DNA-binding properties and antioxidant activity of lanthanide complexes with the Schiff base derived from 3-carbaldehyde chromone and isonicotinyl hydrazine

Article abstract of DOI:10.1080/00958972.2010.496127

Structural analyses indicate that the ligand and lanthanide ions form mononuclear 10-coordinate ([Ln L₂ (NO₃)₂] NO₃ [Ln(III) = La, Sm, Nd, and Yb; L is chromone-3-carbaldehyde- (isonicotinoyl) hydrazone) complexes with 1 : 2 metal-to-ligand stoichiometry. DNA-binding studies show that the ligand and its lanthanide complexes can bind to calf thymus DNA via an intercalation mode with binding constants of 10 ⁵ (mol L^-1)^-1, and the lanthanide complexes bind stronger than the free ligand alone. Antioxidant activities of the ligand and lanthanide complexes were determined by superoxide and hydroxyl radical scavenging methods in vitro. The ligand and complexes possess strong scavenging effects, and the lanthanide complexes show stronger antioxidant activities than the ligand and some standard antioxidants, such as vitamin C.

Full text of DOI:10.1080/00958972.2010.496127

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DNA-binding properties and antioxidant
activity of lanthanide complexes
with the Schiff base derived from
3-carbaldehyde chromone and
isonicotinyl hydrazine
Yong Li a & Zhengyin Yang a
a College of Chemistry and Chemical Engineering, State Key
Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P.R. China
Version of record first published: 25 Jun 2010.
To cite this article: Yong Li & Zhengyin Yang (2010): DNA-binding properties and antioxidant
activity of lanthanide complexes with the Schiff base derived from 3-carbaldehyde chromone and
isonicotinyl hydrazine, Journal of Coordination Chemistry, 63:11, 1960-1968
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Journal of Coordination Chemistry
Vol. 63, No. 11, 10 June 2010, 1960–1968
DNA-binding properties and antioxidant activity of lanthanide
complexes with the Schiff base derived from 3-carbaldehyde
chromone and isonicotinyl hydrazine
YONG LI and ZHENGYIN YANG*
College of Chemistry and Chemical Engineering, State Key Laboratory of Applied Organic
Chemistry, Lanzhou University, Lanzhou 730000, P.R. China
(Received 1 August 2009; in final form 10 April 2010)
Structural analyses indicate that the ligand and lanthanide ions form mononuclear
10-coordinate ([Ln L2 ꢀ (NO3)2] ꢀ NO3 [Ln(III) ¼ La, Sm, Nd, and Yb; L is chromone-
3-carbaldehyde-(isonicotinoyl) hydrazone) complexes with 1 : 2 metal-to-ligand stoichiometry.
DNA-binding studies show that the ligand and its lanthanide complexes can bind to calf
thymus DNA via an intercalation mode with binding constants of 105 (mol Lꢁ1 ꢁ1, and the
)
lanthanide complexes bind stronger than the free ligand alone. Antioxidant activities of the
ligand and lanthanide complexes were determined by superoxide and hydroxyl radical
scavenging methods in vitro. The ligand and complexes possess strong scavenging effects, and
the lanthanide complexes show stronger antioxidant activities than the ligand and some
standard antioxidants, such as vitamin C.
Keywords: Chromone-3-carbaldehyde-(isonicotinoyl) hydrazone; Lanthanide complexes;
DNA-binding properties; Antioxidant activity
1. Introduction
A large percentage of chemotherapeutic anticancer drugs are compounds which interact
with DNA directly or prevent the proper relaxation of DNA (through the inhibition of
topoisomerases). DNA-targeting cancer drugs continue to be developed, as evidenced
by the recent approval of belotecan [1, 2]. Given the applications of DNA-targeting
drugs for cancer and beyond, the investigation of drug–DNA interactions is of
considerable interest. Drug–DNA interactions can be classified into three major
categories: intercalation, groove binding, and external static electronic effects [3].
