Crystal structures, antioxidation, and DNA binding properties of Sm III complexes

Article abstract of DOI:10.1071/CH10302

The dinuclear Sm^III complexes with 1:1 metal to ligand stoichiometry were prepared from Sm(NO₃)₃·6H ₂O and three anionic tetradentate Schiff-base ligands derived from 8-hydroxyquinoline-2-carboxyaldehyde with be

Full text of DOI:10.1071/CH10302

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2011, 64, 345–354
Crystal Structures, Antioxidation, and DNA Binding
Properties of SmIII Complexes
A B
,
A C
,
B
B
Yongchun Liu,
Zhengyin Yang,
Kejun Zhang, Yun Wu,
B
B
Jihua Zhu, and Tianlin Zhou
A
College of Chemistry and Chemical Engineering, State Key Laboratory of Applied
Organic Chemistry, Lanzhou University, 730000 Lanzhou, China.
College of Chemistry and Chemical Engineering, Key Laboratory of Longdong
Biological Resources in Gansu Province, Longdong University,
745000 Qingyang, Gansu, China.
B
C
Corresponding author. Email: yangzy@lzu.edu.cn
The dinuclear SmIII complexes with 1:1 metal to ligand stoichiometry were prepared from Sm(NO3)3ꢀ6H2O and three
anionic tetradentate Schiff-base ligands derived from 8-hydroxyquinoline-2-carboxyaldehyde with benzoylhydrazine,
2-hydroxybenzoylhydrazine, and isonicotinylhydrazine, respectively. All the ligands and complexes can bind strongly
to calf thymus DNA through intercalation with the binding constants at 105–106 Mꢁ1, but complexes present stronger
affinities to DNA than ligands. All the ligands and complexes have strong abilities of antioxidation, but complexes and
ligands containing an active phenolic hydroxy group show stronger scavenging effects on hydroxyl radical, and SmIII
complex containing N-heteroaromatic substituent shows stronger scavenging effects for superoxide radical.
Manuscript received: 12 August 2010.
Manuscript accepted: 7 February 2011.
Introduction
such as carcinogenesis, drug-associated toxicity, inflammation,
atherogenesis, and aging in aerobic organisms.[7] The potential
value of antioxidants has prompted investigators to search for
the cooperative effects of metal complexes and natural com-
pounds for improving antioxidant activity and cytotoxicity.[8]
It has been recently demonstrated that some minor groove
binders for DNA are effective inhibitors of the formation of a
DNA/tumour-associated transplantation antigen(-box-)-binding
protein (TBP) complex or topoisomerases. Adding a reactive
entity endowed with oxidative properties should improve the
efficiency of inhibitors.[9]
Previously, the antioxidation and DNA binding properties
of EuIII complexes derived from these ligands were investi-
gated.[10] In this paper, the SmIII complexes were investigated
as the same methods. Furthermore, the substituent effects of
these compounds on antioxidation and DNA binding properties
were investigated further.
The chemistry of quinoline and its derivatives have attracted
special interest due to their therapeutic properties. Quinoline
sulfonamides have been used in the treatment of cancer, tuber-
culosis, diabetes, malaria, and convulsion.[1] Apart from the
magnetic and photophysical properties, the bioactivities of
lanthanides such as antimicrobe, antitumour, antivirus, anti-
coagulant action, enhancing natural killer and macrophage cell
activities, prevention from arteriosclerosis, etc., have also been
paid attention in recent decades.[2] In addition, Schiff bases are
able to inhibit the growth of several animal tumours, and some
metal chelates also have shown good antitumour activities
against animal tumours.[3] So, well designed organic ligands
enable a fine tuning of special properties of the metal ions.
DNA is an important cellular receptor, and many chemicals
exert their 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 depends on
the mode and affinity of the binding.[4] Several metal chelates,
as agents for mediation of strand scission of duplex DNA
and as chemotherapeutic agents, have been used as probes of
DNA structure in solution.[5] Moreover, AT-rich sequences are
believed to favour metal complex binding at the minor groove
when the handedness of the complex is complementary to that of
the right-handed helix of DNA.[6]
Results and Discussion
Synthesis of Ligands and SmIII Complexes
Three Schiff-base ligands, 8-hydroxyquinoline-2-carboxyaldehyde-
(benzoyl)hydrazone (1a, H2L1), 8-hydroxyquinoline-2-
carboxyaldehyde-(salicyloyl)hydrazone (1b, H2L2), and
8-hydroxyquinoline-2-carboxyaldehyde-(isonicotinyl)hydra-
zone (1c, H2L3) were prepared from equimolar amounts of
8-hydroxyquinoline-2-carboxyaldehyde and benzoylhydrazine,
2-hydroxybenzoylhydrazine and isonicotinylhydrazine as the
literature, respectively.[10] The synthetic routes for ligands are
presented in Scheme 1, then their powdered SmIII complexes
However, an excess of activated oxygen species in the forms
of superoxide anion (Oꢂ2–) and hydroxyl radical (OHꢂ), gener-
ated by normal metabolic processes, may cause various diseases
Ó CSIRO 2011
10.1071/CH10302
0004-9425/11/030345

346
Y. Liu et al.
(2a, 2b, and 2c) were easily prepared from the corresponding
ligands and equimolar amounts of Sm(NO3)3ꢀ6H2O. All the
SmIII complexes are of orange powders, stable in air, and soluble
in DMF and DMSO, but slightly soluble in methanol, ethanol,
acetonitrile, ethyl acetate, acetone, THF, and CHCl3. The
melting points of all of the SmIII complexes exceed 3008C.
suitable for X-ray measurements) at room temperature for
2 weeks. Crystal data and structure refinements for the X-ray
structural analyses, selected bond lengths, and angles of the
SmIII complexes are presented in Tables 1, 2, and Accessory
Publication.
The coordination sphere of ORTEP diagrams (30% prob-
ability ellipsoids) in Fig. 1a and b shows that the compositions
of 2a9 and 2b9 are of [SmL1(NO3)(DMF)2]2 and [SmL2(NO3)
(DMF)2]2, respectively. Either of 1a and 1b acts as a dibasic
tetradentate, binding to SmIII through the phenolate oxygen
atom, the nitrogen atom of quinolinato unit, the C¼N group,
Crystal Structure Analyses of the SmIII Complexes
The orange transparent, X-ray quality crystals of 2a9, 2b9, and
2c9 were obtained by vapour diffusion of diethyl ether into DMF
solution of the metal complexes (recrystallization in DMF
4
5
3
6
7
O
20
17
O
N
19
18
N
N
N
H
11
16
95% ethanol
OH
OH
R1
ϩ
R3
R2
O
1a (H2L1): R1 ϭ C, R2 ϭ H, R3 ϭ H
1b (H2L2): R1 ϭ C, R2 ϭ H, R3 ϭ OH
1c (H2L3): R1 – R2 ϭ N, R3 ϭ H
H2N
N
H
R1
R3
R2
Scheme 1. The synthetic routes for ligands.
