New tetrahedral, square-pyramidal, trigonal-bipyramidal and octahedral organotin(IV) 4-ethoxycarbonylpiperazine-1-carbodithioates: Synthesis, structural properties and biological applications

Article abstract of DOI:10.1016/j.jorganchem.2010.03.008

This article describes the synthesis of triorganotin(IV)-, chlorodiorganotin(IV)- and diorganotin(IV) 4-ethoxycarbonylpiperazine-1-carbodithioates with general R₃SnL {where R = CH₃ (1), n-C₄H₉ (2) and C₆

Full text of DOI:10.1016/j.jorganchem.2010.03.008

Journal of Organometallic Chemistry 695 (2010) 1526–1532
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
New tetrahedral, square-pyramidal, trigonal-bipyramidal and octahedral
organotin(IV) 4-ethoxycarbonylpiperazine-1-carbodithioates: Synthesis,
structural properties and biological applications
Aziz-ur-Rehman a, Mukhtiar Hussain b, Zia-ur-Rehman b, Abdul Rauf a, Faiz-ul-Hassan Nasim a,
Asif Ali Tahir c, Saqib Ali b,
*
a Department of Chemistry, The Islamia University of Bahawalpur, Pakistan
b Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan
c Loughbrough University LE11 3TU, Leicestershire, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 January 2010
Received in revised form 25 February 2010
Accepted 4 March 2010
Available online 10 March 2010
This article describes the synthesis of triorganotin(IV)-, chlorodiorganotin(IV)- and diorganotin(IV) 4-eth-
oxycarbonylpiperazine-1-carbodithioates with general R3SnL {where R = CH3 (1), n-C4H9 (2) and C6H5
(3)}, R2SnClL {where R = CH3 (4), n-C4H9 (5) and C6H5 (6)} and R2SnL2 {where R = CH3 (7), n-C4H9 (8)
and C6H5 (9)}, respectively. The coordination behavior of ligand (L) in all compounds was investigated
by different analytical techniques such as FT-IR and multinuclear NMR. X-ray single crystal analysis con-
firmed supramolecular structure for compounds (3) and (4) with distorted trigonal-bipyramidal and dis-
torted square-pyramidal geometries, respectively. The compounds have pronounced antimicrobial
(antibacterial and antifungal) potency and moderate insecticidal activity. These compounds also inhibit
effectively the activity of urease enzyme.
Keywords:
Organotin(IV) dithiocarboxylates
Secondary interactions
Antifungal
Ó 2010 Elsevier B.V. All rights reserved.
Antibacterial
Insecticidal
Antiurease
1. Introduction
ligand. In addition to the biological applications, organotin dithio-
carboxylates exhibit diverse structural motifs. Depending on the
Dithiocarboxylate anions are distinguished coordinating agents
for metals. The resonance due to these anions is the significant
contribution from dithiocarboxylates anions to stabilize the overall
electronic structure. These ions play a notable role in medicine
also. For example, the diethyldithiocarbamate anion, Et2CNS2 has
been used for clinical use as antidote for copper poisoning, i.e., Wil-
son’s disease [1]. Alkyltin(IV) or aryltin(IV) derivatives of dithiocar-
boxylate ligands have been extensively studied owing to their
enormous biological [2,3] and industrial applications [4] with a
view to establish structure–biological activity relationship [5–8].
Organotins especially, organotin(IV) dithiocarboxylates have po-
tential apoptotic inducing character and have also high therapeutic
index [9–11]. They are good DNA binders and can interact with
DNA in two different ways: electrostatic interaction with phos-
phate group of DNA and intercalative mode in which organotins
establish secondary interactions with the nitrogenous bases
[6,12]. This alteration of structure hinders DNA replication and
the ultimate result is the death of the cancerous cells.
number of R groups present, the mode of coordination of CS2 moi-
ety and the number of ligands attached to Sn atom, organotin may
be tetrahedral, trigonal-bipyramidal, square-pyramidal, octahedral
and pentagonal bipyramidal [6,7,12]. The structure of organotins
may be monomeric, dimeric, trimeric or supramolecular based on
the absence and presence of secondary non-covalent interactions
between the ligand molecules [13]. These interactions play also a
vital role in the biological applications of organotins. In nutshell,
in order to get a good antimicrobial response for the organotins,
the attached ligand must have substituents capable of making
secondary interactions. Keeping all these factors in mind, we
synthesized, characterized organotin(IV) derivatives of a new li-
gand (4-ethoxycarbonylpiperazine-1-carbodithioate) and screened
them for their antimicrobial applications.
