Spectroscopic, catalytic, and biological studies on mononuclear ruthenium(II) ONSN chelating thiosemicarbazone complexes

Article abstract of DOI:10.1080/00958972.2011.556721

A group of new ruthenium(II) thiosemicarbazone complexes, [Ru(CO)(B)(L)] (where B = PPh₃/AsPh₃/Py; L = dibasic tetradentate Schiff-base ligand), have been synthesized by reacting [RuHCl(CO)(PPh ₃)₃], [RuHCl(CO)(AsPh₃)₃], and [RuHCl(CO)(Py)(PPh₃)₂] with the Schiff base in 1 : 1 molar ratio in an ethanol-benzene mixture. These complexes have been characterized by elemental analysis, FT-IR, UV-Vis, NMR, and mass spectroscopy. The redox behaviors of the complexes have been investigated by cyclic voltammetry. These complexes have been examined for their catalytic efficiency for aryl-aryl coupling and oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of oxygen. All the complexes were screened for their antibacterial activity. Further, one complex was tested for its binding with calf thymus-DNA using absorption spectroscopic studies and viscosity measurements.

Full text of DOI:10.1080/00958972.2011.556721

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Spectroscopic, catalytic, and biological
studies on mononuclear ruthenium(II)
ONSN chelating thiosemicarbazone
complexes
G. Raja a , N. Sathya a & C. Jayabalakrishnan a
a Post Graduate and Research Department of Chemistry, Sri
Ramakrishna Mission Vidyalaya College of Arts and Science,
Coimbatore – 641 020, Tamil Nadu, India
Version of record first published: 18 Feb 2011.
To cite this article: G. Raja, N. Sathya & C. Jayabalakrishnan (2011): Spectroscopic, catalytic, and
biological studies on mononuclear ruthenium(II) ONSN chelating thiosemicarbazone complexes,
Journal of Coordination Chemistry, 64:5, 817-831
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Journal of Coordination Chemistry
Vol. 64, No. 5, 10 March 2011, 817–831
Spectroscopic, catalytic, and biological studies on mononuclear
ruthenium(II) ONSN chelating thiosemicarbazone complexes
G. RAJA, N. SATHYA and C. JAYABALAKRISHNAN*
Post Graduate and Research Department of Chemistry, Sri Ramakrishna Mission Vidyalaya
College of Arts and Science, Coimbatore – 641 020, Tamil Nadu, India
(Received 18 June 2010; in final form 3 December 2010)
A group of new ruthenium(II) thiosemicarbazone complexes, [Ru(CO)(B)(L)] (where B ¼ PPh3/
AsPh3/Py; L ¼ dibasic tetradentate Schiff-base ligand), have been synthesized by reacting
[RuHCl(CO)(PPh3)3], [RuHCl(CO)(AsPh3)3], and [RuHCl(CO)(Py)(PPh3)2] with the Schiff
base in 1 : 1 molar ratio in an ethanol–benzene mixture. These complexes have been
characterized by elemental analysis, FT-IR, UV-Vis, NMR, and mass spectroscopy. The
redox behaviors of the complexes have been investigated by cyclic voltammetry. These
complexes have been examined for their catalytic efficiency for aryl–aryl coupling and
oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in
the presence of oxygen. All the complexes were screened for their antibacterial activity. Further,
one complex was tested for its binding with calf thymus-DNA using absorption spectroscopic
studies and viscosity measurements.
Keywords: Thiosemicarbazone; Molecular oxygen; Aryl–aryl coupling; Antibacterial;
DNA-binding
1. Introduction
Thiosemicarbazones are an important class of N, S donors which have pharmacological
interest due to their significant antibacterial, antiviral, antimalarial, antileprotic, and
anticancer activities [1–8]. Thiosemicarbazones usually are chelating ligands with
transition metal ions, bonding through sulfur and hydrazine nitrogen [9–11]. The
chemistry of ruthenium receives attention primarily because of the fascinating electron-
transfer and energy-transfer properties displayed by the complexes of this metal [12].
Ruthenium offers a wide range of oxidation states and reactivity of the ruthenium
complexes depend on the stability and interconvertibility of these oxidation states,
which in turn depend on the nature of the ligands bound to the metal. Transition metal
complexes are effective catalysts in cross-coupling reactions, but their use as catalysts
for aryl–aryl coupling has not been much studied. Mild and efficient aromatic couplings
have been reported [13]. Selective oxidation of alcohols to aldehydes and ketones is a
*Corresponding author. Email: cjayabalakrishnan@gmail.com
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2011 Taylor & Francis
DOI: 10.1080/00958972.2011.556721