Table 1. Crystal data and structure refinement for the metal complexes
Complex
[SmL1(NO3)(DMF)2]2 (2a9)
[SmL2(NO3)(DMF)2]2 (2b9)
2[SmL3(NO3)(DMF)2]2ꢀ5DMF (2c9)
CCDC deposition number
Chemical formula
Formula weight
T [K]
704943
704944
704945
C46H50N12O14Sm2
C46H50N12O16Sm2
1327.70
C103H131N33O33Sm4
2960.81
1295.68
294(2)
294(2)
294(2)
˚
Wavelength [A]
0.71073
0.71073
0.71073
Radiation
Mo-Ka
Monoclinic
Mo-Ka
Monoclinic
Mo-Ka
Triclinic
¯
Pi
Crystal system
Space group
P21/c
P21/c
˚
a [A]
11.3808(10)
11.5812(8)
12.5913(7)
˚
b [A]
˚
c [A]
18.755(2)
18.1196(13)
12.8473(10)
90.00
14.7267(8)
12.4846(12)
17.9592(9)
a [8]
b [8]
g [8]
90.00
90.4910(10)
93.216(2)
95.6680(10)
90.00
90.9250(10)
90.00
100.3210(10)
3275.6(3)
3
˚
V [A ]
2660.6(5)
2682.8(3)
Z
2
2
1
Dc [g cmꢁ3
]
1.617
1.646
1.501
m [mmꢁ1
F(000)
]
2.259
2.245
1.850
1292
1328
1492
Crystal size [mm]
min/max [8]
Index ranges
0.37 ꢃ 0.18 ꢃ 0.08
1.79–25.01
0.15 ꢃ 0.12 ꢃ 0.10
1.77–28.85
0.30 ꢃ 0.28 ꢃ 0.25
1.64–25.50
y
ꢁ13 ꢄ h ꢄ 13, ꢁ22 ꢄ k ꢄ 20,
ꢁ13 ꢄ l ꢄ 14
13176
ꢁ15 ꢄ h ꢄ 12, ꢁ20 ꢄ k ꢄ 24,
ꢁ15 ꢄ l ꢄ 16
16632
ꢁ14 ꢄ h ꢄ 15, ꢁ17 ꢄ k ꢄ 16,
ꢁ21 ꢄ l ꢄ 16
Reflections collected
17264
Independent reflections
Absorption correction
Max. and min. transmission
Refinement method
4661 (Rint ¼ 0.1095)
Semi-empirical from equivalents
0.8400 and 0.4887
Full-matrix least-squares on F2
4661/0/338
6649 (Rint ¼ 0.0355)
Semi-empirical from equivalents
0.7993 and 0.7314
Full-matrix least-squares on F2
6649/0/308
12067 (Rint ¼ 0.0169)
Semi-empirical from equivalents
0.6549 and 0.6069
Full-matrix least-squares on F2
12067/0/839
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I 42s(I)]
1.088
0.977
1.024
R1 ¼ 0.0669, wR2 ¼ 0.1228
R1 ¼ 0.1434, wR2 ¼ 0.1521
1.479/–0.922
R1 ¼ 0.0386, wR2 ¼ 0.0756
R1 ¼ 0.0686, wR2 ¼ 0.0855
0.942/–0.632
R1 ¼ 0.0393, wR2 ¼ 0.1057
R1 ¼ 0.0555, wR2 ¼ 0.1176
0.666/–0.967
R indices (allꢁd3ata)
˚
min/max [e A
r
]

Properties of SmIII Complexes
347
and the ꢁO–C¼N– group (enolized and deprotonated from
O¼C–NHꢁ–) of the aroylhydrazone side chain, where the bond
The data of molar conductance of the SmIII complexes in DMF
solutions indicate that they all act as non-electrolytes.[11]
˚
lengths of O–C and N¼C of 2a9 are 1.289(13) and 1.339(14) A,
˚
respectively, while 1.280(5) and 1.332(6) A for 2b9. In addition,
Infrared Spectrum Study of the Powdered Complexes
The characteristic IR spectrum band [nmax/cmꢁ1] data of the
powdered SmIII complexes are listed in Table S2. Carefully
compared with the characteristic IR bands of ligands, it comes to
the conclusion that: (1) 3429–3399br cmꢁ1 assigned to n(OH) of
H2O, 947–935w cmꢁ1 assigned to rr (H2O) and 656–639w cmꢁ1
assigned to rw (H2O) indicate coordinated water molecules
participating in the SmIII complexes;[12] (2) 1100–1102 cmꢁ1
assigned to n(C–OM) indicate the binding of metal ion to ligand
through an O–M linkage;[13] (3) 1682–1643s cmꢁ1 assigned to
n(CO) and 3576–3359v cmꢁ1 assigned to n(NH) of ligands
disappeared in all the IR spectra of SmIII complexes, indicating
that they participate in the SmIII complexes; (4) 1635–
1601 cmꢁ1 assigned to n(CN) of azomethines of the SmIII
complexes, shifting by 22–6 cmꢁ1 in comparison with bands of
ligands, indicate the nitrogen atoms of azomethines participat-
ing in the complexes; 1565–1548 cmꢁ1 assigned to n(CN) of
pyridines of the SmIII complexes, shifting by 9–16 cmꢁ1, indi-
cate the nitrogen atoms of pyridines also participating in the
complexes. However, the band of 1591 cmꢁ1 can be assigned
to n(CN) of free pyridine of isonicotinylhydrazine side chain;
(5) 535–521w cmꢁ1 assigned to n(MO) and 488–486w cmꢁ1
assigned to n(MN) further indicate that oxygen atom and
nitrogen atom participate in SmIII complexes; (6) all the
SmIII complexes show 1498–1492 (n1), 1316–1311 (n4), 1061–
one DMF molecule is binding orthogonally to the ligand-plane
from one side to the metal ion, while another DMF and a nitrate
(bidentate) are binding from the other. Dimerization of this
monomeric unit occurs through the phenolate oxygen atoms
leading to a central four-membered (SmO)2-ring with the
˚
˚
Smꢀ ꢀ ꢀSm separation of 4.0713(12) A for 2a9 and 4.0599(5) A
for 2b9. At the dimerization site, the ‘set off’ of the two SmL1-
2
planes by 1.702 A takes place and of the two SmL -planes by
˚
˚
1.766 A. However, the 2-hydroxyl substituent of 2b9 may form
an intra-molecular hydrogen bond with the adjacent nitrogen
˚
atom (1.839 A) of the same side chain.
The crystal structure of a dimolecule and dinuclear 2
[SmL3(NO3)(DMF)2]2ꢀ5DMF complex (2c9) with a 1:1 metal
to ligand and nine-coordination is shown in Fig. 1c. Dimeriza-
tion of the monomeric unit of one molecule occurs through the
phenolate oxygen atoms leading to a central four-membered
(SmO)2-ring with the Sm(1)ꢀ ꢀ ꢀSm(1)#1 separation of
˚
4.0291(5) A and another with the Sm(2)ꢀ ꢀ ꢀSm(2)#2 separation
˚
of 4.0171(5) A. At the dimerization sites, the ‘set off’ of the two
3
‘Sm(1)L -planes’ by 1.748 A takes place and of the two ‘Sm(2)
˚
3
L -planes’ by 1.733 A. Moreover, in one molecule (Sm(1))
˚
of the independent crystal cell, the O¼C–NH– group of the
isonicotinylhydrazine side chain has enolized and deprotonated
into ꢁO–C¼N– with the bond lengths of 1.277(7) and
1.320(8) A for ꢁO–C and N¼C, respectively, while in another
˚
1034 (n2), 839–811 (n3), 765–756 (n5), and 184–178 (n1–n4)cmꢁ1
,
molecule (Sm(2)), 1.286(6), and 1.309(7) A for ꢁO–C and
˚
indicating that nitrate ions bidentately participate in the SmIII
complexes.[10]
N¼C, respectively. In addition, there are five free DMF solvent
molecules in the lattice of 2c9, however, parts of them are
disordered.
Additionally, the ESI-MS data show that the m/z ([MþH]þ,
DMF solution) are 1297.1, 1329.2, and 1299.2 for dinuclear
complexes 2a9, 2b9, and 2c9, respectively, indicating that the
four-coordinated water molecules can be replaced by four DMF
molecules when the powdered SmIII complexes are dissolved
in DMF solution. Furthermore, the m/z data ([M/2þH]þ, DMF
solution), 648.2, 665.4, and 649.2, can also be found for 2a9, 2b9,
Structure Analyses of the Powdered SmIII Complexes
Elemental Analysis and Molar Conductance
Elemental analyses indicate that all the powdered SmIII com-
plexes are of 1:1 metal to ligand (stoichiometry) complexes.
