
15–17
3-Oxapentane-1,5-diamine: Synthesised following the procedure in
RNA interaction by non-covalent binding and/or cleavage.
ref. 22. Anal. calcd for C H N O: C, 46.3; H, 11.5; N, 26.9; found: C,
Moreover, interest in the chelation of metal ions by Schiff base
macrocyclic (coronand) and open-chain (podand) ligands has
continually increased owing to the recognition of the role played
by these structures in bioinorganic and medicinal inorganic
4
12
2
–1
4
6.0; H, 11.5; N, 26.8%. FT–IR (KBr ν/cm ): 1120, ν(C–O–C); 3340,
ν(–NH2).
bis(N-Salicylidene)-3-oxapentane-1,5-diamine (H L): Salicylic
2
aldehyde (10 mmol, 1.22 g) in EtOH (5 mL) was added dropwise to
an EtOH solution (5 mL) of 3-oxapentane-1,5-diamine (5 mmol,
18,19
chemistry.
We now present the synthesis, characterisation
and DNA-binding properties of an erbium(III) complex with
a pentadentate Schiff base ligand, bis(N-salicylidene)-3-
oxapentane-1,5-diamine. In addition, the antioxidant properties
of the Er(III) complex are discussed in detail.
0.52 g). After the completion of addition, the solution was stirred
for an additional 4 h at 78 °C. After cooling to room temperature,
the precipitate was filtered. The product was dried in vacuo, to
give a yellow crystalline solid. Yield: 1.2 g (68.5%). Anal. calcd for
1
C H O N : C, 69.2; H, 6.4; N, 9.0; found: C, 69.1; H, 6.5; N, 8.8%. H
18
20
3
2
Experimental
NMR (CDCl 400 MHz) δ/ppm: 8.30 (s, 2H, N=C–H), 6.79–7.33 (m,
3
C, H, and N elemental analyses were determined using a Carlo
Erba 1106 elemental analyser. IR spectra were recorded from
8H, H-benzene ring), 3.66–3.74 (m, 8H, O–(CH ) –N=C). UV-Vis (λ,
nm): 268, 316. FT–IR (KBr ν/cm ): 1637, ν(C=N); 1286, ν(C–O–C);
3458, ν(OH).
2
2
–1
–1
4
000–400 cm with a Nicolet FT-VERTEX 70 spectrometer
Scheme 1 Synthesis of ligand H L.
2
*
Correspondent. E-mail: wuhuilu@163.com
JCR1402418_FINAL.indd 211
27/03/2014 14:00:34

212 JOURNAL OF CHEMICAL RESEARCH 2014
Complex [(NO )Er(µ-L) Er(NO )].2H O (1): To a stirred solution of
Absorption titration experiments were performed with fixed
concentrations of a compound, while gradually increasing the
concentration of CT-DNA. To obtain the absorption spectra, the
required amount of CT-DNA was added to both the compound and
reference solutions, in order to eliminate the absorbance of CT-DNA
3
2
3
2
H L (156 mg, 0.5 mmol) in EtOH (10 mL) was added Er(NO ) (H O)
2
3
3
2
6
(
231 mg 0.5 mmol) and triethylamine (0.3 mL) in EtOH (10 mL). A
yellow sediment was generated rapidly. The precipitate was filtered
off, washed with EtOH and absolute Et O, and dried in vacuo. The
2
dried precipitate was dissolved in DMF to form a yellow solution.
Yellow block crystals of 1, suitable for X-ray diffraction studies, were
obtained by vapour diffusion of diethyl ether into the solution for a few
weeks at room temperature. Yield: 207 mg (53.5%). Anal. calcd for
C H Er N O : C, 38.8; H, 3.6; N, 7.5; found: C, 38.6; H, 3.8; N, 7.4%.
itself. From the absorption titration data, the binding constant (K ) was
determined using the equation:
b
2
6
[DNA]/(ε –ε )=[DNA]/(ε –ε )+1/K (ε –ε )
a
f
b
f
b
b
f
3
6
40
2
6
14
–1
where [DNA] is the concentration of CT-DNA in base pairs, εa
UV-Vis (λ, nm): 269, 316. FT–IR (KBr ν/cm ): 1276, ν(C–O–C); 1382,
ν (NO ); 1055, ν (NO ); 1634 ν(C=N).
