Syntheses, structures and DNA cleavage activity of NNO-tridentate Schiff base copper complexes

Article abstract of DOI:10.1016/j.poly.2012.07.009

A series of heteroleptic copper(II) complexes, [Cu(^RAIMP)(bpy)] (ClO₄) (1-7) and [Cu(^4-OMeQYMP)(B)](ClO₄) (B = bpy (8) or phen (9)), supported by NNO-tridentate Schiff base ligands (AIMP or QYMP) have been synthesized and characterized. X-ray crystal structural studies of complexes 1, 6 and 8, exhibit that these complexes are penta-coordinated mononuclear with a distorted square pyramidal geometry around the Cu center. Experimental results show that all of these complexes reveal good DNA cleavage activity in the presence of reducing agent 3-mercapto-propionic (MPA). However, in the photoinduced experiments at 365 nm, the activity was observed only at high concentration (200 μM) of the Cu complexes. The 1, 10-phenanthroline coordinated complex, 9, shows the higher activity towards DNA photocleavage than its analogue complex 8 with the bipyridine base.

Full text of DOI:10.1016/j.poly.2012.07.009

Polyhedron 45 (2012) 49–54
Contents lists available at SciVerse ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Syntheses, structures and DNA cleavage activity of NNO-tridentate Schiff base
copper complexes
b
c
d
b,
Bao-Tsan Ko a, , Chia-Chih Chang , Shu-Ling Lai , Fun-Jie Lai , Chu-Chieh Lin
⇑
⇑
a Department of Chemistry, Chung Yuan Christian University, Chung Li 320, Taiwan
b Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
c Department of Digital Media Design, Asian University, Taichung 413, Taiwan
d Department of Dermatology, Chi Mei Medical Center, Tainan 710, Taiwan
a r t i c l e i n f o
a b s t r a c t
A series of heteroleptic copper(II) complexes, [Cu(RAIMP)(bpy)](ClO4) (1–7) and [Cu(4-OMeQYMP)(B)]
(ClO4) (B = bpy (8) or phen (9)), supported by NNO-tridentate Schiff base ligands (AIMP or QYMP) have
been synthesized and characterized. X-ray crystal structural studies of complexes 1, 6 and 8, exhibit that
these complexes are penta-coordinated mononuclear with a distorted square pyramidal geometry
around the Cu center. Experimental results show that all of these complexes reveal good DNA cleavage
activity in the presence of reducing agent 3-mercapto-propionic (MPA). However, in the photoinduced
Article history:
Received 5 June 2012
Accepted 8 July 2012
Available online 22 July 2012
Keywords:
Copper complex
Schiff base
NNO-tridentate
DNA photocleavage
experiments at 365 nm, the activity was observed only at high concentration (200 lM) of the Cu com-
plexes. The 1, 10-phenanthroline coordinated complex, 9, shows the higher activity towards DNA photoc-
leavage than its analogue complex 8 with the bipyridine base.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
[23,34,35]. However, no copper complex of NNO-tridentate Schiff
base ligands has been isolated to date, and the electronic effect
Photodynamic therapy (PDT) has been widely used as an alter-
native treatment of localized tumors and intravascular diseases
due to its fewer side effects as compared to chemotherapy and
radiotherapy [1–5]. Psoralan has been used as a clinically drug in
PDT for skin cancers and skin diseases upon excitation using UVA
at 365 nm [6,7]. Recently, transition metal complexes photocleav-
ing DNA under physiological conditions are interested for their
various applications in nucleic acids chemistry [8–17]. Among
transition metals, copper is one of the essential trace elements in
human tissue and is involved in many important biological activi-
ties such as cytochrome c oxidase, superoxide dismutase and etc
[18–20]. Many copper complexes have demonstrated great antitu-
mor activity and are considered having relatively lower side effects
than platinum-based drugs [21,22]. Most recently, heteroleptic
copper(II) complexes associated with a variety pyridine based li-
gands have shown great reactivity toward photocleavage of DNA
[23–29].
of the substituents on the NNO-tridentate Schiff base derivatives
might result in dramatic differences of biological activities. Herein,
we report the syntheses, characterization and DNA cleavage activ-
ity of novel copper derivatives supported by NNO-tridentate Schiff
base ligands.