Table 2. Important bond lengths and angles of 2a9, 2b9, and 2c9 (Sm1) complexes
N1
M
N1
N1
M
O1
N2
O2
O1
N2
O2
O1
N2
O2
N
N
N
OH
M
MЈ
M
MЈ
N
[SmL1(NO3)(DMF)2]2 (2a9)
[SmL2(NO3)(DMF)2]2 (2b9)
2[SmL4(NO3)(DMF)2]2ꢀ5DMF (2c9)
O1–M
2.462(7)
2.545(8)
2.591(9)
2.374(8)
2.420(7)
65.0(3)
2.445(3)
2.522(3)
2.582(3)
2.382(3)
2.426(3)
65.11(10)
61.35(12)
61.34(11)
1.766
2.441(4)
2.544(4)
2.562(5)
2.377(4)
2.423(4)
64.76(14)
61.87(16)
62.00(15)
1.748
N1–M
N2–M
O2–M
O1–M0
O1–M–N1
N1–M–N2
61.6(3)
N2–M–O2
61.5(3)
Distance between the parallel ML-planes
Distance between Mꢀ ꢀ ꢀM0
1.702
4.0713(12)
4.0599(5)
4.0291(5)

348
Y. Liu et al.
C23
N6
(a)
C22
indicating that complexes have paramagnetism or single elec-
trons in their molecular orbits, so the complexes do not have an
S¼0 ground state though they are dinuclear.
C21
C10 C9
C1
N2
C16
C15
C7
DNA Binding Properties
C17
C12
C8
N3
O7
C2
C6
Viscosity Titration Measurements
C4
N1
C3
Sm(1)
Viscosity measurements are very sensitive to changes in the
length of DNA, as viscosity is proportional to L3 for rod-like
DNA of length L. Viscosity titration measurements were carried
out to clarify the interaction mode between the investigated
compounds and CT-DNA. The effects of ligands and SmIII
complexes on the viscosities of CT-DNA are shown in Fig. S2.
With the ratios of the investigated compounds to DNA increas-
ing, the relative viscosities of DNA increase steadily, indicating
that there exists intercalation between all the ligands and SmIII
complexes with the DNA helix.[14,15] In addition, the relative
viscosities of DNA increase with the order of 1a 41b 41c,
the order of 2a 42b 42c and the orders of 1b 41a, 2b 42a,
2c 41c. These suggest the extents of the unwinding and
lengthening of the DNA helix by compounds and the affinities of
compounds binding toDNA, which may beduetothe key roles of
substituent effects and the larger coplanar structures of SmIII
complexes than those of ligands. Intercalation has been tradi-
tionally associated with molecules containing fused bi/tricyclic
ring structures, although atypical intercalators with non-fused
rings systems may be more prevalent than previously recog-
nized.[16] So it is logical that all the large coplanar SmIII com-
plexes containing fused multiple cyclic ring structures and
ligands containing fused bicyclic ring structures can bind to DNA
through intercalation.
C5
O1
C11
O2
O(1)#1
C14 C13
O4
N4
O3
O5
O6
C18
N5
C19
C20
C7
C5
(b)
C8
C6
C4
C3
O8
N6
C1
O7
C9
C10
C2
O6
N1
N3
O1
N2
Sm(1)
O2
O4
O3
C11
C12
O5
Sm(1)#1
O(1)#1
C21
C17
C20
C18
N4
C23
N5
C16
C22
C13
C19
C15
C14
Ultraviolet-visible (UV-vis) Spectroscopy Study
The UV-vis spectra values of the maximum absorption wave-
length (lmax), the molar absorptivity (e), and the hypochromicity
at lmax for ligands and SmIII complexes are listed in Table S3.
The UV-vis spectra of ligands show two types of absorpt-
ion bands at lmax in the regions of 290–295 (e ¼ 2.86–
104 Mꢁ1 cmꢁ1), which can be assigned to p–p* transition within
the organic molecules. The UV-vis spectra of SmIII complexes,
however, show two types of absorption bands at lmax in the
regions of 323–327 (e ¼ 3.66–4.39 ꢃ 104 Mꢁ1 cmꢁ1) and 371–
378 nm (e ¼ 2.75–3.60 ꢃ 104 Mꢁ1 cmꢁ1), which can be respec-
tively assigned to p–p* transition of the larger conjugated
organic molecules and p–p* of the C¼N–N¼C groups coupled
with charge transfer from ligand to metal ion (L-Sm3þ).[12]
The band shift of lmax and the change of e for complex in com-
parison with ligand indicate the formation of the SmIII complex.
Upon successive addition of CT-DNA, the UV-vis absorp-
tion bands of 1a, 1b, and 1c show a progressive hypochromism
of 34.3% at 295 nm, 30.1% at 294 nm, and 8.4% at 290 nm by
C18
(c)
C19
N6
C17
3.55 ꢃ 104 Mꢁ1 cmꢁ1
)
and 323–329 nm (e ¼ 1.78–2.36 ꢃ
O6
O5
O1
C6
N5
N3
O3
C5 O4
C1
O(2)#2
Sm(1)
C4
O2
C2
C13
C12
N2
C3
C14
N4
C8
N1
C20
O7
C11
C15
C16
C7
C10
C9
C22
C21
N7
Fig. 1. Coordination spheres of ORTEP diagrams of (a) [SmL1(NO3)
(DMF)2]2, (b) [SmL2(NO3)(DMF)2]2, and (c) 2[SmL3(NO3)(DMF)2]2ꢀ5DMF
complexes.
approximately saturated titration end points with CDNA:Cligand
¼
1.4–2.0:1, with 1, 3, and 0 nm red shifts respectively, of
absorption bands in the region of 290–295 nm. 1a, 1b, and 1c
show another progressive hypochromism of 11.1% at 323 nm,
18.1% at 329 nm, and 1.0% at 325 nm, respectively, with 1, 3,
and 0 nm blue shifts in the region of 323–329 nm. Similarly,
upon successive addition of CT-DNA, the UV-vis absorption
bands of 2a and 2b show a progressive hypochromism of 24.9%
at 324 nm and 20.6% at 323 nm by approximately saturated
titration end points at CDNA:Ccomplex ¼ 1.4–1.6:1, with 1 and
2 nm red shifts respectively, of absorption bands. However, 2c
and 2c9, respectively, indicating that there exists monomeric
unit in DMF solution. In summary, the results of elemental
analyses, molar conductance, IR and ESI-MS data indicate that
all of the powdered metal complexes are structurally similar to
each other and the compositions are of [SmL1–3(NO3)(H2O)2]2,
which slightly differ from their crystal structures. Furthermore,
compared with the spectrum of free ligand, the 1H NMR spectra
of complexes widen and shift to a certain extent (Fig. S1),

Properties of SmIII Complexes
349
(a) 2.4
2.0
show a slightly unsteady hypochromism of 0.54% at 327 nm and
no band shift in the region of 323–327 nm by the saturated
titration end point at CDNA:Ccomplex ¼ 1.6:1. 2a, 2b, and 2c show
another progressive hypochromism of 22.3% at 371 nm, 21.5%
at 378 nm, and 0.94% at 374 nm, respectively, but all of them
show no band shift in the region of 371–378 nm. In addition,
isosbestic points at 327–343 nm for ligands and 408–422 nm
for SmIII complexes are observed, indicating that a reaction
equilibrium between every investigated compound and DNA
takes place.
1b
1c
1a
1.6
1.2
Absorption titration can monitor the interaction of a com-
pound with DNA. The obvious hypochromism and red shift are
usually characterized by the non-covalently intercalative bind-
ing of a compound to DNA helix, due to the strong stacking
interaction between the aromatic chromophore of the compound
and base pairs of DNA.[17] Some studies have revealed that
hypochromism and no band shift or small red shifts at lmax are
in keeping with groove binding.[18] In order to clarify whether
hypochromism and the red shift of the absorption band can be
used as positive criterions for DNA binding mode, UV-vis
titration experiments of ethidium bromide (EB)-DNA system
were performed by the same methods as these investigated
compounds. The UV-vis titration spectra of EB-DNA system
and the plot of A/Ao versus CDNA/CEB at 285 nm (lmax) are
shown in Fig. S3. Upon successive addition of CT-DNA, the
absorption bands of EB (classical intercalator) at 285 nm show a
progressive hypochromism that can be divided into two regions
by a turning titration ratio of CDNA(nucleotides):CEB at 4.5:1 or
an inverse ratio of CEB:CDNA at 0.22:1, which exactly represents
the maximum number of EB bound per nucleotide of DNA.[19]
Starting with successive addition of CT-DNA to the turning
titration ratio, the UV-vis absorption bandof EB at 285nm shows
a progressive hypochromism of 34.2% with only a 1 nm red shift.
