Synthesis of 5-nitro-salicylaldehyde-N-substituted thiosemicarbazonates of copper(II): Molecular structures, spectroscopy, ESI-mass studies and antimicrobial activity

Article abstract of DOI:10.1016/j.ica.2017.02.032

Equimolar reactions of copper(II) acetate with 5-nitro-salicylaldehyde-N¹-substituted thiosemi carbazones, [5-NO₂-2-HO–C₆H₄-C²(H)[dbnd]N³–N²H–C¹([dbnd]S)–N¹

Full text of DOI:10.1016/j.ica.2017.02.032

Accepted Manuscript
Research paper
Synthesis of 5-nitro-salicylaldehyde-N-substituted thiosemicarbazonates of
copper(II) : Molecular structures, spectroscopy, ESI-mass studies and antimi-
crobial activity
Tarlok S. Lobana, Shikha Indoria, Henna Sood, Daljit S. Arora, Balwinder S.
Randhawa, Isabel Garcia-Santos, Victoria A. Smolinski, Jerry P. Jasinski
PII:
S0020-1693(17)30211-6
http://dx.doi.org/10.1016/j.ica.2017.02.032
ICA 17458
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
14 February 2017
25 February 2017
27 February 2017
Please cite this article as: T.S. Lobana, S. Indoria, H. Sood, D.S. Arora, B.S. Randhawa, I. Garcia-Santos, V.A.
Smolinski, J.P. Jasinski, Synthesis of 5-nitro-salicylaldehyde-N-substituted thiosemicarbazonates of copper(II) :
Molecular structures, spectroscopy, ESI-mass studies and antimicrobial activity, Inorganica Chimica Acta (2017),
doi: http://dx.doi.org/10.1016/j.ica.2017.02.032
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Full paper
Synthesis of 5-nitro-salicylaldehyde-N-substituted thiosemicarbazonates of
copper(II) : Molecular structures, spectroscopy, ESI-mass studies and
antimicrobial activity
Tarlok S. Lobana,*a Shikha Indoria,a Henna Sood,b Daljit S. Arora,b Balwinder S. Randhawa,a
Isabel Garcia-Santos,c Victoria A. Smolinski,d and Jerry P. Jasinskid
aDepartment of Chemistry, Guru Nanak Dev University, Amritsar-143 005, India.
bDepartment of Microbiology, Guru Nanak Dev University, Amritsar-143 005, India
cDepartamento de Quimica Inorganica, Facultad de Farmacia, Universidad de
Santiago, 15782-Santiago, Spain
dDepartment of Chemistry, Keene State College, Keene, NH 03435 USA
E-mail: tarlokslobana@yahoo.co.in (T.S. Lobana); Fax: 91-183-2258820
ABSTRACT
Equimolar reactions of copper(II) acetate with 5-nitro-salicylaldehyde-N1-substituted thiosemi –
carbazones, [5-NO2-2-HO–C6H4-C2(H)=N3–N2H–C1(=S)–N1HR; R = Me, H2L-NHMe; Et, H2L-
NHEt; Ph, H2L-NHPh; H, H2L-NH2], and 4, 4'-dimethyl-2,2'-bipyridine (dm-bipy), 2, 9-
dimethyl-1, 10-phenanthroline (dm-phen) and 3, 4, 7, 8-tetramethyl-1,10-phenanthroline (tm-
phen) have yielded complexes of stoichiometry, [Cu(κ3-O,N,S-5-NO2-stscN1HR)(κ2-N,N-L')] {R
= H (1, 2, 3), Me (4, 5, 6), Et(7, 8, 9), Ph (10, 11, 12); L'= dm-bipy (1, 4, 7, 10) / dm-phen (2, 5,
8, 11) / tm-phen (3, 6, 9, 12)}. They have been investigated by analytical data, infrared and
electronic absorption spectroscopy, electron spin resonance spectroscopy, fluorescence activity,
ESI-mass study and single crystal X-ray crystallography (1, 6, 7). The geometry of complexes is
slightly distorted square pyramidal and have displayed weak to intense fluorescence in the
region, 370-570 nm. Complexes have shown significant antimicrobial activity against methicillin
resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (MTCC740), Klebsiella
1

pneumoniae (MTCC109), Shigella flexneri (MTCC1457), Salmonella typhimurium (MTCC-
439), and Candida albicans (MTCC227). Complexes are cytotoxic against living cells and thus
they are bactericidal / fungicidal.
Keywords: 5-nitro-salicylaldehyde-N1-substituted thiosemicarbazones; 4, 4'-dimethyl-2,2'-
bipyridine, 2,9-dimethyl-1, 10-phenanthroline, copper(II), antimicrobial activity
1. Introduction
Study of the coordination chemistry of thiosemicarbazones (Chart 1, structure I and analogous
ligands) describes molecular structures, variable nuclearity, cyclometallation, catalysis,
analytical chemistry and finally the biochemical applications of metal complexes which
comprise the chief interest of several scientists [1-17]. Biological applications of metal
thiosemicarbazones reported in the literature pertain to in vitro molecular imaging devices,
anticancer activity, inhibition of DNA and RNA synthesis, disruption of ATP production,
neuroprotective activity in cell and animal models of Alzheimer’s disease (AD), antimicrobial
activity, anti-tumor activity and cytotoxicity [18-51].
S
1
R1
N2H
C
2
3
N
N1R3R4
N
N
C
R2
I
bipy
H
7
OH
S
8
3
H
N2
6
1
N3
C
2
C
5
MeO
N
N
4
N1HR
phen
H
II. R = Me, Et, Ph, H
Chart 1. Thiosemicarbazones and col-ligands
Regarding the biochemical status of metal derivatives of salicylaldehyde based
thiosemicarbazones, these complexes exhibited antitumor activity [37, 42], photo-induced DNA
cleavage [43] and antimicrobial activity [44-51]. In order to develop metallo-organic
antimicrobial agents, we have recently reported [18] antimicrobial activity of complexes of
2

