Ru, Rh and Ir metal complexes of pyridyl chalcone derivatives: Their potent antibacterial activity, comparable cytotoxicity potency and selectivity to cisplatin

Article abstract of DOI:10.1016/j.poly.2020.114606

Half sandwich ruthenium, rhodium and iridium complexes containing pyridyl chalcone analogues (L1 and L2) are prepared by the reaction of [(arene)M(μ-Cl)Cl]₂ (arene = benzene, p-cymene, Cp*) and (M = Ru, Rh/Ir)] with L1 and L2 in 1:2 (M:L) ratio. Eight neutral mononuclear complexes (1–8) were obtained and characterized using FT-IR, ¹H NMR, ¹³C NMR, ESI mass and UV–Vis spectroscopic methods. The molecular structures of complexes 2, 4, 5 and 7 are established by single crystal X-ray diffraction studies. Antibacterial studies were tested against three strains of bacterial microorganisms Staphylococcus aureus (gram +ve), Klebsiella pneumoniae (gram ?ve) and Escherichia coli (gram ?ve). Further the cytotoxicity study of the pyridyl chalcone derivatives and their complexes were evaluated against the human colorectal cancer cell lines HT-29, HCT-116 p53^+/+, HCT-116 p53^?/? and ARPE-19 (non-cancer retinal epithelium).

Full text of DOI:10.1016/j.poly.2020.114606

Polyhedron 185 (2020) 114606
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Polyhedron
journal homepage: www.elsevier.com/locate/poly
Ru, Rh and Ir metal complexes of pyridyl chalcone derivatives:
Their potent antibacterial activity, comparable cytotoxicity potency
and selectivity to cisplatin
Lincoln Dkhar a, Venkanna Banothu b, Emma Pinder c, Roger M. Phillips c, Werner Kaminsky d,
Mohan Rao Kollipara a,
⇑
a Centre for Advanced Studies in Chemistry, North-Eastern Hill University, Shillong 793 022, India
b Centre for Biotechnology (CBT), Institute of Science & Technology (IST), Jawaharlal Nehru Technological University Hyderabad (JNTUH), Kukatpally 500 085, Hyderabad, Telangana
State, India
c Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK
d Department of Chemistry, University of Washington, Seattle, WA 98195, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Half sandwich ruthenium, rhodium and iridium complexes containing pyridyl chalcone analogues (L1
and L2) are prepared by the reaction of [(arene)M(m-Cl)Cl]2 (arene = benzene, p-cymene, Cp*) and
(M = Ru, Rh/Ir)] with L1 and L2 in 1:2 (M:L) ratio. Eight neutral mononuclear complexes (1–8) were
obtained and characterized using FT-IR, 1H NMR, 13C NMR, ESI mass and UV–Vis spectroscopic methods.
The molecular structures of complexes 2, 4, 5 and 7 are established by single crystal X-ray diffraction
studies. Antibacterial studies were tested against three strains of bacterial microorganisms
Staphylococcus aureus (gram +ve), Klebsiella pneumoniae (gram Àve) and Escherichia coli (gram Àve).
Further the cytotoxicity study of the pyridyl chalcone derivatives and their complexes were evaluated
against the human colorectal cancer cell lines HT-29, HCT-116 p53+/+, HCT-116 p53À/À and ARPE-19
(non-cancer retinal epithelium).
Received 19 February 2020
Accepted 12 May 2020
Available online 19 May 2020
Keywords:
Rhodium
Iridium
Pyridylchalcone
Antibactrial
Anticancer
Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction
intercalation mode of binding to the DNA [6]. Some of the arene
ruthenium complexes prepared by Sadler et al. showed promising
Cancer is one of the major causes of death in both developed
and developing countries [1]. Although the availability of drugs
has increased over recent years, mortality rates remain high and
long-term responses are thwarted by problems of toxicity and
the emergence of resistance [2]. In recent years, there has been a
resurgence interest in organometallic complexes that have differ-
ent modes of action compared to the platinates [3]. In our quest
to find more effective treatments for cancer, other metal-based
compounds incorporating ruthenium, rhodium and iridium have
been developed and these have shown promising activity [4]. High
selectivity of ruthenium complexes towards cancer cells rather
than healthy cells and their stable oxidation states under bodily
conditions showed that they are promising antitumor agents [5].
The biological activity of the metal complexes of ruthenium, rho-
dium and iridium can be a consequence of the coordination or
anticancer activity both in vitro and in vivo [7]. The anticancer
activities of arene ruthenium complexes can be enhanced based
on the ligand scaffolds, which play an important role in controlling
their activity such as improving their water solubility. For example,
bioactive compounds such as flavonoids, isoflavonoids etc., can be
incorporated to arene Ru(II) complexes to enhance their anticancer
activities [8]. Also, bioactive ligand scaffolds such as chalcone
when combined with these arene metal complexes exhibit better
anticancer activity [9].
The wide range of biological activities associated with chalcone
based compounds, both natural and synthetic, their ease of prepa-
ration, the potential of oral administration, safety and profound
natural abundance have led us to explore their therapeutic poten-
tial when combined with metal complexes. Present-day studies
have identified different chalcones and their hybrids as the active
component for anticancer and antibacterial activity. The increasing
incidence of infection caused by the rapid development of bacterial
resistance to most of the known antibiotics is a serious health
⇑
Corresponding author.
E-mail address: mohanrao59@gmail.com (M.R. Kollipara).
https://doi.org/10.1016/j.poly.2020.114606
0277-5387/Ó 2020 Elsevier Ltd. All rights reserved.

2
L. Dkhar et al. / Polyhedron 185 (2020) 114606
were recorded using Q-T of APCI-MS instrument (model HAB
273). Perkin-Elmer 2400 CHN/S analyzer was used for elemental
analyses of the complexes. All these mononuclear metal complexes
were synthesized and characterized by using FT-IR, 1H NMR, 13C
NMR, ESI mass, CHN, UV–Vis, and Single-crystal X-ray diffraction
techniques.
Chart 1. Ligands used in this study.
2.2. Single-crystal X-ray structures analyses
problem [10]. Thus, research efforts for finding effective nature-
derived therapeutics against these multidrug-resistant microbes
are required. Mai et al. have reported a series of chalcone deriva-
tives where –NH2 group on ring A (Chart 1) play an important role
in the anti-proliferative effect against HT-29 cancer cell [11]. How-
ever, in this work, ring A contains either –NH2 group or –OH group
and ring B is replaced with pyridyl substituent.