But hereafter, red shifts of 6 nm take place with the total
hypochromism of 47.7% by approximately the titration end point
at CDNA:CEB ¼ 10.4:1. It is difficult for most intercalators,
especially the moderates, to reach such an isobath of absorption
bands as EB. In fact, some groove binders of Hoechst 33258
family can also present red shifts or even blue shifts of absorption
bands when they bind to a DNA helix by groove binding modes,
especially for multiple binders.[20] Therefore, the intercalation
between a compound and DNA cannot be excluded only by no
or small red shift of UV-vis absorption band. After all, hydro-
dynamic measurements that are sensitive to length change of
DNA (i.e. viscosity and sedimentation) are regarded as the least
ambiguous and the most critical criterions for binding modes in
solution in absence of crystallographic structural data.[21]
However, the magnitude of hypochromism is parallel to the
intercalative strength and the affinity of a compound binding
to DNA.[22] The appreciable hypochromisms of ligands and
SmIII complexes intercalating to DNA present the order of
1a 41b 41c and 2a 42b 42c, which are in good agreement
with the viscosity titration results. Here, the effect of substituent
may play key roles in the interaction. Besides the same structural
units of these SmIII complexes, as for 2a, the phenyl substituent
may be more accessible to DNA helix and much more favourable
of forming p–p stacking interaction between the aromatic
chromophore of the complex and the base pairs of DNA than 2b.
Inthe latter, the 2-hydroxy locating inbenzoylhydrazine side chain
may induce some non-negligible steric hindrances when inter-
calating into the DNA helix. As for 2c, the N atom of aromatic
sextet of the pyridine ring of isonicotinylhydrazine side chain
has an exposed and non-hybridized p orbit containing long pair
0.8
0
10
20
30
40
50
60
[Q] [µM]
(b) 3.0
2.5
2b
2c
2a
2.0
1.5
1.0
0
10
20
30
40
[Q] [µM]
Fig. 2. SternꢁVolmer plots of Fo /F versus [Q] for (a) ligands and (b) SmIII
complexes.
electrons, which may result in a stronger electronic repulsion and
hinder the p–p stacking interaction. Moreover, the aggregation of
self-stacked molecules of 2c may occur, which will induce the
possibilities of an association-dissociation equilibrium in the
absenceofDNA, andinduceaslightlyunsteadyUV-visabsorption
and a little hypochromism even in an excess of conjugate versus
DNA bps.[20b] For the same reasons, the hypochromicity for
ligands shows the same order as the SmIII complexes.
EB-DNA Quenching Assay
The EB-DNA quenching tests were performed and quantified
by fluorescent titration. The fluorescence emission intensity of
EB-DNA system decreased dramatically upon the increasing
amounts of every ligand and SmIII complex. The Stern–Volmer
equation was used to determine the fluorescent quenching
mechanism.[14a] Plots of Fo/F versus [Q] are shown in Fig. 2 and
the quenching data collected and calculated from the good linear
relationship when P o0.05 are listed in Table 3. As shown, the
data of KSV are 1.405–2.352 ꢃ 104 Mꢁ1 for ligands and 3.463–
8.596 ꢃ 104 Mꢁ1 for SmIII complexes, accordingly, the data of
Kq calculated are 0.7806–1.307 ꢃ 1013
M
ꢁ1 sꢁ1 for ligands and
1.924–4.776 ꢃ 1013 Mꢁ1 sꢁ1 for SmIII complexes, in which the
value of to is taken as 1.8 ꢃ 10ꢁ9 s.[14a] All of the current values
of Kq are much greater than that of Kq(max) (2.0 ꢃ 1010
M
ꢁ1 sꢁ1),

350
Y. Liu et al.
Table 3. Parameters of Kb, KSV, Kq, CF50, IC50 (OHꢂ and O22ꢂ) for ligands and the SmIII complexes
R represents the linear correlation coefficient
Compound Kb ꢃ 105 Mꢁ1 1/nA
KSV ꢃ 104 Mꢁ1 [R]
Kq ꢃ 1013
M
ꢁ1 sꢁ1 FC50 ꢃ 10ꢁ5 M SC50C [mM] for OHꢂ [R] SC50C [mM] for Oꢁ2 ꢂ [R]
B
(Ccompound
/
CDNA, nucleotides
)
1a
1b
1c
2a
2b
2c
2.148 ꢅ 0.205 0.081 2.086 ꢅ 0.014 (0.9997)
9.295 ꢅ 1.315 0.28 2.352 ꢅ 0.018 (0.9998)
1.169
4.818 (12.05)
3.895 (9.738)
6.630 (16.58)
1.386 (3.465)
1.189 (2.973)
3.072 (7.680)
14.66 ꢅ 0.495 (0.9937) 6.831 ꢅ 0.219 (0.9954)
7.716 ꢅ 0.230 (0.9940) 4.308 ꢅ 0.174 (0.9892)
76.10 ꢅ 0.372 (0.9909) 5.131 ꢅ 0.258 (0.9838)
3.792 ꢅ 0.145 (0.9662) 2.696 ꢅ 0.079 (0.9906)
2.127 ꢅ 0.046 (0.9862) 5.678 ꢅ 0.153 (0.9958)
2.194 ꢅ 0.044 (0.9884) 1.727 ꢅ 0.025 (0.9934)
1.307
0.7806
4.643
4.776
1.924
1.329 ꢅ 0.180 0.092 1.405 ꢅ 0.013 (0.9995)
10.91 ꢅ 1.690 0.14
37.32 ꢅ 6.440 0.20
2.562 ꢅ 0.310 0.12
8.358 ꢅ 0.289 (0.9953)
8.596 ꢅ 0.151 (0.9994)
3.463 ꢅ 0.076 (0.9981)
AThe data of 1/n represent moles of the tested compound bound by per mole of base pairs of DNA.
BFC50 represents the molar concentration of the tested compound that caused a 50% loss of the fluorescence intensity of EB-DNA system.
CSC50 represents the molar concentration of the tested compound that caused a 50% inhibitory or scavenging effect on OHꢂ or Oꢁ2 ꢂ, its value was calculated
from regression line of the log of the tested compound concentration versus the scavenging effect [%] of the compound.
the maximum quenching rate constant of bimolecular diffusion
collision, which is indicative of a static type of quenching
mechanism arising from the formation of a dark complex
between the fluorophore and quenching agent.[23]
other weak interactions such as hydrophobic, van der Waals, and
electrostatic forces (pH at 7.20) may not be excluded. In other
words, the interaction mechanism is not only determined by
complex formation but also by certain weak interactions.[25]
More importantly, DNA intercalators have been used exten-
sively as antitumour, antineoplastic, antimalarial, antibiotic,
and antifungal agents.[14a] There is a criterion for screening
out antitumour drugs from others by EB-DNA fluorescent tracer
method, i.e. a compound can be used as a potential antitumour
drug if it causes a 50% loss of fluorescence intensity of EB-DNA
by fluorescent titration before the molar concentration ratio of
the compound to DNA (nucleotide) does not overrun 100:1.[19]
The FC50 value is introduced to denote the molar concentration
of a compound that causes a 50% loss in the fluorescence
intensity of EB-DNA system. According to the data of FC50
and the molar ratios of compounds to DNA as shown in Table 3,
it is interesting that all the molar concentration ratios of the
investigated compounds to DNA are largely under 100:1 at
FC50, indicating that all these ligands and SmIII complexes
may be used as potential antitumour drugs and the antitumour
activities of SmIII complexes are more excellent than those of
the ligands. However, their pharmacodynamical and pharma-
cological properties should be further studied in vivo.
