Synthesis and the characterization of Schiff-base copper complexes: Reactivity with DNA, 4-NPP and BNPP

Article abstract of DOI:10.1016/j.ica.2014.12.034

Two new copper Schiff-base complexes have been synthesized and characterized by use of spectroscopic techniques. The Schiff-base ligands, (E)-N-((1-methyl-1H-imidazol-2-yl)methylene)quinolin-8-amine, MICQ and (E)-1-((quinolin-8-ylimino)methyl)naphthalen-2

Full text of DOI:10.1016/j.ica.2014.12.034

Inorganica Chimica Acta 428 (2015) 176–184
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis and the characterization of Schiff-base copper complexes:
Reactivity with DNA, 4-NPP and BNPP
⇑
Natalia Kozlyuk, Tyler Lopez, Patrick Roth, J. Henry Acquaye
Department of Chemistry, University of Redlands, 1200 East Colton Avenue, Redlands, CA 92373, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 October 2014
Received in revised form 12 December 2014
Accepted 17 December 2014
Available online 7 February 2015
Two new copper Schiff-base complexes have been synthesized and characterized by use of spectroscopic
techniques. The Schiff-base ligands, (E)-N-((1-methyl-1H-imidazol-2-yl)methylene)quinolin-8-amine,
MICQ and (E)-1-((quinolin-8-ylimino)methyl)naphthalen-2-ol, TL1 were obtained from the reaction of
8-aminoquinoline with 1-methyl-2-imidazolecarboxaldehyde and 2-hydroxy-1-napthaldehyde respec-
tively. The reaction of MICQ with copper(II) chloride produced complex 1, [Cu(MICQ)Cl](PF6), whereas
the reaction of TL1 with copper(II) acetate resulted in complex 2, Cu(TL1)(OAc)ꢀCH3OH. The single crystal
X-ray structure determination of both complexes show distorted square planar geometries around the
copper center. The reactivity of the complexes with calf thymus DNA, CT-DNA and plasmid DNA have
been studied using ethidium bromide displacement fluorescence emission, electronic absorption spec-
troscopy and agarose gel electrophoresis analysis. From the fluorescence emission studies Ksv values of
3.70 ꢁ 103 Mꢂ1 and 7.82 ꢁ 103 Mꢂ1 were obtained for complexes 1 and 2, respectively. The absorption
titration resulted in Kb values of 1.52 ꢁ 105 Mꢂ1 for complex 1 and 5.00 ꢁ 105 Mꢂ1 for complex 2. The
results indicate that both complexes significantly interact with CT-DNA and also show cleavage of super-
coiled DNA. In addition, complex 2 was found to hydrolyze the DNA model compounds bis(4-nitro-
phenyl) phosphate, BNPP and 4-nitrophenyl phosphate, 4-NPP.
Keywords:
Schiff-base ligands
Copper complexes
Crystal structures
DNA interaction
BNPP and 4-NPP cleavages
Ó 2015 Elsevier B.V. All rights reserved.
1. Introduction
to exhibit cytotoxicity levels that are comparable to or greater than
that of cisplatin [26–39].
The interaction of transition-metal complexes [1–5] with DNA
continues to attract interest in the search for anticancer chemo-
therapeutic agents due to the success of cisplatin [6]. Cisplatin is
currently used in the treatment of a number of malignancies
including testicular and ovarian cancer. Despite its worldwide
use and success in such treatment, the drug has been found to have
serious side effects such as liver toxicity, nausea and vomiting and
development of drug resistance. These shortfalls have stimulated
researchers to develop new and effective alternatives to cisplatin.
Copper complexes are in the forefront of that search. The biochem-
ical activity of copper in many biological systems makes it a good
choice for use as chemotherapeutic drug [7,8]. During the past few
decades, several copper complexes have been synthesized and
studied for their interaction with DNA [9–25]. Metal complex–
DNA interactions can be classified as intercalation, electrostatic
binding, covalent binding and hydrolytic cleavage. Several copper
complexes have been found to exhibit these modes of interaction.
Furthermore, a number of the copper complexes have been found
Among the various modes of interactions of metal complexes
with DNA, the hydrolysis of phosphate ester bonds in DNA serves
as one important reaction for DNA degradation [40,41]. The DNA
backbone consists of phosphate ester bonds, which impart high
stability to the DNA framework. The half-life of the phosphodiester
bond in DNA is estimated to be 130000 years. Hence the hydrolysis
of the phosphodiester bonds in DNA is kinetically a slow process
under normal physiological conditions. The stability of the phos-
phodiester bonds in DNA is considered to be nature’s mechanism
to safeguard the stability of the genetic make-up of life forms. In
many biological systems, metalloenzymes catalyze the hydrolysis
of the very stable phosphodiester bonds [42,43]. The phosphohy-
drolases generally contain Zn, Mg, Fe, Mn or Ni. Several studies
have been conducted with Cu(II) complexes for the hydrolysis of
phosphodiester bonds [44–49]. The hydrolysis of phosphodiester
bonds and phosphate monoester bonds in model compounds such
as bis(4-nitrophenyl) phosphate (BNPP) and 4-nitrophenyl phos-
phate (4-NPP) respectively constitute important reactions for
understanding the reactivity of metalloenzymes and metal com-
plexes with DNA. Metal complexes imitating hydroxylases could
serve as possible chemotherapeutic anti cancer agents. The devel-
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.ica.2014.12.034
0020-1693/Ó 2015 Elsevier B.V. All rights reserved.

N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
177
opment of metal complexes that could function as metalloenzymes
has therefore been the focus of several researchers [46–49,50–53].
The type of ligands attached to the metal center generally
influences the reactivity of a metal-based chemotherapeutic drug.
Varying the ligands could tune the reactivity of the complex
towards DNA. Planar ligands with pi systems have been noted
to be good intercalators [54–58]. The planarity of such ligands
contributes to the intercalating mode of binding of the complex
to DNA. Copper complexes have been shown to interact non-
covalently with DNA if they contain planar aromatic ring ligands
capable of inserting between the DNA base pairs. A significant
example is the work done by Sigman and co-workers [59] that
led to the discovery that the copper complex [Cu(phen)2]+
(phen = 1, 10-phenathroline) had the ability to intercalate DNA
and cause cleavage. Several other phen and related ligands have
been coordinated to copper and studied. A significant number of
the complexes have been found to exhibit reactivity similar to
nucleases [60–64]. Whereas the phen and related ligands have
seen more frequent applications, other planar pi systems like
quinoline have attracted less attention [65,66]. We are exploring
various Schiff-base ligands containing the quinoline moiety to
synthesize new copper complexes and study their DNA binding
and cleavage capabilities. In this study we report the synthesis
of two copper complexes containing the Schiff-base ligands
derived from 8-aminoquinoline. The structures of the complexes
have been determined by single crystal X-ray diffraction. The
reactivity of the complexes towards calf thymus-DNA (CT-DNA)
and plasmid DNA has been evaluated. In addition, kinetics exper-
iments with BNPP and 4-NPP indicate that the complexes do
hydrolyze the model compounds at reasonable rates.
prior to each scan. Scan rate for each measurement was 100 mV/
s. Plasmid DNA cleavage analyses were performed by gel electro-
phoresis using a Gel Doc-IT imaging System equipped with a Ham-
amatsu camera. Elemental analyses for C, H and N were performed
by Galbraith Laboratories, Inc. Knoxville, TN. The X-ray crystal
structure determinations and ESI-MS were performed by Dr. Fook
S. Tham and Mr. Ron New respectively, of the Department of
Chemistry, University of California, Riverside, CA.
