A Schiff base bis(N-salicylidene)-3-oxapentane-1,5-diamine and its yttrium(III) complex: Synthesis, crystal structure, DNA-binding properties, and antioxidant activities

Article abstract of DOI:10.1080/00958972.2013.812725

A Schiff base bis(N-salicylidene)-3-oxapentane-1,5-diamine (H₂L) and its yttrium(III) (Y(III)) complex, Y₂L₂(NO ₃)₂?2H2O, have been synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of the Y(III) complex has been determined by single-crystal X-ray diffraction, revealing a centrosymmetric binuclear neutral entity where Y(III) centers are bridged by two phenoxo oxygens. The DNA-binding properties of the Schiff base H₂L and the Y(III) complex were investigated by spectrophotometric methods and viscosity measurements. The results suggest that ligand H₂L and Y(III) complex both bind to DNA via groove binding, and the Y(III) complex binds to DNA more strongly than H₂L. The antioxidant activity of the Y(III) complex was determined by superoxide and hydroxyl radical-scavenging method in vitro, which indicates that Y(III) complex scavenges OH? and O₂ radicals.

Full text of DOI:10.1080/00958972.2013.812725

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A Schiff base bis(N-salicylidene)-3-
oxapentane-1,5-diamine and its
yttrium(III) complex: synthesis, crystal
structure, DNA-binding properties, and
antioxidant activities
a
a
a
a
a
Huilu Wu , Guolong Pan , Yuchen Bai , Hua Wang , Jin Kong
a
a
a
,
a
Furong Shi , Yanhui Zhang & Xiaoli Wang
School of Chemical and Biological Engineering, Lanzhou Jiaotong
University , Lanzhou , P.R. China
Accepted author version posted online: 11 Jun 2013.Published
online: 16 Jul 2013.
To cite this article: Huilu Wu , Guolong Pan , Yuchen Bai , Hua Wang , Jin Kong , Furong
Shi , Yanhui Zhang & Xiaoli Wang (2013) A Schiff base bis(N-salicylidene)-3-oxapentane-1,5-
diamine and its yttrium(III) complex: synthesis, crystal structure, DNA-binding properties,
and antioxidant activities, Journal of Coordination Chemistry, 66:15, 2634-2646, DOI:
10.1080/00958972.2013.812725
To link to this article: http://dx.doi.org/10.1080/00958972.2013.812725
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Journal of Coordination Chemistry, 2013
Vol. 66, No. 15, 2634–2646, http://dx.doi.org/10.1080/00958972.2013.812725
A Schiff base bis(N-salicylidene)-3-oxapentane-1,5-diamine
and its yttrium(III) complex: synthesis, crystal structure,
DNA-binding properties, and antioxidant activities
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,
P.R. China
(Received 5 January 2013; in final form 18 April 2013)
2
A Schiff base bis(N-salicylidene)-3-oxapentane-1,5-diamine (H L) and its yttrium(III) (Y(III))
complex, Y (NO ·2H O, have been synthesized and characterized by physico-chemical and
2
L
2
3
)
2
2
spectroscopic methods. The crystal structure of the Y(III) complex has been determined by
single-crystal X-ray diffraction, revealing a centrosymmetric binuclear neutral entity where Y(III)
centers are bridged by two phenoxo oxygens. The DNA-binding properties of the Schiff base H
and the Y(III) complex were investigated by spectrophotometric methods and viscosity measure-
ments. The results suggest that ligand H L and Y(III) complex both bind to DNA via groove
binding, and the Y(III) complex binds to DNA more strongly than H L. The antioxidant activity of
the Y(III) complex was determined by superoxide and hydroxyl radical-scavenging method
2
L
2
2
ꢀ
·
in vitro, which indicates that Y(III) complex scavenges OH· and O2 radicals.
Keywords: Bis(N-salicylidene)-3-oxapentane-1, 5-diamine; Yttrium(III) complex; Crystal structure;
DNA-binding property; Antioxidant activities
1. Introduction
Binding of small molecules with DNA has been studied extensively since DNA is the
material of inheritance and controls the structure and function of cells [1]. Small molecules
possessing DNA-binding abilities include metal complexes, porphyrins, natural antibiotics,
simple aromatic hydrocarbons, and some heterocyclic cations [2–7]. Particularly, the DNA
binding of metal complexes is studied for probes of nucleic acid structure, DNA footprint-
ing, and sequence-specific cleaving agents, antitumor drugs, etc. [8–10]. An understanding
of how these small molecules bind to DNA will be useful in the design of new
compounds, which can recognize specific sites or conformations of DNA [11–13].
Schiff base complexes have been among the most widely studied coordination
compounds, increasingly important as biochemical, analytical, and antimicrobial reagents
[
[
14]. Biological activity and other applications result in increasing interest for lanthanides
15–19]. One of the most studied applications is the use of lanthanide complexes to
address DNA/RNA by non-covalent binding and/or cleavage [20–23].
*
Corresponding author. Email: wuhuilu@163.com
Ó 2013 Taylor & Francis

