Structural studies of diethyltin(IV) derivatives and their biological aspects as potential antitumor agents against Agrobacterium tumefacien cells

Article abstract of DOI:10.1002/aoc.1777

A series of new diethyltin(IV) derivatives of substituted phenyl acrylates have been synthesized and characterized by elemental analysis, IR, multinuclear NMR (¹H, ¹³C, ¹⁹F and ¹¹⁹Sn) and X-ray single crystal analysis. X-ray single crystal diffraction study of complex 8 has shown the formation of secondary O···Sn, F···H and H···O intermolecular interactions. These complexes proved to be good antitumor agents. The antitumor properties are presumably due to the intercalative mode of interaction of these complexes with the tumor cells' DNA.

Full text of DOI:10.1002/aoc.1777

Full Paper
Received: 29 May 2010
Revised: 25 November 2010
Accepted: 25 November 2010
Published online in Wiley Online Library: 14 April 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1777
Structural studies of diethyltin(IV) derivatives
and their biological aspects as potential
antitumor agents against Agrobacterium
tumefacien cells
Mukhtiar Hussaina, Zia-ur-Rehman a, Muhammad Hanifa,
Muhammad Altafb, Aziz-ur-Rehman a, Saqib Alia∗
and Kingsley J. Cavellc
A series of new diethyltin(IV) derivatives of substituted phenyl acrylates have been synthesized and characterized by elemental
analysis, IR, multinuclear NMR (1H, 13C, 19F and 119Sn) and X-ray single crystal analysis. X-ray single crystal diffraction study
· · ·
· · ·
· · ·
of complex 8 has shown the formation of secondary O Sn, F H and H O intermolecular interactions. These complexes
proved to be good antitumor agents. The antitumor properties are presumably due to the intercalative mode of interaction of
c
these complexes with the tumor cells’ DNA. Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: diethyltin(IV) derivatives; substituted phenylacrylates; multinuclear NMR; Agrobacterium tumefacien cells; X-ray structure
Introduction
Experimental
The reagents, phenyl acetic acids, aldehydes and acetic anhydride,
were purchased from commercial sources (Aldrich, USA) and
were used without further purification. The solvents were
dried prior to use by standard procedures.[19] Melting points
were determined with Gallenkemp (UK) apparatus and were
uncorrected. Elemental analyses were carried out using a Leco
CHNS-932 analyzer USA. Infrared spectra were recorded as
KBr pellets on Bio-Rad Excalibur FT-IR, model FTS 300 MX
spectrophotometer,inthefrequencyrangeof4000–400 cm−1.1H,
13C, 19Fand119SnNMRspectrainsolutionwererecordedonBruker
ARX 300 MHz, 400 MHZ and 500 MHz FT-NMR spectrometers,
respectively. Chemical shifts are reported in ppm relative to
the external references, tetramethylsilane (TMS) for 1H, 13C
NMR, trichlorofluoromethane for 19F and tetramethyltin for 119Sn
chemical shifts. X-ray single crystal analysis was made on a Nonius
Kappa CCD diffractometer with graphite monochromated MoKα
radiation.
Cancer and tumor growth in humans and plants are prime chal-
lenges for chemists. In the search for alternatives and effective
metallo-organic anticancer and antitumor drugs, organotin car-
boxylates have received considerable attention on account of
their potential biological applications.[1–7] Our research group
has also contributed towards extensive research on the evalua-
tion of organotin(IV) compounds as potent tumor inhibitors.[8–15]
Organotin(IV) compounds are eco-toxicants whose action de-
pends upon their structure. Owing to higher activity and lower
toxicity of diorganotin derivatives,[16] the compounds of the type
[(RCOOSnR2)2O]2 and (RCOO)2SnR2 have been extensively stud-
ied for their antitumor activity against tumor cell lines.[3] Our
recent investigations[13–15] showed that these compounds in-
teract with DNA in intercalative fashion by making secondary
contacts with the bases, culminating in its structural machinery.
The outcome is that the compounds have the ability to form
strong noncovalent interactions with DNA and should be good
antitumor agents. In order to pursue this idea, and keeping in
view the antitumor potential of diorganotins, we designed nine
new carboxylate ligands with the capability to form secondary
interactions, e.g. hydrogen bonding, π –H and O–H bonding, and
coupled them with diethyltin(IV) moiety. These compounds were
tested against plant tumors and proved effective. Antitumour
studies were carried out against Agrobacterium tumefacien cells.
These are Gram-negative bacteria and infect the plants through
their Ti plasmids. This study is a continuation of our previous
work[12–18] and will be helpful in designing new organotins of
pharmaceutical value.
∗
Correspondence to: Saqib Ali, Department of Chemistry, Quaid-i-Azam
University Islamabad-45320, Pakistan. E-mail: drsa54@yahoo.com
a
DepartmentofChemistry,Quaid-i-AzamUniversityIslamabad-45320,Pakistan
´
Institute of Microtechnology, University of Neuchatel, Rue Emile-Argand 11,
b
´
CH-2009 Neuchatel, Switzerland
c
School of Chemistry, Cardiff University, Main Building Park Place Cardiff C10
3AT, UK
c
Appl. Organometal. Chem. 2011, 25, 412–419
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

Structural studies of diethyltin(IV) derivatives
3-(2,3-Methylenedioxyphenyl)-2-(4-methyoxyphenyl)acrylic acid
(HL5)
13C NMR δ (ppm): 173.2 (1-C), 160.7 (7-C), 148.5 (13-C), 147.4 (12-C),
138.3 (3-C), 132.3 (2-C), 131.8 (4-C), 125.4 (5, 5ꢁ-C), 124.8 (6, 6ꢁ-C),
120.7 (9-C), 120.3 (10-C), 114.7 (8-C), 109.6 (11-C), 103.1(14-C), 54.3
(15-C).