2. Results and discussion
2.1. Synthesis and crystal structure of copper complexes
A series of NNO-tridentate Schiff base ligands (RAIMP-H)
(HAIMP-H: R = 4-H; 5-NEt2AIMP-H: R = 5-NEt2; 4-NO2AIMP-H:
R = 4-NO2; 6-OMeAIMP-H: R = 6-OMe; 5-OMeAIMP-H: R = 5-OMe;
4-OMeAIMP-H: R = 4-OMe; NaphAIMP-H: R = 3,4-naphthalyl) were
prepared in high yield from the reaction of N,N-dimethylethane-
1,2-diamine with a variety of substituted 2-hydroxy-benzalde-
hyde, respectively (Scheme 1). Similarly, 4-OMeQYMP-H was
synthesized by the reaction of 2-hydroxy-5-methoxybenzaldehyde
with 8-aminoquinoline. All of these NNO-tridentate ligands
were characterized by spectroscopic studies as well as microanal-
yses. For instances, the 1H NMR spectra of 4-OMeAIMP-H exhibited
resonances about d 8.26 and 3.65 ppm for aldimine proton (N@CH)
and the methylene protons of –NCH2CH2, and signals of methylene
(d = 2.58 ppm) or methyl (d = 2.30 ppm) protons of –CH2CH2N-
(CH3)2, indicating the formation of the expected NNO-tridentate
Schiff base ligands are among the most versatile and useful li-
gands and their metal complexes have been widely used as cata-
lysts for many organic reactions such as ring-opening
polymerization and oxidation [30–33]. In addition, copper com-
plexes bearing Schiff base have shown good biological activities
⇑
Corresponding authors. Tel.: +886 3 2653327; fax: +886 3 2653399.
E-mail addresses: btko@cycu.edu.tw (B.-T. Ko), cchlin@mail.nchu.edu.tw (C.-C.
Lin).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.07.009

50
B.-T. Ko et al. / Polyhedron 45 (2012) 49–54
Scheme 1. Synthetic routes of ligands RAIMP-H, 4-OMeQYMP-H and complexes (1)–(9).
Schiff base ligand. The heteroleptic copper(II) complexes,
[Cu(RAIMP)(bpy)](ClO4) (1–7) were obtained by stepwise reaction
of Cu(OAc)2ꢀH2O with 2,20-bipyridine (bpy) and RAIMP-H in the
presence of NaClO4 (1.0 molar equiv.) in high yield (P73%). Addi-
tionally, the copper complex, [Cu(4-OMeQYMP)(B)](ClO4) (B = bpy
(8) or phen (9)) was prepared from the reaction of Cu(OAc)2ꢀH2O
with bpy or 1, 10-phenanthroline (phen) followed by the addition
of 4-OMeQYMP-H and NaClO4. All copper complexes were isolated
as crystalline solids and were characterized on the basis of electron
paramagnetic resonance (EPR) and cyclic voltammetry (CV) as well
as elemental analysis. In EPR spectrum, one single peak in the solid
state (Fig. S1) and a quartet splitting in CH2Cl2 solution (Fig. S2) at
298 K due to the coupling of copper nuclei (I = 3/2) and electron
were observed for all the copper(II) complexes. Electrochemical
studies of copper complexes were determined in DMF using
0.1 M tetrabutylammonium perchlorate (TBAP) as buffer solution.
A quasi-reversible peak in CV is obtained at 0.1–0.2 V correspond-
ing to the Cu(II)/Cu(I) redox couple as listed in Table S1, and the
representative cyclic votammetry of complex 7 was exemplified
as shown in Fig. S3. The structures of complexes 1, 6 and 8 were
further verified with X-ray single crystal measurements.
Single crystals of complexes 1, 6 and 8 suitable for X-ray struc-
tural determinations were obtained by slowly cooling their MeOH
solutions. Oak Ridge Thermal Ellipsoid Plots (ORTEP) displays se-
lected bond lengths and angles of the molecular structure of 1, 6
and 8 in Figs. 1–3, respectively. The solid-state structures of com-
plexes 1 and 6 are isostructural, except either a hydrogen (–H) or a
methoxy (–OMe) substituent at the 4-position of the phenoxy
group. Both display a mononuclear species with a five-coordinated
Cu(II) center, containing one six- and two five-membered chelating
ring. Each Cu atom is penta-coordinated by two N atoms and one O
atom from the tridentate-AIMP ligand and the two nitrogen atoms
of the bipyridine group, displaying a distorted square pyramidal
Fig. 1. ORTEP drawing of cationic structure of 1 with probability ellipsoids drawn at
level 30%. Selected bond lengths/Å and angles/deg: Cu(1)–O(1) 1.919(2), Cu(1)–N(1)
1.937(3), Cu(1)–N(2) 2.099(3), Cu(1)–N(3) 2.031(2), Cu(1)–N(4) 2.241(2), O(1)–
Cu(1)–N(1) 93.40(10), O(1)–Cu(1)–N(2) 165.30(11), O(1)–Cu(1)–N(3) 88.07(9),
O(1)–Cu(1)–N(4) 99.16(10), N(1)–Cu(1)–N(2) 83.95(11), N(1)–Cu(1)–N(3)
173.61(9), N(1)–Cu(1)–N(4) 108.80(10), N(2)–Cu(1)–N(3) 93.06(10), N(2)–Cu(1)–
N(4) 95.37(11), N(3)–Cu(1)–N(4) 77.05(9).
