Three- and four-coordinate Ag(I) complexes of crotonate and bis(benzimidazole)-2-oxapropane ligands: syntheses, crystal structures, DNA-binding studies and antioxidant activities

Article abstract of DOI:10.1007/s11243-015-9948-8

Abstract Two V-shaped ligands, namely 1,3-bis(1-ethylbenzimidazol-2-yl)-2-oxapropane (etobb) and 1,3-bis(1-benzylbenzimidazol-2-yl)-2-oxapropane (bobb), have been prepared. Reaction of these ligands with AgNO₃ and sodium crotonate under in the dark afforded the complexes, [Ag(etobb)₂](crotonate)·C₂H₅OH·2(CH₃CN)·2(H₂O) 1 and [Ag(crotonate)(bobb)] 2. Both complexes have been characterized by physicochemical and spectroscopic methods and also by X-ray single-crystal diffraction. The coordination environment of complex 1 can be described as distorted tetrahedral, while complex 2 has as a trigonal planar geometry. The DNA-binding properties of these complexes have been investigated by fluorescence, electronic absorption and viscosity measurements. The experimental results suggest that they bind to DNA by an intercalation mode. Complex 2 also exhibits excellent hydroxyl radical scavenging activity.

Full text of DOI:10.1007/s11243-015-9948-8

Transition Met Chem (2015) 40:555–564
DOI 10.1007/s11243-015-9948-8
Three- and four-coordinate Ag(I) complexes of crotonate
and bis(benzimidazole)-2-oxapropane ligands: syntheses, crystal
structures, DNA-binding studies and antioxidant activities
Huilu Wu1 Fei Wang1 Furong Shi1 Zaihui Yang1
•
•
•
•
Han Zhang1 Hongping Peng1
•
Received: 16 January 2015 / Accepted: 18 May 2015 / Published online: 29 May 2015
Ó Springer International Publishing Switzerland 2015
Abstract Two V-shaped ligands, namely 1,3-bis(1-
ethylbenzimidazol-2-yl)-2-oxapropane (etobb) and 1,3-
bis(1-benzylbenzimidazol-2-yl)-2-oxapropane (bobb), have
been prepared. Reaction of these ligands with AgNO3 and
sodium crotonate under in the dark afforded the complexes,
[Ag(etobb)2](crotonate)ÁC2H5OHÁ2(CH3CN)Á2(H2O) 1 and
[Ag(crotonate)(bobb)] 2. Both complexes have been char-
acterized by physicochemical and spectroscopic methods
and also by X-ray single-crystal diffraction. The coordi-
nation environment of complex 1 can be described as
distorted tetrahedral, while complex 2 has as a trigonal
planar geometry. The DNA-binding properties of these
complexes have been investigated by fluorescence, elec-
tronic absorption and viscosity measurements. The ex-
perimental results suggest that they bind to DNA by an
intercalation mode. Complex 2 also exhibits excellent hy-
droxyl radical scavenging activity.
biologically active compounds and therefore correspond to
significant synthetic targets [11–13]. Compared with other
heterocyclicN-donor ligands, bis-benzimidazoleligandshave
some distinctive structural characteristics. The benzimidazole
ring has a larger conjugated p-system; therefore, p–p stacking
interactions may play important roles in their complexes. The
compounds of Ag(I) with multidentate N-donor ligands have
attracted interest for a number of reasons. The absence of
crystal field stabilization for the d10 monovalent silver cation,
coupledwithitsabilitytotolerateawiderangeofcoordination
geometries (with coordination numbers spanning 2–7), leads
to considerable variation in the geometry and connectivity of
the networks that can be formed when Ag(I) centers act as
connectors [14, 15]. Their various biological applications
have also attracted attention [16].
In this work, two new silver complexes have been
synthesized through the structural variation of flexible
N-donor ligands. The DNA-binding properties and an-
tioxidant activities of the complexes were investigated.
Introduction
Experimental
The rational design and synthesis of coordination frameworks
have attracted much attention for their fascinating structures
[1–3], as well as their potential uses as functional materials
[4–7]. The selection of appropriate ligands as building blocks
is usually a key factor in controlling the structures of such
complexes [8–10]. Benzimidazole derivatives are important
constituents in many pharmacologically, catalytically and
C, H and N elemental analyses were determined using a
Carlo Erba 1106 elemental analyzer. Electrolytic conduc-
tance measurements were made with a DDS-11A-type
conductivity bridge using 10-3 mol L-1 solutions in DMF
at room temperature. IR spectra were recorded in the
4000–400 cm-1 region with a Nicolet FT-VERTEX 70
spectrometer using KBr pellets. Electronic spectra were
recorded on a Lab-Tech UV Bluestar spectrophotometer.