Because DNA intercalators have been extensively used as antitumor, antineoplastic,
antimalarial, antibiotic, and antifungal agents, DNA intercalation binding mode is
widely studied [2]. Chromones (1-benzopyran-4-one), a group of naturally and widely
distributed compounds ubiquitous in nature, especially in the plant kingdom [4], receive
considerable attention, mainly due to their biological and physiological activities, such
as antimycobacterial, antifungal, anticonvulsant, antimicrobial, mushroom tyrosinase
*Corresponding author. Email: yangzy@lzu.edu.cn
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2010 Taylor & Francis
DOI: 10.1080/00958972.2010.496127

Lanthanide Schiff base
1961
inhibition activities, and intermediates to many products of fine chemical industries
[5, 6]. Some hydrazones and their metal complexes often possess diverse biological and
pharmaceutical activities, such as antimicrobial, antituberculostatic, anticancer,
antioxidant properties [7–10]. Furthermore, Schiff bases are also able to inhibit the
growth of several animal tumors, and some chelates have shown good antitumor
activities against tumors [11]. Over production of activated oxygen species, superoxide
anion (Oꢂ2ꢁ) and hydroxyl radical (HO.), generated by normal metabolic process, is
considered to be the main contributor to the oxidative damage of biomolecules, such as
DNA, lipids, and proteins; thus, accelerating cancer, aging, inflammation, cardio-
vascular, and neurodegenerative diseases [12]. The potential value of antioxidants has
already prompted investigators to search for the cooperative effects of metal complexes
and natural compounds to improve the antioxidant activity and cytotoxicity [13].
Herein, we report the synthesis and characterization of a Schiff-base ligand,
chromone-3-carbaldehyde-(isonicotinoyl) hydrazone (L), and its lanthanide complexes.
Their DNA-binding modes and antioxidant activities were investigated systematically.
Our work will be useful to seek and design new antitumor drugs and antioxidants,
as well as to better understand the DNA-binding modes and helical conformation of
nucleic acids.
2. Experimental
2.1. Materials and instrumentation
Ethidium bromide (EB) and calf thymus DNA (CT DNA) were purchased from Sigma
Chemical Co. All chemicals and solvents were of analytical reagent grade, and used
without purification unless otherwise noted.
All the experiments involved with the interaction of the ligand and complexes with
CT DNA were carried out in doubly distilled water buffer containing 5 mmol Lꢁ1 Tris
[Tris(hydroxymethyl)-aminomethane] and 50 mmol Lꢁ1 NaCl and adjusted to pH 7.1
with hydrochloric acid. Solution of CT DNA in Tris-HCl gave ratios of UV absorbance
of about 1.8–1.9 : 1 at 260 and 280 nm, indicating that the CT DNA was sufficiently
free of proteins [14]. The CT DNA concentration per nucleotide was determined
spectrophotometrically by employing an extinction coefficient of 6600 (mol L )
ꢁ1 ꢁ1 cmꢁ1
at 260 nm [15]. The ligand and complexes were dissolved in a solvent mixture of 1%
DMF and 99% Tris-HCl buffer (pH 7.1) at 1.0 ꢃ 10ꢁ5 mol Lꢁ1
.
Carbon, hydrogen, and nitrogen were determined using an Elemental Vario EL
analyzer. The metal contents of the complexes were determined by titration with EDTA
(xylenol orange tetrasodium salt used as indicator and hexamethylidynetetraimine as
buffer). The melting points were determined on a Beijing XT4-100X microscopic
melting point apparatus (the thermometer was not corrected). The IR spectra were
obtained in KBr discs on a Thermo Mattson FTIR spectrophotometer from 4000
to 400 cmꢁ1. 1H NMR spectra were recorded on a Varian VR 300 MHz spectrometer in
DMSO-d6 with tetramethylsilane (TMS) as an internal standard. Mass spectra
were performed on an APEX II FT-ICR MS instrument using DMF as
mobile phase. Conductivity measurements were performed in DMF solution with a
DDS-11C conductometer at 25.0ꢄC. UV-Vis spectra were recorded on a Shimadzu

1962
Y. Li and Z. Yang
UV-240 spectrophotometer. Fluorescence spectra were recorded on a Hitachi RF-4500
spectrofluorophotometer at constant room temperature.