818
G. Raja et al.
key reaction in organic synthesis. The development of new procedures that can use air
or molecular oxygen as oxidant is environmentally attractive [14]. Research has
described the use of solid-supported heterogeneous catalysts, notably ruthenium-based
for the aerobic oxidation of alcohols [15]. DNA-binding metal complexes have been
extensively studied as DNA structural probes, DNA-dependent electron-transfer
probes, DNA foot printing and sequence-specific cleaving agents, and potential
anticancer drugs [16–18].
Here we report the synthesis, characterization, catalytic, biological, and DNA-
binding activities of Ru(II) complexes containing triphenylphosphine/arsine/pyridine as
coligands. Mixed-chelate complexes of ruthenium have been synthesized using
tetradentate Schiff-base ligands derived by the condensation of salicylaldehyde/o-
hydroxyacetophenone/o-vanillin/2-hydroxy-1-naphthaldehyde with thiosemicarbazide
and furfuraldehyde (scheme 1).
2. Experimental
2.1. Materials and measurements
All reagents used were of analar grade. Solvents were purified and dried according to
the literature procedures [19]. RuCl3 ꢀ 3H2O was purchased from Loba Chemie and
used without purification. The starting complexes [RuHCl(CO)(PPh3)3] [20],
[RuHCl(CO)(AsPh3)3] [21], and [RuHCl(CO)(Py)(PPh3)2] [22] were prepared by
literature methods. Microanalyses were performed at Sophisticated Test and
Instrumentation Centre (STIC), Cochin University of Science and Technology,
Kerala. Infrared (IR) spectra were recorded using KBr pellets on a Perkin-Elmer
R3
OH
S
+
R2
+
H2N
O
O
NH C
NH2
H
O
R1
Ethanol
Reflux, 6 h
R3
OH
R2
S
N
N
O
R1
R2
HN C
H
R1
R3
H
Abbreviation
H2L1
H
H
H
CH3
H
H
H2L2
H2L3
H2L4
H
OCH3
H
C4H4
H
Scheme 1. Formation of Schiff-base ligands.

Thiosemicarbazone complexes
819
FT-IR 8000 spectrometer RX1 model from 4000 to 400 cmꢁ1. Electronic spectra of the
complexes were recorded in dichloromethane with a Systronics-2202 double beam
1
spectrophotometer from 800 to 200 nm. The H- and 13C-NMR spectra of the ligands
and complexes were recorded with a Bruker WM 500 DCX MHz instrument using
TMS as an internal standard. 31P NMR spectra were recorded with a Bruker WM 500
DCX MHz instrument using orthophosphoric acid as an internal standard. Mass
spectra were recorded with a JEOL GC make instrument at Indian Institute of
Technology, Chennai. Cyclic voltammetric studies were carried out on a CHN
Instrument in dichloromethane using a glassy carbon working electrode. A platinum
electrode and a saturated calomel electrode were used as counter and reference
electrodes, respectively. Melting points were recorded with a Veego DS Model
apparatus and are uncorrected.
2.2. Preparation of dibasic tetradentate Schiff bases
To an ethanolic solution of salicylaldehyde/o-hydroxyacetophenone/o-vanilin/2-
hydroxy-1-naphthaldehyde (20 mmol), thiosemicarbazide (20 mmol) and furfuralde-
hyde (20 mmol) were added and stirred along with a few drops of glacial acetic acid. The
mixture was then refluxed for 6 h. On cooling, a solid separated out and was
recrystallized from ethanol. The purity of the ligand was checked by thin layer
chromatography (TLC).
2.3. Preparation of ruthenium(II) Schiff-base complexes
The Schiff bases (H2L1–H2L4) (0.1 mmol) were added to
a
solution of
[RuHCl(CO)(EPh3)2B] (where E ¼ P/As, B ¼ PPh3/AsPh3/Py) (0.1 mmol) in 1 : 1
molar ratio in ethanol–benzene (1 : 1) and the mixture was refluxed for 6 h. The
resulting solution was concentrated to about 3 cm3 and the complexes were precipitated
by the addition of a small quantity of petroleum ether (60–80ꢂC). The complexes were
then filtered, washed with petroleum ether and recrystallized from CH2Cl2/petroleum
ether, and dried under vacuum (scheme 2).
2.4. Catalytic oxidation experiments
A solution of alcohol (0.1 mL, 1 mmol) in dichloromethane (20 mL) was added to a
solution of the free ligands, metal precursors, and ruthenium(II) complex (0.01 mmol)
and stirred for 6 h under oxygen at ambient temperature. The mixture was evaporated
to dryness and extracted with petroleum ether (60–80ꢂC). The combined petroleum
ether extracts were filtered and evaporated to give the corresponding carbonyl
compound which was then quantified as their 2,4-dinitrophenyl hydrazones [23].
2.5. Aryl–aryl coupling experiments
Magnesium turnings (0.320 g) were placed in a flask equipped with a CaCl2 guard tube.
A crystal of iodine was added. PhBr [0.75 cm3 of total 1.88 cm3] in anhydrous Et2O
(5 cm3) was added dropwise and the mixture was refluxed for 40 min. To this mixture,