corresponds to the observed extinction coefficient (Aobsd/[M]), ε
s
3
a
3
f
corresponds to the extinction coefficient of the free compound, ε is the
extinction coefficient of the compound when fully bound to CT-DNA,
b
X-ray crystallography
A suitable single crystal of 1 was mounted on a glass fibre, and the
intensity data were collected on a Bruker Smart CCD diffractometer
with graphite-monochromated Mo-Kα radiation (λ=0.71073 Å) at
and K is the intrinsic binding constant. The ratio of slope to intercept
b
in the plot of [DNA]/(ε –ε ) versus [DNA] gave the value of K .
a
f
b
The enhanced fluorescence of EB in the presence of DNA can be
296 K. Data reduction and cell refinement were performed using
16,27
quenched by the addition of a second molecule.
The extent of
2
3
the SMART and SAINT programs. The structure was solved by
direct methods and refined by full-matrix least-squares against
fluorescence quenching of EB bound to CT-DNA can be used to
determine the extent of binding between the second molecule and
CT-DNA. Competitive binding experiments were carried out in the
buffer by keeping [DNA]/[EB]=1 and varying the concentrations of
the compounds. The fluorescence spectra of EB were measured using
an excitation wavelength of 520 nm, and the emission range was set
between 550 and 750 nm. The spectra were analysed according to the
2
24
F of data using SHELXTL software. All H atoms were found in
difference electron maps and subsequently refined in a riding-model
approximation with C–H distances ranging from 0.93 to 0.97 Å and
Uiso (H)=1.2 U (C) or 1.5 U (C). The crystal data and experimental
eq
eq
parameters relevant to the structure determination are listed in Table 1.
Selected bond lengths and angles are presented in Table 2.
28
classical Stern–Volmer equation:
DNA-binding experiments
I0 /I=1+KSV [Q]
Viscosity experiments were conducted on an Ubbelodhe viscometer,
immersed in a water bath maintained at 25.0±0.1 °C. Titrations
were performed for compounds (3–30 μM), and each compound
was introduced into a CT-DNA solution (42.5 μM) present in the
viscometer. Data were analysed as (η/η0) versus the ratio of the
concentration of the compound to CT-DNA, where η is the viscosity
where I and I are the fluorescence intensities at 599 nm in the
absence and presence of the quencher, respectively, KSV is the linear
Stern–Volmer quenching constant, and [Q] is the concentration of
the quencher. In these experiments, [CT-DNA]=2.5×10 mol L ,
0
1
/3
–3
–1
–3
–1
[
EB]=2.2×10 mol L .
of CT-DNA in the presence of the compound and η is the viscosity of
0
CT-DNA alone. Viscosity values were calculated from the observed
flow time of CT-DNA-containing solutions corrected from the flow
Antioxidation study methods
Hydroxyl radicals were generated in aqueous media by a Fenton-
2
5
29
time of buffer alone (t ), η=(t–t ).
