Interaction of di-and triorganotin(IV) compounds with carboxylate ligand: Synthesis, spectral characterization, semi-empirical study and in vitro antimicrobial activities

Article abstract of DOI:10.1002/jccs.201000092

Di-and triorganotin(IV) complexes with the general formulae R _nSnL_4-n, where R = Me, n-Bu, Ph and L = 2-[(2′-methylphenylamido)]benzoic acid have been synthesized by the reaction of triethylammonium salt of 2-[(2′-methylphenylamido)]benzoic acid with di-and triorganotin chloride in dry toluene. All the synthesized complexes were characterized by elemental analysis, FT-IR, multinuclear ( ¹H,¹³C,¹¹⁹Sn) NMR, mass spectrometry and semi-empirical study to assess the binding mode of 2-[(2′- methylphenylamido)]benzoic acid. The diorganotin(IV) derivatives are assessed to adopt distorted octahedral and triorganotin(IV) have linear polymeric trigonal bipyramidal structures in which 2-[(2′-methylphenylamido)]benzoic acid is a monoanionic bidentate, coordinating through C(O)O group. This coordination behaviour is also confirmed by semi-empirical study. The isotopic effect of tin was studied by comparison of experimental data with the simulated isotopic pattern using the Chemtool software package. The insecticidal, antileshmanial, antibacterial, antifungal and cytotoxicity of the synthesized compounds are also reported. Some complexes exhibit good activities comparable to that of standard drugs. Furthermore, triorganotin(IV) derivatives exhibit significantly better activities than the diorganotin(IV) derivatives and have a potential to be used as drug.

Full text of DOI:10.1002/jccs.201000092

Journal of the Chinese Chemical Society, 2010, 57, 659-670
659
Interaction of Di- and Triorganotin(IV) Compounds with Carboxylate
Ligand: Synthesis, Spectral Characterization, Semi-empirical Study and In
Vitro Antimicrobial Activities
Saira Shahzadi,a,* Saqib Ali,b,* Khadija Shahid,b Muhammad Yousaf,a
Saroj K. Sharmac and Kushal Qanungoc
aDepartment of Chemistry, GC University, Faisalabad, Pakistan
bDepartment of Chemistry, Quaid-i-Azam University, 45320-Islamabad, Pakistan
cDeptartment of App. Sci. and Hum., Faculty of Engg. and Tech., Mody Institute of Technology and Science
(Deemed University), Lakshmangargh-332311, Dist Sikar, Raj., India
Di- and triorganotin(IV) complexes with the general formulae RnSnL4-n, where R = Me, n-Bu, Ph and
L = 2-[(2¢-methylphenylamido)]benzoic acid have been synthesized by the reaction of triethylammonium
salt of 2-[(2¢-methylphenylamido)]benzoic acid with di- and triorganotin chloride in dry toluene. All the
synthesized complexes were characterized by elemental analysis, FT-IR, multinuclear (1H, 13C, 119Sn)
NMR, mass spectrometry and semi-empirical study to assess the binding mode of 2-[(2¢-methylphenyl-
amido)]benzoic acid. The diorganotin(IV) derivatives are assessed to adopt distorted octahedral and
triorganotin(IV) have linear polymeric trigonal bipyramidal structures in which 2-[(2¢-methylphenyl-
amido)]benzoic acid is a monoanionic bidentate, coordinating through C(O)O group. This coordination
behaviour is also confirmed by semi-empirical study. The isotopic effect of tin was studied by comparison
of experimental data with the simulated isotopic pattern using the Chemtool software package. The insec-
ticidal, antileshmanial, antibacterial, antifungal and cytotoxicity of the synthesized compounds are also
reported. Some complexes exhibit good activities comparable to that of standard drugs. Furthermore,
triorganotin(IV) derivatives exhibit significantly better activities than the diorganotin(IV) derivatives and
have a potential to be used as drug.
Keywords: 2-[(2¢-Methylphenylamido)]benzoic acid; Organotin(IV) complexes; Spectral charac-
terization; Isotopic pattern; Semi-empirical study; Biological activities.
INTRODUCTION
The organotin complexes have been of great interest
and in other properties and application. The syntheses of
organotin complexes are research area of increased interest
for inorganic, pharmaceutical and medicinal chemistry as
an approach to the development of new drugs.6,7 The coor-
dination chemistry of tin is extensive with various geo-
mertries and coordination numbers known for both inor-
ganic and organometallic complexes.8 Higher coordination
numbers can be generated either by inter- and/or intra-mo-
lecular interaction, especially in complexes where tin
bonds to electronegative atoms, such as oxygen, nitrogen
and sulfur. Studies of adducts of organotin halides continue
to provide fundamental information about both the Lewis
acid-base model and the reactivity of organotin species.9
Many amazing structures have been discovered in orga-
notin carboxylates, which include ladder, drum, cube, clus-
ter and cage.10
for many years because of their versatile bonding modes.
Organotin carboxylates are of interests in view of their con-
siderable structural diversity. Depending on the carboxylic
acid used and the stoichiometry of the reactants, several
products such as monomers, dimers, tetramers, oligomeric
ladders, and hexameric drums can be isolated.1-4 Steric and
electronic attributes of organic substituents on tin and/or
the carboxylate moiety impart significant influence on the
structural characteristics in tin carboxylates. The biochem-
ical activity of organotin compounds is also influenced
greatly by the structure of the molecule and the coordina-
tion number of the tin atoms.5 Therefore, synthesis of new
organotin carboxylates with different structural features is
beneficial in the development of pharmaceutical organotin
* Corresponding author. E-mail: drsa54@yahoo.com (S.A); sairashahzadi@yahoo.com (S.S.)