820
G. Raja et al.
R3
OH
+ [RuHCl(CO)(EPh3)2(B)]
R2
SH
N C
N
N
O
R1
H
Benzene-Ethanol
Reflux, 6 hrs
CO
B
N
R3
O
Ru
S
R2
N
O
R1
H
N C
where R1 = H/CH3; R2 = H/C4H4; R3 = H/OCH3; E = P/As; B = PPh3/AsPh3/Py
Scheme 2. Formation of ruthenium(II) Schiff-base complexes.
1.03 cm3 (0.01 mol) of PhBr in anhydrous Et2O (5 cm3) and the free ligands, metal
precursors, and ruthenium complex (0.05 mmol) chosen for investigation were added
and heated under reflux for 6 h. The reaction mixture was cooled and hydrolyzed with a
saturated solution of aqueous NH4Cl and the ether extract on evaporation gave a crude
product of biphenyl which was chromatographed to get pure biphenyl, which was
compared with an authentic sample (m.p. 69–72ꢂC) [24].
2.6. Antibacterial activities
Solvent, free ligands, metal precursors, and new ruthenium(II) complexes were tested
in vitro for their effect on certain human pathogenic bacteria by the Kirby Bauer
method [25]. The ligands, metal precursor complexes, and their ruthenium(II)
complexes were stored dry at room temperature and dissolved in dichloromethane.
Both the Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli)
bacteria were grown in Muller Hinton agar medium and incubated at 37ꢂC for 24 h
followed by frequent substrate to fresh medium and were inoculated with a loop full of
bacterial culture and spread throughout the petriplates uniformly with a sterile glass
spreader. To each disc, the test samples and reference antibiotic (amikacin) were added
with a sterile micropipette. The plates were then incubated at 35 ꢃ 2ꢂC for 24 h for
bacteria. Plates containing respective solvents served as control. Inhibition was
recorded by measuring the diameter of the inhibitory zone after incubation.
2.7. DNA-binding experiments
All experiments were carried out in buffer (5 mm Tris-HCl, 50 mm NaCl, pH 7.2) at
room temperature. A solution of calf-thymus DNA (CT-DNA) in buffer gave a ratio of

Thiosemicarbazone complexes
Table 1. Analytical data of the ligands and complexes.
821
Calculated (found) (%)
Ligand/complex
Color
Mol. mass
C
H
N
S
H2L1
Brown
Brown
Sandal
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
273
287
303
323
663
677
693
713
707
721
737
757
480
494
510
530
57.13(57.02)
58.52(58.96)
55.43(55.10)
63.14(63.72)
58.00(58.36)
58.57(58.93)
57.22(57.73)
60.67(60.12)
54.39(54.76)
55.00(55.41)
53.81(53.23)
57.14(57.73)
47.59(46.90)
48.68(48.47)
47.15(45.61)
52.17(51.91)
4.06(4.34)
4.56(4.23)
4.32(4.58)
4.05(4.52)
3.65(3.23)
3.87(3.61)
3.78(3.21)
3.68(3.41)
3.42(3.93)
3.64(3.41)
3.56(3.12)
3.46(3.66)
2.94(2.53)
3.27(3.30)
3.17(3.72)
3.05(2.83)
15.37(15.90)
14.62(14.30)
13.85(13.16)
12.99(12.72)
6.34(6.48)
6.21(6.78)
6.07(6.72)
5.90(5.60)
5.95(5.73)
5.83(5.61)
5.70(5.45)
5.55(5.21)
11.69(12.81)
11.35(11.81)
11.00(11.71)
10.58(10.16)
11.73(11.21)
11.16(11.72)
10.57(10.98)
9.92(9.16)
4.84(4.32)
4.74(4.52)
4.63(4.41)
4.50(4.22)
4.54(4.03)
4.45(4.21)
4.35(4.12)
4.24(4.71)
6.69(6.21)
6.50(6.13)
6.29(6.91)
6.06(6.59)
H2L2
H2L3
H2L4
[RuCO(PPh3)L1]
[RuCO(PPh3)L2]
[RuCO(PPh3)L3]
[RuCO(PPh3)L4]
[RuCO(AsPh3)L1]
[RuCO(AsPh3)L2]
[RuCO(AsPh3)L3]
[RuCO(AsPh3)L4]
[RuCO(Py)L1]
[RuCO(Py)L2]
[RuCO(Py)L3]
[RuCO(Py)L4]
UV absorbances at 260 and 280 nm of ca 1.8–1.9 : 1, indicating that the DNA was
sufficiently free of protein [26]. The concentration of CT-DNA per nucleotide was
determined spectrophotometrically ("260 ¼ 6600 (mol L
)
ꢁ1 ꢁ1 cmꢁ1) [27]. Stock solutions
were stored at 4ꢂC and used within 3 days. Titration experiments were performed at a
fixed complex concentration (20 mm), to which CT-DNA stock solution was added up
to a [DNA]/[Ru] ratio of 1 : 1. The mixture was allowed to equilibrate for 5 min before
spectra were recorded.
2.8. Viscosity measurements
For viscosity measurements, the Ubbelohde viscometer was thermostated at 25ꢂC in a
constant temperature bath. The concentration of DNA was 160 mm in NP and the flow-
times were determined with a digital timer (1/R ¼ [Ru]/[DNA] ¼ 0.5).
3. Results and discussion
Light- and air-stable ruthenium(II) complexes [Ru(CO)(B)(L)] [B ¼ PPh3/AsPh3 or
pyridine (py); L ¼ dibasic tetradentate Schiff-base ligand] have been prepared by
reacting [RuHCl(CO)(EPh3)2(B)], where E ¼ P/As; B ¼ PPh3/PPh3/Py with the respec-
tive Schiff bases in a 1 : 1 molar ratio in benzene–ethanol mixture. The analytical data
(table 1) for the complexes agree well with the proposed molecular formulae. In all
reactions, the Schiff bases are binegative tetradendate ligands.
3.1. Spectroscopic studies
3.1.1. FT-IR spectra. FT-IR spectra of the free ligands were compared with those of
the new complexes to confirm coordination of ligand to ruthenium (table 2). The ligand