copper(II)/zinc(II) with salicylaldehyde based thiosemicarbazones (Charts 1 and 2) for methoxy
and/or nitro groups at the 5-position in structure II with bipy, phen, dm-phen and tm-phen co-
ligands[18, 52-54]. These complexes showed significant growth inhibitory activity
(antimicrobial activity) against methicillin resistant Staphylococcus aureus (MRSA),
Staphylococcus aureus, Klebsiella pneumoniae, Shigella flexneri and Candida albicans.
In continuation, in this paper, 5-nitro-salicyaldehyde-N1-substituted thiosemicarbazones
and 4, 4'-dimethyl-2,2'-bipyridine (dm-bipy), 2,9-dimethyl-1,10-phenanthroline (dm-phen) and 3,
4, 7, 8-tetramethyl-1,10-phenanthroline (tm-phen) ligands have been used for the synthesis of
copper(II) complexes (Chart 2). Here, the main objective of the study was to investigate the
effect of substituents in the pyridine rings of 2,2'-bipyridine / 1,10-phenanthroline on
antimicrobial activity.
CH3
H3C
4
'
4
3
3
'
'
2
9
N
N
H
7
R
2
N
N
H3C
CH3
2
OH
S
8
H
N2
Me, H2L-NHMe
6
dm-phen
dm-bipy
1
N3
III
Et,
Ph, H2L-NHPh
H, H2L-NH2
H2L-NHEt
C
2
C
5
3
O2N
4
N1HR
4 CH3
H3C
7
H
3
H3C
CH3
8
N
N
2
tm-phen
Chart 2. Salicylaldehyde thiosemicarbazones and co-ligands used in the present study.
2. Experimental
Copper(II) acetate monohydrate, thiosemicarbazide, N-methylthiosemicarbazide, N-
ethylthio- semicarbazide, N-phenylthiosemicarbazide, 5-nitro-salicylaldehyde, 4, 4′-dimethyl-
2,2-bipyridine (dm-bipy), 2, 9-dimethyl-1,10-phenanthroline (dm-phen) and 3,4,7,8-tetramethyl-
1,10-phenanthroline (tm-phen) were procured from Aldrich Sigma Ltd. The thio-ligands (Chart
2) were prepared as reported earlier [18, 52-54]. Elemental analysis for C, H, and N were carried
out with a thermoelectron FLASHEA1112 analyzer. Melting points were determined with a
Gallenkamp electrically heated apparatus. IR spectra of the compounds were recorded in the
4000 – 450 cm-1region with a Perkin Elmer FT-IR Spectrometer by making their KBr pellets.
3

UV-visible spectra of the compounds (10-3-10-4 M) were recorded in dimethylsulfoxide (dmso)
with the help of a UV-1601 PC Shimadzu spectrophotometer. Fluorescence spectra of the
complexes (10-4 M) were recorded with a Varian Cary Eclipse Fluorescence spectrophotometer.
The ESI-mass spectra were recorded in DMSO using a Bruker Daltonik LS-MS high resolution
microTOF-Q II 10356 spectrometer.
2.1. Synthesis of complexes
2.1.1. [Cu(κ3:O,N3,S-5-NO2-stsc-N1H2)(κ2:N,N-dm-bipy)] (1). To a pale yellow solution of thio-
ligand 5-NO2-H2stsc-N1H2 (0.029 g, 0.127 mmol) in methanol (15 mL) was added dark green
solid Cu(OAc)2·H2O (0.025 g, 0.125 mmol) which led to the formation of light brown compound
which was suspended in a mixture of dichloromethane and methanol (3 : 1 v/v) followed by the
addition of solid dm-bipy (0.017 g, 0.125 mmol) and the contents were stirred for 15 min until a
clear dark green solution was formed. The dark green solution was allowed to evaporate at room
temperature which gave dark green crystals which were grown over a period of 10 days. Yield:
0.036 g, 75%, m.p. 205°C. Anal. Calc. for C20H18CuN6O3S: C 49.43; H 3.73; N 17.29; S 6.60;
Found: C 49.52; H 3.49; N 17.46; S 6.39 %. IR (cm-1 , KBr): ν(N1–H) 3390 w, ν(C–H) 3100 w,
2950 w; ν(C=N) + ν(C=C) + δ(N−H) 1598 s, ν(N=O) 1548 m, δ(C−H) 1489 s, 1470 w; 1380 m,
δ(N=O) 1307 s; other bands, 1244 m, 1150 w, 1100 m, 947 w, 831 s; 805 s; ν(C–S) 784 s; other
bands, 726 s, 652 s, 623 s. Electronic absorption spectrum (DMSO, λmax /nm, ε / L mol-1 cm-1):
[10-3 M] 595 (1.85 x 102); [10-4 M] 394 (1.42 x 104), 333 (1.26 x 104), 280 (1.78 x 104).
ex
em
Fluorescence spectrum: (λmax = 320 nm; λmax
=
433 nm). ESI mass data: calc for,
C20H18CuN6O3S+H, [Cu(5-NO2-stsc-N1H2)(dm-bipy) + H]+ 486.40; obsd. m/z = 486.05.
Complexes 2-12 were prepared by a similar method.
2.1.2. [Cu(κ3:O,N3,S-5-NO2-stsc-N1H2)(κ2:N,N-dm-phen)] (2). Yield: 0.035 g, 74%, m.p. 238°C.
Anal. Calc. for C22H18CuN6O3S: C 51.81; H 3.56; N 16.48; S 6.29 %; Found: C 51.09; H 3.63; N
16.21; S 6.41 %. IR (cm-1 , KBr): ν(N1–H) 3353 w; ν(C–H) 3170 w, 3000 w, 2985 w, ν(C=N) +
ν(C=C) + δ(N−H)1659 m, 1598 s; ν(N=O) 1549 s, δ(C−H) 1500 s, 1442 s; 1370 w, δ(N=O) 1314 s;
other bands, 1220 s, 1153 w, 1100 s, 944 s, 861 w; ν(C–S) 763 s; other bands, 653 s, 626 s.
Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M] 594 (2.24 x 102); [10-4
em
M] 406 (9.23 x 103), 332(8.51 x 103), 275 (1.88 x 104). Fluorescence spectrum: (λmax = 434 nm;
4