2. Experimental
The activity of organotin compounds depends upon the number
and nature of R group linked to metal ion as well as on the anionic
2.1. Materials and methods
The reagents, di- and triorganotin(IV) chlorides, 4-ethoxycar-
bonylpiperazine and CS2 were purchased from commercial sources
(Aldrich, USA) and were used without further purification.
* Corresponding author.
E-mail address: drsa54@yahoo.com (S. Ali).
0022-328X/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.03.008

Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
1527
Methanol was dried before use by the literature procedure [14].
The infrared (IR) measurements were taken as KBr pellets on a
Bio-Rad Excalibur FT-IR, model FTS 4800 MX spectrophotometer
3
3
2
2
O
S
CH3 CH2
O
C
N
N
C
SNa
α
γ
α
5
1
6
4
β
δ
CH2
CH2
CH3
CH3
CH2
(USA) in the frequency range of 4000–200 cmꢀ1 1H, 13C, and
.
,
,
119Sn NMR spectra in solution were undertaken using Bruker
ARX 300, 400 MHz and Bruker 500 MHz-FT-NMR spectrometers,
respectively. The chemical shifts are reported in ppm relative to
the external references, tetramethylsilane (TMS) for 1H, 13C and
tetramethyltin for 119Sn shifts. The crystallographic studies were
carried out on a Nonius Kappa CCD diffractometer with graphite
γ
β
α
δ
γ
β
Scheme 2. Numbering of ligand and Sn moieties for 1H and 13C NMR data.
monochromated Mo Ka radiation.
Calc. for: C, 39.0; H, 6.5; N, 8.3. Found: C, 38.7; H, 6.1; N, 7.8%. IR
2.2. Synthesis
(cmꢀ1
)
m
(C–N) 1471,
m
(C–S) 945,
m
(Sn–C) 524,
0
m
(Sn–S) 409. 1H
0
NMR d (ppm): 2.63–2.68 (4H, m, H2,2 ), 3.24–3.51 (4H, m, H3,3 ),
4.56 (2H, q, H5) 3J[H, H] 7.4 Hz, 1.14 (3H, t, H6) 3J[H, H] 7.4 Hz,
0.72 (9H, s, Hb) 2J[119Sn,1H] = 57 Hz, C–Sn–C 110°. 13C NMR d
2.2.1. Sodium 4-ethoxycarbonylpiperazine-1-carbodithioate [NaL]
stoichiometric amount of 4-ethoxylcarbonylpiperazine
A
(0.72 g, 3.0 mmol) and sodium hydroxide (0.12 g, 3.0 mmol) in
methanol (50 mL) was stirred at room temperature for 1 h. To this
solution, carbon disulfide (3.0 mmol) was added dropwise and the
mixture was stirred for 6 h [13,15]. The solid product (Scheme 1)
was washed with diethyl ether and it was air dried (Yield: 1.4 g,
87%). M.p. 158–163 °C. Anal. Calc. for: C, 37.5; H, 5.1; N, 10.9.
0
0
(ppm): 192.1 (C1), 42.9 (C2,2 ), 51.6 (C3,3 ), 156.0 (C4), 61.8 (C5),
14.6 (C6) ꢀ1.72 (C ) 1J[119Sn,13C] = 386 Hz, C–Sn–C 110°. 119Sn d
a
(ppm): 138.3.
2.2.2.2. Tri-n-butyltin(IV) [4-ethoxylcarbonylpiperazine-1-carbodi-
thioate] (2). Stoichiometric amounts: Tri-n-butyltin(IV) chloride
(0.5 g, 1.53 mmol) and sodium salt of 4-ethoxycarbonylpiper-
azine-1-carbodithioate (0.4 g, 1.53 mmol). (Yield: 88%). M.p. 118–
121 °C. Anal. Calc. for: C, 45.8; H, 7.6; N, 5.3. Found: C, 45.2; H,
Found: C, 36.8; H, 4.9; N, 10.4%. IR
m(C–N) 1471,
m
0
(C–S) 1107,
m
(C@S) 945. 1H NMR d (ppm): 2.58–2.63 (4H, m, H2,2 ), 3.20–3.48
(4H, m, H3,3 ), 4.49 (2H, q, H5) 3J[H, H] 7.4 Hz, 1.09 (3H, t, H6)
0
3J[H, H] 7.4 Hz. 13C NMR d (ppm): 203.1 (C1), 42.9 (C2,2 ), 51.7
0
7.4; N, 4.0%. IR (cmꢀ1):
m
(C–N) 1424,
m(C–S) 957, m(Sn–C) 518,
0
(C3,3 ), 156.1 (C4), 61.8 (C5), 14.4 (C6).
