Synthesis, characterization, and in?vitro anticancer studies of chlorido(triphenylphosphine)ruthenium(II) dithiocarbamate complexes

Article abstract of DOI:10.1080/10426507.2021.1925671

Three chlorido(triphenylphosphine)ruthenium(II) dithiocarbamate complexes - [RuCl(PPh₃)₃(Mbzdtc)] 1, [RuCl(PPh₃)₃(Ppipdtc)] 2, and [RuCl(Ph₃)₃(Mordtc)] 3 with Mbzdtc = N-methylphenyldithiocarbamate, Ppipdtc = phenylpiperazyldithiocarbamate and (Mordtc) = morpholinyldithiocarbamate were synthesized and characterized by elemental analysis and spectroscopic techniques. The Ru(II) atom is six coordinate and displays an octahedral coordination geometry, in which it is bonded to one dithiocarbamato anion acting as bidentate ligand. Electrochemical studies indicate for complexes 1 and 2 a quasi-reversible one electron redox couple due to Ru(III)/Ru(II), whereas complex 3 showed two redox couples due to Ru(III)/Ru(II) and Ru(II)/Ru(I). The E _1/2 values observed toward the cathodic region are consequence of the presence of S-S donor atom of the dithiocarbamate ligand. The anticancer potential of the complexes was assessed using sulforhodamine B (SRB) assay against renal (TK10) melanoma (UACC62) and breast (MCF7) human cancer cell lines. Complex 1 exhibits the highest cytotoxic activity against MCF7 with an IC₅₀ value of 33.36 μM, whereas complex 3 exhibits the lowest activity against TK10 with an IC₅₀ value of 91.95 μM.

Full text of DOI:10.1080/10426507.2021.1925671

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Synthesis, characterization, and
in vitro anticancer studies of
chlorido(triphenylphosphine)ruthenium(II)
dithiocarbamate complexes
Peter A. Ajibade & Fartisincha P. Andrew
To cite this article: Peter A. Ajibade & Fartisincha P. Andrew (2021): Synthesis,
characterization, and in vitro anticancer studies of chlorido(triphenylphosphine)ruthenium(II)
dithiocarbamate complexes, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2021.1925671
To link to this article: https://doi.org/10.1080/10426507.2021.1925671
View supplementary material
Published online: 10 May 2021.
Submit your article to this journal
Article views: 43
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=gpss20

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2021.1925671
Synthesis, characterization, and in vitro anticancer studies of
chlorido(triphenylphosphine)ruthenium(II) dithiocarbamate complexes
Peter A. Ajibade and Fartisincha P. Andrew
School of Chemistry and Physics, University of KwaZulu-Natal, Scottsville, Pietermaritzburg, South Africa
ABSTRACT
ARTICLE HISTORY
Three chlorido(triphenylphosphine)ruthenium(II) dithiocarbamate complexes - [RuCl(PPh ) (Mbzdtc)] 1,
Received 23 October 2020
Accepted 29 April 2021
3
3
[
RuCl(PPh
3
)
3
(Ppipdtc)] 2, and [RuCl(Ph
3
)
3
(Mordtc)] 3 with Mbzdtc ¼ N-methylphenyldithiocarbamate,
Ppipdtc ¼ phenylpiperazyldithiocarbamate and (Mordtc) ¼ morpholinyldithiocarbamate were synthe-
sized and characterized by elemental analysis and spectroscopic techniques. The Ru(II) atom is six
coordinate and displays an octahedral coordination geometry, in which it is bonded to one dithiocar-
bamato anion acting as bidentate ligand. Electrochemical studies indicate for complexes 1 and 2 a
quasi-reversible one electron redox couple due to Ru(III)/Ru(II), whereas complex 3 showed two redox
couples due to Ru(III)/Ru(II) and Ru(II)/Ru(I). The E1/2 values observed toward the cathodic region are
consequence of the presence of S-S donor atom of the dithiocarbamate ligand. The anticancer poten-
tial of the complexes was assessed using sulforhodamine B (SRB) assay against renal (TK10) melanoma
KEYWORDS
Ruthenium(II); dithiocarba-
mate; triphenylphosphine;
anticancer; electrochem-
ical study
(
UACC62) and breast (MCF7) human cancer cell lines. Complex 1 exhibits the highest cytotoxic activity
against MCF7 with an IC50 value of 33.36 lM, whereas complex 3 exhibits the lowest activity against
TK10 with an IC50 value of 91.95 lM.
GRAPHICAL ABSTRACT
Introduction
constrained by severe toxicity, resistance, and narrow activ-
[
3]
ity range. Their nonspecific target of DNA and reaction
with proteins such as metallothioneins, thioredoxine, and
other thiol-containing molecules like cysteine, reduced gluta-
thione and methionine provide a pathomechanism of the
various side effects associated with their clinical applica-
The introduction of cisplatin in 1965 as anticancer agent has
been a great breakthrough in the development of metallo-
pharmaceuticals. This led to the discovery of many other
platinum-based drugs such as nedaplatin, carboplatin, oxali-
platin, heptaplatin, and laboplatin. Although cisplatin and
[
1]
[
4]
tion. Consequently, there has been a consistent search for
analogues are the best metallo-based therapeutic agents that new compounds of other transition metals other than the
[
2]
are used in about 70% of the cancer cases they are often
CONTACT Peter A. Ajibade
ajibadep@ukzn.ac.za
School of Chemistry and Physics, University of KwaZulu-Natal, Scottsville, Pietermaritzburg, South Africa.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2021.1925671.
ß 2021 Taylor & Francis Group, LLC

2
P. A. AJIBADE AND F. P. ANDREW
Table 1. Electronic spectra of ligands and complexes.
and in vitro anticancer screening of chlorido(triphenylphos-
phine) ruthenium(II) dithiocarbamate complexes. The choice
of the dithiocarbamate ligand lies in their ability to stabilize
wide range of metal ions at different oxidation states coupled
Compounds
Wavelength (kmax nm)
Assignment
ꢂ
ꢂ
Mbzdtc, L
Mbzdtc, L
1
258, 285 (shoulder)
261, 286 (shoulder)
261, 287(shoulder)
229
n-p /p-p intraligand
ꢂ
ꢂ
2
n-p /p-p intraligand
ꢂ ꢂ
n-p /p-p intraligand
Mordtc, L
3
ꢂ ꢂ
[RuCl(PPh
[RuCl(PPh
[RuCl(PPh
3
3
3
)
3
(Mbzdtc)] (1)
3
(Ppipdtc)] (2)
3
(Mordtc)] (3)
n-p /p-p intraligand with their rich electrochemistry and excellent biological activ-
2
67–546
230, 259
22–418
229, 264
21–429
MLCT
[24,25]
ity.
