Synthesis characterization and biological study of diorganotin(IV) complexes of monomethyl phthalate

Article abstract of DOI:10.1016/j.saa.2005.12.031

The synthesis and characterization of new coordination compounds of some organotin(IV) chlorides with monomethyl phthalate is reported; the ligand molecules appear to be bound to the tin atom through carbonyl oxygen atoms. Their structures have been characterized by elemental analyses, molar conductance, and bonding in these complexes is discussed in terms of their IR, ¹H, ¹³C, ¹¹⁹Sn NMR and ^119mSn Moessbauer spectral studies. The spectroscopic results obtained are in full agreement with the proposed 2:1 stoichiometry. The complexes soluble in DMSO have been screened against a wide spectrum of bacteria and the results obtained are quite promising. The LD₅₀ values have also been determined in the albino rats. Some of the complexes also exhibit high anti-inflammatory activity.

Full text of DOI:10.1016/j.saa.2005.12.031

Spectrochimica Acta Part A 65 (2006) 689–694
Synthesis characterization and biological study of diorganotin(IV)
complexes of monomethyl phthalate
Wajid Rehmana,∗, Musa Kaleem Balocha, Amin Badshahb, Saqib Alib
a Department of Chemistry, Gomal University, Dera Ismail Khan, Pakistan
b Department of Chemistry, Quaid-e-Azam University, Islamabad, Pakistan
Received 14 August 2005; accepted 17 December 2005
Abstract
The synthesis and characterization of new coordination compounds of some organotin(IV) chlorides with monomethyl phthalate is reported;
the ligand molecules appear to be bound to the tin atom through carbonyl oxygen atoms. Their structures have been characterized by elemental
analyses, molar conductance, and bonding in these complexes is discussed in terms of their IR, 1H, 13C, 119Sn NMR and 119mSn Mo¨ssbauer spectral
studies. The spectroscopic results obtained are in full agreement with the proposed 2:1 stoichiometry. The complexes soluble in DMSO have been
screened against a wide spectrum of bacteria and the results obtained are quite promising. The LD50 values have also been determined in the albino
rats. Some of the complexes also exhibit high anti-inflammatory activity.
© 2005 Elsevier B.V. All rights reserved.
Keywords: Organotin(IV); Monomethyl phthalate; Anti-inflammatory; Acute toxic; Cytostatic
1. Introduction
benzyl) derivatives of monomethyl phthalate, and the results of
this study are reported herein.
Organotin compounds are of interest in view of their con-
siderable structural diversity. Among the compounds, the most
ubiquitous are the carboxylates [1]. The reactions of precursors
with carboxylic acids have been studied in considerable detail.
Depending on the carboxylic acid used and the stoichiometry
of the reactants, several products such as monomers, dimers,
tetramers, oligomeric ladders, and hexameric drums have been
isolated [1]. The increasing interest in organotin(IV) carboxy-
lates that has arisen in the last few decades is attributed to their
significantly important biological properties. Several di- and tri-
organotin(IV)specieshaveshownpotentialasantineoplasticand
antituberculosis agents [2].
In order to widen the scope of investigations on the coor-
dination behavior of various donor ligands towards organotins,
we carried out the investigations on organotin(IV) compounds
containing carboxylate ligands and established their bioactivi-
ties [3–7]. In view of this we have now synthesized, structurally
characterized and determined biological activities of a series of
diorganotin(IV) (R2Sn(IV), R = methyl, ethyl, butyl, phenyl and
2. Experimental
All the diorganotin(IV) compounds except dibenzyltin
dichloride were purchased from Fluka and were used as
such. Dibenzyltin dichloride was synthesized from the liter-
ature method [8]. All the reactions were carried out under
anhydrous and oxygen-free nitrogen atmosphere. The solvents
used were dried before use according to the literature method
[9].
