Synthesis characterization and biological screening of tri-benzyltin(IV) complexes of some Schiff bases

Article abstract of DOI:10.1002/jccs.200400138

Synthesis and characterization of some novel di and tri-benzyltin(IV) complexes of some Schiff bases are reported. The ¹H-NMR, ¹³C-NMR, ¹¹⁹Sn-NMR, IR, Elemental Analysis and ¹¹⁹Sn Moessauber studies are made for structural determination. Spectroscopic data reveals that the ligand molecule is bound to the tin atom through oxygen. On the basis of spectroscopic data tetrahedral geometry is proposed for the synthesized compounds. The synthesized compounds have been tested against various microorganisms. The results obtained show that the synthesized compounds have promising activity against all the tested micro-organisms.

Full text of DOI:10.1002/jccs.200400138

Journal of the Chinese Chemical Society, 2004, 51, 929-934
929
Synthesis Characterization and Biological Screening of Tri-benzyl tin(IV)
Complexes of Some Schiff Bases
Wajid Rehman,a* Amin Badshah,b Musa Kaleem Baloch,a Saqib Ali,b
Gulzar Hameeda and Khalid M. Khanc
aDepartment of Chemistry, Gomal University, Dera Ismail Khan, Pakistan
bDepartment of Chemistry, Quaid-e-Azam University, Islamabad, Pakistan
cHEJ Research Institute, University of Karachi, Karachi, Pakistan
Synthesis and characterization of some novel di and tri-benzyl tin(IV) complexes of some Schiff bases
are reported. The 1H-NMR, 13C-NMR, 119Sn-NMR, IR, Elemental Analysis and 119Sn Mössauber studies are
made for structural determination. Spectroscopic data reveals that the ligand molecule is bound to the tin atom
through oxygen. On the basis of spectroscopic data tetrahedral geometry is proposed for the synthesized com-
pounds. The synthesized compounds have been tested against various microorganisms. The results obtained
show that the synthesized compounds have promising activity against all the tested micro-organisms.
Keywords: Schiff base; Organotin(IV) complexes; Tri-benzyl tin; Activity; Spectra.
INTRODUCTION
Schiff bases play an important role as ligands due to
oxygen free atmosphere. The solvents used were dried before
use according to the literature method.30 The Schiff base
tri-benzyl and I tin(IV) chloride were prepared according to
the methods provided in the literature.29,31 Schiff base II
(compound II) was prepared by refluxing salicyldehyde and
ethylenediamine (2:1) in benzene for 3 hours; the water mole-
cules formed during the reaction were removed aziotropi-
cally using Dean’s stark apparatus. The solid mass formed
was recrystalized from dry acetone.
their ease of preparation and reactivity in organometallic
chemistry.1 Schiff base complexes of organotin(IV) moieties
have been widely investigated and show excellent activity as
fungicides, bactericides, anti-inflammatories, and as PVC
stabilizers.2-4 The increase of the industrial, agriculture and
biological applications of organotin(IV) compounds during
the last few decades has led to their accumulation in the envi-
ronment and finally in the biological systems. However, the
high phytotoxicty of these compounds towards many plants
has restricted their practical use.5 The most recent develop-
ment in the field of organotin(IV) chemistry is their use as
anti-tumor agents. Many di and tri-organotin(IV) complexes
exhibit maximum anti-tumor activity combined with low tox-
icity.6-10 The importance of organotin moieties has been fur-
ther enhanced during the past few decades due to their com-
plexes with biologically important compounds.11-27 In a pre-
vious paper we synthesized organotin(IV) complexes of
Male-imido-Acetic acid.28 As a continuation, we are report-
ing synthesis, characterization and biological elucidation of
tri-benzyl tin(IV) complexes of some reported Schiff bases.29
The melting points were measured on a Reichert ther-
mometer of F. G. Bode Co., Austria. IR spectra were obtained
in KBr using a Perkin Elmer FT IR-1605 Spectrophotometer.