2.2. Preparation of the ligand (L)
Scheme of the synthesis of the ligand is shown in figure 1. 3-Carbaldehyde chromone
was prepared according to the literature methods [16]. An ethanol solution containing
isonicotinyl hydrazine (1.37 g, 10 mmol) was added dropwise to another ethanol
solution containing 3-carbaldehyde chromone (1.74 g, 10 mmol). The mixture was
refluxed on an oil bath for 2 h with stirring and a yellow precipitate was formed. The
yellow precipitate was filtered, washed several times with ethanol, and recrystallized
from DMF and water to give L, which was then dried in a vacuum. Yield: 73.3%; m.p.
187–189ꢄC; Anal. Calcd for C16H11N3O3: C, 65.5; H, 3.8; N, 14.3; Found (%): C, 65.8;
H, 3.7; N, 14.4. IR ꢀmax (cmꢁ1): ꢀ(carbonyl)C¼O: 1648, ꢀ(hydrazonic)C¼O: 1702, ꢀC¼N
:
1601 cmꢁ1. Umax (nm): 266, 302 nm. L (DMSO-d6 300 MHz): ꢁ 11.83 (1H, s, ¼NNH),
8.85 (1H, s, 9-H), 8.78 (2H, d, J ¼ 6.3 Hz, 11, 110-H), 8.64 (1H, s, 2-H), 8.13 (1H, d,
J ¼ 8.7 Hz, 5-H), 7.88 (3H, m, PhH, 7, 10, 100-H), 7.72 (1H, d, J ¼ 1.7 Hz, 8-H), 7.55
(1H, t, J ¼ 8.7, 2.5 Hz, 6-H).
2.3. Preparation of the complexes
The ligand (1.0 mmol, 0.293 g) and La(III) nitrate (0.5 mmol, 0.217 g) were added
together in ethanol (150 mL). The solution was refluxed on an oil bath for 2 h with
stirring and a white precipitate, the La(III) complex, was separated from the solution by
suction filtration, purified by washing several times with ethanol, and dried for 24 h in a
vacuum. Sm(III), Nd(III), and Yb(III) complexes were prepared in the same way. Anal.
Calcd for La(III) complex C32H22N9O15La: C, 42.2; H, 2.4; N, 13.8; La, 15.2; Found
(%): C, 42.3; H, 2.5; N, 13.5; La, 15.2. IR ꢀmax (cmꢁ1): ꢀ(carbonyl)C¼O: 1589,
ꢀ
ꢀ
(hydrazonic)C¼O: 1635, ꢀC¼N: 1560, ꢀNO : 1469, 1388, 1322, 1180, 821, ꢀM–O: 603,
3
M–N: 434 cmꢁ1. Umax (nm): 275, 307 nm. Lm (S cm2 molꢁ1): 80.5. Anal. Calcd for
OH
OH
OCOCH3
COCH3
(CH3CO)2CO
98% H2SO4
AlCl3
POCl3
DMF
D
3
1
2
8
O
O
O
H
7
6
N
N
NH2
2
10
11
9
4
CHO
C
N
NH
N
5
H
O
O
O
11
„
„
10
5
4
Figure 1. Synthesis of the ligand (L).

