Synthesis, spectroscopic characterization, X-ray structures, biological screenings, DNA interaction study and catalytic activity of organotin(IV) 3-(4-flourophenyl)-2-methylacrylic acid derivatives

Article abstract of DOI:10.1016/j.jorganchem.2012.09.011

A series of organotin(IV) carboxylate complexes [Me₂SnL ₂] (1), [Bu₂SnL₂] (2), [Oct₂SnL ₂] (3), [Me₃SnL] (4), [Bu₃SnL] (5) and [Ph ₃SnL] (6), where L = O₂C(CH₃)CCHC ₆H₄F have been successfully synthesized and characterized by FT-IR, NMR (¹H, ¹³C) and single crystal analysis. The ligand coordinates to tin atom via carboxylate group. Compound 1 and 4 have also been studied by single crystal XRD analysis. The synthesized compounds were screened for their biological activities including anti-bacterial, anti-fungal, anti-tumor and cytotoxicity. The compounds 4-6 exhibit excellent anti-bacterial, anti-fungal and anti-tumor activities. The ligand binds with DNA double helix by hydrogen bonding between the ligand and the base pairs in DNA typically to N3 of adenine and O2 of thymine as well as partial intercalation of aromatic ring into the base pairs of DNA. The complexes also interact with DNA via intercalation of aromatic ring into the base pairs of DNA. The catalytic activity of compounds 46 was assessed in transesterification of triglycerides in rocket seed oil into biodiesel. The choice of these compounds is the Lewis acid nature of tin atom. The samples were taken in regular interval of 1, 8, 16 and 24 h and % age conversion was determined by ¹H NMR. All the tested compounds showed good catalytic activity in the order 4 > 5 > 6.

Full text of DOI:10.1016/j.jorganchem.2012.09.011

Journal of Organometallic Chemistry 723 (2013) 79e89
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis, spectroscopic characterization, X-ray structures, biological screenings,
DNA interaction study and catalytic activity of organotin(IV) 3-(4-flourophenyl)-
2-methylacrylic acid derivatives
,
d
Muhammad Tariq a, Niaz Muhammad b, Muhammad Sirajuddin a, Saqib Ali a , Naseer Ali Shah ,
*
Nasir Khalid c, Muhammad Nawaz Tahir e, Muhammad Rashid Khan d
a Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan
b Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan
c Chemistry Division, Pakistan Institute of Nuclear Science and Technology, P.O. Nilore, Pakistan
d Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
e Department of Physics, University of Sargodha, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of organotin(IV) carboxylate complexes [Me2SnL2] (1), [Bu2SnL2] (2), [Oct2SnL2] (3), [Me3SnL] (4),
[Bu3SnL] (5) and [Ph3SnL] (6), where L ¼ O2C(CH3)C]CHC6H4F have been successfully synthesized and
characterized by FT-IR, NMR (1H, 13C) and single crystal analysis. The ligand coordinates to tin atom via
carboxylate group. Compound 1 and 4 have also been studied by single crystal XRD analysis. The
synthesized compounds were screened for their biological activities including anti-bacterial, anti-fungal,
anti-tumor and cytotoxicity. The compounds 4e6 exhibit excellent anti-bacterial, anti-fungal and anti-
tumor activities. The ligand binds with DNA double helix by hydrogen bonding between the ligand
and the base pairs in DNA typically to N3 of adenine and O2 of thymine as well as partial intercalation of
aromatic ring into the base pairs of DNA. The complexes also interact with DNA via intercalation of
aromatic ring into the base pairs of DNA. The catalytic activity of compounds 46 was assessed in
transesterification of triglycerides in rocket seed oil into biodiesel. The choice of these compounds is the
Lewis acid nature of tin atom. The samples were taken in regular interval of 1, 8, 16 and 24 h and % age
conversion was determined by 1H NMR. All the tested compounds showed good catalytic activity in the
order 4 > 5 > 6.
Received 30 July 2012
Received in revised form
13 September 2012
Accepted 18 September 2012
Keywords:
Organotin(IV) carboxylate
Antimicrobial activity
Antitumor activity
Cytotoxicity
DNA interaction
Catalytic activity
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
bonding are mono, di, tetra and oligomeric ladder, cyclic or hex-
americ structure [6e8]. Organotin carboxylates have also a wide
The organotin(IV) carboxylates have been shown significant
antimicrobial properties such as anti-bacterial and anti-fungal [1,2].
The organotin compounds have also received considerable atten-
tion as anti-tumor and anti-cancer drugs. The activity is due to
dissociated organotin(IV) moieties [3]. The biological activity
usually associates with the nature of organic ligand [4,5], since the
organic ligand facilitates the transportation of the complexes across
the cell membrane. Spectroscopic characterizations have confirmed
a great structural variety for organotin(IV) carboxylates both in
solid and solution states. The versatile structural ability is related to
mode of binding of COOꢀ moiety. The well known natures of their
range of industrial applications as catalysts for esterification and
transesterification [9,10], silicone curing [11], formation of poly-
urethane [12], antifouling paints [13e15], PVC stabilization [16], as
homogeneous catalysts [17], and as ion carriers in electrochemical
membranes design [18,19]. Very few reports are available in liter-
ature regarding the use of organotin carboxylates for the trans-
esterification of vegetable oil into biodiesel. Biodiesel is the
monoalkyl ester of long chain fatty acids derived from the renew-
able feed stock, such as vegetable oil or animal fats and is usually
produced by a transesterification of vegetable oil with methanol
[20e23]. The triglycerides in oil are being transesterified with base
catalysts like NaOH, KOH etc [24e26] but these basic catalysts need
excessive water washing and neutralization. Heterogeneous cata-
lysts like CaO, MgO, MgeAl hydrotalcite etc have also been used in
transesterification of oils [27e29] but these take more time and
* Corresponding author. Tel.: þ92 51 90642130; fax: þ92 51 90642241.
E-mail address: drsa54@yahoo.com (S. Ali).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2012.09.011

80
M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
0
higher alcoholic ratio. A very few examples are reported for
transesterification of triglycerides with organotin(IV) carboxylates
as homogeneous metal catalyst [30e33].
(CDCl3, ppm): 11.32 (s, H1,1H), 7.81 (s, H3,1H), 7.10 (d, H5,5 , 2H), 7.43
(d, H6,6 , 2H), 2.15 (s, H8, 3H). 13C NMR (CDCl3, ppm): 174.2 (C-1),
127.2 (C-2), 139.9 (C-3), 131.6 (C-4), 127.3 (C-5), 115.4 (C-6), 164.3
(C-7), 13.6 (C-8).