The melting points were measured on a Reichert thermome-
ter 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 an antipyrene as a reference compound. The
amount of tin was determined using an inductively coupled
plasma atomic emission spectrometry (ICP-AES) method on
ARL 3410. The 1H, 13C and 119Sn NMR spectra were recorded
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 instruments at 50 MHz with 13C probe.
∗
¨
The Mossbauer spectra were recorded at 80 K on a Cryophysics
Corresponding author. Tel.: +92 966 750425x29; fax: +92 966 750255.
E-mail address: sono wai@yahoo.com (W. Rehman).
instrument equipped with a 15 mCi Ca 119SnO3 source. The
1386-1425/$ – see front matter © 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2005.12.031

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W. Rehman et al. / Spectrochimica Acta Part A 65 (2006) 689–694
conductance of the complexes was taken on an Inolab sensor
model tetracon 325 WTW conductometer.
H-6: 7.42–7.44 [2H, phenyl protons]; H-7: 7.57–7.59m [2H,
phenyl protons]; H-␣: 2.0s [6H, 2CH3], 2J(119Sn 1H) = 95 Hz,
θ = 152.4◦. 13C NMR (CDCl3)—C-1: 50.81; C-2: 165.9; C-
3: 130.6; C-4: 127.0; C-5: 130.4; C-6: 128.7; C-7: 128.3;
C-8: 129.8; C-9: 170.9; C-␣: 10.2 1J(119Sn 13C) = 755 Hz.
2.1. Syntheses
2.1.1. Synthesis of ligand acid (monomethyl phthalate)
The phthalic anhydride 50 mmol (9 g) was refluxed in excess
of dry methanol for 8 h under anhydrous conditions; excess of
solvent was removed under reduced pressure. The solid product
thus obtained was then recrystallized from chloroform.
119Sn NMR (CDCl3): −310.5 ppm. 119Sn Mossbauer (CDCl3,
¨
mm s−1)—Δ: 3.52 0.05; δ: 1.26 0.01; Γ 1: 0.84; Γ 2: 0.87.
Molar conductance (methanol, 10−3 M): 3.1 ꢀ−1 cm2 mol−1
.
3.3. Bis(monomethyl phthalate)diethyltin (2)
2.1.2. Synthesis of complexes
Yield: 77%. Physical state: solid; mp = 126–128 ◦C; color:
white; Mol. formula: C22H24O8Sn; Mol. wt.: 508. CHN
analysis—Anal. Calcd. for C22H24O8Sn (%): C, 49.21; H, 4.43;
Sn, 22.34; C, 49.25; H, 4.47; Sn, 22.38. IR (KBr cm−1): 3042w
To a hot methanolic solution of 10 mmol (1.8 g) of
monomethyl phthalate (HL) was added 10 mmol of triethy-
lamine (1.4 g) and this mixture was refluxed for half an hour. To
this, 5 mmol of dimethyl (1.1 g), diethyl (1.5 g), dibutyl (1.2 g),
diphenyl (1.7 g) or dibenzyltin dichloride (1.8 g) in methanol
was added dropwise with constant stirring. The reaction was
then refluxed for 8–10 h under nitrogen. The solid mass formed
during the reaction as triethylamine chloride was centrifuged.
Excess of solvent was evaporated under vacuum, solid product
obtained was then recrystallized form chloroform and petroleum
ether (40–60 ◦C). The complexes were placed under nitrogen for
further study.
(νCH aromatic); 1635sr (νOCO)asym; 1385sr (νOCO)sym
;
ꢁν = 250; 1720sr (νC O); 530sh (νSn C): 470sr (␯Sn O). 1H
NMR (CDCl3)—H-l: 3.81s [6H, OMe]; H-4: 7.77–7.78m [2H,
phenyl protons]; H-5: 7.38–7.40m [2H, phenyl protons]; H-6:
7.42–7.44 [2H, phenyl protons]; H-7: 7.57–7.59m [2H, phenyl
protons]; H-␣: 1.20q [6H, 2 OMe], 2J(119Sn 1H) = 98 Hz,
θ = 157.7◦; H-␤: 1.32t [9H, 3CH3]. 13C NMR (CDCl3)—C-1:
50.83; C-2: 166.0; C-3: 130.70; C-4: 127.6; C-5: 130.8;
C-6: 129.1; C-7: 128.7; C-8: 130.1; C-9: 171.2; C-␣: 7.5
1J(119Sn 13C) = 770 Hz; C-␤: 9.7 2J(119Sn 13C) = 25 Hz.