2.3. Synthesis of ligands
2.3.1. (E)-N-((1-Methyl-1H-imidazol-2-yl)methylene)quinolin-8-
amine, MICQ
This ligand was prepared by the reaction of 1-methyl-2-imi-
dazolecarboxaldehyde (385 mg, 3.50 mmol) and 8-aminoquinoline
(500 mg, 3.50 mmol) in 30 mL toluene. The mixture was refluxed
overnight. The solution was then rotary evaporated to dryness
forming a brown oily product. The oily substance was purified by
column chromatography. The alumina column was first eluted
with dichloromethane yielding a yellow fraction. The column
was then eluted with a 1:1 v/v methanol/dichloromethane solution
that resulted in a brown fraction. This fraction was then covered
loosely with aluminum foil and left in the fume hood for the sol-
vent to evaporate. A brownish-yellow oil was left. This product
was then dissolved in 15 mL of CH2Cl2 and the solution was added
drop-wise into 100 mL of hexane. A light brownish-yellow precip-
itate was collected by vacuum filtration. Yield: 308 mg (37.3%).
Elemental analysis: Found (Calc.) for C14H12N4, C, 72.31 (71.17);
H, 5.37 (5.12); N, 22.01 (23.71). FTIR data (neat, v/cmꢂ1): 3164
(w), 3145 (w), 3036 (w), 1610 (s), 1573 (m), 1504 (s), 1472 (s),
1377 (s), 1334 (s), 1280 (m), 1108 (s), 1082 (m), 1040 (w), 816
(s), 780 (s), 748 (s). 1H NMR (400 MHz, CDCl3): d (ppm) 4.0 (3H,
s), 6.92 (1H, d, J = 7.4 Hz), 7.08 (1H, s), 7.15 (1H, d, J = 8.2 Hz),
7.25 (1H, s), 7.32 (1H, t, J = 7.6 Hz), 7.35 (1H, t, J = 4.1 Hz), 8.05
(1H, dd, J = 8.4, 1.8 Hz), 8.75 (1H, dd, J = 4.3, 1.6), 9.81 (1H, s). 13C
NMR (400 MHz, CDCl3): d (ppm) 35.9, 110.0, 118.0, 121.5, 126.8,
127.3, 129.1, 131.0, 135.0, 135.6, 138.0, 147.4, 148.1, 182.0.
2. Experimental section
2.1. Reagents and materials
All chemicals were purchased commercially and used as
received. Copper(II) chloride, Copper(II) acetate, 8-aminoquinoline,
1-methyl-2-imidazolecarboxaldehyde,
2-hydroxy-1-napthalde-
2.3.2. (E)-1-((Quinolin-8-ylimino)methyl)naphthalen-2-ol, (TL1)
2-Hydroxy-1-napthaldehyde (978 mg, 5.68 mmol) was added to
a solution of 8-aminoquinoline (814 mg, 5.65 mmol) in methanol
(30 mL). The mixture was refluxed for 4 h. After cooling, a yellow-
orange plate like precipitate formed. The product was isolated by
vacuum filtration and re-crystallized from methanol. Yield: 1.45 g
(80.9%). Elemental analysis: Found (Calc.) for C20H14N2O: C, 80.29
(80.51); H, 4.88 (4.73); N, 9.37 (9.39), FTIR data (neat, v/cmꢂ1):
3058 (w), 3040 (w), 1623 (s), 1609 (s), 1590 (s), 1533 (s), 1488
(m), 1472 (m), 1354 (s), 1299 (s), 1205(s), 1081 (m), 956 (m), 787
(s), 744 (s), 735 (s). 1H NMR (400 MHz, CDCl3): d (ppm) 6.90 (1H,
d, J = 9.6 Hz), 7.26 (1H, t, J = 8.0 Hz), 7.46 (1H, t, J = 8.4 Hz, 7.2 Hz),
7.47 (1H, d, J = 8.8 Hz), 7.51 (1H, t, J = 4.4 Hz), 7.57 (1H, d, J = 8.0),
7.63 (1H, d, J = 12.0 Hz), 7.66 (1H, t, J = 10.0 Hz, 9.6 Hz), 7.75 (1H,
dd, J = 7.4 Hz, 1.4 Hz), 7.99 (1H, d, J = 7.6 Hz), 8.18 (1H, dd,
J = 8.0 Hz, 1.6 Hz), 9.07 (1H, dd, J = 4.4 Hz, 1.6 Hz), 9.26 (1H, s) 9.28
(1H, s, absent upon D2O addition), 13C NMR (400 MHz, CDCl3): d
(ppm) 108.76, 113.06, 118.33, 122.30, 123.62, 124.28, 126.52,
126.63, 126.72, 128.34, 128.94, 129.49, 134.19, 135.90, 137.50,
139.39, 139.90, 146.10, 150.25, 181.83.
hyde, ammonium hexafluorophosphate, ethidium bromide (EB),
bis(4-nitrophenyl) phosphate (BNPP) sodium salt, 4-nitrophenyl
phosphate disodium salt (4-NPP), calf-thymus DNA (CT-DNA), tol-
uene, NaH2PO4ꢀH2O and NaCl were purchased from Sigma Aldrich.
Dichloromethane and methanol were purchased from Pharmco-
Aaper. Plasmid DNA pBR322 DNA was purchased from Thermo Sci-
entific. The reagents were used without further purification.
2.2. Methods and instrumentation
1H NMR and 13C NMR were recorded on a Varian 400 MHz spec-
trometer. A Perkin Elmer Spectrum 100 FT-IR spectrometer was
used for the IR spectra. UV–Vis spectra as well as the reactivity
studies and absorption titration studies were recorded on the Shi-
madzu UV-1700 UV–Vis spectrophotometer. Ethidium bromide
competitive binding studies were performed using the Jasco-FP
750 spectrofluorimeter. Cyclic voltammetry measurements were
performed using a BAS CV-50W voltammetric analyzer. A three-
electrode arrangement made up of a glassy carbon working elec-
trode, a platinum wire auxiliary electrode and a Ag/AgCl reference
electrode was used. The glassy carbon electrode was polished
using alumina before each use. The cyclic voltammograms were
recorded in methanol or dichloromethane with tetrabutylammo-
nium hexafluorophosphate, (TBAHP), (0.10 M) as the supporting
electrolyte. The concentrations of the complexes were 5.0 mM. Ini-
tial scans of the supporting electrolyte were made for the back-
ground check. The solutions were purged with N2(g) for 2–3 min
2.4. Synthesis of [Cu(MICQ)Cl](PF6) (1)
The ligand MICQ, (200 mg, 0.856 mmol) was dissolved in 25 mL
of methanol. Copper(II) chloride (144 mg, 0.856 mmol) was
dissolved in 25 mL methanol in a different flask. The copper chlo-
ride solution was then added drop-wise to the ligand solution.
The mixture immediately turned a dark green color. The mixture

178
N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
was heated to 60 °C for 10 min while stirring and then allowed to
cool to room temperature. The precipitate was vacuum filtered,
and the product washed with a small amount of cold methanol.
The product was allowed to dry (212 mg recovered, 67.6% yield).
