Synthesis, crystal structure, DNA-binding properties and antioxidant activities of a lutetium(III) complex with the bis(N-salicylidene)-3-oxapentane- 1,5-diamine ligand

Article abstract of DOI:10.5560/ZNB.2013-2339

A Schiff base ligand bis(N-salicylidene)-3-oxapentane-1,5-diamine (H ₂L) and its lutetium(III) complex, with composition Lu ₂(L)₂ (NO3)₂, were synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of the Lu(III) complex has been determined by single-crystal X-ray diffraction. It reveals a centrosymmetric binuclear neutral entity where Lu(III) metal centers are bridged by two phenoxo oxygen atoms. The DNA-binding properties of the Lu(III) complex were investigated by spectrophotometric methods and viscosity measurements, and the results suggest that the Lu(III) complex binds to DNA via a groove binding mode. Additionally, the antioxidant activity of the Lu(III) complex was determined by the superoxide and hydroxyl radical scavenging methods in vitro, which indicate that it is a scavenger for OH and O₂^- radicals.

Full text of DOI:10.5560/ZNB.2013-2339

Synthesis, Crystal Structure, DNA-binding Properties and Antioxidant
Activities of a Lutetium(III) Complex with the Bis(N-salicylidene)-3-
oxapentane-1,5-diamine Ligand
Guolong Pan, Yuchen Bai, Hua Wang, Jin Kong, Furong Shi, Yanhui Zhang, Xiaoli Wang,
and Huilu Wu
School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070,
P. R. China
Reprint requests to Prof. Huilu Wu. E-mail: wuhuilu@163.com
Z. Naturforsch. 2013, 68b, 257 – 266 / DOI: 10.5560/ZNB.2013-2339
Received December 27, 2012
A Schiff base ligand bis(N-salicylidene)-3-oxapentane-1,5-diamine (H L) and its lutetium(III)
2
complex, with composition Lu (L) (NO ) , were synthesized and characterized by physico-chemical
2
2
3 2
and spectroscopic methods. The crystal structure of the Lu(III) complex has been determined by
single-crystal X-ray diffraction. It reveals a centrosymmetric binuclear neutral entity where Lu(III)
metal centers are bridged by two phenoxo oxygen atoms. The DNA-binding properties of the Lu(III)
complex were investigated by spectrophotometric methods and viscosity measurements, and the re-
sults suggest that the Lu(III) complex binds to DNA via a groove binding mode. Additionally, the
antioxidant activity of the Lu(III) complex was determined by the superoxide and hydroxyl radical
−·
scavenging methods in vitro, which indicate that it is a scavenger for OH· and O2 radicals.
Key words: Lutetium(III) Complex, Crystal Structure, DNA-Binding Properties, Antioxidant
Activities, Bis(N-salicylidene)-3-oxapentane-1,5-diamine
Introduction
the most studied applications is the usage of the lan-
thanide complexes to address DNA/RNA by non-
The interactions of metal complexes with DNA have covalent binding and/or cleavage [11 – 14]. In addition,
been an active area of research at the interface of chem- Schiff bases have been widely studied as they possess
istry and biology [1 – 3]. Numerous biological experi- many interesting features, including photochromic and
ments have demonstrated that DNA is the primary in- thermochromic properties, proton transfer tautomeric
tracellular target of anticancer drugs. Interaction be- equilibria, biological and pharmacological activities,
tween small molecules and DNA can cause damage as well as suitability for analytical applications [15].
in cancer cells, blocking the division and resulting in Now we give a full account of the synthesis, crystal
cell death [4 – 6]. Particularly, some metal complexes structure, DNA-binding properties, and antioxidant ac-
are being used to bind and react at specific sequences tivities of a Lu(III) complex with the Schiff base ligand
of DNA in a search for novel chemotherapeutics, for bis(N-salicylidene)-3-oxapentane-1,5-diamine.
probing DNA and for the development of highly sen-
sitive diagnostic agents [7, 8]. Therefore, the research
on the mechanism of the interaction of complexes with
DNA is attracting more and more attention. The results
will potentially be useful in the design of new com-
pounds that can recognize specific sites or conforma-
tions of DNA [7 – 9].
