Synthesis, characterization, and DNA-binding of enantiomers of iron(II) Schiff base complexes

Article abstract of DOI:10.1016/j.poly.2012.12.027

Two pairs of iron(II) chiral enantiomers fac-Δ-[Fe(S-L1) ₃][ClO₄]₂ and fac-Λ-[Fe(R-L1) ₃][ClO₄]₂ (Δ-1 and Λ-1), fac-Δ-[Fe(S-L2)₃][ClO₄]₂ and fac-Λ-[Fe(R-L2)

Full text of DOI:10.1016/j.poly.2012.12.027

Polyhedron 51 (2013) 186–191
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Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis, characterization, and DNA-binding of enantiomers of iron(II) Schiff
base complexes
a
a
a
a
a
a
Zhi-Guo Gu a,b, , Jing-Jing Na , Fei-Fei Bao , Xin-Xin Xu , Wen Zhou , Chun-Yan Pang , Zaijun Li
⇑
a School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, PR China
b Coordination Chemistry Institute and the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093,
PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two pairs of iron(II) chiral enantiomers fac-
D
-[Fe(S-L1)3][ClO4]2 and fac-
K-[Fe(R-L1)3][ClO4]2 (D-1 and
Received 23 October 2012
Accepted 21 December 2012
Available online 7 January 2013
K
-1), fac-
D
-[Fe(S-L2)3][ClO4]2 and fac-
K
-[Fe(R-L2)3][ClO4]2
(
D
-2 and -2), L1 = (R/S)-( )-1-naphthyl-N-
K
(pyridine-2-ylmethylene)ethanamine, L2 = (R/S)-( )-2-naphthyl-N-(pyridine-2-ylmethylene)ethanamine
were synthesized and characterized by elemental analysis, IR, UV–Vis, CD and 1H NMR spectra. The
X-ray structural analyses of
nation geometry for N6 donor atoms by three bidentate ligands. R-L1 ligand induces the fac-
while S-L2 ligand induces the fac- isomer. The enantioselective binding of iron(II) chiral enantiomers
K
-1 and
D
-2 revealed that the iron(II) complexes possess octahedral coordi-
Keywords:
Schiff base
Iron(II) complexes
Enantiomers
DNA binding
Enantioselectivity
K
isomer,
D
to calf-thymus DNA (ct-DNA) has been investigated by methods of UV–Vis, fluorescence, and circular
dichroism spectrometry. All the complexes could bind to ct-DNA and showed different binding affinities
with the binding constants ranging from 0.91 ꢀ 105 to 1.43 ꢀ 105 Mꢁ1. Moreover, the
D enantiomers
exhibited more efficient DNA interaction with respect to the
K enantiomers.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
straightforward and economical asymmetric synthesis of nonrace-
mic ruthenium(II) polypyridyl complexes based on using the read-
ily available starting material together with chiral auxiliary
[19,20].
In order to develop new homochiral octahedral metal com-
plexes fitting the right-handed DNA and to explore their enanti-
oselectivity, we focused on tris(diimine) iron(II) complexes
In the past few decades, small molecule transition metal com-
plexes that can interact with DNA have attracted much attention
in the field of bioinorganic chemistry [1–5]. In particular, octahe-
dral polypyridyl transition metal complexes with extended aro-
matic heterocyclic ligands have been used extensively as DNA
structural probes, DNA molecular light-switch, DNA electron trans-
fer, DNA cleavaging reagents and potential anti-cancer drugs [6–
10]. Chiral recognition of DNA is crucial for developing structural
probes of DNA conformation and rational drug design. Since natu-
ral B-form DNA with right-handed double helix is inherently chiral,
its interactions with chiral metal complexes should be, in principal