2.099(3) and 2.031(2) Å for 1, which are all within a normal dis-
tance for a Cu–O and Cu–N bond length [23–29,34,35]. It was noted
that the apical nitrogen atom N(4) of bipy is coordinated to copper
with a Cu(1)–N(4) bond distance of 2.241(2) Å, which is longer
than the other Cu–N distances of 1.937(3)–2.099(3) Å in 1. In
comparison, the Cu-containing bond distances of Cu(1)–O(1) =
1.9225(17) Å, Cu(1)–N(1) = 1.954(2) Å, Cu(1)–N(2) = 2.087(2) Å,
geometry (s = 0.13 for 1 and s = 0.24 for 6) [36]. Their principal
structural features include oxygen atom O(1), nitrogen atom N(1)
and N(2) of the tridentate Schiff base and nitrogen atom N(3) of
the bipy co-ligand occupying the square base; the
O(1)N(1)N(2)N(3) are almost coplanar with mean deviation of
0.0755 Å for 1 and 0.1197 Å for 6. The distances between the Cu
atom and atoms O(1), N(1), N(2) and N(3) are 1.919(2), 1.937(3),
Cu(1)–N(3) = 2.035(2) Å, Cu(1)–N(4) = 2.232(2) Å in
6 are all
similar to those found in complex 1. The solid structure of 8 also
reveals a monomeric Cu(II) complex, penta-coordinated by the
NNO-tridentate 4-OMeQYMP ligand and the NN-bidentate bipy
co-ligand with Cu(1)–O(1) = 1.921(2) Å, Cu(1)–N(1) = 1.949(2) Å,

B.-T. Ko et al. / Polyhedron 45 (2012) 49–54
51
2.2. Optical properties
UV–Vis experiment was conducted to explore the optical prop-
erties of copper complexes containing NNO-tridentate Schiff base
ligands. The corresponding absorption wavelengths and molar
absorption coefficients (e) determined in methanol (MeOH) are
summarized in Table 1. The major absorption bands of most com-
plexes 1–7 are all around at 235–254, 275–285 and 354–405 nm,
which can be assigned to intraligand p–
p⁄ transitions of the Schiff
base ligand and the bipy co-ligand. Experimental results show that
the optical properties of these complexes are dramatically influ-
enced by the electron donating and withdrawing group of the
Schiff base ligand. For instance, the long-wavelength absorption
for complex 6 with R = ꢂOMe at the 4-position of phenoxy group
shows a redshift (k = 405 nm), whereas the analogue band of com-
plex 3 with 4-NO2 on the phenoxy group is blue-shifted to
k = 354 nm. In comparison, the long-wavelength absorption band
of complex 6 is red-shifted by 51 nm relative to that of complex
Fig. 2. ORTEP drawing of cationic structure of 6 with probability ellipsoids drawn at
level 30%. Selected bond lengths/Å and angles/deg: Cu(1)–O(1) 1.9225(17), Cu(1)–
N(1) 1.954(2), Cu(1)–N(2) 2.087(2), Cu(1)–N(3) 2.035(2), Cu(1)–N(4) 2.232(2),
O(1)–Cu(1)–N(1) 91.41(8), O(1)–Cu(1)–N(2) 163.27(9), O(1)–Cu(1)–N(3) 88.30(8),
O(1)–Cu(1)–N(4) 99.62(9), N(1)–Cu(1)–N(2) 83.57(9), N(1)–Cu(1)–N(3) 177.74(8),
N(1)–Cu(1)–N(4) 104.78(8), N(2)–Cu(1)–N(3) 96.09(9), N(2)–Cu(1)–N(4) 97.09(9),
N(3)–Cu(1)–N(4) 77.47(8).