λmaxex = 320 nm). ESI mass data : calc. for C22H18CuN6O3S +H, [Cu(5-NO2-stsc-N1H2)(dm-phen) +
H]+ , m/z =510.05; obsd. m/z = 510.04.dm
2.1.3. [Cu(κ3:O,N3,S-5-NO2-stsc-N1H2)(κ2:N,N-tm-phen)]⋅CH3OH (3). Yield: 0.037 g, 76%, m.p.
234°C. Anal. Calc. for C24H22CuN6O3S⋅CH3OH: C 52.67; H 4.60; N 14.74; S 5.62 %; Found: C
52.09; H 4.90; N 15.01; S 6.01 %. IR (cm-1 , KBr): ν(N1–H) 3420 w, ν(O–H)CH3OH 3390 w, ν(C–H)
3139 w, 3020 w; ν(C=N) + ν(C=C) + δ(N−H) 1610 s, 1595 s, ν(N=O) 1548 s, δ(C−H) 1484 s, 1470
s, 1429 s; 1380 m, 1350 m, δ(N=O) 1306 s, 1242 m, 1160 w, 1100 m, 947 w, 831 s, 805 s; ν(C–S)
784 s; 726 s, 652 s, 623 s. Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3
M] 590 (1.61 x 102); [10-4 M] 402 (1.18 x 104), 331 (9.84 x 103), 276 (2.58 x 104). Fluorescence
em
spectrum: (λmax = 436 nm; λmaxex = 320 nm). ESI mass data: calc. for C24H22CuN6O3S⋅CH3OH
+H, [Cu(5-NO2-stsc-N1H2)(tm-phen).CH3OH + H]+ , m/z = 570.11; obsd. m/z = 570.16.
2.1.4. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HMe)(κ2:N,N-dm-bipy)] (4). Yield: 0.037 g, 74%, m.p. 223
°C. Anal. Calc. for C21H20CuN6O3S: C 50.44; H 4.03; N 16.81; S 6.41 %; Found: C 50.32; H
4.29; N 16.72; S 6.30 %. IR (cm-1 , KBr): ν(N1–H) 3373 s; ν(C–H) 3130 w, 2990 w, 2970 w,
2887 w; ν(C=N) + ν(C=C) + δ(N-H) 1598 s, ν(N=O) 1547 m; δ(C-H) 1500 s, 1434 s, 1403 m;
δ(N=O) 1302 s; other bands, 1099 w; 829 w, ν(C–S) 766 s; 516 w. Electronic absorption
spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M] 594 (2.28 x 102); [10-4 M] 394 (2.35 x
104), 332 (2.00 x 104), 283 (2.81 x 104). Fluorescence spectrum : (λmaxem = 436 nm; λmaxex = 320
nm). ESI mass data: calc. for C21H20CuN6O3S+H, [Cu(5-NO2-stsc-N1HMe)(dm-bipy) + H]+, m/z
= 500.06; obsd. m/z = 500.05.
2.1.5. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HMe)(κ2:N,N-dm-phen)] (5). Yield: 0.039 g, 74%, m.p. 205
°C. Anal. Calc. for C23H20CuN6O3S: C 52.71; H 3.85; N 16.04, S 6.12 %.; Found: C 52.43; H 3.65;
N 15.83, S 6.37 %. IR (cm-1 , KBr): ν(N1–H) 3382 w; ν(C–H) 3090 w, 3004 w, 2888 w; ν(C=N) +
ν(C=C) + δ(N−H) 1608 s, 1581 s; ν(N=O) 1550 w; δ(C−H) 1491 s; δ(N=O) 1307 s; 1036 s, 830 s;
ν(C–S) 769 s; 517 w. Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M]
585 (2.54 x 102); [10-4 M] 399 (7.79 x 103), 324 (6.93 x 103), 284 (1.85 x 104). Fluorescence
spectrum: (λmaxem = 434 nm; λmaxex = 320 nm). ESI mass data : calc. for C23H20CuN6O3S+H, [Cu(5-
NO2-stsc-N1HMe)(dm-phen) + H]+ 524.07; obsd. m/z = 524.08.
5

2.1.6. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HMe)(κ2: N, N-tm-phen)]⋅H2O (6). Yield: 0.041 g, 73%, m.p.
243°C. Anal. Calc. for C25H24CuN6O3S⋅H2O: C 52.67; H 4.60; N 14.74, S 5.62 %; Found: C 52.81;
H 4.77; N 15.06, S 5.29 %. IR (cm-1 , KBr): ν(N1–H) + ν(O–H)H2O 3442 br; ν(C–H) 3048 w, 2937
w, 2889 w; ν(C=N) + ν(C=C) + δ(N−H) 1597 s, ν(N=O) 1548 m; 1504 m δ(C−H) 1492 s, 1432 s;
1369 m; δ(N=O) 1308 s; 1242 m, 1192 w, 1146 w, 1102 s, 1069 w, 1011 w, 953 m, 884 m; 819 s;
ν(C–S) 729 s; 698 m, 651 m, 619 w, 514 w, 468 w. Electronic absorption spectrum, (DMSO, λmax
/nm, ε / L mol-1 cm-1): [10-3 M] 589 (1.90 x 102); [10-4 M] 402 (1.44 x 104), 330 (1.29 x 104), 276
(3.59 x 104). Fluorescence spectrum: (λmaxem = 435 nm; λmaxex = 320 nm). ESI mass data: calc. for
C25H24CuN6O3S⋅H2O+H, [Cu(5-NO2-stsc-N1HMe)(tm-phen).H2O + H]+ 570.11; obsd. m/z =
570.18. The crystals were formed after recrystallisation in CH2Cl2 and MeOH. X-ray showed the
presence of CH2Cl2.
2.1.7. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HEt)(κ2:N,N-dm-bipy)]⋅CH2Cl2 (7). Yield: 0.036 g, 71 %,
m.p. 208 °C. Anal. Calc. for C22H22CuN6O3S⋅CH2Cl2: C 46.12; H 4.04; N 14.03; S 5.35 %; Found:
C 45.94; H 4.33; N 14.41; S 5.72 %. IR (cm-1 , KBr): ν(N1–H) 3386 w; ν(C–H) 3145 m, 3056 w,
2880 w; ν(C=N) + ν(C=C) + δ(N−H) 1598 s; ν(N=O) 1549 s; δ(C−H) 1493 s, 1458 w; δ(N=O) 1308
s; 1244 s, 1150 w, 1100 s, 1026 w, 829 w; ν(C–S) 763 s; 427 w. Electronic absorption spectrum,
(DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M] 592 (2.47 x 102); [10-4 M] 398 (2.26 x 104), 333 (1.89
em
x 104), 287 (2.30 x 104). Fluorescence spectrum: (λmax = 440 nm; λmaxex = 320 nm). ESI mass
data: calc. for C22H22CuN6O3S+H, [Cu(5-NO2-stsc-N1HEt)(dm-bipy) + H]+ 514.08; obsd. m/z =
514.45.
2.1.8. [Cu(κ3-O,N3,S-5-NO2-stsc-N1HEt)(κ2-N,N-dm-phen)] (8). Yield: 0.039 g, 74 %, m.p.
195°C. Anal. Calc. for C24H22CuN6O3S: C 53.57; H 4.12; N 15.62; S 6.00 %; Found: C 53.02; H
4.33; N 15.03; S 5.95 %. IR (cm-1 , KBr): ν(N1–H) 3390 s, ν(C–H) 3060 w, 2968 w, 2930 w,
2880 w; ν(C=N) + ν(C=C) + δ(N−H) 1597 s; ν(N=O) 1549 s; δ(C−H) 1501 s, 1430 s; 1397 m,
δ(N=O) 1313 s; 1242 w, 1192 w, 1151 w, 1100 m, 937 w, 858 m, 826 w; ν(C–S) 758 s; 652
m, 513 w. Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M]
605 (2.58 x 102); [10-4 M] 402 (2.27 x 104), 332 (1.84 x 104), 296 (2.55 x 104), 277 (3.80 x
104). Fluorescence spectrum: (λmaxem = 436 nm; λmaxex = 320 nm).
6