diastereoselective [11]. This was indeed observed in particular chi-
ral propeller-like octahedral complexes with two possible confor-
which present a variety of possible isomers (
D and K, fac and
mer). Our strategies employed include the use of rational de-
signed enantiopure unsymmetrical ligand by which chiral infor-
mation can be transferred to the metal centre [21]. In this way, a
predetermination of the absolute configuration at the metal cen-
tre can be reached [22]. We report here the assembly of optically
pure, single diastereomer fac-tris(diimine) Fe(II) complexes fac-
D
-[Fe(S-L1)3][ClO4]2 and fac-
fac- -[Fe(S-L2)3][ClO4]2 and fac-
K-2), by introducing optically pure (R/S)-( )-1-naphthyl-N-(pyri-
K
-[Fe(R-L1)3][ClO4]2
(
D
-1 and
K-1),
mations, i.e. the left-handed
(
K
)
and the right-handed
(
D
)
D
K
-[Fe(R-L2)3][ClO4]2
(D
-2 and
enantiomers [12–17]. However, determination of optical purity of
octahedral metal complexes was challenging, and separation by
diastereomeric crystallization or chromatographic techniques has
inherently low yields [18]. Recently, Muggers’ group introduced a
dine-2-ylmethylene)ethanamine or (R/S)-( )-2-naphthyl-N-(pyri-
dine-2-ylmethylene)ethanamine as ligands (Scheme 1), and the
detailed results of enantioselective studies on the ct-DNA bind-
ing of the iron(II) complexes. It is interesting that complexes 1
with 1-naphthyl groups have stronger DNA binding ability than
⇑
Corresponding author at: School of Chemical and Material Engineering,
Jiangnan University, Wuxi 214122, PR China. Tel.: +86 510 85917090; fax: +86
510 85917763.
complexes 2 with 2-naphthyl groups, and the
exhibited more efficient DNA interaction with respect to the
-enantiomer.
D-enantiomer
K
E-mail address: zhiguogu@jiangnan.edu.cn (Z.-G. Gu).
0277-5387/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.12.027

Z.-G. Gu et al. / Polyhedron 51 (2013) 186–191
187
Scheme 1. The molecular structures of chiral Schiff base Fe(II) complexes.
calibrated conventionally using 0.060% ACS for intensity and a hol-
mium filter for wavelength.
2. Experimental
2.1. Materials and methods
2.2. Synthesis of fac-[Fe(R/S-L1)3][ClO4]2ꢂCH3CN and fac-[Fe(R/S-
L2)3][ClO4]2ꢂ2CH3CN
Calf thymus DNA (ct-DNA) was purchased from Sino-American
Biotechnology Co., Ltd. (R/S)-( )-1-naphthyl-N-(pyridine-2-ylmeth-
ylene)ethanamine, (R/S)-( )-2-naphthyl-N-(pyridine-2-ylmethyl-
ene)ethanamine, Fe(ClO4)2ꢂ6H2O 2-pyridinecarboxaldehyde, and
ethidium bromide (EB) were purchased from Sigma–Aldrich and
used as received. All other reagents and solvents were purchased
from commercial sources and used without further purification.
A mixture of 2-pyridinecarboxaldehyde (0.064 g, 0.6 mmol) and
(R/S)-(1-naphthyl)ethylamine or (R/S)-(2-naphthyl)ethylamine
(0.100 g, 0.6 mmol) dissolved in 30 mL acetonitrile was refluxed
for 3 h. After the mixture cooled to room temperature, Fe(ClO4)2ꢂ
6H2O (0.073 g, 0.2 mmol) was added, and the solution turned pur-
ple immediately. The solution was stirred overnight before diethyl
ether was added dropwise until signs of crystallization. The purple
crystals were filtered and dried under vacuum. The complexes
were recrystallized from acetonitrile by slow diffusion of anhy-
drous ether. All the complexes are stable and nonhygroscopic in
air at room temperature. The complexes were highly soluble in
MeOH, DMSO, MeCN, slightly soluble in water, acetone and EtOH.