Losses of fluorescence intensity at the maximum wavelength
may indicate the displacement of EB from EB-DNA complex
by a compound and the intercalative binding between the
compound with DNA.[15b] Displacement of EB (quantified by
fluorescence) by the titration of a compound is suggestive of an
intercalative or minor groove binding, thus, EB is particularly
suitable as a reporter because of its 24-fold decrease in fluores-
cence as well as shifts in its excitation spectrum when displaced
from an intercalation site.[14b] Fig. S4 shows two representative
fluorescence quenching spectra and the corresponding excita-
tion spectra for the fluorescence quenching of EB-DNA systems
by the titrations of 2b and 2c. Upon increasing amounts of 2b,
the fluorescence emission intensity of the EB-DNA system
decreases dramatically with 5 nm blue shifts, simultaneously,
the fluorescence excitation intensity of the EB-DNA system
decreases dramatically with 7 nm blue shifts at the maximum
wavelength by an approximately saturated end point. Similarly,
with increasing amounts of 2c, the dramatic decrease of fluor-
escence emission intensity with 7 nm red shifts and fluorescence
excitation intensity with 9 nm blue shifts takes place. In fact, for
all the investigated compounds here, there exist 3–7 nm blue
shifts at the maximum wavelength in the fluorescence excitation
spectra (data and figures not shown for the other compounds),
which indicates that most of the EB molecules can be displaced
from EB-DNA complex by every quencher at the saturated end
point although 24-fold decreases in fluorescence have not been
reached. Thus, it is reasonable that there exists intercalation
between DNA and each of the investigated compounds.
Moreover, the Stern–Volmer dynamic quenching constants
can also be interpreted as binding affinities of the complex
reaction.[24] The data of KSV present the orders of 1b 41a 41c,
2b 42a 42c, 2a 41a, 2b 41b, and 2c 41c, which indicate the
abilities of displacement of EB from EB-DNA systems by
compounds and the binding affinities between compounds and
DNA. However, it is not in good agreement with the viscosity
titration and UV-vis spectroscopy study results. In comparison
with the structures of these compounds, for 2a or 2b, the phenolic
hydroxy group that can binds nucleotides and/or the sugar–
phosphate backbone of DNA through hydrogen bond may play
a certain role in the EB-DNA quenching tests. Additionally, the
Fluorescence Spectroscopy Study
When excited at lex ¼ 321–325 nm, ligands show the fluores-
cence maximum wavelengths at lem ¼ 442–443 nm, and when
excited at lex ¼ 321–323 nm, the SmIII complexes show the
fluorescence maximum wavelengths at lem ¼ 440–445 nm.
Upon addition of DNA, the fluorescence emission intensity of
every investigated compound increases steadily. Although the
emission enhancement cannot be regarded as a rigid criterion for
binding mode, it is related to the extent to which the compound
gets into a hydrophobic environment inside DNA and avoids the
effect of solvent water molecules. The intrinsic binding constant
(Kb) can be obtained by the fluorescence titration and the
Scatchard equation.[10,15b] The Scatchard plot should be a
straight line for a simple binding reaction. However, the
Scatchard plot of r/Cf versus r usually presents a deviation from
linearity due to the significant neighbour exclusion properties of
DNA binding to intercalating agents.[26] As shown in Fig. S5,
the plot of r/Cf versus r for each of the compounds shows a
deviation from linearity, so the binding constant was obtained by
the McGhee and von Hippel model.[26b,27] The data of binding

Properties of SmIII Complexes
351
parameters are shown in Table 3. It is clear that the data of Kb
present the orders of 2a 41a, 2b 41b, and 2c 41c, indicating
that the binding of every SmIII complex to DNA is stronger
than that of its ligand. The data of Kb present the order of
1b 41a 41c and 2b 42a 42c, which are consistent with the
EB-DNA quenching results. Although it is a weaker binding
of 2c to DNA, 2a and 2b are stronger intercalators to DNA in
comparison with EB (EB-DNA, Kb ¼ 3.0 ꢃ 106 Mꢁ1 in 5 mM
TrisꢁHCl/50 mM NaCl buffer, pH 7.2),[28] indicating that the
two SmIII complexes can bind to DNA effectively.
scavenging abilities for OHꢂ and O2ꢁꢂ than Vc. Considering
their oxidative properties, these DNA intercalators may be
efficient inhibitors of the formation of a DNA/TBP complex
or topoisomerases.
Conclusion
Three SmIII complexes are prepared from Sm(NO3)3ꢀ6H2O
and Schiff-base ligands derived from 8-hydroxyquinoline-
2-carboxyaldehyde with three aroylhydrazines including
benzoylhydrazine, 2-hydroxybenzoylhydrazine, and isonico-
tinylhydrazine. SmIII and every ligand can form a dinuclear
SmIII complex with a 1:1 metal to ligand stoichiometry and nine-
coordination at the SmIII centre. All the ligands and SmIII
complexes can strongly bind to CT-DNA through intercalation
with the binding constants at 105–106 Mꢁ1. All the ligands and
SmIII complexes may be used as potential anticancer drugs
but the antitumour activities of SmIII complexes may be more
excellent than the ligands. However, their pharmacodynamical
and pharmacological properties should be further studied
in vivo.
In contrast, all the ligands and SmIII complexes have strong
abilities of antioxidation but SmIII complexes present stronger
abilities of scavenging OHꢂ than ligands, especially SmIII
complex containing active phenolic hydroxy group, while the
complex containing N-heteroaromatic substituent shows higher
scavenging effect for Oꢁ2 ꢂ. There are the similar chemical
structures and the similar order of antioxidation and DNA
binding properties between EuIII and SmIII complexes. How-
ever, the complex [EuL2(NO3)(DMF)2]2 presents a much stron-
ger binding to DNA than [SmL2(NO3)(DMF)2]2 and a reversed
order for scavenging Oꢁ2 ꢂ. Considering their oxidative proper-
ties, these DNA binders may be effective inhibitors of the
formation of a DNA/TBP complex topoisomerases, which
should be studied further in vivo. Moreover, the different
mechanism between inhibiting or scavenging OHꢂ and O2ꢁꢂ
should be also studied further.
Antioxidation Properties
Hydroxyl Radical Scavenging Activity
Figs S6A and B show the plots of hydroxyl radical scavenging
effects [%] for ligands and SmIII complexes, respectively, both
of them are concentration-dependant. As shown in Table 3,
the values of SC50 of ligands for OHꢂ are 7.716 ꢅ 0.230–
76.10 ꢅ 0.372 mM with the order of 1bo1a o1c, while the
values of SC50 of SmIII complexes for OHꢂ are 2.127 ꢅ 0.046–
3.792 ꢅ 0.145 mM with the order of 2bo2co2a. It is marked
that the scavenging effects of SmIII complexes for OHꢂ are much
higher than those of ligands. As for 1b and its SmIII complex,
they show higher abilities of scavenging effects for OHꢂ than
other ligands and complexes, possibly due to the key roles of
functional groups, –OH, which can react with OHꢂ to form
stable macromolecular radicals by the typical H-abstraction
reaction.[29] However, there are two types of antioxidation
mechanisms for OHꢂ, in which one represents suppression of the
generation of OHꢂ, and another represents the scavenging of
OHꢂ generated.[30] The production of OHꢂ, detected by ethylene
formation from methional, has been investigated in plasma,
lymph, and synovial fluid.[30] In the presence of added iron-
EDTA as a catalyst, addition of either H2O2 or xanthine and
xanthine oxidase gives rise to OHꢂ formation that in most cases
is not superoxide-dependent. In the absence of the catalyst, the
reaction is hardly detectable, the rate being less than 5% of that
observed with 1 mM iron-EDTA added. In the present study, it is
logical that the chelation between the phenolic hydroxyl group
and the carbonyl group of the 2-hydroxybenzoylhydrazine side
chain of 1b with free Fe2þ in the iron-EDTA reaction system
makes the concentration of free Fe2þ much lower so that the
catalysis becomes very poor and the OHꢂ formation has been
suppressed, therefore, the inhibitive effect of 1b detected for
OHꢂ is higher than other ligands.
