Journal of Undergraduate Chemistry Research, 2008, 7(3), 92
THIOSEMICARBAZONE COMPLEXES OF GROUP 12 ELEMENTS.
1. AN INVESTIGATION OF THE THIOSEMICARBAZONE FROM
p-DIMETHYLAMINOBENZALDEHYDE1
Ryan Harness,* Christopher Robertson and Floyd Beckford†
Science Division, Lyon College, 2300 Highland Road, Batesville AR 72501
Abstract
As a continuation of our interest in thiosemicarbazones and their transition metal complexes, we report the synthetic
and spectroscopic investigations of the thiosemicarbazone from p-dimethylaminobenzaldehyde, dmabTSC, and its
metal complexes of Zn(II), Cd(II), Hg(II) and Cu(II). Elemental analysis and molar conductivity data suggest a bimetallic
copper complex while the other complexes contain a single metal center as expected from the reaction stoichiometry.
In all the complexes dmabTSC coordinates as a neutral bidentate ligand binding through the azomethine nitrogen
and thiocarbonyl sulfur. The ligand and complexes are strongly fluorescent in DMSO but this luminescent is almost
entirely quenched in dichloromethane. In general, the emission intensity of the complexes was less than that for the
free dmabTSC.
Keywords: Fluorescence, Group 12, Infrared, Spectroscopy, Thiosemicarbazone
Introduction
The bioinorganic chemistry of thiosemicarbazones
(TSCs, Figure 1) has become an important area of
study in recent times. Thiosemicarbazones are a class
of Schiff base synthesized by the condensation of
carbonyl compounds with thiosemicarbazides. They
are characterized by having a N,S donor set and this
combination of hard-soft donor character confers very
versatile coordination behavior (1-3). Thiosemicarbazones exhibit thione-thiol tautomerism
presenting several forms of the donor atoms and
generally form four- or five-membered chelate rings
when they bind to metal ions (Figure 1). They are
capable of acting as neutral (thione form) or anionic
(thiolate) ligand moieties. The thione form of the thiosemicarbazones is the most common and the
azomethine group can adopt various positions in
relation to the R′ group (Figure 2) leading to Z, E, and
E′ isomers.
The development of the coordination chemistry of
Figure 1. The thione-thiol tautomerism.
1
thiosemicarbazones is driven by their physiochemical
properties and their quite remarkable range of
biological activities (4-9). The varieties of biological
activity depend on the parent aldehyde or ketone (10).
The heterocyclic thiosemicarbazones (with donor atom
in the 2-position) and their metal complexes, in
particular have been widely studied (11-15). In general
thiosemicarbazones show antibacterial, antimalarial,
antiamoebic, antiviral and anticancer properties
amongst others (11-15).
It is established that metal complexes of thiosemicarbazones are often more biologically active than
the free ligands. For instance, Padhye (16) have
reported that conjugation with metal ions, especially
copper, has been found to synergistically enhance the
antiproliferative activities of thiosemicarbazones from
napthaquinones against MCF-7 breast cancer cells in
vitro.
While there has been considerable interest in the
coordination chemistry of thiosemicarbazones with the
Figure 2. Isomeric forms of thiosemicarbazones.
Part of this work was presented to the Arkansas Academy of Science, April 2008
Journal of Undergraduate Chemistry Research, 2008, 7(3), 93
Figure 3. Structure of p-dimethylaminobenzaldehyde,
thiosemicarbazone dmabTSC.
common transition metals, much less attention has
been paid to the Group 12 elements, particularly
cadmium and mercury- this despite the huge biological
relevance of zinc. In this article we report on an
investigation of the thiosemicarbazone of pdimethylamino-benzaldehyde (dmabTSC, Figure 3)
with the Group 12 elements along with copper.