822
Table 2. IR and electronic spectroscopic data of the ligands and complexes.
FT-IR (cmꢁ1
ꢁ–C¼N– ꢁPh–C–O ꢁ–C–S
G. Raja et al.
)
UV-Vis
Ligand/complex
ꢁPy
ꢂmax (nm)
303, 368
305, 363
"
(dm3 molꢁ1 cmꢁ1
)
max
H2L1
1625
1630
1620
1628
1603
1609
1602
1614
1602
1619
1601
1615
1602
1600
1600
1614
1266
1277
1263
1277
1290
1329
1320
1310
1306
1282
1310
1357
1302
1305
1315
1298
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
395, 498
528, 650
349, 441
315, 397, 467
3190, 3380
3168, 3395
1042, 1063, 1224
792, 369, 539, 173
827, 425, 103
1341, 1375, 1390
1600, 1519, 1499, 478
H2L2
H2L3
308, 368
H2L4
305, 370, 406
254, 355
252, 356
[RuCO(PPh3)L1]
[RuCO(PPh3)L2]
[RuCO(PPh3)L3]
[RuCO(PPh3)L4]
[RuCO(AsPh3)L1]
[RuCO(AsPh3)L2]
[RuCO(AsPh3)L3]
[RuCO(AsPh3)L4]
[RuCO(Py)L1]
[RuCO(Py)L2]
[RuCO(Py)L3]
[RuCO(Py)L4]
746
745
743
744
737
741
737
737
746
738
744
744
252, 294, 363
253, 294, 382, 484
258, 347, 450
252, 314, 342
253, 301, 349, 442
254, 334, 373, 383, 460 1058, 808, 716, 318, 100
1030 254, 294, 362, 456
1027 254, 301, 357
1025 254, 293, 362, 456
3618, 3163, 3085, 738
1731, 1565, 1543
727, 641, 628, 115
1032 253, 286, 373, 392, 472 648, 634, 622, 581, 194
can exhibit thione–thiol tautomerism. The FT-IR spectra of the free ligands showed a
band at 1620–1630 cmꢁ1 characteristic of the azomethine group (4C¼N), whereas in
complexes this band is slightly shifted to lower frequency at 1600–1619 cmꢁ1. This
indicates coordination of the Schiff bases through the azomethine nitrogen [28]. The
band of medium intensity at 1059–1061 cmꢁ1 in all ligands may be assigned to C¼S
stretch. In spectra of the complexes, this band disappears and a new band appears at
737–746 cmꢁ1, attributed to enolization of the –NH–C¼S group and subsequent
coordination through deprotonated sulfur [29]. For the ligands, strong bands at 681–
705 cmꢁ1 are due to the furan ring. On complexation, there is no change in the furan
ring owing to the non-involvement of the hetero atom in coordination. A strong band
due to phenolic C–O was observed at 1263–1277 cmꢁ1 in the ligands, shifted to higher
frequency (1282–1357 cmꢁ1) in the complexes, showing that the other coordination site
was through the phenolic oxygen [30–32]. This was further supported by the
disappearance of the broad band at 3219 cmꢁ1 due to phenolic OH in the complexes.
For all the complexes, IR spectra showed a strong band at 1930–1952 cmꢁ1 due to a
terminally coordinated carbonyl. For [Ru(CO)(Py)(L1)], [Ru(CO)(Py)(L2)],
[Ru(CO)(Py)(L3)], and [Ru(CO)(Py)(L4)], IR spectra showed a medium intensity
band at 1025–1032 cmꢁ1 characteristic of coordinated nitrogen base [22]. Characteristic
bands for triphenylphosphine/arsine were also present in the expected region 1428–
1435 cmꢁ1 [33].
3.1.2. Electronic spectra. Electronic absorption spectra of the free ligands and their
complexes in CH2Cl2 are listed in table 2. Spectra of all the free ligands showed two
types of transition at 303–308 and 363–406 nm due to ꢀ–ꢀ* and n–ꢀ* transitions
involving the benzene ring, –C¼N, and enolic S–H. These bands were shifted in spectra
of the complexes, indicating the involvement of imine group nitrogen and thionyl sulfur
in coordination with the central metal. Spectra of the complexes showed three to four