2.1.9. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HEt)(κ2:N,N-tm-phen)] (9). Yield: 0.042 g, 74%, m.p.
199°C. Anal. Calc. for C26H26CuN6O3S: C 55.16; H 4.63; N 14.84; S 5.66 %; Found: C 54.89;
H 4.21; N 15.09; S 5.76 %. IR (cm-1 , KBr): ν(N1–H) 3345 s, ν(C–H) 3100 w, 3055 w, 2969
w, 2880 w; ν(C=N) + ν(C=C) + δ(N−H) 1601 s; ν(N=O) 1549 s; δ(C−H) 1488 s, 1467 s,
1431 s; 1372 m, δ(N=O) 1310 s; 1240 m, 1194 s, 1147 m, 938 w; 826 s; ν(C–S) 726 m; 697
m, 655 m, 515 w. Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1):
[10-3 M] 590 (2.8 x 102); [10-4 M] 406 (2.69 x 104), 332 (2.63 x 104), 266 (3.95 x 104).
em
ex
Fluorescence spectrum: (λmax = 439 nm; λmax = 320 nm). ESI mass data: calc. for
C26H26CuN6O3S+H, [Cu(5-NO2-stsc-N1HEt)(tm-phen)+H]+ , m/z = 566.12; obsd. m/z =
566.13.
2.1.10. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HPh)(κ2: N,N-dm-bipy)] (10). Yield: 0.039 g, 71 %, m.p.
226°C. Anal. Calc. for C26H22CuN6O3S: C 55.56; H 3.94; N 14.95;S 5.70 %; Found: C 56.01; H
3.63; N 14.73; S 5.45 %. IR (cm-1 , KBr): ν(N1–H) 3386 s, ν(C–H) 3145 w, 3057 m, 2858 w;
ν(C=N) + ν(C=C) + δ(N−H) 1598 s; ν(N=O) 1549 s; δ(C−H) 1493 s, 1470 w; 1375 w; δ(N=O)
1308 s; 1244 m, 1149 w, 1100 m, 948 w, 829 s; ν(C–S) 757 s; 692 w, 567 w, 427 w. Electronic
absorption spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M] 593 (2.25 x 102); [10-4 M] 394
ex
(2.08 x 104), 332 (2.79 x 104), 283 (2.69 x 104). Fluorescence spectrum: (λmaxem = 438 nm; λmax
= 320 nm). ESI mass data: calc. for C26H22CuN6O3S +H, [Cu(5-NO2- stsc-N1HPh)(dm-bipy) +
H]+ 562.08; obsd. m/z = 562.69.
2.1.11. [Cu(κ3:O,N3,S-5-NO2-stsc-N1HPh)(κ2:dm-phen)] (11). Yield: 0.041 g, 75 %, m.p. 201°C.
Anal. Calc. for C28H22CuN6O3S⋅CH2Cl2: C 57.38; H 3.78; N 14.34;S 5.47 %; Found: C 56.82; H
4.13; N 14.29; S 5.79 %. IR (cm-1 , KBr): ν(N1–H) 3314 s, ν(C–H) 2995 w, 2881 w; ν(C=N) +
ν(C=C) + δ(N−H) 1608 s; ν(N=O) 1548 w; δ(C-H) 1509 s, 1470 w; 1375 w; δ(N=O) 1313 s;
1243 w, 1100 m, 943 w, 829 s; ν(C–S) 761 s; 656 m, 574 w, 427 w. Electronic absorption
spectrum, (DMSO, λmax /nm, ε / L mol-1 cm-1): [10-3 M] 595 (2.25 x 102); [10-4 M] 398(1.89 x
104), 332 (2.50 x 104), 291 (2.58 x 104), 277 (3.68 x 104). Fluorescence spectrum: (λmaxem = 436
nm; λmaxex = 320 nm). ESI mass data: calc. for C28H22CuN6O3S⋅CH2Cl2+H, [Cu(5-NO2-stsc-N1
HPh)(dm-phen).CH2Cl2 + H]+ , m/z = 670.03; obsd. m/z = 670.01.
7

2.1.12. [Cu(κ3:O,N3,S-5-NO2- stsc-N1HPh)(κ2:N,N-tm-phen)] (12). Yield: 0.042 g, 75%, m.p.
198°C. Anal. Calc. for C30H26CuN6O3S: C 58.67; H 4.27; N 13.68; S 5.22 %; Found: C 59.01; H
4.36; N 13.58; S 5.38 %. IR (cm-1 , KBr): ν(N1–H) 3384 s, ν(C–H) 3143 br, 3056 m, 2899 w;
ν(C=N) + ν(C=C) + δ(N−H) 1598 s; ν(N=O) 1548 s; δ(C-H) 1487 s, 1487 s; 1374 m; δ(N=O)
1306 s; 1244 m, 1197 w, 1149 w, 1099 s, 948 w, 828 s, ν(C–S) 755 m; 680 w, 653 w, 624 w, 516
w, 420 w. Electronic absorption spectrum, (DMSO, λmax /nm, ε / L mol- 1cm-1) : [10-3 M] 591
(2.33 x 102), [10-3 M] 396 (1.97 x 104), 332 (2.03 x 104), 276 (3.77 x 104). Fluorescence
spectrum: (λmaxem = 437 nm; λex = 320 nm).
2.2. X-ray crystallography
The crystal structures of complexes 1, 6 and 7 were determined by mounting a single
crystal of a complex on a glass fiber and data were measured with an Agilent Eos, Gemini
diffractometer, equipped with graphite monochromated Mo-Kα (λ = 0.71073 Å) radiation at
173(2) K. The structures were solved by direct methods and refined using full-matrix least-
squares techniques based on F2 using ShelXL-2014. In these structures, all non-hydrogen atoms
were refined anisotropically and the hydrogens have been fixed geometrically [55-60].
3. Results and discussion
3.1. Synthesis and IR spectroscopy
Chart 3 shows the formation of copper(II) complexes from 5-nitro-salicylaldehyde-N1-
substituted thiosemicarbazones and N, N-donor co-ligands. During reaction of Cu(OAc)2(H2O)
with a thiosemicarbazone ligand, both -2-OH and –N2-H protons were removed by the acetate
base and the thio-ligand as a dianion bonded to CuII to form a {Cu(O,N,S-L)} moiety which was
treated with N,N-donor heterocyclic Lewis bases, namely, dm-bipy, dm-phen and tm−phen
giving rise to the formation of dark green copper(II) complexes, [Cu(κ3-O,N,S-5-NO2-
stscN1HR)(κ2-N,N-L')] 1-12. These complexes are soluble in dichloromethane, methanol,
acetonitrile and dimethyl sulfoxide and are stable to moisture and air.
8