Elemental analyses were carried out on a Yanaco MT-3
high-speed CHN analyzer with antipyrene as a reference
1
compound. The H- 13C- and 119Sn NMR spectra were re-
corded on a multinuclear FT NMR 200 MHz of JEOL using
TMS as an internal standard. Some of the 13C spectra were
measured on a Bruker AM 270 instrument at 50 MHz with 13
C
probe. The Mössbauer spectra were recorded at 80 K on a
Cryophysics instrument equipped with a 15 mCi Ca 119SnO3
source.
Synthesis of Tri-benzyl tin(IV) Complexes of Schiff
Bases
Tri-ethyl amine chloride (20 mM) was added to a solu-
tion of ligand (10 mM) dissolved in chloroform and the re-
sulting mixture was refluxed for 2-3 hours; to this mixture
tri-benzyl tin chloride (20 mM) in chloroform (50 mL) was
EXPERIMENTAL
All the reactions were carried out under anhydrous and

930 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Rehman et al.
added with continuous stirring.
method of Smith.34
The mixture was again refluxed for 7-8 hours under ni-
trogen. White solid material formed during the reaction was
filtered off. The filtrate was concentrated under vacuum. The
solid obtained was recrystallized from a mixture of 1:1 v/v
(50 mL) acetone and petroleum ether (40-60 °C). Products
obtained were kept under nitrogen for further study.
RESULTS AND DISCUSSION
Schiff base 1 and the tri-benzyl tin chloride were pre-
pared according to the literature methods.29,31 Schiff base 2
(compound I) was prepared by refluxing salicyldehyde and
ethylenediamine (2:1) in benzene for 3 hours (Eqn 1). The
tri-benzyl tin(IV) complexes of Schiff bases 1 & 2 were pre-
pared by refluxing Schiff bases 1 & 2, tri-ethyl amine, and
tri-benzyl tin chloride in chloroform (Eqn 2).
Anti Bacterial Activity
The antibacterial activities were determined by using
the agar well diffusion method.32 The wells were dug in the
media with a sterile borer and an eight-hour-old bacterial
inoculums containing ca. 104 - 106 colony-forming units
(CFU)/mL was spread on the surface of the nutrient agar us-
ing a sterile cotton swab. The recommended concentration of
the test sample (2 mg/mL in DMSO) was introduced into the
respective wells. Other wells containing DMSO and the ref-
erence antibacterial drug served as negative and positive con-
trols, respectively. The plates were incubated immediately at
37 °C for 20 h. The activity was determined by measuring the
diameter of the inhibition zone (in mm) showing complete in-
hibition. Growth inhibition was calculated with reference to
the positive control.
C7H6O2 + 2HN-(CH)2-NH2 ® C16H16N2O2 + H2O. (1)
1L + 2Bz3SnCl + Et3N ® 2Bz3SnL + 2Et3N.HCl. (2)
Where L = Schiff base 1 and Schiff base 2.
H
H
H
CH
CH
N
C
N
C
N
C
2
2
OH
OH
OH
HO
Schiff Base 1.
Schiff Base 2.
(Compound 1)
Antifungal Activity
The different concentrations (50, 100, 250 and 500
ppm) of the test compounds I, II & III were used to study the
effect on germination of C. glocoporiodes, A. brassicicola, A.
brassicae, C. capsici and H. graminium by the hanging drop
method developed by Brine.33 The germination of spores was
observed under the microscope after 8 hours of incubation.
The percentage inhibition of spore germination was calcu-
lated as
Physical parameters and the spectroscopic data
Compound I
Recrystallized from acetone, mp: 87 °C, yield: 85%,
solubility: soluble in chloroform and acetone. CHN analysis:
the calculated values are given in parentheses. C: 71.62
(71.64), H: 5.97 (5.89), N: 10.42 (10.44), 1H NMR (CDCl3):
H-1: 8.02 d (8); H-2: 7.11 d (8); H-3: 7.46 d; H-4: 7.2 d (8);
H-7: 9.1 S; H-8: 3.7 t (7). 13C NMR (CDCl3): C-1: 152.6; C-2:
148.3; C-3: 129.5; C-5: 127.34; C-6: 129.1; C-7: 133.8; C-8:
25.8. IR (KBr, Cm-1): 3050 (CH ar), 1680 (nC=N), 3315
(OH).