The complexes were screened against renal (TK10)
ꢂ
ꢂ
)
)
n-p /p-p intraligand
melanoma (UACC62) and breast (MCF7) human cancer cell
3
MLCT
ꢂ
ꢂ
n-p /p-p intraligand lines to evaluate their anticancer potential.
3
MLCT
2 2
Table 2. Summary of electrochemical data (V) recorded in CH Cl at 25
ꢁ
1
mVs using TBAPF
pc)/2.
6
supporting electrolyte DE
p
¼ Epa – Epc, E1/2 ¼ (Epa
–
Results and discussion
E
Synthesis and physicochemical data
Complexes
E
pc (V) pa (V) DE
E
p
(V)
E
1/2 (V) Range of scan
0.0744 –0.21 to 0.39 V
0.8711 0 to 1.4 V
[RuCl(PPh
[RuCl(PPh
[RuCl(PPh
3
)
3
)
3
)
3
3
3
(Mbzdtc)] (1) –0.0389 0.1877 0.23
(Ppipdtc)] (2) 0.7049 1.0373 0.33
(Mordtc)] (3) 1.0228 1.2091 0.19
The complexes [RuCl(PPh ) (Mbzdtc)], [RuCl(PPh ) (Ppipdtc)],
3
3
3 3
and [RuCl(PPh ) (Mordtc)] were synthesized by the reaction of
1.1160 –0.12 to 1.28 V
3 3
0
.0912 0.3581 0.27
0.2247
chloridotris(triphenylphosphine)ruthenium(II) and N-methylben-
zyl-, phenylpiperazyl-, and morpholinyl-dithiocarbamate ligands
in 1:1 ratio as presented in Scheme 1.
classical platinum-based anticancer agents with the aim of
overcoming the side effect associated with the platinum-
based compounds.
In recent years, ruthenium-based complexes are being
studied as viable alternative to platinum-based anticancer
All the complexes were isolated as air stable solids in
moderate yields with melting points ranging from 189 to
ꢀ
2
17 C. The complexes were highly soluble in dichlorome-
thane, chloroform and DMSO but insoluble in toluene, hex-
agents, which has led to the discovery of the therapeutic ane, and benzene. The molar conductance of the complexes
ꢁ
1
2
ꢁ1
potentials of trans-[Ru(Im)(DMSO)Cl ](Him) (NAMI-A) in the range of 2.94 ꢁ 12.50 Ohm cm mol measured in
4
[
5]
and trans-[Ru(Ind) Cl ](Hind) KP1019 (Ind ¼ imidazole).
DMSO indicated that the complexes are non-electrolytes
2
4
Although the mechanisms of action of these ruthenium in solution.
compounds are still a matter of debate, ruthenium(II) and
ruthenium(III) oxidation states are known to be stable at
physiological conditions and are generally regarded as
[
6–8]
FTIR spectroscopic studies
redox-activatable prodrugs.
NAMI-A and KP1019
belong to this class of compounds and could be activated
in vivo via the reduction of ruthenium(III) to more active
ruthenium(II) species in the low oxygen environment of the
The FTIR spectra of the ligands and complexes due to
ꢀ
(C—N) and ꢀ(C—S) stretching vibrations were compared
to deduce the mode of coordination of the ligands to the
[
9–12]
solid tumors.
Ruthenium belongs to the same triad as
ruthenium(II) ion. A single sharp ꢀ(C—N) vibrational band
iron and could mimic iron in binding to biomolecules, as it
can easily bind proteins such as transferrin (known to trans-
ꢁ1
ꢁ1
was observed at 1498 cm and 1492 cm for complexes 1
and 2, respectively, as compared to those of the correspond-
[
13]
port iron in the body).
Cancer cells possess more trans-
ꢁ1
ꢁ1
ing free ligands, L1 (1625 cm ) and L2 (1494 cm ). In
[
14]
ferrin receptors than normal cells,
although it is argued
complex 3, however, the vibrational frequency is observed at
that binding to transferrin does not necessarily mean tumor
cell accumulation. Tumor cells are believed to require more
iron than the healthier cells because they have more faster
cyclic activity compared to their healthier cell counterparts,
hence, they express large amount of transferrin receptors to
get this essential element. This means tumor cell accumula-
tion by transferrin might influence the ability of ruthenium
ꢁ1
ꢁ1
1
467 cm compared to the free ligand at 1418 cm . Other
studies have shown that single sharp bands in the range of
ꢁ
1
1
450–1550 cm in dithiocarbamate complexes are typical of
carbon nitrogen bond order that is intermediate between the
stretching frequencies associated with C—N single bond
ꢁ
1
ꢁ1 [26,27]
(
1250–1350 cm ) and double bond (1640–1690 cm ).
[
15]
The shift observed in the metal complexes relative to those
of the free ligands is consistent with an increase in double
bond character of the C—N bon as a consequence of the
delocalization of electrons within the dithiocarbamate anion
bonded to the Ru(II) ion. In addition, the presence of a sin-
compounds to bind to DNA or other biomolecules.
The development of metal-based therapeutic agents has
shown that in vitro and in vivo activities of metal complexes
can be fine-tuned by subtle changes in the coordinated
ligands. Many ruthenium complexes with ligands such as
azo-quinolines, polypyridyl, Schiff bases, thiosemicarbazones,
arenes, and dithiocarbamate, have been reported for their
ꢁ
1
gle sharp ꢀ(C—S) band in the region of 1021–1026 cm
indicates a symmetrical coordination of the dithiocarbamate
anions to the Ru(II) ion. This confirmed that the dithiocar-
[
16–21]
cytotoxic activity.
However, very little has been done
on ruthenium(II) dithiocarbamate complexes as anticancer bamate anion acts as a bidentate chelating ligand to the
[
22,23]
agents.
cern in the design of metal complexes as anticancer agents, 1000 ± 70 cm
we report the synthesis, characterization, electrochemistry, tately coordinated dithiocarbamate anion.