Scheme 1. Preparation of o-piperonal.
Synthesis of 2,3-Methylenedioxy Benzaldehyde (o-Piperonal)
and Substituted Phenylacrylic Acids
3-(4-Trifluoromethylphenyl)-2-(4-fluorophenyl)acrylic acid (HL6)
13C NMR δ (ppm): 172.6 (1-C), 164.4 (7-C), 1J[13C, 19F] 245 Hz, 141.0
(3-C), 137.6 (8-C), 133.0 (2-C), 131.7 (4-C), 131.2, 130.8, 130.4 (9, 10,
11, 12, 13-C), 126.5 (5, 5ꢁ-C 3J[13C, 19F] 7 Hz, 124.3 (14-C), 116.2 (6,
6ꢁ-C) 2J[13C, 19F] 24 Hz.
The o-piperonal and substituted phenylacrylic acids were synthe-
sized by reported methods[20,21] as shown in Schemes 1 and 2,
respectively. Ligand acids were synthesized by dissolving phenyl
acetic acids and aromatic aldehydes (1 : 1) in 10 ml of acetic an-
hydride. The mixture was gently heated for 2–3 h. To the cooled
solution, potassium carbonate (0.18–0.25 g, 1.3–1.8 mmol) was
added as basic medium. Neutralization of this solution by hy-
drochloric acid provided the final product as precipitates. It was
purified by washing with water three times.
3-(2-Methylphenyl)-2-(4-chlorophenyl) acrylic acid (HL7)
13C NMR δ (ppm): 172.8 (1-C), 141.8 (3-C), 137.9 (8-C), 135.8 (7-C),
133.6 (13-C), 132.1 (2-C), 131.5 (4-C), 130.7, 129.7 (5, 5ꢁ, 6, 6ꢁ-C),
127.4, 126.8, 125.5, 124. 8 (9, 10, 11, 12-C), 15.8 (14-C).
3-(2, 3-Methylenedioxyphenyl)-2-(4-fluorophenyl)acrylic acid (HL1)
3-(2-Methylphenyl)-2-(4-fluorophenyl) acrylic acid (HL8)
13C NMR δ (ppm): 167.5 (1-C), 162.1 (7-C) 1J[13C, 19F] 244 Hz, 147.9
(13-C), 147.6 (12-C), 140.6 (3-C), 132.1 (2-C), 131.7 (4-C), 126.2 (5,
5ꢁ-C) 3J[13C, 19F] 8 Hz, 121.3 (9-C), 121.1 (10-C), 117.0 (8-C), 115.1
(6, 6ꢁ-C) 2J[13C, 19F] 23 Hz, 107.4 (11-C), 106.3 (14-C).
13C NMR δ (ppm): 173.1 (1-C), 163.7 (7-C) 1J[13C, 19F] 244 Hz, 141.8
(3-C), 137.9 (8-C), 133.6 (13-C), 132.1 (2-C), 131.5 (4-C), 126.4 (5,
5ꢁ-C) 2J[13C, 19F] 8 Hz, 127.2, 126.1, 125.5, 124.9 (9, 10, (11, 12-C),
15.8 (14-C), 115.8 (6, 6ꢁ-C) 2J[13C, 19F] 24 Hz.
3-(2, 3-Methylenedioxyphenyl)-2-(2-fluorophenyl)acrylic acid (HL2)
3-(4-Trifluoromethylphenyl)-2-(3-methylphenyl)acrylic acid (HL9)
13C NMR δ (ppm): 168.9 (1-C), 158.9 (5-C) 1J[13C, 19F] 245 Hz, 147.5
(13-C), 147.4 (12-C), 136.6 (3-C), 132.4 (2-C), 130.3 (4-C), 126.3 (7-C)
3J[13C, 19F] 8 Hz, 124.2 (5, 5ꢁ-C) 3J[13C, 19F] 4 Hz, 123.4 (6-C), 121.3
(9-C), 121.1 (10-C), 116.3 (8-C), 115.9 (6ꢁ-C) 2J[13C, 19F] 23 Hz, 109.6
(11-C), 101.3 (14-C).
13CNMR δ (ppm): 172.8 (1-C), 140.3 (3-C), 138.6 (8-C), 137.8 (6, 6ꢁ-C),
132.2 (2-C), 131.5 (4-C), 130.8, 130.0, 129.3 (9, 10, 11, 12, 13-C),
128.8, 126.7, 125.6, 124.7 (5, 5ꢁ, 6, 7-C), 122.0 (14-C), 21.4 (15-C).
Synthesis of Diethyltin(IV) Derivatives (1–9)
For synthesis of ethyltin(IV) derivatives, sodium salts of HL1–5
and triethylammonium salts of HL6–9 were prepared as reported
earlier.[10,11,17,18] Triethyl ammonium salts were prepared in situ
by reaction of ligand acids and triethylamine (022–0.27 ml,
1.6–1.95 mmol)in1 : 1ratiousing tolueneassolvent. Diethyltin(IV)
dichloride in toluene (70 ml) was added in stoichiometric amounts
(1 : 2) to suspension of sodium–triethyl ammonium salt of ligands
in toluene. The mixture was refluxed for 6–7 h with constant
stirring. Byproducts (NaCl/triethyl ammonium chloride) were
removed by filtration and clear filtrate was evaporated under
reduced pressure, yielding a solid product (Scheme 3).
3-(2, 3-Methylenedioxyphenyl)-2-(4-chlorophenyl) acrylic acid (HL3)
13CNMR δ (ppm): 172.3 (1-C), 147.5 (13-C), 147.4 (12-C), 139.6 (3-C),
135.6 (7-C), 132.5 (2-C), 131.9 (6, 6ꢁ-C), 131.4 (4-C), 129.4 (5, 5ꢁ-C),
121.3 (9-C), 121.2 (10-C), 116.8 (8-C), 108.9 (11-C), 101.4 (14-C).