Experimental
Calf thymus DNA (CT-DNA) and ethidium bromide (EB) were
obtained from Sigma–Aldrich Biotech. Co., Ltd. 8-Hydroxy-
quinoline-2-carboxyaldehyde was obtained form J&K Chemi-
cal Co., Ltd. The stock solution (1.0 mM) of the investigated
compound was prepared by dissolving the powdered material
into an appropriate amount of DMF solution. Deionized double
distilled water and analytical grade reagents were used
throughout. CT-DNA stock solution was prepared by dissolving
the solid material, normally at 0.3 mg mLꢁ1, in 5 mM Tris–HCl
buffer (pH 7.20) containing 50 mM NaCl. Then, the solution
was kept over 48 h at 48C. The resulting somewhat viscous
solution was clear and particle-free. The solution of CT-DNA in
Tris–HCl buffer gave a ratio of UV-vis absorbance at 260 to
280 nm of ,1.8–1.9:1, indicating that the CT-DNA was suffi-
ciently free of protein. The CT-DNA concentration in terms
of base pair Lꢁ1 was determined spectrophotometrically by
employing an extinction coefficient of emax ¼ 13200 Mꢁ1 cmꢁ1
(base pair)ꢁ1 at 260 nm, while the concentration in terms of
nucleotide Lꢁ1 was determined by employing an extinction
coefficient of 6600 Mꢁ1 cmꢁ1 (nucleotide)ꢁ1 at 260 nm.[32] The
CT-DNA stock solution was stored at –208C until it was used. A
working standard solution of CT-DNA was obtained by appro-
priate dilution of the stock solution in 5 mM Tris–HCl buffer
(pH 7.20) containing 50 mM NaCl. EB was dissolved in 5 mM
Superoxide Radical Scavenging Activity
Figs S6C and D show the plots of superoxide radical scavenging
effects [%] for ligands and SmIII complexes, respectively, both
of which are also concentration-dependant. As shown in Table 3,
the values of SC50 of ligands for Oꢁ2 ꢂ are 4.308 ꢅ 0.174–
6.831 ꢅ 0.219 mM with no significantly different order of
1bo1co1a, but the values of SC50 of SmIII complexes for Oꢁ2 ꢂ
are 1.727 ꢅ 0.025–5.678 ꢅ 0.153 mM with a notably different
order of 2co2ao2b. It is clear that the SmIII complex con-
taining N-heteroaromatic substituents shows stronger scaven-
ging effects for Oꢁ2 ꢂ. These results suggest that there are
different mechanisms between scavenging or inhibiting OHꢂ
and Oꢁ2 ꢂ, which should be further studied.
The value of SC50 of ascorbic acid (Vc, a standard agent for
non-enzymatic reaction) for OHꢂ is 1.537 mg mLꢁ1 (8.727mM),
and its scavenging effect for Oꢁ2 ꢂ is only 25% at 1.75 mg mLꢁ1
(9.94 mM) in vitro.[31] It is pronounced that all the ligands and
the SmIII complexes investigated here have much stronger

352
Y. Liu et al.
Tris–HCl buffer (pH 7.20) and its concentration was determined
assuming a molar extinction coefficient of 5600 Mꢁ1 cmꢁ1 at
480 nm.[14a]
concentration CDNA (nucleotide); Fo is the fluorescence emis-
sion intensity in the absence of DNA; Fmax is the maximum
fluorescence emission intensity of the compound totally bound
for DNA at a titration end point. The experimental parameters
Kb and n were adjusted to produce curves that gave, by inspec-
tion, the most satisfactory fits to the experimental data.
The EB-DNA quenching assay was performed as reported
in a literature but a slight amendment.[10,33] DNA (2.0mM, bps)
solution was added incrementally to 0.32mM EB solution, until
the riseinthe fluorescence (lex ¼ 496 nm, lem ¼ 596nm)attained
a saturation. Then, small aliquots of concentrated compound
solutions (1.0mM) were added until the drop in fluorescence
intensity (lex ¼ 525 nm, lem ¼ 587 nm) reached a constant value.
The experiments were measured after 5 min at a constant room
temperature, 298K. The Stern–Volmer equation was used to
determine the fluorescent quenching mechanism:[14a]
The melting points of the compounds were determined on
an XT4–100X microscopic melting point apparatus (Beijing,
China). Elemental analyses of C, N, and H were carried out on an
Elemental Vario EL analyzer. The SmIII content was determined
by complexo-metric titration with EDTA after destruction of the
1
complex in the conventional manner. H NMR spectra were
recorded on a Bruker Avance DRX 200 MHz spectrometer
(DMSO-d6) with TMS as an internal standard. The IR spectra
were recorded on a Nicolet Nexus 670 FT-IR spectrometer using
KBr disc in the 4000–400 cmꢁ1 region. ESI-MS (ESI-Trap/
Mass) spectra were recorded on a Bruker esquire 6000 mass
spectrophotometer.
Viscosity titration experiments were carried on an Ubbe-
lodhe viscometer in a thermostated water-bath maintained at
25.00 ꢅ 0.018C. Titrations were performed for an investigated
compound that was introduced into DNA solution (50 mM, bps)
present in the viscometer. Data were presented as (Z/Zo)1/3
versus the ratio of the compound to DNA, where Z is the
viscosity of DNA in the presence of the compound corrected
from the solvent effect, and Zo is the viscosity of DNA alone.
Relative viscosities for DNA in either the presence or absence of
compound were calculated from the following relation:
Fo=F ¼ 1 þ Kqto½Qꢆ ¼ 1 þ KSV ½Qꢆ ;
ð6Þ
where Fo and F are the fluorescence intensity in the absence and
in the presence of a compound at [Q] concentration, respec-
tively; KSV is the Stern–Volmer dynamic quenching constant; Kq
is the quenching rate constant of bimolecular diffusion collision;
to is the fluorescent lifetime of EB-DNA.
The hydroxyl radicals in aqueous media were generated
through the Fenton-type reaction.[30,34] The 5-mL reaction
mixtures contained 2.0 mL of 100 mM phosphate buffer
(pH ¼ 7.4), 1.0 mL of 0.10mM aqueous safranin, 1 mL of
1.0 mM aqueous EDTA–FeII, 1 mL of 3% aqueous H2O2, and a
series of quantitatively micro-adding solution of the tested com-
pound. The sample without the tested compound was used as the
control. The reaction mixtures were incubated at 378C for 60min
in a water-bath. The absorbance at 520 nm was measured and the
solventeffectwascorrectedthroughout.Thescavengingeffectfor
OHꢂ was calculated from the following expression:[15b,35]
Z ¼ ðt ꢁ toÞ=to ;
ð1Þ
where t is the observed flow time of the DNA containing
solution, and to is the flow time of buffer.[14a,15a]
UV-vis spectra were obtained using a Perkin–Elmer Lambda
UV-vis spectrophotometer. The UV-vis absorption spectra of
the investigated compounds in the absence and in the presence
of the CT-DNA were obtained in 1:100 solution of DMF:
Tris–HCl buffer (5 mM, pH 7.20) containing 50 mM NaCl,
respectively.
Asample ꢁ Ablank
Fluorescence spectra were recorded using RF–5301PC spec-
trofluorophotometer (Shimadzu, Japan) with a 1 cm quartz cell.
All the experiments were measured after 5 min at constant room
temperature, 298 K. The intrinsic binding constant Kb was
obtained by the fluorescence titration and the McGhee and
von Hippel model:[10,26b,27]
Scavenging effect ½%ꢆ ¼
ꢃ 100 ;
ð7Þ
Acontrol ꢁ Ablank
where Asample is the absorbance of the sample in the presence of
the tested compound, Ablank is the absorbance of the blank in the
absence of the tested compound, and Acontrol is the absorbance in
the absence of the tested compound and EDTA–FeII.
ꢀ
ꢁ
The superoxide radicals (Oꢁ2 ꢂ) were produced by the MET–
VitB2–NBT system.[15b,35] The solution of MET (methionine),
VitB2 (vitamin B2), and NBT (nitroblue tetrazolium) were
prepared with deionized double distilled water and avoiding
light. The 5-mL reaction mixtures contained 2.5 mL of 100 mM
phosphate buffer (pH 7.8), 1.0 mL of 50 mM MET, 1.0 mL of
0.23 mM NBT, 0.50 mL of 33 mM VitB2, and a series of
quantitatively microadding solution of the tested compound.