Yttrium(III) Schiff base
2635
Lanthanide ions are oxophilic and we select the yttrium(III) (Y(III)) complex with a
pentadentate Schiff base bis(N-salicylidene)-3-oxapentane-1,5-diamine. The DNA-binding
properties of the complex were investigated by spectrophotometric and viscosity
measurements. In addition, the antioxidant activities of the complex were determined by
ꢀ
superoxide anion (O ) and hydroxyl radical (OH·)-scavenging methods in vitro.
2
2
2
. Experimental
.1. Materials and methods
All chemicals were of analytical grade. Calf thymus DNA (CT-DNA), ethidium bromide
EB), nitroblue tetrazolium nitrate (NBT), methionine (MET), and riboflavin (VitB ) were
(
2
obtained from Sigma-Aldrich Co. (USA) and used without purification. All experiments
involving interaction of the ligand and the complex with CT-DNA were carried out in
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
2
80 nm of about 1.8–1.9, indicating that the CT-DNA was sufficiently free of protein [24].
The CT-DNA concentration per nucleotide was determined spectrophotometrically by
employing an extinction coefficient of 6600 L/M cm at 260 nm [25].
C, H, and N elemental analyses were determined using a Carlo Erba 1106 elemental
ꢀ
1
analyzer. IR spectra were recorded from 4000 to 400 cm with a Nicolet FT-VERTEX 70
spectrometer using KBr pellets. Electronic spectra were taken on Lab-Tech UV Bluestar
and Spectrumlab 722sp spectrophotometers with a spectral resolution of 0.2 nm. Fluores-
1
cence spectra were recorded on a LS-45 spectrofluorophotometer. H NMR spectra were
obtained with a Mercury plus 400 MHz NMR spectrometer with TMS as an internal stan-
dard and CDCl as the solvent.
3
The synthetic route for H L is shown in scheme 1.
2
2
.2. Preparation of H L and its complex
2
2
.2.1. Preparation of 3-oxapentane-1,5-diamine. 3-Oxapentane-1,5-diamine was syn-
thesized following the procedure [26]. 1,5-Dichloro-3-oxapentane was prepared by the
reaction of diethylene glycol and thionyl chloride. Dichloride, potassium phthalimide,
and diethylamine were heated together at 140 °C for 3 h to synthesize 3-oxapentane-1,5-
diphthalimide. After a series of hydrolysis, acidification, and distillation, a colorless
oil was obtained. Anal. Calcd (%) for C H N O: C, 46.25; H, 11.54; N, 26.90.
4
12 2
2
Scheme 1. Synthetic routine of H L.