3-(2, 3-Methylenedioxyphenyl)-2-(4-bromophenyl)acrylic acid (HL4)
13C NMR δ (ppm): 167.1 (1-C), 147.7 (13-C), 147.2 (12-C), 140.3 (3-C),
135.4 (6, 6ꢁ-C), 134.1 (5, 5ꢁ-C), 133.6 (2-C), 131.3 (4-C), 128.8 (7-C),
121.7 (9-C), 121.3 (10-C), 116.5 (8-C), 109.5 (11-C), 101.3 (14-C).
Scheme 2. Preparation of substituted phenylacrylic acids HL1 –HL9.
c
Appl. Organometal. Chem. 2011, 25, 412–419
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

M. Hussain et al.
Scheme 3. Preparation of diethyltin(IV) esters of phenylacrylic acids 1–9.
Diethyltin(IV) bis-[3-(2,3-methylenedioxyphenyl)-2-(4-fluorophenyl)
Diethyltin(IV) bis-[3-(4-trifluoromethylyphenyl)-2-(4-fluorophenyl)
acrylate] (1)
acrylate] (6)
13C NMR δ (ppm): 176.3 (1-C), 164.3 (7-C) 1J[13C, 19F] 247 Hz, 140.0
(3-C), 138.1 (8-C), 133.6 (2-C), 131.6 (4-C), 131.1, 130.5, 129.6 (9, 10,
11, 12, 13-C), 125.8 (5, 5ꢁ-C) 3J[13C, 19F] 8 Hz, 116.1 (6, 6ꢁ-C) 2J[13C,
19F] 22 Hz, 124.2 (14-C), 17.9 (α-C, SnCH2CH3) 1J[119Sn, 13C] 595 Hz,
(C-Sn-C) angle (deg) 129, 9.1 (β-C, SnCH2CH3). 119Sn NMR δ (ppm):
−95. 19F NMR δ (ppm): −63.8 (C-F3), −114.0 (C-F).
13C NMR δ (ppm): 176.7 (1-C), 164.1 (7-C) 1J[13C, 19F] 245 Hz, 147.5
(13-C), 147.0 (12-C), 135.8 (3-C), 132.0 (2-C), 131.6 (4-C), 126.7 (5,
5ꢁ-C) 3J[13C, 19F] 8 Hz, 121.8 (9-C), 121.2 (10-C), 117.1 (8-C), 115.4
(6, 6ꢁ-C),2J[13C, 19F] 24 Hz, 109.1 (11-C), 101.1 (14-C), 17.8 (α-C,
SnCH2CH3), 1J[119Sn, 13C] 778 Hz, (C-Sn-C) angle (deg) 145, 9.1
(β-C, Sn-CH2CH3). 119Sn NMR δ (ppm): −235.4. 19F NMR δ (ppm):
−114.3.
Diethyltin(IV)bis[3-(2-methylphenyl)-2-(4-chlorophenyl)acrylate](7)
13C NMR δ (ppm): 173.1 (1-C), 141.0 (3-C), 136.7 (8-C), 135.6 (7-C),
134.8 (13-C), 132.7 (2-C), 131.4 (4-C), 130.6, 129.2 (5, 5ꢁ, 6, 6ꢁ-C),
127.4, 126.2, 125.4, 124.5 (9, 10, 11, 12-C), 19.1 (14-C), 17.1 (α-C,
SnCH2CH3), 8.2 (β-C, SnCH2CH3). 119Sn NMR δ (ppm): −147.1.
Diethyltin(IV) bis-[3-(2,3-methylenedioxyphenyl)-2-(2-fluorophenyl)
acrylate] (2)
13C NMR δ (ppm): 176.1 (1-C), 161.8 (5-C) 1J[13C, 19F] 246 Hz, 147.4
(13-C), 147.0 (12-C), 135.7 (3-C), 132.9 (2-C), 130.1 (4-C), 126.1 (7-C)
3J[13C, 19F] 8 Hz, 125.3 (5, 5ꢁ-C) 3J[13C, 19F] 6 Hz 124.2 (6, 6ꢁ-C), 121.3
(9-C), 121.2 (10-C), 117.1 (8-C), 115.9 (6-C),2J[13C, 19F] 21 Hz, 109.2
Diethyltin(IV) bis [3-(2-methylphenyl)-2-(4-fluorophenyl) acrylate] (8)
1
(11-C), 101.1 (14-C), 17.9 (α-C, Sn-CH2CH3), J[119Sn, 13C] 561 Hz,
13C NMR δ (ppm): 177.1 (1-C), 163.8 (7-C), 1J[13C, 19F] 245 Hz, 141.1
(3-C), 137.6(8-C), 134.2(13-C), 132.1(2-C), 131.5(4-C), 126.2(5, 5ꢁ-C)
3J[13C, 19F] 8 Hz, 129.6, 128.6, 125.4, 124.8 (9, 10, 11, 12-C), 115.4 (6,
6ꢁ-C) 2J[13C, 19F] 21 Hz, 20.2 (14-C), 17.9 (α-C, SnCH2CH3), 1J[119Sn,
13C] 539 Hz, (C-Sn-C) angle (deg) 124, 9.2 (β-C, SnCH2CH3). 119Sn
NMR δ (ppm): −163.6. 19F NMR δ (ppm): −114.
(C-Sn-C) angle (deg) 126, 8.9 (β-C, SnCH2CH3). 119Sn NMR δ (ppm):
−75.0. 19F NMR δ (ppm): −114.05.
