A zinc(II) quinolinone complex (Et3NH)[Zn(qui)Cl2]: Synthesis, X-ray structure, spectral properties and in vitro cytotoxicity

Article abstract of DOI:10.1016/j.molstruc.2013.12.050

A new zinc(II) complex with 2-phenyl-3-hydroxy-4(1H)-quinolinone (Hqui) of the composition (Et₃NH)[Zn(qui)Cl₂] was prepared and characterized by elemental analysis, FT IR, 1D and 2D NMR, and fluorescence spectroscopy, mass spectrometry and single crystal X-ray analysis. The molecular structure is composed of the triethylammonium (Et₃NH⁺) cations and tetrahedral [Zn^II(qui)Cl₂]^- complex anions, in which the Zn(II) atoms are bidentate coordinated by one qui ligand through keto (O_K) and phenolate (O_P) oxygen atoms and by two chlorido ligands, thus forming the {O₂Cl₂} donor set, with Zn-O_K = 1.9860(14) ?, Zn-O_P 1.9961(14) ? and Zn-Cl = 2.2509(6) ? and 2.2266(6) ?. The complex cations are aligned into 1D supramolecular chains through the NHa?Cl hydrogen bonding between the amine group of the quinolinone ligand and the chlorido ligand of the adjacent complex anion. The amine group from the Et ₃NH⁺ cations provides the NHa?O_P hydrogen bond with the phenolate oxygen atoms from the complex anion. Screening of in vitro cytotoxicity of the compound was studied on human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with IC₅₀ > 50 μM. The fluorescence study showed that the complex exhibits a relatively high integral intensity (29%) as compared to the standard quinine sulfate, and 1.6-fold enhancement of emission with respect to free Hqui.

Full text of DOI:10.1016/j.molstruc.2013.12.050

Journal of Molecular Structure 1060 (2014) 42–48
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
A zinc(II) quinolinone complex (Et3NH)[Zn(qui)Cl2]: Synthesis,
X-ray structure, spectral properties and in vitro cytotoxicity
a
b
b,
⇑
ˇ
ˇ
Roman Buchtík , Ivan Nemec , Zdenek Trávnícek
a Department of Inorganic Chemistry, Faculty of Science, Palacky´ University, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic
b Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacky´ University, 17. listopadu 12, CZ-77146 Olomouc,
Czech Republic
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
ꢀ
ꢀ
The first zinc(II) quinolinone complex
was synthesized and characterized.
The compound is composed of
triethylammonium cation and
[Zn(qui)Cl2] anion.
ꢀ
ꢀ
Secondary structure shows a zig–zag
1D supramolecular architecture.
The fluorescence of the complex is
enhanced as compared to free Hqui
ligand.
ꢀ
The compound displays no relevant
in vitro cytotoxicity against HOS and
MCF7.
a r t i c l e i n f o
a b s t r a c t
Article history:
A
new zinc(II) complex with 2-phenyl-3-hydroxy-4(1H)-quinolinone (Hqui) of the composition
Received 10 September 2013
Received in revised form 2 December 2013
Accepted 4 December 2013
Available online 22 December 2013
(Et3NH)[Zn(qui)Cl2] was prepared and characterized by elemental analysis, FT IR, 1D and 2D NMR, and
fluorescence spectroscopy, mass spectrometry and single crystal X-ray analysis. The molecular structure
is composed of the triethylammonium (Et3NH+) cations and tetrahedral [ZnII(qui)Cl2]ꢁ complex anions, in
which the Zn(II) atoms are bidentate coordinated by one qui ligand through keto (OK) and phenolate (OP)
oxygen atoms and by two chlorido ligands, thus forming the {O2Cl2} donor set, with Zn–OK = 1.9860(14)
Å, Zn–OP 1.9961(14) Å and Zn–Cl = 2.2509(6) Å and 2.2266(6) Å. The complex cations are aligned into 1D
supramolecular chains through the NAHꢂ ꢂ ꢂCl hydrogen bonding between the amine group of the
quinolinone ligand and the chlorido ligand of the adjacent complex anion. The amine group from the
Et3NH+ cations provides the NAHꢂ ꢂ ꢂOP hydrogen bond with the phenolate oxygen atoms from the com-
plex anion. Screening of in vitro cytotoxicity of the compound was studied on human osteosarcoma (HOS)
Keywords:
Zinc(II) complex
Quinolinone
NMR spectroscopy
X-ray structure
Fluorescence
In vitro cytotoxicity
and human breast adenocarcinoma (MCF7) cell lines, with IC50 > 50 lM. The fluorescence study showed
that the complex exhibits a relatively high integral intensity (29%) as compared to the standard quinine
sulfate, and 1.6-fold enhancement of emission with respect to free Hqui.