1H NMR spectra were recorded on a Varian VR300 MHz
spectrometer with TMS as an internal standard. Fluores-
cence spectra were recorded on a Perkin Elmer LS-45
spectrofluorophotometer. The antioxidant activities against
& Huilu Wu
wuhuilu@163.com
1
School of Chemical and Biological Engineering, Lanzhou
Jiaotong University, Lanzhou 730070, Gansu,
People’s Republic of China
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Transition Met Chem (2015) 40:555–564
hydroxyl and superoxide anion radicals were measured in a
water bath with a Spectrumlab 722sp spectrophotometer.
Calf thymus DNA (CT-DNA) and ethidium bromide
(EB) were obtained from Sigma-Aldrich. All chemicals and
solvents were reagent grade and used without further pu-
rification. Tris–HCl buffer, Na2HPO4–NaH2PO4 buffer and
EDTA-Fe(II) solution were prepared using double-distilled
water. Stock solutions of the complexes were prepared in
DMF at 3 9 10-3 mol L-1. The experiments involving the
interactions of the free ligands and complexes with CT-
DNA were carried out in double-distilled buffered water
containing 5 mM Tris and 50 mM NaCl and adjusted to pH
7.2 with hydrochloric acid. A solution of CT-DNA gave a
ratio of UV absorbance at 260 and 280 nm of about 1.8–1.9,
indicating that the CT-DNA was sufficiently free of protein
[17]. The CT-DNA concentration per nucleotide was de-
termined spectrophotometrically by employing an extinction
coefficient of 6600 M-1 cm-1 at 260 nm [18]. Viscosity
experiments were conducted using an Ubbelodhe viscome-
ter, immersed in a water bath maintained at 25.0 0.1 °C.
Titrations were performed for the complex (3 lM), and each
compound was introduced into CT-DNA solution (50 lM)
present in the viscometer. Data were analyzed as (g/g0)1/3
versus the ratio of the concentration of the compound to CT-
DNA, where g is the viscosity of CT-DNA in the presence
of the compound and g0 is the viscosity of CT-DNA alone.
Hydroxyl radicals were generated in aqueous media
through the Fenton-type reaction [19]. The reaction mix-
tures (3 mL) contained 1 mL of 40 lg mL-1 aqueous
safranin, 1 mL of 1.0 mmol aqueous EDTA-Fe(II), 1 mL
of 3 % aqueous H2O2 and a series of quantitative micro-
additions of the test compound. A sample without the test
compound was used as the control. The reaction mixtures
were incubated at 37 °C for 30 min in a water bath. The
absorbance at 520 nm was measured, and the solvent effect
was corrected. The scavenging effect for OHÁ was calcu-
lated from the following expression:
Scheme 1 Synthetic route for ligands, etobb and bobb
756 m(O–Ar), 1083 m(C–O), 1475 m(C=N), 1612 m(C=C). UV–Vis
(DMF): k = 280, 288 nm. Anal. Calcd (%): C, 71.8; H,
6.6; N, 16.8; found (%): C, 71.4; H, 6.5; N, 16.6. KM
(DMF, 297 K): 0.76 S cm2 mol-1
.
Bobb, Yield: 75 %. m. p.: 177–178 °C. 1H NMR
(CDCl3–d1, 400 MHz): d: 7.78–7.80 (m, 4H), 7.17–7.30
(m, 10H), 6.94–6.96 (m, 4H), 5.29 (s, 4H), 4.80–4.82 (m,
4H). FTIR (KBr m/cm-1): 1078 m(C–O–C), 1496 m(C=N), 1463
m
cd (%): C, 78.58; H, 5.71; N, 12.22. found (%): C, 78.51;
(C=N–C=C). UV–Vis (DMF): k = 279, 287 nm. Anal. Cal-
H, 5.73; N, 12.24. KM (DMF, 297 K): 1.13 S cm2 mol-1
.