CH3
H3C
4
'
4
3
3
'
'
=
N
N
N
1, 4, 7, 10
2
N
N
2
dm-bipy
NHR
S
OH
C
S
H
N
C
N2
C
N3
Cu
O2N
2
N1HR
O
N3
2, 5, 8, 11
2
9
N
N
H
H3C
CH3
H2L-NHR
dm-phen
H, 1, 2, 3
Me, 4, 5, 6
Et, 7, 8, 9
R =
1- 12
O2N
CH3
H3C
4
7
3, 6, 9, 12
3
H3C
CH3
Ph, 10, 11, 12
8
N
N
2
tm-phen
Chart 3. Thio-ligands and co-ligands in the formation of complexes 1-12.
IR spectra of the copper(II) complexes shows the absence of diagnostic ν(O−H) and
v(N2−H) bands which support that the thio-ligands (H2L-NHR) are coordinating as dianions (L-
NHR)2-. In a typical example, the IR spectrum of the H2L-NH2 ligand showed vibrational bands
due to ν(N2–H) and ν(O−H) as a broad band at 3221 cm–1. This broad band was found to be
absent in its complex, [Cu(κ3:O,N3,S-5-NO2-stsc-N1H2)(κ2:N,N-dm-bipy)] 1, which suggested
deprotonation of both (N2–H) and (O−H) moieties and thus allowing thio-ligand binding to the
metal as a dianion. The ν(N1−H) vibrational band of the –N1HR moiety appeared at 3390 cm-1
in complex 1. The aromatic ring at the C2 carbon showed a ν(C−H) band at 3059 cm-1 and a
methyl group at N1 atom showed ν(C−H) bands at 3100 and 2950 cm-1. The nitro group (−NO2)
present in the aromatic ring showed a ν(N-O) stretching band at 1548 and and δ(N-O) at 1307
cm-1. The diagnostic ν(C=S) band of the free ligand at 845 cm-1 shifted to low energy at 784 cm-1
in complex 1 [52, 61-65]. The bands due to the ν(C=N), ν(C=C) δ(N−H) and δ(C−H)
,
vibrational modes are listed in the experimental section. Complexes 2-12 showed similar trends
in these vibrational bands (see experimental).
9

3.2. Crystal and molecular structures
Complexes, [Cu(κ3-O, N3, S-5-NO2-stsc-N1H2)(κ2-N, N-dm-bipy)] 1, [Cu(κ3-O, N3, S-5-
NO2-stsc-N1HMe)(κ2-N, N-tm-phen)] 6, and [Cu(κ3-O, N3, S-5-NO2-stsc-N1HEt)(κ2-N, N-dm-
bipy)] 7 gave single crystals while others did not yield crystals suitable for single crystal X-ray
crystallography. Complexes 1, 6 and 7 crystallized in orthorhombic, triclinic and monoclinic
crystal systems in space groups Pccn, P and C2/c, respectively. The crystal data are placed in
Table 1, while Table 2 gives important bond parameters.
The molecular structure of complex 1 is shown in Fig. 1. In this complex, copper(II) is
coordinated to O, N, S donor atoms of the thio-ligand and two nitrogen atoms, N4(eq) and N5(ax)
of the 4, 4′-Me2-bipy co-ligand, (Neq - equatorial nitrogen, Nax - axial nitrogen). The O(1), N(1),
S(1) and N4(eq) atoms occupy a square plane while the N5(ax) nitrogen atom occupies one axial
site. The trans bond angles in the square plane, namely, O-Cu-S, 151.13(6) and N3-Cu-
176.86(8)(N4) as well as the adjacent bond angles in the range, ca. 83-96o, reveal a distorted
square pyramid geometry. It is also added here that the distortion value of a coordination
polyhedron, τ = (β-α)/60, is evaluated by the two largest bond angles in five coordination
geometry (τ = 1 for ideal trigonal bipyramid and 0 for square pyramidal environment) [66], and
this value (τ) is equal to 0.428 for complex 1, which is slightly more than that found in analogous
unsubstituted bipy CuII complex (τ = 0.34) [52]. Another complex [Cu(κ3-O, N3, S-5-NO2-stsc-
N1HEt)(κ2-N, N-dm-bipy)] 7 with an ethyl substitution at N1 nitrogen has a similar structure,
and bond parameters and the τ value = 0.407 (Fig. 2).
The coordination pattern of tm-phen complex, [Cu(κ3-O, N3, S-5-NO2-stsc-N1HMe)(κ2-N, N-
tm-phen)] 6 (Fig. 3), is similar to that of complex 1 except for the difference in the bond angles,
O1-Cu-S1, 164.70(6)º and N-Cu- N5(eq), 172.53(8), which gives rise to a low value of τ = 0.131.
It suggests that the geometry of complex is more closely related to a regular square pyramid. It
may be due to the rigidity of phen ring with lesser coordination flexibility unlike the dm-bipy
complexes 1 and 6 above, which formed distorted square pyramidal complexes. This trend is in
line with a related phen complex, [Cu(5-NO2-stsc-NHEt)(phen)] (τ = 0.132) [52].
10

Fig. 1. Molecular structure of complex, [Cu(κ3-O,N3,S-5-NO2-stsc-N1H2)(κ2-N, N-dm-bipy] (1)
showing the atom numbering scheme and 30% probability ellipsoids.
Fig. 2. Molecular structure of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HEt)(κ2-N,N-dm-bipy]⋅CH2Cl2 (7)
showing the atom numbering scheme and 30% probability ellipsoids.
11

Fig. 3. Molecular structure of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HMe)(κ2-N, N-tm-phen]⋅CH2Cl2 (6)
showing the atom numbering scheme and 30% probability ellipsoids.
Table 1
Crystallographic data for complexes 1, 6 and 7.
Compound
1 (H)
6(Me)
7 (Et)
Chemical
formula
M
C20H18CuN6O3 S
C25H24CuN6O3S,
CH2Cl2
C22H22CuN6O,
CH2Cl2
486.00
173(2)
637.03
598.98
T(K)
173(2)
173(2)
Crystal system
Space group
Orthorhombic
Pccn
Triclinic
P
Monoclinic
C2/c
Unit cell dimensions
a(Å)
18.6471(3)
9.2150(8)
23.4042(7)
12

b(Å)
c(Å)
18.3166(3)
12.5820(2)
10.8294(6)
13.9755(8)
11.0202(4)
20.2999(6)
90
90
84.161(5)
88.599(6)
90
α(°)
β(°)
100.273(3)
90
73.670(6)
90
γ(°)
V(Å3)
4297.40(13)
1331.44(16)
5151.8(3)
Z
8
2
8
Dcalcd(g cm-3)
1.502
1.589
1.545
µ(mm-1)
1.148
1.141
1.174
F(000)
1992
654
2456
Reflections collected
Unique reflections
69707
16506
19270
7573
8760,
8535,
(Rint = 0.0488)
(Rint = 0.0350)
(Rint = 0.0292)
Data/restraints/ parameters 7573/ 0/283
8760/0/357
6734
8535/0/328
6099
5423
Reflens.with [I>2σ(I)]
R Indices
R1
0.0503
0.1169
0.0520
0.1311
0.0669
0.1660
wR2
R indices (all data)
R1
0.0829
0.1353
0.0726
0.0968
wR2
0.1469
0.1893
Largest diff. Peak and hole 0.743 and
-0.495 e. Å-3
0.965 and
-0.979 e.Å-3
0.610 and
-1.185 e. Å-3
CCDC
1523770
1523771
1523772
Table 2
Important bond distances (Å) and bond angles (°) in complexes 1, 6, and 7.
1 (H)
6 (Me)
7(Et)
Cu –O1
Cu–N3
1.9498(16)
1.9493(19)
1.9454(18)
1.9641(18)
1.953(2)
1.955(3)
13