Keeping in mind the anti-proliferative effect of –NH2 sub-
stituent on ring A of chalcone derivatives we are interested to
explore this possibility by complexing pyridyl chalcone derivatives
(Chart 1) with arene ruthenium, rhodium and iridium complexes.
The initial studies designed to assess their cytotoxic potency
against cancer and non-cancer cells are described. Because of the
reported activity of chalcones against microbes, the activity of
these complexes against bacterial strains is also reported.
Single crystal X-ray diffraction data for the complexes (2), (4),
(5) and (7) were collected on an Oxford Diffraction Xcalibur Eos
Gemini diffractometer at 293 K using graphite monochromated
Mo-Ka radiation (k = 0.71073 Å). Suitable crystals were selected
and each mounted on a glass fiber. The strategy for the data collec-
tion was evaluated using the CrysAlisPro CCD software [12]. Crys-
tal data were collected by standard ‘‘phi–omega scan’’ techniques
and were scaled and reduced using CrysAlisPro RED software.
The structures were solved by direct methods using SHELXS-97
and refined by full-matrix least-squares with SHELXL-97 refining
on F2 [13,14]. The positions of all the atoms were obtained by
direct methods. Metal atoms in the complex were located from
the E-maps and non-hydrogen atoms were refined anisotropically.
The hydrogen atoms bound to the carbon were placed in geomet-
rically constrained positions and refined with isotropic tempera-
ture factors, generally 1.2 Ueq of their parent atoms. Fig. 1 was
drawn with the ORTEP3 program [15]. Figs. 2–5 were drawn with
the MERCURY3.6 program [16].
2. Experimental section
2.1. Physical methods and materials
All the reagents were purchased from commercial sources and
used as received. 3-aminopyridine, 2-aminoacetophenone, 2-
hydroxyacetophenone were obtained from Aldrich. The solvents
were purified and dried according to standard procedures. The
starting precursor metal complexes [Cp*MCl2]2 (M = Rh/Ir) were
prepared by a new procedure using Anton Paar Monowave 50 syn-
thesis reactor. Infrared spectra were recorded on a Perkin-Elmer
983 spectrophotometer by using KBr pellets in the range of
2.3. Cell lines testing, culture condition and cytotoxicity studies
The in vitro cytotoxicity of the pyridyl chalcone ligands (L1 and
L2) and their corresponding arene d6 metal complexes were per-
formed at the University of Huddersfield against the HCT-116
p53+/+, HCT-116 p53À/À and HT-29 human colorectal cancer lines.
To compare the activity of complexes against cancer cells com-
pared to non-cancer cells, complexes were also evaluated against
the retinal epithelium cell line ARPE-19. HT-29 and ARPE-19 cells
were originally purchased from ATCC and HCT-116 cells (contain-
ing wild type p53 or deleted p53) were obtained from Professor
Bert Vogelstein’s laboratory [17]. All reagents used were purchased
from Sigma Aldrich Co. Ltd (Dorset, UK) unless otherwise stated.
400–4000 cmÀ1 1H NMR spectra were recorded on a Bruker
.
Avance II 400 MHz spectrometer using DMSO d6 and CDCl3 as
solvents. Absorption spectra were recorded on a Perkin-Elmer
Lambda 25 UV/Visible spectrophotometer in the range of
200–800 nm at room temperature in acetonitrile. Mass spectra
Fig. 1. ORTEP generated molecular structure of complexes 2, 4, 5 and 7 with 50% thermal ellipsoid probability. Hydrogen atoms (except on N2 and O2) are omitted for clarity
purpose.

L. Dkhar et al. / Polyhedron 185 (2020) 114606
3
Fig. 2. Crystal packing of complex 2 showing intramolecular and supramolecular interaction.
Antiproliferative activity of the compounds was evaluated using
the standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-
zolium bromide) cellular viability assay as described elsewhere
[18]. Briefly, cells were seeded into 96 well plates of 1.5 Â 103 cells
per well and incubated for 24 h at 37 °C in an atmosphere of 5% CO2
before drug exposure. Generally, a stock solution was freshly pre-
pared by dissolving each of the compounds in DMSO at a concen-
tration of 100 mM. The highest concentration of drug tested was
resulting solution was recorded at 550 nm using an ELISA spec-
trophotometer. The percentage of cell survival was calculated by
dividing the true absorbance of the treated cell by the true absor-
bance for controls (exposed to 0.1% DMSO). The IC50 values pre-
sented in Table 1 were determined from plots of percentage
survival against drug concentration. Each experiment was per-
formed in triplicate and a mean value obtained and stated as IC50
(lM) SD. To compare the response of non-cancer cells to cancer
100
l
M and the final DMSO concentration applied to cells was
cells, the selectivity index (SI) presented in Table 2 was also calcu-
lated which is defined as the IC50 for ARPE 19 cells divided by the
IC50 for each cancer cell line. Values >1 indicate that complexes
have selective activity against cancer compared to non-cancer cells
in vitro.
0.1% (v/v), which is nontoxic to cells. Cisplatin was dissolved in
phosphate-buffered saline at a stock concentration of 25 mM.
The cells were exposed to a range of drug concentrations for
96 h and cell survival was determined using the MTT assay
[18,19]. Following drug exposure, 20
ll of MTT (0.5 mg/mL) in
phosphate-buffered saline was added to each well and it was fur-
ther incubated at 37 °C for 4 h in an atmosphere containing 5%
CO2. The solution was then removed and the formed formazan
2.4. In vitro antimicrobial evaluation
All the Gram-negative and Gram-positive bacterial strains used
for the present study were obtained from the Department of
crystals were dissolved in 150
lM DMSO. The absorbance of the
Fig. 3. Crystal packing of complex 4 showing inter and intra molecular hydrogen bonding.

4
L. Dkhar et al. / Polyhedron 185 (2020) 114606
Fig. 4. Crystal packing of complex 5 showing inter and intra molecular hydrogen bonding.
Fig. 5. Response of a panel of cancer cells and ARPE-19 non-cancer cells following a continuous exposure (96 h) to complex 1 to 8, ligands 1 to 2 and cisplatin. Each value
represents the mean IC50 standard deviation for three independent experiments. Complex 6, 7 and 8 have IC50 values >100 mM which was the highest dose tested.