type reaction. The aliquots of reaction mixture (3 mL) contained
0
0
1
mL of 0.1 mmol aqueous safranin, 1 mL of 1.0 mmol aqueous
EDTA–Fe(II), 1 mL of 3% aqueous H O , and a series of quantitative
2
2
Table 1 Crystal/structure refinement data for [(NO )Er(µ-L) Er(NO )].2H O (1)
3
2
3
2
microadditions of solutions of the test compound. A sample without
the tested compound was used as the control. The reaction mixtures
were incubated at 37 °C for 30 min in a water bath. The absorbance was
then measured at 520 nm. All the tests were run in triplicate and are
Complex
1
Molecular formula
Molecular weight
Colour, habit
Crystal size/mm
Crystal system
C H Er N O
1115.26
Yellow, block
0.26×0.23×0.21
Monoclinic
C2/c
36 40 2 6
14
3
Table 2 Selected bond lengths (Å) and bond angles (deg) for 1
Bond lengths
Space group
a/Å
Er(1)–O(3)
Er(1)–O(2)
Er(1)–O(1)
Er(1)–N(2)
2.161(4)
2.306(4)
2.449(4)
2.473(5)
Er(1)–O(2)#1a
Er(1)–O(5)
Er(1)–O(4)
Er(1)–N(1)
2.271(4)
2.446(4)
2.469(4)
2.496(5)
29.35(2)
b/Å
11.748(9)
c/Å
β/deg
V/Å
15.231(12)
118.235(6)
4627(6)
4
3.666
296(2)
Bond angles
3
O(3)–Er(1)–O(2)#1 96.45(15)
O(2)#1–Er(1)–O(2) 71.11(15)
O(2)#1–Er(1)–O(5) 156.99(13)
O(3)–Er(1)–O(2)
O(3)–Er(1)–O(5)
O(2)–Er(1)–O(5)
O(2)#1–Er(1)–O(1)
O(5)–Er(1)–O(1)
85.09(14)
95.94(17)
129.34(14)
87.13(14)
71.12(15)
Z
–1
Absorption coefficient/mm
T/K
Dcalcd/g cm−3
1.601
O(3)–Er(1)–O(1)
O(2)–Er(1)–O(1)
O(3)–Er(1)–O(4)
O(2)–Er(1)–O(4)
O(1)–Er(1)–O(4)
140.89(15)
132.05(14)
81.96(16)
78.74(13)
113.08(15)
F (000)/e
2184
O(2)#1–Er(1)–O(4) 149.82(13)
θ range for data collection, deg
hkl range
Reflections collected
2.19 to 25.50
–35, 35/ –11, 14/ –18, 17
11947
O(5)–Er(1)–O(4)
O(3)–Er(1)–N(2)
O(2)–Er(1)–N(2)
O(1)–Er(1)–N(2)
O(3)–Er(1)–N(1)
O(2)–Er(1)–N(1)
O(1)–Er(1)–N(1)
N(2)–Er(1)–N(1)
51.60(14)
74.94(18)
146.97(16)
66.55(18)
151.51(16)
70.80(14)
66.93(15)
133.40(17)
O(2)#1–Er(1)–N(2) 85.08(15)
Independent reflections/Rint
4265/0.0298
4265/3/262
0.0296/0.0756
0.0459/0.0836
1.111
O(5)–Er(1)–N(2)
O(4)–Er(1)–N(2)
79.52(16)
122.86(15)
Data/restraints/parameters
Final R /wR indices [I>2σ(I)]
O(2)#1–Er(1)–N(1) 90.01(15)
1
2
a
O(5)–Er(1)–N(1)
O(4)–Er(1)–N(1)
88.28(17)
78.71(16)
R /wR indices (all data)
1
2
Goodness-of-fit on F2
aSymmetry transformations used to generate equivalent atoms: #1–x+1/2,
y+1/2, –z.
–
3
Largest diff. peak/hole/e Å
0.882/–0.872
–
JCR1402418_FINAL.indd 212
27/03/2014 14:00:34

JOURNAL OF CHEMICAL RESEARCH 2014 213
2
7,29
–1
expressed as the mean and standard deviation (SD).
The scavenging
For the free ligand H L, a strong band is found at 1637 cm
2
–1
effect for OH· was calculated from the following expression:
Scavenging ratio (%)=[(A –A )/(A –A )]×100%
together with a weak band at 1286 cm . By analogy with
previously assigned bands, the former can be attributed to
ν(C=N), while the latter can be attributed to ν(C–O–C). These
i
0
c
0
–1
32
bands were shifted to lower frequency by ca 3–10 cm for 1,
where A =absorbance in the presence of the test compound;
A =absorbance of the blank; A =absorbance in the absence of the test
i
which implies direct coordination of the nitrogen and oxygen
atoms to metal ions. Bands at 1382 and 1055 cm indicate that
nitrate is bidentate and a weak band at 3663 cm is allocated
–1
0
c
compound, EDTA-Fe(II) and H O .
33
–1
2
2
−
6
A nonenzymatic system containing 1 mL 9.9×10 M VitB2, 1 mL
.38×10 M NBT, 1 mL 0.03 M MET was used to produce superoxide
anion (O ), and the scavenging rate of O under the influence of
.1–1.0 μM of the tested compound was determined by monitoring the
as ν(H O), in agreement with the result of X-ray diffraction.
