Solvent induced geometry transformation of trigonal planar Cu(I) complexes of N-((2/4-methyoxy carbonyl) phenyl)-N′-(ethoxy/methoxy carbonyl) thiocarbamides to square-planar Cu(II) complexes: Synthesis, spectral, single crystal, DFT and in vitro cytotoxic

Article abstract of DOI:10.1016/j.ica.2014.08.031

Complexation between copper(II) chloride and three newly synthesized ligands, (N-((2/4-methyoxy carbonyl) phenyl)-N′-(ethoxy carbonyl) thiocarbamides (2/4-MCPET)(1, 2) and (N-(2-methyoxy carbonyl phenyl)-N′-(methoxy carbonyl) thiocarbamide (2-MCPMT)(3) af

Full text of DOI:10.1016/j.ica.2014.08.031

Inorganica Chimica Acta 423 (2014) 386–396
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Solvent induced geometry transformation of trigonal planar Cu(I)
complexes of N-((2/4-methyoxy carbonyl) phenyl)-N0-(ethoxy/methoxy
carbonyl) thiocarbamides to square-planar Cu(II) complexes: Synthesis,
spectral, single crystal, DFT and in vitro cytotoxic study
b
Durga P. Singh a, Seema Pratap a, , Madhulata Shukla
⇑
a Department of Chemistry (M.M.V), Banaras Hindu University, Varanasi 221 005, India
b Department of Chemistry, Banaras Hindu University, Varanasi 221 005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2014
Received in revised form 19 August 2014
Accepted 21 August 2014
Available online 3 September 2014
Complexation between copper(II) chloride and three newly synthesized ligands, (N-((2/4-methyoxy car-
bonyl) phenyl)-N0-(ethoxy carbonyl) thiocarbamides (2/4-MCPET)(1, 2) and (N-(2-methyoxy carbonyl
phenyl)-N0-(methoxy carbonyl) thiocarbamide (2-MCPMT)(3) afforded Cu(I) complexes bis(N-((2/4-
methoxycarbonyl) phenyl)-N’-(ethoxycarbonyl) thiocarbamide) copper(I) chloride (2/4-MCPET)2CuCl(1a,
2a) and bis(N-((2-methoxycarbonyl) phenyl)-N’-(methoxycarbonyl) thiocarbamide) copper(I) chloride
(2-MCPMT)2CuCl(3a). The geometry transformation reaction of above copper(I) complexes in
DCM-DMSO (3:1, v/v) mixture of solvents resulted in dark green Cu(II) complexes bis(N-((2/4-methoxy-
carbonyl) phenyl)-N’-(ethoxycarbonyl) thiocarbamide) copper(II) (2/4-MCPET)2Cu(1a0, 2a0) and bis
(N-((2-methoxycarbonyl) phenyl)-N’-(methoxycarbonyl) thiocarbamide) copper(II) (2-MCPMT)2Cu(3a0).
Spectroscopic studies together with single crystal analysis of (2-MCPMT)2CuCl revealed trigonal planar
structure for Cu(I) complexes in which ligand coordinates to the metal ion in neutral monodentate fash-
ion through sulfur only. The physico-chemical studies of Cu(II) complexes together with single crystal
data of (2/4-MCPET)2Cu(1a0) support their distorted square-planar geometry, with formation of 1,3-N,S
four-membered chelate ring. The N, S coordination observed for the first time in Cu(II) complexes is sta-
bilized by the intramolecular hydrogen bonding present in them. Complex 1a shows quasi-reversible
redox behavior assignable to Cu(I)/Cu(II) one electron transfer. Theoretical study on (2-MCPET)2Cu(1a0)
was performed to concrete the spectral study and structure of the complexes. Ligands and their Cu(I)
complexes have been screened for their in vitro cytotoxicity against five human cancer cell lines.
Ó 2014 Elsevier B.V. All rights reserved.
Keywords:
Single crystal
Copper complexes
Geometry transformation
Thiocarbamides
1. Introduction
has been observed for them but in few cases trans orientation
has also been reported [17,18]. The presence of intramolecular
There is a continued interest in synthesis and structural studies
of transition metal complexes of N-substituted-N0-acyl/alkoxy car-
bonyl thioureas because of their potential applications in analytical
[1–3], material [4–7], biological fields and importance in the area
of coordination chemistry [8–10]. Substituted thioureas have been
reported to display versatile coordination behavior which may be
due to the presence of N, S and O as donor atoms [11–16]. N,
N-disubstituted thioureas in the majority of their complexes with
transition metal ions having d8 and d9 configuration function as
monoanionic bidentate ligand coordinating through O and S.
Predominantly square-planar geometry with cis-configuration
hydrogen bonding and nature of N-substituents in the case of
N,N0-disubstituted thioureas significantly affect their ligational
behavior [8,13,14]. Mainly two modes of coordination have been
reported, the one is coordination through thione S which is very
common and other scantly reported is through N and S. It has been
established that intramolecular hydrogen bonds N–Hꢀ ꢀ ꢀO@C are a
necessary condition for the 1, 3-N,S-chelate ring stabilization in
square-planar complexes. In the present paper we report for the
first time N, S coordination mode of N,N0-disubstituted thioureas
in their Cu(II) complexes. To understand and analyze the
spectroscopic properties of the Cu(II) complexes, an extensive
DFT calculations on (2-MCPET)2Cu(1a0) using B3LYP functional
have been carried out. DFT coupled with TD-DFT calculations have
been performed to ascertain the nature of orbitals involved in
⇑
Corresponding author. Fax: +44 1223 336033.
E-mail address: drseemapratap@gmail.com (S. Pratap).
http://dx.doi.org/10.1016/j.ica.2014.08.031
0020-1693/Ó 2014 Elsevier B.V. All rights reserved.

D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
387
transition processes and to correlate the structural parameters
with the spectroscopic properties of the complex [19–23].
and added fresh culture medium 100
MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bro-
l
l containing 0.5 mg/ml
mide; Sigma) and then incubated at 37 °C for 4 h. The medium
was removed and 100 ll DMSO was added to dissolve the dark
2. Experimental
blue crystals. After incubation for 30 min at room temperature to
ensure that all crystals were dissolved, absorbance was measured
using an ELISA plate reader at 570 nm with a reference wavelength
of 650 nm.