Lanthanide Schiff base
1963
Sm(III) complex C32H22N9O15Sm: C, 41.6; H, 2.4; N, 13.7; Sm, 16.3. Found (%):
C, 41.5; H, 2.5; N, 13.6; Sm, 16.3. IR ꢀmax (cmꢁ1): ꢀ(carbonyl)C¼O: 1616, ꢀ(hydrazonic)C¼O
:
1638, ꢀC¼N: 1576, ꢀNO : 1483, 1394, 1324, 1182, 817, ꢀM–O: 608, ꢀM–N: 420 cmꢁ1. Umax
3
(nm): 273, 307 nm. Lm (S cm2 molꢁ1): 88.5. Anal. Calcd for Nd(III) complex
C32H22N9O15Nd: C, 41.9; H, 2.4; N, 13.8; Nd, 15.7. Found (%): C, 41.8; H, 2.4; N,
13.7; Nd, 15.6. IR ꢀmax (cmꢁ1): ꢀ(carbonyl)C¼O: 1627, ꢀ(hydrazonic)C¼O: 1639, ꢀC¼N: 1562,
ꢀ
NO : 1462, 1390, 1320, 1180, 813, ꢀM–O: 604, ꢀM–N: 427 cmꢁ1. Umax (nm): 275, 308 nm.
3
Lm (S cm2 molꢁ1): 75.7. Anal. Calcd for Yb(III) complex C32H22N9O15Yb: C, 40.6; H,
2.3; N, 13.3;Yb, 18.3. Found (%): C, 40.7; H, 2.4; N, 13.3; Yb, 18.4. IR ꢀmax (cmꢁ1):
ꢀ
(carbonyl)C¼O: 1614, ꢀ(hydrazonic)C¼O: 1636, ꢀC¼N: 1578, ꢀNO3: 1466, 1384, 1322, 1181,
815, ꢀM–O: 601, ꢀM–N: 416 cmꢁ1. Umax (nm): 276, 306 nm. Lm (S cm2 molꢁ1): 91.0.
3. Results and discussion
3.1. Structure of Ln(III) complexes
The lanthanide complexes were prepared by direct reactions of chromone-3-
carbaldehyde-(isonicotinoyl) hydrazone (L) with appropriate mole ratios of
Ln(NO3)3 ꢀ 6H2O (Ln ¼ La, Sm, Nd, and Yb) in ethanol. All the lanthanide complexes
are yellow powders, stable in atmospheric conditions for extended periods, and easily
soluble in DMF and DMSO; slightly soluble in ethanol, methanol, and acetone;
insoluble in benzene, water, and diethyl ether. The melting points of the lanthanide
complexes exceed 300ꢄC. The molar conductivities of lanthanide complexes are around
75.7–91.0 S cm2 molꢁ1 in DMF solution indicating that all of them are 1 : 1 electrolytes
[17]. Elemental analyses indicate that all the lanthanide complexes are 1 : 2 metal-
to-ligand stoichiometry.
IR spectra of the lanthanide complexes are similar. ꢀ(carbonyl)C¼O and ꢀ(hydrazonic)C¼O
of the free ligand appear at 1648 and 1702 cmꢁ1, respectively, and for the complexes
these shift to 1616 and 1638 cmꢁ1 with Dꢀ(ligand–complexes) equal to 30 and 64 cmꢁ1
.
A band at 608 cmꢁ1 is assigned to ꢀM–O, demonstrating that the oxygen of carbonyl
has formed a bond with lanthanide [18]. The shifts of the wavenumbers indicate that
the Ln–O (hydrazonic) bond is stronger than the Ln–O (carbonyl) bond. The band
at 1601 cmꢁ1 for free ligand assigned to ꢀC¼N shifts to 1576 cmꢁ1 for the complexes,
Dꢀ(ligand–complexes) of 25 cmꢁ1. Weak bands at 420 cmꢁ1 are assigned to ꢀM–N in
the complexes, confirming that nitrogen of the imino-group bonds to lanthanide
ions [19]. Absorption bands of the coordinated nitrates were observed at 1483 (ꢀas)
and 817 (ꢀs) cmꢁ1. The ꢀ3 (E0) of free nitrates appear at 1394 cmꢁ1 for the complexes.
In addition, the separation of the two highest frequency bands jꢀ4 – ꢀ1j is approximately
160 cmꢁ1, and accordingly the coordinated NOꢁ3 is bidentate [20].