Therefore, in view of this and the growing con- Ru(II) ion, otherwise two bands at approximately
ꢁ
1
would have been observed for monoden-
[
26–37]

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Table 3. IC50 (lM) values of the Ru(II) complexes tested against renal (TK10), also confirms this redox process. However, complex 3 exhib-
UACC62 (melanoma), and breast (MCF7) cancer lines.
its two quasi reversible redox peaks (Supporting Information
Complexes
TK10 (lM)
UACC62 (lM)
MCF7 (lM)
Figure S22): the first at Epc ¼ 1.0228 V and the correspond-
[
[
[
RuCl(PPh
RuCl(PPh
RuCl(PPh
3
3
3
)
)
)
3
3
3
(Mbzdtc)] (1)
(Ppipdtc)] (2)
(Mordtc)] (3)
79.39
77.18
91.95
4.64
39.28
72.32
90.20
11.37
33.36
38.18
41.07
3.52
ing oxidation peak at Epa ¼ 1.2091 V with DE ¼ 0.19 V
p
and the second at Epc ¼ 0.0912 V and the oxidation peak at
Parthenolide
Epa ¼ 0.3581 V with peak separation DE ¼ 0.27 V. This is
p
also confirmed in the square wave scan (Supporting
Information Figure S23) where two peaks at the same region
were observed. The first peak may be attributed to Ru(III)/
Ru(II) couple and the second may be due to Ru(II)/Ru(I)
couple. The E1/2 values observed toward the cathodic region
in the voltammogram are a consequence of the presence of S-S
donor group of the dithiocarbamate ligands. This is consistent
with the proposition by Devagi et al. that hard donor atoms
tend to give more negative E1/2 values whereas soft donor
Electronic spectra
The electronic spectra of the ligands and the corresponding
Ru(II) complexes are shown in Supporting Information
Figures S5, S10 and S15 for complexes 1, 2, and 3, respect-
ively, and relevant data are presented in Table 1. The spectra
are dominated by ligands to metal charge transfer electronic
transitions.
An electronic transition in the range of 258–261 nm with
a shoulder at 285–286 nm observed in the free ligands was
[42,43]
atoms such as dithiocarbamate give positive E1/2 values.
ꢂ
ꢂ
assigned to n-p /p-p intraligand transitions. These absorp-
tions shifted in all complexes with the appearance of should- Anticancer studies
ers. A broad absorption band in the range of 267–546 nm
The complexes were screened using sulforhodamine B (SRB)
for complex 1, 322–418 nm for complex 2, and 321–429 nm
for complex 3 is assigned to metal to ligand charge transfer
assay for their anticancer activity against renal (TK10),
UACC62 (melanoma), and breast (MCF7) human cancer
cell lines. The half maximum inhibitory concentrations
[
38]
transitions.
(
IC ) that inhibit growth of the cancer cells are presented
50
1
31
H and P NMR spectra
in Table 3. The complexes exhibit low to moderate cytotox-
icity against the three cancer cell lines with IC50 values rang-
ing from 33.36 to 91.95 lM. The anticancer potency of the
cell lines. The activity of the compounds is relatively lower
compared to that reported for Cu(II) and Zn(II) complexes
against these cancer cell lines.
1
The H NMR spectra of the complexes 1 2 3 showed mul-
tiplets in the range 7.70–7.05 ppm (Supporting Information
Figures S16, S17 and S18, respectively). These multiplets are
due to the triphenylphosphine co-ligand and appeared a lit-
tle upfield relative to the aromatic signals of the free dithio-
carbamate ligands. The P NMR spectra showed a single
peak at 29.0 and 25.5 ppm for complexes 1 and 2, respect-
ively, which indicate that the phosphorus atoms of the tri-
phenylphosphine co-ligands are magnetically equivalent in
these complexes. However, complex 3 showed two peaks at
[25,44–46]
Complexes 1, 2, and
3
3
were moderately active against MCF7 with IC50 values of
3.36, 38.18, and 41.07 lM, respectively. Complex 1 also
3
1
exhibits a good activity against UACC62 cell line with IC50
value of 39.28. However, the activity of all complexes was
comparatively low against TK10 cell line with IC50 between
7
7.18 and 91.95 lM. Similarly, the activity of complexes 2
2
9.0 and 53.0 suggesting that the phosphorus atoms of the
and 3 were relatively low against UACC62 with IC50 72.32
and 90.20 lM, respectively. Although one cannot ascertain
the reason for the relative activity of the three compounds
against MCF7, the ruthenium(II) complexes have a capacity
to reduce the energy status in tumors as well as to enhance
tumor hypoxia, which also influences their antitumor activ-
ities.
enhanced biological activity.
[
39]
phosphines are magnetically nonequivalent.
Electrochemistry
The redox properties of the three complexes were probed
using cyclic voltammetry and square wave at a scan rate of
[47]
Similarly, mixed ligand complexes tend to have
2
5 mV/s. The electrochemical data is presented in Table 2.
The voltammogram of complex 1 (Supporting Information
Figure S19) displays a cathodic peak potential of Epc
[48]
¼
ꢁ
0.0389 V and a corresponding anodic peak potential of Epa Experimental
¼
0.1877 V in the range ꢁ0.21 ꢁ 0.39 V. The peak separation
Materials and methods
(
DE ) is 0.23 V and E ¼ 0.0744 V. The increase in the
p
1/2
value of DE with increasing scan rate provides evidence for All starting materials were purchased from Aldrich and used
Similarly, complex 2 without further purification. The H NMR spectra were
Supporting Information Figure S20) was studied at recorded at 400 MHz and the C NMR spectra at 100 MHz
p
[
40,41]
1
quasi-reversible Ru III/II couple.
