Novel bioactive thio- and semicarbazide ligands and their organosilicon (IV) complexes

Article abstract of DOI:10.1080/10426500903348021

Ligational behavior of thiosemicarbazones and semicarbazones derived from 1-phenyl-3-arylpyrazole-4-carboxaldehydes towards triphenylchlorosilane has been investigated by elemental analysis, molar conductivity measurements, and IR, ¹H, ¹³C, and ²⁹Si NMR spectroscopic studies. The ligands and their organosilicon complexes have also been evaluated for in vitro antimicrobial activity against some pathogenic bacteria and fungi. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright

Full text of DOI:10.1080/10426500903348021

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Novel Bioactive Thio- and Semicarbazide
Ligands and Their Organosilicon (IV)
Complexes
Sonika a , Meenakshi a & Rajesh Malhotra a
a Department of Chemistry, Guru Jambheshwar University of Science
and Technology, Hisar, Haryana, India
Published online: 25 Aug 2010.
To cite this article: Sonika , Meenakshi & Rajesh Malhotra (2010) Novel Bioactive Thio- and
Semicarbazide Ligands and Their Organosilicon (IV) Complexes, Phosphorus, Sulfur, and Silicon and the
Related Elements, 185:9, 1875-1885, DOI: 10.1080/10426500903348021
To link to this article: http://dx.doi.org/10.1080/10426500903348021
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Phosphorus, Sulfur, and Silicon, 185:1875–1885, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903348021
NOVEL BIOACTIVE THIO- AND SEMICARBAZIDE
LIGANDS AND THEIR ORGANOSILICON (IV) COMPLEXES
Sonika, Meenakshi, and Rajesh Malhotra
Department of Chemistry, Guru Jambheshwar University of Science and
Technology, Hisar, Haryana, India
Ligational behavior of thiosemicarbazones and semicarbazones derived from 1-phenyl-3-
arylpyrazole-4-carboxaldehydes towards triphenylchlorosilane has been investigated by ele-
mental analysis, molar conductivity measurements, and IR, 1H, 13C, and 29Si NMR spectro-
scopic studies. The ligands and their organosilicon complexes have also been evaluated for
in vitro antimicrobial activity against some pathogenic bacteria and fungi.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Antimicrobial activity; organosilicon (IV) complexes; semicarbazones; spectral
studies; thiosemicarbazones
INTRODUCTION
Thiosemicarbazones and semicarbazones are among the most widely studied nitrogen
and sulfur/oxygen donor ligands.1–5 They are capable of acting as neutral or charged ligand
moieties, as they have interesting coordination properties because only the β-nitrogen
coordinates to the metal atom, while the α-nitrogen atom remains uncoordinated. On the
other hand, the remaining sulfur/oxygen atom has a tendency to form a strong covalent
bond with metal atom. These compounds have remarkable biological activities ranging from
antiprotozoa,6 antifertility,7 antibacterial,8 antifungal,9 antitumoral,10 antiviral activities,11
and especially anti-HIV activity,12,13 properties which have since been shown to be related
to their metal-complexing ability.14
The interest in organosilicon (IV) compounds is due to their versatile applicability in
pharmaceutical and in chemical industries. In addition, the substituted pyrazole ring also
exhibits a broad spectrum of biological activities such as antidiabetic,15 antimicrobial,16–19
and herbicidal.20,21 Moreover, in many cases, by coordination to different transition metal
ions that can be found in biological systems, it is possible to obtain complexes that are
Received 2 June 2009; accepted 18 September 2009.
The authors are grateful to the Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University,
Chandigarh, India, for providing NMR facility and elemental analysis.
Address correspondence to Sonika, Department of Chemistry, Guru Jambheshwar University of Science and
Technology, Hisar-125001, Haryana, India. E-mail: sc ic2001@yahoo.co.in
1875