UV-Vis spectra of the ligand and lanthanide complexes were measured in
Tris-HCl buffer solution. Electronic spectra of the ligand have a strong band at
Umax ¼ 266 nm (" ¼ 1.70 ꢃ 104 (mol L
)
ꢁ1 ꢁ1 cmꢁ1) and a medium band at Umax ¼ 302 nm
(" ¼ 9.36 ꢃ 103 (mol L
)
ꢁ1 ꢁ1 cmꢁ1). Lanthanide complexes also yield two bands,
shifted to 273–276 nm (" ¼ 1.04 – 2.41 ꢃ 104 (mol L
)
ꢁ1 ꢁ1 cmꢁ1
)
and 306–308 nm
(" ¼ 2.51ꢁ2.76 ꢃ 104 (mol L
)
ꢁ1 ꢁ1 cmꢁ1).

1964
Y. Li and Z. Yang
The electrospray ionization (ESI) mass spectra of La(III) complex show peaks at 786,
723, and 294, which can be assigned to the fragments [La(III) complexꢁ2NO3–H]þ,
[La(III) complex–3NO3–2H]þ, and [La(III) complex–3NO3–L–La þ H]þ, respectively.
Since the crystal structures of the Ln(III) complexes have not been obtained, we
determined the structures of Ln(III) complexes on the basis of elemental analyses,
molar conductivities, mass spectra, IR spectra, UV-Vis spectra, and our previous work
[21–23], indicating that the ligand and lanthanide ions form mononuclear 10-coordinate
[Ln L2 ꢀ (NO3)2] ꢀ NO3 [Ln(III) ¼ La, Sm, Nd, and Yb; L is chromone-3-carbaldehyde-
(isonicotinoyl) hydrazone] complexes with 1 : 2 metal-to-ligand stoichiometry at the
Ln(III) centers (figure 2).
3.2. DNA-binding properties
Methods of investigating DNA-binding properties, such as electronic absorption
titration, fluorescence spectra, and viscosity measurements are given in the
Supplementary material. Electronic absorption titration is one of the most useful
techniques for DNA-binding studies of metal complexes. The absorption spectra of the
ligand and complexes in the absence and presence of DNA are similar and absorption
spectra of Nd(III) complex are given (figure S1). In the presence of DNA, absorption
bands at 275 nm for the ligand, La(III), Sm(III), Nd(III), and Yb(III) complexes
exhibited hypochromism of about 14.68%, 31.34%, 24.36%, 41.78%, and 24.57%,
respectively. Absorption bands at 308 nm for the ligand, La(III), Sm(III), Nd(III), and
Yb(III) complexes also exhibited hypochromism of about 32.46%, 41.04%, 37.80%,
41.31%, and 37.30%, respectively, accompanied by a small red shift of no more than
3 nm. Moreover, isobetic points at 335–342 nm for the ligand and complexes are
observed, indicating an equilibrium between the investigated compound and DNA.
These results suggest an intimate association of the compound with DNA via
intercalation. After intercalating the base pairs of DNA into the compound, the ꢂ*
orbital of the intercalated ligand can couple with the ꢂ orbital of the DNA base pairs,
O
H
N
N
N
O
O
O
O
O
O
O
O
N
Ln
·NO3
O
N
O
H
N
N
N
O
Figure 2. Suggested structure of the Ln(III) complexes.

Lanthanide Schiff base
1965
thus, decreasing the ꢂ ! ꢂ* transition energy and resulting in the bathochromism.
The coupling ꢂ orbital is partially filled by electrons, thus, decreasing the transition
probabilities and concomitantly resulting in hypochromism [24]. Nd(III) complex
shows more hypochromicity than the free ligand and other complexes, indicating that
the binding strength of Nd(III) complex is stronger than the other compounds.
In order to test if the compounds bind to DNA via intercalation, EB was employed
(figure S2) because EB interacts with DNA as a typical indicator of intercalation.