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
toxicity in the field of medicinal and bioinorganic chemistry. The
chemists and drug designers have focused their interests on the
In a few past decades, there have been performed massive inves-
tigations in cytotoxicity and genotoxicity of new metal-based anti-
tumor complexes able to overcome cisplatin resistance and its high
preparation and study of a number of transition metal complexes
other than platinum, which could offer unique properties such as
variable redox states, photoluminescence properties and ability of
targeting DNA through non-covalent modes of action [1–6]. In an at-
tempt to obtain non-platinum based biologically active complexes,
which would exceed anticancer effect and concurrently reduce
⇑
Corresponding author. Tel.: +420 585 634 352; fax: +420 585 634 954.
ˇ
E-mail address: zdenek.travnicek@upol.cz (Z. Trávnícek).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.12.050

R. Buchtík et al. / Journal of Molecular Structure 1060 (2014) 42–48
43
toxicity in comparison with clinically-used cisplatin, we recently
published mixed-ligand copper(II) complexes, involving 2-phenyl-
as tropoloid. The complex exhibiting the highest cytotoxicity was
[Zn(bpy-9)(QT)2] (IC50 = 2.8 M), where QT = 4-(3,3-dimethylbuta-
l
3-hydroxy-4(1H)-quinolinone (Hqui) and its derivatives, of
a
noyl)-5-methyl-2-phenyl-1H-pyrazol-3-one [27].
general composition [Cu(qui)(Nlig)]X (Nlig = derivatives of
1,10-phenanthroline or 2,20-bipyridine, X = BF4 or NO3). These com-
plexes showed significantly higher anticancer effect against a series
of human cancer cell lines together with reduced toxicity against
healthy human cells as compared to cisplatin indeed [7–9]. The high-
est cytotoxicity was found for the complexes [Cu(qui)(mphen)]BF4-
Herein, we present the preparation, solid-state and solution
characterizations, and in vitro antitumor screening for
(Et3NH)[Zn(qui)Cl2] (Scheme 1). This compound was studied
primarily due to its possible potential to combine cytotoxic and
luminescent properties and furthermore, the Zn(II) compounds
with the quinolinone derivatives have also never been studied
and structurally characterized yet. (Cambridge Crystallographical
Database (CSD), ver. 5.34, May 2013 update).
ꢂH2O (IC50 = 0.36
(IC50 = 0.66 and 0.73
0.57 M and 0.70 M) (where mphen = 5-methyl-1,10-phenan-
lM
and 0.56
l
M), [Cu(qui)(bphen)]NO3ꢂH2O
lM
lM) and [Cu(qui)(bphen)]BF4 (IC50 =
l
l
throline and bphen = bathophenanthroline) against A2780 (ovarian
carcinoma), and A2780cis (cisplatin-resistant ovarian carcinoma)
2. Experimental
respectively, as compared with the values of 12.0 lM, and 27.0 lM
determined for cisplatin.
2.1. Materials and methods
The originally anticancer inactive Hqui used as a ligand in the
above mentioned and highly cytotoxic Cu(II) complexes belongs
to a vast group of quinolinones which are otherwise generally
known not only for a number of biological activities e.g. cytotoxic-
ity [10–12] but they are also characteristic for their intrinsic pho-
toluminescence [13,14]. Photoluminescence effects, such as
fluorescence could be contributive in the study of cytotoxic com-
pounds, because these physical properties could e.g. enable a de-
tailed investigation of their possible interaction with DNA
through several spectral methods, suggesting partial inter-base
intercalations or other non-covalent DNA interactions [15]. In this
context, the preparation of Zn(II) complexes with the quinolinones
represents the next logical step in our ongoing studies of these or-
ganic compounds as ligands in transition metal complexes, for
multiple reasons: (a) zinc belongs among the most abundant met-
als in human body, and plays an irreplaceable role in loads of bio-
logical processes such as enzymatic regulation [16,17], neural
signal transmission [18,19] and also DNA binding [20]; (b) Zn(II)
complexes frequently exhibit fluorescence and moreover have of-
ten been observed to have higher intensity in comparison with
the parent organic compound due to enhancement of the charge-
transfer character of the excited state of the chromophore
[21,22]; and (c) additionally, in the last decade, there has been a
number of studies on cytotoxicity of Zn(II) complexes, where such
compounds have been found significantly active [23–25], and in
particular, selective against prostatic tumor cells, e.g. Zn(II) com-
Chemicals and solvents were purchased from Sigma–Aldrich Co.