119Sn NMR (CDCl3): −305.8 ppm. 119Sn Mossbauer
¨
3. Spectroscopic data
(CDCl3, mm s−1)—Δ: 3.54 0.05; δ: 1.28 0.01; Γ 1:
Details are given below for each compound, using the follow-
ing conventions. Abbreviations: s, singlet; t, triplet; m, complex
pattern; θ = C Sn C angle; n.o., not observed; sr, strong, med,
medium; w, weak; br, broad, sh, shoulder; Δ = quadrupole split-
ting; δ = isomer shift.
0.92; Γ 2: 0.98. Molar conductance (methanol, 10−3 M):
3.5 ꢀ−1 cm2 mol−1
.
3.4. Bis(monomethyl phthalate)dibutyltin (3)
Yield: 67%. Physical state: solid; mp = 139–141 ◦C; color:
white; Mol. formula: C26H32O8Sn; Mol. wt.: 592. CHN
analysis—Anal. Calcd. for C26H32O8Sn (%): C, 52.66; H, 5.35;
Sn, 20.23; C, 52.70; H, 5.40; Sn, 20.27. IR (KBr cm−1): 3040w
3.1. Ligand acid (HL)
Yield: 88%. Physical state: solid; mp = 77–78 ◦C; Mol. for-
mula: C9H8O4; Mol. wt.: 180. CHN analysis: the calculated
values are given in parentheses. C: 59.97 (60.00); H: 4.42 (4.44).
IR (KBr cm−1): 3027w (νCH); 1715sr (νC O); 3050br (νOH).
1H NMR (CDCl3)—H-1: 3.80s [3H, OMe]; H-4: 7.75–7.80m
[1H, phenyl proton]; H-5: 7.38–7.40m [1H, phenyl proton]; H-
6: 7.41–7.43 [1H, phenyl proton]; H-7: 7.55–7.58m [1H, phenyl
proton];H-11:12.5s[1H, OH]. 13CNMR(CDCl3)—C-1:50.80;
C-2: 165.7; C-3: 130.5; C-4: 126.9; C-5: 130.3; C-6: 128.5; C-
7: 128.1; C-8: 129.5; C-9: 168.7. Molar conductance (methanol,
(νCH aromatic); 1640sr (νOCO)asym; 1393 sr (νOCO)sym
;
ꢁν = 247; 1718sr (νC O); 535sh (νSn C): 488sr (νSn O). 1H
NMR (CDCl3)—H-l: 3.83s [6H, OMe]; H-4: 7.77–7.79m [2H,
phenyl protons]; H-5: 7.38–7.40m [2H, phenyl protons]; H-6:
7.42–7.44 [2H, phenyl protons]; H-7: 7.58–7.60m [2H, phenyl
protons]; H-␣: 1.72–1.74m [4H, 2 CH2]; H-␤: 1.66–1.68m [4H,
2CH3]; H-␥: 1.58–1.60m; H-␦: 0.90t [6H, 2CH3]. 13C NMR
(CDCl3)—C-1: 50.95; C-2: 166.7; C-3: 131.5; C-4: 128.1; C-5:
131.3; C-6: 129.4; C-7: 128.7; C-8: 130.3; C-9: 171.4; C-␣: 24.2
10−3 M): 2.4 ꢀ−1 cm2 mol−1
.
1J(119Sn 13C) = 795 Hz; C-␤: 22.9 J(119Sn 13C) = 29 Hz; C-
2
3
4
␥: 22.7 J(119Sn 13C) = 90 Hz; C-␦: 13.6 J(119Sn 13C) = n.o.