Suitable crystals for structure determination were grown in deion-
ized water with the addition of NH4PF6. Elemental analysis: Found
(Calc.) for C14H12N4ClCuPF6, [Cu(MICQ)Cl](PF6): C, 35.71 (34.99); H,
2.38 (2.52); N, 11.59 (11.66), ESI-MS: m/z = 334 [MꢂPFꢂ6 ]+, FTIR
data (neat, v/cmꢂ1): 3126 (w), 3071 (w), 1604 (m), 1583 (m),
1505 (m), 1484 (m), 1434 (m), 1414 (m), 1392 (m), 1303 (m),
1077 (m), 827 (s), 791 (m), 760(s), 740 (s), UV–Vis: (methanol) kmax
coefficient
l
= 1.637 mmꢂ; 1
maximum/minimum
transmis-
sion = 0.9743/0.4867) to the raw intensity data using the Bruker
TWINABS program [70]. The integrated frames for complex 2 yielded
a total of 40708 reflections at a maximum 2q angle of 58.26°
(0.73 Å resolution), of which 5152 were independent reflections
(Rint = 0.0417,
Rsig = 0.0239,
redundancy = 7.9,
complete-
ness = 99.9%) and 4316 (83.8%) reflections were greater than
2r(I). The unit cell parameters were, a = 8.1846(2) Å, b =
17.7964(5) Å, c = 13.3740(4) Å, b = 100.701(1)°, V = 1914.13(9) Å3,
Z = 4, Dcalc = 1.568 g/cm3. Absorption corrections were applied
(absorption coefficient
l
= 1.176 mmꢂ1; maximum/minimum trans-
240 nm, log
kmax 596 nm, log
e
4.18, kmax 273 nm, log
3.36.
e 4.20, kmax 393 nm, loge 3.65,
mission = 0.9633/0.7937) to the raw intensity data using the SADABS
program [71]. The Bruker SHELXTL software package [72] was used
for phase determination and structure refinement for both com-
plexes. The first twin domain HKL intensity data was used with
the distribution of intensities (E2 ꢂ 1 = 0.898 for complex 1 and
E2 ꢂ 1 = 0.947 for complex 2). Systematic absent reflections indi-
cated one possible space group, P2(1)/c. The space group P2(1)/c
(#14) was later determined to be correct for both complexes. Direct
methods of phase determination followed by two Fourier cycles of
refinement led to an electron density map from which most of the
non-hydrogen atoms were identified in the asymmetry unit of the
unit cell. With subsequent isotropic refinement, all of the non-
hydrogen atoms were identified. The combined (major and minor
components) HKLF 5 intensity dataset was used in the final struc-
ture refinement. There was one cation of [C14H12N4ClCu]+ and one
anion of [PF6]ꢂ present in the asymmetry unit of the unit cell of
complex 1 and one molecule of Cu-complex, [C20H13N2O][CH3-
COO]Cu with one solvent molecule of CH3OH present in the asym-
metric unit of the unit cell of complex 2. The rotational twin law
was 180° rotation about the 100 real axis. The major/minor twin
component ratio was 57%/43%.
e
2.5. Synthesis of Cu(TL1)(OAc)ꢀCH3OH (2)
Copper acetate, (124 mg, 0.70 mmol) was dissolved in methanol
(35.0 mL). The ligand TL1 (206 mg, 0.70 mmol) was dissolved in
methanol (100 mL). The copper acetate solution was added drop-
wise to this solution. An immediate color change to a yellowish
green solution was observed. Once all of the copper acetate solu-
tion had been added the solution was heated and stirred for 2–
3 min. The solution was allowed to cool to room temperature
and then refrigerated for 2 days to allow slow crystallization. The
dark brown needlelike crystals were collected by vacuum filtration
and washed twice with 3–5 mL aliquots of ice-cold methanol and
dried under vacuum. Yield: 0.335 g (68.4%). Elemental analysis:
Found (Calc.) for C23H20N2O4CuꢀCH3OH: C, 60.67 (61.19); H, 4.24
(4.46); N, 6.18 (6.20), ESI-MS: m/z = 360 [MꢂCH3COꢂ2 ]+, FTIR data
(neat, v/cmꢂ1): 3058, 1601, 1575, 1537, 1503, 1457, 1428, 1364,
1322, 1304, 1265, 1239, 1202, 1169, 1093, 1033, 977, 825, 746,
730, 656, UV–Vis: (methanol) kmax 230 nm, log
260 nm, log 4.42, kmax 348 nm, log 3.99, kmax 453 nm, log
4.22, kmax 476 nm, log 4.26.
e 6.68, kmax
e
e
e
Atomic coordinates, isotropic and anisotropic displacement
parameters of all the non-hydrogen atoms were refined by means
of a full matrix least-squares procedure on F2. The H-atoms were
included in the refinement in calculated positions riding on the
atoms to which they were attached. The refinement converged at
e
2.6. X-ray structure determination
A green thin needle-plate fragment (0.51 ꢁ 0.16 ꢁ 0.02 mm3)
was used for single crystal X-ray diffraction data for complex 1,
[C14H12N4ClCu]+[PF6]ꢂ. For complex 2 C20H13N2OCH3COOCuꢀCH3OH,
a black prism (0.21 ꢁ 0.09 ꢁ 0.03 mm3) was used. Each crystal
was coated with paratone oil and mounted on a cryo-loop
glass fiber. X-ray intensity data were collected at 100(2) K on a
Bruker APEX2 [67] platform-CCD X-ray diffractometer system (fine
focus tube, Mo radiation, k = 0.71073 Å, 50 KV/30 mA power). The
CCD detector was placed at a distance of 5.0400 cm from the crys-
tal of complex 1, and at a distance of 5.0700 cm from the crystal
of complex 2. A total of 3600 frames were collected for a sphere
R1 = 0.0386, wR2 = 0.0890, with intensity, I > 2
and at R1 = 0.0350, wR2 = 0.0797, with intensity I > 2
plex 2. The largest peak/hole in the final difference map was
0.781/ꢂ0.594 e Åꢂ3 and 0.960/ꢂ0.470 e Åꢂ3 for complexes 1 and
2, respectively. The intermolecular hydrogen bond distances and
angles for complex 2 are shown in Table 3.
r
(I) for complex 1
r
(I) for com-
2.6.1. Ethidium bromide competitive binding studies
Stock solutions of ethidium bromide and CT-DNA were prepared
using a phosphate buffer (pH 7.2). The concentration of the CT-DNA
solution was determined to be 15.7 ꢁ 10ꢂ3 M by using the molar
absorption coefficient (6600 Mꢂ1 cmꢂ1) at 260 nm. Stock solutions
of reflections (with scan width of 0.3° in
x, starting x and 2h
angles of ꢂ30°, and / angles of 0°, 90°, 120°, 180°, 240°, and
270° for every 600 frames, 80 s/frame exposure time for complex
1 and 30 s/frame exposure time for complex 2). For complex 1,
of complex
1
(1.15 ꢁ 10ꢂ3 M) in methanol and complex
2
(4.10 ꢁ 10ꢂ4 M) in methanol were prepared. Appropriate dilutions
of the stock solutions were made for each experiment. In a typical
the Bruker CELL
NOW program [68] was used to obtain the two dif-
experiment, 2 mL of the ethidium bromide (20.0
transferred into a cuvette. CT-DNA (10 L) was added to the ethi-
dium bromide solution and equilibrated at 37 °C for 15 min. Various
volumes (5–25 L) of the complex were added to the EtBr-DNA solu-
lM) solution was
ferent orientation matrices of the rotational twin components
(Twin law is 180° rotation about the 100 real axis). These matri-
ces were imported into the APEX2 program for Bravais lattice
determination and initial unit cell refinement. The frames were
integrated using the Bruker SAINT software package [69] and using
a narrow-frame integration algorithm. Based on a monoclinic
l
l
tion. A total volume of 2.45 mL was maintained by adding additional
volume of the phosphate buffer to the metal complex-EtBr-DNA
solutions. Each solution was incubated at 37 °C for another
15 min. The changes in the fluorescence intensities were recorded
at 600 nm over a spectra range of 540–700 nm using an excitation
wavelength of 520 nm. The quenching constants (Ksv) were calcu-
lated for each complex using a plot of the Stern–Volmer Eq. (1):
crystal system, the integrated frames yielded
a total of
4480 unique independent reflections [Rint = 0.0474, maximum
2h = 58.26° (0.73 Å resolution), data completeness = 100%] and
4064 (90.7%) reflections were greater than 2
parameters were, a = 14.9130(18) Å,
c = 7.2754(9) Å, b = 95.207(2)°, V = 1667.5(4) Å3, Z = 4, Dcalc
1.913 g/cm3. Absorption corrections were applied (absorption
r(I). The unit cell
b = 15.4330(19) Å,
=
I0=I ¼ 1 þ Ksv½complexꢃ
ð1Þ

N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
179
where I0 and I represent the fluorescence intensities in the absence
3. Results and discussion
and presence of the complex, respectively, and [complex] represent
the total concentration of the complex.