2.1. Physical measurements
Elemental analyses were performed on a CE-440 Exeter Analyt-
ical CHN analyzer. The infrared spectra of the title compounds as
KBr pellets (4000–400 cmꢁ1) were recorded on a Varian 3100 FT-
IR Excalibur series spectrophotometer. 1H and 13C NMR spectra
were obtained on a JEOL FT-NMR AL 300 spectrometer in CDCl3
with chemical shifts relative to SiMe4. Electronic spectra were
recorded on an (UV)-1700 Pharma Spec. Shimadzu UV–Vis spectro-
photometer. The electronic spectra of ligands 1–3 and complexes
1a–3a were recorded in DCM whereas complexes 1a0–3a0 was
recorded in solid state in Nujol. Room temperature magnetic
susceptibility measurements were performed on a Cahn Faraday
balance using Co[Hg(SCN)4] as standard. The magnetic susceptibil-
ity was corrected for diamagnetism using Pascal’s constants [24].
The cyclic voltammogram of (2-MCPET)2CuCl(1a) was recorded at
a Pyrolytic Graphite Electrode (PGE) by using anhydrous solutions
of the metal complex in dichloromethane containing Bu4NClO4
(TBAP) (0.1 m) as supporting electrolyte in the potential range
0.2 to 1.3 V at different scan rates ranging from 20–100 mV/s.
Platinum wire was used as the counter electrode and Ag/AgCl as
reference electrode.
2.4. Synthesis of ligands
The ligands (1–3) were prepared by a slightly altered procedure
to that reported in the literature [31,32]. A solution of ethyl chlo-
roformate/methyl chloroformate in acetone (30 mL) was added
drop wise to the solution of ammonium thiocyanate (10 mmol,
0.76 g) in acetone (30 mL) in ten minutes duration. The resulting
solution was refluxed for 45 min at 70 °C. After cooling to room
temperature, a solution of methyl-2-amino benzoate (10 mmol,
1.30 mL)/methy-4-amino benzoate (10 mmol, 1.51 g) was added
drop wise to the above solution and the resulting mixture was
refluxed for 75 min. The precipitated ammonium chloride was
filtered off and the clear solution was evaporated in vacuum to dry-
ness to yield a crude yellowish product, which was recrystallized
from acetone to obtain X-ray quality single crystals in one week.
2.4.1. N-((2-methoxycarbonyl) phenyl)-N0-(ethoxycarbonyl)
thiocarbamide (2-MCPET) (1)
Yield: 82%, m.p.; 126–128 °C. Anal. Calc. for C12H14N2O4S1: C,
51.07; H, 5.00; N, 9.92. Found: C, 51.15; H, 5.06; N, 10.02%. IR
2.2. Single-crystal structure determination
(KBr, cmꢁ1): (3434, 3292),
m
m
(N–H); 3041,
(–COOMe); 1694,
1579), (Ph, C@C); 1532, d(N–H); 1375,
(N@C@S); (1278, 759),
(C@S). 1H NMR (300 MHz, CDCl3, 25 °C):
m
(aromatic C–H); 2985,
(–COOEt); (1606,
(–NC(S)N); 1177,
m(aliphatic C–H); 1730,
m
m
Crystal data for ligand 2-MCPET(1) was collected on a ‘Xcalibur,
Eos’ diffractometer equipped with graphite monochromated Mo
m
K
a
radiation (k = 0.71073 Å) at 293 K and for complexes
(2-MCPET)2CuCl(1a) and (2-MCPET)2Cu(1a0) on ‘Bruker Apex 2’
diffractometer using graphite monochromated Mo K radiation
d 12.61 (s, 1H, –CSNH), 8.10 (s, 1H, –CONH), 8.46 (d, J = 8.1, 1H,
C6H4), 7.99 (d, J = 6.6 Hz, 1H, C6H4), 7.55 (t, J = 7.2 Hz, 1H, C6H4),
7.26 (t, J = 6.9 Hz, 1H, C6H4), 4.30 (q, J = 4.2 Hz, 2H, OCH2), 3.92 (s,
1H, –COOCH3), 1.33 (t, J = 4.2 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 25 °C): 178.00 (C, C@S), 166.45(C, COOMe), 151.65 (C,
C@O), 138.49, 132.21, 130.49, 126.27, 125.58, 121.93 (C, Aromatic),
62.66 (C, OCH2), 52.32 (C, OCH3), 14.01 (CH3).
a
(k = 0.71073 Å) at 296 K. The structures were solved by direct
methods and refined by full matrix least squares on F2 using
SHELX-97 [25]. The non-hydrogen atoms were refined with aniso-
tropic thermal parameters. All the hydrogen atoms were geometri-
cally fixed and allowed to refine using a riding model. The
refinement converged to a final R1 = 0.0563, wR2 = 0.0799 for 1,
R1 = 0.0451, wR2 = 0.098 for 1a and R1 = 0.0496, wR2 = 0.1168 for
1a0. Drawings were made using ORTEP-III [26] and MERCURY [27].
2.4.2. N-((4-methoxycarbonyl) phenyl)-N0-(ethoxycarbonyl)
thiocarbamide (4-MCPET) (2)
Yield: 80%, m.p.; 170–172 °C. Elemental Anal. Calc. for C12H14N2
O4S1 (%); C, 51.05: H, 4.99: N, 9.92. Found: C, 51.12; H, 5.04; N,
9.98%. IR (KBr, cmꢁ1): (3424, 3156),
m
(N–H); 3048,
(–COOMe); 1798,
(1606, 1579), (Ph, C@C); 1530, d(N–H); 1385, (–NC(S)N)); 1177,
(N@C@S); (1278, 759),
(C@S). 1H NMR (300 MHz, CDCl3, 25 °C):
m
(Aromatic
2.3. Biological assays
C–H); 2968,
m(Aliphatic C–H); 1724,
m
m(–COOEt);
2.3.1. Cell lines
m
Two human cervical cancer cell lines (2008 and C13⁄) and three
ovarian cancer cell lines (IGROV-1, A2780 and A2780/CP) were
used. Among these C13⁄ and A2780/CP are cisplatin (ccDDP) resis-
tant cells [28,29]. Cells were grown as monolayers in RPMI 1640
medium containing 10% heat-inactivated fetal bovine serum and
m
m
d 11.71 (s, 1H, –CSNH), 8.18 (s, 1H, –CONH), 8.06 (d, J = 8.7 Hz,
2H, C6H4), 7.81 (d, J = 8.7 Hz, 2H, C6H4), 4.29 (q, J1 = 7.2 Hz,
J2 = 6.9, J3 = 7.2, 2H, OCH2), 3.91 (s, 3H, –COOCH3), 1.35 (t,
J1 = 7.2 Hz, J2 = 6.9, 3H, CH3); d 13C NMR (75 MHz, CDCl3, 25 °C):
177.37 (C, C@S), 166.30 (C, C@O), 152.77 (C, COOMe), 141.60,
130.39, 127.85, 123.00 (C, Aromatic), 63.25 (C, OCH2), 52.16 (C,
COOCH3), 14.15 (C, CH3).
