Organotin(IV) 4-nitrophenylethanoates: Synthesis, structural characteristics and intercalative mode of interaction with DNA

Article abstract of DOI:10.1016/j.jorganchem.2009.06.036

Four new organotin(IV) carboxylates, [Bu₂SnL₂] (1), [Et₂SnL₂] (2), [Bu₃SnL]_n (3), [Me₃SnL]_n (4), where L = 4-nitrophenylethanoates, were synthesized and characterized

Full text of DOI:10.1016/j.jorganchem.2009.06.036

Journal of Organometallic Chemistry 694 (2009) 3431–3437
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Organotin(IV) 4-nitrophenylethanoates: Synthesis, structural characteristics
and intercalative mode of interaction with DNA
a
Niaz Muhammad a, Afzal Shah a, Zia-ur-Rehman a, Shaukat Shuja a, Saqib Ali a, , Rumana Qureshi ,
*
Auke Meetsma b, Muhammad Nawaz Tahir c
a Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
b Crystal Structure Center, Chemical Physics, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands
c University of Sargodha, Department of Physics, Sargodha, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 April 2009
Received in revised form 18 June 2009
Accepted 23 June 2009
Available online 1 July 2009
Four new organotin(IV) carboxylates, [Bu2SnL2] (1), [Et2SnL2] (2), [Bu3SnL]n (3), [Me3SnL]n (4), where
L = 4-nitrophenylethanoates, were synthesized and characterized by elemental analysis, FT-IR and mul-
tinuclear NMR (1H and 13C). Spectroscopic results authenticated the coordination of ligand to the organo-
tin moiety via COO group while X-ray single crystal analysis revealed bidentate chelating mode of
coordination of ligand in complex 2 and a bridging behavior in complexes 3 and 4. Cyclic voltammetric
(CV) technique was used to evaluate the electrochemical, kinetic and thermodynamic parameters of com-
plexes 1-4, interacting with DNA. The linearity of the plots between the peak current (I) and the square
Keywords:
Organotin
Crystal structures
Intercalation
Prostate cell lines (PC-3)
root of the scan rate (
sion coefficients of the free (Df) and DNA bound forms (Db), standard rate constants (ks) and charge trans-
fer coefficients ( ) were determined by the application of Randle–Sevcik, Nicholson and Kochi equations.
m
1/2) indicated the electrochemical processes to be diffusion controlled. The diffu-
a
Furthermore, the binding constants evaluated from voltammetric data revealed the following increasing
order of binding strength: 2 < 1 < 4 < 3. For 1 and 2, the activity against prostate cancer cell lines (PC-3)
was found consistent with the order obtained from voltammetric behavior.
Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
of intensive investigations [3–5]. However, in spite of such an
importance the number of reports available on organotin(IV) car-
The booming application of metal complexes in the treatment
of numerous human diseases is a vigorously expanding area in bio-
medical and inorganic chemistry [1,2]. The variation in coordina-
tion number, geometries, accessible redox states, thermodynamic
and kinetic characteristics, and the intrinsic properties of the metal
ion are some special characteristics of organometallic complexes
that offer the medicinal chemists to employ different strategies
for their exploitation. Their use in cancer chemotherapy is gaining
mounting importance. Complexes of platinium(II) like cisplatin,
oxalylplatin, nedaplatin and carboplatin have achieved clinical sta-
tus as a result of intensive research focused on anticancer coordi-
nation compounds. However, in spite of having reasonable
therapeutic index, the applications of metal complexes are limited
by serious disadvantages like: (a) poor water solubility (b) toxicity
and (c) the development of tolerance by the tumor. So the synthe-
sis of non-platinum chemotherapeutics with positive, no or limited
side effects is considered reasonable. Due to the potential antibac-
terial, antifungal and anticancer activity, organotins are the subject
boxylates and their DNA binding properties are few. To bridge this
gap we synthesized and structurally analyzed four novel organo-
tin(IV) derivatives of 4-nitrophenylethanoate ligand. Furthermore,
their DNA binding properties and anticancer activities against
prostate cell lines (PC-3) were also evaluated. The objective of
the current study is to provide useful insights in the understanding
of drug-DNA interaction mechanism and drug design.
2. Experimental
All the organotin(IV) precursors were purchased from Aldrich
and were used without further purification. All the solvents were
dried according to reported procedures [6]. The melting points
were recorded on an electrothermal melting point apparatus, mod-
el MP-D mitamura Riken Kogyo (Japan). Microanalysis was done
using a Leco CHNS 932 apparatus. IR spectra were recorded with
KBr pellets in the range from 4000–400 cmꢀ1 using a Bio-Rad Exca-
liber FT-IR, model FTS 300 MX spectrometer (USA). Multinuclear
NMR (1H, 13C) spectra were recorded at room temperature in CDCl3
and DMSO-d6 on a Bruker Advance Digital 300 MHz NMR spec-
trometer (Switzerland). DNA was extracted from human blood by
* Corresponding author. Tel.: +92 (051)90642130; fax: +92 (051)90642241.