m
(Sn–S) 422. 1H NMR d (ppm): 1.59–1.64 (6H, m, H ), 1.31–1.34
a
(6H, m, Hb), 1.21–1.31 (6H, m, H ), 0.83 (9H, t, Hd) 3J[1H,1H] =
2.2.2. General synthetic procedure for compounds (1–9)
c
0
0
7.4 Hz, 2.38–2.57 (4H, m, H2,2 ), 3.42–3.52 (4H, m, H3,3 ), 4.13 (2H,
Stoichiometric amounts of organotin(IV) chlorides in methanol
(30 mL) were added dropwise to the methanolic solution of so-
dium salt of ligand (NaL) as shown in Scheme 1. The mixture
was refluxed for 4 h with constant stirring. The solid product ob-
tained in each case after filtration was recrystallized from chloro-
form/ethanol mixture. The slow evaporation of the mixture gave
crystalline products for compound (3) and (4). The NMR data for
compounds (1–9) given below is in accordance with Scheme 2.
q, H5) 3J[H, H] = 7.2 Hz, 1.31 (3H, t, H6) 3J[H, H] 7.2 Hz.13C NMR d
0
0
(ppm): 194.0 (C1), 44.3 (C2,2 ), 52.7 (C3,3 ), 155.4 (C4), 63.0 (C5),
14.2 (C6), 16.1 (C ) 1J[119Sn,13C] = 353 Hz, C–Sn–C, 107°, 26.5 (Cb),
a
26.1 (C ), 14.0 (Cd). 119Sn NMR d (ppm): 117.4.
c
2.2.2.3. Triphenyltin(IV) [4-ethoxylcarbonylpiperazine-1-carbodithio-
ate] (3). Stoichiometric amounts: Triphenyltin(IV) chloride (0.6 g
1.53 mmol) and sodium salt of 4-ethoxycarbonylpiperazine-1-car-
bodithioate of ligand (0.4 g, 1.53 mmol) (Yield: 84%). M.p. 178–
181 °C. Anal. Calc. for: C, 53.4; H, 4.8; N, 4.8. Found: C, 52.9; H,
2.2.2.1. Trimethyltin(IV) [4-ethoxylcarbonylpiperazine-1-carbodithio-
ate] (1). Stoichiometric amounts: Trimethyltin(IV) chloride (0.4 g,
1.86 mmol) and sodium salt of 4-ethoxycarbonylpiperazine-1-car-
bodithioate (0.5 g, 1.86 mmol). (Yield: 83%). M.p. 138–140 °C. Anal.
4.5; N, 4.3%. IR (cmꢀ1
m
)
m
(C–N) 1461,
m
(C–S) 943,
m
0
(Sn–C) 241,
(Sn–S) 415.1H NMR d (ppm): 2.41–2.56 (4H, m, H2,2 ), 3.12–3.28
R
S
O
C
Sn
R
Cl
O
N
N C
S
R = CH3 (7), C4H9 (8), C6H5 (9)
R
S
O
O
O
C
S
C
O
N
H2
C
CS2
Sn
R
R
C
N
N C
O
N
N
SNa
H3C
O
N
H
NaOH
S
R = CH3 (1), C4H9 (2), C6H5 (3)
R
S
S
O
C
O
C
Sn
R
N
N C
O
C
N
N
O
S
S
R = CH3 (4), C4H9 (5), C6H5 (6)
Scheme 1. Schematic diagram for synthesis of NaL and for organotin(IV) compounds (1–9).

1528
Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
3
3
H, 5.7; N, 5.4%. IR (cmꢀ1
)
m
(C–N) 1424,
m
(C–S) 957,
m
(Sn–C) 518,
0
(4H, m, H3,3 ), 3.96 (2H, q, H5) J[H, H] = 7.4 Hz, 1.21 (3H, t, H6) J[H,
H] = 7.4 Hz, 7.71–7.74 (12H, m, Hb, H ), 7.12–7.17 (3H, m, Hd). 13C
m
(Sn–S) 422. 1H NMR d (ppm): 2.94–3.04 (8H, m, H2,2 ), 3.24–3.47
0
c
(8H, m, H3,3 ), 4.43 (4H, q, H5) 3J[H, H] 7.3 Hz, 1.18 (6H, t H6) 3J[H,
0
0
0
NMR d (ppm): 193.6 (C1), 43.3 (C2,2 ), 52.2 (C3,3 ), 155.6 (C4), 62.3
(C5), 15.0 (C6), 128.6, 129.5, 137.0 142.3 (C , Cb, C , Cd). 119Sn
H] 7.3 Hz, 1.66–1.73 (4H, m, H ), 1.67–1.73 (4H, m, Hb), 1.32–
a
c
a
NMR d (ppm): ꢀ175.5.