660 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Shahzadi et al.
It has well been established that organotin(IV) com-
pounds are very important in cancer chemotherapy because
of their apoptotic inducing character,11-13 while during the
last few year it is noticeable that organotin compounds oc-
cupy an important place in cancer chemotherapy reports.11
Recently, Blower described thirty interesting inorganic
pharmaceuticals, four of which are tin compounds.14 De-
spite this, the exact mechanism of anti-tumor action of
organotin compounds remains unknown. Tin compounds
and their therapeutic potentials have been reviewed,15,16
while a number of early reviews recording advances in the
screening for anti-tumor potential of organotins are also
available.17,18
carboxyl groups [(nasym(COO) and nsym(COO)] in orga-
notin(IV) carboxylates are important and may help in eluci-
dation of the structures and bonding mode of the ligand.21
When the structure changes to higher-coordinated sym-
metry, the nasym(COO) frequencies shift to lower and
nsym(COO) to higher frequency, which causes decrease in
the Dn value.22 Thus, a mark decrease in the Dn values [Dn
= nasym(COO-nsym(COO)] is observed in all the complexes
compared to the corresponding free acid, suggesting a
bidentate coordination of COO group to tin atom for
carboxylate ligand. Di- and triorganotin(IV) complexes ap-
proaches six- and five-coordination, respectively in the
solid state.
RESULTS AND DISCUSSION
Mass Spectrometry
Organotin(IV) complexes have been prepared by the
reaction of the ligand acid and Et3N with corresponding
organotin(IV) chlorides in 1:1 and 1:2 molar ratios in dry
toluene. However, prolonged reflux (8-10 h) is required for
a good yield. All these complexes 1-5 are solid, with sharp
melting points and are stable in air. Physical data are re-
ported in Table 1.
Mass spectra for the investigated compounds are re-
corded at 70 eV for all di- and triorganotin(IV) derivatives.
The molecular ion peaks of very low intensity are observed
in few complexes.23 In di- and triorganotin(IV) derivatives
a rather similar pattern of fragmentation is observed. In
both cases primary fragmention is due to the successive
loss of R groups followed by the elimination of CO2 from
the ligand and then the remaining part of the ligand which
leaves Sn+ or SnH+ as an end product. Mass data is given in
Table 3. Another possible route is disintegration of the
ligand and stepwise elimination of R groups to Sn+ or SnH+
as a residue. Some common and different peaks (with m/z
and % abundance) which were observed in di- and tri-
organotin(IV) derivatives are reported in Experimental
part. Isotopic patterns in mass spectra were studied as given
in the Experimental and representative spectrum is given in
Fig. 1. They show the isotopic effect on M+ ions in complex
4. As Sn has 10 naturally occurring isotopes this effect is
pronounced in the mass spectra presented in (Fig. 1).
Infrared Spectra
Infrared spectra of the investigated compounds and
ligand acid have been recorded as KBr pellets in the range
4000-400 cm-1. The coordinating behaviour of the ligand
with the di- and triorganotin(IV) moieties, can be inferred
by comparing the infrared spectra of synthesized orga-
notin(IV) compounds with that of free acid. The absorp-
tion frequencies assigned to nasym(COO), nsym(COO) and
n(C=O) have been identified in free ligand acid and the
synthesized compounds are reported together with bands
assigned to n(Sn-C) and n(Sn-O). The absorption bands in
the range 1720-1716 cm-1 can most likely be attributed to
the C=O stretching vibration of the ester group of ligand
moiety and confirms the assessment that there is no partici-
pation of the ester group C=O in the bond formation with
tin atom. This evidence predicts the conclusion that the
sharp absorption band at 1555 cm-1 is due to carboxyl
n(COO) stretching and band at 1716 cm-1 is absorption fre-
quency of the ester group, n(C=O), which contradicts the
early report.19 Moreover, absorption bands in the range
480-415 cm-1 and 582-528 cm-1, assigned to Sn-O and
Sn-C bonds, respectively, also support the formation of
complexes.20 Data is given in Table 2.
NMR Spectroscopy
The 1H NMR spectral data (in CDCl3) identifies al-
most all the protons of ligand and complexes by their inten-
sity and multiplicity pattern. 1H NMR chemical shifts and
coupling constant for reported compounds are summarized
in Table 4.
In 1H NMR spectra of all the complexes studied, the
CO(OH) resonance of the ligand is absent which suggests
the replacement of the carboxylic proton by the organo-
tin(IV) moiety. The -NH signal remains almost unchanged
which indicates that this group is not involved in inter/
intramolecular hydrogen bonding or in bonding to organo-
The values of IR stretching vibration frequencies of