Experimental Section
Materials and physical measurements
All chemicals used were of analytical grade. Ethidium
bromide (EB) and calf thymus DNA (CT-DNA) were pur-
chased from Sigma-Aldrich and used without further pu-
rification. All the experiments involving interaction of the
Lanthanide metal complexes have been used as
biological models to understand the structures of ligand and the complex with CT-DNA were carried out in
biomolecules and biological processes [10]. One of doubly distilled water with a buffer containing 5 mM Tris
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G. Pan et al. · A Lutetium(III) Complex
and 50 mM NaCl and adjusted to pH = 7.2 with hydrochlo- diffraction studies were obtained by vapor diffusion of di-
ric acid. A solution of CT-DNA gave a ratio of UV ab- ethyl ether into the solution for a few weeks at room temper-
sorbance at 260 and 280 nm of about 1.8 – 1.9, indicating ature. Yield: 0.198 g (57%). – C36H Lu N O (1094.6):
36
6
2 12
that the CT-DNA was sufficiently free of protein [16]. The calcd. C 39.46, H 3.29, N 7.67; found C 39.36, H 3.42, N
CT-DNA concentration per nucleotide was determined spec- 7.59. – UV/Vis: λ = 269, 317 nm. – IR (KBr): ν = 1243 (C–
−
−1
.
trophotometrically by employing an extinction coefficient of O–C); 1632 (C=N); 1385, 1058 (NO ) cm
3
−
1
−1
6
600 L mol cm at 260 nm [17].
X-Ray crystallography
C, H and N contents were determined using a Carlo Erba
106 elemental analyzer. The IR spectra were recorded in
1
−
1
A suitable single crystal was mounted on a glass fiber,
and the intensity data were collected on a Bruker Smart CCD
diffractometer with graphite-monochromatized MoKα radi-
ation (λ = 0.71073
A˚ ) at 296(2) K. Data reduction and cell
refinement were performed using the programs SMART and
SAINT [19]. The absorption corrections were carried out em-
pirically. The structure was solved by Direct Methods and
the 4000 – 400 cm
region with a Nicolet FT-VERTEX
7
0 spectrophotometer using KBr pellets. Electronic spec-
tra were taken on Lab-Tech UV Bluestar and Spectrumlab
1
7
22sp spectrophotometers. H NMR spectra were obtained
with a Mercury plus 400 MHz NMR spectrometer with TMS
as internal standard and CDCl as solvent. The fluorescence
3
spectra were performed on a LS-45 spectrofluorophotometer
at room temperature. Viscosity experiments were conducted
on an Ubbelohde viscosimeter, immersed in a thermostated
2
refined by full-matrix least-squares against F of data us-
ing the SHELXTL software package [20, 21]. The uncoordi-
nated water molecule was found to be disordered. Its electron
density was removed from the reflection intensities by using
the routine SQUEEZE in PLATON. All H atoms were found
in difference electron maps and were subsequently refined in
◦
water bath maintained at 25.0±0.1 C.
Preparation of 3-oxapentane-1,5-diamine
3
-Oxapentane-1,5-diamine was synthesized following the a riding-model approximation with C–H distances ranging
procedure in ref. [18]. – C H N O (104.1): calcd. C 46.25, from 0.95 to 0.99
A˚ and Uiso(H) = 1.2 Ueq(C) or 1.5 Ueq(C).
4
12 2
H 11.54, N 26.90; found C 45.98, H 11.50, N 26.76. – IR The crystal data and experimental parameters relevant to the
−1
(
KBr): ν = 1120 (C-O-C), 3340 (-NH ) cm
.
structure determination are listed in Table 1. Selected bond
lengths and bond angles are listed in Table 2.
2
Preparation of bis(N-salicylidene)-3-oxapentane-
1
,5-diamine (H L)
Table 1. Crystal data and structure refinement for
2
Lu (L) (NO ) .