Preparation of the complexes
To a stirred solution of sodium crotonate (0.0217 g,
0.20 mmol) in EtOH (5 mL) was added a solution of
AgNO3 (0.0340 g, 0.20 mmol) in EtOH (3 mL). A solution
of etobb (0.0668 g, 0.20 mmol) in ethanol (5 mL) was then
added dropwise. The mixture was vigorously stirred at
room temperature for 4 h until the white precipitate had
disappeared. The resultant solution was filtered, and a few
drops of acetonitrile were added. It was then allowed to
evaporate in the dark at room temperature for several days
to give colorless block crystals of complex 1. Complex 2
was prepared by a similar procedure as for complex 1,
using bobb rather than etobb.
Complex 1, Yield: 69 %. Anal. Calcd for C44H49AgN8-
O4ÁC2H5OHÁ2(CH3CN)Á2(H2O) (%): C, 58.5; H, 6.4; N, 13.6.
Found (%): C, 58.5; H, 6.3; N, 13.7. FTIR (KBr m/cm-1): 746
Scavenging effect % ¼ ðAsample À ArÞ=ðAo À ArÞ Â 100 %
where Asample is the absorbance of the sample in the pres-
ence of the test compound, Ar is the absorbance of the
blank in the absence of the test compound, and Ao is the
absorbance in the absence of the test compound and
EDTA-Fe(II) [20].
m
(O–Ar), 1043 m(C–O), 1558 m(C=N). UV–Vis (DMF): k = 280,
289 nm. KM (DMF, 297 K): 37.1 S cm2 mol-1
.
Complex 2, Yield: 76 %. Anal. Calcd for C34H31-
AgN4O3 (%): C, 62.7; H, 4.8; N, 8.6. Found (%): C, 62.6;
H, 4.8; N, 8.7. FTIR (KBr m/cm-1): 756 m(O–Ar), 1066
m
(C–O), 1556 m(C=N). UV–Vis (DMF): k = 281, 288 nm. KM
Synthesis of etobb and bobb
(DMF, 297 K): 6.6 S cm2 mol-1
.
The free ligands etobb and bobb were synthesized according
to the literature methods [21–23], as shown in Scheme 1.
Etobb, Yield: 64 %. m. p.: 101–103 °C. 1H NMR
(400 MHz, CDCl3,) d: 7.28 (m, 4H, Ph), 4.12 (s, 2H, CH2),
4.91 (s, 2H, OCH2), 1.49 (s, 3H, CH3). FTIR (KBr m/cm-1):
X-ray crystallography
For each complex, a suitable single crystal was mounted on
a glass fiber, and the intensity data were collected on a
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Transition Met Chem (2015) 40:555–564
557
Table 1 Crystal data and
structure refinement for
complexes 1 and 2
Complex
1
2
Empirical formula
Formula weight
Crystal system
space group
C50H65AgN10O7
1025.99
C34H31AgN4O3
651.50
Monoclinic
P21/c
Triclinic
P - 1
˚
a(A)
15.8523(19)
19.987(2)
18.7508(15)
90
10.0850(9)
13.6915(12)
14.2747(10)
71.183(7)
88.486(7)
69.361(8)
1737.5(2)
2
˚
b(A)
˚
c(A)
a(°)
b(°)
c(°)
116.198(7)
90
3
˚
V(A )
5330.7(9)
4
Z
qcalcd (mg m-3
)
1.278
1.245
l (mm-1
)
0.435
0.615
F (000)
Crystal size (mm3)
2152
668
0.38 9 0.23 9 0.20
-18 B h B 13,
-23 B k B 23,
-21 B l B 22
1.58–25.00
1.046
0.35 9 0.27 9 0.24
-12 B h B 12,
-16 B k B 15,
-17 B l B 16
2.93–25.25
h/k/l (max, min)
h range for data collection (°)
Goodness-of-fit on F2
1.040
Final R1, wR2 indices (I [ 2r(I))
R1 = 0.0321,
wR2 = 0.0811
R1 = 0.0445,
wR2 = 0.0916
0.636 and -0.557
R1 = 0.0551,
wR2 = 0.1361
R1 = 0.0809,
wR2 = 0.1560
0.755 and -0.399
R1, wR2 indices (all data)
-3
)
˚
Largest differences, peak and hole (e A
Bruker APEX-II CCD diffractometer with graphite-
˚
as DMF and DMSO, slightly soluble in water, methanol,
ethanol and acetone, but insoluble in Et2O and petroleum
ether. The elemental analysis shows that their compositions
are [Ag(etobb)2](crotonate)ÁC2H5OHÁ2(CH3CN)Á2(H2O)
and [Ag(crotonate)(bobb)], which were confirmed by the
crystal structure analyses. The molar conductance values
show that complex 1 is a 1:1 electrolyte, while complex 2
is a non-electrolyte in DMF [26].