Interaction of Di- and Triorganotin(IV) Compounds
Table 1. Physical data of organotin(IV) carboxylates
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 661
Elemental Analysis %
Calculated (Found)
Quantity Used
2nd Reactant
Comp.
No.
M.P.
(°C)
Yield
(%)
1st Reactant
3rd Reactant
C
H
N
Phthalic
anhydride
10 gm
o-Toluidine
7.2 mL
(6.75 mmol)
70.58
(70.67)
5.09
(5.23)
5.49
(5.59)
HL
-
160-161
88
(6.75 mmol)
Me2SnCl2
0.43 gm
(1.96 mmol)
HL 1 gm
(3.92 mmol)
Et3N 0.54 mL
(3.92 mmol)
58.44
(58.35)
4.56
(4.43)
4.26
(4.17)
1
2
3
4
5
132-133
95-98
85
80
75
70
92
Bu2SnCl2
0.59 gm
(1.96 mmol)
HL 1 gm
(3.92 mmol)
Et3N 0.54 mL
(3.92 mmol)
60.25
(60.12)
5.85
(5.74)
3.90
(3.79)
Me3SnCl
0.78 gm
(3.92 mmol)
HL 1 gm
(3.92 mmol)
Et3N 0.54 mL
(3.92 mmol)
51.67
(51.52)
5.02
(5.13)
3.34
(3.24)
142-144
112-114
75-77
Bu3SnCl
1.06 gm
(3.92 mmol)
HL 1 gm
(3.92 mmol)
Et3N 0.54 mL
(3.92 mmol)
59.55
(59.46)
7.16
(7.29)
2.57
(2.44)
Ph3SnCl
1.51 gm
(3.92 mmol)
HL 1 gm
(3.92 mmol)
Et3N 0.54 mL
(3.92 mmol)
65.56
(65.47)
4.47
(4.33)
2.31
(2.19)
Table 2. Assignment of characteristic FT-IR vibrations of 2-[(2¢-methylphenylamido)]ben-
zoic acid and their organotin(IV) complexes
IR Peak (cm-1)
Comp. No.
nOH
nNH
nC=O
nCOO
Dn
nSn- C
nSn- O
HL
1
3440s
3335s
3330m
3337s
3333s
3335m
3338m
1716s
1555s1 1320s2
235
189
163
125
192
186
-
-
-
-
-
-
-
1719s 1548m 1459m
1711s 1585m 1422s
1709m 1535s
1715s 1572s
582w
528m
560m
535s
226m
415m
462m
480w
472m
445w
2
3
1410s
1380s
4
5
1720s 1567m 1381s
1Antisymmetric 2Symmetric
Abbreviations: s = strong, m = medium, w = weak
tin moiety. All the protons present in the synthesized com-
pounds 1-5 have been identified in position and number
with the protons calculated from increamental method.24
Triphenyltin(IV) complexes show a multiplet in the aro-
matic region of spectra at 7.64-7.68 ppm. Methyl protons
appeared as sharp singlet in both di-n- and tri-methyl-
tin(IV) compounds at 0.26 ppm and -0.03 ppm in solution
state in coordinating solvent, respectively while other pro-
tons show a complex pattern and are assigned according to
earlier reports25 in butyl compounds 2 and 4, protons of
a-carbon show a triplet at 0.87 and 0.94, respectively with
nJ(119Sn-1H) of 78-56 Hz showing the four coordinated na-
ture of this compound in solution.
To confirm the expected structure of the title com-
pounds, 13C NMR data was also recorded for the reported
compounds. 13C NMR data for reported compounds are
given in Table 5. These parameters are useful for the deter-
mination of the coordination number of tin, its molecular
geometry and stereochemistry. In case of diorganotin
dicarboxylates, the geometry around tin could not be deter-

662 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Shahzadi et al.
Table 3. Mass spectral data of organotin(IV) complexes of 2-
[(2¢-methylphenylamido)]benzoic acid at 70 eV
1
2
3
4
5
Fragment Ion
m/z (%) m/z (%) m/z (%) m/z (%) m/z (%)
a
R2SnOO R ¢ 403(8) 487(5) 403(16) 487(8) 527(9)
RSnOOCR¢ 388(6) 430(11) 388(20) 430(10) 450(12)
OCOR¢
bR3Sn+
R2Sn+
RSn+
254(76) 254(81) 254(30) 254(12) 254(8)
164(25) 290(25) 347(16)
-
-
149(56) 233(18) 149(62) 233(50) 271(21)
134(62) 176(42) 134(50) 176(35) 194(31)
76(18) 76(14) 76(30) 76(18) 76(12)
120(11) 120(2) 120(8) 120(6) 120(9)
219(100) 219(100) 219(43) 219(100) 219(26)
57(17) 57(10) 57(100) 57(17) 57(37)
154(20) 154(31) 154(52) 154(24) 154(38)
256(41) 256(53) 256(72) 256(80) 256(100)
+
C6H4
Sn+
+
C14H11O2
+
C4H9
+
C12H9
Fig. 1. Isotopic pattern of M+ ions for compound 4.
HOCOR¢
a R¢ =
CH3
O
mined with certainty due to the fluxional behavior of the
carboxylate oxygens with coordination to tin atom; how-
ever, earlier reports suggest geometry in between penta-
and hexa-coordination.
NH
C
b R = CH3, n-C4H9 and C6H5
The alkyl carbons attached to the tin occurs at the nor-
mal values in case of methyl and butyl tin compounds.26
The aromatic carbon resonances were assigned by the com-
parison of experimental chemical shift with those calcu-
lated from incremental method24 and with literature val-
ues.27 The resonance of the carboxylic carbons in organotin
compounds showed downfield shift (175.5-175.9 ppm)
than in the ligand (172.8 ppm) suggesting the coordination
of the ligand through the carboxylic oxygen, to the organo-
tin(IV) moiety. In 13C NMR data, the measurement of cou-
pling constant helps to determine the molecular structure of
compounds. The value 1J(119Sn-13C) is different in di- and
tri-organotin compounds for tetra and penta-coordinated
nature of tin.
For the n-tributyltin(IV) derivative, with the 1J[119Sn-
13C] value being 350 Hz and by the use of the Holecek and
Lycka equation,27,28 a C-Sn-C value of 111.6° was calcu-
Table 4. 1H NMR dataa of 2-[(2¢-methylphenylamido)]benzoic acid and their organotin(IV) complexes
Chemical Shift (ppm)
Proton
HL
1
2
3
4
5
CH3
2.14(2.3)
2.16(2.5)
2.15(2.5)
2.15(2.4)
2.14(2.3)
2.17(2.6)
7.34-7.41m 7.32-7.41m 7.34-7.39m 7.32-7.41m 7.35-7.42m 7.37-7.42m
- NH
2.24s
7.78-7.82d,d 7.79-7.83d,d 7.80-7.83d,d 7.80-7.86d,d 7.77-7.80d,d 7.81-7.84d,d
(8.1) (8.0) (8.1) (8.2) (7.9) (8.3)
7.95-7.99d,d 7.97-8.00d,d 7.96-7.99d,d 7.96-8.00d,d 7.95-7.99d,d 7.98-8.02d,d
2.25s
2.24s
2.24s
2.23s
2.28s
O
C
O
C
(8.1)
(8.0)
(8.1)
(8.2)
(7.9)
(8.3)
0.26t
0.87t(7.6)
1.35-1.44m
-0.03s
[56]
0.94t(7.6)
1.31-1.34m
R
-
7.64-7.68m
2J[78.9]
a Chemical shifts (d) in ppm. 2J[117/119Sn, 1H]; 2J[119Sn, 1H] and 3J(1H, 1H) in Hz are listed in square brackets
and parenthesis, respectively. Multiplicity is given as: s = singlet, d = doublet, d,d = doublet of doublet, t =
triplet, m = multiplet.