119Sn NMR (CDCl3): −295.5 ppm. 119Sn Mossbauer
¨
3.2. Bis(monomethyl phthalate)dimethylin (1)
(CDCl3, mm s−1)—Δ: 3.58 0.05; δ: 1.34 0.01; Γ 1:
Yield: 84%. Physical state: solid; mp = 90–91 ◦C; color:
white; Mol. formula: C20H20O8Sn; Mol. wt.: 508. CHN
analysis—Anal. Calcd. for C20H20O8Sn (%): C, 47.20; H, 3.89;
Sn, 23.58; C, 47.24; H, 3.93; Sn, 23.62. IR (KBr cm−1): 3038w
0.93; Γ 2: 0.99. Molar conductance (methanol, 10−3 M):
3.3 ꢀ−1 cm2 mol−1
.
3.5. Bis(monomethyl phthalate)diphenyltin (4)
(νCH aromatic); 1620sr (νOCO)asym; 1375sr (νOCO)sym
;
ꢁν = 245; 1722sr (νC O); 530sh (νSn C): 470sr (νSn O).
1H NMR (CDCl3)—H-l: 3.81s [6H, OMe]; H-4: 7.77–7.78m
[2H, phenyl protons]; H-5: 7.38–7.40m [2H, phenyl protons];
Yield: 82%. Physical state: solid; mp = 179–180 ◦C;
color: white; Mol. formula: C28H24O8Sn; Mol. wt.: 608.
CHN analysis—Anal. Calcd. for C28H24O8Sn (%): C,

W. Rehman et al. / Spectrochimica Acta Part A 65 (2006) 689–694
691
55.22; H, 3.90; Sn, 19.70; C, 55.26; H, 3.94; Sn, 19.73. IR
(KBr cm−1): 3046w (νCH aromatic); 1658sr (νOCO)asym
5. Anti-inflammatory activity
;
1405sr (νOCO)sym; ꢁν = 253; 1725sr (νC O); 545sh (νSn C):
492sr (νSn O). 1H NMR (CDCl3): H-l: 3.85s [6H, OMe];
H-4: 7.78–7.79m [2H, phenyl protons]; H-5: 7.62–7.64m
[2H, phenyl protons]; H-6: 7.45–7.47 [2H, phenyl protons];
H-7: 7.58–7.61m [2H, phenyl protons]; H-␣, H-␤, H-␥, H-8:
7.65–7.70m [10H, 2 phenyl protons]. 13C NMR (CDCl3)—C-
1: 50.99; C-2: 166.8; C-3: 131.8; C-4: 128.3; C-5: 131.6;
C-6: 129.6; C-7: 128.9; C-8: 130.6; C-9: 172.4; C-␣: 126.2
1J(119Sn 13C) = 850 Hz; C-␤: 130.5 2J(119Sn 13C) = 20 Hz; C-
␥: 129.1 2J(119Sn 13C) 54 Hz; C-8: 128.2 3J(119Sn 13C) = n.o.
A freshly prepared suspension of carrageenin (0.2 mL, 1.0%
in 0.9% saline solution) was injected subcutaneously into the
plantar aponeurosis of the hind paw of the rats of both sexes
(body weight 120/160 g) by the method of Winter et al. [11].
One group of five rats was kept as a control and the animals of
the other group of five; each was pretreated with the test drugs
given orally 30 min before the carrageenin injection. The paw
volume was measured by a water plethysmometer socrel at the
time of treatment and then at an interval of 1 h for 4 h. The mean
increase of paw volume at each time interval was compared
with that of control group (five rats treated with carrageenin, but
not treated with test compounds) and percent anti-inflammatory
value was calculated as given below:
119Sn NMR (CDCl3): −222.7 ppm. 119Sn Mossbauer
¨
(CDCl3, mm s−1)—Δ: 3.80 0.05; δ: 1.32 0.01; Γ 1:
0.90; Γ 2: 0.95. Molar conductance (methanol, 10−3 M):
4.1 ꢀ −1 cm2 mol−1
.