monochromatized Mo Ka radiation (k = 0.71073 A) at
296(2) K. Data reduction and cell refinement were per-
formed using the SAINT suite of programs [24]. The ab-
sorption corrections were made by empirical methods. The
structures were solved by direct methods and refined by
full-matrix least squares against F2 using SHELXTL soft-
ware [25]. All H atoms were found in difference electron
maps and subsequently refined in a riding model ap-
proximation with C–H distances ranging from 0.95 to
The IR spectra of the free ligand etobb and its
Ag(I) complex 1 were compared. Free etobb exhibits a
characteristic C=N stretching frequency at 1475 cm–1,
while the C=N stretching frequency of the complex is
observed at 1558 cm–1. Hence, the C=N stretching fre-
quencies are shifted upon complexation [27], indicating
that the imine nitrogen atoms are coordinated to the
Ag(I) center. Similar shifts are also observed for complex
2. This deduction agrees with the results of the X-ray
crystal structure determinations.
˚
0.99 A and Uiso(H) = 1.2 Ueq(C) or 1.5 Ueq(Cmethyl). The
crystal data and experimental parameters relevant to the
structure determination are listed in Table 1. Selected bond
distances and angles are given in Table 2.
Results and discussion
Characterization of the complexes
DMF solutions of the free ligands and Ag(I) complexes
show, as expected, almost identical UV spectra. Band ob-
served for free etobb at 288 nm is marginally red-shifted in
the complex 1 by just 1 nm. The absorption band of
All of these compounds are stable under air. The
Ag(I) complexes are soluble in polar aprotic solvents such
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Transition Met Chem (2015) 40:555–564
Table 2 Selected bond lengths
˚
Complex 1
(A) and bond angles (°) of
complexes 1 and 2
Bond distances
Ag(1)–N(1)
2.292(2)
Ag(1)–N(3)
2.2979(19)
2.3476(19)
115.30(7)
110.17(7)
101.55(7)
126.51(15)
125.51(15)
126.27(15)
125.90(16)
Ag(1)–N(7)
2.3006(18)
103.57(7)
117.47(7)
108.70(7)
124.91(16)
128.78(17)
127.06(16)
127.98(17)
Ag(1)–N(5)
Bond angles
N(1)–Ag(1)–N(3)
N(3)–Ag(1)–N(7)
N(3)–Ag(1)–N(5)
C(29)–N(5)–Ag(1)
C(19)–N(3)–Ag(1)
C(39)–N(7)–Ag(1)
C(9)–N(1)–Ag(1)
N(1)–Ag(1)–N(7)
N(1)–Ag(1)–N(5)
N(7)–Ag(1)–N(5)
C(26)–N(5)–Ag(1)
C(16)–N(3)–Ag(1)
C(36)–N(7)–Ag(1)
C(6)–N(1)–Ag(1)
Complex 2
Bond distances
Ag(1)–N(2)
2.214(4)
2.359(4)
143.80(15)
110.35(14)
126.0(3)
122.6(3)
Ag(1)–O(2)
2.238(4)
Ag(1)–N(4)
Bond angles
N(2)–Ag(1)–O(2)
O(2)–Ag(1)–N(4)
C(21)–N(2)–Ag(1)
C(1)–N(4)–Ag(1)
N(2)–Ag(1)–N(4)
105.47(13)
C(22)–N(2)–Ag(1)
C(7)–N(4)–Ag(1)
128.1(3)
125.0(3)
280 nm in the spectrum of free etobb are assigned to p–p*
(imidazole) transition [28]. Analogously, the UV bands of
bobb (279, 287 nm) are also marginally red-shifted by
about 1–2 nm in the spectrum of complex 2.