−
4
2
1
The electronic spectra of the ligand H L and 1 were recorded
in DMF solution at room temperature. The UV bands of H L
268, 316 nm) are marginally shifted in the complex. That two
absorption bands are assigned to π→π*(benzene) and π→π*
−
·
−·
2
2
2
2
0
(
3
0
reduction in rate of transformation of NBT to monoformazan dye.
The solutions of MET, VitB2 and NBT were prepared with 0.02 M
phosphate buffer (pH=7.8) at the condition of avoiding light. The
reactions were monitored at 560 nm with a UV-Vis spectrophotometer,
and the rate of absorption change was determined. The percentage
inhibition of NBT reduction was calculated using the following
3
4
(
C=N) transitions.
X-ray structure of the complex
The crystal structure of 1 consists of discrete [(NO )Er(µ-
L) Er(NO )] units and two H O solvent molecules. The prepared
pentadentate ligand contains strong donors, namely phenoxo-
oxygen atoms as well as imine nitrogen atoms, with excellent
coordination ability for transition/inner-transition metal ions
through its N O donor set. Single crystal X-ray structure
3
2
3
2
31
equation:
Percentage inhibition of NBT reduction=(1–k′/k)×100
2
3
where k′ and k represent the slopes of the straight line of absorbance
values as a function of time in the presence and absence of SOD
mimic compound (SOD is superoxide dismutase), respectively. The
IC50 values for the complexes were determined by plotting the graph
of percentage inhibition of NBT reduction against the increase in the
concentration of the complex. The concentration of the complex which
determination revealed that the complex has a centrosymmetric
neutral homodinuclear entity. An ORTEP illustration of the
complex (Fig. 1a) shows that two adjacent [Er(L)(NO )] moieties
3
arebridgedviatwophenoxogroups. Intheμ -diphenoxobridged
2
binuclear structure, both Er(III) centres are octacoordinated.
The local coordination environment is identical for both centres
causes 50% inhibition of NBT reduction is reported as IC .
5
0
by symmetry and is best described as a distorted square ErN O6
2
antiprism (Fig. 1b). Due to the flexibility of the ligand, it loses
planarity. The nature of coordination of the two identical Schiff
base moieties of the same ligand is completely different and
hence noteworthy. Of the two phenoxo oxygen atoms coming
out of each ligand, one is simply monocoordinated while the
other one bridges the adjacent Er(III) centres as reflected by
the Er–Ophenoxo bond lengths [Er(1)–O(2), 2.306(4) and Er(1)–
O(2A), 2.271(4) Å]. The distance of Er(1)–Er(1A): 3.724(3) Å
is relatively too long to consider any direct intramolecular Er–
Results and discussion
The Er(III) complex 1 was prepared by reaction of H L with
2
Er(NO ) (H O) in ethanol. It is soluble in polar aprotic solvents
3
3
2
6
such as DMF, DMSO and MeCN, slightly soluble in ethanol,
methanol, ethyl acetate, and chloroform and insoluble in water,
Et O and petroleum ether. The elemental analysis shows that its
2
composition is Er (L) (NO ) ·2H O and its was confirmed by
2
2
3
2
2
the crystal structure analysis.
Fig. 1 (a) The molecular structure of Er L (NO ) in the crystal with displacement ellipsoids at the 30% probability level; H atoms are omitted for clarity,
2
2
3 2
3
+
(
b) A distorted square antiprism geometry is formed by donor atoms around the Er centre as illustrated in the polyhedral view.
JCR1402418_FINAL.indd 213
27/03/2014 14:00:34

214 JOURNAL OF CHEMICAL RESEARCH 2014
Fig. 2 A space-filling diagram of the nanosized holes in the Er(III) complex. In order to simplify, water solvent molecules are omitted for clarity.