2
636
H. Wu et al.
ꢀ
1
Found (%): C, 45.98; H, 11.50; N, 26.76. FT–IR (KBr ν/cm ): 1120 ν(C–O–C), 3340
ν(–NH ) stretching frequency, respectively.
2
2
.2.2. Bis(N-salicylidene)-3-oxapentane-1,5-diamine (H L). For the synthesis of H L,
2 2
salicylic aldehyde (10 mM, 1.22 g) in EtOH (5 mL) was added dropwise to 5 mL of an
EtOH solution of 3-oxapentane-1,5-diamine (5 mM, 0.52 g). After 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, giving a yellow crystalline
solid. Yield: 1.19 g (68.5%). Anal. Calcd (%) for C H O N : C, 69.21; H, 6.45; N, 8.97.
1
8 20 3 2
1
Found (%): C, 69.09; H, 6.54; N, 8.83. H-NMR (CDCl 400 MHz) δ/ppm: 8.30 (s, 2H,
3
N = C–H), 6.79–7.33 (m, 8H, H-benzene ring), 3.66–3.74 (m, 8H, O–(CH ) –N = C).
2
2
ꢀ1
UV-vis (λ, nm): 268, 316. FT–IR (KBr ν/cm ): 1637 ν(C = N), 1286 ν(C–O–C), 3458
ν(OH), stretching frequency, respectively.
2
.2.3. Synthesis of Y L (NO ) ·2H O. To a stirred solution of H L (0.156 g, 0.5 mM)
2 2 3 2 2 2
in EtOH (10 mL) were added Y(NO ) (H O) (0.191 g, 0.5 mM) and triethylamine
3
3
2
6
(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 dried precipi-
2
tate was dissolved in DMF to form a yellow solution. Yellow block crystals of
Y L (NO ) ·2H O suitable for X-ray diffraction studies were obtained by vapor diffusion
2
2
3 2
2
of diethyl ether into the solution for a few weeks at room temperature. Yield: 0.198 g
(
4
1
57.1%). Anal. Calcd (%) for C H Y N O : C, 45.10; H, 4.18; N, 8.77. Found (%): C,
36 40 2 6 14
ꢀ1
4.99; H, 4.26; N, 8.63. UV-vis (λ, nm): 269, 316. FT–IR (KBr ν/cm ): 1230 ν(C–O–C),
378 ν (NO ), 1052 ν (NO ), 1631 ν(C = N) stretching frequency, respectively.
s
3
a
3
2
.3. X-ray crystallography
A suitable single crystal was mounted on a glass fiber and intensity data were collected on a
Bruker Smart CCD diffractometer with graphite-monochromated Mo-Kα radiation
(
λ = 0.71073 Å) at 296 K. Data reduction and cell refinement were performed using SMART
and SAINT programs [27]. The structure was solved by direct methods and refined by
2
full-matrix least-squares against F of data using SHELXTL [28]. All hydrogens were found
in difference electron maps and subsequently refined in a riding-model approximation with
C–H distances ranging from 0.93–0.97 Å and Uiso (H) = 1.2 Ueq (C) or 1.5 Ueq (C).
2
2
.4. DNA-binding experiments
.4.1. Viscosity titration measurements. Viscosity experiments were conducted on an
Ubbelodhe viscometer, immersed in a water bath maintained at 25.0 ± 0.1 °C. Titrations
were performed for the complexes (3–30 μM) and each compound was introduced into the
1
/3
CT-DNA solution (42.5 μM) present in the viscometer. Data were analyzed as (η/η0)
versus the ratio of the concentration of the compound to CT-DNA, where η is the viscosity
of CT-DNA in the presence of the compound and η is the viscosity of CT-DNA alone.
0
Viscosity values were calculated from the observed flow time of CT-DNA-containing
solutions corrected from the flow time of buffer alone (t ), η = (t ꢀ t ) [29].
0
0