and Acros Organics Co., and were used as received. 2-Phenyl-3-hy-
droxy-4(1H)-quinolinone (Hqui) was synthesized following the
formerly reported procedure [28] in a high yield (>95%). The com-
pound was characterized by elemental analysis, FT IR and also sin-
gle crystal X-ray analysis [7]. Anal. Calcd for
(M = 237.3 g molꢁ1) (%): C, 75.9; H, 4.7; N, 5.9. Found: C, 75.6; H,
4.3; N, 5.7. FT IR (
ATR/cmꢁ1): 518w, 644w, 693m, 707m, 758s,
842w, 909w, 995m, 1030m, 1150m, 1267vs, 1368vs, 1403s,
1489s, 1550s (C'Carom), 1631vs (C@O).
C15H11NO2
m
m
m
Elemental analyses (C, H, N) were performed on a Flash 2000
CHNO-S Analyser (Thermo Scientific). Conductivity measurements
were carried out on a Cond 340i/SET (WTW) in nitromethane
10ꢁ3 M solution at 25 °C. Electronic absorption spectra of 10ꢁ4
M
ethanolic and/or 0.1 M H2SO4 solutions were recorded with a
Lambda 40 spectrometer (Perkin Elmer instruments) in the range
of 200–1000 nm. Mass spectrometry studies were performed on
an LTQ Fleet (ThermoFisher Scientific) with the ESI-(negative-ion
electrospray ionization) full scan mode in 10ꢁ5 M methanolic solu-
tions. FT IR spectra were recorded on a Nexus 670 FT IR (ThermoN-
icolet) using the ATR technique in the range of 200–4000 cmꢁ1. The
intensities of reported FT IR signals are defined as vs = very strong,
s = strong, m = medium, w = weak and br = broad. 1H and 13C NMR
spectra and 2D correlation experiments (1HA1H gs-COSY, 1HA13C
gs-HMQC and 1HA13C gs-HMBC; gs = gradient selected,
COSY = correlation spectroscopy, HMQC = heteronuclear multiple
quantum coherence and HMBC = heteronuclear multiple bond
coherence) of the DMF-d7 solutions were measured at 300 K on a
Varian 400 device (Varian, Santa Clara, CA, USA) at 400.00 MHz
(1H) and 100.58 MHz (13C). The spectra were adjusted against the
tetramethylsilane (TMS) signals and calibrated against the residual
signals of the DMF adjusted to 8.03 ppm (1H) and 162.3 ppm (13C).
The splitting of proton resonances in the reported 1H spectra is de-
fined as s = singlet, d = doublet, t = triplet, q = quartet, br = broad
band, m = multiplet. Fluorescence solution spectra were recorded
on an AvaSpec HS1024x122TE spectrometer using 0.5 cm cuvettes
at room temperature. The fluorescence relative integral intensity of
plexes with thiosemicarbazones of
a general composition
[Zn(bpy)(L1)], where bpy = 2,20-bipyridine and L1 stands for substi-
tuted semicarbazones. The significant cytotoxicity against the
prostate cancer cell line (PC3) was found e.g. for
[Zn(bpy)(HP)]ꢂ2H2O (IC50 = 0.84
lM), where HP = 4-hydrox-
ysalicylaldiminato-40-phenylthiosemicarbazone [26]. Another
group of zinc complexes showing considerable activity against
PC3 is that of a general composition [Zn(bpy-9)(L2)2], where bpy-
9 = 4,40-dinonyl-2,20-bipyridine and L2 stands for a diketonate such
(Et3NH) [Zn(qui)Cl2] and ligand Hqui were determined in 10ꢁ4
M
ethanolic solutions by a comparison with the fluorescence of qui-
nine sulfate as a reference fluorescence standard (10ꢁ4 M solution
of the standard in 0.1 M sulfuric acid in ethanol) [29]. The mea-
sured compounds were excited at the wavelengths of absorption
maximum of each compound.