Experimental
Materials and methods
Analytical or reagent grade chemicals were used
throughout. All the chemicals including solvents were
obtained from Sigma-Aldrich (St. Louis, MO),
Mallinckrodt Baker, (Phillipsburg, NJ), Fisher
Scientific (Pittsburgh, PA) and used as received.
Microanalyses (C, H, N) were performed by Columbia
Analytical (formerly Desert Analytics, Tucson, AZ).
1 H and 13 C NMR spectra were recorded in
dimethylsulfoxide-d6 (Cambridge Isotope Laboratories, Andover, MA) on a Varian Mercury 300 MHz
spectrometer (Varian Inc, Palo Alto, CA) operating at
room temperature. The residual 1H and 13C present in
DMSO-d6 (2.49 and 39.7 ppm respectively) were used
as internal references. Infrared spectra were obtained
from KBr pellets in the range 4000-500 cm-1 on a
Mattson Satellite FTIR spectrophotometer. The
electronic spectra were recorded in quartz cuvettes on
an Agilent 8453 spectrophotometer (Santa Clara, CA)
in the range 190- 1100 nm using samples dissolved in
DMSO. Fluorescence spectra were recorded on a
Varian Cary Eclipse spectrophotometer (Varian Inc,
Walnut Creek, CA). The molar conductance was
measured on a Denver Instrument model 250
conductivity meter. The values reported are averages
of triplicate measurements. Melting points (triplicate
measurements) were determined in open capillaries
and are uncorrected.
Synthesis of p-dimethylaminobenzaldehyde thiosemicarbazone, dmabTSC
Equimolar amounts (66.3 mmol) of p-dimethyl-
aminobenzaldehyde and thiosemicarbazide were
suspended in 100 mL of absolute ethanol containing a
few drops of glacial acetic acid. The reaction mixture
was heated at reflux for 3.5 h and the light yellow
precipitate that formed was collected by filtration and
washed thoroughly with ethanol and dried on the
vacuum line. Yield: 92%
Synthesis of complexes
The complexes were synthesized according to the
following reaction:
The appropriate amount of the thiosemicarbazone
was suspended in 50 mL of methanol (ethanol for the
zinc and copper reactions) and the suspension heated
to boiling to dissolve the ligand. The metal salt
dissolved in ~ 25 mL of alcohol was added dropwise
and the mixture heated at reflux for 2-4h during which
time a bright yellow suspension formed. The yellow
solid was collected by filtration, washed with copious
amounts of alcohol and ether and then dried on the
vacuum line. For the zinc reaction the product was
deposited upon cooling of the reaction mixture. Yields:
50-85%. (Note: Some mercury and cadmium
compounds are known to be hazardous. There are no
indications to suggest that these complexes are any
more toxic than the starting materials but due care
should be used in their handling).
Results and Discussion
Syntheses and characterization
The ligand, dmabTSC, was synthesized by the acid
catalyzed condensation of p-dimethylaminobenzaldehyde with thiosemicarbazide in ethanol. The
reaction produced a yellow-green microcrystalline
solid. Reaction of dmabTSC with the chloride salts
of Zn(II), Cd(II), Hg(II) and Cu(II) yielded yellow
solids that are insoluble in alcohols and water but are
very soluble in DMSO. From microanalytical and
molar conductivity data (Table 1) we propose the
following formulas for the complexes:
Zn(dmabTSC) 2Cl 2, Cd(dmabTSC)Cl 2, Hg(dmab
TSC)Cl2 and [Cu(dmabTSC)Cl]2. (To our knowledge
these complexes have not been reported before.
dmabTSC have been reported to be a sensitive
fluorescent sensor for Hg2+ in aqueous solution but
the compound was not isolated (17)). The molar
conductivity of the complexes was measured in 10-3
Journal of Undergraduate Chemistry Research, 2008, 7(3), 94
Table 1. Physical properties and analytical dataa for the ligand and its complexes.