0
Keeping in view the versatile applications of organotin(IV)
carboxylates, in the present study, we have synthesized and char-
acterized 3-(4-flourophenyl)-2-methylacrylic acid and its six
organotin(IV) derivatives. These complexes have been screened for
their anti-bacterial, anti-fungal, cytotoxicity and anti-tumor
activity. DNA interaction studies were also conducted for the
synthesized complexes using spectrophotometric technique. The
selected organotin(IV) carboxylates have been assessed as catalyst
in transesterification of triglycerides to produce biodiesel.
2.2.2. Sodium salt of 3-(4-flourophenyl)-2-methylacrylic acid
The sodium salt of ligand, R/COONa, was prepared by dropwise
addition of an equimolar amount of sodium hydrogen carbonate
solution to a methanolic solution of acidic ligand (R/COOH). The
mixture was stirred for 2 h at room temperature, evaporated under
reduced pressure to give a white solid and was vacuum dried.
The following scheme represents numbering in ligand and
organic groups attached to Sn atom as shown by 1H and 13C NMR.
2. Experimental
2.1. Materials and methods
All the diorganotin(IV) and triorganotin(IV) precursors were
purchased from Aldrich and were used without further purifica-
tion. All the solvents used were of analytical grade and dried
according to reported procedures before use [34]. The melting
points were recorded on a Gallenkamp (UK) electrothermal
melting point apparatus. IR spectra were recorded with Thermo
Nicolet-6700 FT-IR Spectrophotometer by measuring the absor-
bance of the samples from 4000 to 400 cmꢀ1 1H and 13C NMR
.
spectra were recorded at room temperature in CDCl3 on a Brucker
Advance Digital 300 MHz NMR spectrometer (Switzerland). The
absorption spectra were recorded on a Shimadzu 1800 UVevis
spectrophotometer. Viscosity for DNA interaction studies of
ligand HL and representative complexes, was measured by an
Ubbelohde viscometer at ambient temperature of 23 ꢁ 1 ꢂC. The X-
ray diffraction data were collected on a Bruker SMART APEX CCD
diffractometer, equipped with a 4 K CCD detector set 60.0 mm
from the crystal. The crystals were cooled to 100 ꢁ 1 K using the
Bruker KRYOFLEX low temperature device and intensity
measurements were performed using graphite monochromated
Mo-Ka radiation from a sealed ceramic diffraction tube (SIEMENS).
Generator settings were 50 kV/40 mA. The structure was solved by
Patterson method and extension of the model was accomplished
by direct method using the program DIRDIF or SIR2004. Final
refinement on F2 carried out by full matrix least squares tech-
niques using SHELXL-97, a modified version of the program PLUTO
(preparation of illustrations) and PLATON package. The rocket
seeds were purchased from a local market. The seeds were washed
with distilled water to remove the dirt and were oven dried at
60 ꢂC till constant weight. The oil was extracted by using electric
oil expeller (KEK P0015-10127) Germany. Methanol (CH3OH),
sodium hydroxide (NaOH) and anhydrous sodium sulfate
(Na2SO4) were of analytical grade obtained from Merck (Germany)
and used as such. Distilled water was used through out the present
studies.
2.2.3. Dimethyltin(IV) [bis(3-(4-flourophenyl)-2-methylacrylate)] (1)
The sodium salt R/COONa (0.6 g, 3 mmol), was refluxed for 10 h
with dimethyltin(IV) dichloride (0.32 g, 1.5 mmol) in dry toluene in
a 250 mL two necked round bottom flask. A turbid solution ob-
tained, was left overnight at room temperature. The sodium chlo-
ride formed was filtered off and the filtrate was rotary evaporated.
The resultant solid mass was recrystallized from chloroform and
n-hexane (4:1) mixture. Yield: (0.54 g, 72%). M.p. 159e160 ꢂC. IR
2.2. Synthesis
2.2.1. 3-(4-flourophenyl)-2-methylacrylic acid
A mixture of 4-flourobenzaldehyde (3.47 g, 28.0 mmol), meth-
ylmalonic acid (6.60 g, 56.0 mmol) and piperidine (4.76 g,
56.0 mmol) in molar ratios of 1:2:2 was refluxed in pyridine as
solvent in two neck round bottom flask on a steam-bath for 24 h
(Scheme 1). The reaction mixture was cooled and added to
a mixture of concentrated HCl and ice. The precipitate formed in the
acidified mixture was filtered off and washed with ice cold water.
The product was recrystallized from an alcoholewater mixture
(4:1). Yield: 3.68 g, 73.6%. M.p. 152e153 ꢂC. IR (cmꢀ1): 3321e2530
(cmꢀ1): 1505
n
(OCO)asym, 1370
n
(OCO)sym, (Dn ¼ 135 cmꢀ1), 523
n
(SneC), 466 n
(SneO). 1H NMR (CDCl3 ppm),: 7.83 (s, H3, 2H),
0
0
7.08 (d, H5,5 , 4H), 7.42 (d, H6,6 , 4H), 2.17 (s, H8, 6H), 1.10 (s, H
a
, 6H,
2J(119/117Sne1H) ¼ 83/80 Hz). 13C NMR (CDCl3, ppm): 173.8 (C-1),
131.9 (C-2), 139.0 (C-3), 127.0 (C-4), 131.6 (C-5), 115.4 (C-6), 160.9
n
(OH), 1675
n
(OCO)asym, 1423
n
(OCO)sym, (Dn ¼ 252 cmꢀ1). 1H NMR
(C-7), 14.3 (C-8), 1.0 (C-a).

M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
81
CH3
COOH
CH3
a)pyridine
b)piperidine
CO2
+
H2O
F
+
CHO
+
H
COOH
C
c)24 h stirring
d) 100 oC
COOH
F
Scheme 1.
2.2.4. Dibutyltin(IV) [bis(3-(4-flourophenyl)-2-methylacrylate)] (2)
Compound 2 was prepared in the same way as 1, using R/COONa
(0.4 g, 2 mmol) and dibutyltin(IV) dichloride (0.30 g, 1.0 mmol) in
2:1 molar ratios. The product was recrystallized from chloroform
and n-hexane (4:1) mixture. Yield: (0.45 g, 78%). M.p. 74e75 ꢂC. IR
and n-hexane (4:1) mixture. Yield: (0.68 g, 74%). M.p. 135e136 ꢂC.