(
13
0
ꢁ 1.4 V potential range. The cathodic peak potential is E
with a Bruker Avance III 400 MHz spectrometer at room
0.7049 V and the corresponding anodic peak potential is temperature using TMS as internal reference. All the proton
pc
¼
E
¼ 1.0373 V. The DEp value is 0.33 V and E1/2
¼
and carbon NMR shifts are quoted in ppm and relative to
pa
0
.8711 V, the increase of DE with increasing scan rate indi- relevant solvent signal. FTIR spectra were recorded in the
p
ꢁ
1
cates a quasi-reversible one electron process due to Ru III/ region 4000–500 cm
using Perkin Elmer spectrum 100
II. The square wave (Supporting Information Figure S21) FTIR spectrometer. The UV–Visible spectra were recorded

4
P. A. AJIBADE AND F. P. ANDREW
3
using Cary100-UV–Vis spectrophotometer. Molar conduct- (400 MHz, D O): d ¼ 7.41 (t, JHH ¼ 8.0 Hz, 2H, C H ,),
2
6
5
3
3
ivity was measured with Jenway 4510 conductivity meter 7.17 (d, J
¼ 8.0 Hz, 2H, C H ,), 7.08 (t, J
¼ 8.0 Hz,
HH
6
5
HH
ꢁ
3
ꢁ1
3
3
using 10 molL freshly prepared solutions of the com- 1H, C H ,), 4.50 (t, J
¼ 8.0 Hz, 4H, CH ,), 3.24 (t, J
6
5
HH
2
HH
1
3
pounds. Human cancer cell lines TK10 (renal), UACC62 ¼ 4.0 Hz, 4H, CH ,). C NMR (400 MHz, D O): d ¼ 209.0
2
2
(
melanoma), and MCF7 (breast) were obtained from (CS), 49.7, 50.5 (N-CH CH N-), 118.0, 122.2, 129.6, 150.3
4
4
National Cancer Institute (NCI) in the framework a collab-
orative research program between the Council for Scientific
and Industrial Research (CSIR), South Africa, and NCI. In
vitro cytotoxic activity of the compounds was tested using
sulforhodamine B (SRB) assay. Electrochemical measure-
ments for the ruthenium complexes were performed with
Autolab potentiostat (with Nova 1.7 software) equipped with
three electrode system; a glassy carbon working electrode
(
-C H ). UV–Vis (H O): k
¼ 261, 286 nm (shoulder).
ꢁ1
6
5
2
max
Selected IR data (solid state): 1494, ꢀ(C-N); 994, ꢀ
cm .
(C-S)
Synthesis of sodium morpholinyldithiocarbamate (Mordtc)
The sodium salt of morpholinedithiocarbamate was prepared
[
40,42,43]
according to literature procedure.
amounts of morpholine (4.44 g, 50 mmol) dissolved in
0 mL of methanol and NaOH (2.0 g, 50 mmol) cold carbon
To equimolar
(GCWE), Ag/AgCl reference electrode and an auxiliary plat-
2
inum counter electrode. Fresh 2 mM solution of the complexes
and the supporting electrolyte (0.1 M tetrabutylammonium
hexafluorophosphate) was prepared in dichloromethane. All
solutions were purged with nitrogen steam for about 10 min
before every experiment. The glassy carbon working electrode
is polished between each run with slurry of alumina and ultra-
pure water on Buehler felt pad and rinsed thoroughly with
ultra-pure water.
disulfide (3.80 g, 50 mmol) was added. The reaction mixture
was stirred for 4 h at 0–4 C; the resulting white precipitate
ꢀ
was filtered, washed several times with diethyl ether, and
ꢀ
dried under vacuum over silica. Yield 65%, m.p 185 C, K
m
ꢁ1
2
ꢁ1
(Ohm
cm
mol ):
66.30.
Anal.
Calcd
for
Na(S CNC H O) ꢃ H O: C, 29.55; H, 4.96; N, 6.89; S, 31.55.
2
4
8
2
1
Found: C, 29.18; H, 5.04; N, 6.92; S, 32.08%. H NMR
3
(
(
400 MHz, D O): d ¼ 4.45 (t, J
¼ 8.0 Hz, 4H, CH ,), 3.84
2
HH
13
2
3
t, J
¼ 8.0 Hz, 4H, CH ). C NMR (400 MHz, D O):
HH
2
2
Synthesis of sodium N-methylbenzyldithiocarba-
mate (Mbzdtc)
d ¼ 209.4 (CS), 51.4, 66.1 (OCH
CH
4
4
N-). UV–Vis (H
2
O):
k
max ¼ 264, 286(shoulder) nm. Selected IR data (solid state):
[
44]
ꢁ1
A method reported in the literature
was adopted for the 1418, ꢀ(
; 979, ꢀ
cm
(C-S)
.
C-N)
synthesis of this ligand. NaOH (2.0 g, 50 mmol) was added
to methanolic solution of N-methylbenzylamine (6.0 g,
5
0 mmol) and stirred for 30 min, followed by the addition of Synthesis of [RuCl(PPh ) (Mbzdtc)] 1
3 3
cold carbon disulfide (3.8 g, 50 mmol). The reaction mixture N-Methylbenzyldithiocarbamate (0.0228 g, 0.104 mmol) and
ꢀ
was stirred for 4 h at 0–4 C; the resulting white precipitate [RuCl
(PPh
2
) ] (0.10 g, 0.104 mmol) were refluxed in 20 mL
3
3
was filtered, washed several times with diethyl ether, and of methanol for 4 h. The resulting greenish like solution was
ꢀ
dried under vacuum over silica. Yield, 96%, m.p 129 C, allowed to cool to ambient temperature. The precipitate
ꢁ
1
2
ꢁ1
K (Ohm
cm
mol ): 44.60, Anal. Calcd for formed was filtered and washed with diethyl ether. Yield
m
ꢀ
Na(S CNCH CH C H ) ꢃ 2 H O: C, 42.34; H, 5.53; N, 5.49; 58%, green solid, m.p 203 C, Anal. Calcd for
2
3
2
6
5
2
1
S, 25.12. Found: C, 42.20; H, 5.60; N, 5.46; S, 25.54%. H
[
Ru(S CNCH CH C H Cl(PPh ) ] ꢃ 4.5 H O: C, 62.70; H,
2
3
2
6
5
3 3
2
3
NMR (400 MHz, D O) d ¼ 7.52 (t, JHH ¼ 8.0 Hz, 2H,
2
5.35; N, 1.18; S, 5.40. Found: C, 62.67; H, 5.19; N, 1.72; S,
5.09%. Km (Ohm cm mol ): 12.50. H NMR (400 MHz,
CDCl ): d ¼ 7.70-7.43 (m, 50H), 5.98 (s, 2H), 3.79 (s, 3H).