X-ray experiment of a selected crystal of (Et3NH) [Zn(qui)Cl2] was
collected on an Xcalibur™2 diffractometer (Oxford Diffraction Ltd.)
with the Sapphire2 CCD detector, and with Mo Ka radiation (Mono-
chromator Enhance, Oxford Diffraction Ltd.). Data collection and
reduction were performed using the CrysAlis software [30]. The
structure was solved by direct methods using SHELXS-97 and
Scheme 1. Structural formula of (Et3NH) [Zn(qui)Cl2] together with the atom
numbering.

44
R. Buchtík et al. / Journal of Molecular Structure 1060 (2014) 42–48
refined on F2 using the full-matrix least-squares procedure (SHELXL-
97) [31]. Non-hydrogen atoms were refined anisotropically and
hydrogen atoms were located in difference Fourier maps and refined
by using the riding model, with CAH = 0.95, 0.98 and 0.99 Å,
NAH = 0.88 and 0.93 Å, and with Uiso(H) = 1.2Ueq (CH, CH2, NH)
and Uiso(H) = 1.5Ueq (CH3). The crystal data and structure refine-
ments are given in Table 1. The molecular graphics as well as addi-
tional structural calculations were drawn using DIAMOND [32].
tetrazolium bromide] on human Caucasian osteosarcoma cells
(HOS; ECACC No. 87070202) and human Caucasian breast adeno-
carcinoma cells (MCF7; ECACC No. 86012803). Human cancer cell
lines were purchased from the European Collection of Cell Cultures
(ECACC). The cells were cultured according to the manufacturer’s
instructions and maintained at 37 °C and 5% CO2 in a humidified
incubator (100% humidity).
The cancer cell lines were treated with the tested compounds
for 24 h, using multi-well culture plates of 96 wells. The tested
compound (Et3NH)[Zn(qui)Cl2] and cisplatin were applied to the
2.2. Synthesis
cells at the concentrations of 0.01, 0.1, 1.0, 5.0, 25.0 and 50.0 lM.
In parallel, the cells were treated with vehicle (DMF; 0.1% v/v)
and Triton X-100 (1% v/v) to assess the minimal (i.e. positive con-
trol) and maximal (i.e. negative control) cell damage, respectively.
Cells were incubated with MTT for 3–4 h, after removal of the med-
ium and washing the cells with the phosphate buffer solution, for-
mazan dye was dissolved in DMF containing 1% of ammonia. The
MTT assay absorbance was measured spectrophotometrically at
540 nm (TECAN, Schoeller Instruments LLC). The data were ex-
pressed as the percentage of viability, when 100% and 0% represent
the treatments with DMF, and Triton X-100, respectively. The data
regarding the cancer cell lines were obtained from three indepen-
The starting ligand Hqui (2 mmol; 474 mg) was dissolved in
50 mL of hot ethanol and then Et3N (2 mmol; 275 lL) was slowly
added. To this mixture, a 10 mL of ethanolic solution of ZnCl2
(2 mmol; 270 mg) was added and refluxed for 1 h. After cooling
down, the solution was filtered and left to stand at ambient tem-
perature. Within two days, golden-yellow crystals of product
started to form. The crystals were filtered off and dried at 40 °C un-
der an infrared lamp. Yield: 628 mg (66%). Anal. Calcd for C21H26-
N2Cl2O2Zn (M = 474.7 g molꢁ1) (%): C, 53.1; H, 5.5; N, 5.9. Found:
C, 53.5; H, 5.8; N, 5.5.
ESI–MS: m/z 236 ([qui]ꢁ, 100%), 334 ([Zn(qui)ClAH]ꢁ, 18%), 372
([Zn(qui)Cl2]ꢁ, 3%), 535 ([Zn(qui)2AH]ꢁ, 3%).
dent cell passages. The obtained IC50 SD (lM) values together
with their standard deviations were calculated from viability
curves.
1H NMR (DMF-d7, TMS, d ppm) J (Hz): 1.28, 9H, t, (7.2), CH3;
3.24, 6H, q, (7.0), CH2; 7.29, 1H, t, (7.6), HC5; 7.42, 1H, t, (7.4)
HC13; 7.51, 3H, m, HC6,12,14; 7.93, 1H, d, (8.6) HC7; 8.24, 3H, d,
(8.2), HC4,11,15; 11.98, 1H, br, HN1.