IR (cmꢀ1): 1507
n
(OCO)asym, 1312
n
(OCO)sym, (Dn ¼ 195 cmꢀ1), 524
n
(SneC), 449
n
(SneO). 1H NMR (CDCl3, ppm): 7.66 (s, H3, H), 7.38
0
0
(d, H5,5 , 2H), 7.05 (d, H6,6 , 2H), 2.11 (s, H8, 3H), 1.75e1.63 (m, H
a
,
6H), 1.45e1.40 (m, Hb, 6H), 1.37e1.31 (m, H
9H). 13C NMR (CDCl3): 173.6 (C-1), 125.3 (C-2), 136.7 (C-3), 132.7
(C-4), 131.3 (C-5), 115.2 (C-6), 160.6 (C-7), 14.3 (C-8), 16.5 (C- ), 21.4
(C- ), 25.3 (C- ), 13.7 (C- ).
g, 6H), 0.92 (t, Hd,
(cmꢀ1): 1507
n
(OCO)asym, 1366
n
(OCO)sym, (Dn ¼ 141 cmꢀ1), 524
n
(SneC), 463
n
(SneO). 1H NMR (CDCl3 ppm),: 7.50 (s, H3, 2H), 7.10
a
0
0
(d, H5,5 , 4H), 7.27 (d, H6,6 , 4H), 2.16 (s, H8, 6H), 2.22e2.21 (m, H
a
C
,
b
g
d
4H),1.81e1.78 (m, Hb, 4H),1.49e1.47 (m, Hg, 4H), 0.96 (t, Hd, 6H). 13
NMR (CDCl3, ppm): 178.3 (C-1), 127.74 (C-2), 134.5 (C-3), 127.0
(C-4), 129.1 (C-5), 115.4 (C-6), 164.2 (C-7), 14.4 (C-8), 21.4 (C- ), 25.4
(C- ), 27.0 (C- ), 13.6 (C- ).
2.2.8. Triphenyltin(IV) 3-(4-flourophenyl)-2-methylacrylate (6)
Compound 6 was prepared in the same way as 1, using R/COONa
(0.5 g, 2.5 mmol) triphenyltin(IV) chloride (0.95 g, 2.5 mmol) in 1:1
molar ratio. The product was recrystallized from chloroform and
n-hexane (4:1) mixture. Yield: (0.87 g, 67%). M.p. 139e140 ꢂC. IR
a
b
g
d
2.2.5. Dioctyltin(IV) [bis(3-(4-flourophenyl)-2-methylacrylate)] (3)
Compound 3 was prepared by using ligand acid, R/COOH (0.54 g,
3.0 mmol) and dioctyltin(IV) oxide (0.54 g, 1.5 mmol). The reactant
mixture was suspended in 100 mL of dry toluene in a round bottom
flask (250 mL), equipped with a DeaneStark apparatus. The
mixture was refluxed for 10 h and water formed during the
condensation reaction was removed at regular intervals. The
resultant clear solution obtained, was cooled to room temperature
and solvent was removed under reduced pressure. The solid ob-
tained was recrystallized from chloroform and n-hexane (4:1)
mixture. Yield: (0.66 g, 68%). M.p. 150e151 ꢂC. IR (cmꢀ1): 1508
(cmꢀ1): 1582
n
(OCO) asym, 1392
n
(OCO) sym, (Dn ¼ 190 cmꢀ1), 536
n
(SneC), 441
n
(SneO). 1H NMR (CDCl3, ppm): 7.63 (s, H3, H), 7.42
0
0
(d, H5,5 , 2H), 7.12 (d, H6,6 , 2H), 2.13 (s, H8, 3H), 7.75e7.71 (Hb, Hg, Hd
15H). 13C NMR (CDCl3, ppm): 171.5 (C-1) 129.3 (C-2), 137.5 (C-3),
132.4 (C-4), 131.5 (C-5), 115.2 (C-6), 160.6 (C-7), 14.5 (C-8), 140.0
(C-a), 137.5 (C-b), 128.5 (C-g), 129.4 (C-d).
2.3. DNA interaction studies by UVevisible spectroscopy
0.2 g of SS-DNA (salmon sperm-DNA) was dissolved in 100 mL of
double deionized water and kept at 4 ꢂC for 2 days. Solutions of DNA
in 20 mM TriseHCl (pH 7.4) gave the ratio of UV absorbance at 260
and 280 nm, (A260/A280) of 1.86 indicating that the DNA is sufficiently
free from protein [35]. The DNA concentration was determined via
absorption spectroscopy using the molar absorption coefficient of
6600 Mꢀ1 cmꢀ1 at 260 nm [36], and was found as 1.86 ꢃ 10ꢀ4 M.
n
(OCO)asym, 1366
n
(OCO)sym, (Dn ¼ 142 cmꢀ1), 532
n
(SneC), 461
(SneO). 1H NMR (CDCl3, ppm): 7.84 (s, H3, 2H), 7.08 (d, H5,5 , 4H),
0
n
0
7.53 (d, H6,6 , 4H), 2.18 (s, H8, 6H), 1.76e1.41 (bs, Ha b, 4H), 1.28e1.26
,
(bs, Hg g , 8H), 0.84 (t, Hd , 6H). 13C NMR (CDCl3, ppm): 178.0 (C-1),
0
0
e
126.0 (C-2), 139.2 (C-3), 132.4 (C-4), 131.6 (C-5), 115.4 (C-6), 160.9
(C-7), 14.4 (C-8), 25.7 (C-
a
g
), 24.6 (C-
b
d
), 33.3 (C-
g), 31.8 (C-d), 29.2
(C-a
0), 29.1 (C- 0), 22.7 (C-
b
0), 14.4 (C-
0).
From this stock solution 13, 26, 39, 52 and 65 mM working solutions
were prepared by dilution method. The complexes were dissolved in
10% DMSO at a concentration of 4 ꢃ 10ꢀ5 M. The UV absorption
titrations were performed by keeping the complexes concentration
fixed while varying the concentration of DNA. Equivalent solutions
of DNA were added to the complex and reference solutions to
eliminate the absorbance of DNA itself. CompoundeDNA solutions
were allowed to incubate for 30 min at ambient temperature before
measurements were made. Absorption spectra were recorded using
cuvettes of 1 cm path length.
2.2.6. Trimethyltin(IV) 3-(4-flourophenyl)-2-methylacrylate (4)
Compound 4 was prepared in the same way as 1, using
R/COONa (0.2 g, 1.0 mmol) and trimethyltin(IV) chloride (0.41 g,
1.0 mmol) in 1:1 molar ratio. The product was recrystallized from
chloroform and n-hexane (4:1) mixture. Yield: (0.51 g, 72%). M.p.