Thiosemicarbazone complexes
823
Table 3. 1H-NMR data of ligands and Ru(II) Schiff-base complexes.
Ligand/complex
1H-NMR spectra
H2L1
6.6–8.2 (Ar, m), 8.4 (H–C¼N, s), 11.3 (SH, s), 9.9 (Ph–OH, s)
H2L2
6.5–8.0 (Ar, m), 8.6 (H–C¼N, s), 11.9 (SH, s), 10.5 (Ph–OH, s), 1.9 (–CH3–C¼N, s)
6.8–7.9 (Ar, m), 8.4 (H–C¼N, s), 11.4 (SH, s), 9.2 (Ph–OH, s), 3.8 (–OCH3, s)
7.2–8.6 (Ar, m), 9.0 (H–C¼N, s), 11.4 (SH, s), 10.5 (Ph–OH, s)
6.5–7.9 (Ar, m), 8.4 (H–C¼N, s)
H2L3
H2L4
[RuCO(PPh3)L1]
[RuCO(PPh3)L2]
[RuCO(PPh3)L3]
[RuCO(PPh3)L4]
[RuCO(AsPh3)L1]
[RuCO(AsPh3)L2]
[RuCO(AsPh3)L3]
[RuCO(AsPh3)L4]
[RuCO(Py)L1]
[RuCO(Py)L2]
[RuCO(Py)L3]
[RuCO(Py)L4]
6.5–7.8 (Ar, m), 8.4 (H–C¼N, s), 2.0 (–CH3–C¼N, s)
6.9–7.7 (Ar, m), 8.5 (H–C¼N, s), 3.7 (–OCH3, s)
6.6–8.3 (Ar, m), 8.8 (H–C¼N, s)
6.5–7.9 (Ar, m), 8.1 (H–C¼N, s)
6.6–8.0 (Ar, m), 8.5 (H–C¼N, s), 2.0 (–CH3–C¼N, s)
6.9–7.9 (Ar, m), 8.4 (H–C¼N, s), 3.5 (–OCH3, s)
6.9–8.6 (Ar, m), 9.1 (H–C¼N, s)
7.7–8.0 (Ar, m), 8.3 (H–C¼N, s)
6.6–7.9 (Ar, m), 8.3 (H–C¼N, s), 2.0 (–CH3–C¼N, s)
6.6–7.8 (Ar, m), 8.4 (H–C¼N, s), 3.5 (–OCH3, s)
6.6–8.3 (Ar, m), 9.1 (H–C¼N, s)
bands at 252–484 nm. All Schiff-base ruthenium complexes were diamagnetic, indicat-
ing the presence of ruthenium(II). The ground state of ruthenium(II) in an octahedral
1
1
environment is A1g and the excited states corresponding to t2g5eg configuration
3
3
1
1
are T1g, T2g, T1g, and T2g. Hence, four bands corresponding to the transitions
1A1g ! T1g, A1g ! T2g, A1g ! T1g, and A1g ! T2g are possible in the order of
increasing energy. The high-intensity bands at 252–349 nm were characterized as ligand-
centered bands, designated as ꢀ–ꢀ* and n–ꢀ* transitions for electrons localized on the
azomethine of the Schiff base. The band at 355–484 nm has been assigned to the spin-
3
1
3
1
1
1
1
1
1
allowed A1g ! T1g transition, based on the low-extinction coefficient values (") as
compared to charge-transfer bands [34–37]. The pattern of the electronic spectra for
the complexes indicates the presence of an octahedral environment around the
ruthenium(II) similar to other ruthenium octahedral complexes [30, 34, 36, 37].
3.1.3. 1H-NMR spectra. 1H-NMR spectra of ligands and complexes were recorded in
DMSO-d6 to confirm the binding mode of the Schiff base to ruthenium ion; the values
are given in table 3 (Supplementary material). Aromatic protons for the ligands appear
as multiplets at 6.5–8.6 ppm. The H–C¼N, –SH, and Ph–OH protons appear as singlets
at 8.4–9.0, 11.3–11.9, and 9.2–10.5 ppm for all the Schiff bases. In H2L2, the azomethine
methyl protons are a singlet at 1.9 ppm. The methoxy protons of H2L3 are a singlet at
3.8 ppm. On complexation, a multiplet at 6.5–8.6 ppm is assigned to aromatic protons,
triphenylphosphine/arsine, and pyridine protons. The azomethine proton signals in the
complexes are at 8.1–9.1 ppm, shifted on complexation indicating coordination through
the azomethine nitrogen to metal ion. The azomethine methyl protons are a singlet at
2.0 ppm for [Ru(CO)(PPh3)L2], [Ru(CO)(AsPh3)L2], and [Ru(CO)(Py)L2], while
methoxy protons of [Ru(CO)(PPh3)L3], [Ru(CO)(AsPh3)L3], and [Ru(CO)(Py)L3] are
a singlet at 3.5–3.7 ppm. The absence of Ph–OH and –SH resonance in the complexes
indicates the deprotonation of phenol and thiol of the Schiff base on complexation and
coordination to ruthenium through phenolic oxygen and thiolic sulfur.