50 lg/ml gentamycin sulfate. All cell media and serum were pur-
chased from Lonza (Verviers, Belgium). Cultures were equilibrated
with humidified 5% CO2 in air at 37 °C. All studies were performed
in Mycoplasma negative cells, as routinely determined with the
MycoAlert Mycoplasma detection kit (Lonza, Walkersville, MD,
USA).
2.4.3. N-((2-methoxycarbonyl) phenyl)-N0-(methoxycarbonyl)
thiocarbamide (2-MCPMT) (3)
Yield: 76%, m.p.; 90–92 °C. Elemental Anal. Calc. for C11H12N2O4S,
M = 268.05: C, 49.25: H, 4.51: N, 10.44. Found: C, 49.32; H, 4.56; N,
2.3.2. Cytotoxicity screening
In vitro cytotoxicity of compounds used in the present study
was determined by MTT assay [30]. The cells were seeded into
96-well plates and cultured overnight. Various concentrations of
the test compounds dissolved in DMSO were then added and
incubated for 72 h. After incubation, the medium was removed
10.48%. Electronic (CH2Cl2, kmax
,
nm)
(
e
,
L molꢁ1 cmꢁ1): 310
(N–H); 3014,
(–COOMe); 1712,
(Ph, C@C); 1540, d(N–H); 1364,
(N@C@S); (1255, 711), (C@S);
(12,880), 245 (22400). IR (KBr, cmꢁ1): (3438, 3171),
m
m
m
m
(aromatic C–H); 2953,
(–NHCOOMe); (1610, 1584),
(–NC(S)N); 1309, (NCN); 1197,
m(aliphatic C–H); 1727, m
m
m
m
m
m

388
D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
Scheme 1. Synthesis of ligands (1–3) and their Cu-1 (1a-3a) and Cu-II (1a0-3a0) complexes.
Table 1
1H NMR (300 MHz, CDCl3, 25 °C): d 12.63 (s, 1H, b–CSNH), 8.14 (s,
1H, –CONH), 8.49 (d, J = 8.4 Hz, 1H, C6H4), 8.01 (d, J = 7.8 Hz, 1H,
C6H4), 7.57 (t, J = 6.9 Hz, 1H, C6H4), 7.28 (t, J = 7.2 Hz, 1H, C6H4),
3.94 (s, 3H, –NHCOOCH3), 3.87 (s, 3H, ArCOOCH3); 13C NMR
(75 MHz, CDCl3, 25 °C): 179.26 (C, C@S), 165.75 (C, C@O), 153.55
(C, –COOMe), 138.10, 132.30, 130.18, 129.35, 127.81, 126.22,
123.73 (C, Aromatic), 52.98 (C, –NHCOOCH3), 52.40 (C, –COOCH3).
Important crystallographic data of ligand (1), complex (1a) and (1a0).
Compound
2-MPECT (1)
(2-MPECT)2CuCl
(1a)
(2-MPECT)2Cu
(1a0)
Empirical formula
C
12H14N2O4S1 C24H28ClCuN4O8
C24H26CuN4O8S2
S2
Formula weight
T (K)
k (Å)
Crystal system
Space group
a (Å)
282.2
663.61
296(2)
0.71073
triclinic
626.15
293(2)
0.71073
triclinic
293(2) K
0.71073
triclinic
ꢀ
ꢀ
ꢀ
P1
P1
P1
8.534(3)
8.851(3)
9.968(3)
70.31(3)
72.74(3)
76.90(2)
670.3(4)
3
8.011(3)
11.180(3)
16.802(5)
79.139(5)
83.134(6)
83.616(6)
1461.2(8)
2
7.643(5)
11.635(5)
15.572(5)
98.979(5)
101.625(5)
98.176(5)
1318.0(11)
2
2.5. Synthesis of complexes 1a–3a and 1a0–3a0
b (Å)
c (Å)
To 30 cm3 of ethanol containing the appropriate ligand
(2 mmol) was added an ethanolic solution of copper(II) chloride
(1 mmol) with constant stirring. The solution was further stirred
at room temperature for 2 h. The complexes precipitated as light
yellow colored solid, were filtered, washed with ethanol and dried
in vacuum. The light yellow crystals suitable for X-ray diffraction
were obtained only in case of 1a in DCM-ACN (3:1, v/v) mixture
of solvents in one week. The Cu(II) complexes 1a0–3a0 were
obtained as green colored solid, during crystallization procedure
of Cu(I) complexes 1a–3a in DCM-DMSO (3:1, v/v) mixture in
one week at 10 °C. Only crystals of 1a0 were found suitable enough
to be diffracted.
a
(°)
b (°)
c
(°)
V (Å3)
Z
qcalc (g cmꢁ3
)
1.399
1.508
1.578
l
(mmꢁ1
)
0.271
1.034
1.043
R (F2o)a
0.0563
0.1631
0.991
0.0451
0.098
1.007
0.0496
0.1168
0.974
Rw (F2o)b
Goodness-of-fit
(GOF)
P
P
a
R = ||Fo| ꢁ |Fc||/ |Fo|.
P
P
Rw = [ w(Fo ꢁ Fc 2)2/ w(Fo4)]1/2.
b
2
Table 2
Selected bond length(Å) and bond angles(°) for 2-MPECT (1) and (2-MPECT)2Cu Cl(1a).