143e145 ꢂC. IR (cmꢀ1): 1573
n(OCO)asym, 1403 n(OCO)sym,
n
(
Dn ¼ 170 cmꢀ1), 528
n
(SneC), 463
(SneO). 1H NMR (CDCl3, ppm):
0
0
7.67 (s, H3, H), 7.42 (d, H5,5 , 2H), 7.05 (d, H6,6 , 2H), 2.11 (s, H8,
3H), 0.52 (s Ha, 9H) 2J(119/117Sne1H) ¼ [58/56 Hz]. 13C NMR
(CDCl3, ppm): 173.8 (C-1), 132.0 (C-2), 137.2 (C-3), 129.7
2.4. Viscosity measurements
(C-4), 131.0 (C-5), 115.2 (C-6), 160.6 (C-7), 14.6 (C-8), ꢀ4.93 (C-
a
), 1J
(
119/117SneC) ¼ [388/379 Hz].
Viscosity measurements were carried out using Ubbelohde
viscometer at ambient temperature of 23 ꢁ 1 ꢂC. Flow time was
measured with a digital stopwatch. Each sample was measured
2.2.7. Tributyltin(IV) 3-(4-flourophenyl)-2-methylacrylate (5)
Compound 5 was prepared in the same way as 1, using R/COONa
(0.4 g, 2.0 mmol) and tributyltin(IV) chloride (0.64 g, 2.0 mmol) in
1:1 molar ratio. The product was recrystallized from chloroform
three times and an average flow time was calculated. Data were
1/3
presented as relative viscosity,
([compound]/[DNA]) where
(h
/ho)
, vs binding ratio
h
is the viscosity of DNA in the

82
M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
presence of complex and ho is the viscosity of DNA alone. Viscosity
values were calculated from the observed flow time of DNA con-
2.8. Anti-tumor studies
taining solution (to),
h
¼ t ꢀ to [37].
The ligand HL and organotin(IV) carboxylates complexes 1e6
were screened for anti-tumor activity using crown gall tumor
inhibition assay (potato disc assay) [40] using Agrobacterium
tumefaciens (strain At10). A. tumefaciens cause Crown gall due to its
Ti (tumor inducing) plasmid which is a neoplasmic disease of plants
[40]. Vincristine was used as reference drug.
2.5. Antibacterial studies
The synthesized ligand and its organotin(IV) complexes were
tested against six bacterial strains; two Gram-positive (Micrococcus
luteus and Staphylococcus aureus) and four Gram-negative
(Escherichia coli, Enterobacter aerogenes, Bordetella bronchiseptica
and Klebsiella pneumoniae). The agar well-diffusion method was
used for the determination of antibacterial activity [37,38]. Broth
culture (0.75 mL) containing ca. 106 colony forming units (CFU) per
mL of the test strain was added to 75 mL of nutrient agar medium at
45 ꢂC, mixed well, and then poured into a 14 cm sterile petri plate.
The media was allowed to solidify, and 8 mm wells were dug with
a sterile metallic borer. Then a DMSO solution of test sample
2.9. Catalytic experiment
Transesterification of rocket seed oil was carried out using tri-
organotin (IV) carboxylate catalysts in molar ratio of 400:100:1 of
methanol, oil and catalyst. 0.01 mol rocket seed oil was trans-
esterified using 0.04 mol methanol and 0.1 mmol catalyst in
a 100 mL two neck round bottom flask equipped with reflux
condenser, magnetic stirrer, thermometer and sampling outlet.
Before the reaction, the triorganotin catalyst was solubilized in
0.5 mL chloroform. The reaction mixture was refluxed and stirred
with a constant speed of 600 rpm. The sample was taken after 1,8,16
and 24 h and was analyzed by 1H NMR to check the % age
conversion of oil into biodiesel.
(100
mL) at 1 mg/mL was added to the respective wells. DMSO
served as negative control, and the standard antibacterial drugs
Roxithromycin (1 mg mLꢀ1) and Cefixime (1 mg mLꢀ1) were used as
positive control. Triplicate plates of each bacterial strain were
prepared which were incubated aerobically at 37 ꢂC for 24 h. The
activity was determined by measuring the diameter of zone
showing complete inhibition (mm).
3. Results and discussion
3.1. Syntheses of complexes 1e6
2.6. Antifungal studies
Diorganotin dichloride with NaL in 1:2, triorganotin chloride
with NaL in 1:1 and R2SnO with HL in 1:2 molar ratios give
complexes according to the following equations
Antifungal activity against five fungal strains (Fusarium mon-
iliformis, Aspergillus niger, Fusarium solani, Mucor species and Asper-
gillus fumigatus) was determined by using Agar tube dilution
method [39]. Screw caped test tubes containing Sabouraud dextrose
agar (SDA) medium (4 mL) were autoclaved at 121 ꢂC for 15 min.
Tubes were allowed to cool at 50 ꢂC and non solidified SDA was
R2SnCl2 þ 2NaL/R2SnL2 þ 2NaCl ð1Þ
R ¼ CH3ð1Þ; nꢀC4H9ð2Þ;
loaded with 66.6
m
L
of compound from the stock solution
R3SnCl þ NaL/R3SnL þ NaCl ð2Þ
R ¼ CH3ð4Þ; nꢀC4H9ð5Þ; C6H5ð6Þ
(12 mg mLꢀ1 in DMSO) to make 200
m
g mLꢀ1 final concentration.
Tubes were then allowed to solidify in slanting position at room
temperature. Each tube was inoculated with 4 mm diameter piece of
inoculum from seven days old fungal culture. The media supple-
R2SnO þ 2HL/R2SnL2 þ H2O ð3Þ R ¼ nꢀC8H17ð3Þ
mented with DMSO and Turbinafine (200
m
g mLꢀ1) were used
as negative and positive control, respectively. The tubes were incu-
bated at 28 ꢂC for 7 days and growth was determined by measuring
linear growth (mm). The growth inhibition was calculated with
reference to growth in vehicle control using the following equation.
3.2. FT-IR analysis
IR spectra of all the complexes (1e6) were analyzed in the range
4000e400 cmꢀ1 and used to identify binding mode of COOꢀ moiety
ꢀ
ꢁ
Linear growth in test sample ðmmÞ
Linear growth in control ðmmÞ
% Growth inhibition ¼ 100 ꢀ
ꢃ 100
2.7. Cytotoxic studies
with Sn atom [41]. In the IR spectra of all complexes, the appear-
ance of a new SneO vibration in the region 436e478 cmꢀ1 indi-
cated the deprotonation of the ligand upon coordination with di
and triorganotin(IV) moiety via two oxygen atoms of the COOꢀ
group [42,43]. Bands in the range of 515e586 cmꢀ1 indicate the
presence of SneC bonds. The Dn difference between nasym(COO)ꢀ
and nsym(COO)ꢀ is important to find out the binding mode of COOꢀ
moiety with Sn atom. According to literature, Dn greater than
250 cmꢀ1 shows a monodentate while a value less than 250 cmꢀ1
shows bidentate binding mode of COOꢀ moiety with Sn atom.