3. On the basis of Beer’s law ([M]0 = 1.0 ꢃ 10ꢂ5 M in MeOH), the
e
of complexes 1–9 at maxima absorption wavelength (kmax) is in a
range of (1.51–3.33) ꢃ 104/Mꢂ1 cmꢂ1, in which copper complex 7
gives the highest absorption among these complexes. For their vis-
ible absorptions (determined by [M]0 = 1.0 ꢃ 10ꢂ3 M in MeOH), the
absorption wavelengths of a very weak d–d transition were ob-
served in the range from 623 to 646 nm with
e .
< 180 Mꢂ1 cmꢂ1
It is worthy of noting that with increasing the conjugate chain of
imine part of the Schiff base ligand cause the obvious red-shift to
the long-wavelength absorption band (405 nm for
6 versus
483 nm for 8). No photoluminescence (PL) was observed for all
copper complexes.
2.3. DNA cleavage studies
The activity of copper(II) complexes 1–9 for cleavage of super-
coiled (SC) pUC19 DNA (0.5
fer (50 mM, pH 7.2) with 10% DMF solution has been investigated.
Preliminary results indicate that all of complexes 1–9 (40 M) are
lg) in a medium of Tris–HCl/NaCl buf-
l
inactive at dark condition (Fig. S4). However, they show good DNA
cleavage activity in the presence of reducing agent 3-mercapto-
propionic acid (MPA) as shown in Fig. 4. In the photo-induced
experiment, the cleavage activity was observed only at high con-
centration (200 lM) of the complexes under irradiation of
365 nm light (Fig. 5). It is worth noting that complex 9 is also active
at 633 nm red light as illustrated in Fig. 6, a potential candidate for
photodynamic therapy. It was therefore concluded that 1, 10-phe-
nanthroline supported complex 9 is more efficient than 2,20-bipyr-
idine supported complex 8 towards DNA cleavage in all the
experimental conditions. Further studies of their bioactivities are
undergoing.
Fig. 3. ORTEP drawing of cationic structure of 8 with probability ellipsoids drawn at
level 30%. Selected bond lengths/Å and angles/deg: Cu(1)–O(1) 1.921(2), Cu(1)–N(1)
1.949(2), Cu(1)–N(2) 2.055(2), Cu(1)–N(3) 2.027(2), Cu(1)–N(4) 2.246(3), O(1)–
Cu(1)–N(1) 93.03(10), O(1)–Cu(1)–N(2) 167.02(10), O(1)–Cu(1)–N(3) 91.53(9),
O(1)–Cu(1)–N(4) 99.45(10), N(1)–Cu(1)–N(2) 82.03(10), N(1)–Cu(1)–N(3)
175.31(9), N(1)–Cu(1)–N(4) 103.22(9), N(2)–Cu(1)–N(3) 93.28(10), N(2)–Cu(1)–
N(4) 93.38(9), N(3)–Cu(1)–N(4) 77.06(9).
Table 1
UV–Vis spectra of complexes 1–9 in methanol at 25 °C.
Cu(1)–N(3) = 2.027(2) Å and Cu(1)–N(4) = 2.246(3) Å, which are
similar to the bond distances observed for complexes 1 and 6.
The geometry around Cu center is also distorted from square pyr-
a
b
Complex
k, nm (10ꢂ3
e
, Mꢂ1 cmꢂ1
)
k, nm (e )
, Mꢂ1 cmꢂ1
1
2
3
4
5
6
7
8
9
243(15.1), 275(14.1), 402(2.32)
236(26.5), 285(19.5), 360(29.1)
244(21.7), 354(14.5)
236(15.8), 279(14.8), 386(2.27)
244(21.9), 285(28.2), 355(6.21)
254(17.7), 275(17.1), 405(2.97)
235(33.3), 285(17.1), 389(4.63)
338(11.9), 483(8.1)
625(171)
628(157)
646(160)
638(133)
637(149)
630(125)
amid (s = 0.14) with an almost coplanar of O(1)N(1)N(2)N(3) and
the Cu(1) atom is ca. 0.0872 Å above the O(1)N(1)N(2)N(3) mean
plane. It is worth to note that Cu(1)–N(2) = 2.055(2) Å in 8
are ꢁ0.04 Å shorter than those bond lengths found in 1 and 6,
indicating the better dative bonding between copper atom and
aromatic nitrogen atom. Interestingly, the six-membered rings,
Cu(1)O(1)C(1)C(6)C(7)N(1), consisting of a Cu center bonded by
the oxygen atom O(1) and nitrogen atom N(1) of the Schiff base
ligand are nearly coplanar with mean deviation of 0.0422 Å for 1
and 0.0850 Å for 8.
623(166)
c
c
334(10.1), 482(6.3)
a
b
c
[M]0 = 1 ꢃ 10ꢂ5 M.