Table 1
IC50 values of pyridyl chalcone (L1 and L2) and complexes 1–8 along with cisplatin against HT-29, HCT-116 p53+/+, HCT-116 p53À/À cancer cell lines and non-cancer cell line
ARPE-19. Each value represents the mean standard deviation from three independent experiments.
Compounds
IC50 (mM)
HT-29
HCT-116 p53+/+
HCT-116 p53À/À
ARPE-19
Ligand 1
Ligand 2
2.10 (+/À 0.19)
54.18 (+/À 2.19)
15.64 (+/À 0.88)
3.35 (+/À 1.73)
4.95 (+/À 0.86)
4.82 (+/À 0.85)
38.21 (+/À 3.42)
>100
>100
>100
2.58 (+/À 0.72)
4.44 (+/À 0.91)
43.83 (+/À 5.39)
15.51 (+/À 1.64)
3.44 (+/À 1.17)
4.09 (+/À 1.38)
4.23 (+/À 0.64)
34.60 (+/À 1.73)
>100
>100
>100
2.78 (+/À 1.4)
4.56 (+/À 1.35)
28.06 (+/À 2.95)
17.56 (+/À 4.04)
2.17 (+/À 0.26)
4.37 (+/À 1.45)
5.17 (+/À 1.13)
39.72 (+/À 3.28)
>100
>100
>100
7.52 (+/À 0.65)
11.21 (+/À 1.82)
39.39 (+/À 7.05)
15.15 (+/À 4.49)
6.18 (+/À 0.68)
8.89 (+/À 4.18)
7.35 (+/À 3.42)
17.96 (+/À 1.55)
>100
>100
>100
6.41 (+/À 0.95)
Complex 1
Complex 2
Complex 3
Complex 4
Complex 5
Complex 6
Complex 7
Complex 8
Cisplatin
NB – values at 100 = >100 indicates no IC50 at the highest dose tested on 100 mM.

L. Dkhar et al. / Polyhedron 185 (2020) 114606
5
Table 2
made from clear wells and the lowest concentration that yielded
no growth after subculturing was taken as the MBC. The MIC and
MBC values of tested compounds were presented in Table 4.
Selectivity ratios of ligands and complexes along with cisplatin in HT-29, HCT-116
p53+/+, HCT-116 p53À/À cancer cell lines.
Compounds Selectivity Ratio Selectivity Ratio
Selectivity Ratio
(HCT-116 p53+/+
)
(HT-29)
(HCT-116 p53+/+
)
2.5. Synthesis of rhodium and iridium dimer
Ligand 1
Ligand 2
5.338
0.727
0.969
1.845
1.796
1.525
0.470
2.484
2.525
0.899
0.977
1.797
2.174
1.738
0.519
2.306
2.458
1.404
0.863
2.848
2.034
1.422
0.452
0.852
In a sample test tube of size 10 ml 500 mg of RhCl3/IrCl3ÁnH2O,
0.4 ml of Cp* and 3 ml of dry methanol were added and mix thor-
oughly. A small size Teflon coated magnetic stirrer was inserted for
stirring purpose. The mixture was sealed tightly and placed into an
Anton Paar Monowave 50 synthesis reactor. The reaction condition
was adjusted by setting the temperature to 110 °C and pressure
will reach around 20 bars over 45 min. The instrument takes about
2–3 min to heat up to the set temperature and the reaction pro-
ceeds smoothly for 45 min. On completion, the reaction cools down
to a temperature of 60 °C. A red–orange crystalline solid was
obtained. The solvent was decanted, washed three times with
diethyl ether and air-dried.
Complex 1
Complex 2
Complex 3
Complex 4
Complex 5
Cisplatin
Microbiology, Osmania General Hospital, Hyderabad. All strains
were tested for purity by standard microbiological methods. The
bacterial stock cultures were maintained on Mueller-Hinton agar
slants and stored at 4ꢀC. An agar-well diffusion method [20] was
employed for the evaluation of antibacterial activities of test com-
pounds. DMSO was used as a negative control. The bacterial strains
were reactivated from stock cultures by transferring into Mueller-
Hinton broth and incubating at 37 °C for 18 h. A final inoculum
containing 106 colonies forming units (1 Â 106 CFU/mL) was added
aseptically to MHA medium and poured into sterile petri dishes.
Different test compounds at a concentration of 200 mg per well
were added to wells (8 mm in diameter) punched on an agar sur-
face. Plates were incubated overnight at 37 °C and the diameter of
inhibition zone (DIZ) around each well was measured in mm.
Experiments were performed in triplicates and these data were
presented in Table 3.
The minimum inhibitory concentration (MIC) and minimum
bactericidal concentration (MBC) was determined by the micro-
broth dilution method done in 96 well plates according to the stan-
dard protocol [21]. A 2-fold serial dilution of the compounds, with
the appropriate antibiotic, was prepared. Initially, 100 ml of MH
broth was added to each well plate. Then 100 ml of compound or
antibiotic was taken from the stock solution and dissolved in the
first well plate. Serial dilution was done to obtain different concen-
trations. The stock concentrations of 2.0 mg/ml 24 h culture turbid-
ity was adjusted to match 0.5 McFarland standards which
correspond to 1 Â 108 CFU/ml. The standardized suspension
(100 ml) of bacteria was added to all the wells except the antibiotic
control well and the 96 well plates were incubated at 37 °C for
24 h. After 24 h of incubation 40 ml of MTT (3-(4,5-dimethlthia-
zol-2-yl)-2,5-diphenyltrazolium bromide) reagent (0.1 mg/ml in
1Â PBS) was added to all the wells. MIC was taken as the lowest
concentration which did not show any growth which was visually
noted from the blue color developed by MTT. Subcultures were
Yield: 87% for Rhodium dimer and 90% for Iridium dimer.
2.6. General procedure for the synthesis of metal complexes (1–8)
To a solution of metal precursor [(arene)MCl2]2 (arene = p-cym-
ene/benzene) and [Cp*MCl2]2 (M = Rh/Ir) complexes (0.1 mmol),
pyridyl chalcone analogue (L1 and L2) (0.2 mmol) were added
and stirred at room temperature in dry methanol (10 ml) for 5 h
(Scheme 1). The product starts to precipitate after 4 h of stirring
and was allowed to stir for another one hour for the overall conver-
sion of the reactant into the desired product. The solid precipitate
was centrifuged, washed thoroughly with diethyl ether and air-
dried.