Ag(I) atom, plus bobb and crotonate ligands (Fig. 4). The
Ag(I) atom is coordinated by one oxygen atom from a
crotonate anion and two nitrogen atoms from a bobb li-
˚
gand. The Ag–O bond distance is 2.238(4) A, falling into
the normal range [29]. Similarly, the units are extended
into a 1D supramolecular chain through p–p stacking in-
teractions between benzimidazole rings and weak hydro-
gen C–H(Benzyl)ÁÁÁO(crotonate) interactions, but these are
different to the complex 1. In complex 1, p–p stacking is
Crystal structure of complex 1
The asymmetric unit of 1 consists of a [Ag(etobb)2]? ca-
tion, a crotonate anion, one ethanol molecule, two ace-
tonitrile molecules and two waters of crystallization. As
shown in Fig. 1, the Ag(I) atom is four coordinate with a
AgN4 chromophore, provided by four nitrogen atoms from
two etobb ligands. The coordination geometry is best de-
scribed as a distorted tetrahedron. Owing to this coordi-
nation geometry, two eight-membered rings are
constructed, which are connected through the Ag(I) center.
In complex 1, the interactions, including p–p interac-
tions and hydrogen bonds, contribute to the formation of a
1D chain and 2D infinite sheet. Similarly, as depicted in
Fig. 2, there are two kinds of p–p interactions in complex
1, between two benzimidazole rings located in the face-to-
˚
present between each unit [d = 3.441(4) A], while in
complex 2 it is not, as shown in Fig. 5.
The intramolecular distances further reveal the presence
of C–HÁÁÁM close intramolecular interactions between the
Ag center and the bobb H(8A) atom (Fig. 5), with an
˚
AgÁÁÁH distances of 2.818(3) A, AgÁÁÁC distances of
˚
3.377(4) A (d(AgÁÁÁH) \ d(AgÁÁÁC)) and C–HÁÁÁAg angle of
117.498(7)° (C–HÁÁÁAg [ 100°), which are similar to the
values for related Ag(I) complexes [30]. Such C–HÁÁÁM
close interactions can be described as weak intramolecular
C–HÁÁÁM hydrogen bonds; this depiction is also chemically
and geometrically reasonable [31–33]. Moreover, from the
viewpoint of geometrical requirements, the weak C–HÁÁÁAg
interactions may facilitate the formation of the coordina-
tion bond between Ag(I) and the N-donor atom of the
benzimidazole ring in the solid state.
˚
face position, d = 3.588(2) and 3.618(4) A. It is precisely
such a layout that makes the produces of an infinite 1D
zigzag chain. The solvent water molecules and counter
anions form strong hydrogen bonds. The hydrogen bonding
˚
distances (A) and angles (°) are listed in Table 3. The 2D
layers are linked together by O–HÁÁÁO and C–HÁÁÁO hy-
DNA-binding properties
drogen bonds, as shown in Fig. 3.
The binding abilities of the free ligand and its metal
complexes with CT-DNA were characterized by measuring
their effects on the UV–Vis spectra. Compounds binding to
DNA through intercalation usually result in hypochromism
and bathochromism due to strong p–p stacking interactions
Crystal structure of complex 2
Complex 2 has a mononuclear three-coordinate con-
figuration. The structure consists of a central metal
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Transition Met Chem (2015) 40:555–564
559
Fig. 1 a Molecular structure of the complex 1 with displacement ellipsoids drawn at the 30 % probability level; the solvent molecules and H
atoms are omitted. b Two eight-membered ring were constructed and connected through the Ag(I) center. c Coordination polyhedron of Ag(I)
Fig. 2 Structure of the complex
1 linked via p–p stacking
interaction (dashed lines)
˚
between the aromatic chromophore and DNA base pairs
[34]. It is generally accepted that the extent of hypochro-
mism in the UV–Vis band is consistent with the strength of
intercalation [35]; hence, these observations suggest that
the compounds interact with CT-DNA by intercalation.