3. Results and discussion
13C NMR (d7-DMF, TMS, d ppm): 8.9 (3CCH3), 46.7 (3CCH2), 118.8
(C7), 119.5 (C3), 122.0 (C5), 124.2 (C4), 128.1 (C12, 14), 128.5 (C6),
129.1 (C13), 129.3 (C11, 15), 131.4 (C9), 134.5 (C10), 135.9 (C1),
149.7 (C8), 172.9 (C2).
3.1. General characterization
The (Et3NH) [Zn(qui)Cl2] compound was obtained in the form of
pale golden-yellow crystals, while its purity, composition and
structure were based on the results following mainly from elemen-
tal analysis, mass spectrometry, NMR data and X-ray analysis. The
molar conductivity value of the studied complex dissolved in nitro-
methane equals 78.5 S cm2 molꢁ1, which fits in the 75–95 S cm2 -
molꢁ1 range that is characteristic for the 1:1 electrolyte for this
type of solvent [33].
FT IR (m
ATR/cmꢁ1): 242w, 268s, 274s, 288vs, 291vs, 310s, 330w,
378m, 391w, 450s, 472s, 492w, 549m, 646m, 660m, 693m, 715m,
729m, 764s, 800m, 834w, 910w, 926w, 999m, 1034m, 1126m,
1153m, 1213s, 1264s, 1365vs, 1388s, 1447vs, 1464vs, 1486vs,
1519s, 1561s, 1579m, 1628s, 2497s, 2629s, 2828br, 2978vs,
3004vs, 3056vs, 3140vs, 3170vs, 3201vs, 3228vs, 3500br.
2.3. In vitro cytotoxicity
3.2. X-ray crystallography
In vitro cytotoxicity of (Et3NH) [Zn(qui)Cl2] was determined by
an MTT assay [MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-
The studied compound (Et3NH) [Zn(qui)Cl2] consists of the tet-
rahedral complex anions [ZnII(qui)Cl2]ꢁ and triethylammonium
(Et3NH+) cations (Fig. 1). The complex crystallizes as yellow planar
crystals in the P21/c space group (Table 1). The complex anions
consist of one the qui ligand coordinated to the Zn(II) atom in a
chelate manner through the keto (OK) and phenolate (OP) oxygen
atoms, and two chlorido ligands thus forming the {ZnO2Cl2} chro-
mophore with the tetracoordinated central Zn(II) atom (Fig. 1). The
ZnO bond lengths are of a similar length with a bit shorter ZnAOK
bond (1.9860(14) Å) in comparison to ZnOP (1.9961(14) Å). Two
chloride anions act as terminal ligands, with d(ZnCl) = 2.2509(6)
and 2.2266(6) Å. These chromophore bond lengths are comparable
to those reported previously for similar systems (Table 2).
The chromophore angles are strongly affected by the chelating
nature of the qui ligand, which induces the formation of a very nar-
row OKAZnAOP angle (85.12(6)°, Table 2). The remaining OZnCl
and ClZnCl angles are in the range of 108.7–117.6°, and such an
angular distortion of the coordination polyhedron is typical for
the tetrahedral complexes with chelating O,Oligands. As an exam-
ple, the bite angles of complexes [Zn(eaa)Cl2] and [Zn(aed)Cl2] can
be mentioned, in which the OAZnAO angles adopt values of
87.52(7)°, and 88.4(2)°, respectively (eaa = N,N0-ethylene-acety-
lacetonimine, aed = (2-hydroxy-4-methoxy acetophenone)ethy-
lenediamine) [37,38].
Table 1
Crystal data and structure refinement for (Et3NH) [Zn(qui)Cl2].
Formula
C21H26Cl2N2O2Zn
474.70
Yellow
Formula weight (g molꢁ1
Crystal color
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
)
150(2)
0.71073
Monoclinic
P21/c
12.0722(5)
9.7792(4)
18.7384(8)
90
b (Å)
c (Å)
a
(°)
b (°)
101.685(4)
90
2166.34(16)
4, 1.593
1.399
c
(°)
V (Å3)
Z, qcalc /g cmꢁ3
l
(mmꢁ1
)
F(000)
Final R indices
[I > 2 (I)]
984
R1 = 0.0264
wR2 = 0.0539
R1 = 0.0402
wR2 = 0.0558
0.903
r
R indices (all data)
GoF on F2
CCDC Ref. no
959886

R. Buchtík et al. / Journal of Molecular Structure 1060 (2014) 42–48
45
3.3. Spectral properties of (Et3NH) [Zn(qui)Cl2]
The band of the characteristic (C'O) vibration of the quinoli-
m
none moiety was observed in the FT IR spectrum of the complex at
1628 cmꢁ1, which might be surprising, because it does not differ
markedly from that of the uncoordinated Hqui found at
1631 cmꢁ1. Nevertheless, this phenomena has already been ob-
served before in the case of Cu(II)-quinolinone complexes [7].