2.6.1. [(p-cymene)Ru(r1(N)-L1)Cl2] (1)
Color: Yellow; Yield: 81%; FT-IR (KBr, cmÀ1): 3406 (ʋN-H), 3291
(ʋN-H), 1651 (ʋC=O), 1616–1584 (ʋC=N); 1H NMR (400 MHz,
DMSO d6) d 9.07 (d, J = 4 Hz, 1H), 8.68 (d, J = 4 Hz, 1H), 8.43 (d,
J = 8 Hz, 1H), 8.21–8.17 (m, 2H), 7.74 (d, J = 16 Hz, 1H), 7.57 (dd,
J = 4, 4 Hz, 1H), 7.38 (t, J = 8 Hz, 1H), 6.89 (d, J = 8 Hz, 1H), 6.68
(t, J = 8 Hz, 1H), 5.91 (d, J = 4 Hz, 2H), 5.87 (d, J = 4 Hz, 2H), 2.91
(sept, 1H), 2.17 (s, 3H), 1.27 (d, J = 8 Hz, 6H); ESI-MS (m/z):
459.21 [MÀCl]+-HCl; UV–Vis {Acetonitrile, kmax nm (
e
/10À4 MÀ1
cmÀ1)}: 239 (4.896), 292 (5.588), 401 (2.013).
2.6.2. [(benzene)Ru(r1(N)-L1)Cl2] (2)
Color: Yellow; Yield: 78%; FT-IR (KBr, cmÀ1): 3421 (ʋN-H), 3312
(ʋN-H), 1650 (ʋC=O), 1615–1589 (ʋC=N); 1H NMR (400 MHz,
DMSO d6): d 9.23 (s, 1H), 8.73 (d, J = 8 Hz, 2H), 8.23 (d, J = 16 Hz,
1H), 8.12 (d, J = 8 Hz, 1H), 7.83 (t, J = 8 Hz, 1H), 7.69 (d,
Table 3
Antibacterial activity (Agar well) of tested compounds.
S. No.
Compound Names
Zone of inhibition (Diameter in mm) at conc. 200 lg
S. aureus
E. coli
K. pneumoniae
1
2
3
4
5
6
7
8
Ligand-L1
Ligand-L2
14 0.22
15 0.35
15 0.26
12 0.12
14 0.38
14 0.26
17 0.58
15 0.35
16 0.56
16 0.29
32 0.40
14 0.18
15 0.48
14 0.16
13 0.12
14 0.24
13 0.16
17 0.62
16 0.45
16 0.68
15 0.19
29 0.10
13 0.10
14 0.15
14 0.32
13 0.23
14 0.36
12 0.08
16 0.45
14 0.22
15 0.35
13 0.15
31 0.20
Complex-1
Complex-2
Complex-3
Complex-4
Complex-5
Complex-6
Complex-7
Complex-8
Ciprofloxacin
9
10
11
S. aureus = Staphylococcus aureus; E. coli = Escherichia coli; K. pneumoniae = Klebsiella pneumoniae, NI: No Inhibition and Data are means (n = 3) Standard deviation of three
replicates.

6
L. Dkhar et al. / Polyhedron 185 (2020) 114606
Table 4
Antibacterial activity (MIC & MBC) of tested compounds.
S. No.
Compound Names
Stock concentration in 2.0 mg/mL
S. aureus
E. coli
K. pneumoniae
MIC
MBC
MIC
MBC
MIC
MBC
1
2
Ligand-L1
Ligand-L2
0.25
0.5
0.5
1.0
0.25
0.25
0.5
0.5
0.25
0.5
0.5
1.0
3
4
5
6
7
8
9
10
11
Complex-1
Complex-2
Complex-3
Complex-4
Complex-5
Complex-6
Complex-7
Complex-8
Ciprofloxacin
0.25
0.5
0.125
0.25
0.25
0.5
0.125
0.25
0.062
0.5
1.0
0.25
0.5
0.5
1.0
0.25
0.5
0.25
0.25
0.125
0.125
0.25
0.25
0.125
0.25
0.5
0.5
0.25
0.25
0.5
0.5
0.25
0.5
0.25
0.25
0.125
0.125
0.25
0.5
0.5
0.25
0.25
0.5
0.25
0.5
0.125
0.125
0.062
0.25
0.25
0.125
0.125
0.031
0.062
S. aureus = Staphylococcus aureus; E. coli = Escherichia coli; K. pneumoniae = Klebsiella pneumoniae.
Scheme 1. Schematic representation for the synthesis of ligands and complexes 1–8.
J = 16 Hz, 1H), 7.30 (t, J = 8 Hz, 1H), 6.81 (d, J = 8 Hz, 1H), 6.59 (t,
J = 8 Hz, 1H), 5.95 (s, 6H); 13C NMR (100 MHz, DMSO d6):
d = 189.6, 152.1, 144.7, 144.4, 140.7, 136.0, 134.7, 131.5, 127.7,
116.9, 114.5, 87.5; ESI-MS (m/z): 403.03 [MÀCl]+-HCl; UV–Vis
85.18, 8.17; ESI-MS (m/z): 551.30 [MÀCl]+-HCl; UV–Vis {Acetoni-
trile, kmax nm (e
/10À4 MÀ1 cmÀ1)}: 235 (3.212), 290 (3.532), 398
(1.157).
{Acetonitrile, kmax nm (e
/10À4 MÀ1 cmÀ1)}: 240 (3.285), 291
(3.806), 402 (1.359).