3.1. Synthesis and characterization
The ligands MICQ [73] and TL1 were prepared by the Schiff-
base condensation reaction of 8-aminoquinoline and the corre-
sponding aldehyde. The products were purified by column chro-
matography. Each ligand was characterized by use of various
spectroscopic methods. Major spectroscopy features are reported
in the synthesis section. Complex 1 was prepared by reacting the
ligand MICQ with a methanol solution of copper(II) chloride
whereas complex 2 was prepared by reacting the ligand TL1 with
copper(II) acetate in methanol. Both complexes are soluble in
DMF and methanol. Complex 2 is also soluble in dichlorometh-
ane. The MS of the complex showed a major cluster at m/z of
334 for the M+, [Cu(MICQ)]+ ion. The UV–Vis spectrum of MICQ
in methanol has two major peaks at 250 nm and 340 nm. These
2.6.2. Absorption titration studies
The absorption titration studies were carried out using a con-
stant concentration of 8.0 ꢁ 10ꢂ5 M of the complex. A solution of
CT-DNA was made in 5.0 mM Tris–HCl/NaCl buffer (pH 7.2). CT-
DNA stock solution concentration was determined to be
1.70 ꢁ 10ꢂ4 M by using the absorbance at 260 nm and the extinc-
tion coefficient at that wavelength of 6600 Mꢂ1 cmꢂ1. The absorp-
tion spectra of the complex in the absence and presence of
increasing concentrations of CT-DNA were determined in 5.0 mM
Tris–HCl/NaCl buffer (pH 7.2). The change in absorbance of the
MLCT absorbance for the complex was monitored with each suc-
cessive addition of CT-DNA. The spectra were recorded after
10 min incubation at 37 °C. The intrinsic binding constants Kb for
complexes 1 and 2 were determined from the Eq. (2):
peaks are assigned to the
trum of complex 1 in methanol exhibits three peaks in the range
p–
p⁄ of the ligand. The UV–Vis spec-
220–700 nm. The two intense peaks at kmax 386.5 nm and
237.5 nm corresponded to the
p–
p⁄ absorption within the ligand.
½DNAꢃ=ðea
ꢂ
ef Þ ¼ ½DNAꢃ=ðeb
ꢂ
ef Þ þ 1=ðKbðeb
ꢂ
ef ÞÞ
ð2Þ
The peak at 651.0 nm corresponds to the metal–ligand charge
transfer (MLCT) absorption. The ESI-MS spectrum of complex 2
showed an m/z at 360 for the [MꢂOAc]+ ion. The electronic spec-
trum of complex 2 in methanol shows five peaks, three peaks in
the UV region and two peaks in the visible region. The peaks in
where [DNA] is the concentration of CT-DNA in base pairs, ea
,
e
f and
eb are the apparent absorption coefficient Aobs/[Cu], the extinction
coefficient for the free copper complex and the extinction coeffi-
cient for the fully bound complex respectively. From the plot of
[DNA]/(ea
the slope and the intercept.
the UV region can be assigned to the
p–
p⁄ absorption within
ꢂ
ef) versus [DNA], Kb was calculated from the ratio of
the ligand TL1, while the two lower energy bands are assigned
to the MLCT bands.
2.6.3. DNA cleavage experiments
3.2. Crystal structure
The DNA cleavage activity of each complex was examined using
super coiled pBR322 DNA. A stock solution of complex 1 was pre-
pared with a concentration of 4.13 ꢁ 10ꢂ4 M. 30.0
lL samples of
The crystal data and structure refinements for complexes 1 and
2 can be observed in Table 1. The crystals for complex 1 were
grown by slow evaporation of an aqueous solution of
[Cu(MICQ)Cl](PF6). The crystal structure of complex 1 is shown in
Fig. 1. The geometry around the copper is a distorted square planar
geometry with the metal coordinated to the tridentate MICQ ligand
and the fourth coordination site occupied by a chlorine. The pack-
ing diagram (Fig. 2) shows a spiral staircase arrangement resulting
in a penta-coordinated copper center with a chlorine ligand from
another unit serving as the axial donor atom. Selected bond lengths
and angles are shown in Table 2. In complex 1, the bond lengths
between the copper and the chlorine ligands are 2.248(9) Å and
2.6269(10) Å for the equatorial and the axial chlorines respectively.
A similar trend has been found in other copper complexes [74]. As
a consequence of the weak Cu–Cl(bridging) bonds such packing
arrangement in complex 1 is not sustained in solution where the
solvent has strong donor atoms [75]. Complex 1 and complex 2
both have identical 8-aminoquinoline rings as part of the triden-
tate ligand. The structure of complex 2 is shown in Fig. 3. The bond
lengths around the copper center from the nitrogen donors of the
8-aminoquinoline moiety are Cu(1)–(N1), 2.002(3) Å and
1.9922(16) Å for complex 1 and complex 2 respectively. The bond
lengths of the Cu(1)–N(2)(imine) are 1.997(2) Å and 1.9416(15) Å for
complex 1 and complex 2, respectively. In addition, complex 1 also
has a Cu(1)–N(3)(imidazole) bond length of 1.984(3) Å. These bond
lengths are comparable to similar 8-aminoquinoline Schiff base
and imidazole copper complexes [51,66,74,76,77]. Complex 2 has
two Cu–O bonds, with bond lengths of Cu(1)–O(1) and Cu(1)–
O(2) being 1.8992(14) Å and 1.9426(13) Å, respectively. The
shorter bond length being the Cu–O(phenolate). This shorter bond
length is due to the phenolate oxygen being a stronger base than
the carboxylate oxygen. The two polycyclic rings of the tridentate
ligand, TL1 are approximately in the same plane. There is one
the plasmid DNA were treated with increasing complex concentra-
tions (2.0–70
lL) and enough buffer solution for a final volume of
100 L. The samples were incubated in the dark for 20 h at 37 °C.
l
The DNA cleavage experiments were analyzed by 1% agarose gel
electrophoresis using 1ꢁ Tris–acetate–EDTA (TAE) running buffer.
10 lL of each reaction solution together with 2.0 lL of the loading
dye was loaded into the wells and subjected to electrophoresis at
60 V for 90 min. The gel was stained with 1% ethidium bromide
and documented using a Gel Doc-IT imaging system. A similar pro-
cedure was used for complex 2.
2.7. Reactivity with BNPP and 4-NPP
The hydrolysis of BNPP and 4-NPP by complex 2 were observed
by monitoring the increase in absorbance at 400 nm due to the for-
mation of the 4-nitrophenolate ion. In a typical experiment, 2.0 mL
of BNPP (2.0 ꢁ 10ꢂ3 M) or 4-NPP (2.7 ꢁ 10ꢂ3 M) in Tris–HCl buffer
(pH 7.2) was transferred into a cuvette in the sample compartment
of the spectrophotometer. A similar solution was placed in the ref-
erence compartment to correct for the hydrolysis in the absence of
the catalyst. 1.0 mL of the buffer was added to the reference cuv-
ette to bring the total volume to 3.0 mL. The cuvettes were equili-
brated at 50.0 °C for 10 min.