2
2
3 2
For the synthesis of H L, salicylic aldehyde (10 mmol,
.22 g) in EtOH (5 mL) was added dropwise to 5 mL of
an EtOH solution of 3-oxapentane-1,5-diamine (5 mmol,
2
Complex
Lu2(L)2(NO3)2
1
Molecular formula
Molecular weight
Color, habit
C36H36Lu2N6O12
1094.65
Yellow, block
0.25 × 0.24 × 0.21
Monoclinic
C2/c
29.177(11)
11.652(5)
15.236(6)
0
.52 g). After the completion of addition, the solution was
◦
3
stirred for an additional 4 h at 78 C. After cooling to room
temperature, the precipitate was filtered. The product was
dried in vacuo and obtained as a yellow crystalline solid.
Crystal size, mm
Crystal system
Space group
a , A˚
Yield: 1.19 g (69%). – C H O N (312.4): calcd. C 69.21,
18 20 3 2
b , A˚
c , A˚
β, deg
H 6.45, N 8.97; found C 69.09, H 6.54, N 8.83. – UV/Vis
(
1
DMF): λ = 268, 316 nm. – IR (KBr): ν = 1286 (C-O-C);
119.115(3)
4525(3)
−
1
1
637 (C=N); 3458 (-OH) cm . – H NMR (400 MHz,
˚ 3
V, A
CDCl ): δ = 8.30 (s, 2H, N=C-H), 6.79 – 7.33 (m, 8H, H-
Z
4
4.4
296(2)
1.61
3
−1
benzene ring), 3.66 – 3.74 (m, 8H, O-(CH ) -N=C).
µ(MoKα ), mm
T, K
Dcalcd., g cm
F(000), e
2
2
−3
Preparation of Lu (L) (NO )
3 2
2
2
2128
θ range data collection, deg
hkl range
2.20 – 25.50
±35, ±14, ±18
15 874 / 4214 / 0.0453
4214 / 0 / 253
0.0273 / 0.0583
0.0439 / 0.0635
0.957
To a stirred solution of H L (0.156 g, 0.5 mmol) in EtOH
2
(
10 mL) was added Lu(NO ) (H O) (0.191 g, 0.5 mmol) in
3 3 2
6
Reflections collected / unique / Rint
Data / restraints / parameters
Final R1 / wR2 indices [I > 2σ(I)]
R1 / wR2 indices (all data)
EtOH (10 mL). A yellow sediment was generated rapidly.
The precipitate was filtered off, washed with EtOH and ab-
solute Et O, and dried in vacuo. The dried precipitate was
2
2
Goodness-of-fit on F
dissolved in DMF to form a yellow solution. The yellow
−3
Largest diff. peak / hole, e A˚
0.70 / −0.98
block-shaped crystals of Lu (L) (NO ) suitable for X-ray
2
2
3 2
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G. Pan et al. · A Lutetium(III) Complex
259
Table 2. Selected bond lengths (
A˚ ) and
Bond lengths
Lu(1)–O(3)
Lu(1)–O(2)#1
Lu(1)–O(2)
a
2.134(3)
2.228(3)
2.280(3)
2.410(3)
Lu(1)–O(1)
Lu(1)–N(2)
Lu(1)–O(4)
Lu(1)–N(1)
2.427(3)
2.431(4)
2.441(3)
2.455(4)
bond angles (deg) for Lu2(L)2(NO3)2.
Lu(1)–O(5)
Bond angles
O(3)–Lu(1)–O(2)#1
O(3)–Lu(1)–O(2)
O(2)#1–Lu(1)–O(2)
O(3)–Lu(1)–O(5)
O(2)#1–Lu(1)–O(5)
O(2)–Lu(1)–O(5)
O(3)–Lu(1)–O(1)
O(2)#1–Lu(1)–O(1)
O(2)#1–Lu(1)–O(4)
O(5)–Lu(1)–O(4)
N(2)–Lu(1)–O(4)
O(2)#1–Lu(1)–N(1)
O(5)–Lu(1)–N(1)
N(2)–Lu(1)–N(1)
97.22(12)
83.49(11)
70.95(12)
95.68(13)
156.44(11)
130.27(11)
142.02(12)
86.88(11)
149.78(11)
52.21(11)
122.70(12)
90.14(12)
88.49(13)
134.25(15)
O(2)–Lu(1)–O(1)
O(5)–Lu(1)–O(1)
O(3)–Lu(1)–N(2)
O(2)#1–Lu(1)–N(2)
O(2)–Lu(1)–N(2)
O(5)–Lu(1)–N(2)
O(1)–Lu(1)–N(2)
O(3)–Lu(1)–O(4)
O(2)–Lu(1)–O(4)
O(1)–Lu(1)–O(4)
O(3)–Lu(1)–N(1)
O(2)–Lu(1)–N(1)
O(1)–Lu(1)–N(1)
O(4)–Lu(1)–N(1)
132.61(11)
70.94(12)
75.60(14)
85.23(12)
145.98(13)
78.99(13)
67.11(14)
80.87(12)
78.89(11)
113.21(11)
149.93(13)
71.42(12)
67.21(13)
78.30(12)
a
Symmetry transformations used to generate equivalent atoms: #1 −x+1/2, −y+1/2,
z.