Moreover a Dn value between 150 and 250 cmꢀ1 indicates
a bridging behavior while a value less than 150 cmꢀ1 exhibits
Cytotoxicity was studied by the brine-shrimp lethality assay
method [37,38]. Brine-shrimp (Artemia salina) eggs were hatched in
artificial sea water (3.8 g sea salt Lꢀ1) at ambient temperature of
23 ꢁ 1 ꢂC. After two days these shrimps were transferred to vials
containing 5 mL of artificial sea water (10 shrimps per vial) with 10,
100 and 1000
m
g mLꢀ1 final concentrations of each compound
taken from their stock solutions of 12 mg mLꢀ1 in DMSO. After 24 h,
number of surviving shrimps were counted. Data was analyzed
with a Biostat 2009 computer programme (Probit analysis) to
determine LD50 values.

M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
83
Fig. 1. Platon drawing of complex 1 with atomic numbering scheme.
ꢀ
ꢀ
a chelate structure [41]. In the present study, the complexes 1e3
exhibit chelating behavior while 4e6 show a bridging mode of
coordination in solid state. These findings are well matched with
X-ray crystal structures of complexes 1 and 4.
O3eC11 ¼ 1.240(3) A, O4-C11 ¼ 1.299(2) A as depicted in Table 2.
The geometry, bond lengths (Sn1eO1, Sn1eO2, Sn1eO3, Sn1eO4)
and angles (O2eSn1eO1, O2eSn1eO3, O3eSn1eO1, O4eSn1eO1,
O4eSn1eO2, O4eSn1eO3) are comparable with literature values
[52,53].
3.3. NMR studies
The structure of complex 4 is shown in Fig. 2. The crystal data,
selected bond length and bond angles of complex 4 are listed in
Tables 1 and 3. The complex 4 showed polymeric structure with
trigonal bipyramidal geometry. The carboxylate oxygen make zig
zag chain with antiesyn configuration. The CeSneC angles
are in the range 112.0(2)e124.5(2)ꢂ. The axial positions are occu-
pied by the two oxygen atoms of bridging carboxylate ligands
having OeSneO angle 172.30(4)ꢂ. Thus carboxylate ligand
bridges the two symmetry related Sn atoms and gives rise to
the unequal SneO bond distances which are reflected in the asso-
ciated CeO bond lengths, the longer CeO bond is involved in the
shorter SneO interaction and vice versa. These bond lengths are in
accordance with the reported triorganotin(IV) carboxylates [54,55].
The polymeric bridging behavior is comparable with literature
[49,50].
3.3.1. 1H NMR spectra
The 1H NMR spectra represent the integration and multiplicities
of all the protons in the ligand and in 1e6 complexes. The expected
ppm values of aliphatic and aromatic protons showed good
matching. The coordination of COOꢀ moiety with Sn atom was
confirmed by disappearance of acid proton signal at 11.32 ppm and
the formation of SneO bond [44,45]. The structural information
was obtained by the coupling constant 2J [119Sn/117Sn, 1H]. The 2J
[
119Sn/117Sn, 1H] coupling constant value of 83/81 Hz, indicates six
co-ordination behavior having octahedral geometry while 2J
[
119Sn/117Sn, 1H] of 58/56 Hz, indicates four coordination behavior
having tetrahedral geometry [46e48] in solution. In 1H NMR of
compound 1 and 4, the 2J [119Sn/117Sn, 1H] values are 83/80 and 58/
56 Hz, indicating six and four coordination behavior in solution,
respectively.
3.3.2. 13C NMR spectra
Table 1
Crystal data and structure refinement parameters for complexes 1 and 4.
In 13C NMR, the different R (Me, n-But, n-Oct, Ph) groups
attached to Sn atom gave signals in the expected region. The 1J
Compound
1
4
[
119Sn/117Sn, 13C] coupling constant for compound 1 and 4 are 570
Chemical formula
Formula mass (g molꢀ1
Crystal system
C22H22F2O4Sn
507.09
Monoclinic
P 21/c
C13H17FO2Sn
342.96
Monoclinic
P 21/c
)
and 378 Hz, which indicate six and four coordination behavior in
solution, respectively.
Space group
Unit cell dimensions
ꢀ
3.4. Crystal structure of complex 1 and 4
a (A)
9.9206(3)
17.0397(5)
13.3651(3)
90.00
6.7977(2)
9.7882(3)
21.0089(7)
90.00
ꢀ
b (A)
ꢀ
c (A)
The structure of complex 1 is shown in Fig. 1. The crystal data,
selected bond lengths and bond angles of complex 1 are listed
in Tables 1 and 2. The carboxylate moiety COOꢀ of ligand is
bonded as anisobidentate mode with two shorter bonds (Sn1eO2
and Sn1eO4) and two longer bonds (Sn1eO1, Sn1eO3) in asym-
metric way as depicted in Table 2. The geometry at the central Sn
atom is skew-trapezoidal in which the basal plane is defined by four
oxygen atoms derived from the two chelating carboxylate ligands
whereas the remaining two positions are occupied by two methyl
groups. The longer SneO distances are significantly less than the
a
b
g
(ꢂ)
(ꢂ)
(ꢂ)
109.7080(10)
90.00
97.884(2)
90.00
3
ꢀ
Volume (A )
Z
2126.95(10)
4
1384.66(7)
4
Temperature (K)
296(2)
296(2)
Density (calculated) (g cmꢀ3
)
1.584
1.645
Absorption coefficient (mmꢀ1
F(000)
)
1.243
1.845
1016
680
Radiation (A0) (Mo K/
Index ranges
a
)
0.71073
0.71073
h: ꢀ8 / 8;
k: ꢀ11 / 12;
l: ꢀ25 / 25
2.30e26.00
2718
h: ꢀ11 / 11;
k: ꢀ20 / 20;
l: ꢀ15 / 16
2.18e25.24
3839
ꢀ
sum of the van der Waal’s radii (3.68 A) [49], and the coordination
number of Sn is unambiguously assigned as six. The methyl
groups do not occupy the exact axial positions as a result CeSneC
angle is 134.99(9)ꢂ which falls in the range (122.6e156.9) for
skew-trapezoidal geometry [50,51]. The asymmetric mode of coor-
dination of the carboxylate ligands is further confirmed by unequal
q
(ꢂ) Min Max
Total reflections
Data/restraints/parameters
Rall, Rgt
WRref, WRgt
3839/0/267
0.0222, 0.0197
0.0528, 0.0506
1.053
2718/0/159
0.0377, 0.0352
0.0884, 0.0875
1.287
Goodness-of-fit
ꢀ
ꢀ
CeO bond distances; O1eC1 ¼ 1.241(2) A, O2eC1 ¼ 1.300(2) A and

84
M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
Table 2
of thymine [60] resulting in bathochromism or classical electro-
static interaction due to protonated ligand [61]. While the orga-
notin(IV) carboxylates 1 and 4 (Figs. 4 and 5) showed significant
hypochromic effect. This suggest mainly intercalation as well as by
groove mode of binding which may be due to presence of phenyl
group of ligand that facilitates the interaction with DNA [56,62].