1.52 (4H, m, H ), 0.84 (6H, t, Hd) 3J[H, H] 7.6 Hz. 13C NMR d
c
0
0
(ppm): 195.5 (C1), 42.8 (C2,2 ), 51.6 (C3,3 ), 154.8 (C4), 60.8 (C5),
2.2.2.4. Chlorodimethyltin(IV) [4-ethoxylcarbonylpiperazine-1-car-
bodithioate] (4). Stoichiometric amounts: Dimethyltin(IV) dichloride
(0.50 g, 2.27 mmol) and sodium salt of 4-ethoxycarbonylpiper-
azine-1-carbodithioate (0.58 g, 2.27 mmol). (Yield: 69%). M.p.
143–146 °C. Anal. Calc. for: C, 28.7; H, 4.5; N, 6.6. Found: C, 28.4;
14.8 (C6), 24.4 (C ) 1J[119Sn, 13C] = 585 Hz, C–Sn–C 128° 27.3 (Cb),
a
26.4 (C ), 14.1 (Cd). 119Sn NMR d (ppm): ꢀ153.6.
c
2.2.2.9. Diphenyltin(IV) bis[4-ethoxylcarbonylpiperazine-1-carbodi-
thioate] (9). Stoichiometric amounts: Diphenyltin(IV) chloride
(0.40 g, 1.56 mmol) and sodium salt of 4-ethoxycarbonylpiper-
azine-1-carbodithioate (1.06 g, 3.12 mmol). (Yield: 74%). M.p. 93–
96 °C. Anal. Calc. for: C, 45.4; H, 4.8; N, 7.3. Found: C, 44.8; H,
H, 4.3; N, 6.2%. IR (cmꢀ1
)
m
(C–N) 1476,
m
(C–S) 917,
m
(Sn–C) 538,
(Sn–Cl) 312. 1H NMR d (ppm): 2.46–2.58 (4H, m, H2,2 ), 3.28–
0
m
3.43 (4H, m, H3,3 ), 4.37 (2H, q, H5) 3J[H, H] = 7.5 Hz, 1.14 (6H, t,
0
H6) 3J[H, H] = 7.5 Hz, 1.06 (6H, s, H ) 2J[119Sn,1H] = 75 Hz, C–Sn–C
4.5; N, 7.3%. IR (cmꢀ1):
m
(C@N) 1483,
m
(C–S) 968,
m
(Sn–C) 262,
a
125°. 13C NMR d (ppm): 198.0 (C1), 43.1 (C2,2 ), 51.5 (C3,3 ), 155.5
(Sn–S) 421. 1H NMR d (ppm): 2.73–2.85 (8H, m, H2,2 ), 3.06–3.47
0
0
0
m
(C4), 62.5 (C5), 14.3 (C6), 7.5 (C ) 1J[119Sn,13C] = 607 Hz, C–Sn–C
(8H, m, H3,3 ), 4.26 (4H, q, H5) 3J[H, H] = 7.3 Hz, 1.16 (6H, t, H6)
a
0
130°. 119Sn NMR d (ppm): ꢀ185.8.
3J[H, H] = 7.3 Hz, 7.57–7.64 (8H, m, Hb, H ), 7.42–7.48 (2H, m,
c
Hd). 13C NMR d (ppm): 197.5 (C1), 43.3 (C2,2 ), 52.3 (C3,3 ), 155.4
0
0
(C4), 62.6 (C5), 15.0 (C6), 129.5 (C ) 1J[119Sn, 13C] = 589 Hz, C–Sn–
2.2.2.5. Chlorodi-n-butyltin(IV) [4-ethoxylcarbonylpiperazine-1-car-
bodithioate] (5). Stoichiometric amounts: Di-n-butyltin(IV) dichlo-
ride (0.5 g, 1.64 mmol) and sodium salt of 4-ethoxycarbonyl-
piperazine-1-carbodithioate (0.42 g, 1.64 mmol). (Yield: 67%).