Formula
Color
ΛMb
C%
H%
N%
Melting point (°°C)
Yield g (%)
a
b
dmabTSC
C10H14N4S
Green-yellow
54.23 (54.03)
6.11 (6.35)
25.29 (25.20)
210
13.5(92)
Zn(dmabTSC)2Cl2
C20H28ZnCl2N8S2
Yellow
9
41.35 (41.39)
4.86 (4.60)
19.29 (19.08)
196 - 200
0.39(60)
Cd(dmabTSC)Cl2
C10H14CdCl2N4S
Yellow
11
29.66 (29.61)
3.49 (3.48)
13.58 (13.81)
243
0.78(85)
Hg(dmabTSC)Cl2
C10H14HgCl2N4S
Yellow
6
24.51 (24.32)
2.83 (2.86)
11.30 (11.35)
179
0.78(71)
[Cu(dmabTSC)Cl]2
C20H28Cu2Cl2N8S2
Salmon
26
38.85 (37.38)
4.41 (4.39)
17.61 (17.44)
198
0.72(50)
The elemental analysis values shown are: found (calculated)
Molar conductance in Ω-1cm2mol-1 determined in 10-3 M DMSO
M DMSO solutions. The measurements suggest that
the complexes are non-electrolytes in solution. In
particular, the value of 9 and 26 Ω-1cm2 mol-1 for the
zinc and copper complexes respectively imply that in
DMSO solutions they exist as non-electrolytes (18).
It can be inferred from this that the chloride ions are
in the coordination sphere of the metal and so are not
free in solution. Together with thespectroscopic data
below we propose the structures in Figure 4. The
proposed binuclear - (bridging chlorides) – structure
for the copper complex is not unusual as there have
been other reports of similar complexes (19-21).
Infrared spectra
The most significant IR bands of dmabTSC and its
metal complexes in the region 4000-500 cm-1 are
collected in Table 2. It can be found that the
characteristic absorption peaks of all complexes are
similar. The absence of a ν(S-H) absorption in the
region 2600-2500 cm-1 is considered as evidence that
the thione form of the ligand exist in the solid state
(Figure 1) (22). There are three bands in the ν(N-H)
region and the band at 3152 cm-1 which is assigned to
the Nb-H group, support the thione formulation of the
ligand. The other two bands (at 3373 and 3250 cm-1)
are the stretching vibrations of the terminal Na-H2
Figure 4. Proposed structures.
Table 2. Selected IRa data for dmabTSC and its complexes
Assignmentb
dmabTSC
Zn(II)
Cd(II)
Hg(II)
Cu(II)
νNH2
3373
3250
3152
1600
826
1065
2904 - 2803
3363
3225
3168
1586
822
1049
2910 - 2805
3322
3381
3263
3172
1585
812
1065
2910 – 2815
3427
3257
3139
1597
806
1060
2990 - 2800
νNH
νC=N
νC=S
νN-N
νCH3
a
(KBr); b in cm-1
3178
1591
803
1065
2900 - 2814
Journal of Undergraduate Chemistry Research, 2008, 7(3), 95
Table 3. 1H and 13C spectral data (DMSO-d6; δ = ppm) for dmabTSC and the metal complexes
Compound
dmabTSC
[Zn(dmabTSC)2Cl2]
Hg(dmabTSC)Cl2
Cd(dmabTSC)Cl2
H NMR
HC=N HNb
H2N
7.92
8.01
8.05
7.92
8.01
7.91
9.05
8.12
1
11.18
11.19
11.26
11.31
C NMR
C=N
C=S
144
144
149
145
178
177
168
177
13
a
group. The ligand shows a medium intensity band at
1600 cm-1 that we ascribe to the ν(C≡N). The major
bands of the ligand shift upon complexation.