% anti-inflammatory = (1 − DT/DC) × 100
where DT and DC are the volumes of paw edema in drug treated
and control groups, respectively.
3.6. Bis(monomethyl phthalate)dibenzyltin (5)
Yield: 73%. Physical state: solid; mp = 155–157 ◦C; color:
white; Mol. formula: C32H32O8Sn; Mol. wt.: 660. CHN
analysis—Anal. Calcd. for C32H32O8Sn (%): C, 58.13;
H, 4.20; C, 58.18; Sn, 18.14; H, 4.24; Sn, 18.18. IR
6. Acute toxicity study
ALD50 (average lethal dose at 50% survival) of the com-
pounds was determined in albino mice. The mice of either
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 method of Smith [12].
(KBr cm−1): 3035w (νCH aromatic); 1646sr (νOCO)asym
;
1398sr (νOCO)sym; ꢁν = 248; 1718sr (νC O); 538sh (νSn C):
485sr (νSn O). 1H NMR (CDCl3)—H-l: 3.83s [6H, OMe];
H-4: 7.70–7.71m [2H, phenyl protons]; H-5: 7.48–7.52m
[2H, phenyl protons]; H-6: 7.40–7.42 [2H, phenyl protons];
H-7: 7.55–7.58m [2H, phenyl protons]; H-␣: 2.58 s [4H,
2CH2], 2J(119Sn 1H) = 105 Hz, θ = 171.2◦; H-␤: 7.53–7.54m
[2H, phenyl protons]; H-␥: 7.20–7.22m [2H, phenyl protons]; H-
␦: 7.25–7.27 [2H, phenyl protons]; H-␻: 7.30–7.32 [2H, phenyl
protons]. 13C NMR (CDCl3)—C-1: 50.85; C-2: 165.8; C-3:
131.3; C-4: 127.8; C-5: 131.1; C-6: 129.1; C-7: 128.4; C-8:
130.2; C-9: 171.6; C-␣: 30.3 1(119Sn 13C) = 759 Hz; C-␤: 135.6
2J(119Sn 13C) = 20 Hz; C-␥: 129.3 3J(119Sn 13C) = 53 Hz; C-␦:
7. Cytostatic activity
Cytostatic activity was assayed against the established cell
line KB, which derives from a human oral epidermoid carci-
noma. Stock cultures were grown in 25 cm3 flasks containing
10 mL of buffered Eagle’s minimum essential medium (MEM)
supplemented with glutamine, non-essential amino acids (1%)
and new born calf serum (10%), according the literature [13].
The cell population doubling time was approximately 24 h. The
cells were dissociated with 0.05% trypsin solution, plated at
density of 5 × 105 cells per well in 24-well cell culture clusters
(Costar) containing 1.0 mL of MEM per well, and preincubated
for 24 h to allow adhesion to the substrate. Subsequently, the
compounds to be tested were dissolved immediately before use
in DMSO and these solutions were diluted with the growth
medium to the desired concentrations before addition to the
wells. At least five concentrations of each compound were used,
with eight cell culture wells for each concentration. Each com-
pound was assayed on at least three separate occasions. Each
assay included a blank containing complete medium without
cells.
4
5
127.5 J(119Sn 13C) = 12 Hz; C-␻: 124.2 J(119Sn-13C) = n.o.
119Sn NMR (CDCl3): −290.8 ppm. 119Sn Mossbauer (CDCl3,
¨
mm s−1)—Δ: 3.50 0.05; δ: 1.22 0.01; Γ 1: 0.86; Γ 2: 0.88.
Molar conductance (methanol, 10−3 M): 3.4 Q−1 cm2 mol−1
.