A solution of the complex
(4.13 ꢁ 10ꢂ4 M), (1.0 mL), which had been equilibrated at 50.0 °C,
was immediately added to the BNPP solution and the measure-
ments were recorded. The observed rate constant kobs were deter-
mined from the plots of ln(Ainf ꢂ At) versus time (s) where At is the
absorbance at time t seconds and Ainf is the absorbance at the
end of the reaction. In one experiment, complex 1 showed hydro-
lysis of BNPP, however this experiment for complex 1 was not
reproducible.

180
N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
Table 1
Crystal data and structure refinement for complexes 1 and 2.
1
2
Empirical formula
Formula weight
T (K)
C
14H12ClCuF6N4P
C23H20CuN2O4
451.95
100(2)
480.24
100(2)
k (Å)
0.71073
monoclinic
P2(1)/c
0.71073
monoclinic
P2(1)/c
Crystal system
Space group
Unit cell dimensions
a (Å)
14.9130(18)
8.1846(2)
b (Å)
15.4330(19)
17.7964(5)
c (Å)
7.2754(9)
13.3740(4)
a
(°)
90
90
b (°)
95.207(2)
100.701(1)
c
(°)
90
1667.5(4)
90
V (Å3)
1914.13(9)
Z
4
4
Dcalc (Mg mꢂ3
)
1.913
1.637
956
1.568
1.176
932
Absorption coefficient (mmꢂ1
F(000)
)
Crystal size (mm)
Theta range for data collection (°)
Index ranges
0.51 ꢁ 0.16 ꢁ 0.02
0.21 ꢁ 0.09 ꢁ 0.03
1.90–29.13
1.93–29.13
ꢂ20 6 h 6 20, 0 6 k 6 21, 0 6 l 6 9
9514
ꢂ11 6 h 6 11, ꢂ24 6 k 6 24, ꢂ18 6 l 6 18
40708
Reflections collected
Independent reflections (Rint
)
4480 (0.0474)
5152 (0.0417)
Completeness to theta = 29.13°
Absorption correction
Maximum and minimum transmission
Refinement method
100.0%
99.9%
semi-empirical from equivalents
0.9743 and 0.4867
Full-matrix least-squares on F2
4480/0/246
semi-empirical from equivalents
0.9633 and 0.7937
Full-matrix least-squares on F2
5152/0/276
Data/restraints/parameters
Goodness-of-fit (GOF) on F2
1.086
1.063
Final R indices [I > 2
R indices (all data)
r
(I)]
R1 = 0.0386, wR2 = 0.0890
R1 = 0.0474, wR2 = 0.0954
0.781 and ꢂ0.594
R1 = 0.0350, wR2 = 0.0797
R1 = 0.0464, wR2 = 0.0843
0.960 and ꢂ0.470
Largest difference in peak and hole (e Åꢂ3
)
Table 2
Selected bond lengths and bond angles complexes 1 and 2.
Complex 1
Complex 2
Bond lengths (Å)
Cl(1)–Cu(1)
Cl(1)–Cu(1)#1
Cu(1)–N(3)
2.2485(9)
2.6269(10)
1.984(3)
Cu(1)–O(1)
Cu(1)–N(2)
Cu(1)–O(2)
Cu(1)–N(1)
1.8992(14)
1.9416(15)
1.9426(13)
1.9922(16)
Cu(1)–N(2)
1.997(2)
Cu(1)–N(1)
2.002(3)
Cu(1)–Cl(1)#2
2.6269(10)
Bond angles (°)
Cu(1)–Cl(1)–Cu(1)#1
N(3)–Cu(1)–N(2)
N(3)-Cu(1)-N(1)
115.32(4)
80.72(10)
161.25(11)
80.72(11)
98.58(8)
158.86(9)
97.76(8)
94.10(8)
97.78(8)
91.01(9)
103.34(3)
O(1)–Cu(1)–N(2)
O(1)–Cu(1)–O(2)
N(2)–Cu(1)–O(2)
O(1)–Cu(1)–N(1)
N(2)–Cu(1)–N(1)
O(2)–Cu(1)–N(1)
92.58(6)
90.27(6)
176.59(6)
173.69(6)
83.41(7)
93.91(6)
N(2)–Cu(1)–N(1)
N(3)–Cu(1)–Cl(1)
N(2)–Cu(1)–Cl(1)
N(1)–Cu(1)–Cl(1)
N(3)–Cu(1)–Cl(1)#2
N(2)–Cu(1)–Cl(1)#2
N(1)–Cu(1)–Cl(1)#2
Cl(1)–Cu(1)–Cl(1)#2
Fig. 1. Crystal structure of the complex [Cu(MICQ)Cl]PF6 (1). Crystal data are given
in Table 1, selected bond lengths and bond angles are in Table 2.
Table 3
Hydrogen bonds for complex 2 [Å and °].
3.3. Electrochemistry
D–H. . .A
d(D–H)
0.80(3)
d(H. . .A)
1.94(3)
d(D. . .A)
<(DHA)
174(3)
O(1S)–H(1D). . .O(2)
2.737(2)
Cyclic voltammetry of complex 1 was performed in methanol
using a glassy carbon-working electrode, a silver chloride reference
electrode and a platinum wire auxiliary electrode in the potential
range of +0.6 to ꢂ0.4 V. All potentials are with reference to Ag/
AgCl. Fig. 4 shows a reduction peak at ꢂ0.085 V corresponding to
the Cu2+ ? Cu+ and a less reversible oxidation peak at 0.18 V for
complex 1. The nature of the oxidation peak suggests that Cu+ spe-
cies is not stable in the solution. Neves and co-workers [51] have
Symmetry transformations used to generate equivalent atoms: ꢂx + 1, ꢂy + 1,
ꢂz + 1.
hydrogen bond interaction in complex 2 involving the alcohol
group of methanol and one of the carboxylate oxygen of the coor-
dinated acetate.

N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
181
Fig. 4. Cyclic voltammogram for the complex [Cu(MICQ)Cl]PF6 (1) in methanol with
TBAHP (0.10 M) as the supporting electrolyte, at scan rate of 100 mV/s, potential
expressed with reference to Ag/AgCl electrode.
Fig. 2. Packing diagram for the complex [Cu(MICQ)Cl]PF6 (1). The anion has been
omitted for clarity.
Fig. 5. Cyclic voltammogram for the complex [Cu(TL1)(OAc)]ꢀCH3OH (2) in meth-
anol with TBAHP (0.10 M) as the supporting electrolyte, at scan rate of 100 mV/s,
potential expressed with reference to Ag/AgCl electrode.
[21–23]. Whereas the cyclic voltammogram of complex 1 shows
an irreversible reduction peak, the cyclic voltammogram of com-
plex 2 shows quasi-reversible peaks. The difference in the redox
potential of the complexes is a result of the structural difference
of the two complexes. The much higher potential for complex 2
could be attributed to the coordination of the phenolate oxygen
and the presence of the pi framework of the naphthalene group.
Fig. 3. Crystal structure of the complex [Cu(TL1)(OAc)]ꢀCH3OH (2). Crystal data are
given in Table 1, selected bond lengths and bond angles are in Table 2.