Yttrium(III) Schiff base
2637
2.4.2. Electronic absorption titration. Absorption titration experiments were performed
with fixed concentrations of the complexes, 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 itself. From the absorption titration data, the binding constant (K ) was
b
determined using the equation [30]:
½
DNAꢁ=ðe ꢀ e Þ ¼ ½DNAꢁ=ðe ꢀ e Þ þ 1=K ðe ꢀ e Þ
a
f
b
f
b
b
f
where [DNA] is the concentration of CT-DNA in base pairs, ɛa corresponds to the
observed extinction coefficient (Aobsd/[M]), ɛ corresponds to the extinction coefficient of
f
the free compound, ɛ is the extinction coefficient of the compound when fully bound to
b
CT-DNA, and K is the intrinsic binding constant. The ratio of slope to intercept in the
b
plot of [DNA]/(ɛ ꢀ ɛ ) versus [DNA] gave the value of K .
a
f
b
2
.4.3. Fluorescence studies. Enhanced fluorescence of EB in the presence of DNA can
be quenched by the addition of a second molecule [31, 32]. The extent of 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
analyzed according to the classical Stern–Volmer equation [33]:
I
0
=I ¼ 1 þ KSV½Qꢁ
where I and I are the fluorescence intensities at 599 nm in the absence and presence of
0
the quencher, respectively, KSV is the linear Stern–Volmer quenching constant, and [Q] is
ꢀ
3
the concentration of the quencher. In these experiments, [CT-DNA] = 2.5 ꢂ 10 M/L,
EB] = 2.2 ꢂ 10ꢀ M/L.
3
[
2
2
.5. Antioxidant property
.5.1. Hydroxyl radical assay. Hydroxyl radicals were generated in aqueous media
through the Fenton-type reaction [34, 35]. Aliquots of the reaction mixture (3 mL)
contained 1 mL of 0.1 mM aqueous safranin, 1 mL of 1.0 mM aqueous EDTA–Fe(II), 1 mL
of 3% aqueous H O , and a series of quantitative microadditions of solutions of the test
2
2
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. Absorbance was then
measured at 520 nm. All the tests were run in triplicate and are expressed as the mean and
standard deviation (SD) [36]. The scavenging effect for OH· was calculated from the
following expression:
Scavenging ratio ð%Þ ¼ ½ðA ꢀ A Þ=ðA ꢀ A Þꢁ ꢂ 100%
i
0
c
0
where A = absorbance in the presence of the test compound; A = absorbance of the blank;
i
0
A = absorbance in the absence of the test compound, EDTA-Fe(II) and H O .
c
2 2

2
638
H. Wu et al.
2
9
.5.2. Superoxide radical assay.
A
non-enzymatic system containing 1 mL
ꢀ
6
ꢀ4
.9 ꢂ 10 M VitB2, 1 mL 1.38 ꢂ 10 M NBT, and 1 mL 0.03 M MET was used to
ꢀ
ꢀ
2
produce superoxide anion (O ), and the scavenging rate of O under the influence of 0.1–
2
1
.0 μM of the tested compound was determined by monitoring the reduction in the rate of
transformation of NBT to monoformazan dye [37]. The solutions of MET, VitB2, and
NBT were prepared with 0.02 M phosphate buffer (pH = 7.8) in the absence of 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 calcu-
0
lated using the equation [38]: percentage inhibition of NBT reduction = (1 ꢀ k =k) ꢂ 100,
0
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 dismu-
tase), 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 causes 50% inhibition of NBT
reduction is reported as IC .
5
0
3
. Results and discussion
H L and Y(III) complex are stable in air. The Y(III) complex is remarkably soluble in
2
polar aprotic solvents such as DMF, DMSO, and MeCN, slightly soluble in ethanol,
methanol, ethyl acetate, and chloroform and insoluble in water, Et O, and, petroleum ether.
2
3
.1. IR and electronic spectra
ꢀ1
ꢀ1
For free H L, a strong band is found at 1637 cm with a weak band at 1286 cm . By
2
analogy with assigned bands, the former can be attributed to ν(C = N), while the latter can
ꢀ
1
be attributed to ν(C–O–C). These bands shift to lower frequency by ca. 6–56 cm for the
Y(III) complex [39], which implies direct coordination of nitrogen and oxygen. The bands
ꢀ
1
at 1378 and 1052 cm
3
indicate that nitrate is bidentate [40] and a weak band at
ꢀ
1
675 cm is allocated as ν(H O), in agreement with the result of X-ray diffraction.
2
The electronic spectra of H L and Y(III) complex were recorded in DMF solution at room
2
temperature. The UV bands of H L (268 and 316 nm) are marginally shifted in the complex.
2
⁄
⁄
Two absorptions are assigned to π→π (benzene) and π→π (C = N) transitions [41].
3
.2. X-ray structure of the complex
Basic crystal data, description of the diffraction experiment, and details of the structure
refinement are given in table 1. Selected bond distances and angles are presented in table 2.
3
.2.1. The crystal structure of Y L (NO ) ·2H O. The crystal structure of the Y(III)
2 2 3 2 2
complex consists of discrete Y L (NO ) and two H O molecules. The prepared pentaden-
2
2
3 2
2
tate ligand contains strong donors, phenoxo and imine nitrogen with excellent coordination
ability through its N O donor set. Single-crystal X-ray structure determination reveals that
2
3
the complex has a centrosymmetric neutral homobinuclear entity. An ORTEP illustration
of the complex (figure 1(a)) shows that two adjacent [Y(L)(NO )] moieties are coupled
3
together via two phenolato bridges belonging to the two ligands. In the μ -diphenoxo
2
bridged binuclear structure, both the Y(III) centers are eight-coordinate (figure 1(b)).