Interaction of Di- and Triorganotin(IV) Compounds
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 663
Table 5. 13C and 119Sn NMR dataa-c of 2-[(2¢-methylphenyl-
downfield shifts from the reference compound having a
positive sign. As the electron-releasing power of the alkyl
group increases the tin atom becomes progressively more
shielded and d(119Sn) value moves to higher field. These
values are also dependent upon the nature of X in RnSnX4-n
and generally move to lower field as the electronegativity
of the latter increases. A very important property of the
119Sn chemical shift is that an increase in coordination num-
ber of the tin atom from four to five, six or seven usually
produces a large upfield shift of d(119Sn).29 In triorgano-
tin(IV) complexes, 119Sn chemical shifts value lie in the tet-
rahedral environment around the tin atom as in non-coordi-
nating solvent whereas the diorganotin(IV) compounds
show the higher coordination, probably five or six. These
values are strongly dependent upon the nature and orienta-
tion of the organic groups bonded to tin. The shifts ob-
served in complexes can be explained quantitatively in
terms of an increase in electron density on the tin atom as
the coordination number increases.29
amido)]benzoic acid and their organotin(IV) complexes
Carbon
HL
1
2
3
4
5
1
2
3
4
5
6
7
8
136.2
131.8
134.2
128.5
127.2
126.5
028.9
167.2
130.4
123.6
118.6
131.0
172.6
136.4
131.9
134.3
128.6
127.6
126.7
028.2
167.3
130.3
123.4
118.4
131.2
175.8
136.3
131.8
134.4
128.7
127.5
126.6
028.4
167.5
130.6
123.8
118.3
131.3
175.6
136.7
131.5
134.7
128.9
127.9
126.3
028.6
167.7
130.7
123.3
118.6
131.1
175.5
136.6
131.3
134.6
128.3
127.0
126.2
028.7
167.6
130.2
123.7
118.8
131.6
175.7
136.9
131.7
134.8
128.8
127.3
126.1
028.3
167.4
130.5
123.9
118.5
131.7
175.9
9
10,10¢
11,11¢
12
13
a Compound 1: Sn-CH3, (C- a) 29.5. d 119Sn = -101.6. Compound
2: Sn-CH2CH2CH2CH3, (C- a) 29.5, (C- b) 27.4, (C- g) 26.8,
(C- d) 14.0. d 119Sn = -129.6. Compound 3: Sn-CH3, (C- a) -2.2
1J[379,398]. d 119Sn = +144.4. Compound 4: Sn-
CH2CH2CH2CH3, (C- a) 29.5 [350], (C- b) 27.2 2J[21.3], (C- g)
26.7 3J[63.5], (C- d) 14.2. d 119Sn = +155.25. Compound 5: Sn-
C6H5, (C- a) 137.8 1J[640.2,660.2], (C- b) 137.5 2J[49.0], (C- g)
136.0, (C- d) 129.32. d 119Sn = -83.6.
As increase in coordination number is accompanied
by an appropriate upfield shift. It is generally accepted that
compounds with a specific geometry about the tin atom
produce shifts in moderately well defied ranges.
b Chemical shifts (d) in ppm: nJ[119Sn, 13C] in Hz is listed in
parenthesis.
c
O
O
R
R
Semi-empirical study
12
9
NH
C
C
O
Sn
R
In 2-[(2¢-methylphenylamido)]benzoic acid HL, the
mean planes of the two phenyl rings make an angle of
48.72° with each other. The two C-O bonds are 1.21 and
1.35 Å, respectively. The C=O and C-N bond length of
NH-CO group being 1.22 and 1.41 Å, respectively. The se-
lected bond length and angles of the optimized structure are
given in Table 6. The optimized and chemical structure is
shown in Fig. 2.
8
13
7
1
10
10
H3C
2
6
11
11
3
5
4
R¢ = R for triorganotin, R¢ = L for diorganotin
lated, which corresponds to a quasi-tetrahedral geometry in
CDCl3 solution. The geometric data calculated, as just de-
scribed, are consistent with tetrahedral geometries for the
triorganotin(IV) species, i.e., monomer in solution. For the
diorganotin(IV) species, for which earlier results indicate
five coordination, the calculated C-Sn-C angles are consis-
tent with the skew-trapezoidal bipyramidal geometries,
with the lower apparent coordination number arising from
the asymmetric coordination mode of the carboxylate
ligand. The value of d 119Sn defines the region of various
coordination number of central tin atom.29 The results are
listed in Table 5.
In all the five compounds 1-5, the carboxylate group
binds in an anisobidentate mode to the Sn atom. The bond
lengths and angles are similar to those in the literature.30 In
compound 1, the Sn atom is 2.01 and 2.70 Å away from the
oxygen’s of the carboxylic group. The two long Sn-O bond
being trans to each other. The C-O bond are also unequal
they are 1.31, 1.23 Å the shorter C-O bond corresponding
to the weakly coordinating oxygens. The two methyl
groups are equidistant from Sn (2.07 Å) and complete the
coordination sphere of Sn. The Me(C)-Sn-(C)Me angles
are 114.3°. The O-Sn-O and O-C-O angles are 50.4 and
110.6°, respectively for both the carboxylic ligands. The
mean planes of the two phenyl groups of the carboxylic
ligand make an angle of 47.8° with each other for one
In all complexes, 119Sn spectra show only a sharp sin-
glet indicting the formation of single species. 119Sn chemi-
cal shift d(119Sn) of organotin compounds cover a range of
over 600 ppm and are quoted relative to tetramethyltin with