Cu–S1
2.3174(7)
2.2577(7)
2.2579(9)
Cu–N(eq)
2.013(2) (N4)
2.189(2) (N5)
100.37(8) (N5)
151.13(6)
2.0305(19)(N5)
2.3086(19)(N4)
91.17(7)(N4)
164.70(6)
2.009(3)(N4)
2.217(3)(N5)
99.92(11)(N5)
150.82(9)
Cu–N(ax)
O1-Cu-N(ax)
O1-Cu-S1
O1-Cu-N(eq)
N3-Cu-S1
88.95(7)(N4)
83.66(6)
88.52(7)(N5)
84.84(6)
89.11(10)(N4)
85.25(7)
N3-Cu-O1
92.64(7)
93.21(7)
92.97(10)
N3-Cu- N(eq)
N4(eq)-Cu- N5(ax)
τ value
176.86(8)(N4)
78.24(8)
172.53(8)(N5)
76.40(7)
175.25(10)(N4)
77.59(10)
0.428
0.131
0.407
Nax = Naxial; Neq = Nequatorial
3.3. ESR spectroscopy
The X-band ESR spectra of microcrystalline samples of copper(II) complexes 1-12 have
been recorded and the important parameters are listed in Table 3. Figures 4-9 depict the
representative ESR spectra of these complexes which unequivocally confirm the presence of a
divalent oxidation state (3d9) of copper in all these complexes. Probably, due to the distortion in
geometry, all ESR signals expected in the parallel and the perpendicular regions involving
63
coupling from Cu (I = 3/2) nucleus are not observed. The ESR signals observed in the two
regions are either partially resolved or merge into one another making it difficult to analyze the
ESR spectra in the context of electron spin-nuclear spin coupling. However, an attempt is made
to calculate A, g and G parameters for these complexes and infer the possible information from
the spectra obtained (Table 3). Complex 1 has shown inverted axial ESR spectrum which is
interesting and g parameters are : gII =2.026 ; g⊥ = 2.154 (Fig. 4) which suggests dz2 ground
state. Complexes 2, 4-7, 9 and 11 have shown axial ESR spectra (Figs 5-8) with g parameters in
the trend : gII > g⊥ > 2 which implies that dx2–y2 is the ground state of copper(II) in these
complexes [67, 68]. Complexes 3, 10 and 12 have shown rhombic spectra (Figs. 8 and 9) and
their g1, g2, g3 values calculated are : 3, 2.196, 2.082 2.026; 10, 2.110, 2.050, -; 12, 2.198, 2.085
and 2.030. Finally complex 8 has shown an isotropic spectrum suggesting symmetrical
14

environments (Fig. 4) with giso = 2.083. The exchange interaction between copper centers in the
polycrystalline compound is revealed by the geometric parameter G, which is calculated using
the equation, G = gII-2.003/g⊥-2.003. The G values calculated for complexes 2, 4-7, 9, 11 fall in
the range, 2.65 to 4.04 and as for most of complexes G < 4, it shows considerable exchange
interaction in the solid complexes [67, 68].
Table 3
ESR data of complexes 1-12
Complex
g-values
giso
G
2.026(gII)
2.191(gII)
2.111
2.098
2.101
0.15
3.67
-
1
2
3
2.154(g⊥)
2.052(g⊥)
g1 = 2.196, g2 = 2.082,
g3 = 2.026
2.186(gII)
2.072(g⊥)
2.110
2.108
2.101
2.101
2.65
3.18
3.76
2.74
4
5
6
7
2.197(gII)
2.064(g⊥)
2.195(gII)
2.053(g⊥)
2.173(gII)
2.065(g⊥)
g = 2.083
2.083
2.098
2.080
2.097
-
8
9
2.194(gII)
2.050(g⊥)
3.82
-
g1 = 2.110, g2 = 2.050
10
11
2.193(gII)
2.050(g⊥)
4.04
g1 = 2.198 , g2 = 2.085
g3 = 2.030
2.104
-
12
15

1
8
Fig. 4. The X-band ESR spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1H2)( κ2-N,N-dm-bipy)] (1) and
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HEt)(κ2-N,N-dm-phen] (8).
16

4
5
Fig. 5. X-band ESR spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HMe)(κ2-N,N-dm-bipy)] (4) and
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HMe)(κ2-N,N-dm-phen] (5).
7
6
Fig.6. The X-band ESR spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HMe)(κ2-N,N-tm-phen]⋅H2O
(6) and [Cu(κ3-O,N3,S-5-NO2-stsc-N1HEt)(κ2-N,N-dm-bipy)]⋅CH2Cl2 (7)
17

2
9
Fig. 7. [Cu(κ3-O,N3,S-5-NO2-stsc-N1H2)(κ2-N,N-2, 9-Me2-phen] (2) and and [Cu(κ3-O,N3,S-
5-NO2-stsc-N1HEt)(κ2-N,N-tm-phen] (9)
3
11
Fig.8. The X-band ESR spectra of [Cu(κ3-O,N3,S-5-NO2- stsc-N1HPh)(κ2-N,N-dm-phen)] (11)
18

and [Cu(κ3-O,N3,S-5-NO2-stsc-N1H2)(κ2-N,N-tm-phen]⋅CH3OH (3)
12
10
Fig.9. The X-band ESR spectra of [Cu(κ3-O,N3,S-5-NO2- stsc-N1HPh)(κ2-N,N-dm-bipy] (10)
and [Cu(κ3-O,N3,S-5-NO2- stsc-N1HPh)(κ2-N,N-tm-phen)] (12).
3.4. ESI Mass Studies
The ESI-mass studies of complexes have been carried out primarily to determine the
molecular ion formation and confirm the molecular structures. Complexes (1-7, 9- 11) have
shown the molecular ions, [Cu(ONS-L)(NN-L')+H]+, which are listed in the experimental
section. In addition, complexes 1, 4-7 and 9 have shown the formation of dimeric species,
[Cu2(ONS)2(NN)2+H]+ (Chart 4) (ONS- a thio-ligand; N,N- dm-bipy, dm-phen and tm-phen
Lewis bases). Representative isotopic pattern and mass spectral peaks of both the species shown
by complex 4 are displayed in Figs.10 and 11 (See supporting information for ESI-mass details –
Figures 1S to 25S).
19