Bond length (Å)
2-MPECT(1)
Bond length
(2-MPECT)2Cu Cl(1a)
S(1)–C(9)
C(10)–O(3)
N(2)–C(9)
N(1)–C(9)
N(2)–C(10)
Bond angles
N(1)–C(9)–S(1)
N(2)–C(9)–S(1)
N(1)–C(9)–N(2)
C(10)–N(2)–C(9)
O(3)–C(10)–N(2)
O(4)–C(10)–N(2)
O(3)–C(10)–O(4)
C(10)-O(4)-C(11)
1.653(3)
1.195(4)
1.400(4)
1.346(4)
1.384(4)
S(1A)–C(9A)
C(10A)–O(3A)
N(2A)–C(9A)
N(1A)–C(9A)
N(2A)–C(10A)
Cu–S(1A)
1.690(3)
1.195(4)
1.369(4)
1.334(4)
1.385(4)
2.2177(11)
2.2343(10)
S(1B)–C(9B)
C(10B)–O(3B)
N(2B)–C(9B)
N(1B)–C(9B)
N(2B)–C(10B)
Cu–S(1B)
1.679(3)
1.196(4)
1.370(4)
1.334(4)
1.373(4)
2.2178(10)
127.2(2)
118.2(2)
114.5(3)
127.8(2)
126.4(3)
108.4(3)
125.2(3)
115.4(2)
Cu–Cl(1)
Bond angles
S(1A)–Cu–Cl(1)
C(9A)–S(1A)–Cu
N(1A)–C(9A)–N(2A)
N(1A)–C(9A)–S(1A)
N(2A)–C(9A)–S(1A)
S(1A)-Cu-S(1B)
123.61(4)
111.09(10)
116.6(3)
123.9(2)
119.5(2)
113.04(3)
S(1B)–Cu–Cl(1)
C(9B)–S(1B)–Cu
N(1B)–C(9B)–N(2B)
N(1B)–C(9B)–S(1B)
N(2B)–C(9B)–S(1B)
123.04(4)
111.27(10)
116.6(3)
123.1(2)
120.3(2)

D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
389
Table 3
Selected bond length and bond angles of (2-MCPET)2Cu(1a0). DFT calculated values are given in parenthesis.
Bond length
(2-MPECT)2Cu (1a0)
Bond angles (°)
(2-MPECT)2Cu (1a0))
Cu–N(1A)
Cu–N(1B)
Cu–S(1A)
Cu–S(1B)
C(9A)–S(1A)
S(1B)–C(9B)
C(9A)–N(1A)
C(9B)–N(1B)
N(2A)–C(9A)
N(2B)–C(9B)
1.9639(1.97)
1.9598(1.97)
2.3492(2.48) Å
2.3472(2.48) Å
1.721(1.78)
1.711(1.78)
1.355(1.37)
1.350(1.37)
1.343(3)
S(1B)–Cu–S(1A)
N(1A)–Cu–N(1B)
N(1A)–Cu–S(1A)
N(1B)–Cu–S(1B)
N(1A)–Cu–S(1B)
N(1B)–Cu–S(1A)
N(1A)–C(9A)–S(1A)
N(1B)–C(9B)–S(1B)
C(9A)–N(1A)–Cu
C(10A)–N(1A)–Cu
C(9B)–N(1B)–Cu
C(10B)–N(1B)–Cu
C(9A)–S(1A)–Cu
C(9B)–S(1B)–Cu
175.47(179.9ꢁ)
172.49(172.1ꢁ)
70.93(70.2ꢁ)
71.02(70.2)
107.40(109.7)
110.07(108.4)
109.60(109.8)
110.31(109.5)
101.64(104.5)
134.40(132.5)
101.17(104.2)
135.26(132.5)
77.75(75.4)
1.339(3)
77.43(75.4)
Found: C, 43.50; H, 4.27; N, 8.53%. IR (KBr, cmꢁ1): 3168,
m
(N–H);
Table 4
Important hydrogen bonding interactions of (1), 1a and 1a0[Å and °].
3071,
1720,
m
m
(aromatic C–H); 2951,
(–COOEt); (1606, 1560),
(N@C@S); (729, 1260), m
m
(aliphatic C–H); 1722,
(Ph, C@C); 1524, d(N–H); 1373,
(C@S). 1H NMR
m(–COOMe);
m
D–H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
<(DHA)
m(–NC(S)N); 1179,
m
1
(300 MHz, CDCl3, 25 °C): d 11.83 (s, 2H, –CSNH), 11.01 (s, 2H,
–CONH), 8.07 (d, J = 8.4 Hz, 4H, C6H4), 7.57 (d, J = 8.4 Hz, 4H,
C6H4), 4.37 (q, J = 7.2 Hz, 4H, OCH2), 3.92 (s, 6H, –COOCH3), 1.40
(t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3, 25 °C): d 175.82
(C, C@S), 166.05 (C, –COOMe), 153.99 (C, C@O), 140.21, 130.52,
129.10, 124.91 (C, Aromatic), 63.71 (C, OCH2), 52.34 (C, –COOCH3),
14.15 (CH3).