The maximal absorption of EB at 479 nm decreases and shifts to 486 nm in the presence
of CT DNA, which is a characteristic of intercalation. Curve (b) shows the absorption
of a mixed solution of EB, DNA, and Nd(III) complex. The absorption at 494 nm
increases compared with curve (c). These may result from two reasons: (1) EB bound to
the free ligand and complexes strongly, resulting in decrease of the amount of EB
intercalated into DNA; (2) there exists competitive intercalation between the
compounds and EB with DNA, so releasing some free EB from the DNA–EB
system. However, the former reason could be precluded because there were no new
absorption peaks appearing.
Upon addition of DNA, the fluorescence emission intensity of every investigated
compound increases steadily at room temperature (figure S3). According to the
Scatchard equation, a plot of r/Cf versus r gave the intrinsic binding constants Kb of
(2.2 ꢅ 0.3) ꢃ 105, (4.0 ꢅ 0.6) ꢃ 105, (2.6 ꢅ 0.5) ꢃ 105, (7.6 ꢅ 0.9) ꢃ 105, (3.1 ꢅ 0.5) ꢃ 105
(mol Lꢁ1 ꢁ1
from the fluorescence data for the ligand, La(III), Sm(III), Nd(III), and
)
Yb(III) complexes, respectively. The Stern–Volmer plot is linear, indicating that only
one type of binding process occurs. Fluorescence increasing may be attributed to the
compounds protected from solvent water by the hydrophobic environment inside the
DNA helix [25]. Results obtained from fluorescence titrations show that the lanthanide
complexes bind to DNA more strongly than the free ligand, probably attributed to the
extension of the ꢂ system of the intercalated ligand and the coordination of lanthanide
ions, which can lead to a planar area greater than that of the free ligand and the
coordinated ligand penetrating more deeply into and stacking more strongly with
the DNA base pairs.
The emission spectra of EB bound to DNA in the absence and the presence of every
compound have been recorded for [EB] ¼ 4 ꢃ 10ꢁ7 M, [DNA] ¼ 5 ꢃ 10ꢁ6 M for
increasing amounts for every compound; emission fluorescence intensities of the
DNA–EB system decrease with the increasing amounts of Nd(III) complex (figure S4).
The emission band at 589 nm of the DNA–EB system decreases in fluorescence intensity
upon addition of every compound at diverse r (¼[Compound]/[DNA]) values indicating
competition of the compounds with EB in binding to DNA. The observed quenching of
DNA–EB fluorescence intensity for the compounds suggests that they displace EB from
the DNA–EB system and interact with DNA via the intercalative mode [26]. The
quenching constants Kq are often used to evaluate the quenching efficiency for every
compound and vary with experimental conditions. Kq values are given by the ratio of
the slope to the intercept and Kq values for the ligand and La(III), Sm(III), Nd(III), and
Yb(III) complexes are (2.57 ꢅ 0.03) ꢃ 104 (mol L
)
ꢁ1 ꢁ1, (3.2 ꢅ 0.2) ꢃ 104 (mol Lꢁ1 ꢁ1
) ,
and (3.1 ꢅ 0.3) ꢃ 104
(2.7 ꢅ 0.2) ꢃ 104 (mol Lꢁ1 ꢁ1
)
,
(5.7 ꢅ 0.4) ꢃ 104 (mol Lꢁ1 ꢁ1
)
,
(mol L )
ꢁ1 ꢁ1, respectively. Experimental results indicate that all compounds bind to
DNA via intercalation and the complexes bind to DNA more strongly than the free
ligand [27].

1966
Y. Li and Z. Yang
A useful technique to prove intercalation is viscosity measurements, which are
sensitive to length changes of DNA and regarded as the least ambiguous and the most
critical tests of binding mode in the solution in the absence of crystallographic
structural data or NMR spectra [28]. Under appropriate conditions, the intercalation of
drugs, such as EB causes a significant increase in the viscosity of DNA solution due to
the increase in separation of base pairs of intercalation sites and hence results in an
increase in overall DNA contour length. On the other hand, drugs such as [Ru(bpy)3]2þ
,
which interacts with DNA by an electrostatic binding mode, have no influence on DNA
viscosity [29]. Upon increasing the amounts of our compounds, the relative viscosities
of DNA increase steadily with the increasing concentrations of compounds (figure S5).