Ultrapure water (18.2 M
X cm) was used in all experiments. The
solution of DNA was prepared in 5 mM tris(hydroxymethyl)meth-
anamin–HCl (Tris–HCl) buffer with 50 mM NaCl, pH 7.2, and all
DNA experiments were conducted in this buffer solution. Given
the ratio of UV absorbance at 260 and 280 nm, A260/A280 = 1.9, the
DNA was sufficiently free of protein [23]. The DNA concentration
(represented by molar concentration of bases pairs) was determined
spectroscopically by using the molar extinction coefficient at the
maximum of the long wavelength absorbance:
e
= 6600 cmꢁ1
molꢁ1 dm3. Concentration of stock solutions of the metal complexes
were 10ꢁ3 M in acetonitrile. fac-[Fe(R/S-L1)3][ClO4]2ꢂCH3CN 1 and
fac-[Fe(R/S-L2)3][ClO4]2ꢂ2CH3CN 2 were synthesized as described
below. 1H NMR spectra were recorded on AVANCE III (400 MHz)
instrument at 298 K using standard Bruker software. The spectra
were internally referenced using the residual protio solvent reso-
nance relative to tetramethylsilane (d = 0 ppm). Infrared spectra
were measured on an ABB Bomem FTLA 2000–104 spectrometer
with KBr pellets in the 400–4000 cmꢁ1 region. Element analyses
were conducted on elementar corporation vario EL III analyzer.
Circular dichroism (CD) spectra was carried out using a MOS-450/
AF-CD spectropolarimeter at room temperature, which was
2.2.1. fac-
K
-[Fe(R-L1)3][ClO4]2ꢂCH3CN (
K-1)
Purple crystalline solid (68%): IR (KBr cmꢁ1):
m
= 3444 (w), 2975
(w), 2936 (w), 2360 (w), 2341 (w), 1638 (s), 1379 (m), 1113 (w),
1088 (s), 760 (s), 703 (m), 620 (s); 1H NMR (400 MHz, (CD3)2SO
dppm): 8.634 (s, 1H, H–C@N), 8.553 (d, J = 10.8 Hz, 1H, Py), 8.319
(d, J = 8.4 Hz, 1H, Py), 8.068 (m, 1H, Py), 7.960 (m, 1H, Py), 7.890–
7.760 (broad m, 3H, naph), 7.644–7.450 (broad m, 4H, naph),
5.535 (q, J = 7.5 Hz, 1H, C–H), 1.665 (d, J = 6.4 Hz, 3H, CH3); Anal.
Calc. for C56H51Cl2FeN7O8: C, 62.46; N, 9.11; H, 4.77. Found: C,
62.31; N, 9.02; H, 4.86%. UV–Vis kmax: 569, 519, 333, 280 nm. CD
(nm): 593 (negative), 522 (positive), 361 (positive), 323 (negative),
285 (positive).

188
Z.-G. Gu et al. / Polyhedron 51 (2013) 186–191
Table 1
2.2.2. fac-
D
-[Fe(S-L1)3][ClO4]2ꢂCH3CN (
D-1)
Purple crystalline solid (63%): IR (KBr cmꢁ1):
m = 3428 (w), 2968
Summary of crystallographic data for the complexes
K
-1 and
-2
D-2.
(w), 2924 (w), 2367 (w), 2335 (w), 1638 (s), 1379 (m), 1120 (w),
1088 (s), 765 (s), 712 (m), 620 (s); 1H NMR (400 MHz, (CD3)2SO
dppm): 8.634 (s, 1H, H–C@N), 8.553(d, J = 10.8 Hz, 1H, Py), 8.319
(d, J = 8.4 Hz, 1H, Py), 8.068 (m, 1H, Py), 7.960 (m, 1H, Py), 7.890–
7.760 (broad m, 3H, naph), 7.644–7.449 (broad m, 4H, naph),
5.533 (q, J = 7.5 Hz, 1H, C–H), 1.665 (d, J = 6.4 Hz, 3H, CH3); Anal.
Calc. for C56H51Cl2FeN7O8: C, 62.46; N, 9.11; H, 4.77. Found: C,
62.28; N, 9.06; H, 4.91%. UV–Vis kmax: 569, 519, 333, 280 nm. CD
(nm): 593 (positive), 522 (negative), 361 (negative), 323 (positive),
285 (negative).