3
3
ꢁ
1
2
ꢁ1
1
C H ,), 7.42 (t, J
4
¼ 8.0 Hz, 1H, C H ,), 7.36 (d, J
¼
6
5
HH
6
5
HH
13
.0 Hz, 2H, C H ,), 5.50 (s, 2H), 3.50 (s, 3H). C NMR
6 5
3
(
400 MHz, D O): d ¼ 210.1 (CS), 42.7 (N-CH ), 59.6 (N- 31
2
3
P NMR (400 MHz, CDCl ): d ¼ 29.0. Selected IR data
3
CH -(C H )), 136.8, 126.8, 127.4, 128.9 (-C H ), UV–Vis
ꢁ1
2
6
5
6
5
(
(
solid state): 1498, ꢀ
; 1024, ꢀ
cm . UV–Vis
(
C-N)
(C-S)
(
H O): k
¼ 258, 285 nm. Selected IR data (solid state):
2
max
CH Cl ): k
max
¼ 229, 267–546 nm.
2
2
ꢁ1
1
625, ꢀ(C-N); 949, ꢀ
cm .
(C-S)
Synthesis of [RuCl(PPh ) (Ppipdtc)] 2
3
3
Synthesis of sodium phenylpiperazyldithiocarba-
mate (Ppipdtc)
The ligand was prepared according to literature.
Phenylpiperazyldithiocarbamate (0.104 mmol, 0.0270 g) and
45] [RuCl (PPh ) ] (0.104 mmol, 0.10 g) were refluxed in 20 mL
[
2
3 3
methanol for 4 h, the resulting greenish like solution was
allowed to cool. The precipitate formed was filtered and
washed with diethyl ether. Yield 52%, green solid, m.p
Two milliltre of a cold aqueous solution of NaOH (2.0 g,
0 mmol) was added to 15 mL of a cold methanolic solution
5
of 1-phenylpiperazine (8.07 g, 50 mmol) followed by the add-
ition of cold carbon disulfide (3.80 g, 50 mmol). The reaction
ꢀ
ꢁ1
2
ꢁ1
1
89 C, K (Ohm
cm mol ): 11.11. Anal. Calcd for
m
ꢀ
[
Ru(S CNC H NC H )Cl(PPh ) ] ꢃ 2 H O: C, 65.23; H, 5.22;
mixture was stirred for 4 h at 0–4 C; the resulting white
2
4
8
6
5
3 3
2
precipitate formed was filtered, washed several times with N, 2.34; S, 5.36. Found: C, 65.55; H, 4.95; N, 2.01; S, 5.79%.
1
ꢀ
diethyl ether and dried over silica. Yield 78%, m.p 159 C,
H NMR (400 MHz, CDCl
): d ¼ 7.79-7.06 (m, 50H), 5.94 (s,
3
ꢁ
1
2
ꢁ1
31
Km (Ohm cm mol ): 67.52, white solid, Anal. Calcd for 4H), 3.50 (s, 4H). P NMR (400 MHz, CDCl
): d ¼ 29.0,
3
ꢁ
1
Na(S CNC H NC H ) ꢃ 2 H O: C, 44.58; H, 5.78; N, 9.45; S, Selected IR data (solid state): 1492, ꢀ(C-N); 1026, ꢀ(C-S) cm
.
2
4
8
6
5
2
1
2
1.64. Found: C, 44.28; H, 5.82; N, 9.35; S, 21.92%. H NMR UV–Vis (CH Cl ): k
max
¼ 230, 259, 322–418 nm.
2
2

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Scheme 1. Synthesis of complexes 1–3.
Synthesis of [RuCl(Ph ) (Mordtc)] 3
breast (MCF7) using sulforhodamine B (SRB) assay.
3
3
Morpholinyldithiocarbamate (0.104 mmol, 0.0193 g) and Complex 1 with methyl benzyldithiocarbamate is the most
RuCl (PPh ) ] (0.104 mmol, 0.10 g) were refluxed in 20 mL active followed by complex 2 with phenylpiperazyldithiocar-
[
2
3 3
of methanol for 4 h. The resulting greenish like solution was bamate while complex 3 with morpholinyldithiocarbamate
allowed to cool to ambient temperature. The precipitate showed low anticancer activity. The results indicate that
formed was filtered and washed with diethyl ether. Yield
coordination of different dithiocarbamate anions with to
chlorido(triphenylphosphine) ruthenium(II) result in differ-
ent cytotoxic activities against the cancer cell lines. The
design of the complexes can be modified to obtain more
potent compounds.
ꢀ
ꢁ1
2
ꢁ1
5
2
6
0
8%, m.p. 217 C, green solid, Km (Ohm
cm mol ):
.94. Anal. Calcd for [Ru(S CNC H OCl(PPh ) ] ꢃ 2 H O: C,
2
4
8
3 3
2
3.06; H, 4.74; N, 1.27; S, 5.81. Found: C, 63.01; H, 4.87; N,
1
.82; S, 5.99%. H NMR (400 MHz, CDCl ): d ¼ 7.70-7.06
3
31
(m, 45H), 5.95 (s, 4H), 3.50 (s, 4H). P NMR (400 MHz,
CDCl ): d ¼ 29.0. Selected IR data (solid state): 1467, ꢀ(C-N);
3
ꢁ
1
Disclosure statement
1
021, ꢀ(
cm . UV–Vis (CH Cl ): k
max
¼ 229, 264,
C-S)
2
2
3
21-429 nm.
No potential conflict of interest was reported by the authors.
Conclusion
Funding
Three chlorido(triphenylphosphine)ruthenium(II) dithiocar- The authors acknowledge the financial support of Sasol and of
bamate complexes - [RuCl(PPh ) (Mbzdtc)], [RuCl(PPh )
3 3
National Research Foundation, South Africa.
3
3
(
Ppipdtc)], and [RuCl(PPh ) (Mordtc)] – were synthesized
3 3
and characterized by FTIR, UV–Vis, and NMR spectros-
copy, elemental analysis, and cyclic voltammetry. The elem-
ental and spectroscopic data agree with the proposed
composition and structure of the compounds. The electro-
chemical studies showed one reversible Ru(III)/Ru(II) redox
couple in the voltammogram of complexes 1 and 2, whereas
for complex 3 two redox couples due to Ru(III)/Ru(II) and
Ru(II)/Ru(I) were observed, which was further confirmed by
their square wave plots. The in vitro anticancer activity of
the Ru(II) complexes was evaluated against three human
cancer cell lines: renal (TK10), melanoma (UACC62), and
References
[1] Vajs, J.; Steiner, I.; Brozovic, A.; Pevec, A.; Ambriovi ꢀc -Ristov, A.;
Matkovi ꢀc , M.; Piantanida, I.; Urankar, D.; Osmark, M.; Ko ꢁs mrlj, J.