M.p. 110–113 °C. Anal. Calc. for: C, 38.2; H, 6.2; N, 5.6. Found: C,
a
C 128°, 128.7, 136.3, 142.2, (Cb, C , Cd). 119Sn NMR d (ppm): ꢀ314.2.
c
3. Results and discussion
37.9; H, 5.7; N, 5.4%. IR (cmꢀ1
) m(C–N) 1433, m(C–S) 941, m(Sn–C)
(Sn–Cl) 323. 1H NMR d (ppm): 2.42–2.51 (4H,
3.1. IR spectroscopy
541,
m
(Sn–S) 457,
m
m, H2,2 ), 3.36–3.47 (4H, m, H3,3 ), 4.07 (2H, q, H5) 3J[H, H] 7.4,
0
0
1.16 (3H, t, H6), 3J[H, H] 7.4 Hz, 1.63–1.66 (4H, m, H ), 1.53–1.63
In the IR spectra of compounds (1–9), the vibration modes C–N
and CS2 are of prime interest to differentiate between mono and
bidentate coordination of 1,1-dithiolate moiety. The single band
appears at 917–976 cmꢀ1 is assignable to the CS2 absorption fre-
quency which indicates the bidentate coordination of 1,1-dithiol-
ate moiety of the ligand to the Sn atom [16,17]. The stretching of
the C–N was positioned at frequency (1424–1483 cmꢀ1) that corre-
sponds to a partial double bond character in C–N moiety [6,7]. The
presence of delocalized double bond in NCS2 moiety was further
confirmed by X-ray single crystal analysis for complexes 3 and 4.
The observed Sn–C peak, in compounds 1–9, matched-well with
early reports [12,13].
a
(4H, m, Hb), 1.53–1.63 (4H, m, H ), 0.89 (6H, t, Hd) 3J[H, H]
c
7.3 Hz. 13C NMR d (ppm): 195.7 (C1), 42.4 (C2,2 ), 53.1 (C3,3 ),
0
0
155.7 (C4), 61.4 (C5), 13.8 (C6), 25.3 (C ) 1J[119Sn, 13C] = 604 Hz,
a
C–Sn–C 129°, 27.4 (Cb), 26.2 (C ), 13.8 (Cd). 119Sn NMR d (ppm):
c
ꢀ228.3.
2.2.2.6. Chlorodiphenyltin(IV) [4-ethoxylcarbonylpiperazine-1-car-
bodithioate] (6). Stoichiometric amounts: Diphenyltin(IV) chloride
(0.40 g, 1.56 mmol) and sodium salt of 4-ethoxycarbonylpiper-
azine-1-carbodithioate (0.54 g, 1.56 mmol). (Yield: 70%). M.p.
104–108 °C. Anal. Calc. for: C, 44.3; H, 4.2; N, 5.2. Found: C, 44.0;
H, 3.7; N, 4.6%. IR (cmꢀ1
) m(C–N) 1463, m(C–S) 976, m(Sn–C) 248,
m
(Sn–S) 429,
m
(Sn–Cl) 361. 1H NMR d (ppm): 2.46–2.52 (4H, m,
3.2. NMR spectroscopy
H2,2 ), 3.09–3.16 (4H, m, H3,3 ), 3.84 (2H, q, H5) 3J[H, H] = 7.5 Hz,
0
0
1.19 (3H, t, H6) 3J[H, H] = 7.5 Hz, 7.59–7.70 (8H, m, Hb, H ), 7.42–
The 1H NMR spectra were recorded for the compounds (1–9) in
DMSO-d6. The chemical shifts were identified by their intensity
and multiplicity patterns. The total numbers of protons, calculated
from the integration curves, are in agreement with the expected
molecular composition of the compounds. The piperazine protons
display two multiplets at chemical shift value of 2.63–2.68 and
3.24–3.31 ppm in the aliphatic region. The 2J[119Sn, 1H] of the or-
ganic groups attached to Sn atom is of special significance for
structure elucidation of organotins in solution. In methyl deriva-
tives (1), (4) and (7) small satellites are clearly visible along with
the chemical shift value of the methyl moiety, providing 2J[119Sn,
1H] coupling values of 57, 75 and 79 Hz, respectively. These values
correspond to C–Sn–C bond angle of 110°, 125° and 130° thus sug-
gested four (1) and penta-coordinated (4 and 7) Sn [4,18–20].