K
-1
D
Formula
C
56H51Cl2FeN7O8
C58H54Cl2FeN8O8
1117.84
triclinic
Formula weight
Crystal system
Space group
a (Å)
b (Å)
c (Å)
1076.79
cubic
P213
17.370(2)
17.370(2)
17.370(2)
90
P1
11.689(3)
11.845(3)
12.183(3)
106.183(5)
110.174(4)
107.910(5)
1359.6(5)
1
1.365
298(2)
0.439
2.00–25.10
582
a
(°)
b (°)
90
90
c
(°)
V (Å3)
5240.9(12)
4
1.365
298(2)
0.452
1.66–27.52
2240
ꢁ19 6 h 6 22,
ꢁ21 6 k 6 22,
ꢁ22 6 l 6 18
3962/8/223
Z
Dcalc (g cmꢁ3
T (K)
)
2.2.3. fac-
K
-[Fe(R-L2)3][ClO4]2ꢂ2CH3CN (
K-2)
Purple crystalline solid (72%): IR (KBr cmꢁ1):
m
= 3474 (w), 2943
l
(mmꢁ1
)
(w), 2926 (w), 2329 (w), 2287 (w), 1608 (s), 1379 (m), 1113 (w),
1088 (s), 759 (s), 696 (m), 620 (s); 1H NMR (400 MHz, (CD3)2SO
dppm): 8.629 (s, 1H, H–C@N), 8.550(d, J = 10.4 Hz, 1H, Py), 8.320
(d, J = 8.4 Hz, 1H, Py), 8.067 (m, 1H, Py), 7.959 (m, 1H, Py), 7.907–
7.759 (broad m, 3H, naph), 7.642–7.451 (broad m, 4H, naph),
5.533 (q, J = 7.6 Hz, 1H, C–H), 1.665 (d, J = 6.4 Hz, 3H, CH3); Anal.
Calc. for C58H54Cl2FeN8O8: C, 62.32; N, 10.02; H, 4.87. Found: C,
62.18; N, 9.87; H, 4.95%. UV–Vis kmax: 568, 519, 341, 279 nm. CD
(nm): 590 (negative), 515 (positive), 358 (positive), 313 (negative),
286 (positive).
h (°)
F(000)
Index ranges
ꢁ96h 6 13,
ꢁ14 6 k 6 12,
ꢁ14 6 l 6 14
5995/1580/697
Data/restraints/
parameters
Goodness-of-fit
0.881
1.019
(GOF) on (F2)
R1a, wR2b (I > 2
r
(I)) 0.0489, 0.1133
0.0750, 0.1789
0.0978, 0.2224
0.00(2)
R1a, wR2 (all data) 0.0792, 0.1225
b
Flack X
0.01(3)
a
R1
wR2 = [
=
R
||Fo| ꢁ |Fc||/
RFo|.
2.2.4. fac-
D
-[Fe(S-L2)3][ClO4]2ꢂ2CH3CN (
D-2)
R .
w(Fo2)]1/2
b
2
Purple crystalline solid (74%): IR (KBr cmꢁ1):
m
= 3468 (w), 2975
R
w(Fo ꢁ Fc2)2/
(w), 2954 (w), 2322 (w), 2265 (w), 1608 (s), 1379 (m), 1113 (w),
1088(s), 752(s), 698(m), 620(s); 1H NMR (400 MHz, (CD3)2SO
dppm): 8.630 (s, 1H, H–C@N), 8.551(d, J = 10.4 Hz, 1H, Py), 8.320
(d, J = 8.4 Hz, 1H, Py), 8.067 (m, 1H, Py), 7.959 (m, 1H, Py), 7.907–
7.757 (broad m, 3H, naph), 7.642–7.451 (broad m, 4H, naph),
5.533 (q, J = 7.6 Hz, 1H, C-H), 1.665 (d, J = 6.4 Hz, 3H, CH3); Anal.
Calc. for C58H54Cl2FeN8O8: C, 62.32; N, 10.02; H, 4.87. Found: C,
62.15; N, 9.91; H, 4.99%. UV–Vis kmax: 568, 519, 341, 279 nm. CD
(nm): 590 (positive), 515 (negative), 358 (negative), 313 (positive),
286 (negative).
Table 2
Selected bond lengths (Å) and angles (°) for
K
-1 and
D
-2.