−
Scheme 1. Synthetic route for H L.
2
CCDC 916623 contains the supplementary crystallo- IR and electronic spectra
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
For the free ligand H L, a strong band is found at
637 cm together with a weak band at 1286 cm .
2
−1
−1
1
By analogy with previous assignments, the former
can be attributed to ν (C=N), while the latter can be
attributed to ν (C-O-C). These bands were shifted to
Results and Discussion
−
1
The synthetic route for the ligand precursor H L is lower frequencies by ca. 5 ∼ 43 cm for the Lu(III)
2
shown in Scheme 1.
complex, which implies direct coordination of the nitro-
The Lu(III) complex Lu (L) (NO ) was pre- gen and oxygen atoms to the metal ion. Bands at 1385
2
2
3 2
−
1
pared by reaction of H L with Lu(NO ) (H O)
and 1058 cm indicate that nitrate is bidentate [22], in
in ethanol. It is soluble in polar aprotic solvents agreement with the result of X-ray diffraction.
such as DMF, DMSO and MeCN, slightly soluble The electronic spectra of the ligand H L and the
2
3 3
2
6
2
in ethanol, methanol, ethyl acetate, and chloroform Lu(III) complex were recorded in DMF solution
and insoluble in water, Et O and petroleum ether. at room temperature. The UV bands of H L (268,
2
2
The elemental analysis shows that its composition 316 nm) are marginally shifted in the complex. The
∗
is Lu L (NO ) which was confirmed by the crystal two absorption bands are assigned to π → π (ben-
2
2
3 2
∗
structure analysis.
zene) and π → π (C=N) transitions [23].
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60
G. Pan et al. · A Lutetium(III) Complex
Fig. 1 (color online). (a) The molec-
ular structure of the Lu(III) com-
plex in the crystal with displace-
ment ellipsoids at the 30% prob-
ability level; H atoms are omitted
for clarity; (b) a distorted square an-
tiprism geometry is formed by the
donor atoms around the Lu center
as illustrated in the representation of
the coordination polyhedron.
X-Ray structure of the complex
of this structure is the intermolecular hydrogen bond
that exists among the Lu(III) complexes, which also
3
The prepared pentadentate ligand contains strong leads to large solvent-accessible voids of 521 A˚ which
donors, namely phenoxo oxygen atoms as well as might trap guest molecules. Thus the solid may have
imine nitrogen atoms with an excellent coordina- the potential for practical applications such as gas ab-
tion ability for transition/inner-transition metal ions sorption [24].