Diethyltin(IV) bis-[3-(2,3-methylenedioxyphenyl)-2-(4-chlorophenyl)
acrylate] (3)
13C NMR δ (ppm): 176.1 (1-C), 147.4 (13-C), 146.9 (12-C), 137.0 (3-C),
134.9 (7-C), 133.4 (2-C), 131.7 (6, 6ꢁ-C), 131.2 (4-C), 128.6 (5, 5ꢁ-C),
121.8 (9-C), 121.2 (10-C), 117.2 (8-C), 108.9 (11-C), 101.1 (14-C), 18.0
Diethyltin(IV) bis [3-(4-trifluoromethylphenyl)-2-(3-methyl) acrylate]
(9)
13C NMR δ (ppm): 175.2 (1-C), 141.3 (3-C), 137.9 (8-C), 135.4 (6,
6ꢁ-C), 132.2 (2-C), 131.4 (4-C), 130.5, 129.6, 128.7 (9, 10, 11, 12,
13-C), 127.6, 126.3, 125.6, 124.9 (5, 5ꢁ, 6, 7-C,), 123.2 (14-C), 20.5
(15-C), 16.9 (α-C, SnCH2CH3) 1J[119Sn, 13C] 504 Hz, (C-Sn-C) angle
(deg) 122, 8.0 (β-C, SnCH2CH3). 119Sn NMR δ (ppm): −166.7. 19F
NMR δ (ppm): −63.4.
1
(α-C, SnCH2CH3), J[119Sn, 13C] 504 Hz, (C-Sn-C) angle (deg) 121,
8.7 (β-C, SnCH2CH3). 119Sn NMR δ (ppm): −165.8.
Diethyltin(IV) bis-[3-(2,3-methylenedioxyphenyl)-2-(4-bromophenyl)
acrylate] (4)
13C NMR δ (ppm): 176.6 (1-C), 146.9 (13-C), 147.5 (12-C), 138.4 (3-C),
136.0 (6, 6ꢁ-C), 134.7 (5, 5ꢁ-C), 132.6 (2-C), 131.6 (4-C), 129.5 (7-C),
122.1 (9-C), 121.8 (10-C), 116.9 (8-C), 109.2 (11-C), 101.2 (14-C), 17.9
Results and Discussion
Physical data of ligand acids (HL1 –HL9) and diethyltin(IV)
1
(α-C, SnCH2CH3), J[119Sn, 13C] 584 Hz, (C-Sn-C) angle (deg) 128,
complexes (1–9) is given in Table 1.
9.1 (β-C, SnCH2CH3). 119Sn NMR δ (ppm): −75.0.
Infrared Spectroscopy
Diethyltin(IV) bis-[3-(2,3-methylenedioxyphenyl)-2-
(4-methoxyphenyl) acrylate] (5)
In the IR spectra of all complexes (Table 2), the appearance of a
−1
· · ·
new Sn O vibration in the region 436–478 cm indicated the
13C NMR δ (ppm): 177.4 (1-C), 160.3 (7-C), 147.7 (13-C), 147.2 (12-C),
136.7 (3-C), 132.9 (2-C), 131.3 (4-C), 124.9 (5, 5ꢁ-C), 122.2 (6, 6ꢁ-C),
121.4 (9-C), 121.3 (10-C), 114.3 (8-C), 109.2 (11-C), 101.4 (14-C), 55.3
(15-C), 18.2 (α-C, SnCH2CH3,), 1J[119Sn, 13C] 527 Hz, (C-Sn-C) angle
(deg) 123, 9.5 (β-C, SnCH2CH3). 119Sn NMR δ (ppm): −125.
deprotonation of the ligand upon coordination with diethyltin(IV)
moiety via two oxygen atoms of the COO group.[16] The difference
between asymmetric and symmetric stretching frequencies (ꢀν)
is an excellent indicator to assess the mode of coordination of the
ligand. The calculated ꢀν values lie in the range 170–188 cm−1
,
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 412–419

Structural studies of diethyltin(IV) derivatives
Table 1. Physical data of ligand acids (HL1 –HL9) and complexes 1–9
Reactants
Elemental analysis
Molecular
formula
Melting Yield
point (◦C) (%)
%C calcd %H calcd
HL/complex Phenyl acetic acid
Aldehyde
(found)
(found)
HL1
HL2
HL3
HL4
HL5
HL6
HL7
HL8
HL9
4-Fluoro (0.5 g, 3.25 mmol) o-Piperonal (0.49 g, 3.25 mmol)
2-Fluoro (0.5 g, 3.25 mmol) o-Piperonal (0.49 g, 3.25 mmol)
4-Chloro (0.5 g, 2.93 mmol) o-Piperonal (0.44 g, 2.93 mmol)
C16H11O4F
C16H11O4F
C16H11O4Cl
C16H11O4Br
C17H14O5
203–205
173–176
186–188
213–215
229–231
163–166
175–177
170–172
185–188
83 67.1 (67.6) 3.8 (4.2)
88 67.1 (66.4) 3.8 (3.2)
75 63.5 (64.0) 3.6 (4.0)
78 55.3 (55.7) 3.2 (3.7)
65 68.5 (67.8) 4.7 (4.1)
78 61.9 (62.3) 3.2 (3.8)
81 70.4 (70.0) 4.8 (4.1)
82 75.0 (75.4) 5.0 (5.5)
76 66.6 (67.1) 4.2 (4.8)
4-Bromo (0.5 g, 2.3 mmol)
o-Piperonal (0.35 g, 2.3 mmol)
4-Methoxy (0.5 g, 3.0 mmol) o-Piperonal (0.45 g, 3.0 mmol)
4-Fluoro (0.5 g, 3.25 mmol) 4-CF3 benzaldehyde (0.56 g, 3.25 mmol)
4-Chloro (0.5 g, 2.93 mmol) o-Tolualdehyde (0.35 g, 2.93 mmol)