After 24 h, the spectrum was again taken and obtained the same
results which confirm the stability of drugeDNA complex.
The intrinsic binding constant K of the ligand HL and organo-
tin(IV) carboxylates 1 and 4 were calculated in order to compare
binding strengths of ligandeDNA and complexeDNA by using
BenesieHildebrand equation [40]:
ꢂ
ꢀ
Selected bond lengths (A) and bond angles ( ) of complex 1.
ꢀ
Bond lengths (A)
SneC21
SneC22
Sn1eO1
Sn1eO2
Sn1eO3
Bond angles (ꢂ)
O2eSn1eO1
O2eSn1eO3
O3eSn1eO1
O4eSn1eO1
O4eSn1eO2
O4eSn1eO3
O4eSn1eC21
2.101(2)
2.087(2)
2.5352(15)
2.0937(13)
2.4846(15)
Sn1eO4
O1eC1
O2eC1
O3eC11
O4eC11
2.0937(12)
1.241(2)
1.300(2)
1.240(3)
1.299(2)
55.47(5)
138.82(5)
165.69(5)
138.21(5)
82.75(5)
C22eSn1eO1
C22eSn1eO3
C22eSn1eO4
C21eSn1eO1
C21eSn1eO3
C22eSn1eC21
88.64(7)
85.61(7)
107.15(7)
86.59(7)
88.23(8)
134.99(9)
56.09(5)
105.90(8)
A0
εG
εG
1
¼
þ
ꢃ
A ꢀ A0
εHꢀG ꢀ εG εHꢀG ꢀ εG K½DNAꢄ
3.5. DNA binding studies
where K is the binding constant, A0 and A are the absorbance of the
drug and its complex with DNA, and εG and εHꢀG are the absorption
coefficients of the drug and the drugeDNA complex, respectively.
The binding constants were obtained from the intercept-to-slope
ratios of A0/(A ꢀ A0) vs. 1/[DNA] plots. The binding constants
were found to be 3.5 ꢃ 104 Mꢀ1 (HL), 6.37 ꢃ 103 Mꢀ1 (1) and
The mode of interaction of organotin(IV) carboxylates with DNA
was determined by UVevisible absorption spectroscopy which is
one of the useful techniques for this purpose [56e58]. The
comparison of absorbance and shift in the wavelength of ligand and
complexes with and without SS-DNA give the idea about the
interaction of ligand or metal complexes with DNA [59].
5.0 ꢃ 104
M
ꢀ1 (4).
The Gibb’s free energy (DG) of the ligand HL and organotin(IV)
The absorption spectra of ligand HL and organotin(IV) carbox-
ylates 1 and 4 in the absence and presence of SS-DNA (salmon
sperm) have been recorded at different concentration of DNA by
keeping concentration of ligand HL and organotin(IV) carboxylates
constant. There exists a single band in the absorption spectrum at
266.80 nm (HL), 260 nm (1) and 260.50 nm (4). The UV studies of
ligand HL showed (Fig. 3) hyperchromic effect. This suggests that
HL binds with DNA double helix by hydrogen bonding between the
ligand and the base pairs in DNA typically to N3 of adenine and O2
carboxylates 1 and 4 were determined by using the following
equation:
D
G ¼ ꢀRT lnK
where R is general gas constant (8.314 J Kꢀ1 molꢀ1) and T is the
temperature (298 K). The Gibb’s free energies were found ꢀ11.3
(HL), ꢀ9.43 (1), and ꢀ11.64 kJ molꢀ1 (4), indicating the interaction
of the compounds with DNA is a spontaneous process.
Fig. 2. Platon drawing of complex 4 with atomic numbering scheme.

M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
85
Table 3
ꢂ
ꢀ
Selected bond lengths (A) and bond angles ( ) of complex 4.
ꢀ
Bond lengths (A)
SneC11
SneC12
SneC13
2.125(5)
2.109(5)
2.125(5)
O1eC1
O2eC1
Sn1eO1
1.297(6)
1.229(6)
2.116(3)
Bond angles (ꢂ)
O1eSneO2
O1eSneC11
O1eSneC12
O1eSn1eC13
172.30(4)
92.19(18)
97.50(19)
99.21(19)
C11eSneC12
C12eSneC13
C11eSneC113
C1eO1eSn1
119.9(2)
124.5(2)
112.0(2)
120.2(3)
Fig. 5. Absorption spectra of 0.04 mM compound 4 in the absence (a) and presence
of 13
mM (b), 26 mM (c), 39 mM (d), 52 mM (e) and 65 mM (f) DNA. The arrow
direction indicates increasing concentrations of DNA. Inside graph is the plot of Ao/
(A ꢀ Ao) vs. 1/[DNA] for the determination of binding constant and Gibb’s free energy of
complex 1 e DNA adduct.
helix as the base pairs were separated to accommodate the binding
complex, leading to an increase in DNA viscosity [63]. There is
a marked effect of HL, 1 and 4 on the viscosity of SS-DNA as shown
in Fig. 6. With the increase in the concentration of HL, the relative
viscosity of HLeDNA mixture remains almost constant and then
starts increasing with further increase in HL concentration which
indicates that groove binding also contribute to some extent. After
that the increase in the effective length of DNA supports that HL
binds through intercalation mode but with different affinity, i.e.,
also show some affinity for binding with grooves of DNA through
hydrogen bonding. However, strong binding is presumably due to
intercalation with DNA [64]. The viscosity of mixture of complexes
1 and 4 with SS-DNA was increased gradually with the increase in
the concentration of the complexes, indicating intercalative inter-
action mode of theses complexes with SS-DNA [37].
Fig. 3. Absorption spectra of 0.04 mM HL in the absence (a) and presence of 13
mM (b),
26 M (c), 39 M (d), 52 M (e), 65 M (f) DNA. The arrow direction indicates
m
m
m
m
increasing concentrations of DNA. Inside graph is the plot of Ao/(A ꢀ Ao) vs. 1/[DNA] for
the determination of binding constant and Gibb’s free energy of HL e DNA adduct.