N(1)–H(1 N)ꢀ ꢀ ꢀO(3)
N(1)–H(1 N)ꢀ ꢀ ꢀO(1)
N(2)–H(2 N)ꢀ ꢀ ꢀO(1)#1
0.92(3)
0.92(3)
0.90(3)
2.02(3)
2.19(3)
2.17(3)
2.709(3)
2.684(3)
2.970(3)
130(2)
113(2)
148(2)
1a
N(1A)–H(1AA)ꢀ ꢀ ꢀO(3A)
0.82(3)
0.82(3)
0.81(3)
0.84(3)
0.84(3)
0.84(3)
0.84(3)
1.95(3)
2.19(3)
2.50(3)
1.93(3)
2.19(4)
2.19(4)
2.48(3)
2.655(4)
2.631(4)
3.292(3)
2.646(3)
2.696(15)
2.696(15)
3.308(3)
144(3)
115(3)
168(3)
143(3)
119(3)
119(3)
168(3)
N(1A)–H(1AA)ꢀ ꢀ ꢀO(2A)
N(2A)–H(2AB)ꢀ ꢀ ꢀCl(1)
N(1B)–H(1BA)ꢀ ꢀ ꢀO(3B)
N(1B)–H(1BA)ꢀ ꢀ ꢀO(2BA)
N(1B)–H(1BA)ꢀ ꢀ ꢀO(2BA)
N(2B)–H(2BB)ꢀ ꢀ ꢀCl(1)
2.5.3. Bis (N-((2-methoxycarbonyl) phenyl)-N0-(methoxycarbonyl)
thiocarbamide) copper(I) chloride (2-MCPMT)2CuCl (3a)
1a0
Yield: 70%, m.p.; 126–128 °C. Elemental Anal. Calc. for C22H24
ClCuN4O8S2, M = 635.58, (%), C, 41.57; H, 3.80; N, 8.81. Found, C,
C8AAa–H8AAa...O(1B)#1
C8AAa–H8ACa...O3BAa#1
C8ABb–H8ADb...O(1B)#1
C8ABb–H8AEb...O3BBb#1
N(2A)–H(2NA)ꢀ ꢀ ꢀO(1A)
N(2A)–H(2NA)ꢀ ꢀ ꢀO3AAa
N(2A)–H(2NA)ꢀ ꢀ ꢀO3ABb
C(2A)–H(2AA)ꢀ ꢀ ꢀS(1A)
N(2B)–H(2NB)ꢀ ꢀ ꢀO(1B)
N(2B)–H(2NB)ꢀ ꢀ ꢀO3BAa
N(2B)–H(2NB)ꢀ ꢀ ꢀO3BBb
C(2B)–H(2BA)ꢀ ꢀ ꢀS(1B)
0.96
0.96
0.96
0.96
0.75(2)
0.75(2)
0.75(2)
0.93
0.72(2)
0.72(2)
0.72(2)
0.93
2.47
2.24
2.56
2.54
2.10(2)
2.09(3)
2.19(3)
2.43
2.11(2)
2.13(3)
2.22(3)
2.64
3.050(15)
3.09(2)
3.177(12)
3.037(14)
2.711(3)
2.68(2)
2.774(14)
3.130(2)
2.678(3)
2.668(15)
2.728(10)
3.144(2)
118.8
147.2
121.8
112
140(2)
136(2)
136(2)
132.2
136(2)
132(2)
129(2)
114.4
41.64; H, 3.82; N, 8.86%. Electronic (CH2Cl2, kmax, nm) (
e
, L molꢁ1
cmꢁ1): 398 (1,720), 291 (8,250). IR (KBr, cmꢁ1): 3117,
m
(N–H);
3090,
m
(aromatic C–H); 2960,
m
(aliphatic C–H); 3171,
m
(N–H);
3014, (aromatic C–H); 2953,
m
(aliphatic C–H); 1727, m(–COOMe);
1720,
1363,
m
(–NHCOOMe); (1607, 1585) (Ph, C@C); 1526, d(N–H);
m
(–NC(S)N); 1189, (N@C@S); (705, 1234),
m
m
(C@S). 1H NMR
(300 MHz, CDCl3, 25 °C): d 12.51 (s, 2H, –CSNH), 11.14 (s, 2H,
–CONH), 8.03 (d, J = 7.8 Hz, 2H, C6H4), 7.98 (d, J = 8.1, 2H, C6H4),
7.54 (t, J = 7.2 Hz, 2H, C6H4), 7.34 (t, J = 7.2 Hz, 2H, C6H4), 3.92 (s,
6H, –NHCOOCH3), 3.92 (s, 6H, –ArCOOCH3); 13C NMR (75 MHz,
CDCl3, 25 °C): 178.47 (C, C@S), 166.04 (C, –COOMe), 153.60 (C,
C@O), 136.97, 132.45, 130.97, 127.90, 127.15, 123.78 (C, Aromatic),
53.93 (C, –NHCOOCH3), 52.61 (C, –COOCH3).
Symmetry transformations used to generate equivalent atoms: #1 x, y, z + 1.
2.5.1. Bis (N-((2-methoxycarbonyl) phenyl)-N0-(ethoxycarbonyl)
thiocarbamide) copper(I) chloride (2-MCPET)2CuCl (1a)
Yield: 70%, m.p.; 185–187 °C. Elemental Anal. Calc. for C24H28-
ClCuN4O8S2, M = 663.63 (%), C, 43.43; H, 4.25; N, 8.44. Found: C,
2.5.4. Bis (N-((2-methoxycarbonyl) phenyl)-N0-(ethoxycarbonyl)
thiocarbamide) copper(II) (2-MCPET)2Cu (1a0)
Yield: 75%, m.p.; decompose at 265–267 °C. Elemental Anal.
Calc. for C24H26CuN4O8S2, M = 626.16, (%), C, 46.03; H, 4.18; N,
8.94. Found: C, 46.09; H, 4.21; N, 9.01%. IR (KBr, cmꢁ1): 3095,
43.51; H, 4.29; N, 8.52%. IR (KBr, cmꢁ1): 3153,
m
(N–H); 3004,
(–COOMe);
(Ph, C@C); 1541, d(N–H); 1346,
(C@S); 1H NMR
m
(aromatic C–H); 2983,
m
(Aliphatic C–H); 1725, m
1724,
m
m(–COOEt); (1606, 1581), m
(–NC(S)N); 1176,
m
(N@C@S); (1260, 714),
m
m
(N–H); 3019,
m
(aromatic C–H); 2985,
m
(aliphatic C–H); 1714,
(–COOEt); (1605, 1581), (C@C, Ph); 1528,
(N@C@S); (1273, 698), (C@S);
(300 MHz, CDCl3, 25 °C): d 12.53 (s, 2H, –CSNH), 11.01 (s, 2H,
–CONH), 8.07 (m, 4H, C6H4), 7.53 (d, J = 7.5 Hz, 2H, C6H4), 7.33
(d, J = 7.5 Hz, 2H, C6H4), 4.38 (q, J = 7.2 Hz, 4H, OCH2), 3.92 (s, 6H,
–COOCH3), 1.40 (t, J = 7.2 Hz, 6H, CH3); 13C NMR (75 MHz, CDCl3,
25 °C): 178.46 (C, C@S), 165.99 (C, –COOCH3), 153.15 (C, C@O),
136.95, 132.37, 130.90, 127.88, 127.06, 123.78 (C, Aromatic),
63.36 (C, OCH2), 52.62 (C, –COOCH3), 14.18 (CH3).
m(–COOMe); 1676,
m
m
d(N–H); 1329,
m(–NC(S)N); 1140,
m
m
Electronic (solid state, kmax, nm): 285, 310, 402, 648.
2.5.5. Bis (N-((4-methoxycarbonyl) phenyl)-N0-(ethoxycarbonyl)
thiocarbamide) copper (II) (4-MCPET)2Cu (2a0)
Yield: 76%, m.p.; decompose at 248–250 °C. Elemental Anal.