Er interaction. Hydrogen-bonding interactions play important
roles in crystal packing in the complex. An interesting feature
of this structure is the intermolecular hydrogen bond that exists
among the Er(III) complexes, which also affords voids to trap
guest molecules (Fig. 2). Note that intermolecular interactions
have the potential to assemble smaller and simpler fragments
into desired cavities under favourable conditions, which is
important in host–guest chemistry and has applications in
chemistry, biology and materials science.
cause less pronounced (positive or negative) or no change in
DNA solution viscosity.
35
The effects of H L and 1 on the viscosity of CT-DNA are
2
shown in Fig. 3. The experimental results show that the addition
of H L and 1 causes no significant viscosity change. Therefore,
2
according to a previous report relating to DNA-binding
16,35
lanthanide complexes,
we can deduce that H L and 1 most
2
probably bind to DNA in a groove mode. The reason for the
DNA–binding modes for the ligand and 1 can be attributed to
steric hindrance and electron density, which are both caused by
the geometric structure.
DNA-binding properties
Viscosity measurements
Electronic absorption spectroscopy
Viscosity titration measurements were carried out to further
clarify the interaction modes between the investigated
compounds and CT-DNA. Hydrodynamic measurements that
are sensitive to changes in the length of DNA (i.e. viscosity
and sedimentation) are regarded as the least ambiguous and
the most critical tests of binding in solution in the absence of
The application of electronic absorption spectroscopy is one
of the most useful techniques in DNA-binding studies. To
clarify the interactions between the compounds and DNA,
17
the electronic absorption spectra of the ligand H L and its 1 in
2
the absence and in the presence of the CT-DNA (at a constant
concentration of the compounds) were obtained and are shown
in Fig. 4. With increasing DNA concentrations, the absorption
2
7
crystallographic structural data. The classic intercalation
model involves the insertion of a planar molecule between
DNA base pairs, which results in a decrease in the DNA helical
twist and lengthening of the DNA, the molecule will also be in
bands at 394 nm of H L show a hypochromism of 32.5%; the
2
absorption bands at 392 nm of 1 show a hypochromism of
63.8%. The hypochromism observed for the π→ π* transition
2
9
close proximity to the DNA base pairs. In contrast, molecules
that bind exclusively in the DNA grooves by partial and/or non-
classical intercalation, under the same conditions, typically
bands indicating strong binding of H L and complex to DNA.
2
To compare quantitatively the affinity of H L and 1 towards
2
DNA, the intrinsic binding constants K of the two compounds
b
a
b
Fig. 3 Effect of increasing amounts of H L(a) and 1(b) on the relative viscosity of CT-DNA at 25.0±0.1 °C.
2
JCR1402418_FINAL.indd 214
27/03/2014 14:00:34

JOURNAL OF CHEMICAL RESEARCH 2014 215
Fig. 4 Absorption spectra of compound in the presence of CT-DNA (the DNA absorption was subtracted). The concentration of H L (a) and 1(b), was kept
2
–
5
–1
constant at 3×10 M . Arrows show the absorbance changes upon increasing DNA concentration. Inset: Plots of [DNA] /(ε –ε ) versus [DNA] for the
a
f
titration of DNA with compound; ■, experimental data points; solid line, linear fitting of the data.
to CT-DNA were determined by monitoring the changes of
absorbance with increasing concentration of DNA. The intrinsic
a typical indicator of intercalation, EB is a weakly fluorescent
compound, but in the presence of DNA, its emission intensity
is greatly enhanced because of its strong intercalation between
3
–1
binding constant K of H L and of 1 were (5.30±0.096)×10 M
b
2
4
–1
38
(
1
R=0.99 for 16 points) and (3.19±0.104)×10 M (R=0.99 for
6 points), respectively, from the decay of the absorbances.
the adjacent DNA base pairs. In general, measurement of the
ability of a complex to affect the intensity of EB fluorescence in
the EB-DNA adduct allows determination of the affinity of the
complex for DNA. If a complex can displace EB from DNA, the
fluorescence of the solution will be reduced due to the fact that
The K values obtained here are lower than that reported for
b
a classical intercalator (for ethidium bromide and [Ru(phen)
6
7
–1 36,37
DPPZ], binding constants are of the order of 10 –10 M ).