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SONIKA ET AL.
N
R
N
R
N
N
N
NH2
N
NH2
H
HN
C
H
N
C
X
XH
Ligand HLI
HLII HLIII HLIV HLV HLVI HLVII HLVIII HLIX HLX
R
X
H
CH3 OCH3
Br
S
Cl
S
H
O
CH3 OCH3
Br
O
Cl
O
S
S
S
O
O
Figure 1 Structure of the ligands.
more efficient drugs than the corresponding free ligands. So, the present situation prompted
us to produce such work with monofunctional bidentate azomethine moieties in which
the combined effect of silicon along with plus role of pyrazole ring and sulfur/oxygen is
applicable. The imines used during these studies were derived from thiosemicarbazones and
semicarbazones of 1-phenyl-3-arylpyrazole-4-carboxaldehyde derivatives and are shown
in Figure 1.
RESULTS AND DISCUSSION
The reactions of triphenylchlorosilane with the sodium salts of ligands in 1:1 molar
ratio in dry methanol proceed smoothly with the precipitation of NaCl, and lead to the
formation of triorganosilicon complexes (Scheme 1).
3'
4'
2'
5'
1'
1
2
N
6'
2''
3''
N
N
R
N
1''
3
4''
R
Ph3SiCl
MeOH
5
4
6'' 5''
N
NH2
H
N
N
C
H
N
C
Ph
Ph
X-Na+
Si
X
NH2
Ph
Scheme 1 Synthesis of triphenylsilicon (IV) complexes.
All the newly synthesized complexes have been obtained as solids and are insoluble
in common organic solvents. The molar conductivities of these complexes have low values
(5–15 ohm−1 cm2 mol−1), indicating non-electrolytic nature. The monomeric nature of these
complexes is confirmed by the molecular weight determinations. The stereochemistry of

BIOACTIVE THIO- AND SEMICARBAZIDE LIGANDS
1877
these complexes has been determined spectroscopically using IR and NMR (1H, 13C, and
29Si) spectral data.
IR Spectra
The infrared spectra of the complexes were compared with those of the free ligands
(HLI–HLX) to ascertain the coordination sites on the basis of shifting in the frequency of
various groups and/or from the lowering in the intensities of the absorptions. The broad
and medium intensity bands attributable to v(NH) modes in the region 3200–3100 cm−1
disappear in the silicon complexes, indicating the loss of a proton on the α-nitrogen due
to tautomerization after complexation of the silicon atom to sulfur/oxygen atom. The
bands observed at about 3446 and 3334 cm−1 due to the symmetric and asymmetric
modes of the NH2 group are at virtually the same frequencies in the spectra of silicon
complexes, suggesting the non-involvement of this amino group in chelation.7 In the IR
spectra of the ligands, a sharp band in the region 1605 15 cm−1 can be attributed to the
C N group.22 This band shifts slightly toward lower frequency in the silicon complexes,
indicating the coordination of the azomethine nitrogen to the silicon atom. The ν (C S)
band in thiosemicarbazones and ν (C O) band in semicarbazones appear at 1040 and 1685
cm−1, respectively. These bands disappear upon complexation, which is due to the covalent
bond formation of the ligand with the silicon atom through the sulfur or oxygen atoms.
The formation of the resulting complexes has also been supported by the presence of new
bands due to v(Si O),23 v(Si S), and v(Si N) at 740 10, 540 10, and 580 5 cm−1
,
respectively.9 The appearance of medium to strong intensity bands around 1450–1400,
1130–1085, 800–685, and 690–620 cm−1 have been assigned to (Si C6H5) modes.
1H NMR Spectra
1
The H NMR spectra of the ligands and their corresponding organosilicon (IV)
complexes were recorded in CDCl3 with a few drops of DMSO-d6 using TMS as the
internal standard and are presented in Tables I and II, respectively. In the 1H NMR spectra
of the free thio- and semicarbazide ligands, a broad signal due to the NH proton was
observed at δ 11.14–11.33 and δ 9.98–10.13, respectively, which was absent in the spectra
of complexes, showing the bonding of thiolic sulfur/enolic oxygen to silicon after the
deprotonation of the functional group. The appearance of a signal due to the NH2 group at
about the same position in the ligand and its metal complexes shows the non-involvement
of this group in coordination. The azomethine proton signal shifts downfield in the spectra
of complexes due to the formation of a coordinate linkage between nitrogen and silicon
atom. In the spectra of Ph3SiLI, the new complex multiplet centered at about δ 7.59–7.63
(m, 6H) was due to the ortho- protons, and at about δ 7.31–7.49 (m, 9H) was due to the
meta- and para- protons of the triphenylsilane group.
13C NMR Spectra
The 13C NMR spectra of the ligands and their corresponding organosilicon (IV)
complexes are presented in Tables III and IV, respectively. In the 13C NMR spectra of
free ligands, the thiolo, amido, and azomethine carbons showed signals at δ 177.0, 155.0,
and 133.0–136.0, respectively. These peaks were slightly altered upon complexation with
triphenylsilicon (IV) chloride, indicating the bonding of thiolic sulfur/enolic oxygen and