through its N O donor set. Single-crystal X-ray
2
3
structure determination has revealed that the com- DNA-binding properties
plex has a centrosymmetric neutral homobinuclear en-
tity. An ORTEP illustration of the complex (Fig. 1a) Viscosity measurements
shows that two adjacent [Lu(L)(NO )] moieties are
3
bridged via two phenoxo groups. In the µ -diphenoxo
Hydrodynamic measurements that are sensitive to
2
bridged binuclear structure both Lu(III) centers are changes in DNA length are regarded as the least am-
octa-coordinated. The local coordination environment biguous and most critical tests of a binding model in
is identical for both the centers by symmetry and is solution in the absence of crystallographic data [25,
best described as a distorted square LuN O antiprism 26]. In classical intercalation, the DNA helix length-
2
6
(Fig. 1a). Due to the flexibility of the ligand, it loses ens as base pairs are separated to accommodate the
its planarity (Fig. 1b). The bond lengths are in the bound complex, leading to increased DNA viscosity,
range Lu(1)–Nimine 2.431(4) – 2.455(4), Lu(1)–Oether whereas a partial, non-classical complex intercalation
˚
2
.427(3) and Lu(1)–Onitrate 2.410(3) – 2.441(3) A. The causes a bend (or kink) of the DNA helix and reduces
nature of coordination of the two Schiff base moi- its effective length and thereby its viscosity [27]. Vis-
eties of the same ligand is completely different. cosity experiments were conducted on an Ubbelohde
Of the two phenoxo oxygen atoms of each ligand, viscosimeter, immersed in a water bath maintained at
◦
one is simply mono-coordinated while the other one 25.0 ± 0.1 C. Titrations were performed for the com-
bridges the adjacent Lu(III) centers as reflected by plex (3 – 30 µM), and the compound was introduced
the Lu–Ophenoxo bond lengths [Lu(1)–O(2) 2.280(3), into CT-DNA solution (42.5 µM) present in the vis-
1
/3
˚
Lu(1)–O(3) 2.134(3) A]. The distance Lu(1)–Lu(1A) cosimeter. Data were analyzed as (η/η0)
vs. the
˚
of 3.6711(14) A is too long to consider any direct in- ratio of the concentration of the compound to CT-
tramolecular Lu–Lu interaction. An interesting feature DNA, where η is the viscosity of CT-DNA in the
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G. Pan et al. · A Lutetium(III) Complex
261
presence of the compound and η is the viscosity of intense absorption bands observed for the ligand and
0
∗
CT-DNA alone. Viscosity values were calculated from for the complex are attributed to π → π transitions
the observed flow time of CT-DNA-containing solu- of the ligands. From the absorption titration data, the
tions corrected for the flow time of buffer alone (t0), binding constant was determined using the following
η = (t −t ) [28].
equation [32]:
0
Intercalating agents are expected to increase the vis-
cosity of DNA because of a lengthening of the dou-
[
DNA]/(εa −ε ) = [DNA]/(ε −ε )+1/K (ε −ε )
f
b
f
b
b
f
ble helix due to the accommodation of the ligands in where [DNA] is the concentration of DNA in base
between the base pairs [29]. On the contrary, a par- pairs, εa corresponds to the extinction coefficient ob-
tial and/or non-classical intercalation of the complex served (A /[M]), ε corresponds to the extinction
obsd
f
in the DNA grooves typically causes little (positive or coefficient of the free compound, ε is the extinction
b
negative) or no change in DNA solution viscosity [30]. coefficient of the compound when fully bound to DNA,
The effects of H L and of the Lu(III) complex on the and K is the intrinsic binding constant. The ratio of
2
b
viscosity of CT-DNA is shown in Fig. 2. The experi- slope to intercept in the plot of [DNA]/(εa − ε ) vs.
f
mental results have exhibited that the addition of ligand [DNA] gives the values of K . The absorption spectra
b
and complex causes no significant viscosity change, in- of H L and of the Lu(III) complex in the absence and
2
dicating that these compounds can bind to DNA in the presence of CT-DNA are given in Fig. 3.
groove mode.
With increasing DNA concentrations, the absorp-
tion bands at 394 nm of H L show a hypochromism
2
Electronic absorption
of 32%; the absorption bands at 391 nm of the Lu(III)
complex show a hypochromism of 63%, suggesting
The application of electronic absorption spec- that H L and the Lu(III) complex interact with CT-
2
troscopy in DNA-binding studies is one of the most DNA [33]. The intrinsic binding constant K of H L
b
2
3
−1
useful techniques [31]. Absorption titration experi- and of the Lu(III) complex were 5.30 × 10 L mol
4
−1
ments were performed with fixed concentrations of (R = 0.99 for 16 points) and 2.30 × 10 L mol (R =
the complex, while gradually increasing the concentra- 0.99 for 16 points), respectively, from the decay of the
tion of DNA. While measuring the absorption spectra, absorbances. The K values obtained here are lower
b
a proper amount of DNA was added to both the com- than that reported for a classical intercalator (for ethid-
pound solution and the reference solution to eliminate ium bromide and [Ru(phen)DPPZ], binding constants
6
7
−1
the absorbance of DNA itself. In the UV region, the are of the order of 10 –10 L mol ) [34 – 37]. The
Fig. 2 (color online). Effect of increasing amounts of (a) H L and (b) Lu(III) complex on the relative viscosity of CT-DNA at
2
◦
2
5.0±0.1 C.