[M]0 = 1 ꢃ 10ꢂ3 M.
Not available.

52
B.-T. Ko et al. / Polyhedron 45 (2012) 49–54
were determined by JASCO U-530 UV–Vis spectrometer at 25 °C
using CH2Cl2 as solvent. (E)-2-((2-(dimethylamino)ethylimi-
no)methyl)phenol (HAIMP-H) and (E)-1-((2-(dimethyl-aminoeth-
ylimino)methyl)-naphthalen-2-ol (NaphAIMP-H) were preparated
according to the literature method.
4.2. General procedures for tridentate-Schiff base ligands 5-NEt2AIMP-
Hꢁ4-OMeAIMP-H are followed the procedures for the preparation of
HAIMP-H
Fig. 4. Cleavage of SC pUC19 DNA (0.5 lg) by complexes 1–9 (40 lM) in the
presence of MPA (5 mM) using using 10% DMF 50 mM Tris–HCl/NaCl buffer solution
(pH 7.2). Lane 1, DNA control; lane 2, DNA + 1; lane 3, DNA + 2; lane 4, DNA + 3; lane
5, DNA + 4; lane 6, DNA + 5; lane 7, DNA + 6; lane 8, DNA + 7; lane 9, DNA + 8; lane
10, DNA + 9.
4.2.1. (E)-5-Diethylamino-2-((2-(dimethylamino)ethylimino)methyl)-
phenol (5-NEt2AIMP-H)
4-Diethyaminosalicylaldehyde (0.97 g, 5.0 mmol) was used.
Yield: 1.09 g (83%). 1H NMR (CDCl3, ppm): 8.00 (1H, s, N@CH),
6.97 (1H, d, J = 8.7 Hz, ArH), 6.13 (1H, dd, J = 8.7, 2.7 Hz, ArH),
6.08 (1H, d, J = 2.4 Hz, ArH), 3.59 (2H, t, J = 6.9 Hz, NCH2), 3.36
(4H, q, J = 7.2, CH2), 2.57 (2H, t, J = 6.6 Hz, NCH2CH2), 2.29 (6H, s,
N(CH3)2), 1.18 (6H, t, J = 7.2, CH3). 13C NMR (CDCl3, ppm): 167.43
(C@N), 162.96 (COH), 151.69, (CN(CH2)2(CH3)2), 132.82, 108.14,
102.87, 98.31 (Ar), 59.89 (CC@NCH2), 54.58 (CC@NCH2CH2),
45.58, 45.34, 44.29 ppm (N(CH3)2, and (CN(CH2)2(CH3)2)). Anal.
Calc. for C15H25N3O: C, 68.40; H, 9.57; N, 15.95%. Found: C,
67.84; H, 8.97; N, 16.03%.
Fig. 5. Cleavage of SC pUC19 DNA (0.5 lg) by 1–9 (200 lM) in 50 mM 10% DMF
Tris–HCl/NaCl solution (pH 7.2) under UV light (365 nm, 8 W, 30 min) exposure
followed by incubation under dark conditions and electrophoresis. Lane 1, DNA + 1;
lane 2, DNA + 2; lane 3, DNA + 3; lane 4, DNA + 4; lane 5, DNA + 5; lane 6, DNA + 6;
lane 7, DNA + 7; lane 8, DNA + 8; lane 9, DNA + 9.
4.2.2. (E)-4-Nitro-2-((2-(dimethylamino)ethylimino)methyl)phenol
(
4-NO2AIMP-H)
2-Hydroxy-5-nitrobenzaldehyde (0.84 g, 5.0 mmol) was used.
Yield: 1.03 g (87%). 1H NMR (CDCl3, ppm): 8.36 (1H, s, N@CH),
8.24 (1H, d, J = 2.7 Hz, ArH), 8.17 (1H, dd, J = 9.0, 3.0 Hz, ArH),
6.93 (1H, d, J = 9.3 Hz, ArH), 3.75 (2H, t, J = 6.3 Hz, NCH2), 2.66
(2H, t, J = 6.3 Hz, NCH2CH2), 2.31 (6H, s, N(CH3)2). 13C NMR (CDCl3,
MHz): d171.90 (C@N), 164.91 (COH), 137.57, 129.13, 128.46,
120.12, 115.67 (Ar), 58.75 (CC@NCH2), 53.84 (CC@NCH2CH2),
45.41 ppm (N(CH3)2). Anal. Calc. for C11H15N3O3: C, 55.69; H,
6.37; N, 17.71. Found: C, 55.31; H, 6.08; N, 17.81%. Mp: 110–
112 °C.