The bands centred at 3228 and 3201 cmꢁ1 are assignable to the
(NAH)aromatic stretching vibrations, while the bands at 3056 and
3140 cmꢁ1 may be connected with
m(CAH)aromatic. The presence
of the triethylammonium cation can be supported by the existence
of bands at 2828, and 2497 and 2629 cmꢁ1, which may be attribut-
able to the NAH protonated, and CH2 and CH3 vibrations, respec-
tively [42]. The band belonging to the ZnACl stretchning
vibration was observed at ca 290 cmꢁ1 [43,44], while the band re-
Fig. 1. Molecular structure of (Et3NH) [Zn(qui)Cl2] together with the atom
numbering scheme. The non-H atoms are drawn as thermal ellipsoids at the 50%
probability level.
corded at 450 cmꢁ1 may be associated with
m(Zn–O) [45].
The mass spectrum of (Et3NH) [Zn(qui)Cl2] was measured in the
ESI-mode. The peak with m/z = 372 corresponds to the complex an-
ion [Zn(qui)Cl2]ꢁ with the characteristic zinc isotopic distribution.
The peak with the 100% relative intensity observed at m/z = 236
represents the ligand [qui]ꢁ. There are also two other fragments,
the first observed at m/z = 334, corresponding to [Zn(qui)ClAH]ꢁ,
and the next one detected at m/z = 535 assignable to [Zn(qui)2AH]ꢁ
species (Fig. 3).
The qui ligand involves benzene and pyridine rings, which are
nearly coplanar with the dihedral angle being 3.99(6)°, while the
least-square planes fitted through the qui and phenyl moieties
make a dihedral angle of 50.71(6)°.
The composition of (Et3NH) [Zn(qui)Cl2] was assigned through a
detailed data analysis of 1H and 13C NMR experiments. The protons
at aliphatic trimethylammonium and aromatic rings carbons were
assigned by their chemical shifts d (ppm) and multiplicity. The sig-
nals in the 1H NMR spectrum showed a very high purity (>98%) of
the measured compound. The 1H NMR spectra contain the triplet
and quartet at 1.28, and 3.24 ppm, respectively, belonging to the
three CH3A groups and three CH2A groups of the triethylammo-
nium cation. The peaks in the range of 7.29–8.24 ppm correspond
to the eight protons bound to the carbons of the two aromatic rings
(quinolinone and phenyl), which have been assigned using 1HA1H
gs-COSY and 1HA13C gs-HMQC experiments (Fig. 4). The singlet
found at 11.98 ppm can be assigned to the proton at the nitrogen
atom of quinoxalinone moiety in the position 1. The 13C strong sig-
nals at 8.8 ppm and 46.7 ppm respectively, belong to the triethyl-
ammonium cation. The rest of the 15 carbon signals in the range
of 118.8–172.9 ppm belong to the carbons forming the quinolinone
and phenyl aromatic rings.
The crystal structure of (Et3NH) [Zn(qui)Cl2] is stabilized by a
network of non-covalent contacts of the NAHꢂ ꢂ ꢂO, NAHꢂ ꢂ ꢂCl,
CAHꢂ ꢂ ꢂO and CAHꢂ ꢂ ꢂCl types, and can be formally classified as
one-dimensional due to a presence of chain sub-structures of the
complex anions bonded together through the NAHꢂ ꢂ ꢂCl hydrogen
bonds (with the Nꢂ ꢂ ꢂCl distance of 3.255(2) Å) forming between
the amine groups of the qui ligand and the chlorido ligands of
the adjacent complex anions (Fig. 2, top). The Et3NH+ cations are
in interactions with the complex anions by NAHꢂ ꢂ ꢂOP hydrogen
bonds of a moderate strength: d(N1Aꢂ ꢂ ꢂOP) = 2.773(2) Å (Fig. 2,
down left). From the other non-covalent interactions presented in
(Et3NH) [Zn(qui)Cl2], the centrosymmetric pairs of CAHꢂ ꢂ ꢂO inter-
actions between quinolinone aromatic CH groups and keto oxygen
atoms has to be mentioned (a ring synthon R22(10), Fig. 2, down
right): d(Cꢂ ꢂ ꢂkOK) = 3.462(3) Å. These contacts represent the most
important non-covalent interconnections between the 1D chains
of the complex anions in the crystal structure of (Et3NH)
[Zn(qui)Cl2].