Percentage inhibition of spore germination =
Total no. of ungerminated spores
´ 100
Compound II
Total no. of spores
Recrystallized from chloroform and petroleum ether
(40-60 °C), Melting Point: 159 °C. Yield: 83%, Molecular
formula: C40H32N2O4Sn, Molecular wt: 724. CHN analysis:
C: 66.27 (66.30), H: 4.40 (4.41), N: 1.91 (1.93). Sn: 16.55
(16.58). IR (KBr, cm-1): 3038 (n CH aromatic), 1678 (nC=N),
535 (nSn-O), 480 (nSn-C). 1H NMR (CDCl3): H-2: 7.7 d (8);
H-3: 7.2 d (8); H-4: 7.15 d (8); H-5: 7.5 d (8); H-7: 9.1 S; H-8:
Acute Toxicity
ALD50 (average lethal dose at 50% survival) of the
compounds was determined in albino mice. The mice of ei-
ther sex (body weight 20-25 g) were used. The test compound
was injected intraperitoneally at different dose levels in
groups of 10 animals and percent mortality in each group was
observed after 24 h of drug administration. The ALD50 value
(1 mg kg-1) was calculated from the data obtained by the
7.8 d (8). H-a: 1.25 S: H-b: H-g:, H-d:, H-w: 7.35-7.40 m. 13
C
NMR (CDCl3): C-1: 154.7; C-2: 141.6; C-3: 138.7; C-4:

Tri-benzyl tin(IV) Complexes of Some Schiff Bases
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 931
128.9; C-5: 140.8; C-6: 135.6; C-a: 29.5; C-b: 132.5; C-g:
129.8; C-d: 133.8; C-w: 123.1. 119Sn NMR (CDCl3): -22.1
ppm. 119Sn Mössbauer (mm-1 s 80 K): Q.S: 3.80; I.S: 1.38; G1:
1.10; G2: 1.12. QS = Quadrupole splitting; IS = Isomer shift;
G1 & G2 = Line widths.
Compound III
Recrystallized from acetone and petroleum ether (40-
60 °C). Melting Point: 177 °C. Yield: 75%, Molecular for-
mula: C58H56N2O2Sn2, Molecular wt: 1052. CHN analysis: C:
66.13 (66.15), H: 5.30 (5.32), N: 2.63 (2.66), Sn: 22.79
(22.81). IR (KBr, cm-1): 3042 (n CH aromatic), 1683 (nC=N),
527 (nSn-O), 447 (nSn-C). 1H NMR (CDCl3): H-2: 7.8 d (8);
H-3: 7.10 d (8); H-4: 7.05 d (8); H-5: 7.6 d (8); H-7: 8.9 S;
H-8: 3.5 t (7). H-a: 2.1 S: H-b:, H-g:, H-d:, H-w: 7.65-7.78 m.
13C NMR (CDCl3): C-1: 155.0; C-2: 141.8; C-3: 138.8; C-4:
129.1; C-5: 141.2; C-6: 136.2; C-7: 122.4; C-8: 143.1; C-9:
134.2; C-a: 30.1; C-b: 134.4; C-g: 128.4; C-d: 127.1; C-w:
123.8. 119Sn NMR (CDCl3): -170.0 ppm. 119Sn Mössbauer
(mm-1 s 80 K): Q.S: 3.77; I.S: 1.40; G1: 0.98; G2: 1.05. QS =
Quadrupole splitting; IS = Isomer shift; G1 & G2 = Line
widths.
Proposed Structure for Complexes II & III
Spectral Results
1
The H NMR chemical shifts have been shown to be
very important in structure elucidation of the coordination
number and geometries of organotin(IV) compounds.35-36
The aromatic protons are in the range of 7.2-7.8 ppm; the up
fielding of aromatic protons is due to ring current effect. The
azomethinic protons resonate at 8-9-9.1 ppm, respectively,
which is in accordance with the earlier reported com-
pounds.37
The 13C NMR spectra of the synthesized compounds
are properly resolved. The 13C chemical shifts of the benzyl
Table 1. Anti bacterial bioassay resultsa,b,c,d for R2SnL2 and R3SnL (inhibition zone in mm)
Micro-Organisms
Ligand 1 Ligand 2
*Cpd I
Cpd II Standard Drug
Gram-Positive
Bascillus subtilis
Staphlococcus aures
Gram-negative
16
24
18
24
20
26
24
32
31
43
Escherichia coli
na
10
12
20
na
12
14
24
12
16
16
28
16
18
20
32
30
33
25
41
Shigella flexenari
Pseudomonas aeruginosa
Salmonella typhi
a Concentration used: 1.00 mg/1.00 mL of DMSO.
b Size of well: 6 mm (diameter).
c Standard drug: Imipinem.
d n.a: no activity.