824
G. Raja et al.
Table 4. 13C-NMR spectra of Ru(II) Schiff-base complexes.
Ligand/complex
13C-NMR spectra
H2L1
112–132 (Ar, C), 140 (C–S), 156.2 (C¼N)
H2L2
114–125 (Ar, C), 131 (C–S), 150 (C¼N), 19(CH3)
112–121 (Ar, C), 139 (C–S), 148 (C¼N), 56 (–OCH3)
118–132 (Ar, C), 143 (C–S), 157 (C¼N)
H2L3
H2L4
[Ru(CO)(PPh3)(L4)]
[Ru(CO)(AsPh3)(L1)]
[Ru(CO)(AsPh3)(L2)]
[RuCO(Py)L3]
128–134 (Ar, C), 123 (C–S), 144 (C¼N), 180(CꢄO)
126–135 (Ar, C), 126 (C–S), 140 (C¼N), 177(CꢄO)
128–133 (Ar, C), 126 (C–S), 135 (C¼N), 19(CH3), 175(CꢄO)
128–134 (Ar, C), 123 (C–S), 148 (C¼N), 55 (–OCH3), 180(CꢄO)
3.1.4. 13C-NMR spectra. 13C-NMR data were recorded in CDCl3 solution and the
assignments of ligands and complexes are listed in table 4 (Supplementary material).
13C-NMR spectra of H2L1–H2L4 display a single resonance at 148–157 ppm for
azomethine carbons, which confirms the structure of ligands. The thiolic carbon of the
Schiff bases appeared at 131–143 ppm. The signal due to the methyl carbon of H2L2 and
methoxy carbon of H2L3 appear at 19 and 56 ppm, respectively. The aromatic carbons
for all the ligands appear at 112–132 ppm. For [Ru(CO)(PPh3)L4], [Ru(CO)(AsPh3)L1],
[Ru(CO)(AsPh3)L2], and [Ru(CO)(Py)L3], aromatic carbons appear at 126–135 ppm.
The thiolic carbon and azomethine carbons appear at 123–126 and 135–148 ppm [38],
respectively. The signals due to methyl carbon of [Ru(CO)(AsPh3)L2] and methoxy
carbon of [Ru(CO)(Py)L3] appear at 19 and 55 ppm, respectively. For all complexes, the
terminal carbonyl group appears at 175–180 ppm [39].
3.1.5. 31P-NMR spectra. 31P-NMR spectra were recorded for two complexes to
confirm the presence of triphenylphosphine and to determine the geometry of the
complexes. [Ru(CO)(PPh3)L4] has one signal at 28.62 ppm, confirming the presence of
only one triphenylphosphine.
3.1.6. Mass spectra. The mass spectrum of [RuCO(Py)L2] was recorded and the
appearance of molecular ion peak at 493.65 confirms the proposed molecular formula
of the complex. The mass spectrum of the complex is shown in Supplementary material.
3.2. Electrochemical study
Electrochemical properties of all the complexes were studied in dichloromethane
solution by cyclic voltammetry and voltammetric data are presented in table 5. Cyclic
voltammograms of all the complexes exhibit a quasireversible oxidation and an
irreversible reduction at scan rate of 100 mV sꢁ1. Representative cyclic voltammogram
of [Ru(CO)(PPh3)L3] is shown in Supplementary material. In Ru(III)–Ru(II) couple,
the complexes [Ru(CO)(PPh3)L1], [Ru(CO)(PPh3)L4], and [Ru(CO)(PPh3)L1] are
irreversible and [Ru(CO)(AsPh3)L2] and [Ru(CO)(Py)L1] are reversible, while the
remaining complexes are quasireversible [40] with peak to peak separation (DEp) of
130–740 mV. This is attributed to slow electron transfer and adsorption of the