Chemical shifts of n-butyl and aromatic protons are difficult to as-
sign because of their peaks multiplicity and consequently overlap-
ping of signals. In compounds (4), (5) and (6) integration values
demonstrate the attachment of only one ligand to Sn atom.
c
7.48 (2H, m, Hd). 13C NMR d (ppm): 195.4 (C1), 42.8 (C2,2 ), 52.1
0
(C3,3 ), 154.8 (C4), 61.5 (C5), 14.9 (C6), 129.4 (C ) 1J[119Sn,
0
a
13C] = 594 Hz, C–Sn–C 129°, 128.6, 135.5, 142.6 (Cb, C , Cd). 119Sn
c
NMR d (ppm): ꢀ337.2.
2.2.2.7.
Dimethyltin(IV)bis[4-ethoxycarbonylpiperazine-1-carbodi-
thioate] (7). Stoichiometric amounts: Dimethyltin(IV) chloride
(0.40 g, 1.56 mmol), sodium salt of 4-ethoxycarbonylpiperazine-
1-carbodithioate (0.69 g, 3.1 mmol). (Yield: 75%). M.p. 140–
142 °C. Anal. Calc. for: C, 35.0; H, 5.2; N, 9.1. Found: C, 34.6; H,
4.8; N, 8.6%. IR (cmꢀ1
)
m
(C–N) 1471,
m
(C–S) 945,
m
(Sn–C) 524,
(Sn–S) 409. 1H NMR d (ppm): 2.59–2.62 (8H, m, H2,2 ), 3.31–3.45
0
m
(8H, m, H3,3 ), 4.62 (4H, q, H5) 3J[H, H] = 7.2 Hz, 1.08 (6H, t, H6)
0
3J[H, H] = 7.2 Hz, 1.13 (6H, s, H ) 2J[119Sn,1H] = 79 Hz, C–Sn–C 130°.
a
13C NMR d (ppm): 196.3 (C1), 43.7 (C2,2 ), 52.4 (C3,3 ), 156.0 (C4),
0
0
62.5 (C5), 15.3 (C6), 6.5 (C ) 1J[119Sn, 13C] = 593 Hz, C–Sn–C 129°.
a
119Sn NMR d (ppm): ꢀ197.3.
The 13C NMR chemical shifts due to methyl, n-butyl and phenyl
groups, attached to Sn atom, were observed at positions compara-
ble to the other similar compounds [21,22]. All the chemical shifts
of carbon atoms due to ligand moiety remain unchanged in com-
pounds 1–9 except the CS2 carbon, that shift upfield, thus con-
firmed the coordination of ligand via S, S atoms. The unchanged
2.2.2.8. Di-n-butyltin(IV) bis[4-ethoxylcarbonylpiperazine-1-carbodi-
thioate] (8). Stoichiometric amounts: Di-n-butyltin(IV) chloride
(0.5 g, 1.64 mmol) and sodium salt of 4-ethoxycarbonylpiper-
azine-1-carbodithioate (0.84 g, 3.28 mmol). (Yield: 71%). M.p.
110–113 °C. Anal. Calc. for: C, 38.2; H, 6.2; N, 5.6. Found: C, 37.9;

Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
1529
chemical shift value for carbonyl carbon in all compounds con-
firmed no coordination through this site. The most distinct feature
of 13C NMR is 1J[119Sn, 13C] values that can be used to assess mono
or bidentate coordination of ligand to the Sn atom. On the basis of
1J[119Sn,13C] values, trimethyltin(IV) and tri-n-butyltin(IV) deriva-
tives [386 and 353 Hz, respectively] are tetrahedral [23,24]. In case
of diorganotin(IV) compounds (4–9) the 1J[119Sn,13C] coupling con-
stant values in the range 585–607 Hz are in agreement with the
analogous five- and six-coordinated organotins [25,26]. It has been
suggested that the coupling constants values are associated with
the hybridization of the tin atom in organotin compounds and
are measured of the percentage of the s orbital character in the
Sn–C bond [27]. The Sn–C bond in tetrahedral, trigonal-bipyrami-
dal and octahedral arrangements at the tin atom proceed via sp3,
sp2 and sp hybridization. An increase of the s orbital character
(s-orbital electron participation) in the Sn–C bond causes an in-
crease in values of the coupling constants [28]. The coupling con-
stants, 2J[119Sn, 1H] provide an effectively informative probe for
the assessment of the coordination of tin [27].
(0.55) confirmed distorted trigonal-bipyramidal geometry around
Sn. Furthermore, the angle of axial S1–Sn–C21 is 156.19° that
showed a marked deviation from 180°. These bond distances and
angles are in agreement with the corresponding values found for
similar Sn complexes [30]. The packing diagram shows (Fig. 2)
supramolecular structure mediated by OCOꢁꢁꢁH–phenyl intermo-
lecular interactions. No secondary intermolecular SnꢁꢁꢁS interaction
is evident in structure of 3.