E-mail address: drsa54@yahoo.com (S. Ali).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.06.036

3432
N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
Falcon method [7]. The purity of DNA was checked from the ratio
of absorbance at 260 and 280 nm (A260/A280 = 1.85). The concentra-
tion of the stock solution of DNA (2.5 mM in nucleotide phosphate,
NP) was determined by monitoring the absorbance at 260 nm,
2.1.4. Tributyltin(IV) 4-nitrophenyl ethanoate (3)
Compound 3 was prepared in the same way as 1, using equimo-
lar molar amounts, R0COONa (1.02 g, 5 mmol) and tributyltin(IV)
chloride (1.63 g, 5 mmol). The product was recrystallized from
chloroform and n-hexane (4:1) mixture (Yield: 1.98 g, 84%). M.p.
60 °C. Anal. Calc. for C20H33O4NSn: C, 51.09; H, 7.07; N, 2.98.
using the molar extinction coefficient (e
) of 6600 Mꢀ1 cmꢀ1. Elec-
trochemical grade tetrabutylammonium fluoroborate (TBAFB) pur-
chased from Fluka was used as supporting electrolyte.
Dimethylsulphoxide (DMSO) with 99.5% purity was obtained from
Riedal-de-Haën. Nitrogen saturated solutions were obtained by
bubbling high purity N2 for at least 10 min in the solution and
keeping the environment of the pure gas over the solution during
the voltammetric experiments. Electrochemical experiments were
carried out using an Autolab PGSTAT 302 running with GPES (Gen-
eral-Purpose Electrochemical System) version 4.9, software (Eco-
Chemie, Utrecht, The Netherlands). Voltammograms were re-
corded at room temperature using a three-electrode system. The
working electrode was a glassy carbon electrode of 0.071 cm2 area;
saturated calomel electrode (SCE) was used as a reference elec-
trode and a platinum wire as counter electrode. Prior to every elec-
trochemical assay, the glassy carbon working electrode was
Found: C, 51.04; H, 7.04; N, 2.94%. IR (cmꢀ1): 1553
m(OCO)asym,
1392
m(OCO)sym, 584
m
(Sn–C), 451
m
(Sn–O). 1H NMR (CDCl3 and
0
<DMSO-d6>, ppm): 3.73 <3.56> (s, H2, 2H), 7.47 <7.49> (d, H4,4
,
,
0
2H), 8.18 <8.14> (d, H5,5 , 2H), 1.69-1.24 <1.54-1.18> (m, H
a,b,c
18H), 0.90 <0.82> (t, Hd, 9H). 13C NMR (CDCl3 and <DMSO-d6>,
ppm), nJ[(119Sn, 13C), Hz] : 175.1 <173.6> (C-1), 42.1 <43.6> (C-2),
143.5 <146.2> (C-3), 130.2 <131.0> (C-4), 123.6 <123.4> (C-5),
146.8 <146.3> (C-6), 16.6 <19.3> {C-a, [354, <470>]}, 27.7 <28.1>
{C-b, [19, <27>]}, 27.0 <26.9> {C- , [65 <75>]}, 13.6 <14.1> (C-d).
c
2.1.5. Trimethyltin(IV) 4-nitrophenylethanoate (4)
Compound 4 was prepared in the same way as 1, using equimo-
lar molar amounts, R0COONa (1.02 g, 5 mmol) and trimethyltin(IV)
chloride (1.00 g, 5 mmol). The product was recrystallized from
chloroform and n-hexane (4:1) mixture (Yield: 1.28 g, 74%). M.p.
142–144 °C. Anal. Calc. for C11H15O4NSn: C, 38.41; H, 4.40; N,
polished with 0.25 lm diamond paste on a nylon buffing pad, fol-
lowed by washing with water. All the experiments were carried
out at room temperature (ca. 25 1 °C).
4.07. Found: C, 38.36; H, 4.33; N, 4.04%. IR (cmꢀ1): 1514
m
(OCO)a-
(Sn–O). 1H NMR (CDCl3
and <DMSO-d6>, ppm), 2J[(119Sn, 1H), Hz]: 3.74 <3.55> (s, H2, 2H),
sym, 1343 m(OCO)sym, 554 m(Sn–C); 472 m
2.1. Synthesis
0
0
7.47 <7.48> (d H4,4 , 2H), 8.19 <8.14> (d H5,5 , 2H), 0.57 <0.37> {s,
H , 9H, [58 <70>]}. 13C NMR (CDCl3 and <DMSO-d6>, ppm),
2.1.1. Synthesis of Na-salt of 4-nitrophenylethanoic acid
The sodium salt of ligand, R0COONa, was prepared by dropwise
addition of an equimolar amount of sodium hydrogen carbonate
dissolved in distilled water to a methanolic solution of ligand acid
(R0COONa). The solution was stirred for 2 h at room temperature
and was evaporated under reduced pressure to give a white solid
which was vacuum dried.
a
nJ[(119Sn, 13C), Hz]: 175.3 <173.8> (C-1), 41.7 <43.2> (C-2), 143.2
<146.0> (C-3), 130.3 <131.0> (C-4), 123.6 <123.5> (C-5), 146.9
<146.3> (C-6), -2.3 <0.7> {C-a, [386 <527>]}.