3.4. Reactivity of the complexes with DNA
reported similar cyclic voltammograms for their imidazole rich
copper complexes. In methanol, complex 2 showed no active redox
behavior in the scan range of ꢂ0.40 V to 1.60 V. The cyclic voltam-
mogram of complex 2 (Fig. 5) was recorded in dichloromethane.
The E1/2 for complex 2 was found to be 1.482 V, which is more posi-
tive compared to values reported for similar copper complexes
Fluorescence spectroscopy studies were used to assess the
binding abilities of the complexes with CT-DNA. Unbound ethi-
dium bromide is weakly fluorescent, however, this ability is tre-
mendously increased when ethidium bromide interacts with
DNA. The displacement of ethidium bromide from CT-DNA and
ethidium bromide bound complex by a metal complex results in

182
N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
1.15
1.1
1.05
1
0.95
0.00E+002.00E-054.00E-05
[Complex] M
Fig. 6. Changes in the fluorescence emission spectra of CT-DNA and ethidium
bromide bound complex in Tris–HCl buffer (pH = 7.2) with increasing concentration
of the complex [Cu(MICQ)Cl]PF6 (1). [CT-DNA] = 1.60 ꢁ 10ꢂ4 M, [EB] = 2.00 ꢁ 10ꢂ5 M,
kex = 520 nm. Inset shows the plot of emission intensity I0/I versus [complex].
Fig. 9. Absorption spectra of the complex [Cu(TL1)(OAc)]ꢀCH3OH (2) in the absence
and presence of increasing concentrations of CT-DNA (0–84.3 M) at 37 °C. The
inset shows the plot of [DNA]/(ea f) versus [DNA].
l
ꢂ
e
the decrease in the emission intensity of the CT-DNA and ethidium
bromide bound complex. The accepted conclusion from such stud-
ies is that the metal complex preferentially and strongly binds to
the CT-DNA compared to ethidium bromide through intercalation.
Figs. 6 and 7 show changes in the emission spectra observed upon
the addition of solution of complex 1 and complex 2 respectively to
a solution of CT-DNA and ethidium bromide bound complex. In
both cases, the observed trend is a decrease in the emission inten-
sity with increasing concentration of the complex. These observa-
tions are in good agreement with the Stern–Volmer expression.
The Stern–Volmer quenching plot of I0/I versus concentration of
the copper complex gave Ksv values of 3.70 ꢁ 103 Mꢂ1 and
7.82 ꢁ 103 Mꢂ1 for complexes 1 and 2, respectively. The Ksv value
for complex 2 is approximately twice the value for complex 1 indi-
cating stronger binding by complex 2. Structurally, complex 2 con-
tains more planar polycyclic rings than complex 1. Complexes with
planar polycyclic rings as part of the ligand moiety have been
found to be good DNA intercalators [54–58,60].
Fig. 7. Changes in the fluorescence emission spectra of CT-DNA and ethidium
bromide bound complex in Tris–HCl buffer (pH = 7.2) with increasing concentration
of
the
complex
[Cu(TL1)(OAc)]ꢀCH3OH
(2),
[CT-DNA] = 1.60 ꢁ 10ꢂ4 M,
[EB] = 2.00 ꢁ 10ꢂ5 M, kex = 520 nm. Inset shows the plot of emission intensity I0/I
versus [complex].
The reactivity of the complexes with DNA was also studied
through absorption titration by monitoring the absorbance
changes at 383 nm for complex 1 and 453 nm for complex 2, upon
addition of increasing amounts of DNA to a fixed amount of the
complex. The absorption spectra of complex 1 (Fig. 8) in the pres-
ence of CT-DNA displayed a hypochromic shift whereas the absorp-
tion spectra of complex 2 (Fig. 9) showed a hyperchromic shift. The
increase in absorbance for complex 2 is an indication for minor
groove binding of the complex to DNA [74]. The intrinsic binding
constant for each complex was determined from the plot of
[DNA]/(ea
ꢂ
ef) versus [DNA]. The ratio of the slope and intercept
from gave intrinsic binding constant Kb of 1.52 ꢁ 105 Mꢂ1 for com-
plex 1 and Kb of 5.0 ꢁ 105 Mꢂ1 for complex 2. The Kb values also
suggest a stronger binding affinity of complex 2 for DNA compared
with complex 1. This result supports the earlier suggestion that the
difference in the Ksv values could be attributed to the extra planar
ring in complex 2 resulting in stronger binding of complex 2 to the
DNA. It is noteworthy to mention that the Kb values obtained for
complex 1 and complex 2 are about ten times greater than the
value reported for the DNA intercalator complex [Ru(phen)2(-
dpq)]2+. A Kb value of 1.41 ꢁ 105 Mꢂ1 has been reported for some
copper complexes [76].
Fig. 8. Absorption spectra of the complex [Cu(MICQ)Cl]PF6 (1) in the absence and
presence of increasing concentrations of CT-DNA (0–84.3
shows the plot of [DNA]/(ea f) versus [DNA].
lM) at 37 °C. The inset
ꢂ
e

N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
183
Fig. 10. Agarose gel electrophoresis analysis of the cleavage of SC pBR322 DNA by complex 1 (top) and complex 2 (bottom) at increasing concentrations of the complexes.
Lane 1 DNA only, Lane 2: metal complex only, Lane 3: DNA + 0.04, Lane 4: DNA + 0.08, Lane 5: DNA + 0.12, Lane 6: DNA + 0.16, Lane 7: DNA + 0.20, Lane 8: DNA + 0.25 mM of
complex.
3.5. Plasmid DNA cleavage studies
The gel electrophoresis studies make it possible for the separa-
tion of the various forms of the DNA after cleavage. Generally, the
super-coiled DNA, form I, has a greater mobility than the open-cir-
cular DNA, form II as a result of the differences in the shape to
charge ratio. Cleavage of the super-coiled DNA, form I, produces
the open-circular DNA, form II. The agarose gel electrophoresis
analysis indicated that both complex 1 and complex 2 exhibit
cleavage activities towards plasmid DNA. As can be seen from
Fig. 10, cleavage of the plasmid DNA increased as the concentra-
tions of the metal complexes were increased resulting in corre-
sponding decrease in the intensity of form I.
3.6. BNPP and NPP hydrolysis
The hydrolysis of the model phosphate ester compound as BNPP
is an efficient procedure to probe the hydrolytic properties of metal
complexes. The hydrolysis of BNPP produces the 4-nitophenolate
ions that were monitored spectrophotometrically at 400 nm.
Fig. 11 shows the absorbance versus time plot for the reaction of
complex
2
with BNPP. An observed rate constant of
1.43 ꢁ 10ꢂ2 sꢂ1 was calculated for the reaction of complex 2 with
BNPP. A similar reaction using complex 2 and 4-NPP was carried
out. Interestingly, the observed rate constant was determined to
be 8.01 ꢁ 10ꢂ2 sꢂ1, which is about six times faster than that deter-
mined for the BNPP reaction.
4. Conclusion
Two copper complexes have been synthesized and character-
ized by spectroscopic and electrochemical methods. In addition,
the crystal structures of the complexes have been determined
which show the coordination of the tridentate ligands to the cop-
per center. In complex 1 a chloride ligand completes the coordina-
tion sphere whereas in complex 2 an acetate ligand occupies the
fourth coordination site. In both complexes the coordination
around the copper center for each molecular unit is pseudo square
planar. However, in complex 1 the packing diagram shows the each
copper atom is coordinated to a chloride ligand from another
molecular unit. This representation results in a square-based pyra-
Fig. 11. Absorbance versus time (s) plot for the hydrolysis of (a) BNPP (2.15 mM)
and (b) 4-NPP (2.10 mM) in Tris–HCl buffer (pH = 7.2) by the complex
[Cu(TL1)(OAc)]ꢀCH3OH (2) (0.45 mM) in methanol at 37 °C. Absorbance monitored
at kmax 400 nm.