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SONIKA ET AL.
N
Ph
X
Si
Ph
Ph
N
X
donor sites for the ligand molecules.
Figure 2 Suggested structure for the complexes, X = S or O, and
azomethine nitrogen to the silicon atom. The signals due to ring carbons of phenyl group
attached to silicon appeared at δ 124.5, 128.2, 134.1, and 140.2.
29Si NMR Spectra
The 29Si NMR of complexes gives sharp signals at δ −80 to −110, which clearly
indicates the pentacoordinated environment around the silicon atom and is well in agree-
ment with the reported values.24 Thus on the basis of the foregoing spectral features, the
pentacoordinated structure of the complexes shown in Figure 2 has been proposed.
ANTIMICROBIAL ACTIVITY
The ligands and their silicon complexes were evaluated for in vitro antibacterial
activity against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus and
Gram-negative bacteria Escherichia coli, and in vitro antifungal activity against Candida
albicans and Aspergillus niger fungi. Minimum inhibitory concentrations (MICs) were
determined by means of twofold serial dilution technique25,26 and are presented in Table S1
(available online in the Supplementary Materials).
CONCLUSION
Isolated organosilicon (IV) complexes of thiosemicarbazones and semicarbazones
derived from 1-phenyl-3-arylpyrazole-4-carboxaldehydes were tested against pathogenic
bacteria and fungi. The activity of the ligands were due to the presence of toxophori-
cally important CON or CSN groups. Upon complexation, the activity was further
enhanced against the most of the microorganisms under identical experimental conditions.
EXPERIMENTAL
All the operations were carried out under nitrogen atmosphere using vacuum line. All
the solvents used were dried by conventional methods. Triphenylchlorosilane was obtained
through Aldrich and was used as such without any further purification. IR spectra were
obtained as KBr pellets using a Perkin Elmer Spectrum RX1 instrument. 1H, 13C NMR, and
29Si spectra were determined on a Bruker Avance II 400 MHz NMR Spectrometer in CDCl3

BIOACTIVE THIO- AND SEMICARBAZIDE LIGANDS
1883
and two drops of DMSO-d6 using TMS as an internal standard. Elemental analyses were
carried out on Perkin Elmer 2400. Molecular weights of the complexes were determined
by cryoscopic method in dry nitrobenzene. Molar conductance measurements were carried
out using a Model-306 Systronics conductivity bridge in DMSO solvent. Silicon was
determined gravimetrically as SiO2.
Preparation of Ligands
The 1-phenyl-3-arylpyrazole-4-carboxaldehydes were prepared in two steps. The first
one was the reaction between acetophenone derivatives (20.0 mmol) and phenylhydrazine
(2.16 g, 20.0 mmol) in ethanol (50 mL). The hydrazone derivatives (4.00 mmol) were treated
with the Vilsmeier–Haack reagent, i.e., a cold solution of dimethylformamide (10 mL) and
phosphorus oxychloride (0.5 mL, 6 mmol), leading to the corresponding 4-carboxaldehyde
functionalized pyrazole heterocyclic ring in mild operating conditions. Three equivalents
of this reagent, instead of two as described by Kira et al.,27 were necessary to obtain the
aldehydes in good yields. The condensation of 1-phenyl-3-arylpyrazole-4-carboxaldehydes
(10.0 mmol) with thiosemicarbazide (0.91 g, 10.0 mmol) and semicarbazide hydrochlo-
ride (1.11 g, 10.0 mmol) in the presence of sodium acetate (0.86 g, 10.5 mmol) in
ethanol (30 mL) resulted in the formation of thiosemicarbazone and semicarbazone deriva-
tives, respectively. These were characterized by elemental analyses, IR and NMR spectra
studies.
Preparation of Complexes
To a weighed quantity of triphenylchlorosilane (1.18 g, 4.0 mmol) in dry methanol
(20 mL), sodium salt of the ligands (4.0 mmol) was added. Sodium salt of the ligands was
prepared by adding sodium (0.10 g, 4.50 mmol) to the ligands (4.0 mmol) in dry methanol
(10 mL). The mixture was refluxed for 12–16 h. After the completion of the reaction, the
precipitated sodium chloride was filtered off, and the excess solvent was removed under
vacuum. The residues were dried under vacuum for 3–4 h. The compound was washed
with n-hexane or a mixture of methanol and n-hexane (50:50 v/v) to ensure the purity of
the product and finally dried over a vacuum pump. The elemental analyses and physical
properties of these silicon complexes are given in Table V.
Biological Assays: Antimicrobial Activity
The in vitro antibacterial and antifungal activity of ligands and their organosilicon (IV)
complexes were carried out against the bacteria Bacillus subtilis, Staphylococcus aureus,
and Escherichia coli and fungi Candida albicans and Aspergillus niger using serial dilu-
tion technique in double strength nutrient broth-I.P. and Sabouraud dextrose broth-I.P. as a
medium. The conventional bactericides tetracycline, chloramphenicol, kanamycin, cefazo-
line sodium, and cefotaxime and fungicides cycloheximide, carbendazim, and fluconazole
were used as standards for comparing the activity of compounds. Experimental details for
the antibacterial and antifungal assays are presented in the Supplemental Materials.