2.2. X-ray crystallographic studies
A crystal fragment, cut to size to fit in the homogeneous part of
the X-ray beam, was mounted on top of a glass fiber and aligned on
a Bruker SMART APEX CCD diffractometer (Platform with full
three-circle goniometer). The crystal was cooled to 100(1) K using
the Bruker KRYOFLEX low-temperature device. Intensity measure-
ꢀ
2.1.2. Dibutyltin(IV) bis(4-nitrophenylethanoate) (1)
The sodium salt R0COONa (1.02 g, 5 mmol), was refluxed for
10 h with dibutyltin(IV) dichloride (0.76 g, 2.5 mmol) in dry tolu-
ene contained in a 250 mL two neck round bottom flask. A turbid
solution obtained, was left overnight at room temperature. The
precipitated sodium chloride was filtered off and the filtrate was
rotary evaporated. The resultant solid mass was recrystallized from
chloroform and n-hexane (4:1) mixture. (Yield: 1.14 g, 77%). M.p.
89–92 °C. Anal. Calc. for C24H30O8N2Sn: C, 48.59; H, 5.10; N, 4.72.
ments were performed using graphite monochromatized Mo-K
a
radiation from a sealed ceramic diffraction tube (SIEMENS). Data
integration and global cell refinement was performed with the pro-
gram SAINT [8]. The program suite SAINTPLUS was used for space group
determination (XPREP) [8]. The structure was solved by Patterson
method; extension of the model was accomplished by direct meth-
od and applied to difference structure factors using the program
DIRDIF [9]. All refinement calculations and graphics were per-
formed with the program PLUTO and PLATON package.
Found: C, 48.54; H, 5.07; N, 4.66%. IR (cmꢀ1): 1518
m(OCO)asym,
1396
m
(OCO)sym, 511
m(Sn–C), 468
m
(Sn–O). 1H NMR (CDCl3 and
0
<DMSO>, ppm): 3.80 <3.72> (s, H2, 4H); 7.50 <7.53> (d H4,4 , 4H);
0
8.21 <8.17> (d, H5,5 , 4H); 1.66-1.28 <1.33–1.108> (m, H
,
a,b,c
12H); 0.83 <0.73> (t, Hd, 6H). 13C NMR (CDCl3 and <DMSO-d6>,
ppm), nJ[(119Sn, 13C), Hz]: 180.3 <177.6> (C-1), 40.9 <41.6> (C-2),
141.7 <144.6> (C-3), 130.2 <131.1> (C-4), 123.8 <123.8> (C-5),
3. Results and discussion
147.2 <146.7> (C-6), 25.34 <30.0> {C-
a, [545<815>]}, 26.5 <27.2>
3.1. Synthesis of complexes 1–4
{C-b, [36<39>]}, 26.2 <26.1> {C- , [87<90>] 13.5 <17.1> (C-d).
c
Reaction of R3SnCl/R2SnCl2 with NaL in 1:1/1:2 molar ratios,
respectively lead to the formation of complexes according to Eqs.
(1) and (2) (Scheme 1). The resulting complexes were obtained in
good yield (74–89%). All the complexes were white solids, stable
in air and were soluble in CHCl3 and DMSO. The numbering scheme
of ligand and alkyl groups attached to Sn is shown in scheme 1.
2.1.3. Diethyltin(IV) bis(4-nitrophenylethanoate) (2)
Compound 2 was prepared and was recrystallized in the same
way as 1. R0COONa (1.02 g, 5 mmol), diethyltin(IV) dichloride
(0.62 g, 2.5 mmol) (Yield: 1.20 g, 89%). M.p. 121–122 °C. Anal. Calc.