K-1
Fe(1)–N(1)
N(1A)–Fe(1)–N(2)
N(1)–Fe(1)–N(2)
1.971(3)
91.60(11)
81.45(12)
Fe(1)–N(2)
N(1A)–Fe(1)–N(1)
N(2A)–Fe(1)–N(2)
1.998(3)
92.14(12)
95.16(11)
D
-2
Fe(1)–N(4)
Fe(1)–N(2)
Fe(1)–N(5)
N(4)–Fe(1)–N(1)
N(1)–Fe(1)–N(2)
N(1)–Fe(1)–N(3)
N(4)–Fe(1)–N(6)
N(2)–Fe(1)–N(6)
N(2)–Fe(1)–N(5)
1.954(9)
1.974(8)
1.991(9)
92.3(3)
81.0(3)
94.6(3)
96.5(3)
94.0(3)
92.2(3)
Fe(1)–N(1)
Fe(1)–N(3)
Fe(1)–N(6)
N(4)–Fe(1)–N(2)
N(4)–Fe(1)–N(3)
N(3)–Fe(1)–N(6)
N(1)–Fe(1)–N(5)
N(3)–Fe(1)–N(5)
N(6)–Fe(1)–N(5)
1.972(7)
1.987(8)
1.991(8)
94.7(3)
81.1(3)
91.0(3)
92.0(3)
92.2(3)
79.7(3)
2.3. X-ray crystallography
The crystal structures were determined on a Bruker APEX-II dif-
fractometer with a CCD area detector at 298 K with Mo K
a radia-
tion (k = 0.71073 Å). Cell parameters were retrieved using SMART
software and refined using SAINT [24] on all observed reflections.
Data were collected using a narrow-frame method with scan
Symmetry codes: A z + 1/2, ꢁx + 3/2, ꢁy + 1.
widths of 0.30° in
x and an exposure time of 10s/frame. The highly
redundant data sets were reduced using SAINT [24] and corrected for
Lorentz and polarization effects. Absorption corrections were ap-
plied using SADABS [25] supplied by Bruker. Structures were solved
by direct methods using the program SHELXS-97 [26]. The positions
of metal atoms and their first coordination spheres were located
from direct-methods E-maps; other non-hydrogen atoms were
found in alternating difference Fourier syntheses and least-squares
refinement cycles and, during the final cycles, refined anisotropi-
cally. Hydrogen atoms were placed in calculated position and re-
concentration of acetonitrile as 1% throughout the experiments.
Accordingly, incremental quantity of DNA solution from 0 to
84
lM was added to the fixed concentration of metal complex
solution 30
lM, NaCl and Tris–HCl buffer concentrations remained
constant. UV–Vis absorbance spectra were collected on Shimadzu
UV-2101 PC scanning spectrophotometer.
fined as riding atoms with
a uniform value of Uiso. Final
crystallographic data and values of R1 and wR are listed in Table 1.
Relevant bond distances and angles are listed in Table 2.
2.4.2. Ethidium bromide (EB) fluorescence competition binding assay
The fluorescence spectra recorded in Tris–HCl buffer of the
complex concentration was incrementally increased from 0 to
2.4. DNA-binding studies
30
(4
l
M while keeping the concentrations of DNA (80
lM) and EB
2.4.1. Absorption spectroscopy
lM) constant. Fluorescence spectra were collected on a Shima-
The stock solution of chiral Schiff base iron(II) complexes in ace-
tonitrile (1 mM) were used for spectroscopic titration of DNA solu-
tion in Tris–HCl buffer (5 mM, 50 mM NaCl, pH 7.2), by keeping the
dzu RF-5301 spectrofluorometer with excitation at 528 nm, excita-
tion slit 5.0 and emission slit 5.0 nm. The emission spectra were
recorded at 550–700 nm.

Z.-G. Gu et al. / Polyhedron 51 (2013) 186–191
189
2.4.3. Circular dichroism spectroscopy
The circular dichroism (CD) titration series was carried out
using a MOS-450/AF-CD spectropolarimeter at room temperature
with the fixed concentration constant at 30 lM of the chiral metal
complexes. The baseline was subtracted from Tris–HCl buffer
(5 mM, 50 mM NaCl, pH 7.2) for each data set. By adding equal vol-
umes of the concentrated DNA solution to the 1 cm path length
flow cell, the DNA:metal complex ratios are 1:6, 1:3, 1:2, 2:3,
1:1, respectively. Each CD spectrum has been subtracted by free
DNA thus the spectrum purely reflect the changes in the enantio-
mer of the complex upon binding DNA.