Calc. for C24H26CuN4O8S2, M = 626.16, (%), C, 46.03; H, 4.18; N,
8.94. Found: C, 46.11; H, 4.24; N, 8.98%. IR (KBr, cmꢁ1): 3215,
2.5.2. Bis (N-((4-methoxycarbonyl) phenyl)-N’-(ethoxycarbonyl)
thiocarbamide) copper (I) chloride (4-MCPET)2CuCl (2a)
Yield: 70%, m.p.; 170–172 °C. Elemental Anal. Calc.
m(N–H); 3057,
m(aromatic C–H); 2993,
m(aliphatic C–H); 1726,
C24H28ClCuN4O8S2, M = 663.63 (%), C, 43.43; H, 4.25; N, 8.44.
m(–COOMe); 1659,
m
(–COOEt); 1593, (C@C, Ph); 1553, d(N–H);
m

390
D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
Fig. 1. (a) ORTEP view of (2-MCPET)2CuCl (1). (b) Unit cell diagram of 1.
Fig. 2. ORTEP view of (2-MCPET)2CuCl (1a). Hydrogen bonds are shown by dashed lines.

D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
391
Fig. 3. ORTEP view of (2-MCPET)2Cu (1a0). Hydrogen bonds are shown by dashed lines.
Fig. 4. Packing diagram of complex (2-MCPET)2CuCl(1a).
1369,
m(–NC(S)N); 1180, m(N@C@S); (1230, 689), m(C@S); Elec-
3. Results and discussion
tronic (solide state, kmax, nm): 283, 314, 408, 646.
3.1. Synthesis and characterization
2.5.6. Bis (N-((2-methoxycarbonyl) phenyl)-N0-(methoxycarbonyl)
thiocarbamide) copper (II) (2-MCPMT)2Cu (3a0)
Yield: 72%, m.p.; decompose at 266–268 °C. Elemental Anal.
Calc. for C24H26CuN4O8S2, M = 598.11, (%), C, 44.17; H, 3.70; N,
10.62. Found: C, 44.23; H, 3.75; N, 10.71%. IR (KBr, cmꢁ1): 3101,
Ligands were prepared as one-pot synthesis by the reaction of
ethoxy/methoxycarbonyl isothiocyanate and respective amine.
Their copper (I) complexes were prepared by the reaction of
ligands with hydrated copper (II) chloride with constant stirring.
The Cu(II) complexes were obtained as dark green solid, during
crystallization procedure of Cu(I) complexes in DCM-DMSO (3:1,
v/v) mixture in one week at 10 °C (Scheme 1).
m
m
(N–H); 3033,
(–COOMe); 1681,
m
(aromatic C–H); 2957,
m
(aliphatic C–H); 1734,
(–COOEt); (1607, 1581), (C@C, Ph); 1535,
(N@C@S); (1269, 706), (C@S);
m
m
In our view, the probable reason for the geometric transforma-
tion of trigonal planar Cu(I) complex to square-planar Cu(II)
d(N–H); 1328,
m
(–NC(S)N); 1182,
m
m
Electronic (Nujol, kmax, nm): 288, 312, 410, 645.

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D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
(Fig. 1a). Weak intermolecular hydrogen bonding interactions like
C–Hꢀ ꢀ ꢀS and C–Hꢀ ꢀ ꢀO lead to an infinite chain length (Fig. 1b).
The geometry of complexes 1a and 1a0 are trigonal planar and
distorted square-planar, respectively. The structure of complex
1a is similar to bis(N-(p-nitrophenyl)-N0-(ethoxycarbonylthiourea)
copper (I) chloride [31] and bis(N-(o-methylphenyl)-N0-(eth-
oxycarbonylthiourea) copper (I) chloride [33]. Coordination of
ligand to Cu(I) through thiocarbonyl sulfur is supported by a slight
increase in the C–S bond length S(1A)–C(9A)(1.690(3) Å and S(1B)–
C(9B) (1.679(3) Å) as compared to ligand S(1)–C(9) (1.653(3) Å
(Table 2). Almost trigonal planar geometry formed by two S and
one Cl atoms of complex 1a is supported by bond angles S(1A)–
Cu–Cl(1) = 123.61(4), S(1B)–Cu–Cl(1) = 123.04(4) and S(1A)–Cu–
S(1B) 113.04(3) [31,33]. The Cu(I) ion deviates by 0.0310 Å from
least square plane Cu/Cl/S1A/S1B. The cis-conformation of acyl
thiourea moiety in the complex is stabilized by intramolecular
hydrogen bonding between N–H and coordinated chlorine
(Table 4).
In complex 1a0 the ligand coordinates to Cu(II) ion in monoan-
ionic bidentate fashion through thiolate S and imine N forming
four membered 1, 3-N, S chelate ring. The molecular structure of
Fig. 5. Packing diagram of complex (2-MCPET)2Cu(1a0).
Cu(II) complex and 1, 3-N,
S coordination is similar to
complex could be the oxidation of Cu(I) to Cu(II) by the DMSO and
to maintain electroneutrality the coordination mode of ligand has
been changed from neutral monodentate to uninegative bidentate.
Ni[PhNHC(S)NP(O)(OPr-i)2-N,S]2 [37] and [Ni(L-N,S)2] [38]. The N,
S coordination is supported by an increase in C–S and decrease in
C–N bond lengths as compared to the ligand (Table 3) [34,37,38].
The dihedral angle 7.47(0.15)° formed between the least square
planes Cu–N1A–C9A–S1A and Cu/N1B/C9B/S1B and deviation of
bond angles N2–Cu–N4 (172.73(13)° and S1–Cu–S2 (175.61(4)
(Table 2) from 180° suggest slight distortion in square-planar
geometry. Cu(II) ion deviates by 0.0150 Å from plane Cu/N1B/
C9B/S1B. The distortion in the geometry could be due to steric
interactions between the substituents present on thiourea moiety.
Intramolecular hydrogen bonding interactions N–Hꢀ ꢀ ꢀO@C present
in the complex is a prerequisite for the stabilization of 1, 3-N, S
chelate ring [38], and is probably responsible for nonparticipation
of carbonyl oxygen in bonding and coplanarity of thiourea core.
Different types of weak intermolecular interactions (C–Hꢀ ꢀ ꢀC,
N–Hꢀ ꢀ ꢀO, C–Hꢀ ꢀ ꢀO, Cuꢀ ꢀ ꢀS) stabilize the crystal packing and lead
to infinite chain length of a wave-like arrangement along b-axis
(Fig. 6).