for C20H22O8N2Sn: C, 44.72; H, 4.13; N, 5.22. Found: C, 44.41; H,
4.07; N, 5.19%. IR (cmꢀ1): 1521
m(OCO)asym, 1389 m(OCO)sym, 505
m
(Sn–C), 476
m
(Sn–O). 1H NMR (CDCl3 and <DMSO-d6>, ppm),
2J[(119Sn, 1H), Hz]: 3.80 <3.71> (s, H2, 4H), 7.49 <7.53> (d, H4,4
,
3.2. IR spectra
0
0
4H), 8.20 <8.20> (d, H5,5 , 4H), 1.64 <1.30> {q, H , 4H [75]}, 1.22
a
<1.05> (t, Hb, 6H). 13C NMR (CDCl3 and <DMSO>, ppm), nJ[(119Sn,
13C), Hz]: 179.9 <177.4> (C-1), 40.9 <46.1> (C-2), 141.9 <144.9>
(C-3), 130.2 <131.1> (C-4), 123.8 <123.6> (C-5), 147.1 <146.5>
By comparing the IR spectra of the free ligand with complexes
1–4, the most explicit feature is the absence of a band in the region
3114–2571 cmꢀ1, which was due to –OH stretching vibration in
the free ligand acid, thus signifying metal–ligand bond formation
(C-6), 17.8 <23.6> {C-a, [584, <904>]}, 8.8 <10.0> {C-b, [<48.3>].

N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
3433
R2SnCl2 + 2NaL
R = n-Butyl (1), Ethyl (2)
R2SnL2 + 2NaCl
(1)
(2)
R3SnCl + NaL
R3SnL + NaCl
R = n-Butyl (3), Methyl (4)
4
5
Fig. 1. ORTEP drawing of compound 2 with atomic numbering scheme.
H2
δ
2
1
C
CH3
β
α
3
α
6
γ
α
H2C
β
OOC H2C
NO2
CH3
,
,
H2C CH3
,
C
H2
4'
5'
The data indicated an increase in coordination sphere around Sn
atom as can be seen from 1J [119Sn, 13C] coupling constant values
of complexes 1–4.
Scheme 1.
via this site. The absorption in the region 496–451 cmꢀ1, which
was absent in the spectrum of the ligand acid, is assigned to the
Sn–O stretching mode. All these values are consistent with litera-
3.4. Crystal structure of complex 2, 3 and 4
The structure of complex 2 is shown in Fig. 1. Crystal data and
selected interatomic parameters are collected in Tables 1 and 2,
respectively. The Sn atom in 2 is coordinated by two ethyl groups
and two ligand molecules, with the later adopting different coordi-
nation modes. The two ligands are chelated to Sn in anisobidentate
fashion, with one longer and one shorter Sn–O bond. The longer
Sn–O distances are significantly less than the sum of the van der
Waal’s radii (3.68 Å) [17], and the coordination number of Sn is
unambiguously assigned as six. The overall geometry at Sn is, how-
ever, highly distorted from the trans octahedral: the C–Sn–C angle
is only 146.23 (15)°, so the Sn and four oxygen atoms of the two
ligands are nearly coplanar but are highly distorted from square-
planar geometry. The bond angles subtended at the Sn atom by
the methylene carbons, O1 and O5 atoms vary from 101.67 (13)°
to 104.23 (13)°, demonstrating that the Sn–C bonds are bent to-
ward the longer Sn–O bonds. Thus, the coordination geometry
about the Sn atom in compound 2 is best described as being dis-
torted trapezoidal-bipyramidal. The geometry, bond lengths and
angles of SnC2O4 core are comparable with literature values [5].
The molecular structures for complexes 3 and 4 are shown in
Figs. 2 and 3, respectively. Pertinent crystallographic parameters,
selected bond lengths and bond angles are given in Tables 1 and
3 (for compound 3) and Table 4 (for compound 4), respectively.
The compounds 3 and 4 are zigzag chain polymers associating
via bridging carboxylate ligands with anti-syn configuration. The
Sn atoms in these polymeric structures exist in distorted trigonal
bipyramidal environment with trigonal plane being defined by
the three alkyl groups. The C–Sn–C angles are in the range,
115.95(17)–125.68(16)° and 117.37(8)–121.86(8)° for compounds
3 and 4, respectively. The axial positions are occupied by two oxy-
gen atoms of bridging carboxylate ligands with O–Sn–O angle is of
the order of 177.38(10) and 170.30(4)° for tributyl- and trimethyl-
tin(IV) derivatives, respectively. Thus, carboxylate ligand chelates
the two symmetry related Sn atoms and gives rise to the unequal
Sn–O bond distances. The inequality in the Sn–O bonds is reflected
in the associated C–O bond lengths, the longer C–O bond is in-
volved with shorter Sn–O interaction and vice versa. These bond
lengths are in accord with the reported triorganotin(IV) carboxyl-
ates [18].
ture values for
a number of organotin–oxygen derivatives
[10,11]. For organotin(IV) carboxylates, IR spectroscopy is helpful,
pertaining to the mode of coordination of COO moiety [12]. The
carboxylate group is acting as bidentate, if the
D
m
{
m
asym(COO)ꢀ
m-
sym(COO)} value, is smaller than 250 cmꢀ1. Values less than
150 cmꢀ1 suggest a chelate structure, while difference between
150 cmꢀ1 to 250 cmꢀ1 put forward a bridged form. On the other
hand, variation greater than 250 cmꢀ1 would propose a monoden-
tate coordination of the ligand. On the basis of
Dm, the ligand sur-
round the Sn atom in a chelated bidentate mode giving octahedral
geometry to the complexes 1 and 2, while the values observed for 3
and 4, are compatible with a bridging bidentate bonding of the li-
gand in solid state. The structures proposed by the IR data match-
well with X-ray structures for complexes 2, 3 and 4.