Yttrium(III) Schiff base
2639
2 2 3 2 2
Table 1. Crystal data and structure refinement for Y L (NO ) ·2H O.
Complex
2 2 3 2 2
Y L (NO ) ·2H O
Molecular formula
Molecular weight
Color
36 40 2 6 14
C H Y N O
958.56
Yellow
0.25 ꢂ 0.23 ꢂ 0.20
Monoclinic
C2/c
29.310(7)
11.726(3)
15.169(4)
90
3
Crystal size, mm
Crystal system
Space group
a, Å
b, Å
c, Å
α, deg
β, deg
118.039(2)
90
4601.7(19)
4
γ, deg
3
V, Å
Z
T, K
296(2)
1.384
ꢀ3
D
Calcd, g cm
F (000), e
1952
h range for data collection, deg
hkl range
Reflections collected
Independent reflections
Refinement method
2.20–25.50
1ꢀ6 3, 34 768h 6 35, ꢀ14 6 k 6 13, ꢀ18 6 l 6 18
4265 [Rint = 0.0403]
2
Full-matrix least-squares on F
Data/restraints/parameters
4265/3/262
Final R
1
/wR
2
indices [I P 2σ(I)]
0.0397/0.1264
0.0706/0.1416
1.074
0.743 and ꢀ0.274
R
1
/wR
2
indices (all data)
2
Goodness-of-fit on F
Largest diff. peak and hole, e Å
ꢀ
3
2 2 3 2 2
Table 2. Selected bond distances (Å) and angles (°) in Y L (NO ) ·2H O.
Complex
Y
2
L
2
(NO
3
)
2
2
·2H O
Bond distances
Y(1)–O(3)
2.164(3)
2.271(3)
2.310(3)
Y(1)–O(1)
Y(1)–O(5)
Y(1)–N(2)
Y(1)–N(1)
2.451(3)
2.470(3)
2.473(4)
a
Y(1)–O(2)#1
Y(1)–O(2)
Y(1)–O(4)
2.450(3)
2.505(4)
Bond angles
O(3)–Y(1)–O(2)#1
O(3)–Y(1)–O(2)
O(2)#1–Y(1)–O(2)
O(2)–Y(1)–O(1)
O(3)–Y(1)–O(1)
O(2)#1–Y(1)–O(1)
O(2)#1–Y(1)–O(5)
O(1)–Y(1)–O(5)
O(2)#1–Y(1)–N(2)
O(1)–Y(1)–N(2)
O(3)–Y(1)–N(1)
O(2)–Y(1)–N(1)
O(4)–Y(1)–N(1)
O(5)–Y(1)–N(1)
96.20(11)
85.94(10)
71.26(10)
131.42(10)
140.61(11)
87.02(10)
150.03(10)
112.52(11)
84.90(11)
66.46(13)
152.38(12)
70.64(11)
87.93(13)
78.36(11)
O(3)–Y(1)–O(4)
O(2)#1–Y(1)–O(4)
O(2)–Y(1)–O(4)
O(4)–Y(1)–O(1)
O(3)–Y(1)–O(5)
O(2)–Y(1)–O(5)
O(4)–Y(1)–O(5)
O(3)–Y(1)–N(2)
O(2)–Y(1)–N(2)
O(4)–Y(1)–N(2)
O(5)–Y(1)–N(2)
O(2)#1–Y(1)–N(1)
O(1)–Y(1)–N(1)
N(2)–Y(1)–N(1)
96.20(13)
156.87(10)
129.11(10)
71.09(11)
83.01(12)
78.82(10)
51.34(10)
74.72(13)
147.48(12)
79.65(12)
123.14(11)
90.07(11)
66.38(11)
132.76(13)
a
Symmetry transformations used to generate equivalent atoms: #1 ꢀx + 1/2, ꢀy + 3/2, ꢀz.
The local coordination environment is identical for both centers and is best described as a
distorted square YN O antiprism (figure 1(c)). Due to flexibility of the ligand, it loses pla-
2
6
narity. The bond distances are Y(1)–Nimine: 2.473(4)–2.505(4), Y(1)–Oether: 2.451(3), and
Y(1)–Onitrate: 2.450(3)–2.470(3) Å. Coordination of the two identical Schiff bases of the