* Cpd = compound.
Table 2. Toxic effect of compound I
% Inhibition (dose ppm)
Name of Fungi
500
250
100
50
C. capsici
++
++
++
++
++
+
+
+
+
+
+
na
+
+
na
+
na
+
na
na
C. gloeosporioides
A. brassicicola
A. brassicae
H. graminium
+ = low activity, ++ = medium activity, +++ = high activity, na = no activity.

932 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Rehman et al.
groups attached to the tin are observed at the positions com-
parable with similar reported compounds.38-40
Table 3. Toxic effect of compound II
% Inhibition (dose ppm)
119Sn chemical shift of organotin(IV) compounds cover
a range of 600 ppm, for compound I 119Sn signal is observed
at -22.1 ppm and for compound II 119Sn signal is observed at
-170 ppm showing tetrahedral and octahedral geometry, re-
spectively. The results obtained are in accordance with ear-
lier reported compounds.41-44
Name of Fungi
500
250
100
50
C. capsici
+++
++
++
+++
++
++
+
+
++
+
+
na
+
+
na
+
na
+
C. gloeosporioides
A. brassicicola
A. brassicae
na
na
H. graminium
119Sn Mössbauer spectra are sensitive and the most im-
portant tool for the coordination number and for the geometry
of organotin(IV) complexes.45-48 119Sn Mössbauer quadrupole
splitting (QS) value obtained for compound I is 2.88 mm-1
and for compound II is 3.88 mm-1 s. The data obtained
prooves tetrahedral and octahedral geometry of the synthe-
sized compounds.
+ = low activity, ++ = medium activity, +++ = high activity, na =
no activity.
Table 4. Toxic effect of compound III
% Inhibition (dose ppm)
Name of Fungi
500
250
100
50
In the IR spectra of the synthesized compounds the ab-
sorption bands for Sn-O & Sn-C are in consistent with earlier
reported work.49-53
C. capsici
++
+++
++
+++
++
+
++
+
++
+
+
+
-
+
na
na
+
na
+
C. gloeosporioides
A. brassicicola
A. brassicae
Biological Studies
H. graminium
na
Anti-bacterial activity
+ = significant activity, ++ = medium activity, +++ = high
activity, na = no activity.
Antibacterial studies were performed against two Gram
positive (Bacillus subtilus, Staphloccus aureus) and 4 Gram-
negative (Escherichia coli, Schigella flexenaria, Pseudomo-
nas aeruginosa, Salmonella typh) bacteria, and the results are
summarized in Table 1. In order to compare the results ob-
tained the Impinem is used as standard drug. The results ob-
tained show that synthesized compounds have higher activity
than the corresponding ligand but lower activity than the
standard drug.
Table 5.
Compound
ALD50 (mg kg-1)
*Phenyl butazone.
Complex I.
Complex II.
> 500
> 400
> 400
> 400
Complex III.
* Standard drug.
Anti fungal activity
Anti fungal results of the synthesized compounds are
summarized in Tables 2-4. The results show significant activ-
ity at higher concentrations against all plant pathogens. The
increase in toxicity of organotin(IV) compounds may be due
to the coordination of tin(IV) atom with the oxygen of the lig-
ands. The toxicity is also due to the lone pair of electrons on
the oxygen and nitrogen, which may get free in solution and
play a role in increasing the toxic effect of the synthesized
compounds.
rivatives.
ACKNOWLEDGEMENT
We are very greatful to the HEJ Research Institute Uni-
versity of Karachi, for spectroscopic studies and University
of Malaya, Malaysia for recording Sn Mössbauer spectra. Dr.
Mukhtiar Hassan of the Chemistry Department Gomal Uni-
versity is acknowledged for providing useful suggestions
during the work.