39
It is clear that the hypochromism and K values can suggest
free EB molecules are readily quenched by the solvent water.
b
an intimate association of the compounds with CT-DNA and
For ligand H L and 1, no emission was observed neither alone
2
indicate that the binding strength of 1 is higher than for H L.
Based on the above results, the affinity for DNA is stronger
nor in the presence of CT-DNA in the buffer. The fluorescence
quenching of DNA–bound EB by the ligand and complex
2
for 1 than H L. We consider that the most likely reason is that
are shown in Fig. 5. The behaviour of H L and 1 are in good
2
2
the charge transfer of coordinated H L, caused by coordination
agreement with the Stern–Volmer equation, which provides
further evidence that the two compounds bind to DNA. The
2
of the central atom, results in the decrease of charge density
of the planar conjugated system. This change will lead to
4
Ksv values for H L and 1 are (0.35±0.010)×10 (R=0.98 for
2
2
7,29
4
–1
complexes binding to DNA more easily.
Moreover, the
21 points in the line part) and (2.51±0.083)×10 M (R=0.98
for 13 points), respectively, reflecting the higher quenching
helix structure of the Er(III) complex is able to provide lots of
grooving positions to stack more strongly with the base pairs of
efficiency of 1 relative to that of H L. This result suggests that
2
16
the DNA helix.
the DNA-binding of 1 is stronger than that of H L. Such a trend
2
is consistent with the previous absorption spectral results.
Fluorescence spectra
In order to further study the binding properties of the complexes
with DNA, competitive binding experiments were carried out.
Antioxidant activities
According to relevant reports in the literature,
4
0,41
the rare earth
Relative binding of H L and 1 to CT-DNA was studied by the
fluorescence spectral method using ethidium bromide (EB)
bound CT-DNA solution in Tris-HCl/NaCl buffer (pH=7.2). As
complexes may exhibit antioxidant activity. We therefore also
conducted an investigation to explore whether 1 has antioxidant
activities.
2
–
5
–1
Fig. 5 Fluorescence spectra of the DMF solution of H L (a) and 1 (b) in Tris–HCl buffer upon addition of CT-DNA. [Compound]=3×10 M . Arrows show the
2
intensity changing upon increasing CT-DNA concentrations. Sterne–Volmer quenching plots of the ligand and 1 are inset in their own fluorescence spectra
with increasing concentrations of CT-DNA.
JCR1402418_FINAL.indd 215
27/03/2014 14:00:34

216 JOURNAL OF CHEMICAL RESEARCH 2014
–
5
value of (5.19±0.089)×10 M (Fig. 7), which indicates that it
−·
has potent scavenging activity for superoxide radical (O ). This
2
indicates that 1 might be an inhibitor (or a drug) to scavenge
−·
O2 in vivo, which merits further investigation.
Conclusions
In this work, a pentadentate Schiff base ligand bis(N-
salicylidene)-3-oxapentane-1,5-diamine and its Er(III)
complex have been synthesised and characterised. The binding
modes of these compounds with CT-DNA have been studied
by electronic absorption titration, ethidium bromide–DNA
displacement experiments and viscosity measurements. The
results indicate that the ligand H L and complex 1 bind to DNA
2
in a groove mode, and the affinity for DNA is stronger for 1
when compared with the ligand. In addition, 1 also has active
−·
scavenging effects on the OH· and O2 radicals. Our research
should be valuable for seeking and designing new antitumour
drugs and antioxidants, as well as for understanding the
mechanism of DNA-binding.
Crystallographic data (excluding structure factors) for the
structure in this paper have been deposited with the Cambridge
Crystallographic Data Centre, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK. Copies of the data can be obtained
free of charge on quoting the depository number CCDC-936140
Fig. 6 The inhibitory effect of the ligand and 1 on OH· radicals; the
suppression ratio increases with increasing concentration of the test
compound.
(
Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk,
http://www.ccdc.cam.ac.uk).
The present research was supported by the National Natural
Science Foundation of China (Grant No. 21367017), the
Fundamental Research Funds for the Gansu Province
Universities (212086), National Natural Science Foundation
of Gansu Province (Grant No. 1212RJZA037), and ‘Qing Lan’
Talent Engineering Funds for Lanzhou Jiaotong University.