184
N. Kozlyuk et al. / Inorganica Chimica Acta 428 (2015) 176–184
[28] C. Rajarajeswari, R. Longanathan, M. Palaniandavar, E. Suresh, A. Riyasdeen,
M.A. Akbarsha, Dalton Trans. 42 (2013) 8347.
[29] S. Sathiyaraj, K. Sampath, G. Raja, R.J. Butcher, S.K. Gupta, Inorg. Chim. Acta 406
(2013) 44.
[30] V.M. Manikandamathavan, B.U. Nair, Eur. J. Med. Chem. 68 (2013) 244.
[31] L. Giovagnini, S. Sitran, M. Montopoli, L. Caparrotta, M. Corsini, C. Rosani, P.
Zanello, Q.P. Dou, D. Fregona, Inorg. Chem. 47 (2008) 6336.
[32] P.U. Maheswari, M. van der Ster, S. Smulders, S. Barends, G.P. van Wezel, C.
Massera, S. Roy, H. den Dulk, P. Gamez, J. Reedijk, Inorg. Chem. 47 (2008) 3719.
[33] A. Kumar, J.P. Chinta, A.K. Ajay, M.K. Bhat, C.P. Rao, Dalton Trans. 40 (2011)
10865.
[34] S. Ramakrishnan, D. Shakthipriya, E. Suresh, V.S. Periasamy, M.A. Akbarsha, M.
Palniandavar, Inorg. Chem. 50 (2011) 6458.
[35] M. Alagesan, N.S.P. Bhuvanesh, N. Dharmaraj, Dalton Trans. 42 (2013) 7210.
[36] S. Kashanian, M.M. Khodael, H. Roshanfekr, N. Shahabadi, A. Rezvani, G.
Mansouri, DNA Cell Biol. 30 (2011) 287.
midal arrangement for complex 1. The reaction of complexes 1 and
2 with CT-DNA were studied by emission spectra and UV–Vis
absorption. The results of these studies suggest that both com-
plexes strongly interact with CT-DNA. In addition, both complexes
also promote plasmid pBR322 DNA cleavage. Furthermore, com-
plex 2 was found to hydrolyze BNPP and 4-NPP. We observed dif-
ferences in reactivity towards DNA by the two complexes. Since
both complexes contain 8-aminoquinoline groups, the differences
in reactivity towards DNA could be reasonably attributed to the
presence of the naphthalene moiety in complex 2.
Acknowledgements
[37] R. Loganathan, S. Ramakrishnan, E. Suresh, A. Riyasdeen, M.A. Akbarsha, M.
Palaniandavar, Inorg. Chem. 51 (2012) 5512.
[38] S. Ishida, F. McCormick, K. Smith-McCune, D. Hannahan, Cancer Cell 17 (2010)
574.
[39] W. Zhou, X. Wang, M. Hu, C. Zhu, Z. Guo, Chem. Sci. 5 (2014) 2761.
[40] (a) G. Pratviel, J.B. Meunier, Adv. Inorg. Chem. 45 (1998) 251;
(b) S. Anbu, M. Kandaswamy, Inorg. Chim. Acta 385 (2012) 45.
[41] C. Liu, M. Wang, T. Zhang, H. Sun, Coord. Chem. Rev. 248 (2004) 147.
[42] J. Suh, Acc. Chem. Res. 25 (1992) 273.
[43] M.J. Jedrzejas, P. Setlow, Chem. Rev. 101 (2001) 608.
[44] P. Molenvald, J.F.J. Engbersen, D.N. Reinhouldt, Chem. Soc. Rev. 29 (2000) 75.
[45] L. Zhu, O. dos Santos, C.W. Koo, M. Rybstein, L. Pape, J.W. Canary, Inorg. Chem.
42 (2003) 7912.
The authors thank the University of Redlands for providing the
funding for this work. Many thanks also to Dr. Fook Tham and Mr.
Ron See of University of California, Riverside, CA for determining
the single crystal X-ray structures and the ESI-MS, respectively.
Appendix A. Supplementary material
CCDC 800315 and 900831 contain the supplementary crystallo-
graphic data for complexes 1 and 2. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif. Supplementary data
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.ica.2014.12.034.
[46] L. Tjioe, A. Meininger, T. Joshi, L. Spiccia, B. Graham, Inorg. Chem. 50 (2011)
4327.
[47] K.M. Deck, T.A. Tseng, J.N. Burstyn, Inorg. Chem. 41 (2002) 669.
[48] M.J. Belousoff, L. Tjioe, B. Graham, L. Spiccia, Inorg. Chem. 47 (2008) 8641.
[49] L. Tjioe, T. Joshi, J. Brugger, B. Graham, L. Spiccia, Inorg. Chem. 50 (2011) 621.
[50] E.L. Hegg, S.H. Mortimore, C.L. Cheung, J.E. Huyett, D.R. Powell, J.N. Burstyn,
Inorg. Chem. 38 (1999) 2961.
References
[51] M. Scarpellini, A. Neves, R. Homer, A.J. Bortouzzi, B. Szpoganics, C. Zucco, R.A.
Nome, Inorg. Chem. 42 (2003) 8353.
[52] F.H. Fry, A.J. Fischmann, M.J. Belousoff, L. Spiccia, J. Brugger, Inorg. Chem. 44
(2005) 941.
[1] C.G. Hartinger, S. Zorbas-Seifried, M.A. Jakupec, B. Kynast, H. Zorbas, B.K.
Keppler, J. Inorg. Biochem. 100 (2006) 891.
[53] (a) J. He, J. Sun, Z.-W. Mao, L.-N. Ji, H. Sun, J. Inorg. Biochem. 103 (2009) 851;
(b) S. Dhar, P.A.N. Reddy, A.R. Chakravarty, Dalton Trans. (2004) 697;
(c) B. Selvakumar, V. Rajendiran, P.U. Maheswari, H. Stoeckli-Evans, M.
Palaniandavar, J. Inorg. Biochem. 100 (2006) 316.
[2] C.X. Zhang, S.J. Lippard, Curr. Opin. Chem. Biol. 7 (2003) 481.
[3] M. Groessl, E. Reisner, C.G. Hartinger, R. Eichinger, O. Semenova, A.R.
Timerbaev, M.A. Jakupec, V.B. Arion, B.K. Keppler, J. Med. Chem. 50 (2007)
2185.
[54] A.M. Thomas, M. Nethaji, S. Mahadevan, A.R. Chakravarty, J. Inorg. Biochem. 94
(2003) 171.
[55] L.T. Ellis, D.F. Perkins, P. Turner, T.W. Hambley, Dalton Trans. (2003) 2728.
[56] W. Xu, X. Yang, L. Yang, Z.-L. Jia, L. Wei, F. Liu, G.-Y. Lu, New J. Chem. 34 (2010)
2654.
[57] M. Tian, H. Ihmels, E. Brotz, Dalton Trans. 39 (2010) 8195.
[58] A. Kumar, J.P. Chinta, A.K. Ajay, M.K. Bhat, C.P. Rao, Dalton Trans. 40 (2011)
10865.
[59] K.A. Reich, L.E. Marshal, D.R. Graham, D.S. Sigman, J. Am. Chem. Soc. 103 (1981)
3582.
[60] Z. Molphy, A. Prisecaru, C. Slator, N. Barron, M. McCann, J. Colleran, D.
Chandran, N. Gathergood, A. Kellett, Inorg. Chem. 53 (2014) 5392.