4-Fluoro (0.5 g, 3.25 mmol) o-Tolualdehyde (0.39 g, 3.25 mmol)
3-Methyl (0.5 g, 3.33 mmol) 4-CF3 benzaldehyde (0.58 g, 3.33 mmol)
C16H10O2F4
C16H13O2Cl
C16H13O2F
C17H13O2F3
Ligand (NaL1–5/HL6–9
)
Diethyltin(IV) dichloride
Complex 1
Complex 2
Complex 3
Complex 4
Complex 5
Complex 6
Complex 7
Complex 8
Complex 9
NaL1 (0.31g, 1.0 mmol)
NaL2 (0.31g, 1.0 mmol)
NaL3 (0.32g, 1.0 mmol)
NaL4 (0.37g, 1.0 mmol)
NaL5 (0.32g, 1.0 mmol)
HL6 (0.5g, 1.6 mmol)
HL7 (0.5g, 1.8 mmol)
HL6 (0.5g, 1.95 mmol)
HL6 (0.5g, 1.6 mmol)
(C2H5)2SnCl2 (0.5 g, 2.0 mmol)
(C2H5)2SnCl2 (0.5 g, 2.0 mmol)
(C2H5)2SnCl2 (0.5 g, 2.0 mmol)
(C2H5)2SnCl2 (0.5 g, 2.0 mmol)
(C2H5)2SnCl2 (0.5 g, 2.0 mmol)
(C2H5)2SnCl2 (0.8 g, 3.2 mmol)
(C2H5)2SnCl2 (0.9 g, 3.6 mmol)
(C2H5)2SnCl2 (0.97 g, 3.9 mmol)
(C2H5)2SnCl2 (0.8 g, 3.2 mmol)
C36H30O8F2Sn 160–163
C36H30O8F2Sn 170–172
C36H30O8Cl2Sn 115–120
C36H30O8Br2Sn 172–176
85 57.9 (57.2) 4.0 (4.7)
84 57.9 (57.3) 4.0 (4.7)
71 55.4 (55.6) 3.9 (4.3)
80 49.7 (49.0) 3.5 (3.6)
74 59.2 (58.6) 4.7 (5.4)
74 54.4 (55.3) 3.6 (4.1)
68 60.0 (60.4) 4.8 (4.9)
79 62.9 (63.0) 5.0 (4.7)
78 58.0 (58.3) 4.4 (4.9)
C38H36O10Sn
199–201
C36H28O4F8Sn 134–138
C36H34O4Cl2Sn 174–176
C36H34O4F2Sn 138–143
C38H34O4F6Sn 157–161
Table 2. Infrared data of ligand acids (HL1 –HL9) and complexes 1–9
ν(COO)
HL/complex
ν(C–H)
ν(OH)
νAsym
νSym
ꢀν
ν(O–CH2 –O)
ν(Sn–C)
ν(Sn–O)
HL1
3063
3110
3134
3105
3141
3150
3132
3144
3150
3138
3134
3139
3130
3149
3154
3138
3150
3153
2900–2512
1669
1677
1667
1656
1671
1679
1671
1670
1679
1630
1638
1628
1630
1620
1629
1620
1622
1620
1420
1425
1412
1406
1431
1416
1419
1422
1422
1460
1452
1442
1451
1441
1450
1432
1446
1440
249
255
255
250
240
263
252
248
252
170
186
186
179
179
179
188
176
180
930
928
931
930
929
–
–
–
–
–
HL2
2908–2516
HL3
2880–2540
–
–
HL4
2916–2538
–
–
HL5
2946–2532
–
–
HL6
3033–2506
–
–
HL7
3041–2506
–
–
–
HL8
3015–2514
–
–
–
HL9
3020–2524
–
–
–
Complex 1
Complex 2
Complex 3
Complex 4
Complex 5
Complex 6
Complex 7
Complex 8
Complex 9
–
–
–
–
–
–
–
–
–
923
930
927
929
933
–
538
538
556
539
544
536
562
537
553
436
467
462
456
430
456
478
430
470
–
–
–
which is a shift of ∼80 cm−1 towards lower energies than ligand
acids (249–255 cm−1). This further supports ligand coordination
with the Sn center in bidentate fashion, thus rendering octahedral
geometry to these compounds in the solid state.[17] The band
associated with ν(Sn–C) vibration was located in the region
given in Table 3. The total numbers of protons calculated were
in agreement with the expected molecular composition. The
resonances have been assigned for all protons, as shown in
Scheme 4. However, multiplets are observed in some cases. In
compounds 1–5, the protons of the aromatic ring having 2,3-
methylenedioxy group appeared as two doublets (6.26–6.34 and
6.62–6.74 ppm) and a triplet (6.47–6.58 ppm). Methylene protons
of OCH2O resonate as singlets at downfield (5.90–5.92 ppm) with
no 119Sn, 1H coupling satellites that confirmed noncoordination of
this site to tin atom. In ligands with flouro groups directly attached
538–562 cm−1 [18]
.
NMR Spectroscopy
The 1H NMR resonances were assigned on the basis of chemical
shifts, multiplicities and coupling constants. 1H NMR data is
c
Appl. Organometal. Chem. 2011, 25, 412–419
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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M. Hussain et al.