The crystal data and structure refinement parameters of com-
pound 4 are given in Table 1. The selected bond lengths and angles
are shown in Table 2. The crystal structure is shown in Fig. 3. The
tin atom is five-coordinated, being chelated by an asymmetrically
coordinating dithiocarboxylate ligand, a chloride and two methyl
substituents. The Sn1–S1 bond distance (2.70 Å) approximately
trans- to the chloride atom is longer than the other Sn1–S2 bond
distance (2.48 Å) and is an indicative of asymmetric coordination
of the ligand. The Sn–Sshorter and Sn–Slonger distances are compara-
ble with our early reported methyltin(IV) analogue [12]. The coor-
dination geometry is almost intermediate between square-
pyramidal and trigonal-bipyramidal having a small bias towards
119Sn NMR spectroscopy has also been very supportive for the
revelation of environment around Sn atom in the organotin(IV)
dithiocarboxylates. The presence of single 119Sn peak in the spectra
of all compounds indicates the formation of single species. On the
basis of d(119Sn) value, Sn atom in these organotin is four- (1 and
2), five- (3–6) and six-coordinated (7–9).
the former, at least based on the values of
s (0.38). The deviation
of coordination geometry towards square-pyramidal is presumably
3.3. Crystallographic studies
In compound 3, the geometry around Sn atom can be described
as distorted trigonal-bipyramidal with the equatorial plane com-
prising the C9 and C15 of the phenyl moiety and a sulfur atom,
S2, of the ligand. The second sulfur (S1) and a C21 of phenyl group
occupied the apical positions (Fig. 1). The Sn–Sax bond length
[2.7099(9) Å] is greater than Sn–Seq bond distance indicating
asymmetric coordination of ligand. The bond length, Sn–Seq is close
to the covalent radii of Sn–S [2.4841(9) Å] and the axial Sn–S bond
distance is much shorter than the van der Waals radii of the two
atoms (4.0 Å). The asymmetric coordination of ligand is also re-
flected in C–S bonds, the longer C–S bond is connected with shorter
Sn–S bond and vice versa. For a five-coordinated metal, a structural
Fig. 2. Packing diagram of compound (3).
index
are the consecutive largest angles around the metal center. For
perfect square-pyramidal and trigonal-bipyramidal geometry, the
value is zero and one, respectively [29]. The calculated value
s
, can be calculated by equation,
s
= (b ꢀ
a)/60, where b and
Table 1
a
Crystal data and structure refinement parameters for complexes 3 and 4.
Empirical formula
Formula weight
Crystal system
Space group
A (Å)
C26H28N2O2S2Sn (3)
583.31
C10H13ClN2O2S2Sn (4)
411.48
Monoclinic
C2/c
27.718(2)
9.2064(7)
12.5099(9)
90.00
105.5020(10)
90.00
s
s
Triclinic
ꢀ
P1
9.0433(8)
11.1221(10)
13.0875(11)
100.4480(10)
94.1200(10)
1264.54(19)
1264.54(19)
2
B (Å)
C (Å)
a
(°)
b (°)
c
(°)
V (Å3)
3076.1(4)
8
Z
Density (calculated) (mg/
1.532
1.777
m3)
Crystal size (mm3)
F(0 0 0)
0.40 ꢂ 0.20 ꢂ 0.20
592
0.25 ꢂ 0.20 ꢂ 0.20
1616
Total reflections
Independent reflections
R indices (all data)
5080
4117
7855 [Rint = 0.0176]
R1 = 0.0263,
wR2 = 0.0628
R1 = 0.0239,
wR2 = 0.0613
1.030
3153 [Rint = 0.0314]
R1 = 0.0338,
wR2 = 0.0720
R1 = 0.0288,
wR2 = 0.0700
1.054
Final R indices [I > 2
a(I)]
Goodness-of-fit (GOF)
h Range for data collection 2.22–26.32
(°)
2.34–26.26
Data/restraints/
7855/0/298
3153/0/164
parameters
Fig. 1. ORTEP drawing of compound (3) with atom numbering scheme.