+
+
N3
N
N
N
S
N
N
S
O
O
O
+H
M
M
N
M
+H
N3
S
N3
1-7, 9-11
[Cu(ONS)(NN)+H]+
1, 4-7, 9
[Cu2(ONS)2(NN)2+H]+
Chart 4: Different species identified from ESI-mass study
Intens.
[%]
+MS, 0.1-0.2min #3-12
1+
500.0591
25
20
15
10
5
1+
502.0577
1+
501.0615
1+
503.0592
1+
504.0578
499.0619
498.0646
0
498
500
502
504
506
508
510 m/z
[%]
CuC₂₁H₂₀N₆SO₃, M+nH, 500.0686
1+
500.0686
100
80
60
40
20
0
1+
502.0671
1+
501.0714
1+
503.0696
1+
504.0670
498
500
502
504
506
508
m/z
Fig. 10. ESI-mass peak due to molecular ion, [Cu(5-NO2-stsc-N1HMe)(4,4′-Me2-bipy)+ H]+
(m/z = calcd, 500.07, obsd. 500.06) with isotopic pattern (complex 4).
20

Intens.
300
+MS, 0.1-0.5min #3-29
1001.0997
999.1034
200
1000.1052
1002.1019
1003.1011
100
0
996
998
1000
1002
1004
1006
1008
1010
1012
m/z
C₄₂H₄₀Cu₂N₁₂O₆S₂, M+nH, 999.1300
2500
2000
1500
1000
500
1+
1001.1289
1+
999.1300
1+
1002.1311
1+
1000.1327
1+
1004.1296
0
996
998
1000
1002
1004
1006
1008
1010
1012
m/z
Fig.11. ESI-mass peak of dimeric [Cu2(5-NO2-stsc-N1HMe)2(4,4′-Me2-bipy)2+ H]+ (m/z = calcd,
999.13, obsd. 999.10) with isotopic pattern (complex 4).
3.5. Electronic absorption and fluorescence spectroscopy
The electronic absorption spectra of 10-3 M solutions of complexes 1-12 in DMSO have
shown low intensity, broad d-d electronic absorption bands in the range, λmax = 591-605 nm,
attributed to the presence of copper(II). The 10-4 M solutions showed electronic spectral bands
in the region, 277-287 nm and are assigned to π→π* transitions. Bands in the region, 330-333
nm are assigned to n→π* transitions (intra-ligand) and bands in the region, 398-406 nm are due
to MLCT transitions [60-63, 69] (see experimental for more details). The electronic spectra are
displayed in Figures.13-16.
21

0.5
0.45
0.4
3.5
3
1
2
3
1
2
3
2.5
2
0.35
0.3
0.25
0.2
1.5
1
0.15
0.1
0.5
0
0.05
0
250
350
450
550
450
550
650
750
Wavelength (nm)
Wavelength (nm)
(b) [10-4] M solutions
(a) [10-3] M solutions
Fig. 13. UV-Vis spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1H2)(κ2-N,N-L')] (L' = dm-bipy 1; dm-
phen 2; tm-phen 3
4
3.5
3
0.5
0.45
0.4
4
5
6
4
5
6
0.35
0.3
2.5
2
0.25
0.2
1.5
1
0.15
0.1
0.05
0
0.5
0
450
550
650
750
250
300
350
400
450
500
550
Wavelength (nm)
Wavelength (nm)
(a) [10-3] M solutions
(b) [10-4] M solutions
Fig. 14. UV-Vis spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HMe)(κ2-N,N-L')] )] (L' = dm-bipy 4;
dm-phen 5, tm-phen 6)
22

0.5
0.45
0.4
4
3.5
3
7
8
9
7
8
9
0.35
0.3
2.5
2
0.25
0.2
1.5
1
0.15
0.1
0.05
0
0.5
0
450
500
550
600 650
Wavelength (nm)
700
750
250
300
350
400
450
500
Wavelength (nm)
(a) [10-3] M solutions
(b) [10-4] M solutions
Fig. 15. UV-Vis spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HEt)(κ2-N,N-L')] )] (L' = dm-bipy 7;
dm-phen 8, tm-phen 9)
4
3.5
3
0.5
0.45
0.4
10
11
12
10
11
12
0.35
0.3
2.5
2
0.25
0.2
1.5
1
0.15
0.1
0.5
0
0.05
0
450
550
650
750
250
300
350
400
450
500
550
Wavelength(nm)
Wavelength (nm)
(b) [10-4] M solutions
(a) [10-3] M solutions
Fig. 16. UV-Vis spectra of [Cu(κ3-O,N3,S-5-NO2-stsc-N1HPh)(κ2-N,N-L')] )] (L' = dm-bipy 10;
dm-phen 11, tm-phen 12)
23

These complexes have shown fluorescence with λmax at 433-437 nm corresponding to the
excitation wavelength, λex = 320 nm (Fig. 17). It may be noted that complexes with methyl
substituted phen complexes 2, 3, 5, 6, 8, 9, 11 and 12 displayed more intense fluorescent bands
(Fluorescence Intensity, F.I. = 110-135 a.u.) in comparison to methyl substituted bipy complexes
1, 4, 7 and 10 (F.I. = 90 a.u.; Fig.17). The difference in fluorescence intensity may be attributed
to the fact that there occurs more conjugation in complexes with phen as a co-ligand than that in
complexes with bipy as a co-ligand. It may also be noted that fluorescence intensity decreases
when the R3 group at N1 nitrogen of thio-ligand changes from H to Ph. The fluorescence
intensity of complexes 1-12 are in the range, 90-135 a.u., which is lower than that shown by
unsubstituted bipy/phen complexes (180-270 a.u.) [52]. The difference is attributed to the
inductive effect of an electronic withdrawing -NO2 group which decreases the electron density on
the complex and hence decreases the fluorescence intensity.
2,9 Me2-phen co-ligand
4,4'-Me2-bipy co-ligand
120
3
1
100
6
4
90
80
70
60
50
40
30
20
10
0
100
80
60
40
20
0
9
7
12
10
368
418
468
518
568
370
420
470
520
570
Wavelength (nm)
Wavelength (nm)
24

3,4,7,8-Me4-phen co-ligand
2
140
120
100
80
5
8
11
60
40
20
0
370
420
470
520
570
Wavelength (nm)
Fig. 17. Fluorescence spectra of complexes 1-12 {λem = 433 (1), 434 (2), 436 (3), 436 (4), 434
(5), 435 (6), 440 (7), 436 (8), 439 (9), 438 (10), 436 (11), 437 (12) nm; λex = 320 nm}.
3.6. Antimicrobial activity-zone of inhibition
Table 4 lists the zone of inhibition data which is a measure of antimicrobial activity of
copper(II) complexes with 5-nitro-salicylaldehyde-N1-substitutedthiosemicarbazones, [Cu(κ3-
O,N3,S-5-NO2-stsc-N1HR3) -(κ2-N,N-L')] (R3 = H 1-3, Me 4-6, Et 7-9, Ph 10-12; N, N- L' = dm-
bipy, 1, 4, 7, 10; dm-phen, 2, 5, 8, 11 and tm-phen, 3, 6, 9, 12). Complexes 1, 5, 6, 7 and 10
have shown antimicrobial activity ranging from 18-24 mm zone of inhibition (zoi) against
methicillin resistant staphylococcus aureus (MRSA), while other complexes (2, 3, 4, 8 , 9, 11
and 12) showed very low activity (13-17 mm zoi). This activity is important as the
commercially available Gentamicin was found to be inactive against the MRSA bacterial strain.
As regards Staphylococcus aureus, complexes 1, 4, 5, 7, 10 and 12 exhibited activity in the
range, 24-28 mm zoi which falls in the range of activity shown by Gentamicin (25 mm zoi); the
activity of other complexes for this bacterial strain was less (16-22 mm zoi). Likewise, the
activity of 1, 5, 6 and 10 against Klebsiella pneumoniae is either close or higher (26-35 mm zoi)
than the activity of Gentamicin (32 mm zoi); other complexes (2-4,7-9,11 and 12) showed lower
activity(18-24 mm zoi). The activity against Shigella flexneri was shown only by complex 5 (18
mm zoi) close to that of Gentamicin (17 mm zoi). In the case of Selmonella typhimurium,
several complexes (1-7, 10-12) exhibited antimicrobial activity in the range, 20-33 mm zoi and
25