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REFERENCES
1. M. J. Campbell, Coord. Chem. Rev., 15, 279 (1975).
2. S. Padhye and G. B. Kauffman, Coord. Chem. Rev., 63, 127 (1985).
3. D. X. West, A. Liberta, S. B. Padhye, R. C. Chikate, P. B. Sonawane, A. S. Kumbhar, and R. G.
Yerande, Coord. Chem. Rev., 123, 49 (1993).
4. D. X. West, S. B. Padhye, and P. B. Sonawane, Structure and Bonding, Vol. 76 (Springer-Verlag,
New York, 1991), pp. 1–49.
5. J. S. Casas, M. S. Garcia-Tasende, and J. Sordo, Coord. Chem. Rev., 209, 197 (2000).
6. H. Cerecetto and M. Gonzalez, Curr. Topics Med. Chem., 2, 1187 (2002).
7. R. V. Singh, S. C. Joshi, A. Gajraj, and P. Nagpal, Appl. Organomet. Chem., 16, 713 (2002).
8. T. Rosu, A. Gulea, A. Nicolae, and R. Georgescu, Molecules, 12, 782 (2007).
9. S. Belwal, N. Fahmi, and R. V. Singh, Appl. Organomet. Chem., 22, 615 (2008).
10. D. K. Sau, R. J. Butcher, S. Chaudhuri, and N. Saha, Mol. Cell Biochem., 253, 21 (2003).
11. T. Vardinova, D. K. Demertzi, M. Rupelieva, M. Demertzis, and P. Genova, Acta Virol., 45, 87
(2001).
12. V. Mishra, S. N. Pandeya, C. Pannecouque, M. Witvrouw, and E. D. Clercq, Arch Pharm., 335,
183 (2002).
13. T. R. Bal, B. Anand, P. Yogeeswari, and D. Sriram, Bioorg. Med. Chem. Lett., 15, 4451 (2005).
14. H. Beraldo and D. Gambinob, Mini Rev. Med. Chem., 4, 31 (2004).
15. K. L. Kees, J. J. Fitzgerald Jr., K. E. Steiner, J. F. Mattes, B. Mihan, T. Tosi, D. Mondero, and
M. L. McCaled, J. Med. Chem., 39, 3920 (1996).
16. R. Aggarwal, V. Kumar, P. Tyagi, and S. P. Singh, Bioorg. Med. Chem., 14, 1785 (2006).
17. V. Kumar, R. Aggarwal, P. Tyagi, and S. P. Singh, Eur. J. Med. Chem., 40, 922 (2005).
18. O. Prakash, R. Kumar, and V. Parkash, Eur. J. Med. Chem., 43, 435 (2008).
19. O. Prakash, R. Kumar, and R. Sehrawat, Eur. J. Med. Chem., 44, 1763 (2009).
20. G. Meazz, F. Bettarini, P. La Porta, and P. Piccardi, Pest Manag. Sci., 60, 1178 (2004).
21. J. C. Jung, E. B. Walkins, and M. A. Avery, Tetrahedron, 58, 3639 (2002).
22. R. Malhotra, J. Mehta, and J. K. Puri, Cent. Eur. J. Chem., 5, 858 (2007).
23. S. P. Narula, N. Kapur, C. R. Rana, and R. Malhotra, Inorg. Chim. Acta, 159, 87 (1989).
24. J. Wagler, U. Bohme, E. Brendler, B. Thomas, S. Goutal, H. Mayr, B. Kempf, G. Y. Remennikov,
and G. Roewer, Inorg. Chim. Acta, 358, 4270 (2005).
25. R. Malhotra, J. Mehta, K. Bala, and A. K. Sharma, Indian J. Chem., 47A, 58 (2008).
26. B. G. Tweedy, Phytopathology, 55, 910 (1964).
27. M. A. Kira, M. O. Abdel-Raeman, and K. Z. Gadalla, Tetrahedron Lett., 2, 109 (1969).