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62
G. Pan et al. · A Lutetium(III) Complex
Fig. 3 (color online). Electronic spectra of (a) H L, (c) Lu(III) complex in Tris-HCl buffer upon addition of CT-DNA. [Com-
2
−
5
−5
pound] = 3.0 × 10 M, [DNA] = 2.5 × 10 M. Arrows show the emission intensity changes upon increasing the DNA
concentration. Plots of [DNA]/(εa–ε ) vs. [DNA] for the titration of (b) H L, (d) Lu(III) complex with CT-DNA.
f
2
hypochromism and the K values are not a strict evi- ond molecule [38, 39]. To further clarify the interac-
b
dence, but suggest an intimate association of the com- tion of the complex with DNA, a competitive bind-
pounds with CT-DNA and indicate that the binding ing experiment was carried out in a buffer by keeping
strength of the complex is higher than for H L.
[DNA]/[EB] = 1 and varying the concentrations of the
complex. The fluorescence spectra of EB were mea-
sured using an excitation wavelength at 520 nm. The
emission range was set between 550 and 750 nm. The
2
Fluorescence spectra
No luminescence was observed for the complex spectra were analyzed according to the classical Stern-
at room temperature in aqueous solution, in the or- Volmer equation [40, 41]:
ganic solvent examined and in the presence of calf
thymus (CT-DNA). So the binding of the complex
Io/I = I +Ksv[Q]
cannot be directly followed in the emission spectra. where I andI are the fluorescence intensities at 599 nm
0
The enhanced fluorescence of EB in the presence in the absence and presence of the quencher, respec-
of DNA can be quenched by the addition of a sec- tively, Ksv is the linear Stern-Volmer quenching con-
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G. Pan et al. · A Lutetium(III) Complex
263
Fig. 4 (color online). Emission spectra of EB bound to CT-DNA in the presence of (a) H L and (c) Lu(III) complex; [Com-
2
−
5
pound] = 3.0 × 10 M; λex = 520 nm. The arrows show the intensity changes upon increasing the concentrations of the
complexes. Fluorescence quenching curves of EB bound to CT-DNA by (b) H L and (d) Lu(III) complex. (Plots of I /I vs.
2
0
[Complex]).
stant, and [Q] is the concentration of the quencher. The complex, emission was observed neither for the com-
fluorescence quenching of EB bound to CT-DNA by ponents alone nor in the presence of CT-DNA in the
H L and Lu(III) complex is shown in Fig. 4.
2
buffer. The behavior of H L and of the Lu(III) com-
2
In general, measurements of the ability of a com- plex is in good agreement with the Stern-Volmer equa-
plex to affect the intensity of an EB fluorescence in the tion, which provides further evidence that the two com-
EB-DNA adduct allow the determination of the affinity pounds bind to DNA. The Ksv values for H L and for
2
4
−1
of the complex for DNA, whatever the binding mode the Lu(III) complex are 0.35 × 10 L mol (R = 0.98
4
−1
may be. If a complex can displace EB from DNA, the for 21 points in the line part) and 1.07 × 10 L mol
fluorescence of the solution will be reduced due to the (R = 0.99 for 12 points), respectively, reflecting the
fact that free EB molecules are readily quenched by the higher quenching efficiency of the Lu(III) complex rel-
solvent water [42]. For the ligand H L and the Lu(III) ative to that of H L.
2
2
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64
G. Pan et al. · A Lutetium(III) Complex
Fig. 5 (color online). Plots of antioxidation properties for the Lu(III) complex; (a) represents the hydroxyl radical scavenging
effect (%) for the Lu(III) complex; (b) represents the superoxide radical scavenging effect (%) for the Lu(III) complex.