Thiosemicarbazone complexes
825
Table 5. Cyclic voltammetry data of the Ru(II) Schiff-base complexes.a
RuIII–RuII
RuII–RuI
Epa (V) Ef (V)
Complex
Epc (V)
Epa (V)
Ef (V)
DEP (mV)
Epc (V)
DEP (mV)
[RuCO(PPh3)L1]
[RuCO(PPh3)L2]
[RuCO(PPh3)L3]
[RuCO(PPh3)L4]
[RuCO(AsPh3)L1]
[RuCO(AsPh3)L2]
[RuCO(AsPh3)L3]
[RuCO(AsPh3)L4]
[RuCO(Py)L1]
–
0.82
0.82
1.22
0.84
–
0.99
0.84
1.01
0.81
0.74
1.18
0.67
–
–
ꢁ0.71
–
ꢁ0.81
ꢁ0.63
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
0.44
0.50
–
0.63
1.11
–
380
720
–
–
80
540
740
100
130
490
270
0.94
0.91
0.30
0.27
0.91
0.87
0.69
0.94
–
ꢁ0.79
0.95
0.57
0.64
0.86
0.81
0.94
0.81
ꢁ0.30
–
–
–
–
–
–
ꢁ0.85
ꢁ0.82
ꢁ0.12
ꢁ0.16
–
[RuCO(Py)L2]
–
ꢁ0.73
–
–
ꢁ0.43
–
–
610
–
[RuCO(Py)L3]
[RuCO(Py)L4]
aSupporting electrolyte [NBu4]ClO4 (0.1 mol Lꢁ1); all potentials are referenced to Ag/AgCl; Ef ¼ 0.5(Epa þ Epc), where Epa
and Epc are anodic and cathodic peak potentials, respectively; scan rate, 100 mV sꢁ1
.
complexes on to the electrode surface [41]. The reason for the irreversibility observed
for the reductive response of the complexes may be due to a short-lived reduced state of
the metal ion or due to the oxidative degradation of the ligands [42]. The different redox
behavior of the complexes can be accredited to the different substituents present in the
thiosemicarbazone ligands [43]. From the electrochemical data, the present system
stabilizes the higher oxidation state of ruthenium.
3.3. Catalytic activity studies
3.3.1. Oxidation of alcohols. Activation of molecular oxygen by transition metals for
catalytic oxidation of organic substrates is of interest in organic synthesis [44, 45].
Catalytic oxidation of primary and secondary alcohols by free ligands, metal
precursors, and ruthenium(II) Schiff-base complexes were carried out in CH2Cl2
under oxygen at room temperature; the results are summarized in table 6 for
benzylalcohol, cyclohexanol, propane-1-ol, and butane-1-ol. After stirring for 6 h the
resulting carbonyl compounds were quantified as 2,4-dinitrophenyl hydrazone deriv-
atives by gravimetric estimation. Without the catalyst, only a very small amount of
carbonyl compound is formed during oxidation, which is insignificant compared with
the yields of carbonyl compounds obtained from reactions catalyzed by free ligands,
metal precursors, and ruthenium complexes. The precursor complexes have higher
activity than free ligands but lower than the newly synthesized complexes. All the new
complexes catalyze the oxidation of alcohol to aldehyde or ketone, but the yields and
turnover vary with different catalysts. Compared to other metal complexes, ruthenium
complexes have better catalytic activities for catalytic oxidation [44]. Catalytic
efficiencies of complexes derived from salicylaldehyde, 2-hydroxy-1-naphthaldehyde,
and amines were lower than those derived from o-hydroxyacetophenone and o-vanillin.
The essential difference between these complexes is that the hydrogen of the aldehyde of
salicylaldehyde and 2-hydroxy-1-naphthaldehyde is replaced by the electron-donating
methyl in o-hydroxyacetophenone and methoxy group in o-vanillin. Thus, it seems that

826
G. Raja et al.

Thiosemicarbazone complexes
827
the presence of electron-donating methyl and methoxy enhances the catalytic activity of
acetophenone and o-vanillin complexes over the other two, in agreement with earlier
observations [46]. However, there is a report in which the catalytic activity is increased
by electron-donating substituent [47, 48]. The relatively higher product yield
obtained for the oxidation of benzyl alcohol compared with the other alcohols is
because the ꢃ-CH of benzyl alcohol is more acidic than cyclohexanol, 1-propanol,
and butane-1-ol [49].
3.3.2. Aryl–aryl coupling reaction. The free ligands, metal precursors, and new
ruthenium(II) complexes have been used as catalysts for phenyl–phenyl coupling; the
results are summarized in table 6. The system chosen for study is the coupling of phenyl
magnesium bromide with bromobenzene to give biphenyl as product. Bromobenzene
was first converted into the corresponding Grignard reagent. Then bromobenzene
followed by the ligands and the complex chosen for investigations was added to the
above reagent and the mixture was heated under reflux for 6 h. After 6 h, the mixture
yielded biphenyl, which was compared with an authentic sample. Only a very small
amount of biphenyl was isolated when the reaction was carried out without the catalyst
[30]. The yield of biphenyl, obtained from the reaction catalyzed by the new
ruthenium(II) complexes, are low when compared to the yield obtained from reactions
catalyzed by [NiCl2(PPh3)2]. This may be due to the active species derived from
ruthenium complexes being less stable than the active species from [NiCl2(PPh3)2],
as the effectiveness of the catalysts is directly related to their ability to generate the
corresponding active species [24].
3.4. Antibacterial activity
The free ligands, metal precursors, and Schiff-base complexes were screened in vitro for
their antibacterial activity against certain pathogenic bacteria at four different
concentrations using the Kirby Bauer method [25]. These compounds exhibit
considerable activity against Gram positive (S. aureus) and Gram negative (E. coli)
bacteria. Test solutions were prepared in dichloromethane and the results are
summarized in table 7. Ruthenium chelates possess higher antibacterial activity than
the respective free ligands and metal precursors against the same bacteria, suggesting
that chelation facilitates the ability of a complex to cross a cell membrane [50–53].
Furthermore, the mode of action of the compounds may involve the hydrogen bond
through 4C¼N group with active centers of all cell constituents resulting in
interference with normal cell process [53]. The o-hydroxyacetophenone Schiff-base
complex showed more activity than salicylaldehyde Schiff-base complex due to the
presence of more electron-donating (–CH3) group in these complexes [54]. The present
results show that the ruthenium(II) carbonyl Schiff-base complexes possess better
cytotoxicity than other metal complexes against the same bacteria [55]. Although the
complexes were active, they did not reach the effectiveness of the conventional
bacteriocide amikacin.
3.5. DNA-binding studies – adsorption spectroscopic studies
DNA binding of [RuCO(PPh3)L2] was determined by following the changes in the
absorbance and shift in wavelength on each addition of DNA solution to the complex.