Received 21 January 2014; accepted 7 February 2014
Paper 1402418 doi: 10.3184/174751914X13933417974082
Published online:2 April 2014
Fig. 7 The inhibitory effect of 1 on O2−· radicals; the suppression ratio
increases with increasing concentration of the test compound.
References
1
Y.B. Zeng, N. Yang, W.S. Liu and N. Tang, J. Inorg. Biochem., 2003, 97,
58.
2
2
V. Rajendiran, R. Karthik, M. Palaniandavar, H. Stoeckli-Evans, V.S.
Periasamy, M.A. Akbarsha, B.S. Srinag and H. Krishnamurthy, Inorg.
Chem., 2007, 46, 8208.
M. Demeunynck, C. Bailly and W.D. Wilson (eds.) Small molecule DNA
and RNA binders:from synthesis to nucleic acid complexes. Wiley-VCH,
Weinheim (2003).
R.W.Y. Sun, D.L. Ma, E.L.M. Wong and C.M. Che, J. Chem. Soc. Dalton
Trans, 2007, 2007, 4884.
C. Moucheron, New J. Chem., 2009, 33, 235.
M.J. Hannon, Chem. Soc. Rev., 2007, 36, 280.
G.L. Pan, Y.C. Bai, H. Wang, J. Kong, F.R. Shi, Y.H. Zhang, X.L. Wang
and H.L. Wu, Z. Naturforsch. B, 2013, 68, 257.
K.E. Erkkila, D.T. Odom and J.K. Barton, Chem. Rev., 1999, 99, 2777.
L.N. Ji, X.H. Zou and J.G. Liu, Coord. Chem. Rev., 2001, 216–217, 513.
B.M. Zeglis, V.C. Pierre and J.K. Barton, Chem. Commun., 2007, 44, 4565.
Hydroxyl radical scavenging activity: Figure 6 shows the
plots of hydroxyl radical scavenging effects (%) for the ligand
and 1. The values of IC50 of the ligand and 1 for hydroxyl
3
4
–
5
radical scavenging effects are (7.13±0.097)×10 M and
–
5
(
3.99±0.070)×10 M, respectively. It is thus proved that the
hydroxyl radical scavenging effect of 1 is much higher than that
of the ligand. Moreover, we compared the abilities of the present
compounds to scavenge hydroxyl radical (OH·) with those of
the well-known natural antioxidants mannitol and vitamin
5
6
7
42
C, using the same method as reported in a previous paper.
The 50% inhibitory concentration (IC ) value of mannitol and
8
9
5
0
–3
–3
vitamin C are about 9.6×10 and 8.7×10 M, respectively. The
results imply that 1 has a greater ability to scavenge hydroxyl
radical (OH·) than mannitol and vitamin C. It can be concluded
that a much less or no scavenging activity was exhibited by
the ligand when compared to that of its complex, which is due
1
0
11 F.H. Lia, G.H. Zhao, H.X. Wu, H. Lin, X.X. Wu, S.R. Zhu and H.K. Lin, J.
Inorg. Biochem., 2006, 100, 36.
1
1
2
3
H.X. Xu, H.Y. Zhang and X.G. Qu, J. Inorg. Biochem., 2006, 100, 1646.
A. Cha, G.E. Snyder, P.R. Selvin and F. Bezanilla, Nature, 1999, 402, 809.
P. Caravan, J. Ellison, T. McMurry and R. Lauffer, Chem. Rev., 1999, 99,
1
4
42
to the chelation of ligand with the central metal atom. The
2
293.
15 M. Marinić, I. Piantanida, G. Rusak and M. Źinić, J. Inorg. Biochem.,
006, 100, 288.
Z.Y. Yang, B.D. Wang and Y.H. Li, J. Organometal. Chem., 2006, 691,
156.
17 P. Kapoor, R.V. Singh and N. Fahmi, J. Coord. Chem., 2012, 65, 262.
observed IC values for 1 suggest that it could be considered as
5
0
2
a potential drug to eliminate the hydroxyl radical.