Table 3. 1H NMR data of ligand acids (HL1 –HL9) and complexes 1–9
H
HL1
HL2
HL3
HL4
HL5
HL6
HL7
HL8
HL9
10.12 (s)
7.33 (s)
7.19 d(8.0)
7.19 d(8.0)
7.30 dd(8.1)
7.30 dd(8.1)
–
9.98 (s)
8.15 (s)
–
9.98 (s)
8.05 (s)
11.2 (s)
7.95 (s)
10.76 (s)
8.01 (s)
10.36 (s)
7.98 (s)
–
10.48 (s)
8.19 (s)
9.30
7.94 (s)
3
8.16 (s)
5
5ꢁ
7.23 d(8.4) 7.25 d(8.4) 7.17 d(8.0)
7.14 d(8.4)
7.14 d(8.4)
7.49 dd(8.7)
7.49 dd(8.7)
–
6.90 d(8.1)
6.90 d(8.1)
6.76 d(7.8)
6.76 d(7.8)
–
6.79 d(7.5)
6.79 d(7.5
6.94 dd(6.0)
6.94 dd(6.0)
–
7.0–7.28 (m)
7.0–7.28 (m)
7.0–7.28 (m)
–
7.14–7.41 (m) 7.23 d(8.4) 7.25 d(8.4) 7.17 d(8.0)
7.14–7.41 (m) 7.38 d(8.4) 7.59 d(8.7) 6.97 d(7.5)
7.14–7.41 (m) 7.38 d(8.4) 7.59 d(8.7) 6.97 d(7.5)
6
6ꢁ
7
7.14–7.41 (m)
–
–
–
7.0–7.28 (m)
7.32 d(7.5)
7.46 d(8.4)
–
9
6.77 d(7.2)
6.54 t(8.1)
6.34 d(8.1)
–
6.55 d(7.5)
6.74 d(7.8) 6.79 d(9.0) 6.83 d(8.1) 7.18–7.28 (m) 7.01–7.24 (m) 7.15–7.21 (m)
6.58 t(8.1) 6.59 t(8.1) 6.77 t(7.8) 7.18–7.28 (m) 7.01–7.24 (m) 7.15–7.21 (m)
6.27 d(8.1) 6.29 d(8.1) 6.44 d(7.6) 7.01–7.24 (m) 7.15–7.21 (m)
7.18–7.28 (m) 7.01–7.24 (m) 7.15–7.21 (m)
10
11
12
13
14
15
1H
3
6.30 t(8.0)
6.28 t(8.1)
–
–
–
–
–
7.46 d(8.4)
7.32 d(7.5)
–
–
–
5.92 (s)
–
–
5.95 (s)
–
–
6.01 (s)
–
–
7.18–7.28 (m)
–
–
–
6.0 (s)
6.01 (s)
3.73 (s)
2.18 (s)
–
2.41 (s)
–
–
–
2.36 (s)
Complex 1
8.10 (s)
7.10 d(8.5)
7.10 d(8.5)
7.30 dd(8.1)
7.30 dd(8.1)
–
Complex 2
8.14 (s)
–
Complex 3 Complex 4 Complex 5
8.02 (s) 8.08 (s) 7.95 (s)
7.23 d(8.4) 7.18 d(8.1) 7.13 d(8.7)
Complex 6
8.02 (s)
Complex 7
8.01 (s)
6.80 d(8.0)
6.80 d(8.0)
6.70 d(7.6)
6.70 d(7.6)
–
Complex 8
8.21 (s)
Complex 9
7.88 (s)
5
5ꢁ
7.10 d(8.4)
7.10 d(8.4)
7.48 dd(8.7)
7.48 dd(8.7)
–
6.99 d(7.5)
6.99 d(7.5)
6.81 dd(8.7)
6.81 dd(8.7)
–
6.69–7.11 (m)
6.69–7.11 (m)
6.69–7.11 (m)
–
7.01–7.37 (m) 7.23 d(8.4) 7.18 d(8.1) 7.13 d(8.7)
7.01–7.37 (m) 7.34 d(8.4) 7.52 d(8.4) 6.77 d(7.7)
7.01–7.37 (m) 7.34 d(8.4) 7.52 d(8.4) 6.77 d(7.7)
6
6ꢁ
7
7.01–7.37 (m)
6.70 d(7.5)
6.55 t(8.0)
6.34 t(8.1)
–
–
–
–
6.69–7.11 (m)
7.19 d(7.4)
7.35 d(8.2)
–
9
6.73 d(7.5)
6.58 t(8.1)
6.26 d(8.1)
–
6.71 d(7.6) 6.74 d(7.5) 6.62 d(7.7) 7.18–7.26 (m) 7.01–7.16 (m) 7.12–7.22 (m)
6.54 t(8.0) 6.57 t(8.1) 6.47 t(8.0) 7.18–7.26 (m) 7.01–7.16 (m) 7.12–7.22 (m)
6.30 d(8.1) 6.32 d(8.1) 6.26 d(8.2) 7.01–7.16 (m) 7.12–7.22 (m)
7.18–7.26 (m) 7.01–7.16 (m) 7.12–7.22 (m)
10
11
12
13
14
15
α
–
–
–
–
7.35 d(8.2)
7.19 d(7.4)
–
–
–
–
5.90 (s)
–
–
5.92 (s)
–
–
7.18–7.26 (m)
–
2.29 (s)
–
–
2.29 (s)
–
5.92 (s)
–
5.92 (s)
–
5.91 (s)
3.76 (s)
–
–
2.24 (s)
1.75 q(7.9) [92]
1.75 q(8.0)
[76]
1.73 q(8.1) 1.73 q(7.8) 1.63 q(7.9)
1.78 q(8.1)
[79]
1.72 q(8.0)
[72]
1.82 q(8.7)
[71]
1.60 q(7.5)
[68]
[67]
[76]
β
1.37 t(8.0)
1.37 t(7.8)
1.39 t(8.0)
1.36 t(8.0)
1.27 t(7.9)
1.39 t(8.1)
1.32 t(8.0)
1.45 t(7.9)
1.18 t(7.2)
Scheme 4. Numbering scheme of ligand acids (HL1 –HL9) and compounds 1–9.