Fig. 6. Cleavage of SC pUC19 DNA (0.5 lg) by 1–9 (40 lM) in 50 mM 10% DMF Tris–
HCl/NaCl solution (pH 7.2) under 633 nm (3 W, 3 h) exposure followed by
incubation under dark conditions and electrophoresis. Lane 1, DNA + 1; lane 2,
DNA + 2; lane 3, DNA + 3; lane 4, DNA + 4; lane 5, DNA + 5; lane 6, DNA + 6; lane 7,
DNA + 7; lane 8, DNA + 8; lane 9, DNA + 9.
4.2.3. (E)-6-Methoxy-2-((2-(dimethylamino)ethylimino)methyl)phenol
(
6-OMeAIMP-H)
2-Hydroxy-3-methoxybenzaldehyde (0.76 g, 5.0 mmol) was
3. Conclusions
used. Yield: 0.89 g (80%). 1H NMR (CDCl3, ppm): 8.31(1H, t,
J = 1.2 Hz, N@CH), 6.72–6.89 (3H, m, ArH), 3.86 (3H, s, OCH3),
3.68 (2H, t, J = 6.6 Hz, NCH2), 2.60 (2H, t, J = 6.6 Hz, NCH2CH2),
2.27 (6H, s, N(CH3)2). 13C NMR (CDCl3, MHz): d165.17 (C@N),
152.09, 148.15 (COH and COCH3), 122.54, 118.01, 117.21, 113.48
(Ar), 59.33 (CC@NCH2), 56.61 (OCH3), 55.60 (CC@NCH2CH2),
45.31 ppm (N(CH3)2). Anal. Calc. for C12H18N2O2: C, 64.84; H,
8.16; N, 12.60. Found: C, 64.39; H, 8.06; N, 12.66%.
Nine new copper complexes bearing NNO-Schiff base ligands
and the bipy or phen co-ligand are synthesized and characterized
by EPR, CV and UV–Vis spectroscopic studies as well as X-ray single
crystal determinations. Structural characterizations of complexes
1, 6 and 8 were also discussed, in which the main feature was that
the central Cu(II) ion possesses a distorted square pyramidal geom-
etry. Experimental results indicate that the complex 9 with hetero-
cyclic base 1, 10-phenanthroline is more active than 8 with
bipyridine base, towards DNA cleavage in the presence of MPA or
under irradiation light (365 or 633 nm). In an investigation of
NNO-tridentate Schiff base-related Cu complexes for DNA photoc-
leavage, different Cu systems using various bipyridine based li-
gands as the co-ligands are in progress in our group.
4.2.4. (E)-5-Methoxy-2-((2-(dimethylamino)ethylimino)methyl)phenol
(
5-OMeAIMP-H)
2-Hydroxy-4-methoxybenzaldehyde (0.76 g, 5.0 mmol) was
used. Yield: 0.90 g (81%). 1H NMR (CDCl3, 300 MHz): d8.13 (1H, s,
N@CH), 7.05 (1H, d, J = 8.4 Hz, ArH), 6.36 (1H, d, J = 2.4 Hz, ArH),
6.33 (1H, dd, J = 8.4, 2.7 Hz, ArH) 3.77 (3H, s, OCH3), 3.61 (2H, t,
J = 6.9 Hz, NCH2), 2.58 (2H, t, J = 6.9 Hz, NCH2CH2), 2.27 (6H, s,
N(CH3)2). 13C NMR (CDCl3, MHz): d166.47 (C@N), 163.97,
163.56.15 (COH and COCH3), 132.43, 111.87, 105.96, 101.07 (Ar),
59.51 (CC@NCH2), 55.22 (OCH3), 54.95 (CC@NCH2CH2),
45.39 ppm (N(CH3)2). Anal. Calc. for C12H18N2O2: C, 64.84; H,
8.16; N, 12.60. Found: C, 64.41; H, 7.96; N, 12.68%.