3. Results and discussion
3.1. Synthesis and characterization
Fig. 1. Structure of the cation in the asymmetric unit of fac-
K
-[Fe(R-L1)3]
The diamagnetic tris-pyridine/imine Schiff base Fe(II) com-
plexes were prepared by a one-pot strategy, mixing iron(II) per-
chlorate hexahydrate into a solution of the appropriate chiral
naphthylethylamine and 2-pyridinecarboxaldehyde in acetonitrile.
This led to the immediate formation of intense purple solutions,
from which the perchlorate salt crystals could be readily obtained
with high yields by diffusion of anhydrous ether. The complexes 1
and 2 were characterized by various spectroscopic and analytical
techniques. Solid IR spectroscopic analysis revealed intense
[ClO4]2ꢂCH3CN (
K-1) with thermal ellipsoids are shown at 30% probability. H
atoms, counterions and solvent molecules omitted for clarity. (Symmetry codes: A
z + 1/2, ꢁx + 3/2, ꢁy + 1; B ꢁy + 3/2, ꢁz + 1, x ꢁ ½.)
[Fe(R-L1)3]2+ and [Fe(S-L2)3]2+ adopt exclusively
K and D form,
respectively. It seems that the stereochemically active groups of
the ligands orient the configuration of the overall complexes,
where the ligands transfer their chirality to the metal centre, pre-
absorptions at 1638 for 1 and 1608 cmꢁ1 for 2, due to the mC
@
N
venting the classical racemization of
of -1 and
K
/
D
species [22]. The cations
contacts be-
K
D
-2 pack through weak T-shaped C–Hꢂ ꢂ ꢂ
p
stretching vibration of the Schiff base ligands at room temperaturꢁe,
while peeks at 1088 and 620 cmꢁ1 revealed the existence of ClO4
.
tween the phenyl groups, resulting in the formation of three-
dimensional supramolecular structures with channels filled with
UV–Vis spectra for all the complexes show the absorption bands
for coordinated ligand at 280 nm, and the characteristic MLCT tran-
ꢁ
ClO4 anions and acetonitrile molecules.
sition at 568 nm. The CD spectra of
D-1 and K-1, D-2 and K-2 are
mirror images of each other which contain intense features span-
ning the whole UV–Vis region, demonstrating their absolute con-
figuration and enantiopurity. The 1H NMR spectra for all the
iron(II) complexes showed only one set of coordinated ligand sig-
nals, hence a single diastereoisomer with a C3-symmetric fac struc-
3.2. DNA binding experiments
3.2.1. Electronic absorption spectroscopy
UV–Vis spectroscopy is the most useful technique in DNA-
binding studies [28]. Hypochromism and red shift are usually ob-
served when a complex binds to DNA. The extent of the hypochro-
mism commonly parallels the binding strength. Fig. S1 and Table 3
ture is formed. Take
K-2 as an example, it showed doublet at 1.665
for the CH3 protons, quartet at 5.533 for CH proton, singlet at 8.629
for H–C@N proton. The protons of pyridine appeared at 8.550–
7.959, the multiplet at 7.907–7.759 and 7.642–7.451 are belonging
to the seven protons of naphthalene. Extensive overlapping of the
1H signals in the aromatic region renders complete spectral assign-
ment difficult.
show the results of the UV–Vis spectroscopy of the complexes
-1, -2 and -2 titrated against DNA at a constant complexes
concentration of 30 M. All complexes showed some extent of
hypochromism by increasing DNA concentrations from to
84 M. Meanwhile, different complexes with different chirality
D-1,
K
D
K
l
0
l
To further confirm the structures of the chiral Schiff base Fe(II)
complexes, the crystal structures of
X-ray crystallography revealed that
K
-1 and
D
-2 were determined.