The application of electronic absorption spectroscopy in
DNA-binding studies is one of the most useful techniques
[36]. To obtain the absorption spectra, the required amount
of CT-DNA was added to both the compound and refer-
ence solutions to eliminate the absorbance of CT-DNA
itself. From the absorption titration data, the binding con-
stant (Kb) was determined using the following equation
[37]:
Table 3 Selected hydrogen bonding distances (A) and angles (°) for
complex 1
D–HÁÁÁA
d(D–H) d(HÁÁÁA) d(DÁÁÁA) \(DHA)
O(7)–H(3 W)ÁÁÁO(6)#1
O(6)–H(2 W)ÁÁÁO(4)#1
O(6)–H(1 W)ÁÁÁO(4)#3
0.87
0.85
0.85
2.11
1.92
2.00
2.57
2.57
2.51
2.50
2.59
2.880(5) 146.9
2.766(5) 175.0
2.833(5) 166.3
3.244(3) 126.8
3.253(3) 127.7
3.404(4) 160.5
3.446(4) 165.8
3.522(5) 161.9
C(40)–H(40B)ÁÁÁN(5)#1 0.97
C(30)–H(30B)ÁÁÁN(7)#1 0.97
C(23)–H(23)ÁÁÁO(6)#1
C(40)–H(40A)ÁÁÁO(3)#2 0.97
C(37)–H(37A)ÁÁÁO(3)#2 0.97
0.93
Symmetry transformations used to generate equivalent atoms: #1 x, y,
z; #2 –x ? 1, y - 1/2, -z ? 1/2; #3 –x ? 2, -y ? 1, -z ? 1
½DNAŠ=ðea À efÞ ¼ ½DNAŠ=ðeb À efÞ þ 1=Kbðeb À efÞ
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Transition Met Chem (2015) 40:555–564
Fig. 3 2D layer generated by
hydrogen bonds (dashed lines)
in complex 1
Fig. 4 Environment of the
Ag(I) cation in complex 2
showing 30 % thermal
probability ellipsoids. The H
atoms are omitted
Fig. 6. A band is observed at 270 nm for both complexes 1
and 2. Upon addition of increasing CT-DNA concentra-
tions, these bands exhibited hypochromism of 49.8 and
49.0 %, respectively. From the electronic absorption
spectroscopy experiments, Kb values for complexes 1 and 2
were obtained as 3.88 9 105 and 1.31 9 105 M-1, re-
spectively. The charge transfer of the ligands resulting
from coordination of the ligands to the Ag(I) atom should
reduce the charge density of the planar conjugate system,
which is conducive to intercalation [38].
where [DNA] is the concentration of CT-DNA in the base
pairs, ea corresponds to the observed extinction coefficient
(Aobsd/[M]), ef corresponds to the extinction coefficient of
the free compound, eb is the extinction coefficient of the
complex when fully bound to CT-DNA, and Kb is the in-
trinsic binding constant. The ratio of slope to intercept in
the plot of [DNA]/(ea - ef) versus [DNA] gave the value of
Kb.
The electronic absorption spectra of the two complexes
in the absence and presence of CT-DNA are shown in
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Transition Met Chem (2015) 40:555–564
561
Fig. 5 The 1D supramolecular
chain of complex 2 formed via
p–p stacking interactions,
C–HÁÁÁO hydrogen bonding
interactions and C–HÁÁÁAg
H-bonding
Fig. 6 Electronic spectra of the complex 1 (a) and complex 2 (b) in
Tris–HCl buffer upon addition of CT-DNA. The arrow shows the
emission intensity changes upon increasing DNA concentrations.
[DNA]/(ea - ef) versus [DNA] for the titration of the complex 1
(c) and complex 2 (d) with CT-DNA
Next, the DNA binding was investigated by fluorescence
spectroscopy. EB does not show any appreciable emission
in buffer solution due to fluorescence quenching by the
solvent. Upon addition of the ligand or complex to a so-
lution containing EB, no change in the fluorescence spectra
was observed. However, the fluorescence intensity of EB is
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Transition Met Chem (2015) 40:555–564
Fig. 7 Emission spectra of EB bound to CT-DNA in the presence of
complex 1 (a) and complex 2 (b), kex = 596 nm. The arrows show
the intensity changes upon increasing concentrations of the
complexes. Fluorescence quenching curves of EB bound to CT-
DNA by the complex 1 (c) and complex 2 (d). [Plots of I0/I vs.
(Complex).]