2.6.5. [(p-cymene)Ru(r1(N)-L2)Cl2] (5)
Color: Yellow; Yield: 86%; FT-IR (KBr, cmÀ1): 3447 (ʋO-H), 1637
(ʋC=O), 1607–1581 (ʋC=N); 1H NMR (400 MHz, DMSO d6) d 12.48 (s,
1H), 9.14 (s, 1H), 8.72 (d, J = 4 Hz, 1H), 8.47 (d, J = 8 Hz, 1H), 8.35 (d,
J = 8 Hz, 1H), 8.26 (d, J = 16 Hz, 1H), 7.95 (d, J = 16 Hz, 1H), 7.68 (t,
J = 8 Hz, 1H), 7.61 (t, J = 8 Hz, 1H), 7.13–7.10 (m, 2H), 5.91 (d,
J = 4 Hz, 2H), 5.87 (d, J = 4 Hz, 2H), 2.91 (hept, J = 6.7 Hz, 1H),
2.17 (s, 3H), 1.27 (d, J = 8 Hz, 6H); ESI-MS (m/z): 460.23 [MÀCl]+-
2.6.3. [Cp*Rh(r1(N)-L1)Cl2] (3)
Color: Orange; Yield: 85%; FT-IR (KBr, cmÀ1): 3423 (ʋN-H), 3308
(ʋN-H), 1652 (ʋC=O), 1615–1584 (ʋC=N); 1H NMR (400 MHz,
DMSO d6) d 8.92 (s, 1H), 8.49 (d, J = 4 Hz, 1H), 8.39 (d, J = 8 Hz,
1H), 7.97 (d, J = 16 Hz, 1H), 7.90 (d, J = 8 Hz, 1H), 7.50 (d,
J = 8 Hz, 1H), 7.46 (d, J = 16 Hz, 1H), 7.09 (t, J = 8 Hz, 1H), 1.40
(s, 15H); ESI-MS (m/z): 461.24 [MÀCl]+-HCl; UV–Vis {Acetonitrile,
HCl; UV–Vis {Acetonitrile, kmax nm (e
/10À4 MÀ1 cmÀ1)}: 210
(6.895), 305 (6.406), 348 (2.558).
kmax nm (
(1.540).
e
/10À4 MÀ1 cmÀ1)}: 233 (4.831), 283 (3.675), 402
2.6.6. [(benzene)Ru(r1(N)-L2)Cl2] (6)
2.6.4. [Cp*Ir(r1(N)-L1)Cl2] (4)
Color: Yellow; Yield: 78%; FT-IR (KBr, cmÀ1): 3445 (ʋO-H), 1647
(ʋC=O), 1585–1506 (ʋC=N); 1H NMR (400 MHz, DMSO d6): d 12.37 (s,
1H, OH), 9.03 (s, 1H), 8.62 (d, J = 4 Hz, 1H), 8.25 (d, J = 8 Hz, 1H),
8.12 (d, J = 12 Hz, 1H), 7.85 (d, J = 16 Hz, 1H), 7.57 (d, J = 8 Hz,
2H), 7.51 (dd, J = 4, 4 Hz, 1H), 7.04–6.99 (m, 3H), 5.95 (s, 6H);
13C NMR (100 MHz, DMSO d6): d = 193.2, 161.7, 151.2, 150.5,
141.1, 136.4, 135.2, 130.9, 130.2, 128.2, 123.7, 120.7, 119.2,
117.7, 85.5; ESI-MS (m/z): 404.05 [MÀCl]+-HCl; UV–Vis {Acetoni-
Color: Yellow; Yield: 83%; FT-IR (KBr, cmÀ1): 3430 (ʋN-H), 3312
(ʋN-H), 1652 (ʋC=O), 1615–1583 (ʋC=N); 1H NMR (400 MHz,
DMSO d6) d 9.00 (s, 1H), 8.60 (d, J = 4 Hz, 1H), 8.37 (d, J = 8 Hz,
1H), 8.12–8.08 (m, 2H), 7.64 (d, J = 16 Hz, 1H), 7.50 (dd, J = 4,
4 Hz, 1H), 7.28 (t, J = 8 Hz, 1H), 6.80 (d, J = 12 Hz, 1H), 6.58 (t,
J = 8 Hz, 1H), 1.62 (s, 15H); 13C NMR (100 MHz, DMSO d6 + CDCl3):
d = 198.75, 150.43, 134.00, 130.36, 124.51, 116.92, 114.89, 92.16,

L. Dkhar et al. / Polyhedron 185 (2020) 114606
7
trile, kmax nm (
(2.005).
e
/10À4 MÀ1 cmÀ1)}: 201 (7.565), 305 (5.061), 348
3.2.2. 1H NMR spectra of complexes
The 1H NMR spectra of the complexes displayed signals associ-
ated with the ligand protons and signals due to p-cymene and Cp*
ring protons. The 1H NMR spectra of the ligand L1 displayed one
singlet at 9.40 ppm assigned to the CH proton of the pyridine ring,
the NH2 proton signals were not observed due to solvent exchange
with DMSO d6, the trans-CH protons with J = 16 Hz coupling con-
stant were observed as a doublet at 7.68 and 8.26 ppm respectively
and the aromatic protons of the ligand L1 were observed in the
downfield region around 6.55–8.96 ppm. The 1H NMR spectra of
the ligand L2 displayed one singlet at 12.68 ppm assigned to the
OH proton, a singlet at 8.89 ppm assigned to the CH proton of
the pyridine ring, the trans-CH protons with J = 16 Hz coupling con-
stant were observed at 7.73 and 7.90 ppm respectively and the aro-
matic protons of the ligand L2 were observed in the downfield
region around 6.95–8.89 ppm. To further reveal the coordination
behavior of these ligands to metals and the formation of com-
plexes, 1H NMR analyses of all these complexes were recorded in
deuterated DMSO d6 solvent at room temperature. The ligand aro-
matic protons of complexes 1–8 displayed the same splitting pat-
tern with a slight shift of proton signals towards the downfield
or upfield region which resulted from coordination of the metals
to the ligand. The binding of the pyridyl chalcone ligand to the
ruthenium atom for complex 1 and 5 was confirmed by the distinct
splitting of the p-cymene ring protons upon coordination of the
ligand to the p-cymene moiety. The signals associated with the
p-cymene ligand consisted of two doublets around 5.86–
5.91 ppm for the ring protons, one singlet at 2.17 ppm for the
methyl protons and one doublet at 1.27 ppm for the isopropyl
group. Also, the methine proton of the p-cymene group exhibited
septet at around 2.86–2.96 ppm. Ruthenium benzene complexes
2 and 6 displayed one singlet at 5.95 assigned to the CH protons
of the benzene ring. Rhodium and iridium complexes 3, 4, 7 and
8 bearing Cp* analog displayed one singlet in the range of 1.40–
1.74 ppm. The NH2 proton signals of the complexes 1–4 were not
observed due to solvent interaction with DMSO d6 whereas the
OH proton signals of complexes 5–8 were observed in the range
of 12.37–12.69 ppm. The 1H NMR of all these complexes were
given in supplementary data (Figs. S1–S10) (S1-S9).