[61] A. Kellett, M. O’Connor, M. McCann, M. McNamara, P. Lynch, G. Rosair, V.
McKee, B. Creaven, M. Walsh, S. McClean, A. Foltyn, D. O’Shea, O. Howe, M.
Devereux, Dalton Trans. 40 (2011) 1024.
[62] A.K. Patra, S. Dhar, M. Nethaji, A.R. Chakravarty, Dalton Trans. (2005) 896.
[63] J. Madureira, C.I.V. Ramos, M. Marques, C. Maia, B. de Sousa, L. Campino, M.G.
Santana-Marques, N. Farrell, Inorg. Chem. 52 (2013) 8881.
[64] P.P. Silva, W. Guerra, J.N. Silveira, A.M. da C. Ferreira, T. Bortolotto, F.L. Fischer,
H. Terenzi, A. Neves, E.C. Pereira-Maia, Inorg. Chem. 50 (2011) 6414.
[65] S. Nayak, P. Gamez, B. Kozlevcar, A. Pevec, O. Robeau, S. Dehnen, J. Reedijk,
Polyhedron 29 (2010) 2291.
[66] B.-T. Ko, C.-C. Chang, S.-L. Lai, C.-C. Lin, Polyhedron 45 (2012) 49.
[67] Bruker, APEX 2, version 2010.3-0, Bruker AXS Inc., Madison, Wisconsin, USA, 2010.
[68] Bruker, CELL_NOW, version 2008/2, Bruker AXS Inc., Madison, Wisconsin, USA,
2008.
[69] Bruker, SAINT, version V7.60A, Bruker AXS Inc., Madison, Wisconsin, USA, 2009.
[70] Bruker, TWINABS, version 2008/2, Bruker AXS Inc., Madison, Wisconsin, USA, 2008.
[71] Bruker, SADBAS, version 2008/1, Bruker AXS Inc., Madison, Wisconsin, USA, 2008.
[72] Bruker, SHELXTL, version 2008/4, Bruker AXS Inc., Madison, Wisconsin, USA,
2008.
[4] S.J. Tan, Y.K. Yan, P.P. Lee, K.H. Lim, Future Med. Chem. 2 (2010) 1591.
[5] P.C.A. Bruijnincx, P.J. Sadler, Curr. Opin. Chem. Biol. 12 (2008) 197.
[6] E.R. Jamieson, S.J. Lippard, Chem. Rev. 99 (1999) 2467.
[7] E.I. Solomon, D.E. Heppner, E.M. Johnston, J.W. Ginsbach, J. Cirera, M. Qayyum,
M.T. Kieber-Emmons, C.H. Kjaergaard, R.G. Hadt, L. Tian, Chem. Rev. 114 (2014)
3659.
[8] (a) D. Chen, Q.C. Cui, Q.P. Dou, Cancer Res. 66 (2006) 10425;
(b) C. Cen, D. Brayton, B. Shahandeh, F.L. Meyskens, P.J. Farmer, J. Med. Chem.
47 (2004) 6919;
(c) L. Giovagnini, S. Sitran, M. Montopoli, L. Caparrotta, M. Corsini, C. Rosani, P.
Zanello, Q.P. Dou, D. Fregona, Inorg. Chem. 47 (2008) 6336.
[9] V.M. Manikandamathavan, V. Rajapandian, A.J. Freddy, T. Weyhermuller, V.
Subramanian, B.U. Nair, Eur. J. Med. Chem. 57 (2012) 449.
[10] S. Dhar, M. Nethaji, A.R. Chakravarty, Inorg. Chem. 45 (1050) (2006). 11043-1.
[11] C. Marzano, M. Pellei, F. Tisato, C. Santini, Anticancer Agents Med. Chem. 9
(2009) 15.
[12] V. Uma, M. Elango, B.U. Nair, Eur. J. Inorg. Chem. (2007) 3484.
[13] P.U. Maheswari, K. Lappalaien, M. Sfregola, S. Barends, P. Gamez, U. Tureinen, I.
Mutikainen, G.P. van Wezel, J. Reedijk, Dalton Trans. (2007) 3676.
[14] A. Pal, B. Biswas, S.K. Mondal, C.-H. Lin, R. Ghosh, Polyhedron 31 (2012) 671.
[15] Q. Wang, Z. Yu, Q. Wang, W. Li, F. Gao, S. Li, Inorg. Chim. Acta 383 (2012) 230.
[16] S.S. Massoud, R.S. Perkins, K.D. Knierim, S.P. Comiskey, K.H. Otero, C.L. Michel,
W.M. Juneau, J.H. Albring, F.A. Mautner, W. Xu, Inorg. Chim. Acta 399 (2013)
177.
[17] M. Tabatabaee, M. Bordbar, M. Ghassemzadehh, M. Tahriri, M. Tahrir, Z.M.
Lighvan, B. Neumuller, Eur. J. Med. Chem. 70 (2013) 364.
[18] D. Li, J. Tian, Y. Kou, F. Huang, G. Chen, W. Gu, X. Liu, D. Liao, P. Cheng, S. Yan,
Dalton Trans. (2009) 3574.
[19] A. Solanki, S.B. Kumar, A.A. Doshi, C.R. Prabha, Polyhedron 63 (2013) 147.
[20] P. Kumar, B. Baidya, S.K. Chaturvedi, R.H. Khan, D. Manna, B. Mondal, Inorg.
Chim. Acta 376 (2011) 264.
[73] During the preparation of this manuscript, the reaction of 1-methyl-2-
imidazolecarboxaldehyde and 8-aminoquinoline was reported: S. Mandal,
D.K. Poria, D.K. Seth, P.S. Ray, P. Gupta, Polyhedron 73 (2014) 12.
[74] J. Lu, Q. Sun, J.-L. Li, L. Jiang, W. Gu, X. Liu, J.-L. Tian, S.-P. Yan, J. Inorg. Biochem.
137 (2014) 46.
[21] Q. Wang, Z. Yu, Q. Wang, W. Li, F. Gao, S. Li, Inorg. Chim. Acta 383 (2012) 230.
[22] P. Rabindra, N. Raju, Polyhedron 44 (2012) 1.
[23] Y.-C. Liu, J.-H. Wei, Z.-F. Chen, M. Liu, Y.-Q. Gu, K.-B. Huang, Z.-Q. Li, H. Liang,
Eur. J. Med. Chem. 69 (2013) 554.
[24] B.-T. Ko, C.-C. Chang, S.-L. Lai, F.-J. Lai, C.-C. Lin, Polyhedron 45 (2012) 49.
[25] G.-Y. Li, K.-J. Du, J.-Q. Wang, J.-W. Liang, J.-F. Kou, X.-J. Hou, L.-N. Ji, H. Chao, J.
Inorg. Biochem. 119 (2013) 43.
[75] I. Lumb, M.S. Hundal, M. Corbella, V. Gomez, G. Hundal, Eur. J. Inorg. Chem.
(2013) 4799.
[76] P. Kumar, S. Gorai, M.K. Santra, B. Mondal, D. Manna, Dalton Trans. 41 (2012)
7573.
[77] H. Liu, F. Gao, D. Niu, J. Tian, Inorg. Chim. Acta 362 (2009) 4179.
[26] S.S. Bhat, A.A. Kumbhar, H. Heptullah, A.A. Khan, V.V. Gobre, S.P. Gejji, V.G.
Puranik, Inorg. Chem. 50 (2011) 545.
[27] A. Barve, A. Kumbhar, M. Bhat, B. Joshi, R. Butcher, U. Sonawane, R. Joshi, Inorg.
Chem. 48 (2009) 9120.