Fig. 8 Effect of increasing amounts of the complexes on the relative
viscosity of DNA at 25.0 0.1 °C
Fig. 9 Plots of hydroxyl radical scavenging effect (%) for the
complex 2
greatly enhanced upon addition of CT-DNA, due to its
strong intercalation within the DNA base pairs. Addition of
a second molecule, which may bind to DNA more strongly
than EB, can result in a decrease in the DNA-induced EB
emission by displacement of EB [39]. To further clarify the
interaction of the complex with DNA, a competitive
binding experiment was carried out in a buffer by keeping
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Transition Met Chem (2015) 40:555–564
563
[DNA]/[EB] = 1.13 and varying the concentration of the
complex. Fluorescence spectra of EB were measured using
an excitation wavelength of 520 nm, and the emission
range was set between 550 and 750 nm. The spectra were
analyzed according to the classical Stern–Volmer equation
[40]:
with those of the well-known natural antioxidants mannitol and
vitamin C, using the same method as reported in a previous
paper [44, 45]. The 50 % inhibitory concentration (IC50) values
of mannitol and vitamin C are ca 9.6 9 10-3 and
8.7 9 10-3 M, respectively. According to the antioxidant ex-
periments, the IC50 value of the Ag(I) complex 2 is
7.95 9 10-3 M, which implies that complex 2 is a
better scavenger of hydroxyl radicals than both mannitol and
vitamin C.
I0=I ¼ 1 þ Ksv½QŠ
where I0 and I are the fluorescence intensities at 599 nm in
the absence and presence of the quencher, respectively, Ksv is
the linear Stern–Volmer quenching constant, and [Q] is the
concentration of the quencher. In these experiments, [CT-
Conclusion
DNA] = 2.5 9 10-3 and [EB] = 2.2 9 10-3 mol L-1
.
The addition of the compounds results in a significant
decrease in the intensity of the emission band of the DNA-
EB system at 593 nm, indicating competitive binding of
the compounds to DNA. The Stern–Volmer plots (Fig. 7)
show that the quenching of EB by the complexes follows a
linear relationship, consistent with intercalation of the test
compounds. The Ksv values for complexes 1 and 2 were
3.58 9 103 and 1.61 9 103 M-1, respectively. Moreover,
the binding strengths of the complexes followed the same
order as from the UV–Vis experiments.
Two Ag(I) complexes with different flexible bis(benzimida-
zole) ligandsandthe samecrotonateanionhavebeenprepared
and characterized through single-crystal X-ray diffraction
analyses. These compounds display diverse architectures
from 1D to 3D. The results indicate that the bis(benzimida-
zole) ligands and crotonate ligands both have important ef-
fects on structures of the complexes. DNA-binding studies
indicate that both complexes bind to DNA via intercalation.
Complex 2 can bind to DNA more strongly than complex 1
and also has hydroxyl radical scavenging activity. These re-
sults suggest that the Ag(I) complexes could be useful in de-
sign of new antitumor drugs.
Hydrodynamic measurements that are sensitive to DNA
length changes are regarded as the least ambiguous and
most critical test of a binding model in solution in the
absence of crystallographic structural data [41, 42]. Vis-
cosity values were calculated from the observed flow times
of CT-DNA solutions corrected for the flow time of buffer
alone (t0), g = (t - t0) [43].
As increasing amounts of the complexes were added, the
viscosity of the DNA increased steadily. The values of (g/
g0)1/3 were plotted against [compound]/[DNA] (Fig. 8). In
classical intercalation, the DNA helix lengthens as base
pairs are separated to accommodate the bound ligand,
leading to increased DNA viscosity as observed for known
intercalators [35], whereas a partial, non-classical ligand
intercalation causes a bend (or kink) in the DNA helix,
reducing its effective length and therefore its viscosity [19].
Hence, these results provide further evidence that these
complexes intercalate with CT-DNA [39] and their DNA-
binding affinities follow the order: 1 [ 2. The reason for
the different binding affinities can be attributed to differ-
ences in steric hindrance and electron density, resulting
from the different substituents and geometric structures.
Supplementary material
Crystallographic data (excluding structure factors) for the
structure in this article have been deposited with the
Cambridge Crystallographic Data Center as supplementary
publication CCDC 1000103 and CCDC 1000104. Copies
of the data can be obtained, free of charge, on application
to the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.
Acknowledgments The present research was supported by the
National Natural Science Foundation of China (Grant No. 21367017),
the Fundamental Research Funds for the Gansu Province Universities
(212086), Natural Science Foundation of Gansu Province (Grant No.
1212RJZA037) and ‘Qing Lan’ Talent Engineering Funds for Lanz-
hou Jiaotong University.
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