2
640
H. Wu et al.
Figure 1. (a) The molecular structure of Y
2
L
2
(NO
3
)
2
in the crystal with displacement ellipsoids at 30%
3+
probability level; hydrogens are omitted for clarity, (b) perspective disposition of the donor sites around each Y3
center shown in Neumann projection, (c) a distorted square antiprism geometry is formed by donors around Y
as illustrated in the polyhedral view.
+
same ligand is different. Of the two phenoxo oxygens of each ligand, one is simply
monocoordinated while the other bridges the adjacent Y(III) centers as reflected by the
Y–Ophenoxo bond lengths [Y(1)–O(2), 2.310(3) and Y(1)–O(3), 2.146(3) Å]. The distance
of Y(1)–Y(1A), 3.7230(11) Å, is relatively too long to consider any direct Y–Y interaction.
Hydrogen-bonding interactions play important roles in crystal packing in the complex
[
42]. The hydrogen C(11) forms a hydrogen bond to O(6) with dimensions Cꢃ ꢃ ꢃO 3.46 Å,
C–Hꢃ ꢃ ꢃO 145.4°, and Hꢃ ꢃ ꢃO 2.62 Å to result in a 1-D polymeric structure (figure 2). An
Figure 2. Packing diagram of Y(III) complex showing the 1D H-bonded network; hydrogens except H(11B)
have been excluded for clarity.

Yttrium(III) Schiff base
2641
interesting feature of this structure is the intermolecular hydrogen bond that exists among
the Y(III) complexes, which also affords voids to trap guest molecules, suggesting
potential application for gas absorption [43].
3
3
.3. DNA-binding properties
.3.1. Viscosity titration measurements. Viscosity titration measurements were carried
out to further clarify the interaction between the investigated compounds and CT-DNA.
Hydrodynamic measurements that are sensitive to changes in the length of DNA (i.e. vis-
cosity and sedimentation) are critical tests of binding in solution in the absence of crystal-
lographic structural data [44]. The classic intercalation model involves 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 be in close proximity to the DNA base
pairs as well [45–47]. In contrast, the molecule that binds exclusively in the DNA grooves
by partial and/or non-classical intercalation, under the same conditions, typically
causes less pronounced (positive or negative) or no change in the DNA solution viscosity
[48, 49].
The effects of H L and Y(III) complex on the viscosity of CT-DNA are shown in figure
2
3
. The experimental results indicate that the addition of H L and Y(III) complex causes no
2
significant viscosity change. Therefore, according to the previous report related to
DNA-binding lanthanide complexes [50–54], we can deduce that H L and Y(III) complex
2
probably bind to DNA in a groove mode.
3
.3.2. Absorption spectroscopic studies. Application of electronic absorption spectros-
copy in DNA-binding studies is one of the most useful techniques [55]. To clarify the
interactions between the compounds and DNA, the electronic absorption spectra of H2L
and its Y(III) complex in the absence and presence of the CT-DNA (at a constant concen-
tration of the compounds) were obtained, as shown in figure 4. With increasing DNA con-
centrations, the absorption bands at 394 nm of H L show a hypochromism of 32.35%; the
2
absorption bands at 393 nm of the Y(III) complex show a hypochromism of 58.24%.
Figure 3. Effect of increasing amounts of (a) H
at 25.0 ± 0.1 °C.
2
L and (b) Y(III) complex on the relative viscosity of CT-DNA