3.2. Crystal Structure Study
The crystallographic data and structural refinement details of
compounds 2-MCPET (1), (2-MCPET)2CuCl (1a) and (2-MCPET)2Cu
(1a0) are given in Table 1. Selected inter-atomic distances, bond
angles, intra and intermolecular hydrogen bonding and nonbond-
ing distances are collected in Tables 2–4 respectively. The ORTEP
picture of compounds 1, 1a and 1a0 are shown in Figs. 1a, 2 and
3 and their unit cell diagrams are shown in Figs. 1b, 4 and 5,
respectively.
In crystal structure of the ligand 1 (Fig. 1a) the carbonyl and
thiocarbonyl group point in approximately opposite direction.
The phenyl and ethoxycarbonyl group lie respectively, cis and trans
relative to the sulfur atom across the thiourea C–N bonds. The C–S
bond length is of typical double bond (1.65–1.66 Å) character
whereas all the C–N bond lengths are shorter than single C–N bond
length inferring the involvement of resonance in them. All the
bond lengths and bond angles are consistent with the related
substituted thiocarbamides [34,36]. The noncoplanar structure of
the ligand 2-MCPET (1) is reflected by the dihedral angles
54.82(0.11)°, 8.02(0.17)° formed between the mean plane of cen-
tral thiourea fragment (N1/C9/S1/N2) and mean planes of phenyl
ring (C1/C2/C3/C4/C5/C6) and ethyl ester group (O3/O4/C10/C11/
C12), respectively. An intra-molecular hydrogen bond, N–Hꢀ ꢀ ꢀO
between N1/H6 and oxygen atom of amidic group locks the
–C(O)–NH–C(S)NHR unit into a planar six membered ring structure
3.3. Spectroscopic study
The IR spectra of ligands display bands at 3424–3432, 1690–
1727, 1260–1240 and 759–750 cmꢁ1 regions assignable to their
–NH, –C@O, –C@N and –C@S stretching vibrations, respectively.
In Cu(I) complexes the bands due to m(C@S) and m(C@O) suffer a
negative and a positive shift of about 15 and 20 cmꢁ1 respectively
owing to coordination through thione sulfur [33,35]. The disap-
pearance of bands due to
m
(NH) and
m
(C@S) and appearance of
new band at ꢂ644 cmꢁ1 due to
m(C–S) in the spectra of Cu(II)
complexes is suggestive of coordination through thiolate sulfur.
Fig. 6. The long-range C-H. . .S, C-H. . .C and Cu. . .S interaction lead to a wave-like arrangement along b axis.

D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
393
Fig. 7. Experimental (curve line) and TD-DFT calculated (vertical lines) absorption spectra of (a) ligand 1, (b) complex 1a and (c) complex 1a0.
for N1H proton is due to its involvement in intramolecular hydro-
gen bonding with carbonyl oxygen. In spectra of Cu(I) complexes
the N1H proton signal suffers a downfield shift of ꢂ2.0 ppm owing
to its involvement in intramolecular hydrogen bonding with chlo-
rine. In the 13C NMR spectra of Cu(I) complexes, the C@S carbon
signal resonates at an upfield position (175–178 ppm) in compar-
ison to the ligands (177–179) supporting coordination through thi-
one sulfur. The observed chemical shift values in 1H and 13C NMR
spectra of ligands and their copper(I) complexes matched well
with related thiourea compounds H2net, H2nmt, [Cu(H2net)2-
Cl]CH2Cl2, [Cu(H2nmt)2Cl]2CHCl3 [31].
Absorption spectra of ligand 1, its Cu(I) (1a) and Co(III) (1b)
complexes are shown in Fig. 7. Absorption spectra of complexes
1a–3a consists of mainly two bands. The bands in 305–307 nm
and 397–399 nm regions may be assigned to intra-ligand charge
transfer (ILCT) and metal to ligand charge transfer (MLCT) transi-
tions, respectively. The spectra of complexes 1a0–3a0 exhibit two
bands, one sharp band in 401–403 nm region and a broad band
in 647–650 nm region assignable to 2B2g ? 2Eg and 2B1g ? 2A1g
transitions, respectively, in square-planar geometry around Cu(II)
[32,39].
Fig. 8. Cyclic voltammogram of (2-MCPET)2CuCl (1a).
Coordination through imine nitrogen is supported by a positive
and a negative shift of ꢂ45 cmꢁ1 and ꢂ30 cmꢁ1, respectively, in
C–N and –C@O stretching vibrations [34].
3.4. Magnetic and electrochemical studies
The 1H NMR spectra of the ligands display singlet due to N1H
and N2H protons considerably downfield in the range 8.10–8.18
and 11.61–12.63 ppm, respectively. The high chemical shift value
The RT magnetic moment values for complexes 1a0–3a0 (1.76
BM), correspond to one unpaired electron whereas those of
complexes 1a–3a show them to be diamagnetic.

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D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
Fig. 9. Optimized structure of (2-MCPET)2Cu (1a0).
Fig. 10. Experimental IR spectrum (smooth line) and its correlation with calculated IR bands (vertical line). (a) Complex (2-MCPET)2Cu (1a0). (b) The linear correlation
between experimental and theoretical vibrational frequencies of complex (2-MCPET)2Cu (1a0).
Fig. 11. The frontier molecular orbital (FMO) pictures of complex (2-MCPET)2Cu (1a0) involved in electronic transitions.

D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
395
The electrochemical parameters for complex 1a are given in
Supplementary Table S1. The cyclic voltammogram of 1a exhibits
one cathodic and one anodic peak with respect to Ag/AgCl refer-
ence electrode (Fig. 8). The potential difference between the peaks
(160 mV) at scan rate of 20 mV/s and its linear increase with
increasing scan rate is clearly indicative of the occurrence of a
quasi-reversible redox process assignable to Cu(I)/Cu(II).
in gaseous phase using coordinates of single crystal X-ray diffrac-
tion structure (SCXRD). Absence of any imaginary vibrational fre-
quencies indicates that the complex geometry was at the
minimum of the potential energy surface.
The main geometrical parameters obtained from DFT calcula-
tions and those obtained from single crystal X-ray analysis are in
close proximity (Table 3). Fig. 9 depicts the optimized structure
of complex 1a0. Computed dipole moment value for the complex
1a0 is 0.00 Debye indicating symmetrical arrangement of atoms
in its crystal packing structure.