664 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Table 6. Bond lengths (Å) and angles (°) for HL
Shahzadi et al.
Table 7. Bond lengths (Å) and angles (°) for compound 1
C4
C2
C3
C3
C7
1.40
1.39
C3 C2
C2 C1
N12 C14
O27 C26
1.40
1.48
1.41
1.21
Sn1 O2 2.01
Sn1 C37 2.07
O2 C3 1.31
C61 C62 1.38
Sn1 C33
Sn1 O41
C3 O4
Sn1 O43
2.07
2.01
1.23
2.70
N12 1.44
C14 C16 1.50
C3
C4
C5
C3
C2
C3
C4
C7
N12 119.62
C3 120.02
118.82
C3 C2 C1 122.30
C2 C3 N12 120.23
C2 C7 C6 120.94
N12 C14 O15 122.17
C33 Sn1 C37 114.29
O2 Sn1 O43 83.39
C33 Sn1 O4 90.30
O41 Sn1 O43 50.37
C33 Sn1 O41 101.37
C33 Sn1 O43 148.89
C37 Sn1 O4 148.83
O41 Sn1 O4 83.29
N12 C14 124.77
also unequal being 1.23 and 1.31 Å with the shorter C-O
bond for the weakly coordinated longer Sn-O. The three
methyl groups are equidistant from Sn (2.10 Å) and com-
plete the coordination. The Me-Sn-Me angles are 110.0,
114.3 and 110.5°. The O-Sn-O and O-C-O angles are 49.7
and 111.4°, respectively. The mean planes of the two
phenyl groups of the carboxylic ligand make an angle of
76.7° with each other. The selected bond length and angles
of the optimized structure are tabulated in Table 9. The op-
timized and chemical structure is shown in Fig. 5.
ligand and 47.3° for the other. The selected bond length and
angles of the optimized structure are tabulated in Table 7.
The optimized and chemical structure is shown in Fig. 3.
In compound 2, the Sn atom is 2.01 and 2.71 Å away
from the oxygen’s of the carboxylic group. The two long
Sn-O bond being trans to each other. The C-O bonds are
nearly equal (1.31 Å). The two butyl groups are equidistant
from Sn (2.10 Å) and complete the coordination sphere of
Sn. The Bu(C)-Sn-(C)Bu angles are 117.2°. The O-Sn-O
and O-C-O angle are 50.2 and is 110.8°, respectively for
both the carboxylic ligands. The mean planes of the two
phenyl groups of the carboxylic ligand make an angle of
35.3° with each other for one ligand and 44.8° for the other.
The selected bond length and angles of the optimized struc-
ture are given in Table 8. The optimized and chemical
structure is shown in Fig. 4.
In compound 4, the Sn atom is asymmetrically at-
tached to carboxylic acid with displacement of Sn atom
from the O atoms being 2.02, 2.74 Å. The C-O bonds are
also unequal being 1.23 and 1.31 Å with the shorter C-O
bond for the weakly coordinated longer Sn-O. The three
butyl groups are equidistant from Sn (2.14 Å) and complete
the coordination. The Bu-Sn-Bu angles are 112.2, 111.4
In compound 3, the Sn atom is asymmetrically at-
tached to carboxylic acid with displacement of Sn atom
from the O atoms being 2.02, 2.74 Å. The C-O bonds are
Fig. 3. Geometry optimised and chemical structure of
Fig. 2. Geometry optimised and chemical structure of
compound 1.
2-[(2¢-methylphenylamido)]benzoic acid HL.

Interaction of Di- and Triorganotin(IV) Compounds
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 665
Table 9. Bond lengths (Å) and angles (°) for compound 3
Table 8. Bond lengths (Å) and angles (°) for compound 2
Sn1 O2 2.01
Sn1 C46 2.11
O2 C3 1.31
Sn1 C33 2.10
Sn1 O59 2.01
Sn1 O61 2.71
C9 C10 1.39
Sn1 O2 2.74
Sn1 C33 2.10
O2 C3 1.23
Sn1 O32 2.02
O23 C6
1.22
C38 C37 1.51
C18 C23 1.40
C6 C5 1.50
C5 C4 1.39
O2 Sn1 C33 86.46
O2 Sn1 C41 146.64
C33 Sn1 C37 114.38
C9 C8 N7 119.94
O2 Sn1 C33 109.34
O2 Sn1 O61 82.55
C46 Sn1 O41 47.92
O59 Sn1 O4 83.22
O2 Sn1 O59 121.67
C33 Sn1 C46 117.20
O59 Sn1 O61 50.25
O61 Sn1 O4 76.80
O2 Sn1 O32 49.68
O2 Sn1 C37 86.67
O32 Sn1 C41 96.95
C4 C27 C26 120.24
and 108.3°. The O-Sn-O and O-C-O angles are 49.7 and
111.4°, respectively. The mean planes of the two phenyl
groups of the carboxylic ligand make an angle of 77.3°
with each other. The selected bond length and angles of the
optimized structure are tabulated in Table 10. The opti-
mized and chemical structure is shown in Fig. 6.
Table 10. Bond lengths (Å) and angles (°) for compound 4
C13 C12 1.38
O23 C6
1.22
Sn1 O2 2.74
Sn1 C33 2.14
Sn1 C59 2.13
O2 Sn1 O32 49.65
O2 Sn1 C46 86.26
O32 Sn1 C33 113.81
C46 Sn1 C59 111.42
Sn1 O32 2.02
Sn1 C46 2.13
C11 C10 1.38
Sn1 C33 86.79
Sn1 C59 146.54
O2
O2
In compound 5, the Sn atom is asymmetrically at-
tached to carboxylic acid with displacement of Sn atom
from the O atoms being 2.01, 2.74 Å. The C-O bonds are
also unequal being 1.23 and 1.31 Å with the shorter C-O
bond for the weakly coordinated longer Sn-O. The three
phenyl groups are are nearly equidistant from Sn (2.06 Å)
and complete the coordination. The Ph(C)-Sn-(C)Ph an-
gles are 110.3, 108.8 and 116.1°, respectively. The O-Sn-O
and O-C-O angles are 49.6 and 111.2°, respectively. The
mean planes of the two phenyl groups of the carboxylic
ligand make an angle of 75.5° with each other. The selected
O32 Sn1 C59 96.91
Sn1 C33 C34 110.02
bond length and angles of the optimized structure are tabu-
lated in Table 11. The optimized and chemical structure is
shown in Fig. 7.
Microbial Assay
Antibacterial activity
Organotin(IV) complexes were tested against the
three Gram-positive bacterial strains, Bacillus subtilis
Fig. 5. Geometry optimised and chemical structure of
Fig. 4. Geometry optimised and chemical structure of
compound 3.
compound 2.