16
Superoxide radical scavenging activity: As another assay
4
−·
of antioxidant activity, superoxide radical (O ) scavenging
2
activity has been investigated. Complex 1 has good superoxide
radical scavenging activity. The Er(III) complex shows an IC50
18
W. Radecka-Paryzek, V. Patroniak and J. Lisowski, Coord. Chem. Rev.,
2005, 249, 2156.
JCR1402418_FINAL.indd 216
27/03/2014 14:00:35

JOURNAL OF CHEMICAL RESEARCH 2014 217
1
2
9
0
P.A. Vigato and S. Tamburini, Coord. Chem. Rev., 2004, 248, 1717.
S. Satyanaryana, J.C. Dabrowiak and J.B. Chaires, Biochemistry, 1993, 32,
32 W.K. Dong, G. Wang, S.S. Gong, J.F. Tong, Y.X. Sun and X.H. Gao,
Transit. Metal Chem., 2012, 37, 271.
2
573.
33 K. Nakamoto, Infrared and Raman spectra of inorganic and coordination
compounds, 4th edn. John Wiley & Sons, New York, 1986, p. 284.
34 L. Casella, M. Gullotti, A. Pintar, L. Messori, A. Rockenbauer and M.
Györ, Inorg. Chem., 1987, 26, 1031.
35 B.D. Wang, Z.Y. Yang, P. Crewdson and D.Q. Wang, J. Inorg. Biochem.,
2007, 101, 1492.
2
1
J. Marmur, J. Mol. Biol., 1961, 3, 208.
2
2
2
2
3
4
S.M. Nalson and V. Knox, J. Chem. Soc. Dalton Trans., 1983, 1983, 2525.
Bruker, Smart saint and sadabs. Bruker Axs, Inc, Madison, WI, 2000.
G.M. Sheldrick, SHELXTL, Siemens Analytical X-ray Instruments, Inc.,
Madison, Wisconsin, 1996.
2
2
2
5
6
7
C.P. Tan, J. Liu, L.M. Chen, S. Shi and L.N. Ji, J. Inorg. Biochem., 2008,
36 V.G. Vaidyanathan and B.U. Nair, J. Inorg. Biochem., 2003, 94, 121.
37 R. Vijayalakshmi, M. Kanthimathi, V. Subramanian and B.U. Nair,
Biochim. Biophys. Acta, 2000, 1475, 157.
38 H.L. Wu, J.K. Yuan, Y. Bai, H. Wang, G.L. Pan and J. Kong, J. Photochem.
Photobiol. B, 2012, 116, 13.
39 J.B. LePecq and C. Paoletti, J. Mol. Biol., 1967, 27, 87.
40 Q. Wang, Z.Y. Yang, G.F. Qi and D.D. Qin, Eur. J. Med. Chem., 2009, 44,
2425.
41 Z.A. Taha, A.M. Ajlouni, W.A. Momani and A.A. Al-Ghzawi,
Spectrochim. Acta A, 2011, 81, 570.
102, 1644.
A.M. Pyle, J.P. Rehmann, R. Meshoyrer, C.V. Kumar, N.J. Turro and J.K.
Barton, J. Am. Chem. Soc., 1989, 111, 3051.
H.L. Wu, J.K. Yuan, Y. Bai, G.L. Pan, H. Wang, J. Kong, X.Y. Fan and
H.M. Liu, J. Chem. Soc. Dalton Trans., 2012, 2012, 8829.
J.R. Lakowicz and G. Webber, Biochemistry, 1973, 12, 4161.
H.L. Wu, J.K. Yuan, Y. Bai, G.L. Pan, H. Wang and X.B. Shu, J. Photochem.
Photobiol. B, 2012, 107, 65.
2
2
8
9
3
31
0
C. Beauchamp and I. Fridovich, Anal. Biochem., 1971, 44, 276.
Q.H. Luo, Q. Lu, A.B. Dai and L.G. Huang, J. Inorg. Biochem., 1993, 51,
42 T.R. Li, Z.Y. Yang, B.D. Wang and D.D. Qin, Eur. J. Med. Chem., 2008, 43,
1688.
655.
JCR1402418_FINAL.indd 217
27/03/2014 14:00:35

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and
its content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.