to the aromatic ring, doublets of doublets were observed but in
compounds 1, 6 and 8, the protons of the aromatic ring close
to the flouro group demonstrated a doublet of doublet owing to
participation of the fluoro group in coupling as well. The proton
chemical shift values for diethyl moieties were straightforward
from the multiplicity pattern and 2J(119Sn-1H) coupling constant
values. The CSnC angles (148.2–117◦) calculated by Lockhart’s
equation[22] supports a five-coordinate environment around Sn
in complexes 2–4 and 6–9.[23] The tendency of going from six-
coordination to five may be due to the fluxional behavior as shown
in Scheme 5. Compound 1 maintained its solid-state octahedral
geometry even in solution, as evident from the 2J [119Sn, 1H]
coupling value.[16]
13C NMRspectraldatainCDCl3 solutionresolvedtheresonances
corresponding to the magnetically nonequivalent carbon atoms.
Thearomaticcarbonresonanceswereassignedbythecomparison
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 412–419

Structural studies of diethyltin(IV) derivatives
Scheme 5. Fluxional behavior of compounds 2–4 and 6–9.
Figure 1. Ortep diagram of compound (8) with numbering scheme and secondary interactions.
of experimental chemical shifts with those calculated from the
Table 4. Crystal data and structure refinement parameters for
complex 8
incremental method.[24] In order to gain further information
about the possible coordination geometries in solution, a close
examination of the 1J[119Sn,13C] was undertaken. On the basis of
Empirical formula
C36H34Cl2O4Sn1
1
the calculated J[119Sn,13C] values, a skew trapezoidal geometry
Formula weight
Crystal system
Space group
Unit cell dimensions
A (Å)
720.26
Triclinic
P − 1
was assignable to compound 1, whereas compounds 2–9
exhibited a five-coordinated environment around the Sn atom
[23].
In 119Sn NMR spectra, the presence of a single peak for
all compounds confirmed the formation of single species.
In compounds 2–9 the 119Sn value ranged from −75 to
−166.7 ppm authenticated penta-coordinated Sn atom.[16,23] The
119Snresonancefor1at−235.4 ppm, matchedwellwithbidentate
coordination of the two ligands which in turn rendered octahedral
geometry around Sn.[23] These values strongly depend upon the
nature and the orientation of organic groups bonded to tin.
The shifts observed in the tested compounds can be explained
quantitatively in terms of an increase in electron density on the tin
atom as the coordination number increases.
11.101(2)
11.247(2)
B (Å)
C (Å)
13.805(3)
α (deg)
73.054(5)
β (deg)
74.136(6)
γ (deg)
80.308(10)
1578.57(5)
2
V (Å3)
Z
Dc (g cm−3
)
1.52
Crystal size (mm)
0.20 × 0.25 × 0.38
732
F(000)
The 13C chemical shift data elucidated fluoro substituent
chemical shift values in the aromatic system studied in our
work. In compounds 1, 2 and 6, the aromatic carbons appeared
further downfield (161.8–164.3 ppm) than expected owing to the
presence of electron-withdrawing fluoro group. Moreover, 1J[19F,
13C], 2J[19F, 13C] and 3J[19F, 13C] coupling values were in the ranges
245–247, 21–22and7–8 Hz, respectively, inthesecompounds.[25]
In 19F NMR, compounds 1, 2, 6 and 8 fluorine resonance were
observed in the range −114.0 to −114.3 ppm and fluoro groups
of CF3 group appeared at −63.4 ppm (6 and 9).
Total reflections
13 572
Independent reflections
R indices (all data)
Final R indices [I > 2σ(I)]
Goodness-of-fit
7227
R1 = 0.084, wR2 = 0.214
R1 = 0.074, wR2 = 0.198
0.963
Theta range for data collection (deg)
3.176–27.494
C–Sn–C angle is 141.78(14)◦. The four oxygen atoms occupy
the corners of the trapezoidal plan coordinated with the Sn
atom in an anisobidentate fashion with two shorter and two
X-ray Crystallography
· · ·
longer tin–oxygen bonds [Sn–O = 2.135(18) Å and Sn O =
The molecular structure of 8 is shown in Fig. 1. The most
relevant crystallographic data and selected geometric parameters
are summarized in Tables 4 and 5. The Sn center is hexa-
coordinate having a skew-trapezoidal geometry, in which the
axial positions are occupied by two ethyl groups and four
oxygen atoms of the carboxylic group are at the plan positions.
Owing to steric reasons and electronic repulsion, ethyl groups
cannot occupy the exact trans positions to one another and the
· · ·
2.462(18) Å; and Sn–O = 2.120(18) Å and Sn O = 2.540(18) Å)].
The short Sn–O bonds are close to the covalent radii of tin
and oxygen atoms but the longer Sn–O bonds are significantly
smaller than the sum of van der Waals radii of the two atoms
(3.68 Å). These Sn–O and Sn O values agree well with early
reports.[22] Asymmetric coordination of the two ligands is also
reflected in C–O bonds; the oxygen with the longer Sn–O bond
· · ·
c
Appl. Organometal. Chem. 2011, 25, 412–419
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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M. Hussain et al.