After incubation at 308C for 10 min in a water bath and then
illuminated with a fluorescent lamp (4000 Lux), the absorbance
of the sample was measured at 560 nm and the solvent effect was
corrected throughout. The sample reaction mixtures without
the tested compound were used as the control. The scavenging
effect for Oꢁ2 ꢂ was calculated from the following expression:
n ꢁ 1
r
1 ꢁ nr
¼ Kbð1 ꢁ nrÞ
;
ð2Þ
Cf
1 ꢁ ðn ꢁ 1Þr
where r is the moles of compound bound per mole nucleotides of
DNA; Cf is the molar concentration of free compound; Kb is the
intrinsic binding constant; n is the exclusion parameter in DNA
base pairs, while the data of 1/n represent moles of the tested
compound bound by per mole of base pairs of DNA. Cf and r
were calculated according to the following equations:
Cf ¼ Ct ꢁ Cb
ð3Þ
ð4Þ
ð5Þ
Cb ¼ CtðF ꢁ FoÞ=ðFmax ꢁ FoÞ
Ao ꢁ Ai
r ¼ Cb=CDNA
;
Scavenging effect ½%ꢆ ¼
ꢃ 100 ;
ð8Þ
Ao
where Ct is the total molar concentration of compound; Cb is
the molar concentration of compound bound for DNA; F is
the observed fluorescence emission intensity at a given DNA
where Ai is the absorbance in the presence of the tested
compound and Ao is the absorbance in the absence of the tested

Properties of SmIII Complexes
353
compound. The data for antioxidation presented as means ꢅ s.d.
of three determinations and followed by Student’s t-test. Differ-
ences were considered to be statistically significant if Po0.05.
The SC50 value was introduced to denote the molar concentra-
tion of the tested compound, which caused a 50% scavenging
Acknowledgement
This study was supported by the National Natural Science Foundation of
China (20975046) and Gansu CSRPS (1010B-04).
effect on OHꢂ or O2ꢁꢂ
.
References
[1] (a) L. H. Schmidt, Annu. Rev. Microbiol. 1969, 23, 427. doi:10.1146/
ANNUREV.MI.23.100169.002235
Preparation of Ligands and Complexes
(b) A. A. El-Asmy, A. Z. El-Sonbati, A. A. Ba-Issa, M. Mounir,
Transition Met. Chem. 1990, 15, 222. doi:10.1007/BF01038379
[2] (a) D. Parker, R. S. Dickins, H. Puschmann, C. Crossland, J. A. K.
Howard, Chem. Rev. 2002, 102, 1977. doi:10.1021/CR010452þ
(b) M. Albrecht, O. Osetska, R. Fro¨hliich, Dalton Trans. 2005, 23,
3757. doi:10.1039/B507621H
Ligands 1a–c were prepared using a previously described lit-
erature method.[10] Complex 2a was prepared by refluxing and
stirring equimolar amounts of a 40-mL methanol solution of 1a
(0.058 g, 0.2 mmol) and Sm(NO3)3ꢀ6H2O on a water-bath. After
refluxing for 30 min, triethylamine (0.020 g, 0.2 mmol) was
added into the reaction mixtures dropwise to deprotonate the
phenolic hydroxyl substituent of the 8-hydroxyquinolinato unit.
Then, the mixtures were refluxed and stirred continuously for
8 h. After cooling to room temperature, the precipitate was
centrifuged, washed with methanol, and dried in vacuum
over 48 h to give an orange powder. Yield 87.0% (0.094 g).
m/z (ESI-MS) 1297.1 [MþH]þ, 648.2 [M/2þH]þ (DMF solu-
(c) R. B. Hunter, W. Walker, Nature 1956, 178, 47. doi:10.1038/
178047A0
(d) D. M. Kramsch, A. J. Aspen, L. J. Rozler, Science 1981, 213, 1511.
doi:10.1126/SCIENCE.6792706
[3] (a) E. M. Hodnett, P. D. Mooney, J. Med. Chem. 1970, 13, 786.
doi:10.1021/JM00298A065
(b) E. M. Hodnett, W. J. Dunn, J. Med. Chem. 1972, 15, 339.
doi:10.1021/JM00273A037
[4] (a) Y. B. Zeng, N. Yang, W. S. Liu, N. Tang, J. Inorg. Biochem. 2003,
tion). Lm (DMF) 37.3 cm2 Oꢁ1 molꢁ1
. Anal. Calc. for
97, 258. doi:10.1016/S0162-0134(03)00313-1
(b) A. M. Pyle, T. Morii, J. K. Barton, J. Am. Chem. Soc. 1990, 112,
9432. doi:10.1021/JA00181A077
C34H30N8O14Sm2 (1075.8): C 37.93, H 2.79, N 10.41, Sm 27.96.
Found. C 38.03, H 2.79, N 10.38, Sm 27.91%.
Complex 2b was prepared from equimolar amounts of Sm
(NO3)ꢀ6H2O and 2b as the method of 2a. Yield 90.2%. m/z (ESI-
MS) 1329.2 [MþH]þ, 665.4 [M/2þH]þ (DMF solution). Lm
(DMF) 38.8 cm2 Oꢁ1 molꢁ1. Anal. Calc. for C34H30N8O16Sm2
(1107.8): C 36.83, H 2.71, N 10.11, Sm 27.15. Found. C 36.80,
H 2.70, N 10.08, Sm 27.22%.
(c) J. K. Barton, J. M. Goldberg, C. V. Kumar, N. J. Turro, J. Am.
Chem. Soc. 1986, 108, 2081. doi:10.1021/JA00268A057
[5] (a) S. Mahadevan, M. Palaniandavar, Inorg. Chim. Acre 1997, 254,
291. doi:10.1016/S0020-1693(96)05175-4
(b) S. J. Lippard, Acc. Chem. Res. 1978, 11, 211. doi:10.1021/
AR50125A006
(c) S. M. Hecht, Acc. Chem. Res. 1986, 19, 383. doi:10.1021/
AR00132A002
[6] (a) N. Grover, N. Gupta, H. H. Thorp, J. Am. Chem. Soc. 1992, 114,
Complex 2c was prepared from equimolar amounts of Sm
(NO3)ꢀ6H2O and 1c as the method of 2a. Yield 88.3%. m/z (ESI-
MS) 1299.2 [MþH]þ, 649.2 [M/2þH]þ (DMF solution). Lm
(DMF) 30.1 cm2 Oꢁ1 molꢁ1. Anal. Calc. for C32H28N10O14Sm2
(1077.8): C 35.63, H 2.60, N 12.99, Sm 27.91. Found. C 35.60, H
2.61, N 13.03, Sm 27.85.
3390. doi:10.1021/JA00035A034
(b) L. J. Govenlock, C. E. Mathieu, C. L. Maupin, D. Parker,
J. P. Riehl, G. Siligardi, J. A. G. Williams, Chem. Commun. 1999,
17, 1699. doi:10.1039/A904257A
[7] (a) B. N. Ames, M. K. Shigenaga, T. M. Hagen, Proc. Natl. Acad. Sci.
USA 1993, 90, 7915. doi:10.1073/PNAS.90.17.7915
(b) A. A. Horton, S. Fairhurst, Crit. Rev. Toxicol. 1987, 18, 27.
doi:10.3109/10408448709089856
(c) H. L. Wang, Z. Y. Yang, B. D. Wang, Transition Met. Chem. 2006,
31, 470. doi:10.1007/S11243-006-0015-3
[8] S. F. Lo, V. Mulabagal, C. L. Chen, C. L. Kuo, H. S. Tsay, J. Agric.