The 1,3-Diaryltriazenido(p-Cymene)Ruthenium(II) Complexes with
a High In Vitro Anticancer Activity. J. Inorg. Biochem. 2015, 153,
42–48. DOI: 10.1016/j.jinorgbio.2015.09.005.
[
2] Adeniyi, A. A.; Ajibade, P. A. Computational Properties of g6-
Toluene and g6-Trifluorotoluene Half-Sandwich Ru(II)
Anticancer Complexes. J. Biomol. Struct. Dyn. 2014, 32,
1351–1365. DOI: 10.1080/07391102.2013.819299.

6
P. A. AJIBADE AND F. P. ANDREW
[3] McWhinney, S. R.; Goldberg, R. M.; McLeod, H. L. Platinum [19] Wei, J.; Renfrew, A. K. Photolabile Ruthenium Complexes to
Neurotoxicity Pharmacogenetics. Mol. Cancer Ther. 2009, 8,
0–16. DOI: 10.1158/1535-7163.MCT-08-0840.
4] Shahsavani, M. B.; Ahmadi, S.; Aseman, M. D.; Nabavizadeh,
Cage and Release a Highly Cytotoxic Anticancer Agent. J.
Inorg. Biochem. 2018, 179, 146–153. DOI: 10.1016/j.jinorgbio.
2017.11.018.
1
[
S. M.; Rashidi, M.; Asadi, Z.; Erfani, N.; Ghasemi, A.; Saboury, [20] Tang, B.; Wan, D.; Lai, S. H.; Yang, H. H.; Zhang, C.; Wang,
A. A.; Niazi, A.; et al. Anticancer Activity Assessment of Two
Novel Binuclear Platinum (II) Complexes. J. Photochem.
Photobiol. B 2016, 161, 345–354. DOI: 10.1016/j.jphotobiol.
X. Z.; Zeng, C. C.; Liu, Y. J. Design, Synthesis and Evaluation
of Anticancer Activity of Ruthenium (II) Polypyridyl
Complexes. J. Inorg. Biochem. 2017, 173, 93–104. DOI: 10.1016/
j.jinorgbio.2017.04.028.
2016.05.025.
[
[
5] Stevens, S. K.; Strehle, A. P.; Miller, R. L.; Gammons, S. H.; [21] Dou, Y.-H.; Xu, S.-D.; Chen, Y.; Wu, X.-H. Synthesis,
Hoffman, K. J.; McCarty, J. T.; Miller, M. E.; Stultz, L. K.;
Hanson, P. K. The Anticancer Ruthenium Complex KP1019
Induces DNA Damage, Leading to Cell Cycle Delay and Cell
Characterization, and Anticancer Activity of Dithiocarbamate
Ruthenium(II) Complexes. Phosphorus Sulfur Silicon Relat. Elem.
2017, 192, 1219–1223. DOI: 10.1080/10426507.2017.1359594.
Death in Saccharomyces cerevisiae. Mol. Pharmacol. 2013, 83, [22] Ali, I.; Wani, W. A.; Saleem, K.; Hseih, M. F. Design and
2
25–234. DOI: 10.1124/mol.112.079657.
Synthesis of Thalidomide Based Dithiocarbamate Cu(II), Ni(II)
and Ru(III) Complexes as Anticancer Agents. Polyhedron 2013,
56, 134–143. DOI: 10.1016/j.poly.2013.03.056.
6] Dragutan, I.; Dragutan, V.; Demonceau, A. Editorial of Special
Issue Ruthenium Complex: The Expanding Chemistry of the
Ruthenium Complexes. Molecules 2015, 20, 17244–17274. DOI: [23] Scintilla, S.; Brustolin, L.; Gambalunga, A.; Chiara, F.; Trevisan,
1
0.3390/molecules200917244.
A.; Nardon, C.; Fregona, D. Ru(III) Anticancer Agents with
Aromatic and Non-Aromatic Dithiocarbamates as Ligands:
Loading into Nanocarriers and Preliminary Biological Studies. J.
Inorg. Biochem. 2016, 165, 159–169. DOI: 10.1016/j.jinorgbio.
2016.11.018.
[
7] Graf, N.; Lippard, S. J. Redox Activation of Metal-Based
Prodrugs as a Strategy for Drug Delivery. Adv. Drug Deliv. Rev.
2
8] Lee, H. Z. S.; Buriez, O.; Labb ꢀe , E.; Top, S.; Pigeon, P.; Jaouen,
012, 64, 993–1004. DOI: 10.1016/j.addr.2012.01.007.
[
G.; Amatore, C.; Leong, W. K. Oxidative Sequence of a [24] Hogarth, G. Metal-Dithiocarbamate Complexes: Chemistry and
Ruthenocene-Based Anticancer Drug Candidate in a Basic
Environment. Organometallics 2014, 33, 4940–4946. DOI: 10.
Biological Activity. Mini Rev Med Chem 2012, 12, 1202–1215.
DOI: 10.2174/138955712802762095.
1
021/om500225k.
[25] Andrew, F. P.; Ajibade, P. A. Metal Complexes of Alkyl-Aryl
Dithiocarbamates: Structural Studies, Anticancer Potentials and
Applications as Precursors for Semiconductor Nanocrystals. J. Mol.
Struct. 2018, 1155, 843–855. DOI: 10.1016/j.molstruc.2017.10.106.
[26] Ajibade, P. A.; Mbese, J. Z.; Omondi, B. Group 12
Dithiocarbamate Complexes: Synthesis, Characterization, and
X-Ray Crystal Structures of Zn(II) and Hg(II) Complexes and
Their Use as Precursors for Metal Sulphide Nanoparticles.
Inorg. Nano- Met. Chem. 2017, 47, 202–212. DOI: 10.1080/
15533174.2015.1137589.
[
9] Furrer, J.; S u€ ss-Fink, G. Thiolato-Bridged Dinuclear Arene
Ruthenium Complexes and Their Potential as Anticancer
Drugs. Coord. Chem. Rev. 2016, 309, 36–50. DOI: 10.1016/j.ccr.
2015.10.007.
[
[
[
10] Li, X.; Gorle, A. K.; Sundaraneedi, M. K.; Keene, F. R.; Collins,
J. G. Kinetically-Inert Polypyridylruthenium(II) Complexes as
Therapeutic Agents. Coord. Chem. Rev. 2017, 32, 33–47. DOI:
1
0.1016/j.ccr.2017.11.011.