4. Experimental
4.1. General procedures
1H and 13C NMR spectra were recorded on a Varian Mercury-
400 (400 MHz for 1H and 100 MHz for 13C) spectrometer with
chemical shifts given in ppm from the internal TMS or the center
line of CHCl3. Microanalyses were performed using a Heraeus
CHN-O-RAPID instrument. EPR spectra were determined by Bruker
EMX-10: CW EPR at 25 °C using CH2Cl2 as solvent. UV–Vis spectra
4.2.5. (E)-4-Methoxy-2-((2-(dimethylamino)ethylimino)methyl)phenol
(
4-OMeAIMP-H)
2-Hydroxy-5-methoxybenzaldehyde (0.76 g, 5.0 mmol) was
used. Yield: 0.87 g (78%). 1H NMR (CDCl3, ppm): d8.26 (1H, s,

B.-T. Ko et al. / Polyhedron 45 (2012) 49–54
53
N@CH), 6.84–6.85 (2H, m, ArH), 3.71 (3H, s, OCH3), 3.65 (2H, t,
J = 6.3 Hz, NCH2), 2.58 (2H, t, J = 6.3 Hz, NCH2CH2), 2.30 (6H, s,
N(CH3)2). 13C NMR (CDCl3, MHz): d165.06 (C@N), 154.95, 151.63
(COH and COCH3), 118.90, 118.16, 117.33, 114.51 (Ar), 59.54
(CC@NCH2), 57.41 (OCH3), 55.51 (CC@NCH2CH2), 45.37 ppm
(N(CH3)2). Anal. Calc. for C12H18N2O: C, 64.84; H, 8.16; N, 12.60.
Found: C, 63.90; H, 8.91; N, 12.32%.
C, 48.80; H, 4.90; N, 10.63%. IR (KBr, cmꢂ1): 1631.9 (C@N). Mp:
242–244 °C.
4.3.5. [Cu(5-OMeAIMP)(bpy)](ClO4) (5)
5-OMeAIMP-H (0.54 g, 2.4 mmol) was used. Yield: 0.81 g (75%).
Anal. Calc. for C22H25ClCuN4O6: C, 48.89; H, 4.66; N, 10.37. Found:
C, 48.66; H, 4.79; N, 9.97%. IR (KBr, cmꢂ1): 1606.0 (C@N).
4.3.6. [Cu(4-OMeAIMP)(bpy)](ClO4) (6)
4.3. General procedures for the preparation of [Cu(RAIMP)(bpy)](ClO4)
(1-7) and [Cu(4-OMeQYMP)(B)](ClO4) (B = bpy (8) or phen (9))
4-OMeAIMP-H (0.54 g, 2.4 mmol) was used. Yield: 0.89 g (82%).
Anal. Calc. for C22H25ClCuN4O6: C, 48.89; H, 4.66; N, 10.37. Found:
C, 48.59; H, 4.90; N, 10.39%. IR (KBr, cmꢂ1): 1632.4 (C@N). Mp:
216–218 °C.
4.3.1. [Cu(HAIMP)(bpy)](ClO4) (1)
A mixture of Cu(OAc)2ꢀH2O (0.40 g, 2.0 mmol), 2,20-bipyridine
(0.35 g, 2.2 mmol) in MeOH (5.0 mL) was stirred at 25 °C for
30 min and (E)-2-((2-(dimethylamino)-ethylimino)methyl)phenol
(HAIMP-H) (0.47 g, 2.4 mmol) in MeOH (2.0 mL) was added and
the resulting mixture was stirred for another 1 h. NaClO4 (0.25 g,
2.0 mol) was then added resulting green precipitation after
30 min. The precipitate was filtered and washed with MeOH
(5 mL) three times and dried under vacuum. Yield: 0.77 g (75%).
Anal. Calc. for C21H23ClCuN4O5: C, 49.41, H, 4.54; N, 10.98. Found:
C, 48.96; H, 4.95; N, 10.44%. IR (KBr, cmꢂ1): 1634.2 (C@N). Mp:
218–220 °C.
4.3.7. [Cu(NaphAIMP)(bpy)](ClO4) (7)
NaphAIMP-H (0.59 g, 2.4 mmol) was used. Yield: 0.94 g (84%).
Anal. Calc. for C25H25ClCuN4O5: C, 53.57; H, 4.50; N, 10.00. Found:
C, 53.48; H, 4.72, N, 10.04%. IR (KBr, cmꢂ1): 1619.8 (C@N). Mp:
240–242 °C.
4.3.8. [Cu(4-OMeQYMP)(bipy)](ClO4) (8)
4-OMeQYMP-H (0.67 g, 2.4 mmol) was used. Yield: 0.98 g (82%).
Anal. Calc. for C27H21ClCuN4O6: C, 54.37, H, 3.55; N, 9.39. Found:
C, 53.90; H, 4.60; N, 9.35%. IR (KBr, cmꢂ1): 1602.3 (C@N). Mp:
228–230 °C.