Table 2
Selected bond lengths (Å) and angles (°) for (Et3NH) [Zn(qui)Cl2] and their comparison with complexes involving the {ZnO2Cl2} chromophore, and deposited in Cambridge
Structural Database.
Complex
d(ZnAO)/Å
d(ZnACl)/Å
\(OAZnAO)
\(ClAZnACl)
Refs.
[Zn(qui)Cl2]
1.9860(14)
1.9961(14)
1.950(2)a
1.9783(11)a
1.949(3)
1.963(2)
2.001(4)
2.008(3)
1.957(5)
1.976(5)
1.979(9)a
1.959(2)
1.985(2)
1.992(2)
2.008(2)
2.2509(6)
2.2266(6)
2.2430(7)a
2.2314(3)a
2.2552(13)
2.2570(12)
2.213(2)
85.12(6)
112.69(2)
This work
[Zn(val)2Cl2]
[Zn(gly)2Cl2]
[Zn(dnb)2Cl2]2
91.77(9)
97.79(4)
95.44(5)
110.48(3)
106.67(2)
113.26(4)
ACETUX [34]
AFEMEE [35]
AVUHO [36]
[Zn(eaa)Cl2]
[Zn(aed)Cl2]
87.52(7)
88.4(2)
117.52(6)
116.03(9)
DIWLAW [37]
NESDAR [38]
2.208(2)
2.219(2)
2.233(2)
[Zn(mqo)2Cl2]
[Zn(gbp)2Cl2]
2.238(5)a
2.2517(9)
2.2580(10)
2.195(2)
107.89(4)
94.21(8)
120.43(2)
110.56(3)
AFUSEZ [39]
DOBBIG [40]
[Zn(H2O)2Cl2]
103.91(7)
125.12(8)
ELUCAQ [41]
2.197(2)
List of abbreviations: eaa = N,N0-ethylene-acetylacetonimine, aed = (2-hydroxy-4-methoxy acetophenone)ethylenediamine, val = D,L-valine, gly = glycine, mqo = 2-methyl-
quinoline N-oxide, gbp = gabapentine, dnb = 3,5-dinitrobenzoate.
a
Only symmetrically independent bond lengths are displayed.

46
R. Buchtík et al. / Journal of Molecular Structure 1060 (2014) 42–48
Fig. 2. A part of the crystal structure of (Et3NH) [Zn(qui)Cl2] showing non-covalent interactions. A perspective view on one-dimensional supramolecular substructure formed
by NAHꢂ ꢂ ꢂCl hydrogen bonding (top). Symmetry codes: (i) 1 ꢁ x, 0.5 + y, 1.5 ꢁ z; (ii) x, 1 + y, z; (iii) 1 ꢁ x, 1.5 + y, 1.5 ꢁ z; (iv) 1 ꢁ x, –0.5 + y, 1.5 ꢁ z; (v) x, ꢁ1 + y, z; (vi) 1 ꢁ x,
ꢁ1.5 + y, 1.5 ꢁ z. The NAHꢂ ꢂ ꢂO hydrogen bond between the cation and complex anion (down left) and the CAHꢂ ꢂ ꢂO interactions between the complex anions (down right). The
non-covalent contacts are displayed as black dashed lines. Hydrogen atoms (except for those involved in non-covalent interactions) are omitted for clarity.
Fig. 3. ESI–MS spectrum of (Et3NH) [Zn(qui)Cl2], 10ꢁ5 M in methanol, showing the
peak of the complex anion [Zn(qui)Cl2]ꢁ and its fragmentation to [Zn(qui)ClAH]ꢁ
and [qui]ꢁ together with the recombination of the ligand and Zn(II), thus creating
[Zn(qui)2AH]ꢁ.
3.4. UV absorption and fluorescence studies
Fig. 4. 1HA13C gs-HMQC spectra (inset: 1HA1H gs-COSY spectra) of (Et3NH)
[Zn(qui)Cl2].