4. Antibacterial activity
The antibacterial activities were determined by using the agar
welldiffusionmethod [10]. Thewellswereduginthemediawith
a sterile borer and 8-h-old bacterial inocula containing ca. 104 to
106 colony-forming units (CFU)/mL were spread on the surface
of the nutrient agar using a sterile cotton swab. The recom-
mended concentration of the test sample (2 mg/mL in DMSO)
was introduced into the respective well. Other wells containing
DMSO and the reference antibacterial drug served as negative
and positive controls, 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) show-
ing complete inhibition. Growth inhibition was calculated with
reference to the positive control.
The cells were incubated with the compounds to be tested
at 37 ◦C in an atmosphere that was 5% CO2 and had a relative
humidity of 100%. The incubation time was 72 h, during which
period the control cells showed exponential growth.
Cells growth was terminated by in situ fixation and fol-
lowed by staining with the protein-binding dye sulforhodamine

692
W. Rehman et al. / Spectrochimica Acta Part A 65 (2006) 689–694
B (SRB) [14]. Specifically, adherent cell cultures were fixed in
situ by addition of 250 ␮L of cold 50% (w/v) trichloroacetic
acid (TCA) and were kept for 60 min at 4 ◦C. The supernatant
was then discarded and the plates were washed three times
with deionized water and dried. SRB solution (500 ␮L, 0.4%
(w/v) in 1% AcOH) was added to each well, and the cells were
allowed to stain for 20–30 min at room temperature. Unbound
SRB was removed by washing three times with 1% AcOH, and
the plates were then air dried while bound stain was solubilized
with unbuffered Tris base [tris(hydoxymethyl)aminomethane].
Optical densities at 565 nm were read on a Perkin-Elmer 550 SE
spectrophotometer.
Cytostatic activity was evaluated from the inhibition of cell
growth in the treated cultures with respect to the controls.
IC50, the concentration of the test compound at which cell pro-
liferation was 50% of that observed in control cultures, was
determined by linear regression analysis. The statistical signifi-
cance of these results was estimated by means of Student’s t-test
(P < 0.01).
8. Results and discussion
Reactions of R2SnCl2 with monomethyl phthalate and tri-
ethylamine in 1:2 molar ratios, respectively, led to the formation
of complexes according to Eq. (1).
The above reactions were found to be quite facile and were
completed within 8–9 h of refluxing. The resulting complexes
were obtained in good yield (70–90%). The resulting com-
plexes were white solids, stable in air and soluble in methanol,
chloroform, DMSO and DMF. The analytical data are in good
agreement with the proposed stoichiometry of the complexes.
The molar conductance values of 10−3 M solution of the com-
Scheme 1.
which is characteristic of ester-type carboxylate groups [17]. It
has been further confirmed by the presence of bands in the range
528–538 and 466–492 cm−1 for Sn C and Sn O, respectively
[18,19]. Thus the IR data provide reasonable evidence for com-
plexation through carboxylate group.
plexes in methanol are in the range of 2.4–4.4 ꢀ−1 cm2 mol−1
,
indicating their non-electrolytic nature [15]. Structural propos-
als are based on FT-IR, 1H NMR, 13C NMR, 119Sn and 119mSn
10. NMR studies
¨
Mossbauer studies:
1
The H NMR chemical shift assignments of the diorgan-
R2SnCl2 + 2HL + 2Et3N → R2SnL2 + 2Et3N · HCl
(1)
otin moiety are straightforward from the multiplicity pattern
and/or resonance intensities; whereas the ligand skeleton was
assigned by multiplicity patterns and/or resonance intensities.
The absence of a signal due to the hydroxyl proton at 12.5 ppm
suggests deprotonation of carboxylic oxygen atom of the lig-
and upon complexation. For dimethyl, diethyl and dibenzyltin
derivatives 2J(119Sn 1H) = 95, 98 and 105 Hz, respectively,
which falls in the range of a octahedral environment around
the tin atom which is further supported by C Sn C angle (θ),
which was calculated using Lockhart’s equation [20]. In case
where R = methyl, ethyl, butyl, phenyl and benzyl (Scheme 1).