3.3. NMR spectra
The assignment of the proton resonances were made by their
peaks multiplicity, intensity pattern and comparison of the inte-
gration values of the protons with the expected composition. In
the spectra of complexes 1–4, the ligand furnished a sharp singlet
in the aliphatic region due to CH2 protons while aromatic protons
gave two doublets in the expected region because of two non-
equivalent sets of protons. The protons of the alkyl groups attached
to Sn presented signals as expected [13,14]. The coordination
around Sn atom was deduced from [2J(119Sn, 1H)] coupling con-
stant for compound 2 and 4, the values observed were 75 and
58 Hz, respectively and consistent with CSnC angles of 124.96°
and 111°, thus confirming five and four coordinated Sn atom in 2
and 4, respectively, in solution [15]. 1H NMR of complexes was also
recorded in DMSO-d6 and the data are given in brackets, < >. The [2J
(
119Sn, 1H)] coupling constant in DMSO-d6 indicated an increase in
coordination number in 4, thus confirm the coordination of DMSO
with Sn atom.
The presence of the exact number of carbon resonances for li-
gand and alkyl groups as anticipated from the structures, in spectra
of all complexes; validate the formation of complexes 1–4. Further-
more, the signal of the carboxylic carbon of the ligand shifted
downfield upon complexation. The 1J [119Sn, 13C] coupling constant
can be used to assess the coordination number of the Sn atom in
organotin compounds. The coupling constants were calculated
and found to be in the order of 545 Hz for dibutyltin 1 and
584 Hz for diethyltin 2 compounds which are consistent with the
range reported for five coordinate Sn atom [13]. The calculated va-
lue of the 1J [119Sn, 13C] coupling constant for 3 and 4 are 354 and
386 Hz, respectively describing the tetrahedral environment about
the Sn atom in these compounds [16]. In order to check the effect
of coordinating solvent, the 13C NMR was also made in DMSO-d6.
3.5. Cyclic voltammetry of complexes 1–4
The cyclic voltammetric behavior of complexes 1–4 on bare
glassy carbon electrode was studied in the absence and presence
of DNA, in 10% aqueous DMSO at 25 °C. The voltammograms of
all of the complexes showed
a pair of redox waves with
D
Ep = 124–207 mV, indicating quasi-reversibility of their electro-
chemical processes. Typical CV behavior of 1, with and without
DNA is shown in Fig. 4. Due to the instability of Sn+3, the voltam-

3434
N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
Table 1
Crystal data and structure refinement parameters for compound 2, 3 and 4.
Compound
2
3
4
Moiety formula
Formula weight
C20H22N2O8Sn
537.09
C20H33NO4Sn
470.20
C11H15NO4Sn
343.95
Crystal system
Space group
Triclinic
P-1
Tetragonal
P43212
Monoclinic
P21/c
Unit cell dimensions
a (Å)
9.6184(5)
9.6208(6)
10.6979(5)
b (Å)
10.7133(5)
–
10.0491(5)
c (Å)
11.2762(5)
49.564(6)
12.4860(6)
b (°)
98.992(2)
1085.23(9)
–
107.2835(7)
1281.69(11)
V (Å3)
4587.6(7)
h ranges for data collection (°)
1.85–28.73
2.45–26.37
2.65–28.28
Z
2
8
4
qcalc. (g cmꢀ3
F(0 0 0)
)
1.644
540
1.361
1936
1.782
680
crystal size mm
Index ranges
Total data
0.30 ꢁ 0.22 ꢁ 0.15
h: ꢀ12 ? 12; k: ꢀ14 ? 14; l: ꢀ15 ? 15
20328
0.23 ꢁ 0.19 ꢁ 0.15
h: ꢀ11 ? 12; k: ꢀ12 ? 11; l: ꢀ61 ? 59
36409
0.32 ꢁ 0.26 ꢁ 0.14
h: ꢀ14 ? 14; k: ꢀ12 ? 13; l: ꢀ16 ? 16
11327
Unique data (Rint
)
549 (0.0381)
4668 (0.0759)
3189 (0.0169)
Final R indices (I>/4
r(I))
R1 = 0.0375
R1 = 0.0378
R1 = 0.0191
wR2 = 0.1015
wR2 = 0.0794
wR2 = 0.0478
Table 2
Selected bond lengths (Å) and bond angles (°) of compound 2.