666 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Shahzadi et al.
(ATCC 6633), Micrococcus leuteus (ATCC 10240) and
Staphlococcus aureus (ATCC 6538)] and three Gram-neg-
ative bacterial strains, Escherichia coli (ATCC 15224),
Enterobactor aerogenes (ATCC 13048) and Bordetella
bronchiseptica (ATCC 4617). The agar well-diffusion
method31 was used in this assay and each experiment was
done in triplicate. The results are listed in Table 12. The an-
tibacterial studies exhibited that the complex 3 and 4 does
not show activity towards Escherichia coli. But the com-
plex 5 shows the significant activity against all bacterial
strains.
Table 11. Bond lengths (Å) and angles (°) for compound 5
Sn1 O2 2.01
Sn1 C55 2.06
C5 C6 1.39
Sn1 C33 2.06
O2 C3 1.31
C3 O4 1.23
C3 C5 1.48
C18 C19 1.40
O2 Sn1 C55 97.39
C44 Sn1 C55 108.84
Sn1 C33 C34 119.96
O2 Sn1 C33 111.05
C33 Sn1 C44 116.06
C55 Sn1 O4 147.03
Sn1 O2 C3 116.78
O2 C3
O4 111.22
azole and Amphotercin B. were used as standard drugs.
When the reported compounds were screened against dif-
ferent plant pathogens using tube diffusion method,31 it
was observed that all compounds show the significant
antifungal activity as compared to synthesized ligand.
Cytotoxicity
Brine Shrimp method31 has been used to check the
toxicity of the synthesized compounds by using Etoposide
as standard drug. Cytotoxicity data are given in Table 13.
Highest toxicity was shown by compound 1, whose LD50
value is 17.99 mg/mL, while the lowest toxicity is shown by
compound 4, whose LD50 value is 5.18 mg/mL as compared
to standard drug.
Insecticidal Activity
Insecticidal activity data was collected by contact
toxicity method31 and the data is reported in Table 15 for
complexes 1-5. Premethrin was used as standard drug with
concentration 235.7 mg/cm2. Complex 1, 4 and 5 shows the
activity against all insects while the complex 2 and 3 does
not show any insecticidal activity against Tribolium casta-
neum.
Antifungal Ativity
The present inhibition of the synthesized ligand and
compounds are given in Table 14. Miconazole, Ketocon-
Fig. 7. Geometry optimised and chemical structure of
Fig. 6. Geometry optimised and chemical structure of
compound 5.
compound 4.

Interaction of Di- and Triorganotin(IV) Compounds
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 667
Table 12. Antibacterial activitya-c (diameter of inhibition zone after 20 h) of 2-[(2¢-methylphenyl-
amido)]benzoic acid and their organotin(IV) complexes
Inhibition Zone Diameter (mm)
Reference
Drug
Bacterium (ATCC No.)
HL
1
2
3
4
5
-
-
-
-
-
-
Escherichia coli (11229)
Bacillus subtilis (11774)
Shigella flexenari (10782)
Stephlococcus aureus (25923)
Pseudomonas aeruginosa (10145)
Salmonella typhi (10749)
15
20
11
-
-
14
16
-
13
12
10
10
-
-
-
10
09
13
-
12
18
16
12
15
16
35
38
32
38
29
28
15
14
16
-
-
a In vitro, agar well diffusion method, conc. 3 mg/mL of DMSO
b Reference drug, Imipenum
c Clinical Implication: Escherichia coli, infection of wounds, urinary tract and dysentery; Bacillus
subtilis, food poisoning; Shigella flexenari, blood diarrhea with fever and severe prostration;
Staphlococcus aureus, food poisoning, scaled skin syndrome, endrocarditis; Pseudomonas
aeruginosa, infection of wounds, eyes, septicemia, Salmonella typhi, typhoid fever, localized
infection.
concentration which produced 50% reduction in parasites
Table 13. Brine Shrimp (Artemia salina) lethality bioassay of 2-
after 72 h of incubation.31 Compounds 1-5 show good anti-
leishmanial activity. Amphotericin B. was used as standard
drug with the concentration 0.19 mg/mL.
[(2¢-methylphenylamido)]benzoic acid and their
organotin(IV) derivatives
Comp. Dose No. of No. of
LD50 Standard LD50
No.
(mg/mL) Shrimps Survivors (mg/mL) Drug (mg/mL)
The results obtained support the earlier reports that
there is direct relation between the activity and the coordi-
nation environment of the metal. Function of the ligand is
to support the transport of the active organotin moiety to
the site of the action where it is released by hydrolysis.32
The anionic ligand also plays an important role in deter-
mining the degree of the activity of organotin compounds.
As the triorganotin(IV) compounds show tetrahedral ge-
ometry in solution and they show significant activity which
is consistent with literature that species generating the tet-
rahedral geometry in solution are more active.33,34
100
10
1
30
30
30
0
14
22
HL
-
Etoposide 7.46
100
10
1
30
30
30
0
13
25
1
2
3
4
5
17.99 Etoposide 7.46
13.92 Etoposide 7.46
100
10
1
30
30
30
0
8
21
100
10
1
30
30
30
6
10
10
-
Etoposide 7.46
Thus the presence of an organic group directly at-
tached to tin is an important factor which is responsible for
enhanced activity of organotin(IV) complexes. This indi-
cates that the alkyl group directly appended to the central
tin atom is important contributor to the activity.
100
10
1
30
30
30
0
0
4
5.18 Etoposide 7.46
9.14 Etoposide 7.46
100
10
1
30
30
30
0
10
17
EXPERIMENTAL
Physical measurements
Melting points were determined in capillary tubes us-
ing a MP-D Mitamura Riken Kogyo (Japan) electrothermal
melting point apparatus and are uncorrected. Infrared ab-
sorption spectra were recorded as KBr (4000-400 cm-1)
pellets on Bio-red FTIR spectrophotometer.
1H, 13C and 119Sn NMR spectra were recorded on a
Antileishmanial Activity
The antiprotozoal activity of the compounds 1-5
against the pathogenic Leishmania was obtained and data
are given in Table 16. Reported compounds produced a sig-
nificant reduction in viable promastigotes. The minimum
protozoa concentration for promastogotes, defined as that