Biological Studies
Table 5. Selectedbondlengths(Å)andbondangles(deg)ofcomplex
8
Antitumor Assay
For antitumor activity, Crown gall tumor inhibition assay[28] was
performed for all these synthesized compounds (1–5). In this
assay, potato disks (0.5 cm thickness) were obtained from surface-
sterilized potatoes using a metallic cork borer and special cutter
under completely aseptic conditions. These potato disks were
then transferred to Petri plates each containing 25 ml of 1.5% agar
solution. Then 0.5 ml of stock (10 mg ml−1) of the test sample was
added to 2 ml of a broth culture of Agrobacterium tumefaciens
strain At-10 (48 h culture containing 5 × 109 cells ml−1) and 2.5 ml
of autoclaved distilled water was added to make 1000 ppm final
concentration. One drop of these cultures was poured on each
potato disk. The Petri plates were incubated at 28 ◦C. After 21 days
incubation, the number of tumors was counted with the aid of
a dissecting microscope after staining with Lugol’s solution (10%
KI, 5% iodine). the following formula was used to determine the
percentage inhibition of each concentration:
Bond lengths (Å)
Sn1–O4
Sn1–O5
Sn1–O8
Sn1–O10
O4–C13
Sn1–C25
Sn1–C32
F2–C35
O8–C13
O5–C9
2.135(18)
2.540(18)
2.462(18)
2.120(18)
1.303(3)
2.122(3)
2.124(3)
1.367(3)
1.239(3)
1.240(3)
Bond angles (deg)
O4–Sn1–O5
O4–Sn1–O8
O5–Sn1–O8
O4–Sn1–C9
C9–O5–Sn1
C13–O8–Sn1
C13–O4–Sn1
C9–O5–Sn1
C9–O10–Sn1
C25–Sn1–O5
136.43(7)
56.29(7)
167.16(7)
110.12(12)
83.64(15)
85.72(15)
99.20(16)
83.64(15)
101.28
percentage inhibition = 100
− [no. of tumors with sample/no. of tumors with control
× 100]
Theantitumorpotatodiskassaywasperformedfordiethyltin(IV)
derivatives of substituted phenylacrylic acids using Agrobacterium
tumefacien (At-10) and results are summarized in Table 6. The
activity decreased in the sequence: 4 ≈ 6 > 1 > 2 >
3 > 5. These complexes exert their toxic action presumably
by interacting with the DNA in intercalative mode. In such
interactions the compound makes noncovalent contacts with
DNA bases that cause unwinding of the local structure of
DNA and thus culminates in the damage of the DNA storage,
transcription and genetic transformation machinery.[12] The
proposition of such kind of mechanism is based on the capability
of these compounds to form noncovalent interactions (Fig. 2)
and our recent investigations on the mechanism of organotin(IV)
derivatives by cyclic voltammetry.[13] The high activity for 4 may
be due to the highly polarizable bromo group whereas the high
activityfor6canbeattributedtothepresenceoffourfluorogroups
that can make strong hydrogen bonds with the DNA bases. The
lower activity of 2 than 1 can be explained by the steric effect of
the closely associated COO group which partially masks the fluoro
group involved in hydrogen bonding. The higher activity of 3 than
5 is presumably due to the presence of the chloro group, which
can interact strongly with the DNA bases as compared with the
methoxy group.
83.87(9)
Table 6. Antitumor activities of diethyltin(IV) esters of potential
ligandsa
Average number
of tumors SE
Percentage inhibition
of tumors
Test agents
1
3.9 0.56
2.8 2.77
2.3
80.1
73.4
66.6
100
10.0
100
100
–
2
3
4
0.0
5
6.3
6
0.0
Vincristine
DMSO
0.0 0.0
7.6 0.686
a Potato disk antitumor assay, concentration: 1000 µg ml−1 in DMSO.
More than 20% tumor inhibition is significant. Data represent mean
value of 15 replicates.
Conclusions
is associated with the shorter C–O bond and vice versa. The
molecular structure of compound 8 is mediated by intermolecular
The antitumor activities of the complexes are, in broader terms,
excellent and far exceed the level for free ligands. The influence of
the metal is clearly visible. The activity is maximized for complexes
4and6,althoughallorganotincomplexeshavereasonableactivity.
This study provides a further step in designing potent plant tumor
inhibitors.
· · ·
· · ·
Sn O and F H interactions. The presence of intermolecular
· · ·
Sn O interactions presumably has three causes: (a) the presence
of small ethyl groups allows close contact of the molecules; (b) the
ethyl groups are bent towards one side of the octahedral plan,
which provides enough room for oxygen atoms to interact with
Sn; and (c) the electron-withdrawing oxygen atoms make the Sn
electrondeficient. Itcanbeobservedfromthestructurethatligand
in the title compound exists in E configuration, in agreement with
earlier reports.[26,27] This can be confidently interpreted for all
ligands and complexes.
Acknowledgments
Thanks to the Higher Education Commission of Pakistan (HEC) for
financial support.
c
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Structural studies of diethyltin(IV) derivatives
Figure 2. Closed packing diagram of compound (7).
Supplementary Information
[10] M. Hussain,M. S. Ahmad,A. Siddique,M. Hanif,S. Ali,B. Mirza,Chem.
Biol. Drug Des. 2009, 74, 183.
Supporting information can be found in the online version of
this article. Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre,
CCDC no. 699543 for complex 8. Copies of these information
may be obtained on request from the Director, CCDC, 12 Union
Road, Cambridge CBZ 1EZ, UK (Fax: +44-1223-336033; email:
deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk).
[11] M. S. Ahmad, M. Hussain, M. Hanif, S. Ali, B. Mirza, Molecules 2007,
12, 2348.
[12] Zia-ur Rehman , A. Shah, N. Muhammad, S. Ali, R. Qureshi,
A. Meetsma, I. S. Butler, Eur. J. Med. Chem. 2009, 44, 3986.
[13] Zia-ur-Rehman , A. Shah, N. Muhammad, S. Ali, R. Qureshi,
I. S. Butler, J. Organomet. Chem. 2009, 694, 1998.
[14] N. Muhammad, Zia-ur-Rehman , S. Ali, A. Meetsma, F. Shaheen,
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[16] C. Pettina, M. Pellei, F. Marchetti, C. Santina, M. Miliani, Polyhedron
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Appl. Organometal. Chem. 2011, 25, 412–419
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