Considering the two principal bands, the ν(C≡N) band
shift by 3-15 cm-1 to lower wavenumbers. This
negative shift indicates that the azomethine nitrogen
(Nb) coordinates to the metal (23,24). That the Nb-H
stretching frequency also shifts (due to change in the
electron density upon complexation of the thiocarbonyl
sulfur) supports this theorization. The involvement of
the thiocarbonyl group can similarly be inferred from
the wavenumber shifts that occur on binding. The band
in the free ligand at 826 cm-1 which we attribute to the
C=S group shifts to lower frequencies by 4-23 cm-1.
The amount of the shifts suggest that the ligand
coordinates as a neutral, bidentate (through the
azomethine nitrogen and thiocarbonyl sulfur) ligand
in all the complexes. This is supported by the absence
of all the tell-tale signs of thiolate formation - the
presence of the Nb-H in all the complexes and the lack
of a ν(S-H) band.
NMR spectral studies
The NMR spectra of the ligand and its metal
complexes were run in DMSO-d6 as they are very
soluble in this solvent. The major resonance signals
are shown in Table 3 Figure 3 shows the atom
numbering used for assignment of protons in the
ligand. The 1H NMR spectrum of dmabTSC shows a
singlet at d 11.18. On the basis of spectroscopic data
available in the literature it is suggested that this is
due to the Nb-H proton (24). This signal is also
diagnostic for isomer identification. According to
Afrasiabi (25) it falls between d 13-15 for the E form
and d 9-12 for the Z form (Figure 2). Using that
analysis the ligand under our conditions exists as the
Z isomer. Coupled with the lack of a resonance signal
at ca. d 4.0 attributable to a -SH proton resonance, we
can say that the ligand also exist in the thione form in
solution (of even a polar solvent as DMSO). The ligand
spectrum exhibits two resonances at d 8.01 and d 7.77
which we assign to the germinal Na-H2 protons. This
7.77
7.78
8.91
7.94
is not uncommon (26) and indicates hindered rotation
due to the SC-NaH2 bond containing some double
character (27). However Yu (17) has reported that from
their synthesis of this ligand, the NaH2 signal was seen
as a singlet d 6.7. For our ligands the H2 protons
showed at d 7.56 (J = 9 Hz) and the H1 protons came
at d 6.67 (J = 9 Hz). The signal at 7.92 is assigned to
the H3 proton. The methyl protons came at d 2.93. It
was possible to assign almost all the resonance signals
in the 13C NMR spectrum. The primary assignments
are for the two low-field signals at d 178 assigned to
the C=S and d 144 assigned to the C=N group. The
aromatic signals show up in the usual place (d 110130) and the methyl signals are buried under the
solvent peak. Comparison of the NMR spectra of the
ligand and the metal complexes allows the following
observations:
(i)The presence of the NbH signal in the spectra of the
complexes is indicative of the non-deprotonation of
the ligand confirming the neutrality of the coordinated
dmabTSC. The general downfield shift (0.01-0.13)
reflects coordination through the azomethine nitrogen.
(ii) The signal ascribed to the NaH2 protons in the free
ligand generally move downfield (dramatically for the
mercury complex). This is indicative of the binding
of the thiocarbonyl group and is a result of a decrease
in the electron density caused by electron withdrawal
by the metal ions from the thione sulfur.
(iii) With the exception of the cadmium complex which
shows no shift, the H3 proton is shifted downfield of
the free dmabTSC by an average of 0.13 ppm which
supports azomethine coordination to the metal centers.
(iv) The 13C spectra show that the thiocarbonyl carbon
is shielded in all the complexes. In the mercury
complex the effect is again quite pronounced, the
signal moving to δ 168 from δ 178 in the free ligand.
This behavior for Hg(II) complexes has been noted
by West (24). The signal for the azomethine group
Journal of Undergraduate Chemistry Research, 2008, 7(3), 96
Figure 5. The fluorescence characteristics of the ligand and its metal complexes in various solvents of different
polarity.
shifts to lower fields on complexation. The shifts are
consistent with the participation of the azomethine
group in the metal coordination.