9. Spectroscopy
9.1. Infrared
Infrared O C O stretching frequencies were used to distin-
guish from coordinated from non-coordinated carboxyl groups,
and also to identify the nature of bonding of carboxylic group.
The carboxylic group in organotin(IV) derivatives generally
adopt a bridged structure in the solid state unless the organic
substituents at tin are bulky or unless the carboxylate group is
branched at the ␣-carbon [16]. The strong band at 3015 cm−1
for ligand is absent for all organotin complexes indicating the
deprotonation of carboxylic oxygen of the monomethyl phtha-
late upon complexation with the tin metal, as expected. Further,
the νasym(OCO) and νsym(OCO) stretches have been detected
and the magnitude of ꢁv(OCO) is in the range 245–250 cm−1
n
of n-butyl and phenyl derivatives, J(119Sn 1H) couplings are
not visible due to a complex multiplet pattern. The signals for
the alkyl protons attached to the tin(IV) atom are obtained as
expected [21].
1H NMR measurements for all the complexes were also per-
formed in DMSO solution, showing that no dissociation occurs
in this solvent over 48 h, contrary to the findings for analogous
compounds [22].
The characteristic resonance peaks in 13C NMR spectra of
the complexes were recorded in CDCl3. The conclusions drawn

W. Rehman et al. / Spectrochimica Acta Part A 65 (2006) 689–694
693
from the IR and 1H NMR spectra are concurrent with 13C spec-
Table 1
Anti bacterial bioassay resultsa,b for R2SnL2 (inhibition zone in mm)
tral data regarding the authenticity of the proposed structures.
Various carbons have been successfully assigned. The spectra
of organotin(IV) derivatives are consistent with the following
observations:
Micro-organism
HL
1
2
3
4
5
Imipinemb
Gram-positive
Bacillus subtilis
Staphlococcus aureus
15 18 22 20 25
16 n.a. 20 25 34
20
19
31
43
Gram-negative
Escherichia coli
Schigella flexenari
Pseudomonas aeruginosa 12 12 12 14 21
Salmonella typhi 15 18 20 20 35
• The resonance of the carboxylic carbon in organotin(IV) com-
pounds are observed at larger δ (δ 170.9–172.4 ppm) than
in the ligand (δ 168.7 ppm), suggesting the coordination of
ligand through the carboxylic oxygen, to the organotin(IV)
moiety [23].
n.a. 16 21 22 25
n.a. n.a. n.a. n.a. 22
18
16
18
20
30
33
25
41
a
Concentration used: 1.00 mg/1.00 mL of DMSO. Size of well: 6 mm (diam-
• The 13C chemical shifts of alkyl groups attached to tin are
observed at positions comparable with other, similar com-
pounds [23].
eter). n.a: no activity.
b
Standard drug.
• Coordination of the tin atom in organotins has been related
to the 1J(119Sn 13C) coupling constants. The 1J(119Sn 13C)
coupling constants for the synthesized compounds ranged
from 755 to 850 Hz which is indicative of six-coordinated
compounds [24].
pounds show higher activity than the ligand but slightly lower
than the standard drug.
The anti-inflammatory activity (% inhibition) of the syn-
thesized complexes was conducted on adult albino rats
(body weight 120–160 g) of Froster Charles species against
carrageenin-induced edema in the doses of 50 mg kg−1 given
orallyandtheacutetoxicity(ALD50)wasstudiedonalbinomice
(body weight 20–25 g) of either sex. The results are presented
in Table 2. The activity of the standard drug, phenyl butazone,
is used for the comparison.
In order to obtain further structural evidence, the 119Sn NMR
spectra of the representative complexes were recorded. As the
electron releasing power of alkyl group bonded to the tin
increases, tin atom becomes progressively more shielded and
119Sn chemical shift moves to higher field [25]. According to the
literature reported work 119Sn chemical shift is directly linked
to the coordination, tin shifts are normally higher with phenyl
compared to that of alkyl substituents [26]. The results further
confirm the octahedral structure to synthesized diorganotin(IV)
complexes.