The increased degree of viscosity, which depend on the binding affinity of compounds
to DNA, follow the order Nd(III) complex 4 La(III) complex 4 Yb(III) complex 4
Sm(III) complex 4 L. Experimental results suggest that all the complexes and ligand
intercalate between DNA base pairs and the binding affinities of the complexes are
higher than that of the free ligand.
On the basis of all the spectroscopic studies together with the viscosity measurements,
we find that the free ligand and its lanthanide complexes bind to DNA via an
intercalative mode and the complexes bind to DNA more strongly and deeply than the
free ligand (figure 3).
3.3. Antioxidant activity
Methods of investigating antioxidant activity of the ligand and its complexes are given
in the Supplementary material. IC50 values for the ligand and complexes for HO. are
28.55 and 3.62–10.48 mmol Lꢁ1, respectively (figure S6a). The inhibitory effect of the
compounds is marked and the average suppression ratio for HO. increases with
increasing compound concentration. The average suppression ratio of the lanthanide
complexes is higher than the free ligand due to the chelation of organic molecules to
La(III), Sm(III), Nd(III), Yb(III), which can exert selective effects on scavenging
radicals of the biological system. The plots of superoxide radical scavenging effect (%)
for the ligand and complexes have been made (figure S6b). Inhibitory effect of the
compounds tested on Oꢂ2ꢁ is concentration dependent and the suppression ratio
increases with the increasing sample concentrations in the range tested. The average
suppression ratio of the free ligand (IC50 ¼ 96.02 mmol Lꢁ1) for O2ꢂꢁ is the least and
La(III) complex (IC50 ¼ 2.34 mmol Lꢁ1) is the most effective. The IC50 value of ascorbic
Figure 3. Molecular mode for Ln(III) complexes (via an intercalation mode).

Lanthanide Schiff base
1967
acid (Vc, a standard agent for non-enzymatic reaction) for HO. is 1.537 mg mlꢁ1
(8.727 mmol), and the scavenging effect for Oꢂ2ꢁ is only 25% at 1.75 mg mlꢁ1
(9.94 mmol) [30]. Notably, the investigated ligand and lanthanide complexes have
much stronger scavenging abilities for HO. and O2ꢂꢁ radicals than the standard
antioxidant (vitamin C).
4. Conclusion
A novel ligand, chromone-3-carbaldehyde-(isonicotinoyl) hydrazone, and its La(III),
Sm(III), Nd(III), and Yb(III) complexes were synthesized. The structures of the Ln(III)
complexes were determined on the basis of elemental analyses, molar conductivities,
1
IR spectra, H NMR spectra, mass spectra, and UV-Vis spectra. With the changes of
UV-Vis spectra, fluorescence spectra, and relative viscosities of DNA, DNA-binding
studies indicate that the ligand and lanthanide complexes bind to DNA via an
intercalation mode and the lanthanide complexes bind to DNA more strongly and
deeply than the free ligand. This is due to the lanthanide complexes having two parallel
M–L planes, which may well be an indicator of the intercalation behavior of these
complexes binding to DNA. The lanthanide complexes possess better antioxidant
activity than the ligand because of the chelating effects between the ligand and
lanthanide ions. Results obtained from this work would be useful to understand
the mechanism of interactions of small molecules binding to DNA and helpful in
the development of potential applications in the biological, pharmaceutical, and
physiological fields in the future.
Acknowledgments
This work is supported by the National Natural Science Foundation of China
(20475046) and Gansu NSF (0710RJZA012).
References
[1] M. Hegde, A.D. Schmidt. Annu. Rep. Med. Chem., 40, 443 (2005).
[2] R. Palchaudhuri, P.J. Hergenrother. Curr. Opin. Biotechnol., 18, 1 (2007).
[3] S. Mahadevan, M. Palaniandavar. Inorg. Chim. Acta, 254, 291 (1997).