828
G. Raja et al.
Table 7. Antibacterial studies of metal precursors, ligands and Ru(II) Schiff-base complexes.
Diameter of inhibition zone (mm)
S. aureus
E. coli
Ligands, metal
precursors and
complexes
0.5%
1.0%
1.5%
2.0%
0.5%
1.0%
1.5%
2.0%
[RuHCl(CO)(PPh3)3]
[RuHCl(CO)(AsPh3)3]
[RuHCl(CO)(Py)(PPh3)2]
H2L1
–
3
5
5
8
10
12
10
15
10
5
5
5
6
7
9
7
9
9
2
4
5
–
–
4
3
5
6
8
–
5
8
5
7
7
13
–
7
6
7
9
5
5
6
8
11
8
10
23
29
28
25
25
32
28
23
23
31
29
23
26
30
29
–
12
14
15
17
13
21
17
8
15
19
17
13
13
20
18
–
18
23
19
21
18
30
25
18
19
25
23
18
18
25
25
–
H2L2
10
14
21
20
20
28
–
23
29
31
32
35
29
27
26
26
H2L3
12
15
14
16
20
–
14
21
24
26
20
21
21
20
23
H2L4
8
[RuCO(PPh3)L1]
[RuCO(PPh3)L2]
[RuCO(PPh3)L3]
[RuCO(PPh3)L4]
[RuCO(AsPh3)L1]
[RuCO(AsPh3)L2]
[RuCO(AsPh3)L3]
[RuCO(AsPh3)L4]
[RuCO(Py)L1]
[RuCO(Py)L2]
[RuCO(Py)L3]
[RuCO(Py)L4]
Amikacin
10
12
14
–
8
9
12
10
7
14
15
18
20
15
13
14
21
9
10
12
8
9
9
19
7
13
10
–
20
22
23
26
A representative absorption spectrum is given in figure 1. In the figure, the blank
represents the absorption spectra without DNA and 5, 10, 15, and 20 mmol represents
the concentration of the CT-DNA. The ruthenium(II) complex in DMSO buffer
mixture exhibits an intense transition around 360–310 nm, which is attributed to a
ꢀ ! ꢀ* intraligand transition. On titration of CT-DNA with the complex, considerable
increase or decrease in the absorption along with small red or blue shift was observed.
The titration process was repeated until no further change was observed in the
spectrum. The complex exhibits 52% hypochromicity and 2 nm bathochromism in the
presence of DNA at saturation. During the titration, the extent of hypochromicity
and bathochromism varied, implying binding of the complex to DNA through
different modes [56]; the hypochromism confirms strong binding of the complex
to DNA.
3.6. Viscosity measurements
Viscosity measurements which are sensitive to length change are regarded as the most
critical tests for binding mode. Changes in relative viscosity provide a reliable method
for distinguishing between intercalators and electrostatic binders of DNA. The effect of
[RuCO(PPh3)L2] on the viscosity of CT-DNA is shown in figure 2. With the increasing
amounts of the complex, the viscosity of DNA increases steadily showing that the
complex binds to CT-DNA through intercalation [56].

Thiosemicarbazone complexes
829
Figure 1. Absorption titration of [RuCO(PPh3)L2] with CT-DNA.
1.20
1.18
1.16
1.14
1.12
1.10
1.08
1.06
1.04
1.02
1.00
a
b
0
10
20
30
40
50
–3
µ10
1/R = {[Ru-complex]/[DNA]}
Figure 2. The effect of (a) [RuCO(PPh3)L2] and (b) CT-DNA on the viscosity of CT-DNA at 1/R ¼ 0.5
relative viscosity vs. 1/R.
4. Conclusion
A group of mononuclear octahedral ruthenium(II) Schiff-base complexes have been
synthesized. All ruthenium(II) Schiff-base complexes have been examined for their
catalytic efficiency in oxidation of alcohols to their corresponding carbonyl compounds
with molecular oxygen at room temperature and also for C–C coupling reactions.
Compared to previous literature [57,58], certain newly synthesized complexes show
good antibacterial activity, higher than their respective standards. Finally, with

830
G. Raja et al.
absorption titration studies and viscosity measurements, it can be concluded that the
complexes bind to CT-DNA through intercalation.
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