(v) The other protons and carbons in complexes
resonate nearly in the same region as that of the free
dmabTSC.
Electronic spectra
The fluorescence characteristics of the ligand and
its metal complexes in various solvents of different
polarity are shown in Figure 5. It can be seen that the
emission intensity of the compounds is strongest in
DMSO, the most polar of the solvents studied, and
weakest for dichloromethane. In fact, in dichloromethane the fluorescence of the ligand is almost
entirely quenched on coordination to the cadmium ion.
With DMSO as the solvent the mercury complex is
the least luminescent of the complexes. In general there
is a red shift of the emission maxima as the polarity of
the solvent increases. For the cadmium complexes the
maxima is at 414, 420, and 425 nm for dichloromethane, acetone and DMSO respectively. In line with
basic electrostatic theory polar excited sates are
expected to be stabilized by polar solvents. Dipoledipole interactions and hydrogen bonding with solvent
molecules lower the energy of the excited states
(relative to the ground state) leading to the
bathochromic shift going from a non-interactive
solvent like dichloromethane to DMSO. So it may be
presumed that the excited states of most of the
compounds are more polar than the ground state.
The electronic spectra of the ligand and the
complexes were studied in DMSO solutions. All the
complexes show medium to strong bands at 356 and
367 nm (343 nm for the copper complex). These bands
are assigned to the ligational transitions in the
azomethine group (28). For the copper complex one
broad band was seen at relatively low energy (470 nm).
Journal of Undergraduate Chemistry Research, 2008, 7(3), 97
This band can be reasonably assigned to a combination
of ligand to metal charge transfer and metal d-d
transitions. This band is at the higher end of the range
expected for square planar copper complexes (29) and
at the lower end of the range characteristic of metalthiolate complexes (30).
Acknowledgement
The project described was supported by NIH Grant
Number P20 RR-1646 from the IDeA Networks of
Biomedical Research Excellence (INBRE) Program
of the National Center for Research Resources.
References
(1). M. Akbar Ali and S.E. Livingstone. Coord. Chem. Rev.,
1974, 101, 13.
(2). M. Hossain, S.K. Chattopadhyay and S. Ghosh.
Polyhedron, 1997, 16, 4313.
(3). M. Maji, S.K. Chattopadhyay and S. Ghosh.
Transition Met. Chem., 1998, 23, 81.
(4). D. Kovala-Demertzi, M.A. Demertzis, J.R. Miller, C.
Padapoulou, C. Dodorou, and G. Filousis. J. Inorg.
Biochem., 2001, 86, 555.
(5). A.G. Quiroga, J.M. Perez, L-. Solera, J.R. Masaguer,
A. Luque, P. Roman, A. Edwards, C. Alonso and C.NRanninger. J. Med. Chem., 1998, 41, 1399.
(6). D.H. Petering. Bioinorg. Chem., 1972, 1, 255.
(7). D. Kovala-Demertzi, M. Domopoulou, M.A. Demertzis,
G. Valle and A. Papageorgiuo. J. Inorg. Biochem., 1997,
68,147.
(8). D. Kovala-Demertzi, P.N. Yadav, M.A. Demertzis, and
M. Coluccia. J. Inorg. Biochem., 2000, 78, 347.
(9). D.T. Minkel and D.H. Petering. Cancer Res., 1978, 38,
117.
(10). S. Padhye and G.B. Kauffman, Coord. Chem. Rev.,
1985, 63, 127.
(11). O.E. Offiong and S. Martelli, Il Farmaco, 1994, 49,
513.
(12). E. Parmejo, K. Carbello, A. Castineiras, R. Domingues,
C. Maichle-Mossner, J. Strale and D.X. West,
Polyhedron, 1999, 18, 3695.
(13). P.M. Loiseau and D.X. Nguyen, Trop. Med. Int. Health,
1996, 1, 379.