3.6. Viscosity measurements
To further clarify the binding modes of the HL and its repre-
sentative complexes 1 and 4 with DNA, viscosity measurements
were carried out. Hydrodynamic measurements that are sensitive
to length change (i.e., viscosity) are regarded as the least ambig-
uous and the most critical tests of the binding model in solution. A
classical intercalation model resulted in the lengthening of the DNA
3.7. Biological studies
3.7.1. Antibacterial studies
In vitro biological screening tests of the synthesized ligand HL
and its organotin(IV) complexes (1e6) were carried out for anti-
bacterial activity. The experiment was performed in triplicate by
Fig. 4. Absorption spectra of 0.04 mM compound 1 in the absence (a) and presence of
13 mM (b), 26 mM (c), 39 mM (d), 52 mM (e), 65 mM (f) and 78 mM (g) DNA. The arrow
direction indicates increasing concentrations of DNA. Inside graph is the plot of Ao/
(A ꢀ Ao) vs. 1/[DNA] for the determination of binding constant and Gibb’s free energy of
complex 4 e DNA adduct.
Fig. 6. Effects of increasing concentration of HL, complexes
viscosity of SS-DNA at 25 ꢁ 0.1 ꢂC. [DNA] ¼ 1.86 ꢃ 10ꢀ4 M.
1 and 4 on relative

86
M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
Table 4
Antibacterial data of HL and its organotin(IV) complexes (1e6).
Compound
Average zone of inhibition (mm)
Staphylococcus aureus
Escherichia coli
Bordetella bronchiseptica
Pseudomonas aeruginosa
Micrococcus luteus
Klebsiella pneumoniae
HL
1
2
3
4
5
6
0
15
0
15
14
20
20
20
25
17
25
25
0
15
0
0
0
0
15
14
13
0
20
18
25
25
30
0
10
11
0
15
12
12
22
30
0
0
0
22
22
30
22
25
25
24
35
20
25
18
17
15
23
25
Cefixime
Roxithromycin
Concentration: 1 mg/mL of DMSO. Reference drugs, Roxythromycin and Cefixime 1 mg/mL.
agar well-diffusion method. Roxithromycin and Cefixime were used
as positive control. The results are shown in Table 4. Criteria for
activity is based on zone of inhibition (mm); inhibition zone more
than 20 mm shows significant activity, for 18e20 mm inhibition
activity is good, 15e17 mm is low, and below 11e14 mm is non-
significant [37]. The antibacterial study demonstrates that all
compounds except ligand HL and complex 3 have activity toward
tested bacteria. Complex 6, exhibited greater activity against two
pathogenic strains, S. aureus and B. bronchiseptica than both stan-
dard drugs while good activity against M. luteus. The complexes 4
and 5 showed significant activity against four strains S. aureus,
E. coli, B. bronchiseptica and M. luteus, whereas the activity exhibited
against B. bronchiseptica is better than Cefixime, used as positive
control. Complex 1 showed non significant to low activity against
all pathogenic strains. Complex 2 showed non significant to good
activity against all tested strains.
significant inhibiting activity against three fungal strains, A. flavus,
A. niger, and F. solani.
Significantly higher antimicrobial activity of the reported
complexes as compared to organotin carboxylates could probably
be due to the presence of highly polar flouro group on benzene ring
which offers greater interaction with the cell constituents of the
microorganisms [65].
3.7.3. Cytotoxic studies
The cytotoxicities of ligand HL and its organotin(IV) complexes
(1e6) were studied in vitro against the brine-shrimp lethality
method by using reference drug MS-222 (Tricaine methanesulfo-
nate) and the results are summarized in Table 6. The data is based
on mean value of 2 replicates each of 10, 100 and 1000 m
g mLꢀ1. The
LD50 data exhibited that ligand HL and all the tested organotin(IV)
complexes are toxic having values in the range 0.108e
46.31
Complexes 2, 4e6 were proved to be most toxic as compared to
m m .
g mLꢀ1 with reference having the value 4.3 g mLꢀ1
3.7.2. Antifungal studies
The ligand HL and its organotin(IV) complexes (1e6) were also
screened for antifungal activity against five fungal strains (Asper-
gillus flavus, A. niger, A. fumigatus, F. solani and M. species) by using
Agar tube dilution method. The results are shown in Table 5. Ter-
binafine was used as standard drug in this assay. Criteria for activity
is based on percent growth inhibition; more than 70% growth
inhibition was considered as significant activity, 60e70% inhibition
activity as good, 50e60% inhibition activity as moderate while
below 50% inhibition activity was considered as non-significant.
The results show that the synthesized organotin(IV) complexes in
general have more activity than the ligand HL except for complexes
1 and 3 which exhibited non-significant against all the tested
strains. Complexes 4 and 5 showed 100% growth inhibition against
all tested fungal strains like the reference drug used. The complex 5
exhibited 100% growth inhibition against three fungal strains, A.
niger, A. fumigatus, and M. species while complex 2 exhibited
tested compounds and reference drugs.
3.7.4. Anti-tumor studies
The anti-tumor activity of ligand HL and organotin(IV)
complexes (1e6) was evaluated by crown gall tumor inhibition
assay (potato disc assay) because the mechanism of tumor
Table 6
Cytotoxicity data of HL and its organotin(IV) complexes (1e6).
Compound
No. of shrimps killed out of 20 per dilutiona
LD50
1000
m
g mLꢀ1
100
m
g mLꢀ1
10 m
g mLꢀ1
HL
1
2
3
4
5
6
20
20
20
20
20
20
20
0
17
11
18
18
20
20
19
0
0
5
15
5
20
20
18
0
13.01
46.31
1.81
22.08
e
e
0.108
Vehicle control
Table 5
Antifungal activity data of HL and its organotin(IV) complexes (1e6).
a
Against brine-shrimps (in vitro).
Compound
Mean value of percent growth inhibition (%)
Aspergillus
flavus
Aspergillus
niger
Aspergillus
fumigatus
Fusarium
solani
Mucor
species
Table 7
Antitumor data of HL and its organotin(IV) complexes (1e6).
HL
1
2
3
4
5
6
40
10
77
0
100
40
62.5
20
85
0
10
0
0
0
85
10
100
45
55
40
Compound no.
No. of tumors
No. of tumors/disc
% Inhibition
HL
1
2
3
4
5
6
27
4.0
15
2.3
0.4
1.7
2.1
0.3
0.2
0.0
0.0
7.5
69
95
77
72
96
47.5
10
100
100
100
100
20
45
100
100
100
100
100
100
100
100
25
3.0
2.0
0.0
0.0
82
100
100
100
100
97
Terbinafine
100
100
e
In vitro agar tube dilution method, concentration: 200 mg/mL of DMSO. % Inhibition
Vincristine
Control
of fungal growth ¼ 100 ꢀ gt/gc ꢃ 100. Gt ¼ linear growth in test (mm) and
gc ¼ linear growth in vehicle control (mm).