The 10ꢁ4 M solution UV–vis absorption spectra were measured
in order to find out the absorption maxima of each of the corre-
sponding compounds, i.e. free Hqui, (Et3NH) [Zn(qui)Cl2] and qui-
shifted. This feature may pointed out that the absorption may be
associated with the coordination of the Hqui ligand to zinc and
should not be ascribed to ligand-to-metal and/or metal-to-ligand
charge transfer transitions.
nine sulfate as a standard (Fig. 5). The UV–vis spectrum of the
free Hqui ligand displays the absorption bands with maxima at
259 nm (
362 nm (
e e
= 10 270 Mꢁ1 cmꢁ1), 314 nm ( = 1 660 Mꢁ1 cmꢁ1) and
e
= 3590 Mꢁ1 cmꢁ1) from which the latter value was cho-
To evaluate the fluorescence characteristics of (Et3NH)
[Zn(qui)Cl2], the 10ꢁ4 M ethanolic solutions of the complex, qui-
nine sulfate (standard) and free Hqui ligand were measured at
room temperature. Their fluorescence properties are depicted
and compared in Fig. 5. It is shown that the complex displays
one emission band centered at 477 nm (kex = 397 nm) which is
red-shifted as compared to that of free Hqui ligand with the max-
imum at 465 nm (kex = 362 nm). In connection with these results it
sen as the excitation wavelength for subsequent fluorescent study.
The bands associated with these maxima can be attributed to the
p–
p⁄ and/or n–p⁄ transitions. The (Et3NH) [Zn(qui)Cl2] complex
shows very similar spectrum as compared with the free Hqui li-
gand, involving bands with the maxima at 268 (
= 14 120 Mꢁ1
= 4 720 Mꢁ1
-
e
e
cmꢁ1), 312 nm (
e
= 1 810 Mꢁ1 cmꢁ1) and 397 nm (
cmꢁ1), however, especially the band centred at 397 nm, which
was chosen as the excitation wavelength, is broadened and red-

R. Buchtík et al. / Journal of Molecular Structure 1060 (2014) 42–48
47
Fig. 5. Electronic absorption spectra (left) of the complex (c = 1.0 ꢃ 10ꢁ4 M) in ethanol (green full line) and Hqui (c = 1.0 ꢃ 10ꢁ4 M) in ethanol (red dotted line), together with
1.0 ꢃ 10ꢁ4 M solution of the standard quinine sulfate in 0.1 M H2SO4 (blue dashed line). Part of fluorescence emission spectra (right) of the complex (c = 1.0 ꢃ 10ꢁ4 M) in
ethanol (green full line) and Hqui (c = 1.0 ꢃ 10ꢁ4 M) in ethanol (red dotted line) in comparison with the standard 1.0 ꢃ 10ꢁ4 M solution of quinine sulfate in 0.1 M H2SO4 (blue
dashed line). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
may be proposed that the complex shows ligand-based
fluorescence emission, which character may be associated with
Acknowledgements
the
p
–
p
⁄ and/or n– ⁄ transitions of the coordinated qui ligand.
p
This research was supported by the Operational Program Re-
search and Development for Innovations – European Regional
Development Fund (CZ.1.05/2.1.00/03.0058), Operational Program
Education for Competitiveness – European Social Fund (CZ.1.07/
2.3.00/20.0017) of the Ministry of Education, Youth and Sports of
The observed relative integral intensity of the complex and Hqui
was found to be 29%, and 8.5%, respectively, of the intensity of
the quinine sulfate used as a standard. On the other hand, the
complex showed 1.6-fold enhancement of the emission with re-
spect to free Hqui.
´
the Czech Republic and by Palacky University in Olomouc
ˇ
(PrF_2013_015). The authors would like to thank Dr. Michal Cajan
3.5. In vitro cytotoxicity
ˇ
for fluorescence measurements, Dr. Radka Krikavová for NMR
experiments, Dr. Jana Gáliková for FT IR spectra, Mr. Tomáš Šilha
Although the non-substituted 2-phenyl-3-hydroxy-4(1H)-quin-
olinone does not exhibit a relevant cytotoxic effect [8], we strived
to find out how and/or whether the cytotoxicity could be affected
by the coordination with biologically available zinc(II) atom. In or-
der to find this out, we carried out in vitro cytotoxicity screening of
(Et3NH) [Zn(qui)Cl2] against two human cancer cell lines (HOS and
MCF7) and compared it with antitumor activity of cisplatin as a
standard chemotherapeutic drug. Unfortunately, in spite of the fact
ˇ
ˇ
for CHN analysis, and Prof. Zdenek Dvorák for in vitro cytotoxicity
testing.
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