K
-1 and
D-2 crystallized in the
chiral space groups P213 and P1, respectively. The two structures
both consist of one [Fe(L)3]2+ cation, two perchlorate counterions,
and uncoordinated acetonitrile molecules (Figs. 1 and 2). The Fe(II)
sites with N6 coordination environments in
distorted octahedral geometries. The average iron–nitrogen bond
lengths of 1.984(5) for -1 and 1.978(1) for -2 are consistent
with the low-spin state at 298 K [27]. The three unsymmetrical li-
gands in -1 and -2 mount a face of the octahedron designating a
fac arrangement, in which each of the three pyridine units forms an
intramolecular stacking interaction with a naphthyl unit on a
K-1 and D-2 both form
K
D
K
D
p–p
neighboring ligand. The average centroid-to-centroid distances are
3.997 Å and 3.558 Å, and the average angles between arene planes
are 16.441° and 5.932° for
lel-displaced interactions of the rings could account for the
extraordinary stereoselectivity for the fac structures observed in
-1 and -2. Comparable stacking effects have been observed
K-1 and D-2, respectively. These paral-
p–p
K
D
p–p
between the pyridine group and the phenyl ring in the fac-Fe(II)
complexes with diimine ligands derived from 2-iminopyridine
and (R)-2-phenylglycinol derivatives [21]. The octahedral cations
Fig. 2. Structure of the cation in the asymmetric unit of fac-
ꢂ2CH3CN ( -2) with thermal ellipsoids are shown at 30% probability. H atoms,
counterions and solvent molecules omitted for clarity.
D-[Fe(S-L2)3][ClO4]2-
D

190
Z.-G. Gu et al. / Polyhedron 51 (2013) 186–191
Table 3
base complexes (Fig. S2). This might be due to the displacement
The data for UV–Vis titration of complexes
K-1, D-1, K-2, and D-2 against DNA.
of EB by bivalent metal complex cations results from charge neu-
tralization on the DNA backbone, which is accompanied by a part
of collapse of linear DNA. The EB insert in this area deviated from
the base pair [32]. Moreover, the binding equilibrium of EB to-
wards the solution phase shifted, which is confirmed by the change
of peak data of luminescence [33] (peak data see Table 4).
Based on Fig. S2, the Stern–Volmer constants were calculated by
using following functional equation [34]:
Complexes kmax (free)
kmax (bound)
D
(nm)
k
Hypochromism
(%)
(nm)
(nm)
K
-1
-1
-2
-2
569 258
569 258
569 258
569 258
572 259
572 258
570 258
569 258
3
3
1
0
1
0
0
0
16.9
17.3
8.2
D
K
D
10.1
Table 4
Binding constant of complexes
I0=I ¼ 1 þ K ꢂ r
ð1Þ
K
-1,
D
-1,
K
-2, and D-2.
In the above equation I0 and I are the emission intensities in the
absence and presence of metal complexes; r is the ratio of the total
concentration of chiral metal complexes to DNA; and K is the
Stern–Volmer quenches constant. The apparent binding constants
Complexes Hypochromism kmax
kmax
K
Kapp/105
(%)
(DNA + EB) (DNA + EB+
complexes)
(Mꢁ1
)
K
D
K
D
-1
-1
-2
-2
55.9
64.6
51.8
52.5
600
603
600
600
607
609
607
607
3.40 0.045 1.11
4.87 0.015 1.43
2.87 0.015 0.91
2.96 0.021 0.98
(Kapp) for enantiomers are calculated from KEB ꢀ [EB] = Kapp
ꢀ
[drug], where [EB] is the concentration of EB (4 M); [drug] is
l
the concentration of chiral metal compounds at a 50% reduction
of fluorescence; and KEB is known (KEB = 1.3 ꢀ 106 Mꢁ1 for
ct-DNA) [35]. The data were shown in Table 4. The results of fluo-
rescence experiment are in accordance with the UV/vis titration
results presented above. The values of K are sufficiently large to
conclude that in the experiments reported herein all the iron(II)
metal complexes can bind to DNA, and the qualitative ranking of
caused varying changes in their electronic absorption spectros-
copy. The bands around 569 nm of iron(II) metal ? ligand charge
transfer (MLCT) displayed minor red shift and hypochromism, indi-
cating mainly groove binding mode instead of intercalative. When
the chiral mononuclear iron(II) complexes with two positive
charges bind with DNA in the groove, the negative charges on
the phosphates of the DNA backbone will be neutralized. There-
fore, the structure of DNA becomes loosen or collapse at the bind-
ing area, and the configuration of DNA shows some extent of
bending or distortion [29,30]. The hypochromic rates at kmax (free)
of enantiomers are showed in Table 3. Interestingly, among all the
the DNA binding strength is
D-1 > K-1 > D-2 > K-2.