668 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Shahzadi et al.
Table 14. Antifungal activitya-c (% inhibition) of 2-[(2¢-methylphenylamido)]benzoic acid and their
organotin(IV) complexes
Inhibition (%)
MIC
(mg/mL)
Fungus (ATCC No.)
Standard Drug
HL
1
2
3
4
5
Trichophyton longifusus (22397)
0
0
79.8
0
100
0
Miconazole
Ketoconazole
Miconazole
070.0
Candida albicans (2192)
Aspergillus flavis (1030)
Microsporum canis (9865)
Fusarium solani (11712)
Candida glaberata (90030)
0
0
0
0
0
72.5 85.5
66.6 89.2
0
0
0
0
100 100
90.0 70.2 Amphotercin B.
110.8
020.0
098.4
073.2
110.8
0
100 80.2
0
86.4
95.4
Miconazole
Miconazole
Miconazole
95.8 100
0
0
0
90.2
0
a Concentration: 100 mg/mL of DMSO
b MIC: Minimum inhibitory concentration
c Percent inhibition (standard drug) = 100
Table 15. Insecticidal biassaya-c of organotin(IV) complexes of
200736 program in gas phase using PM3 method.37,38 The
newer PM6 method gave unsatisfactory results for com-
pounds 1-5, therefore for sake of uniformity PM3 method
was used for the free ligand HL as well. Selected parts of
the complexes not containing the metal ion were pre-
optimised using molecular mechanics methods. Several cy-
cles of energy minimisation had to be carried for each of the
molecules. Molecular Mechanics correction was applied to
the -CO-NH- barrier. Geometry was optimized using Eigen
vector following the Root Mean Square Gradient for mole-
cules was found to be (HL) 0.035 (1) 0.073 (2) 0.009 (3)
0.100 (4) 0.093 and (5) 0.052. Self consistent field was
achieved in each case. The final heat of formation of mole-
cules (in Kcal.) are as follows HL -80.10415, 1 -86.78979,
2 -127.8883, 3 -162.0344 4 -190.6807 and 5 18.43217.
Materials and chemicals
2-[(2¢-methylphenylamido)]benzoic acid
% Mortality
Insects
1
2
3
4
5
Tribolium castaneum
Sitophilus oryzae
20
20
25
30
-
25
20
-
-
18
22
19
25
20
18
16
28
25
20
30
Rhyzopertha dominica
Callosbruchus analis
a Concentration of sample: 1571.3 mg/cm2
b Standard drug: Permethrin
c Concentration of standard drug: 237.7
Table 16. Antileishmanial activity biassaya-d of organotin(IV)
complexes of 2-[(2¢-methylphenylamido)]benzoic acid
Compound No.
1
2
3
4
5
All the glass apparatus with standard quick fit joints
were used throughout the work after cleaning and drying at
120 °C. Di- and triorganotin(IV) salts were purchased from
Aldrich. All other reagents were of the purest grade avail-
able. Solvents were purified as in previously published
methods.39 The o-toluidine and phthalic anhydride were
commercial products and used without further purification.
General Procedure for Synthesis of 2-[(2¢-methyl-
phenylamido)]benzoic acid HL
% Inhibition
IC50 (mg/mL)
Standard drug (mg/mL) 0.19
100
68.1
100
67.1
0.19
100
67.1
0.19
100
67.5
0.19
100
67.5
0.19
a Test organism: Leishmania major (DESTO)
b Standard drug: Amphotericin.B
c Incubation period: 72 h
d Incubation temperature: 22 °C
Bruker AM-250 spectrometer (Germany), using CDCl3 as
an internal reference [d 1H(CDCl3) = 7.25 and d 13C(CDCl3)
= 77.0]. 119Sn NMR spectra were obtained with Me4Sn as
external reference [d(Sn) = 37.290665]. Mass spectral data
were measured on a MAT 8500 Finnigan 70 eV mass spec-
trometer (Germany). The stimulated isotopic distribution
was computed with the CHEMTOOL Software Package.35
The HL and complexes 1-5 were modeled by MOPAC
A solution of phthalic anhydride (5 mmol) in HOAc
(300 mL) was added to a solution of o-toluidine (5 mmol)
in HOAc (150 mL) and the mixture was stirred overnight at
room temperature. The pale yellow precipitates were fil-
tered, washed with cold distilled H2O (200 mL) and air
dried.