ꢁ
11] Lazarevi ꢀc , T.; Rilak, A.; Bugar ꢁc i ꢀc , ZD. Platinum, Palladium, Gold
and Ruthenium Complexes as Anticancer Agents: Current Clinical [27] Mbese, J. Z.; Ajibade, P. A. Synthesis, Structural and Optical
Uses, Cytotoxicity Studies and Future Perspectives. Eur. J. Med.
Chem. 2017, 142, 8–31. DOI: 10.1016/j.ejmech.2017.04.007.
12] Wan, D.; Tang, B.; Wang, Y. J.; Guo, B. H.; Yin, H.; Yi, Q. Y.;
Properties of ZnS, CdS and HgS Nanoparticles from
Dithiocarbamato Single Molecule Precursors. J. Sulf. Chem.
2014, 35, 438–449. DOI: 10.1080/17415993.2014.912280.
Liu, Y. J. Synthesis and Anticancer Properties of Ruthenium [28] Giovagnini, L.; Mancinetti, E.; Ronconi, L.; Sitran, S.; Marchi oꢂ , L.;
(
II) Complexes as Potent Apoptosis Inducers through
Mitochondrial Disruption. Eur. J. Med. Chem. 2017, 139,
80–190. DOI: 10.1016/j.ejmech.2017.07.066.
13] Michlewska, S.; Ionov, M.; Maroto-D ꢀı az, M.; Szwed, A.; Ihnatsyeu-
Castagliuolo, I.; Brun, P.; Trevisan, A.; Fregona, D. Preliminary
Chemico-Biological Studies on Ru(III) Compounds with S-Methyl
Pyrrolidine/Dimethyl Dithiocarbamate. J. Inorg. Biochem. 2009,
103, 774–782. DOI: 10.1016/j.jinorgbio.2009.01.019.
1
[
Kachan, A.; Loznikova, S.; Shcharbin, D.; Maly, M.; Ramirez, [29] Khan, S. Z.; Amir, M. K.; Ullah, I.; Aamir, A.; Pezzuto, J. M.;
R. G.; de la Mata, F. J.; Bryszewska, M. Ruthenium Dendrimers as
Carriers for Anticancer siRNA. J. Inorg. Biochem. 2018, 181,
Kondratyuk, T.; Gariepy, F. B.; Ali, A.; Khan, S. New
Heteroleptic Palladium(II) Dithiocarbamates: Synthesis,
1
8–27. DOI: 10.1016/j.jinorgbio.2018.01.001.
Characterization, Packing and Anticancer Activity against Five
Different Cancer Cell Lines. Appl. Organomet. Chem. 2016, 30,
392–398. DOI: 10.1002/aoc.3445.
[
[
[
14] Timerbaev, A. R. Role of Metallomic Strategies in Developing
Ruthenium Anticancer Drugs. TrAC Trends Anal. Chem. 2016,
8
0, 547–554. DOI: 10.1016/j.trac.2016.04.015.
[30] Bonati, F.; Ugo, R. Organotin(IV) N,N-Disubstituted
Dithiocarbamates. J. Organomet. Chem. 1967, 10, 257–268.
DOI: 10.1016/S0022-328X(00)93085-7.
15] Bergamo, A.; Sava, G. Ruthenium Anticancer Compounds: Myths
and Realities of the Emerging Metal-Based Drugs. Dalton Trans.
2
011, 40, 7817–7823. DOI: 10.1039/C0DT01816C.
[31] Mansouri-Torshizi, H.; Saeidifar, M.; Divsalar, A.; Saboury,
16] Kaulage, M. H.; Maji, B.; Pasadi, S.; Bhattacharya, S.; Muniyappa,
K. Novel Ruthenium Azo-Quinoline Complexes with Enhanced
Photonuclease Activity in Human Cancer Cells. Eur. J. Med.
Chem. 2017, 139, 1016–1029. DOI: 10.1016/j.ejmech.2017.08.059.
17] Sahyon, H. A.; El-Bindary, A. A.; Shoair, A. F.; Abdellatif, A. A.
A. A. Interaction Studies between a 1,10-Phenanthroline
Adduct of Palladium(II) Dithiocarbamate anti-Tumor Complex
and Calf Thymus DNA. A Synthesis Spectral and In-Vitro
Study. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2010, 77,
312–318. DOI: 10.1016/j.saa.2010.05.029.
[
Synthesis and Characterization of Ruthenium(III) Complex [32] Ferreira, I. P.; de Lima, G. M.; Paniago, E. B.; Takahashi, J. A.;
Containing 2-Aminomethyl Benzimidazole, and Its Anticancer
Activity of In Vitro and In Vivo Models. J. Mol. Liq. 2018, 255,
Pinheiro, C. B. Synthesis, Characterization and Antifungal
Activity of New Dithiocarbamate-Based Complexes of Ni(II),
Pd(II) and Pt(II). Inorg. Chim. Acta 2014, 423, 443–449. DOI:
10.1016/j.ica.2014.09.002.
122–134. DOI: 10.1016/j.molliq.2018.01.140.
[
18] Tikum, A. F.; Jeon, Y. J.; Lee, J. H.; Park, M. H.; Bae, I. Y.;
Kim, S. H.; Lee, H. J.; Kim, J. Cytotoxic and Anticancer [33] Manav, N.; Mishra, A. K.; Kaushik, N. K. In Vitro Antitumour
Properties of New Ruthenium Polypyridyl Complexes with
Different Lipophilicities. J. Inorg. Biochem. 2018, 180, 204–210.
DOI: 10.1016/j.jinorgbio.2018.01.003.
and Antibacterial Studies of Some Pt(IV) Dithiocarbamate
Complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2006,
65, 32–35. DOI: 10.1016/j.saa.2005.09.023.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
[34] Shaheen, F.; Badshah, A.; Gielen, M.; Dusek, M.; Fejfarova, K.; [41] Kulkarni, A. D.; Patil, S. A.; Badami, P. S. Electrochemical
de Vos, D.; Mirza, B.; B. Synthesis, Characterization,
Antibacterial and Cytotoxic Activity of New Palladium(II)
Complexes with Dithiocarbamate Ligands: X-Ray Structure of
Bis(Dibenzyl-1-S:S0 - Dithiocarbamato)Pd(II). J. Organomet.