2.6.7. [Cp*Rh(r1(N)-L2)Cl2] (7)
Color: Orange; Yield: 82%; FT-IR (KBr, cmÀ1): 3435 (ʋO-H), 1647
(ʋC=O), 1593–1489 (ʋC=N); 1H NMR (400 MHz, DMSO d6): d 12.69 (s,
1H), 9.39 (s, 1H), 9.13 (s, 1H), 8.14 (d, J = 8 Hz, 1H), 8.03 (d, J = 8 Hz,
1H), 7.97 (d, J = 16 Hz, 2H), 7.87 (d, J = 16 Hz, 1H), 7.66 (t, J = 8 Hz,
1H), 7.57 (t, J = 8 Hz, 1H), 7.17 (d, J = 8 Hz, 1H), 7.10 (t, J = 8 Hz, 1H),
1.74 (s, 15H); UV–Vis {Acetonitrile, kmax nm (e
/10À4 MÀ1 cmÀ1)}:
208 (6.325), 306 (5.466), 348 (2.361).
2.6.8. [Cp*Ir(r1(N)-L2)Cl2] (8)
Color: Yellow; Yield: 83%; FT-IR (KBr, cmÀ1): 3433 (ʋO-H), 1647
(ʋC=O), 1588–1491 (ʋC=N); 1H NMR (400 MHz, DMSO d6) d 12.38 (s,
1H), 9.03 (s, 1H), 8.62 (d, J = 8 Hz, 1H), 8.37 (d, J = 8 Hz, 1H), 8.25 (d,
J = 8 Hz, 1H), 8.16 (d, J = 16 Hz, 1H), 7.85 (d, J = 16 Hz, 1H), 7.58 (t,
J = 8 Hz, 1H), 7.50 (dd, J = 4, 4 Hz, 1H), 7.03 – 7.00 (m, 2H), 1.62 (s,
15H); 13C NMR (100 MHz, DMSO d6 + CDCl3): d = 193.19, 162.27,
150.96, 150.35, 141.19, 136.31, 135.15, 130.18, 123.70, 123.15,
118.90, 117.66, 91.96, 8.18; UV–Vis {Acetonitrile, kmax nm
(e
/10À4MÀ1 cmÀ1)}: 210 (6.088), 305 (6.088), 348 (2.683).
3. Results and discussion
3.1. Synthesis of complexes
In the present work, we have carried out the synthesis and bio-
logical activity evaluation of metal complexes of ruthenium, rho-
dium and iridium bearing pyridyl chalcone derivatives. Pyridyl
chalcone derivatives (Scheme 1) were obtained following the pro-
cedure reported in the literature [22]. Treatment of [(arene)Ru(m-
Cl)Cl]2, (arene = benzene, p-cymene), [Cp*M(m-Cl)Cl]2 (M = Rh
and Ir) with ligand (L1 or L2) in 1:2 (M:L) ratio has yielded a series
of neutral monodentate mononuclear complexes 1–8 with the
chemical formula [(arene)M{j1(N)L1/L2}Cl2]. Despite having extra
binding sites of ligands towards metal, these ligands bind exclusively
through pyridyl nitrogen. Ruthenium and iridium complexes are yel-
low in color while rhodium complexes are orange in color. These
complexes are stable in the air as well as in solution and they are sol-
uble in MeOH and partially soluble in dichloromethane, chloroform
and acetonitrile and insoluble in solvents like hexane, diethyl ether
and petroleum ether. The analytical data of these compounds are
consistent with the formulations. All complexes were fully charac-
terized by 1H NMR, 13C NMR, IR, CHN and Mass spectroscopy. The
molecular structure of the complexes determined by single-crystal
X-ray diffraction method, revealed the coordination of the metals
to the ligands (L1 and L2) only through the pyridyl nitrogen atom.
3.2.3. 13C NMR spectra of complexes
The 13C NMR spectra of the complexes further confirmed the
formation and coordination of the metals to the ligands. The 13C
NMR spectra of the complexes displayed signals associated with
the carbon of the ligands, the p-cymene moiety, and the Cp* group.
The aromatic signals for the ligand part of the complexes were
observed in the range of 114.5–162.4 ppm. The carbonyl group car-
bon of the complexes displayed a signal around 189.6–198.7 ppm.
The ring carbons of the p-cymene moiety displayed signals around
82.9–106.8 ppm whereas the methyl, methine and isopropyl car-
bons signals were observed around 17.8–29.9 ppm. The benzene
ring carbons of the ruthenium benzene complexes displayed sig-
nals around 87.5–87.5 ppm. The Cp* methyl carbons signal was
observed around 8.1 ppm and the Cp* ring carbons signal was
observed at 91.9–92.1 ppm. These data are in good agreement with
the previously reported complexes done by our group [23] thus
supporting the formation of the complexes. The 13C NMR spectra
of some of the complexes were given in supplementary data
(Figs. S11–S14) (S10-S14).
3.2. Spectral studies of complexes (1–8)
3.2.1. Infrared spectra (IR) of ligands and complexes
Information on the nature of the functional group attached to
the metal atom was obtained using IR spectroscopy. The ligand
L1 IR spectrum displayed two bands at 3413 and 3284 cmÀ1 for
the NH2 group while ligand L2 displayed one broadband at
3447 cmÀ1 for the OH group. Both the carbonyl group of the
ligands displayed a strong band at around 1648–1653 cmÀ1. All
the complexes exhibited characteristic bands corresponding to
C@N, C@O, C@C, OH and NH2 stretching frequencies. The NH2 fre-
quencies were observed in the range of 3150–3480 cmÀ1. The C@N
and C@C bond vibrated at a higher frequency region as compared
to the free ligand around 1583–1616 cmÀ1 and 1450–1546 cmÀ1
indicating the coordination of the metals to the ligands through
the pyridine ring.
3.2.4. Mass spectra of complexes
The mass spectra of the complexes further confirmed the for-
mation of metal complexes. The mass spectra of all the complexes
except for complex 2 exhibited their predominant molecular ion
peaks at m/z value, which corresponds to [MÀCl]+-HCl ion peak.
For instance, the mass spectrum of complexes 1 displayed its pre-

8
L. Dkhar et al. / Polyhedron 185 (2020) 114606
dominant molecular ion peak at m/z: 459.21, similarly for com-
plexes 3, 4, 5 and 6 displayed their predominant molecular ion
peak at m/z: 461.24, 551.30, 460.23 and 404.05 respectively which
corresponds to [MÀCl]+-HCl ion peak. In complex 2 the molecular
ion peak was observed at m/z: 224.93, which is due to [MÀCl]+-
HCl-Ru-benzene ion peak. The mass ion peaks observed in these
complexes are in accordance with similar reported complexes
[23]. The mass spectra of some of the complexes were given in sup-
plementary data (Figs. S19–24) (S15-S22).