Interaction of Di- and Triorganotin(IV) Compounds
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 669
Biological activity data shows that all the complexes are
biologically active with few exceptions and can be used as
drug.
ACKNOWLEDGEMENTS
SA is thankful to Quaid-i-Azam University, Islama-
bad for financial support. SKS and KQ thanks the Head,
App Sci. and Dean FET, MITS for encouragement and sup-
port.
Received April 9, 2010.
REFERENCES
1. Holmes, R. R. Acc. Chem. Res. 1989, 22, 190.
2. Tiekink, E. R. T. Trends Organomet. Chem. 1994, 1, 71.
3. Chandrasekhar, V. S.; Nagendran, Baskar, V. Coord. Chem.
Rev. 2002, 235, 1.
4. Prabusankar, G.; Murugavel, R. Organometallics 2004, 23,
5644.
General Procedure for Synthesis of Organotin(IV)
complexes
5. Zhang, R.; Sun, J.; Ma, C. J. Organomet. Chem. 2005, 690,
4366.
6. Cini, R.; Comments, R. Inorg. Chem. 2000, 22, 151.
7. Marileno, K. V. Breast Cancer Res. 2004, 6, R63.
8. Smith, P. J. Chemistry of Tin, 2nd ed.; Blackie London, 1998.
9. Yoder, C. H.; Margolis, L. A.; Horne, J. M. J. Organomet.
Chem. 2001, 633, 33.
2-[(2¢-methylphenylamido)]benzoic acid (1 mmol)
was suspended in dry toluene (100 mL) and treated with
Et3N (0.29 mL, 1 mmol). The mixture was refluxed for 2-3
hours. To this stirring solution, diorganotin dichloride (0.5
mmol) or triorganotin chloride (1 mmol) was added as solid
and the reaction mixture was refluxed for 8-10 hours. The
reaction mixture contained Et3NHCl was filtered off. The
solvent was removed through rotary apparatus. The mass
left behind was recrystallized from CHCl3 and n-hexane
(1:1).
10. Chandrasekhar, V.; Gopal, K.; Thilagar, P. Acc. Chem. Res.
2007, 40, 420.
11. Tabassum, S.; Pettinari, C. J. Organomet. Chem. 2006, 691,
1761.
12. Pellerito, C.; Agati, P. D.; Fiore, T.; Mansueto, C.; Mansueto,
V.; Stocco, G.; Nagy, L.; Pellerito, L. J. Inorg. Biochem.
2005, 99, 1294.
13. Cima, F.; Ballarin, L. Appl. Organomet. Chem. 1999, 13,
697.
CONCLUSIONS
Organotin(IV) derivatives have been synthesized in
the quantitative yield by refluxing the synthesized car-
boxylic acid and respective organotin(IV) chlorides in dry
toluene for 8-10 hours. The FT-IR spectra clearly demon-
strate that the organotin(IV) moieties react with [O,O] at-
oms of the ligand and ligand behave as bidentate group for
coordination to tin. Semi-empirical study shows that in the
compounds 1-5, the carboxylate group binds in an aniso-
bidentate mode to the Sn atom. Mass spectrometry reveals
that the primary fragmentation is due to the loss of the alkyl
or aryl group followed by elimination of CO2 and the re-
maining part of the ligand, which leaves Sn+ as the end
product. NMR shows that in solution the bidentate car-
boxylate group is cleaved and the resulting monomer con-
tains four coordinated tin with a tetrahedral arrangement.
14. Blower, P. J. Annu. Rep. Prog. Chem. Sect. A. 2004, 100,
633.
15. Pellerito, C.; Nagy, L.; Pellerito, L.; Szorcsik, A. J.
Organomet. Chem. 2006, 691, 1733.
16. Kovala-Demertzi, D. J. Organomet. Chem. 2006, 691, 1767.
17. Saxena, A. K.; Huber, F. Coord. Chem. Rev. 1989, 95, 109.
18. Gielen, M. Coord. Chem. Rev. 1996, 151, 41.
19. Leung, M. K.; Frechet, J. M. J. J. Chem. Soc., Perkin Trans.
2 1993, 2, 2329.
20. Deacon, G. B.; Phillips, R. Coord. Chem. Rev. 1980, 33, 227.
21. Ruzicka, A.; Dostal, L.; Buchta, V. R.; Brus, J.; Cisarova, I.;
Holcapek, M.; Hokcek, J. Appl. Organomet. Chem. 2002,
16, 315.
22. Sadiq-ur-Rehman, A. S.; Parvez, M.; Mazhar, M.; Badshah,
A. Heteroat. Chem. 2004, 15, 398.
23. Willem, R.; Bouhdid, A.; Mahieu, B.; Ghys, L.; Biesemans,

670 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Shahzadi et al.
M.; Tiekink, E. R. T.; de Vos, D.; Gielen, M. J. Organomet.
Chem. 1997, 531, 151.
32. Jain, M.; Gaur, S.; Singh, V. P.; Singh, R. V. Appl. Orga-
nomet. Chem. 2004, 18, 73.
24. Kalinowski, H. O.; Berger, S.; Brown, S. 13C NMR Spectro-
skopie; Thieme Verlag: Stuttgart, Germany, 1984.
25. Bhatti, M. H.; Ali, S.; Masood, H.; Mazhar, M.; Qureshi, S. I.
Synth. React. Inorg. Met. Org. Chem. 2000, 30, 1715.
26. Sadiq-ur-Rehman, A. S.; Shahzadi, S. Heteroat. Chem.
2008, 19, 612.
33. Sexena, C.; Singh, R. V. Phosphorus, Sulfur Silicon Relat.
Elem. 1994, 97, 17.
34. Pearson, R. D.; Manian, A. A.; Hall, D.; Harcus, J. L.
Antimicrob. Agents and Chemother. 1984, 25, 571.
35. Frank, S. Chem. Tool Prog. 1990.
36. MOPAC 2007, Stewart, J. J. P. Stewart Computational,
Chemistry, Version 7.334W.
27. Shahzadi, S.; Shahid, K.; Ali, S.; Bakhtiar, M. Turk. J.
Chem. 2008, 32, 333.
37. H, C, N, O, Cl (PM3): Stewart, J. J. P. J. Comp. Chem. 1989,
10, 209.
28. Holecek, J.; Lycka, A. Inorg. Chim. Acta. 1986, 118, L15.
29. Saraswati, B. S.; Mason, J. Polyhedron 1986, 5, 1449.
30. Shahzadi, S.; Ali, S. J. Iran. Chem. Soc. 2008, 5, 16.
31. Rahman, A.; Choudhary, M. I.; Thomsen, W. J. Bioassay
Techniques for Drug Development; Hardward Academic
Press: Amsterdam, 2001.
38. Sn: (PM3): Stewart, J. J. P. J. Comp. Chem. 1991, 12, 320.
39. Armarego, W. L. F.; Chai, C. L. L. Purification of Labora-
tory Chemicals, 5th ed.; Butterworth- Heinemann: London,
and New York, 2003.