Sn1–O1
Sn1–O2
Sn1–O5
Sn1–O6
Sn1–C9
2.116(2)
2.606(3)
2.110(2)
2.629(3)
2.111(3)
Sn1–C19
O1–C1
O2–C1
O5–C11
O6–C11
2.111(4)
1.281(4)
1.239(4)
1.282(4)
1.228(4)
C9–Sn1C19
C9–Sn1–O1
C9–Sn1––O2
C9–Sn1–O5
C9–Sn1–O6
C19–Sn1–O1
C19–Sn1–O2
C19–Sn1–O5
146.23(15)
102.77(12)
85.63(13)
101.67(13)
88.37(12)
102.19(12)
90.98(13)
104.23(13)
C19–Sn1–O6
O1–Sn1-O2
O1–Sn1–O5
O1–Sn1–O6
O2–Sn1–O5
O2–Sn1–O6
O5–Sn1–O6
89.93(12)
54.01(10)
81.40(9)
134.83(10)
135.17(10)
170.51(9)
53.43(10)
Fig. 3. ORTEP drawing of compound 4 with atomic numbering scheme.
peak potential shift in positive direction. The shift of peak potential
to less negative values is suggestive of intercalation of 1 into DNA
[19]. The observed decrease in peak current indicates the forma-
tion of large and slowly diffusing 1-DNA adduct due to which the
free drug concentration (which is mainly responsible for the con-
duction of the current) is lowered. The electrochemical parameters
of complexes 1–4, in the absence and presence of 60 lM DNA are
listed in Table 5. The results reveal that the formal potential varies
in the sequence: 1 > 3 > 4 > 2, suggesting more easy oxidation of 1
and 3, which can be due to the strong electron-donating ability of
Table 3
Fig. 2. ORTEP drawing of compound 3 with atomic numbering scheme.
Selected bond lengths (Å) and bond angles (°) of complex 3.
Sn–O1
Sn–O2_a
Sn–C9
2.189(3)
2.377(3)
2.146(4)
1.245(5)
Sn–C13
Sn–C17
O1–C1
2.152(5)
2.147(4)
1.273(5)
metric response is attributed to the 2e redox process of Sn+2/Sn+4
couple. In the absence of DNA, compound 1 registered a cathodic
peak at ꢀ1.212 V and anodic peak at ꢀ1.014 V. The large peak to
O2–C1
O1–Sn–C9
89.95(13)
96.38(14)
96.28(14)
177.38(10)
116.65(17)
115.95(17)
C9–Sn–O2_a
C13–Sn–C17
C13–Sn–O2_a
C17–Sn–O2_a
Sn–O1–C1
87.52(12)
125.68(16)
84.16(14)
85.45(14)
115.9(2)
peak potential difference (DEp) of 198 mV is suggestive of electro-
O1–Sn–C13
O1–Sn–C17
O1–Sn–O2_a
C9–Sn–C13
C9–Sn–C17
chemical reaction coupled with a chemical reaction. With the in-
crease in concentration of DNA in constant amount of
a
compound 1, the voltammetric response of the compound altered
as is manifested by the sequential drop in peak current and gradual

N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
3435
Table 4
Selected bond lengths (Å) and bond angles (°) of compound 4.
120
1
100
80
60
40
20
0
Sn–O1
Sn–O2_b
Sn–C9
2.5422(13)
2.1717(12)
2.123(2)
Sn–C11
O1–C1
O2–C1
2.121(2)
1.238(2)
1.285(2)
4
2
3
Sn–C10
2.1177(19)
O1–Sn–O2_b
O1–Sn–C9
O1–Sn–C10
O1–Sn–C11
O2_b–Sn–C9
170.30(4)
86.34(6)
87.28(6)
81.44(6)
94.73(7)
O2_b–Sn–C10
O2_b–Sn–C11
C9–Sn–C10
C9–Sn–C11
C10–Sn–C11
100.71(6)
89.85(7)
117.37(8)
121.86(8)
118.49(8)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
υ
1/2(Vs-1)1/2
-60
-40
-20
0
a
g
Fig. 5. Plots of I vs.
1, 2, 3 and 4. Scan rates: 0.02, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 Vsꢀ1
m
1/2, for the determination of the diffusion coefficients of 3 mM
.
70
60
50
40
30
20
10
0
1
20
40
4
2
3
60
-0.4
-0.6
-0.8
-1
-1.2
-1.4
-1.6
-1.8
E/V vs. SCE
Fig. 4. CV behavior of 3 mM 1 at GC electrode in the absence (a) and presence of 10
(b), 20 (c), 30 (d), 40 (e), 50 (f) and 60 M DNA (g) in 10 % aqueous DMSO with 0.1 M
TBAFB as supporting electrolyte at 0.1 V/s scan rate.