2
642
H. Wu et al.
⁄
Hypochromism observed for the π→π transitions indicate strong binding of H L and
2
complex to DNA.
To compare quantitatively the affinity of H L and Y(III) complex towards DNA, the
2
intrinsic binding constants K of the two compounds to CT-DNA were determined by mon-
b
itoring the changes of absorbance with increasing concentrations of DNA. The intrinsic
3
ꢀ1
binding constant K of H L and of the Y(III) complex were 5.30 ꢂ 10 M (R = 0.99 for
b
2
4
ꢀ1
1
6 points) and 2.30 ꢂ 10 M (R = 0.99 for 16 points), respectively, from the decay of the
absorbances. The K values obtained here are lower than that reported for a classical
b
6
intercalator (for EB and [Ru(phen)DPPZ], the binding constants are of the order of 10 –
0 M ) [56–59]. It is clear that the hypochromism and Kb values are not enough
7
ꢀ1
1
evidence, but these results suggest an intimate association of the compounds with CT-DNA
and indicate that the binding strength of the complex is higher than that for H L.
2
Based on the above results, the affinity for DNA is stronger for the Y(III) complex than
the ligand. We attribute the reason as the charge transfer of coordinated H L caused by
2
coordination which results in the decrease of charge density of the planar conjugated
system. This change will lead to complexes binding to DNA more readily [60, 61]. The
Figure 4. Electronic spectra of (a) H
2
L, (c) Y(III) complex in Tris–HCl buffer upon the addition of CT-DNA.
ꢀ
5
ꢀ5
[
Compound] = 3 ꢂ 10 M, [DNA] = 2.5 ꢂ 10 M. Arrow shows the emission intensity changes upon increasing
DNA concentration. Plots of [DNA]/(ɛ
a
f 2
ꢀ ɛ ) vs. [DNA] for the titration of (b) H L, (d) Y(III) complex with
CT-DNA.

Yttrium(III) Schiff base
2643
helical structure of the Y(III) complex is able to provide lots of groove positions to stack
more strongly with the base pairs of the DNA helix [62].
3.3.3. Fluorescence spectroscopic studies. To further study the binding properties of
the complexes with DNA, competitive binding was carried out. Relative binding of H2L
and Y(III) complex to CT-DNA was studied by the fluorescence spectral method using
ethidium bromide (EB)-bound CT-DNA solution in the Tris-HCl/NaCl buffer (pH = 7.2).
As a typical indicator of intercalation, EB is a weak fluorescent compound. But in the
presence of DNA, the emission intensity of EB is greatly enhanced because of its strong
intercalation between the adjacent DNA base pairs [32]. In general, measurement of the
ability of a complex to affect the intensity of EB fluorescence in the EB-DNA adduct
allows the determination of the affinity of the complex for DNA, whatever the binding
mode may be. If a complex can displace EB from DNA, the fluorescence of the solution
will be reduced due to free EB molecules that are readily quenched by water [63]. For
H L and the Y(III) complex, no emission was observed either alone or in the presence of
2
CT-DNA in the buffer. The fluorescence quenching of DNA–bound EB by the ligand and
the complex are shown in figure 5. The behavior of H L and Y(III) complex is in agree-
2
ment with the Stern–Volmer equation, which provides further evidence that the two com-
4
pounds bind to DNA. The Ksv values for H L and Y(III) complex are 0.35 ꢂ 10 (R = 0.98
2
4
ꢀ1
for 21 points) and 1.25 ꢂ 10 M (R = 0.99 for 13 points), respectively, reflecting the
higher quenching efficiency of the Y(III) complex relative to that of H L. This suggests
2
that DNA-binding of the Y(III) complex is stronger than that of H L. Such a trend is
2
consistent with the absorption spectral results.
3
.4. Antioxidant property
According to relevant reports in the literature [64, 65], rare earth complexes may exhibit
antioxidant activity. We, therefore, conducted an investigation to explore whether the
Y(III) complex has antioxidant activities.
3
.4.1. Hydroxyl radical-scavenging activity. We compared the abilities of the present
compounds to scavenge hydroxyl radicals with those of the well-known natural antioxi-
dants mannitol and vitamin C, using the same method as reported in a previous paper
ꢀ
3
[
66]. The 50% inhibitory concentrations (IC ) of mannitol and vitamin C are 9.6 ꢂ 10
5
0
ꢀ3 ꢀ1
and 8.7 ꢂ 10
M , respectively. As shown in figure 6(a), according to the antioxidant
M , which implies that the
Y(III) complex exhibits better scavenging activity than mannitol and vitamin C. Much less
ꢀ5
ꢀ1
experiments, the IC value of Y(III) complex is 3.73 ꢂ 10
5
0
scavenging activity was exhibited by H L when compared to that of Y(III) complex. Due
2
to the observed IC50 values, the Y(III) complex can be considered as a potential drug to
eliminate the hydroxyl radical.
3
.4.2. Superoxide radical-scavenging activity. As another assay of antioxidant activity,
ꢀ
superoxide radical (O )-scavenging activity has been investigated. The Y(III) complex has
2
good superoxide radical-scavenging activity.