(cf. Gentamicin with 20 mm zoi). The highest activity against yeast, Candida albicans was
shown by complex 5 with zoi of 31 mm, close to that of commercial Amphotericin (34 mm zoi);
other complexes showed low activity (15-22 mm zoi).
Table 4
Antimicrobial activitya,b,c of complexes 1-12 (zone of inhibition)
Complex
No.(R3)
MRSA
S.
K.
S.
S.
C.
aureus
pneumoniae flexneri typhimurim Albicans
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-dm-bipy)]
1 (H)
4 (Me)
7 (Et)
18
17
19
18
26
24
26
24
26
22
24
26
N.A
N.A
N.A
N.A
28
23
26
26
22
20
21
22
10 (Ph)
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-dm-phen)]
2 (H)
5 (Me)
8 (Et)
15
24
15
13
16
28
21
20
18
35
21
21
N.A
18
23
33
18
23
17
31
18
20
N.A
11 (Ph)
N.A
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-tm-phen)]
3 (H)
6 (Me)
13
18
13
17
N.A
-
17
22
18
24
25
-
18
26
18
22
32
-
N.A
N.A
N.A
N.A
17
20
25
15
22
20
-
17
22
15
19
-
9 (Et)
12 (Ph)
Gentamicind
Amphotericine
-
34
a)All measurements are in mm diameter of the inhibition zone (N.A indicates no activity); b)The
c)
standard deviation varied in the range 0-1 based on three readings; Studies were made in
DMSO; d,e) Commercially available anti-microbial agents. d)Gentamicin acts as positive control
against bacteria (MRSA, S. aureus, K. pneumoniae, S. flexneri, S. typhimurium) and
e)Amphotericin acts as positive control against yeast (Candida albicans).
26

Minimum inhibitory concentration (MIC) and cyctotoxicity
It can be seen from Table 5 that several complexes were active at a minimum inhibitory
concentration (MIC) of 5-7 µg/mL {Staphylococcus aureus: 1, 5, 7; Klebsiella pneumoniae: 1, 5,
7, 9, 10; Selmonella typhimurium; 1, 5, 7, 9, 10}, MIC of 10 µg/mL {Staphylococcus aureus: 8,
9, 11; Klebsiella pneumoniae: 4, 11, 12; Selmonella typhimurium: 3, 12; Candida albicans: 1, 4,
7, 9-12} and MIC of 50 µg/mL {methicillin resistant staphylococcus aureus: 5; Staphylcoccus
aureus: 4, 10, 12; Selmonella typhimurium; 2, 4, 11}. Further, MIC of 750-1000 µg/mL was
required for methicillin resistant staphylococcus aureus: 1, 2, 4, 7-10, 12, Staphylococcus
aureus: 2, 3, 6; Klebsiella pneumoniae: 2, 3, 6, 8; Shigella flexneri: 5 and Selmonella
typhimurium: 6, 8; Candida albicans: 2, 3, 6, 8. All these complexes were further tested for
cellular toxicity testing using sheep blood cells and it has been observed that the viability of
living cells was very low and thus cellular toxicity of these complexes is high. In comparison,
copper(II) complexes of the title ligands with un-substituted bipy/phen complexes displayed low
cellular toxicity[52].
Table 5
Minimum Inhibitory concentration (MIC in µg/mL) of copper (II) complexes, 1-12
Complex
No.(R3)
MRSA
S.
K.
S.
S.
C.
aureus
pneumoniae
flexneri
typhimurium
Albicans
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-dm-bipy)]
N.A
1 (H)
750
7
7
7
10
27

N.A
N.A
N.A
4 (Me)
7 (Et)
750
750
750
50
7
10
5
50
7
10
10
10
10 (Ph)
50
7
7
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-dm-phen)]
N.A
750
N.A
N.A
2 (H)
5 (Me)
8 (Et)
1000
50
750
7
750
5
50
5
750
5
1000
-
10
1000
750
750
10
11 (Ph)
10
10
50
[Cu(κ3-O,N3,S-5-NO2-stsc-N1HR)(κ2-N,N-tm-phen)]
N.A
N.A
N.A
N.A
3 (H)
6 (Me)
9 (Et)
-
750
750
10
750
750
7
10
1000
7
750
1000
10
-
750
750
12 (Ph)
50
10
10
10
4. Conclusion
The structures of these complexes are distorted square pyramidal and displayed intense
fluorescence. The introduction of methyl substitution in the pyridyl rings of bipy/ phen co-
ligands lowered fuorescence intensity vis-à-vis which was shown by similar complexes with the
unsubstituted bipy/phen as co-liagnds [2]. ESI-mass spectral study supported the formation of
molecular ions [M + H]+ that supported the molecular structure of these complexes determined
by X-ray crystallography. The antimicrobial activity of these complexes appeared to vary in the
order : R = Me > Ph ~ Et > H. Among all the complexes investigated, complex [Cu(κ3-O,N3,S-
5-NO2-stsc-N1HMe)(κ2-N,N-dm-bipy)] 5 was most active against methicillin resistant
Staphylococcus aureus (MRSA), Staphylococcus aureus (MTCC740), Klebsiella pneumoniae
(MTCC109), Shigella flexneri (MTCC1457), Salmonella typhimurium (MTCC-439), and
Candida albicans (MTCC227). These complexes are bactericidal / fungicidal and are toxic to
living cells.
28

Supporting Information
Appendix A. Supplementary data CCDC 1523770, 1523771 and 1523772 contains the
supplementary crystallographic data for complexes 1, 6 and 7, respectively. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44)1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk. Supplementary data associated with
this article can be found, in the online version, at http://dx.doi.org/.)
Acknowledgment
Financial assistance from the University Grant Commission (BSR, UGC); the Council of
Scientific and Industrial Research (CSIR), New Delhi; Emeritus Scientist Grant [21(0904)/12-
EMR-II] to TSL. JPJ acknowledges the NSF--MRI program (Grant No. CHE-1039027) for funds
to purchase the X-ray diffractometer.
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29