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
l
υ1/2(Vs-1)1/2
Fig. 6. Plots of I vs.
1, 2, 3 and 4, in the presence of 60
0.4, 0.5 and 0.6 Vsꢀ1
m
1/2, for the determination of the diffusion coefficients of 3 mM
M DNA. Scan rates: 0.02, 0.05, 0.08, 0.1, 0.2, 0.3,
l
butyl groups. The behavior is consistent with the generalization
that electron-donating groups facilitate oxidation by shifting the
formal potential (Eo) in more negative direction while electron-
withdrawing groups make the oxidation difficult by shifting the
Eo to less negative values. The shift of formal potentials of these
complexes to less negative values by the addition of DNA could
be correlated to their intercalation into the stacked base pairs
pockets of DNA as suggested by the previous researchers [19].
.
species, Do is the diffusion coefficient (cm2 sꢀ1) and
m is the scan
rate (V sꢀ1).
The linearity of I vs m
1/2 plots (Figs. 5 and 6) demonstrates, that
the main mass transport of these complexes (in the absence and
presence of DNA) to the electrode surface is diffusion controlled.
The values of the diffusion coefficient (Df) listed in Table 6 vary
in the order: 1 > 2 > 4 > 3, indicating greater Df of 1 and 2 than 4
and 3, owing to higher coordination number which effectively
blocks the central metal ion (Sn+4), thereby decreasing the chances
of its attachment with the solvent. In case of 3 and 4, the lower
coordination number allows the central metal ion to be interacted
by the solvent, thereby minimizing their rates of diffusion. The
greater Df value of 1 as compared to 2 can be explained by the pres-
ence of more lyophobic butyl groups than ethyl groups. The lower
Df value of 3 than 4 is due to higher molecular weight, confirming
The values of
DEp > 60 < 212 and Ipc/Ipa > 1 shown in Table 5, reflect
the redox processes of the free and DNA-bound complexes to be
quasi-reversible.
The diffusion coefficients of the free and DNA-bound complexes
were determined by the application of Randle–Sevcik expression
[20,21]:
I ¼ 2:69 ꢁ 105n3=2ACoDo1=2m1=2
ð1Þ
where, I is the peak current (A), A is the surface area of the electrode
(cm2), Co is the bulk concentration (mol cmꢀ3) of the electroactive
Table 5
CV data of compounds 1–4.
Compound
CV data
Epa (V)
Epc (V)
D
Ep (mV)
Es (V)
Ipa
(lA)
Ipc
(l
A)
Ipc/Ipa
1
ꢀ1.014
ꢀ0.890
ꢀ1.019
ꢀ0.885
ꢀ1.043
ꢀ0.921
ꢀ1.044
ꢀ0.897
ꢀ1.212
ꢀ1.097
ꢀ1.187
ꢀ1.063
ꢀ1.173
ꢀ1.063
ꢀ1.170
ꢀ1.046
198
207
168
178
130
153
126
149
ꢀ1.113
ꢀ0.994
ꢀ1.103
ꢀ0.974
ꢀ1.108
ꢀ0.992
ꢀ1.107
ꢀ0.972
41.91
27.63
21.75
15.16
21.14
11.33
24.04
13.08
53.99
34.48
38.81
23.90
28.71
16.39
32.38
18.88
1.29
1.25
1.78
1.58
1.36
1.45
1.35
1.44
1-DNA
2
2-DNA
3
3-DNA
4
4-DNA
All potentials were measured versus SCE in 10% aqueous DMSO at 0.1 Vsꢀ1
Ep = (EpaꢀEpc).
Es = (Epa + Epc)/2.
.
D

3436
N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
Table 6
Summary of kinetic and thermodynamic data of free and DNA bound forms of compounds 1–4, as obtained from electrochemical measurements.
Compound
Kinetic data
Thermodynamic data
Df ꢁ 107 (cm2/s)
Db ꢁ 107 (cm2/s)
ks ꢁ 104 (cm/s)
a
K ꢁ 10ꢀ4 (Mꢀ1
)
D
G (kJmol-1
)
1
6.54 ( 0.19)
–
2.85( 0.09)
–
1.70( 0.07)
–
2.80( 0.08)
–
–
5.04( 0.20)
2.86( 0.14)
4.39( 0.17)
2.44( 0.15)
5.91( 0.26)
2.73( 0.17)
8.64( 0.35)
2.95( 0.16)
0.54( 0.02)
0.51( 0.01)
0.54( 0.02)
0.51( 0.01)
0.63( 0.03)
0.54( 0.02)
0.53( 0.02)
0.62( 0.03)
–
–
1-DNA
2
2-DNA
3
3-DNA
4
4-DNA
2.44( 0.11)
–
1.08( 0.05)
–
0.756( 0.04)
–
0.764( 0.04)
1.11( 0.04)
–
0.85( 0.03)
–
1.46( 0.05)
–
1.39( 0.07)
23.08( 0.93)
–
22.42( 0.89)
–
23.76( 1.19)
–
ꢀ23.64( 1.18
the idea that a heavy molecule diffuses slowly to the electrode
surface.