Chem. 2007, 692, 3019–3026. DOI: 10.1016/j.jorganchem.2007.
Properties of Some Transition Metal Complexes: Synthesis,
Characterization and In-Vitro Antimicrobial Studies of Co(II),
Ni(II), Cu(II), Mn(II) and Fe(III) Complexes. Int. J.
Electrochem. Sci. 2009, 4, 717–729.
[
42] Botha, N. L.; Ajibade, P. A. Effect of Temperature on Crystallite
Sizes of Copper Sulfide Nanocrystals Prepared from Copper(II)
Dithiocarbamate Single Source Precursor. Mater. Sci. Semicon.
Process. 2016, 43, 149–154. DOI: 10.1016/j.mssp.2015.12.006.
43] Devagi, G.; Dallemer, F.; Kalaivani, P.; Prabhakaran, R.
Organometallic Ruthenium(II) Complexes Containing NS
Donor Schiff Bases: Synthesis, Structure, Electrochemistry,
DNA/BSA Binding, DNA Cleavage, Radical Scavenging and
Antibacterial Activities. J. Organomet. Chem. 2018, 854, 1–14.
DOI: 10.1016/j.jorganchem.2017.10.036.
0
3.019.
[
[
35] Abdullah, N. H.; Zainal, Z.; Silong, S.; Tahir, M. I. M.; Tan,
K. B.; Chang, S.; K. Synthesis of Zinc Sulphide Nanoparticles
from Thermal Decomposition of Zinc N-Ethyl Cyclohexyl
Dithiocarbamate Complex. Mater. Chem. Phys. 2016, 173,
[
3
3–41. DOI: 10.1016/j.matchemphys.2016.01.034.
36] Prakasam, B. A.; Lahtinen, M.; Peuronen, A.; Muruganandham,
M.; Kolehmainen, E.; Haapaniemi, E.; Sillanp €a €a , M. Synthesis,
NMR Spectral and Structural Studies on Mixed Ligand Complexes
of Pd(II) Dithiocarbamates: First Structural Report on
[
44] Andrew, F. P.; Ajibade, P. A. Synthesis, Characterization and
Anticancer Studies of Bis- (N-Methyl-1-Phenyldithiocarbamato)
Cu(II), Zn(II), and Pt(II) Complexes: Single Crystal X-Ray
Structure of the Copper Complex. J. Coord. Chem. 2018, 71,
ꢁ
Palladium(II) Dithiocarbamate with SCN Ligand. J. Mol. Struct.
2016, 1108, 195–202. DOI: 10.1016/j.molstruc.2015.11.076.
[
37] Onwudiwe, D. C.; Ajibade, P. A.; Omondi, B. Synthesis,
2776–2786. DOI: 10.1080/00958972.2018.1489537.
0
Spectral and Thermal Studies of 2,2 -Bipyridyl Adducts of
[
45] Andrew, F. P.; Ajibade, P. A. Synthesis, Characterization and
Anticancer Studies of Bis(1-Phenylpiperazine Dithiocarbamato)
Cu(II), Zn(II) and Pt(II) Complexes: Crystal Structures of 1-
Bis(N-alkyl-N-Phenyldithiocarbamato)Zinc(II). J. Mol. Struct.
2
011, 987, 58–66. DOI: 10.1016/j.molstruc.2010.11.060.
[
38] Govindaswamy, P.; Mozharivskyj, Y. A.; Kollipara, M. R. Synthesis
0
Phenylpiperazine dithiocarbamato-S,S Zinc(II) and Pt(II). J. Mol.
and Characterization of Cyclopentadienylruthenium(II) Complexes
0
Struct. 2018, 1170, 24–29. DOI: 10.1016/j.molstruc.2018.05.068.
46] Ajibade, P. A.; Andrew, F. P.; Botha, N. L.; Solomane, N.
Synthesis, Crystal Structures and Anticancer Studies of
Morpholinyldithiocarbamato Cu(II) and Zn(II) Complexes.
Molecules 2020, 25, 3584. DOI: 10.3390/molecules25163584.
47] Vijayan, P.; Viswanathamurthi, P.; Sugumar, P.; Ponnuswamy,
M. N.; Balakumaran, M. D.; Kalaichelvan, P. T.; Velmurugan,
K.; Nandhakumar, R.; Butcher, R. J. Unprecedented Formation
of Organo-Ruthenium(II) Complexes Containing 2-Hydroxy-1-
Naphthaldehyde S-Benzyldithiocarbazate: Synthesis, X-Ray
Crystal Structure, DFT Study and Their Biological Activities
In Vitro. Inorg. Chem. Front. 2015, 2, 620–639. DOI: 10.1039/
C5QI00029G.
Containing N,N -Donor Schiff Base Ligands: Crystal and Molecular
[
[
5
Structure of [(g -C
5
H
5
)Ru(C
5
H
4
N-2-CHN–C
6
H
4
–p- OCH
3
)(PPh
3
)]
6
PF . Polyhedron 2004, 23, 1567–1572. DOI: 10.1016/j.poly.2004.03.
007.
[
39] Santos, K.; Dinelli, L. R.; Bogado, A. L.; Ramos, L. A.; Cavalheiro,
E. T.; Ellena, J.; Castellano, E. E.; Batista, A. A. Crystal Structure
and Catalytic Activity of Ruthenium (II)/Dithiocarbamate
Complexes in the Epoxidation of Cyclooctene. Inorg. Chim. Acta
2015, 429, 237–242. DOI: 10.1016/j.ica.2015.02.014.
[
40] Darwish, H. W.; Barakat, A.; Nafady, A.; Suleiman, M.; Al-
Noaimi, M.; Hammouti, B.; Radi, S.; Hadda, T. B.; Abu-Obaid,
A.; Mubarak, M. S.; Warad, I. Design, Synthesis,
Characterization of Novel Ruthenium(II) Catalysts: Highly [48] Ramesh, R.; Sivagamasundari, M. Synthesis, Spectral and
Efficient and Selective Hydrogenation of Cinnamaldehyde to
E)-3-Phenylprop-2-en-1-ol. Molecules 2014, 19, 5965–5980.
DOI: 10.3390/molecules19055965.
Antifungal Activity of Ru(II) Mixed-Ligand Complexes.
Synth. React. Inorg. Met. 2003, 33, 899–910. DOI: 10.1081/
SIM-120021656.
(