2.4167–2.439 Å while that of complex 5 were found to be slightly
shorter at 2.402(2) Å. These data are consistent with the previ-
ously reported complexes of pyridyl-base ligands [26,27]. The
carbonyl (C@O) bond distances for complexes 2, 4 and 7 are in
the range of 1.228–1.247 Å, whereas complex 5 carbonyl bond
distance is found to be slightly longer at 1.370(13) Å. The bond
angle values Cl(1)-M(1)-Cl(2) of these complexes are in the range
of 86.99–91.65° and the Cl(1)-M(1)-N(1) and Cl(2)-M(1)-N(1)
bond angle is also found to be in the range of 85.44–88.22° which
are consistent with the piano stool arrangement of various groups
about the metal center and is comparable to previously reported
values [26,28].
3.2.5. UV–visible spectra of complexes
The electronic spectra of the monodentate mononuclear pyridyl
chalcone complexes were recorded in acetonitrile at 10À4 M con-
centration at room temperature and the respective plots are shown
in (Fig. S25) (S23). The electronic spectra of the mononuclear com-
plexes display two absorption bands in the higher energy region
around 230–240 nm which can be assigned as ligand centered or
3.4. Non-covalent interaction
From the crystal packing of some of the complexes, it was
observed that complex (2) possessed intramolecular hydrogen
bonding NAHÁ Á ÁO with 2.024 Å bond distance and 134.38° bond
angle. Non-covalent interaction CAHÁ Á ÁCl with 2.774 Å bond dis-
tance and 143.76° was observed between the CH group from the
trans-CH=CH of ligand and chloride atom (Fig. 2). Interestingly
intra ligand
ing to n-
p
-
p
* and low energy band at 290–305 nm correspond-
p*
transition [24,25]. Medium intensity band at
340–410 nm were also observed corresponding to metal to ligand
charge transfer where from Ru (4d) orbitals to the low-lying empty
orbitals
complexes provide filled d
low lying * orbitals of the pyridyl chalcone ligands and therefore
we can expect a band attributable to metal to ligand charge trans-
fer MLCT band.
p
* orbitals of the ligand. The low spin Rh(III) and Ir(III)
the crystal packing in complex (2) formed a dimeric unit via p-p
p
(t2g) orbitals which can interact with
stacking (3.582 Å) interaction known as supramolecular interac-
tion. Complex 4, on the other hand, possessed intramolecular
hydrogen bonding NAHÁ Á ÁO with 2.010 Å bond distance and
128.93° bond angle and intermolecular hydrogen bonding
CAHÁ Á ÁCl with 2.766 Å bond distance and 140.66° bond angle.
p
3.3. Description of the molecular structures of complexes
CAHÁ Á Áp interaction involving the methyl CAH of the cp* ring
and the phenyl ring of the ligand was also observed H3CÁ Á ÁH
(4.861 Å) (Fig. 3). Further, the crystal structure of complex (5) crys-
tallized with one CH3OH molecule which formed one intramolecu-
lar hydrogen bonding OAHÁ Á ÁO with 1.804 Å bond distance and
146.61° bond angle and four different types of non-covalent
CAHÁ Á ÁCl (2.852, 2.931, 2.613 and 2.884 Å) interactions between
chloride of the metal center and hydrogen atom from ligand and
methanol molecule (Fig. 4). Apart from these interactions complex
5 displayed interaction between the solvent of crystallization
(CH3OH) oxygen and the hydrogen from the pyridine ring of
the ligand forming inter hydrogen bonding OÁ Á ÁH (2.613 Å)
Supplementary data (S24-S26).
The solid-state structures of some of the mononuclear com-
plexes were established by single-crystal X-ray crystallography.
The ORTEP view of the complexes along with the atom numbering
scheme is shown in Fig. 1. The summary of the crystal data, data
collection and structure refinement parameters are summarized
in Table S1. Selected bond lengths, bond angles and metal atom
involving ring centroid values are listed in Table S2.
Single crystal analyses for the complexes were carried out to
have a deeper understanding of the geometry of the complexes.
By carrying out single-crystal analyses of the complexes we were
able to confirm the bonding modes associated with the ligand.
Single crystals suitable for X-ray diffraction analysis were
obtained for complexes 2, 4, 5 and 7. These crystals are yellow,
orange and red in color and were obtained by the solvent diffu-
sion method for all the complexes. In all the complexes with both
ligands, the preferable mode of coordination of the metal is
through pyridine nitrogen of the pyridyl chalcone forming mon-
odentate mononuclear complexes. All these half-sandwich com-
plexes adopt a typical three-legged ‘‘piano-stool” geometry in
which the metal center is coordinated through one nitrogen
donor atoms from the pyridine ring of the ligand and two termi-
nal chloride which represents the three-leg of a piano while the
arene ring (arene = p-cymene, benzene, Cp*) represent the seat
of a piano. The molecular structure of these mononuclear com-
plexes strongly supports the formation of these complexes and
the coordination of ligands that occur through the pyridine nitro-
gen N(1) forming monodentate complexes (Fig. 1). Complexes 2, 4
and 7 crystallizes in monoclinic system with P21/n and Cc space
group while complex 5 crystallizes in a triclinic system with P
space group. The distance between the metal to the centroid of
the p-cymene/Cp* ring of complexes 2, 4, 5 and 7 is 1.657 Å,
1.779 Å, 1.667 Å and 1.783 Å respectively. The M(1)-N(1) bond
distances in these mononuclear complexes are in the range of
2.116–2.146 Å. The M(1)-Cl(1) bond distances for complexes 2,
4 and 7 are in the range of 2.410–2.4170 Å while that of complex
5 were found to be slightly longer at 2.4320(19) Å. The M(1)-Cl(2)
bond distances for complexes 2, 4 and 7 are in the range of
3.5. Cytotoxicity studies against cancer cell lines
The response of cell lines to complexes 1–8, ligands 1–2 and cis-
platin are presented in Fig. 5. Complexes 6–8 were inactive against
all four cell lines at the highest dose tested (100 lM) whereas com-
plex 5 and ligand 2 were moderately toxic to cells. In both cases,
the activity of complex 5 and ligand 2 was greater against ARPE-
19 non-cancer cells (except for HCT-116 p53À/À cells treated with
ligand 2). This is reflected in the poor selectivity indices presented
in Fig. 6. In sharp contrast, ligand L1 and complexes 1–4 were
potent cytotoxic agents with comparable IC50 values to cisplatin.