4.8
4.7
4.6
4.5
4.4
4.3
4.2
4.1
The Db values of the DNA bound complexes, summarized in Ta-
ble 6, follow the same order as was observed for the Df of the free
complexes. The Db values are lower than the Df values because of
the interaction of these complexes to the large and slowly moving
DNA.
The values of standard rate constant (ks) of the electron transfer
reaction of these complexes at the electrode surface were obtained
from Nicholson equation [22]:
ks
w ¼
ð2Þ
h
i
1=2
nf
RT
m
p
Do
where w is a dimensionless parameter (depending upon peak sepa-
ration,
DEp) and all other parameters have their usual significance.
0
0.2
0.4
0.6
0.8
1
An examination of Table 6 reflects that the values of ks are of
the order of 10ꢀ4 cmsꢀ1, offering another evidence for the quasi-
reversibility of the redox processes with slow electron transfer
kinetics. Table 6, further signifies lower ks values of complex–
DNA adducts as compared to the free complexes due to their lower
diffusion coefficients.
log (I H-G/I G-I H-G
)
Fig. 7. Plots of log (IH–G/(IGꢀIH–G)) vs. log (1/[DNA]) used to calculate the binding
constants of 2-DNA (j) and 1-DNA (N) complexes.
Table 7
The values of charge transfer coefficient (
a
) were determined by
In vitro anticancer results (IC50, lg/mL) of compounds 1 and 2.
the application of Kochi formula [23]:
"
#
Compound no.
PC-3
ðE1=2 ꢀ Ec Þ
p
1
2
2.53 0.94
7.92 0.65
0.912
a
a
¼
ð3Þ
ðEap ꢀ EcpÞ
aDoxorubicin
with values of more than 0.5 for all the four complexes (with and
without DNA) further established the quasi-reversibility of the elec-
a
Standard drug used.
trochemical processes.
The gradual decay in peak current of the complexes by the addi-
tion of varying concentration of DNA, ranging from 20 to 60 lM,
standard Gibbs free energy (
ity of the binding interaction of these complexes with DNA.
D
G = ꢀRT ln K) indicate the spontane-
can be used to quantify the binding constant by using the following
equation [24]:
3.6. Anticancer activity
log ð1=½DNAꢂÞ ¼ log K þ log ðIH—G=ðIG ꢀ IH—GÞÞ
where, K is the binding constant, IG and IH–G are the peak currents of
the free guest (G) and the complex (H–G), respectively.
ð4Þ
The in vitro anticancer activity of compounds 1 and 2 against
prostate cancer cells (PC-3) was evaluated according to the litera-
ture reported method [28]. The data (Table 7) indicate that the
compound 1 is a potential anticancer agent as compared to 2,
and consistent with the trend observed in electrochemical study.
The binding constant, K = 1.11 ꢁ 104 and 8.50 ꢁ 103 Mꢀ1, for the
interaction of 1 and 2 with DNA were obtained, respectively from
the intercept of log (1/[DNA]) versus log (IH–G/(IGꢀIH–G)) plots
(Fig. 7). The greater K of 1 than 2, is presumably due to the addi-
tional hydrophobic interactions of the bulky butyl groups with
the nucleotide bases as compared to ethyl groups [25]. The same
4. Conclusion
The outcome of the present study is that the di- and triorgano-
tin(IV) 4-nitrophenylethanoates demonstrated different structural
motifs in solution and solid states. Regarding the DNA-binding
study, the most promising feature is the intercalative mode of
interaction of these complexes with DNA with experimental proof
from electrochemical study which according to our survey is a new
contribution to organotin(IV) carboxylates. Apart from this, the dif-
fusion coefficient of the compounds decrease with the increase in
molecular weight but is not a sole factor because geometry also
attribution is assigned to the strong binding constant of
3
(K = 1.46 ꢁ 104 Mꢀ1) than 4 (K = 1.39 ꢁ 104 Mꢀ1). The results fur-
ther verified that complexes 3 and 4 show stronger affinity for
DNA than 1 and 2. The greater K of these Sn complexes than those
observed for similar DNA-intercalating Cr and Ru complexes;
[CrCl2(dicnq)2]+ and [Ru((dicnq)3]+2
,
with
K
reported as
1.20 ꢁ 103 and 9.70 ꢁ 103 Mꢀ1 [25–27], suggests their potential
candidature as chemotherapeutic agents. The negative values of

N. Muhammad et al. / Journal of Organometallic Chemistry 694 (2009) 3431–3437
3437
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