[4] V.Y. Sosnovskikh. Russ. Chem. Rev., 72, 489 (2003).
[5] G. Singh, R. Singh, N.K. Girdhar, M.P.S. Ishar. Tetrahedron, 58, 2471 (2002).
[6] L.Z. Piao, H.R. Park, Y.K. Park, S.K. Lee, J.H. Park, M.K. Park. Chem. Pharm. Bull., 50, 309 (2002).
[7] B.K. Kaymakcioglu, S. Rollas. Farmaco, 57, 595 (2002).
[8] S. Kuc¸ ukguzel, S. Rollas, I. Kuc¸ ukguzel, M. Kiraz. Eur. J. Med. Chem., 34, 1093 (1999).
¨ ¨ ¨ ¨ ¨ ¨
[9] S.R. Zhang, A.D. Sherry. J. Solid State Chem., 171, 38 (2003).
[10] Z.Y. Yang. Synth. React. Inorg. Met. Org. Chem., 30, 1265 (2000).
[11] E.M. Nddnett, P.D. Mooney. J. Med. Chem., 15, 339 (1972).
[12] S.Y. Yu, S.X. Wang, Q.H. Luo, L.F. Wang, R.P. Zhou, G. Xing. Polyhedron, 12, 1093 (1993).
[13] S.Y. Chiang, J. Welch, F.J. Rauscher, T.A. Beerman. Biochemistry, 33, 7033 (1994).
[14] Y.Z. Cai, Q. Luo, M. Sun, H. Corke. Life Sci., 74, 2157 (2004).
[15] K.E. Heim, A.R. Tagliaferro, D.J. Bobilya. J. Nutr. Biochem., 13, 572 (2002).

1968
Y. Li and Z. Yang
[16] A. Nohara, T. Umetani, Y. Sanno. Tetrahedron Lett., 14, 1995 (1973).
[17] W.J. Geary. Coord. Chem. Rev., 7, 81 (1971).
[18] F. Marchetti, C. Pettinari, R. Pettinari, A. Cingolani, D. Leonesi, A. Lorenzotti. Polyhedron, 18, 3041
(1999).
[19] K.K. Narang, V.P. Singh. Transition Met. Chem., 18, 287 (1993).
[20] B.D. Wang, Z.Y. Yang, D.W. Zhang, Y. Wang. Spectrochim. Acta, Part A, 63, 213 (2006).
[21] B.D. Wang, Z.Y. Yang, Q. Wang, T.K. Cai, P. Crewdson. Bioorg. Med. Chem., 14, 1880 (2006).
[22] B.D. Wang, Z.Y. Yang, D.D. Qin, Z.N. Chen. J. Photochem. Photobiol. A: Chem., 194, 49 (2008).
[23] B.D. Wang, Z.Y. Yang, T.R. Li. Bioorg. Med. Chem., 14, 6012 (2006).
[24] A.M. Pyle, J.P. Rehmann, R. Meshoyrer, C.V. Kumar, N.J. Turro, J.K. Barton. J. Am. Chem. Soc., 111,
3051 (1989).
[25] H. Xu, K.C. Zheng, L.J. Lin, H. Li, Y. Gao, L.N. Ji. J. Inorg. Biochem., 98, 87 (2004).
[26] M. Lee, A.L. Rhodes, M.D. Wyatt, S. Forrow, J.A. Hartley. Biochemistry, 32, 4237 (1993).
[27] M. Chauhan, K. Banerjee, F. Arjmand. Inorg. Chem., 46, 3072 (2007).
[28] S. Satyanarayana, J.C. Dabrowiak, J.B. Chaires. Biochemistry, 31, 9319 (1992).
[29] S. Satyanarayana, J.C. Dabrowiak, J.B. Chaires. Biochemistry, 32, 2573 (1993).
[30] R. Xing, H. Yu, S. Liu, W. Zhang, Q. Zhang, Z. Li, P. Li. Bioorg. Med. Chem., 13, 1387 (2005).