Except for complex 1, complexes 2–4 and ligand 1 showed compa-
rable or enhanced selectivity for cancer as opposed to non-cancer
cells. Of particular interest is the observation that HCT-116
p53À/À cells are less responsive to cisplatin than HCT-116 with
wild type p53 (Fig. 5). In contrast, complexes 2–4 remain active
against HCT-116 cells with defective p53 and consequently retain
their good selectivity index for these cancer cells compared to
ARPE-19 cells (Fig. 6). As colorectal tumors with mutant or dys-
functional p53 are widely regarded as chemotherapy-resistant
more aggressive cancers [29] this observation is potentially signif-
icant and worthy of further investigation. In general the tested
compounds for anticancer activity against HCT-116 p53+/+, HCT-
116 p53À/À and HT-29 human colorectal cancer cell lines and were
found that ligand L1 and its complexes 1–4 show excellent activity.

L. Dkhar et al. / Polyhedron 185 (2020) 114606
9
Fig. 6. Selectivity ratios for complexes 1 to 5, ligands 1 and 2 and cisplatin. The selectivity ratio is defined as the ratio of IC50 values for ARPE-19 divided by the IC50 for each
cancer cell line. Values greater than 1 (as indicated by the broken line) represent compounds that are preferentially active against cancer cells compared to non-cancer ARPE-
19 cells. As the selectivity ratio is calculated using the mean IC50 values, no error bars are presented on this figure.
Ligand L2 and complex 5 displayed moderate activity whereas
complexes 6–8 lacked activity even at a higher dose (>100 mM).
Furthermore, ligand L1 and complexes 2, 3 and 4 displayed a level
selectivity comparable to cisplatin. Mai et al. reported chalcone
derivatives containing –NH2 group on ring A and phenyl group
on ring B showed better cytotoxicity activity with IC50 = 4.39 mM
against HT-29 cancer cell [11]. However, in this work when ring
A of chalcone derivatives contain –NH2 group and ring B is replaced
with pyridyl substituent an improved cytotoxicity activity with
IC50 = 2.10 mM against HT-29 cancer cell was observed which is
even better than that of cisplatin. Hence, we can conclude that a
slight change in the structure of the compound can have a signifi-
cant effect on the activities of the whole ligand and complexes.
Also, ligand L1 and ligand L2 differ only at ring A with R = NH2
for L1 and R = OH for L2 whereas the activity of L1 is 5 to 10 times
more than that of L2.
3.6. In vitro antimicrobial activity of complexes and ligands
The synthesized ligands and complexes were evaluated for their
in-vitro antibacterial activity against gram-positive; Staphylococcus
aureus and gram-negative; Escherichia coli, Klebsiella pneumoniae
strains by using standard techniques. The zones of inhibition
(mm) in comparison with ciprofloxacin were given in Table (3)
and the chart representation was given in Fig. 7. All the compounds
exhibited potent antibacterial activity against the tested organ-
isms. In-vitro assay results revealed that complex
(17 0.58 mm) and complex 7 (16 0.56 mm) have better activity
against gram-positive (Staphylococcus aureus). Complex
5
5
(17 0.62 mm) and complex 7 (16 0.68 mm) also showed highest
activity against gram-negative (Escherichia coli) while complex 5
(16 0.45 mm) and complex 7 (15 0.35 mm) showed moderate
activity against gram-negative (Klebsiella pneumoniae).
Fig. 7. Figure showing antimicrobial activity (Agar well) of the studied compounds.

10
L. Dkhar et al. / Polyhedron 185 (2020) 114606
Fig. 8. Figure showing MIB and MIC of tested compounds.
The minimum inhibitory concentration (MIC) and minimum
Declaration of Competing Interest
bactericidal concentration (MBC) results were listed in Table 4
and their chart representation was given in Fig. 8. The MIC &
MBC values of the compounds ranged from 0.125 to 1.0 mg/mL
against all three organisms. Complex 3 and complex 7 values ran-
ged from 0.125 to 0.25 mg/mL for S. aureus, E. coli and Klebsiella
pneumoniae. The MIC & MBC values of ciprofloxacin ranging from
0.031 to 0.062 mg/mL and 0.062 to 0.0125 mg/mL against the
tested organisms were taken as standard.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
Lincoln Dkhar thanks SAIF-NEHU for spectral analyses and DST-
PURSE SCXRD, India for providing Single Crystal X-ray analysis.
Lincoln Dkhar also thank the Department of Science and Technol-
ogy (DST), India for providing financial assistance under the Inno-
vation in Science Pursuit for Inspired Research (INSPIRE)
fellowship.
4. Conclusion
All together eight new complexes have been synthesized. All
the complexes were isolated as neutral compounds. The ligands
and complexes were obtained in good yields and were character-
ized by analytical and spectral methods. Single crystal X-ray
diffraction study reveals that the pyridyl chalcone ligands coordi-
nated to the metal center only through the nitrogen atom of the
pyridine ring forming neutral monodentate complexes. Cytotoxic-
ity studies against cancer (HCT-116 p53+/+, HCT-116 p53À/À and
HT-29 human colorectal cancer cells) and non-cancer (ARPE-19
retinal epithelium) cells demonstrated that ligand L1 and its asso-
ciated complexes were more active compared to ligand L2 and its
associated complexes. Furthermore, the increased potency is
accompanied by a significant increase in selectivity, particularly
with regards to HCT-116 cells with defective p53. Whilst potency
and selectivity were comparable to cisplatin, the fact that com-
plexes 2–4 retained activity against HCT-116 p53À/À cells marks
these compounds as having different properties to cisplatin. Anti-
bacterial studies for all the compounds have also been carried
out and they were found to be active against all the three bacterial
strains.
Appendix A. Supplementary data
CCDC 1908852 (2), 1908853 (3), 1908854 (5) and 1908855 (7)
contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.cam.ac.
uk/data_request/cif, by e-mailing data_request@ccdc.cam.ac.uk,
or by contacting The Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033. Sup-
plementary data to this article can be found online at https://doi.
org/10.1016/j.poly.2020.114606.
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