−
3
Antioxidant activities
value of mannitol and vitamin C are about 9.6 × 10
3
−
−1
and 8.7 × 10 L mol , respectively. According to the
Hydroxyl radical scavenging activity
antioxidant experiments, the IC50 values of the Lu(III)
−5
−1
complex is 4.44 × 10 L mol (Fig. 5a), which im-
Hydroxyl radicals were generated in aqueous media plies that the complex exhibits better scavenging activ-
through the Fenton-type reaction [43, 44]. The reac- ity than mannitol and vitamin C.
tion mixture (3 mL) contained 1 mL of 0.1 mmol aque-
ous safranin, 1 mL of 1.0 mmol aqueous EDTA-Fe(II), Superoxide radical scavenging activity
1
mL of 3% aqueous H O , and a series of quantita-
2 2
tive microadditions of solutions of the test compound.
A
nonenzymatic system containing 1 mL
−6
−4
A sample without the test compound was used as the 9.9 × 10
M VitB2, 1 mL 1.38 × 10
M NBT,
◦
control. The reaction mixtures were incubated at 37 C 1 mL 0.03 M MET was used to produce the superox-
−
·
−·
for 30 min in a water bath. The absorbance was then ide anion (O ), and the scavenging rate of O under
2
2
measured at 520 nm. All the tests were run in tripli- the influence of 0.1 – 1.0 µM of the test compound
cate, and the results are expressed as the mean and was determined by monitoring the reduction in rate
standard deviation (SD) [45]. The scavenging effect for of transformation of NBT to monoformazan dye [47].
OH· was calculated from the following expression:
The solutions of MET, VitB2 and NBT were prepared
with 0.02 M phosphate buffer (pH = 7.8) avoiding
light. The reactions were monitored at 560 nm with
a UV/Vis spectrophotometer, and the rate of ab-
sorption change was determined. The percentage
Scavenging ratio (%) =[(A −A )/(Ac −A )]
i
0
0
×
100%
where A = absorbance in the presence of the test com- inhibition of NBT reduction was calculated using the
i
pound; A = absorbance of the blank; Ac = absorbance following equation [48]: percentage inhibition of NBT
0
0
0
in the absence of the test compound, EDTA-Fe(II) and reduction = (1 − k /k) × 100, where k and k present
H O . the slopes of the straight line of absorbance values as
2
2
We compared the ability of the present compound a function of time in the presence and absence of SOD
to scavenge hydroxyl radicals with those of the well- mimic compound (SOD is superoxide dismutase),
known natural antioxidants mannitol and vitamin C, respectively. The IC50 values for the complexes
using the same method as reported in a previous pa- were determined by plotting the graph of percentage
per [46]. The 50% inhibitory concentration (IC ) inhibition of NBT reduction against the increase in
5
0
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G. Pan et al. · A Lutetium(III) Complex
265
the concentration of the complex. The concentration studied by electronic absorption titration, ethidium
of the complex which causes 50% inhibition of NBT bromide-DNA displacement experiments and viscos-
reduction is reported as IC .
ity measurements. The results indicate that the Lu(III)
5
0
The Lu(III) complex shows an IC value of complex shows higher affinity than the free ligand and
5
0
−5
−1
4
.06 × 10 L mol (Fig. 5b), which indicates that it interacts with CT-DNA through the groove mode. In
has potent scavenging activity for the superoxide radi- addition, the antioxidant activities of the complex were
−
·
cal (O ). The Lu(III) complex exhibits good superox- investigated. The Lu(III) complex exhibited activities
2
·
−·
2
ide radical scavenging activity and may be an inhibitor against OH and O radicals in in vitro studies. Re-
−·
or a drug) to scavenge superoxide radicals (O ) in sults obtained from our present work could be useful
2
(
vivo which needs further investigation.
to understand the mechanism of interactions of small
molecules with DNA and thus be helpful in the devel-
opment of biological, pharmaceutical and physiologi-
cal implications.
Conclusions
In summary, a novel Lutetium(III) complex based
on the Schiff base ligand bis(N-salicylidene)-3-
oxapentane-1,5-diamine has been synthesized and
characterized. Its crystal structure has been determined
Acknowledgement
The authors acknowledge the financial support and grant
from ‘Qing Lan’ Talent Engineering Funds by Lanzhou Jiao-
by X-ray crystallography. The binding modes of the tong University. This work was also supported by the Funda-
ligand and the complex with CT-DNA have been mental Research Funds for the Universities (212086).
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