M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
87
Table 8
expansion which may play an important role in the catalytic
activity of different substituted organotin compounds. The activa-
tion of carbonyl groups in triglycerides to increase the electrophi-
licity of the carbonyl carbon and a subsequent interaction with tin
atom. Since Lewis acid catalysts can activate carbonyl groups, our
interest was concentrated on metal complexes with fluorinated
ligands, whose Lewis acidity may depend on the groups attached to
metal (e.g. Sn) and nucleophilicity by fluorinated ligand.
The transesterification reaction was carried out in molar ratio of
400:100:1 (methanol, oil and catalyst) as reported in literature [30].
The conditions for experiments were not optimized and no attempt
was made to remove the added catalyst from the reaction mixture.
The sample was taken from the reaction mixture at regular interval
of 1, 8, 16 and 24 h and was analyzed by 1H NMR to calculate % age
conversion of triglycerides into fatty acid methyl esters (FAMEs)
[66,67]. The results are summarized in Table 8. The equation used to
quantify the extent of transesterification was:
% age conversion of triglycerides in rocket seed oil to FAMEs.
Catalyst
Time (h)
% Conversion
Me3SnL (4)
1
8
16
24
1
0.0
35.21
65.73
84.19
0.0
21.56
30.82
53.73
0.0
Bu3SnL (5)
Ph3SnL (6)
NaOH
8
16
24
1
8
17.45
29.34
43.0
16
24
1.5
88.49
induction is similar to that seen in animals. All the complexes
showed significant levels of tumor inhibition, as shown in Table 7.
The complexes 1e6 exhibited more activity than ligand HL. The
complex 6 exhibited 100% anti-tumor activity. Moreover complexes
4e6 exhibited excellent activity than complexes 1e3 which is
consistent to the earlier reports on organotin(IV) carboxylates [40].
The results showed the order 6 > 5 > 4 > 1 > 2 > 3.
2AMe
C ¼ 100
(4)
3ACH
2
where
C ¼ percentage conversion of triglycerides to corresponding
methyl esters
3.8. Catalytic activity of compounds 4e6
AMe ¼ integration value of the methoxy protons of the methyl
esters and
The catalytic activity of triorganotin(IV) carboxylates 4e6 was
investigated in a transesterification reaction on triglycerides in oil
with methanol. The tin complexes are selected due to the Lewis
acid character of tin. The tin atom has the property of coordination
ACH ¼ integration value of
a-methylene protons
2
All the experiments were carried out in the presence of ligand
HL as catalyst but transesterification was not detected at all. The
a
b
O
R
..
..
O
+
R
O
C
R1
C
3
CH .O.H
R
O
Sn
Sn
O
C
R1
O
R
R3
R2
+
R
R
R
R
O
C
+
OH
R
H3C
O
R
R1
R=Me,Bu,Ph
Sn
O
R
R1
C
Sn
+ O
O
R
R3
R2
O
C
R1= F
C
H
C
..
CH3OH
R2
C
..
R
O
C
..
..
R
H
R
OR3
Sn
R1
O
O
..
H3C
+
O
O
..
O
O
R
R1
C
O
Sn
R3
R2
O
C
R
R3
R2
Triglycerides-representation
where
O
C
R
CH3OH
+
R
O
C
R
R
R3
CH2
R1
=
Sn
O
O
C
CH
O
..
CH3O
R2
HOR3
glycerin
O
C
+
..
..
..
methyl ester
+
HOR3
CH2
R3
O
R2
CH3O
R2
+
C
methyl ester
glycerin
H
CH3O
R2= C12-C24
Proposed mechanism 1
Proposed Mechanism 2
Fig. 7. a and b: Proposed mechanism for transesterification of triglycerides into fatty acid methyl esters (biodiesel).

88
M. Tariq et al. / Journal of Organometallic Chemistry 723 (2013) 79e89
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catalytic activity of triorganotin(IV) carboxylates 4e6 was also
compared with traditional base catalyst NaOH [68] using molar
ratio of methanol, oil and catalyst 6:1:0.75. The results are
summarized in Table 8. Although base catalyst gave high % age
conversion in less time as compare to triorganotin(IV) carboxylates
4e6, which work slowly and gave almost the same % age conver-
sion (compound 4) in 24 h but this research may open new ways to
overcome the problems associated with use of base catalysts. The
proposed mechanisms for the catalytic activity of organotin(IV)
carboxylates is the Lewis acid character of tin atom [69e71] as in
case of polyesterification and are shown in Fig. 7aeb). The Lewis
acidity of Sn atom increase in the order, Me < Bu < Ph because
methyl and butyl groups are electron donating while phenyl is
electron withdrawing group [72,73]. The stronger the Lewis acidity,
greater would be catalytic efficiency but in our studies catalytic
performance is in reverse order which may be due to size of groups
(Me, Bu, Ph) attached to Sn atom. As the group attached to Sn atom
increase in size, the attack on the bulky triglycerides becomes
difficult so Me3SnL perform better than Bu3SnL and Ph3SnL.
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4. Conclusion
Six organotin(IV) carboxylate complexes of 3-(4-flourophenyl)-
2-methylacrylic acid were synthesized with the aim to develop new
biologically active compounds. The complexes were characterized
by FT-IR, NMR (1H and 13C) and X-ray crystallography. The inter-
actions of ligand HL and complexes 1 and 4 were studied with SS-
DNA using UVevisible spectroscopy and viscosity measurements.
The results indicated intercalation mode of binding for complexes 1
and 4 while hydrogen bonding between the ligand and the base
pairs in DNA or classical electrostatic interaction due to protonated
ligand. The intrinsic binding constants K were found to be 3.5 ꢃ 104,
6.37 ꢃ 103 and 5.0 ꢃ 104 Mꢀ1 for HL, complexes 1 and 4, respec-
tively. The antimicrobial results showed that triorganotin(IV)
carboxylates complexes 4e6 exhibit greater activity than dio-
rganotin(IV) carboxylates complexes 1e3. The cytotoxic studies
revealed that complexes 4e6 were the most toxic as compared to
tested compounds and reference drugs. The anti-tumor activities
revealed that complex 6 has 100% inhibition while overall order is
6 > 5 > 4 > 1 > 2 > 3 > HL. The catalytic activity of compounds 4e6
was assessed for transesterification of rocket seed oil using meth-
anol, oil, catalyst molar ratio of 400:100:1. The Me3SnL exhibited
good catalytic activity as compare to Bu3SnL and Ph3SnL which is
reverse the order of Lewis acidity because groups (Me, Bu, Ph)
attached to Sn atom play important role on attacking of bulky
triglyceride molecule to the Sn center.
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Acknowledgments
M. Tariq (Pin No. 074-0616-Ps4-099) is thankful to higher
education commission of Pakistan for financial support during the
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