(14). S. Singh, N. Bharti, F. Naqvi and A. Azam. Eur. J.
Med. Chem., 2004, 39, 459.
(15). F. Bregant, S. Pacor, S. Ghosh, S.K. Chattopdhyay
and G. Sava. Anticancer Res., 1993, 13, 1007.
(16). N.G. Gokhale, S.B. Padhye, C.J. Newton and R.
Pritchard. Metal Based Drugs, 2000, 7, 121.
(17). W.J. Geary. Coord. Chem. Rev., 1971, 7, 81.
(18). M.M. Mostafa, A. El-Hammid, M. Shallaby, and A.A.
El-Asmay. Transition Met. Chem., 1981, 6, 303; D.X.
West, A.E. Liberta, S.B. Padhye, R.C. Chikate, P.B.
Sonawane, A.S. Kumbher and R.G. Yerande. Coord.
Chem. Rev., 1993, 123, 49.
(19). H. Beraldo, W.F. Nacif, L.R. Teixeria, and J. S.
Reboucas. Tansition Met. Chem., 2002, 27, 85.
(20). D.X. West, J.K. Swearigen, J. Valdee-Martinez, S.
Hernandez-Ortegs, A.K. El-Sawaf, F. van Meurs, A.
Castineiras, I. Garcia and E. Bermejo. Polyhedron, 1999,
18, 2919.
(21). Z. Afrasiabi, E. Sinn, P. Kulkami, V. Ambike, S.
Padhye, D. Deobagakar, M. Heron, C. Gabbutt, C. Anson
and A. Powell. Inorg. Chim. Acta, 2005, 358, 2023.
(22). F. Beckford and A. Holt. J. Und. Chem. Res., 2007,
6(4), 176; M. Beliochi-Ferrari, F. Biscoglie, C. Cavalieri,
G. Pelosic and P. Tarasconi. Polyhedron, 2007, 26, 3774.
(23). T.S. Lobana and A. Castinieras. Polyhedron, 2002,
21, 1603.
(24). Y. Yu, L.-R. Lin, K.-B. Yang, X. Zhang, R.-B. Huang,
and L.-S. Zheng. Talanta, 2006, 69, 103.
(25). E. Gao, S. Bi and H. Sun. Synth. React. Inorg. Met.Org. Chem., 1997, 27(8), 1115; M.M. Taqui Khan. N.H.
Khan, R.I. Kuresky, A.B. Boricha and Z.A. Shaikh. Inorg.
Chim Acta, 1990, 170, 213.
(26). G.S. Vigee and J. Selbin. J. Inorg. Nucl. Chem., 1969,
31, 3187.
(27). B.S. Gorg, M.R.P. Kurup, S.K. Jain and Y.K. Bhoon.
Transition Met. Chem., 1988, 13, 309.
(28). E. Gao, S. Bi and H. Sun. Synth. React. Inorg. Met.Org. Chem., 1997, 27(8), 1115, and M.M. Taqui Khan.
N.H. Khan, R.I. Kuresky, A.B. Boricha and Z.A. Shaikh.
Inorg. Chim Acta, 1990, 170, 213.
(29). G.S. Vigee and J. Selbin. J. Inorg. Nucl. Chem., 1969,
31, 3187.
(30). B.S. Gorg, M.R.P. Kurup, S.K. Jain and Y.K. Bhoon.
Transition Met. Chem., 1988, 13, 309.
(31). The fluorescence spectra were typically obtained in
10-4 M solutions. For the dichloromethane solutions, a 1
in 10 dilution of a saturated solution was used as the
compounds were not sufficiently soluble. The excitation
wavelengths (nm) were (DMSO, acetone, CH2Cl2):
dmabTSC - 391, 385, 390; Zn(dmabTSC)2Cl2] - 394,
398, 360; Cd(dmabTSC)Cl2 - 392, 358;
Hg(dmabTSC)Cl2 - 326, 338, 386.