3.5. Thermal study
The thermal properties of complex 1a0 was studied by thermo-
gravimetric analysis (TGA) in the temperature range 30–800 °C
under nitrogen atmosphere at a heating rate of 5 °C minꢁ1. The
thermogram of 1a0 exhibits four distinct decompositions at 126,
245, 418 and 605 °C (Supplementary Fig. S1). The first weight loss
(43.90%) could be due to methyl benzoate moiety (C8H8NO2) of the
ligand. The second decomposition at 245 °C corresponds to
the weight loss (21.10%) of ethoxycarbonyl group (C3H5O2) from
the ligand unit. The total weight loss of 85.26% was reached at
605 °C and no further weight loss was observed. The 14.73% resi-
due left corresponds to copper sulfide which is in good agreement
with calculated value (14.53%).
IR spectrum of the complex 1a0 along with the calculated fre-
quencies (shown as vertical lines) obtained by using LANL2DZ
basis set at B3LYP level is shown in Fig. 10a. The most significant
experimental vibrational frequencies along with DFT calculated
frequencies (in parenthesis) are presented in Table S2 (Supplemen-
tary material). A linear correlation graph between experimental
and calculated vibrational frequencies for complex 1a0 (Fig. 10b)
with the linear equation Y = 1.0122x ꢁ 31.3912. R2 = 0.9988 and
SD = 826.9748 predicts appreciably good agreement between
them. At higher wavenumber regions a little difference between
theoretically calculated and experimentally observed frequencies
are due to increase in anharmonicity in bonds stretching.
The calculated absorption bands for 1a0 in the ground state,
their oscillator strengths, energies and the transitions are gathered
in Table S3 (Supplementary material). TD-DFT calculated electronic
bands correlated well with experimentally observed UV–Vis spec-
tral bands. The assignments of the calculated electronic transitions
were based on an overview of the contour plots and relative ener-
gies of different molecular orbitals (MO) involved in the electronic
transitions. Frontier molecular orbital (FMO) pictures of different
orbitals involved in transitions are shown in Fig. 11. The high
3.6. DFT study
To get a deep insight of the vibrational frequencies and elec-
tronic transitions involved, DFT calculations on complex 1a0 was
performed using GAUSSIAN-03 program. DFT computation was
performed at Becke’s three-parameter hybrid model using
Lee–Yang-Parr (B3LYP) correlation functional [40,41]. Molecular
structure of complex 1a0 was optimized at B3LYP/LanL2DZ level
Table 5
IC50 Values (l
M) for the ligands 1–3 and their Cu(I) complexes against two human cervical cancer cell lines (2008 and C13⁄) and three human ovarian carcinoma cell lines (A2780,
A2780/CP and IGROV-1).
Compounds
2008 cells
C13⁄ cells
A2780 cells
A2780/CP cells
IGROV-1 cells
2-MCPET(1)
4-MCPET(2)
2-MCPMT(3)
(2-MCPET)2CuCl-(1a)
(4-MCPET)2CuCl-(2a)
(2-MCPMT)2CuCl-(3a)
Cisplatin
90.6
72.4
89.9 11
43.4 11
27.9
42.5
1.9 0.5
4.1 0.3
9
3
93.5
75.6
94.4
47.8
33.8
46.6
19.4
7
5
9
4
5
5
1
78.5
71.5
77.7
37.6
32.5
37.0
7
4
5
6
5
4
72.9
68.1
72.5
39.5
35.6
39.7
19.9
4
2
4
8
3
5
2
68.5
73.4
69.9
42.5
32.5
41.5
6
6
7
9
7
6
3
9
2.1 0.4
5.5 0.3
1.6 0.2
5.1 0.2
5-FU
8.5 0.5
12.8 0.5
Compounds
Fig. 12. Cytotoxicity of ligands 1–3 and their Cu (I) complexes 1a-3a.

396
D.P. Singh et al. / Inorganica Chimica Acta 423 (2014) 386–396
energy absorption band in 285–330 nm region involves a multi-
tude of electronic transitions but maximum contribution is from
HOMO-7 to LUMO + 2 at 303 nm which is mainly due to ILCT tran-
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplemen-
tary data associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.ica.2014.08.031.
sition (p
(Ph) ? p⁄(Ph)). Band at 385 nm corresponds to HOMO to
LUMO + 1 transition assignable to LLCT (
p
(S) ? p⁄(Ph)) with a
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at 633 nm corresponds to HOMO-3 to LUMO transition and is
due to mixed ILCT and LMCT transitions (p
(S) ? p⁄(S)/d(Cu2+)).
3.7. Cytotoxic study
The ligands and their copper (I) complexes have been tested for
their in vitro cytotoxicity against two human cervical carcinoma
(2008 and C13⁄) and three ovarian carcinoma (A2780, A2780/CP
and IGROV-1) cell lines in which C13⁄ and A2780/CP are cisplatin
resistant cells. The IC50 values (the concentration which produces
50% growth inhibition of cell lines) for the compounds along with
two standard drugs are given in Table 5. From the IC50 values it is
clear that all the compounds in general exhibited moderate to good
activity against all the cancer cell lines tested. The copper(I) com-
plexes exhibited stronger cytotoxicity than the ligands (Fig. 12).
The better activity of copper complexes may be related to the
redox behavior of copper, which is believed to initiate the produc-
tion of highly reactive hydroxyl radicals responsible for damaging
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4. Conclusion
Geometry transformation of trigonal planar Cu(I) complexes
afforded square planar Cu(II) complexes in which the ligand binds
to the copper ion through N and S forming a four-membered che-
late ring. This geometry transformation is probably due to solvent
induced oxidation of Cu(I) to Cu(II) in DCM-DMSO (3:1) mixture of
solvents. The intramolecular hydrogen bonding and electron delo-
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Acknowledgements
The author, DPS is grateful to Banaras Hindu University, Varana-
si, India for the financial assistance and research scholarship. I am
thankful to Prof. G. Marverti, Department of Biomedical Sciences,
Metabolic and neurosciences, University of Modena, Italy for cyto-
toxicity studies. I am also very thankful to Prof. R. J. Butcher,
Department of Chemistry, Howard University, 525 College Street
NW, Washington, DC 20059, USA for X-ray study.
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Appendix A. Supplementary data
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CCDC 864540, 998948 and 998949 contain the supplementary
crystallographic data for ligand 1, complex 1a and 1a0. These data
can be obtained free of charge from The Cambridge Crystallographic