The studies on the structure–activity correlation of organ-
otin(IV) compounds reveal that the following structural features
characterize the active compounds:
(i) the availability of coordination positions at tin;
(ii) the occurrence of stable ligand–Sn bonds viz., Sn O bond.
11. 119mSn Mo¨ssbauer study
Among the synthesized complexes, as revealed from the data
presented in Table 2, the diphenyltin(IV) complex is found to be
more active than the others. Lower activity of dialkyltin com-
plexes except diphenyltin(IV) complex is probably due to the
fact that the former form the most stable bonds upon complexa-
tion than the latter ones. The higher activity of diphenyltin(IV)
complexes is also probably due to less number of coordination
sites/bonds, which facilitate the easier formation of Ph2Sn2+(IV)
moiety as a part of inhibition. It may be due to stronger interac-
tions in dialkyltin(IV) complexes except diphenyl tin(IV) com-
plex in which there are weaker interactions of ligand with tin,
thereby, regulating the formation of R2Sn2+ (IV) moiety.
119m
¨
Sn Mossbauer parameters have been utilized as a
The
diagnostic tool for proposing the structure that a particular com-
plex can adopt in the solid state. The spectra of the complexes
display a characteristic doublet absorption indicating a single
tin site. The R2Sn derivatives show isomer shift (δ) values typ-
ical of quadrivalent organotin derivatives, similar in alkyl2Sn
moieties and higher with respect to Ph2Sn. The quadrupole split-
ting (Δ) values of complexes are in the range 3.72–3.97 mm s−1
in alkyl2Sn and 3.61 mm s−1 in Ph2Sn derivatives, suggesting
trans-R2Sn octahedral structure [27].
12. Biological studies
Table 2
ALD50 (in mg kg−1), anti-inflammatory activity of diorganotin (IV) complexes
Ligand acid (HL) and its organotin(IV) derivatives exhibit
varying degrees of inhibitory effects on the growth of a wide
spectrum of microorganisms. All the complexes were very active
against all of microorganisms used.
Antibacterial activity was performed against two Gram pos-
itive (Bacillus subtilis, Staphylococcus aureus) and four Gram-
negative (Escherichia coli, Schigella flexenari, Pseudomonas
aeruginosa, Salmonella typhi) bacteria and the results are sum-
marized in Table 1. In order to compare the results obtained the
Imipinem is used as standard drug. All the synthesized com-
Cpd
ALD50 (mg kg−1
)
Anti-inflammatory activity
(% inhibition) 50 mg kg−1 po
Phenyl butazonea
HL
1
2
3
–
<400
<500
>500
>500
>500
>500
38.4
15.5
20.4
22.5
25.7
32.2
28.5
4
5
a
Standard drug.

694
W. Rehman et al. / Spectrochimica Acta Part A 65 (2006) 689–694
Table 3
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Results of in vitro cytostatic assays against cell line KB
Compound
IC50 (␮g mL−1 medium)
IC50 (␮M)
HL
1
2
3
4
5
0.10
0.21
3.30
0.14
0.36
0.20
0.11
0.18
0.70
6.50
0.34
0.62
0.38
0.37
Cis-[PtCl2(NH3)2]a
a
Standard drug.
ALD50 values of the studied diorganotin(IV) derivatives is
greater than 500 mg kg−1 (the maximum dose tested), whereas
ALD50 value for the ligand is <400 mg kg−1 indicating that the
bigger bimolecules lower the toxicities but increase the activities
of the resulting organotin(IV) complexes.
The results of cytostatic activity are summarized in Table 3.
IC50 valuesofthecompoundsareexpressedin␮M, togetherwith
that of cis-[PtCl2(NH3)2] for comparison. All complexes show
significant cytostatic activity. In particular, dibutyltin complex
is even more active than the cis-[PtCl2(NH3)2].
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