3.2.3. Circular dichroism spectroscopy
CD is the difference in absorption of left and right circularly
polarized light, and is uniquely sensitive to any asymmetric inter-
action such as that between the chiral DNA and the chiral metal
complex. Therefore it has been utilized as a powerful tool for pro-
viding valuable information on the mode of binding between DNA
helix and chiral complexes [36,37]. The changes in intrinsic CD of
chiral complexes reflect the binding geometry and binding mode
of the complexes as well as the DNA bases. The CD spectra of
complexes we studied, the
D-enantiomers had better binding effi-
ciency than their -enantiomers.
K
3.2.2. Ethidium bromide fluorescence competition binding assay
The ethidium bromide (EB) displacement assay was usually
used to determine Stern–Volmer constant of the complex to bind
DNA particularly when the complex failed to show any lumines-
cence upon excitation of CT and LMCT band. In the present study,
D
-1 and
images of one another. With increasing addition of ct-DNA, the
CD spectra of -1, -1, -2, and -2 recorded from 400 to
K-1, D-2 and K-2 enantiomers are expected mirror
D
K
D
K
650 nm (MLCT region) are shown in Fig. 3. Compared with the
absorption spectra, the CD spectra showed dramatic distinction
in the bond strength between the different compounds upon addi-
tion of ct-DNA. In the MLCT wavelength region the decreases in
the solutions of chiral complexes
D-1, K-1, D-2, and K-2 in differ-
ent solvents did not show any luminescence irrespective of the
presence and absence of DNA. Therefore, EB which is known to
emit intense fluorescence in the presence of DNA due to the strong
intercalation of EB between the base pairs of DNA was used as a
spectral probe [31]. The EB competition assay was carried out for
each complex with the concentrations of DNA and EB being con-
stant. The intense fluorescence obtained by the interaction of EB
and DNA got diminished by the addition of chiral iron(II) Schiff
intensity for
changes of
D
-2 and
-1 and
K
-1 enantiomers are apparent, while the
D
K-2 are comparatively slight. This indicates
complexes 1 have better interaction with DNA than complexes 2
due to their special structures that can bind DNA in groove more
suitable. With increasing DNA, the MLCT region band is more
perturbed in the case of
D-enantiomer. This suggests that the
Fig. 3. The CD spectral profiles developing in the MLCT region upon the binding of
D-1, K-1, D-2, K-2 (30 lM) to ct-DNA in the presence of increasing concentration of
ct-DNA (0–30 lM), pathlength 1 cm (400–650 nm).

Z.-G. Gu et al. / Polyhedron 51 (2013) 186–191
191
D
K
-enantiomer interacts more strongly with DNA, compared to the
-isomer. For the -enantiomer, the right-handed propeller-like
structure with appropriate steric matching with right-handed ct-
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.poly.2012.12.027.
D
DNA displays a greater affinity than the
K
-enantiomer.
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This work was supported by the National Natural Science Foun-
dation of China (21101078 and 21276105), the Program for New
Century Excellent Talents in University of China (NCET-11-0657),
and the Natural Science Foundation of Jiangsu Province
(BK2011143), the Fundamental Research Funds for the Central Uni-
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Appendix A. Supplementary material
CCDC 894297 and 894298 contain the supplementary crystallo-
graphic data for
K-1 and D-2. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: (+44) 1223 336 033; or e-mail: de-
posit@ccdc.cam.ac.uk. Supplementary data associated with this