2
644
H. Wu et al.
Figure 5. Emission spectra of EB bound to CT-DNA in the presence of (a) H
[
2
L and (c) Y(III) complex;
compound] = 3 ꢂ 10 M; λex = 520 nm. The arrows show the intensity changes upon increasing concentrations of
the complexes. Fluorescence quenching curves of EB bound to CT-DNA by (b) H L and (d) Y(III) complex.
Plots of I /I vs. [complex].)
ꢀ
5
2
(
0
Figure 6. Plots of antioxidation properties for the Y(III) complex. (a) The hydroxyl radical-scavenging effect
%) for the Y(III) complex. (b) The superoxide radical-scavenging effect (%) for the Y(III) complex.
(

Yttrium(III) Schiff base
2645
ꢀ
5
ꢀ1
The Y(III) complex shows an IC50 value of 4.23 ꢂ 10
M
(figure 6(b)), which indi-
ꢀ
cates that it has potent scavenging activity for superoxide radical (O ). This indicates that
2
the Y(III) complex exhibits good superoxide radical-scavenging activity and may be an
ꢀ
inhibitor (or a drug) to scavenge superoxide radical (O ) in vivo.
2
4
. Conclusion
A new ligand, bis(N-salicylidene)-3-oxapentane-1,5-diamine and its Y(III) complex have
been synthesized and characterized. The crystal structure of Y L (NO ) ·2H O shows
2
2
3 2
2
eight-coordinate yttrium adopting a distorted square antiprism geometry. The DNA-binding
experiments suggest that H L and Y(III) complex bind to DNA in a groove mode, and the
2
affinity for DNA is stronger in the case of Y(III) complex when compared with the ligand.
ꢀ
The Y(III) complex exhibited potential antioxidant activities against OH· and O2 radicals
in vitro. These findings indicate that Y(III) complex has many potential applications for
the development of nucleic acid molecular probes and new therapeutic reagents for dis-
eases at the molecular level, and warrant further in vivo experiments and pharmacological
assays.
Supplementary material
Crystallographic data (excluding structure factors) for the structure reported in this paper
have been deposited with the Cambridge Crystallographic Data Center with reference
number CCDC 917806. Copies of the data can be obtained, free of charge, on application
to the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Tel: +44 01223 762910; Fax:
+
44 01223 336033; E-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk.
Acknowledgments
The authors acknowledge the financial support and grant from ‘Qing Lan’ Talent
Engineering Funds by Lanzhou Jiaotong University. This work is also supported by the
Fundamental Research Funds for the Gansu Province Universities (212086).
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