Acute toxicity studies
The ALD50 values of the studied tri-bezyl tin(IV) de-
rivatives were found to be more than 400 mg kg-1 (the maxi-
mum dose tested), suggesting the safety margin of these de-
Received March 4, 2004.

Tri-benzyl tin(IV) Complexes of Some Schiff Bases
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 933
26. Buza’s, N.; Gyuresik, B.; Nagy, L.; Zhang, Y. X.; Korecz, L.;
Burger, K. Inorg. Chimica Acta 1994, 218, 65.
27. Jansco, A.; Nagy, L.; Sletten, E. J. Chem. Soc., Dalton
Trans. 1999, 1587.
REFERENCES
1. Joshi, K. C.; Pathak, V. N.; Panwar, P. Agic. Boil. Chem.
1977, 41, 543.
28. Ashfaq, M.; Khan, M. I.; Baloch, M. K.; Malik, A. J.
Organomet. Chem. (Accepted).
2. Mehrotra, R. C.; Srivastava, G.; Saraswat, B. S. Revs. Si, Ge,
Sn, Pb compounds 1982, 6, 171, and references cited therein.
3. Molloy, K. C. In Bioorganotin Compounds; Hartley, F. R.,
Ed.; The Chemistry of Metal-Carbon Bond, John Wiley and
Sons: London, 1989; vol. 5; p 465.
29. Hopfl, H.; Sanchez, M.; Farfan, N.; Barba, V. Can. J. Chem.
1998, 76, 1352.
30. Perrin, D. D.; Armengo, W. L. F. Purification of Laboratory
Chemicals; 3rd Ed.; Pergamon: Oxford, 1988.
31. Sisido, K.; Takeda, Y.; Kingawa, Z. Direct Synthesis of
Organotin Compounds. I. Di- and tribenzyltin chloride. J.
Am. Chem. Soc. 1961, pp 538-541.
4. Tsangaris, J. M.; Williams, D. R. Appl. Organomet. Chem.
1992, 6, 3.
5. Crowe, A. J. Appl. Organomet. Chem. 1987, 1, 143.
6. Crowe, A. J. Appl. Organomet. Chem. 1987, 1, 331.
7. Blunden, S. J.; Cusack, P. A.; Hill, R. The Industrial Uses of
Tin Compounds; Royal Society of Chemistry: London, 1985.
8. Crowe, A. J.; Hill, R.; Smith, P. J. Laboratory Evaluation of
Tributyl tin Compounds as Wood Preservatives; Interna-
tional Tin Research Institute: London, 1979.
9. David, S.; Hanessian, S. Tetrahedran 1985, 41, 643.
10. Patel, A.; Poller, R. C. Rev. Sil. Ger. Tin Lead Comps. 1985,
8, 263.
32. Rahman, A.; Choudhary, M. I.; Thomsen, W. J. Bioassay
Techniques for Drug Development; Harwood Academic Pub-
lishers: The Netherlands, 2001.
33. Brian, Pw. Trans, Brit. Mycol. Soc. 1960, 43, 1.
34. Smith, Q. E. Pharmacological-screening Test Progress in
Medicinal Chemistry I; Butter worth: London, 1960.
35. Lycka, A.; Holecek, J.; Schneider, B.; Straka, J. J.
Organomet. Chem. 1990, 29, 389.
36. Shahid, K.; Ali, S.; Shahzadi, S.; Badshah, A.; Akhtar, Z.
Turk. J. Chem. 2003, 27, 1.
11. Burger, K.; Nagy, L. In Metal Complexes of Carbohydrates
and Sugar Type Ligands; Burger, K., Ed.; Biocoordination
Chemistry, Ellis Horwood: London, 1990; Chapter VI, p
236.
37. Shahid, K.; Ali, S.; Shahzadi, S.; Badshah, A.; Khan, K. M.;
Maharvi, M. Synth. React. Inorg. Met.-Org. Chem. 2003, 33,
1223.
12. Smith, P. J. Chemistry of Tin; 2nd ed., Blackie Academic &
Professional: London, 1997.
38. Xie, Q. L.; Yang, Z. Q.; Jiang, L. Main Group Met. Chem.
1996, 19, 509.