Food Chem. 2004, 52, 6916. doi:10.1021/JF040017R
[9] (a) S. Y. Chiang, J. Welch, F. J. Rauscher, T. A. Beerman, Biochem-
istry 1994, 33, 7033. doi:10.1021/BI00189A003
Determination of Crystal Structures
The radiation used for a crystal was graphite-monochromated
˚
Mo Ka radiation (0.71073 A) and the data were collected on a
Bruker APEX area-detector diffractometer by the v–2y scan
technique at 298(2) K. The structures were solved by direct
methods. All non-hydrogen atoms were refined anisotropically
by full-matrix least-squares methods on F2. Primary non-
hydrogen atoms were found from direct methods and secondary
non-hydrogen atoms were found from difference maps. The
hydrogen atoms were added geometrically and their positions
and thermal vibration factors were constrained. All calculat-
ions were performed using the programs SHELXS-97 and
SHELXL-97.[36]
(b) J. M. Woynarowski, M. Mchugh, R. D. Sigmund, T. A. Beerman,
Mol. Pharmacol. 1989, 35, 177.
(c) A. Y. Chen, C. Yu, B. Gatto, L. F. Liu, Proc. Natl. Acad. Sci. USA
1993, 90, 8131. doi:10.1073/PNAS.90.17.8131
[10] Y. C. Liu, Z. Y. Yang, J. Inorg. Biochem. 2009, 103, 1014.
doi:10.1016/J.JINORGBIO.2009.04.013
[11] W. J. Geary, Coord. Chem. Rev. 1971, 7, 81. doi:10.1016/S0010-8545
(00)80009-0
[12] (a) M. M. Moawad, W. G. Hanna, J. Coord. Chem. 2002, 55, 439.
doi:10.1080/00958970211906
(b) T. M. A. Ismail, J. Coord. Chem. 2005, 58, 141. doi:10.1080/
0095897042000274733
[13] J. M. Ou-Yang, J. Inorg. Chem 1997, 13, 315 (in Chinese).
[14] (a) D. Suh, J. B. Chaires, Bioorg. Med. Chem. 1995, 3, 723.
doi:10.1016/0968-0896(95)00053-J
Accessory Publication
Supporting information containing the crystal data, UV-vis
spectra values, characteristic IR band data, McGhee and von
Hippel plots and plots of antioxidation properties for the
investigated compounds are available from the Journal’s
website. CCDC 704943 (2a9), 704944 (2b9), and 704945 (2c9)
contain the supplementary crystallographic 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.
(b) R. Palchaudhuri, P. J. Hergenrother, Curr. Opin. Biotechnol. 2007,
18, 497. doi:10.1016/J.COPBIO.2007.09.006
[15] (a) S. Satyanarayana, J. C. Dabrowiak, J. B. Chaires, Biochemistry
1992, 31, 9319. doi:10.1021/BI00154A001

354
Y. Liu et al.
(b) B. D. Wang, Z. Y. Yang, P. Crewdson, D. Q. Wang,
J. Inorg. Biochem. 2007, 101, 1492. doi:10.1016/J.JINORGBIO.
2007.04.007
[24] (a) L. A. Bagatolli, S. C. Kivatinitz, G. D. Fidelio, J. Pharm. Sci. 1996,
85, 1131. doi:10.1021/JS960142K
(b) M. M. Yang, P. Yang, L. W. Zhang, Chin. Sci. Bull. 1994, 9, 31.
[25] A. Ayar, B. Mercimek, Process Biochem. 2006, 41, 1553. doi:10.1016/
J.PROCBIO.2006.02.016
[26] (a) L. M. Berezhkovskiy, I. V. Astafieva, C. Cardoso, Anal. Biochem.
2002, 308, 239. doi:10.1016/S0003-2697(02)00211-7
(b) J. B. Chaires, N. Dattagupta, D. M. Crothers, Biochemistry 1982,
21, 3933. doi:10.1021/BI00260A005
[27] J. D. McGhee, P. H. von Hippel, J. Mol. Biol. 1974, 86, 469.
doi:10.1016/0022-2836(74)90031-X
[16] R. D. Snyder, Mutat. Res. 2007, 623, 72. doi:10.1016/J.MRFMMM.
2007.03.006
[17] (a) J. K. Barton, A. T. Danishefsky, J. M. Goldberg, J. Am. Chem. Soc.
1984, 106, 2172. doi:10.1021/JA00319A043
(b) H. L. Lu, J. J. Liang, Z. Z. Zeng, P. X. Xi, X. H. Liu, F. J. Chen,
Z. H. Xu, Transition Met. Chem. 2007, 32, 564. doi:10.1007/S11243-
007-0202-X
[18] (a) V. G. Vaidyanathan, B. U. Nair, Eur. J. Inorg. Chem. 2004, 1840.
doi:10.1002/EJIC.200300718
(b) P. X. Xi, Z. H. Xu, X. H. Liu, F. J. Chen, L. Huang, Z. Z. Zeng,
Chem. Pharm. Bull. 2008, 56, 541. doi:10.1248/CPB.56.541
[19] Z. L. Li, J. H. Chen, K. C. Zhang, M. L. Li, R. Q. Yu, Sci. China Series
B. Chem. 1991, 11, 1193 (in Chinese).
[28] (a) M. Baldini, M. Belicchi-Ferrari, F. Bisceglie, G. Pelosi, S. Pinelli,
P. Tarasconi, Inorg. Chem. 2003, 42, 2049. doi:10.1021/IC026131D
(b) Y. Wang, Z. Y. Yang, Z. N. Chen, Bioorg. Med. Chem. Lett. 2008,
18, 298. doi:10.1016/J.BMCL.2007.10.085
[29] J. I. Ueda, N. Saito, Y. Shimazu, T. Ozawa, Arch. Biochem. Biophys.
[20] (a) C. Behrens, N. Harrit, P. E. Nielsen, Bioconjug. Chem. 2001, 12,
1996, 333, 377. doi:10.1006/ABBI.1996.0404
1021. doi:10.1021/BC0100556
[30] C. C. Winterbourn, Biochem. J. 1981, 198, 125.
[31] R. Xing, H. Yu, S. Liu, W. Zhang, Q. Zhang, Z. Li, P. Li, Bioorg. Med.
Chem. 2005, 13, 1387. doi:10.1016/J.BMC.2004.11.002
[32] F. Zsila, Z. Bika´di, M. Simonyi, Org. Biomol. Chem. 2004, 2, 2902.
doi:10.1039/B409724F
(b) S. Frau, J. Bernadou, B. Meunier, Bioconjug. Chem. 1997, 8, 222.
doi:10.1021/BC970007E
[21] (a) D. S. Sigman, A. Mazumder, D. M. Perrin, Chem. Rev. 1993, 93,
2295. doi:10.1021/CR00022A011
(b) Y. Wang, Z. Y. Yang, Q. Wang, Q. K. Cai, K. B. Yu,
J. Organomet. Chem. 2005, 690, 4557. doi:10.1016/J.JORGANCHEM.
2005.07.046
[33] A. G. Krishna, D. V. Kumar, B. M. Khan, S. K. Rawal, K. N. Ganesh,
Biochim. Biophys. Acta 1998, 1381, 104.
[34] C. C. Winterbourn, Biochem. J. 1979, 182, 625.
[35] Z. Y. Guo, R. Xing, S. Liu, H. H. Yu, P. B. Wang, C. P. Li, P. C. Li,
Bioorg. Med. Chem. Lett. 2005, 15, 4600. doi:10.1016/J.BMCL.2005.
06.095
[36] G. M. Sheldrick, Acta Crystallogr. A 1990, 46, 467. doi:10.1107/
S0108767390000277
[22] J. Z. Wu, B. H. Ye, L. Wang, L. N. Ji, J. Y. Zhou, R. H. Li, Z. Y. Zhou,
J. Chem. Soc., Dalton Trans. 1997, 8, 1395. doi:10.1039/A605269J
[23] (a) Y. C. Liu, Z. Y. Yang, J. Du, X. J. Yao, R. X. Lei, X. D. Zheng,
J. N. Liu, H. S. Hu, H. Li, Chem. Pharm. Bull. 2008, 56, 443.
doi:10.1248/CPB.56.443
(b) Y. C. Liu, Z. Y. Yang, J. Du, X. J. Yao, R. X. Lei, X. D. Zheng,
J. N. Liu, H. S. Hu, H. Li, Immunobiology 2008, 213, 651. doi:10.1016/
J.IMBIO.2008.02.003