4.3.2. [Cu(5-NEt2AIMP)(bpy)](ClO4) (2)
Similar to the methods used for 1 with (E)-5-(diethylamino)-2-
(((2-(dimethylamino)-ethyl)imino)methyl)phenol
(0.64 g, 2.4 mmol) was used. Yield: 0.84 g (73%). Anal. Calc. for
4.3.9. [Cu(4-OMeQYMP)(phen)](ClO4) (9)
4-OMeQYMP-H (0.67 g, 2.4 mmol) and 1, 10-phenanthroline
(0.40 g, 2.2 mmol) were used. Yield: 1.02 g (82%). Anal. Calc. for
(
5-NEt2AIMP-H)
C
29H22ClCuN4O6: C, 56.04, H, 3.57; N, 9.01. Found: C, 56.35; H,
C
25H32ClCuN5O5: C, 51.63; H, 5.55; N, 12.04. Found: C, 51.71; H,
3.99; N, 9.04%. IR (KBr, cmꢂ1): 1603.5 (C@N). Mp: >300 °C.
5.39; N, 12.31%. IR (KBr, cmꢂ1): 1598.3 (C@N). Mp: 244–246 °C.
4.4. DNA cleavage experiments
4.3.3. [Cu(4-NO2AIMP)(bpy)](ClO4) (3)
4-NO2AIMP-H (0.57 g, 2.4 mmol) was used. Yield: 0.89 (80%).
Anal. Calc. for C21H22ClCuN5O7: C, 45.41; H, 3.99; N 12.61. Found:
C, 45.10; H, 4.20; N, 12.55%. IR (KBr, cmꢂ1): 1641.3 (C@N). Mp:
254–256 °C.
The photocleavage of (SC) pUC19 DNA by the copper(II) com-
plexes was investigated by the agarose gel electrophoresis method.
The reactions were carried out under illuminated conditions using
a UV lamp of 365 nm (8 W, Vilber Lourmat). Eppendorf was used
for respective UV experiments in a dark room at 25 °C using (SC)
4.3.4. [Cu(6-OMeAIMP)(bpy)](ClO4) (4)
pUC19 DNA (1
taining NaCl (50 mM) and the copper complex (1.8
with constant concentrations. The concentration of the complexes
l
L, 0.5
lg) in a 50 mM Tris–HCl buffer (pH 7.2) con-
6-OMeAIMP-H (0.54 g, 2.4 mmol) was used. Yield: 0.84 g (78%).
Anal. Calc. for C22H25ClCuN4O6: C, 48.89; H, 4.66; N, 10.37. Found:
lL in DMF)
Table 2
Crystallographic data of complexes 1, 6 and 8.
Complex
1
6
8
Empirical formula
Formula weight
T (K)
Crystal system
Space group
a (Å)
C
21H23ClCuN4O5
C22H25ClCuN4O6
540.45
293(2)
monoclinic
P2(1)/c
15.4296(10)
11.9065(8)
14.1178(9)
90
113.3030(10)
90
2382.0(3)
4
1.507
1.075
C27H21ClCuN4O6
596.47
293(2)
monoclinic
C2/c
23.503(2)
17.1647(16)
13.9247(14)
90
109.503(2)
90
510.42
293(2)
triclinic
ꢀ
P1
7.4484(5)
12.2457(8)
12.7337(9)
88.7370(10)
73.1390(10)
84.5000(10)
1106.39(13)
2
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
5295.2(9)
8
1.496
Z
Dcalc (Mg/m3)
1.532
1.149
l
(MoKa
) (mmꢂ1
)
0.975
F(000)
526
1116
2440
Reflections collected
No. of parameters
6020
289
12609
308
5209
352
Independent reflections (Rint
)
4249(0.0133)
0.0465
0.1769
4657(0.0215)
0.0390
0.1299
5209(0.0000)
0.0455
0.1370
1.071
R1 [I > 2
wR2 [I > 2
Goodness-of-fit on F2
r
(I)]
r(I)]
1.006
1.015

54
B.-T. Ko et al. / Polyhedron 45 (2012) 49–54
in DMF corresponded to the quantity after dilution of the 1.8
lL
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Acknowledgments
We gratefully acknowledge the financial support from the Na-
tional Science Council, Taiwan (NSC98-2113-M-005-MY3 to C.-C.
Lin, NSC97-2314-B384-004 and 99-2314-B-384-002-MY3 to F.-J.
Lai, and NSC99-2113-M-033-007-MY2 to B.-T. Ko).
Appendix A. Supplementary data
CCDC 884542–884544 contain the supplementary crystallo-
graphic data for complexes 1, 6 and 8. These data can be obtained
free of charge via 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
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.poly.2012.07.009.
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