13. Davies, A. G. Organotin Chemistry; VCH: Weinheim, Ger-
many, 1997.
39. Camacho, C. C.; deVos, D.; Mahieu, B.; Gielen, M.;
Kemmer, M.; Biesemans, M.; Willem, R. Main Group Metal
Chem. 2000, 23, 433.
14. Guli, G.; Gennaro, G.; Pellerito, L.; Stocco, G. C. Appl.
Organomet. Chem. 1993, 7, 407.
40. Bonire, J. J.; Fricker, S. P. J. Inorg. Biochem. 2001, 83, 217.
41. Khoo, L. E.; Charland, J. P.; Gabe, E. J.; Smith, F. E. J. Inorg.
Chimica. Acta 1987, 128, 139.
15. Nath, M.; Pokharia, S.; Yadav, R. Coord. Chem. Rev. 2001,
215, 99.
16. Gielen, M. Coord. Chem. Rev. 1996, 151, 41.
17. Tiekink, E. R. T. Appl. Organomet. Chem. 1991, 5, 1.
18. Holloway, C. E.; Melink, M. Main Group Met. Chem. 1998,
21, 371.
42. Grindley, T. B.; Curtis, R. D.; Thangarasa, R.; Wasylishen,
R. E. Can. J. Chem. 1990, 68, 2102.
43. Grindley, T. B.; Thangarasa, R. Can. J. Chem. 1990, 112,
1364.
19. Saxena, A. K.; Huber, F. Coord. Chem. Rev. 1989, 95, 109,
and references cited therein.
44. Blunden, S. J.; Smith, P. J.; Beynon, P. J.; Gilles, D. G.
Carbohydr. Res. 1981, 88, 9.
20. Huber, F.; Barbieri, R. Metal Complexes in Cancer Chemo-
therapy; Keppler, B. K., Ed.; VCH: Basel, 1993; p 351.
21. Clarke, M. J.; Zhu, F.; Frasca, D. R. Chem. Rev. 1999, 99,
2511, and references cited therein.
45. Barbiere, R.; Huber, F.; Pellerito, L.; Ruisi, G.; Silverstri, A.
In Chemsitry of Tin; Smith, P. J., Ed.; Blackie Academic &
Professional: Glasgow, 1997; 496-539.
46. Buzas, N.; Pujar, M. A.; Nagy, L.; Vertes, A.; Kuzmann, E.;
Mehner, H. J. Radioanal. Nucl. Chem. 1995, 189, 237.
47. Nagy, L.; Korecz, L.; Kiricsi, I.; Zsikla, L.; Burger, K.
Struct. Chem. 1991, 2, 231.
22. Barbieri, R. Inorg. Chimica Acta 1992, 191, 253.
23. Barbieri, R.; Ruisi, G.; Atassi, G. J. Inorg. Biochem. 1991,
41, 25.
24. Barone, G.; Barbieri, R.; LaManna, G.; Koch, M. H. J. Appl.
Organomet. Chem. 2000, 14, 189.
48. Vertes, A.; Suveghi, K.; Kuzmann, E.; Burger, K.; Nagy, L.;
Schrantz, K.; Buzas, N. J. Radioanal. Nucl. Chem. 1996,
203, 399.
25. Girasolo, M. A.; Pizzino, T.; Mansueteo, C.; Valle, G.;
Stocco, G. C. Appl. Organomet. Chem. 2001, 14, 97.

934 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Rehman et al.
49. Nath, M.; Yadav, R.; Eng, G.; Musingarimi, P. J. Chem. Res.
(M) 1998, 1730.
Organomet. Chem. 1999, 13, 29.
52. Nath, M.; Yadav, R. Bull. Chem. Soc. Jpn. 1998, 71, 1355.
53. Sandhu, G. K.; Kaur, G.; Holecek, J.; Lycka, A. J.
Organomet. Chem. 1989, 365, 215.
50. Nath, M.; Yadav, R.; Eng, G.; Nguyen, T.; Kumar, A. J.
Organomet. Chem. 1999, 577, 1.
51. Nath, M.; Yadav, R.; Eng, G.; Musingarimi, P. Appl.