1530
Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
Table 2
By comparing the two structures it is obvious that the complex
3 and 4 exist in distorted trigonal-bipyramidal and distorted
square-pyramidal geometry, respectively. This difference can be
attributed to the presence of secondary intermolecular SnꢁꢁꢁS inter-
actions in the later. The occurrence of such kind of interactions in
complex 4 only, is due to less steric methyl groups that allow close
packing of the molecules and owing to the electron withdrawing
chloro group that makes the Sn center electron deficient. These
two factors allow the neighboring sulfur to interact with Sn atom
of the adjacent molecule. The absence of intermolecular SnꢁꢁꢁS
interactions, in complex 3, can be explained on the basis of steric
reasons of the bulky phenyl groups. In addition to this, the back-
donation capability of the phenyl groups stabilize Sn atom d-orbi-
tals, rendering its interaction with S atom of the adjacent molecule.
Selected bond lengths (Å) and angles (°) for complexes 3 and 4.
Ph3SnL (3)
Me2SnClL (4)
Sn1C9
Sn1C21
Sn1C15
Sn1S2
S1C1
S2C1
C9–Sn1–C15
C15–Sn1–C21
C15–Sn1–S2
C1–S2–Sn1
C9–Sn1–C21
C9–Sn1–S2
C21–Sn1–S2
C6–N2–C4
N1–C1–S1
S1–Sn–C21
2.134(3)
2.164(3)
2.144(3)
2.4683(8)
1.687(3)
1.748(3)
117.80(11)
105.12(11)
119.87(8)
97.18(10)
104.79(11)
111.85(8)
92.36(8)
124.5(3)
123.3(2)
156.19
Sn1S2
Sn1S1
Sn1C10
Sn1C9
Sn1Cl1
S2C1
C9–Sn1–C10
C10–Sn1–S2
C10–Sn1–Cl1
C9–Sn1–S1
S2–Sn1–S1
C9–Sn1–S2
C9–Sn1–Cl1
S2–Sn1–Cl1
C10–Sn1–S1
Cl1–Sn1–S1
2.4841(9)
2.7099(9)
2.131(3)
2.122(3)
2.4957(9)
1.746(3)
131.88(14)
109.85(10)
95.94(10)
93.17(10)
68.86(3)
117.64(10)
94.47(10)
86.14(3)
96.88(10)
154.57(3)
4. Biological studies
4.1. Antibacterial activity
The compounds 1–9 have been tested against six different
strains of bacteria by agar well diffusion method and the results
are listed in the Table 3. The data revealed the following sequence
of activity against different strains: Pseudomonas aeruginosa >
Shigella flexenari > Bacillus subtilis ꢃ Escherichia coli > Salmonella
typhi > Staphylococcus aureus. In general, triorganotin(IV) deriva-
tives are more active than the diorganotin(IV) compounds and
their activity vary in the sequence: Me (Mr = 398) > Bu (Mr =
524) > Ph (Mr = 584). This trend can be explained on the basis of
ease of diffusion of lighter molecules (low molecular weight)
through the bacterium cell membrane than the heavier ones. The
high activity of tributyltin(IV) compounds than trimethyltin(IV)
derivatives, in some cases, can be attributed to the high lipophilic
character of the large butyl groups. The high activity of chlorod-
iorganotin(IV) derivatives than the corresponding diorganotin(IV)
compounds may be described on the basis of labile nature of the
chloro group and may be due to their low molecular weight that
facilitate diffusion.
Fig. 3. ORTEP drawing of compound (4) with atom numbering scheme.
4.2. Antifungal activity
The fungicidal test for compounds 1–9 against six fungi; Trich-
ophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum
canis, Fusarium solani and Candida glaberata were carried out using
Miconazole and Amphotericin-B as standard drugs. These com-
pounds showed (Table 4) pronounced activity against different
fungi, especially the complexes 2, 3, 5, 6 and 9, for which the per-
cent inhibition is almost comparable with standard drugs against
some fungi (Table 4). The remaining derivatives exhibited moder-
ate activity.
Fig. 4. Packing diagram for compound (4).
4.3. Insecticidal activity
due to the presence of intermolecular secondary SnꢁꢁꢁS interactions
that lead to the formation of a supramolecular zig-zag chain
(Fig. 4). The atoms, S2, Cl1, C9 and C10 are at the plane positions.
Being a part of chelate S1 cannot occupy the exact axial position
of the plan and the S(1)–Sn–S(2) angle is not 90° but only 69°.
Due to steric and electronic reasons, Cl1 is bent towards S2 atom
of the plan as can be seen from S2–Sn–Cl1 [86.14°]. The angle be-
tween the pseudo axial sulfur and chlorine atoms is 154.57° and is
comparable with similar square-pyramidal complexes [31]. The
sum of equatorial angles formed in the complex is 359°, showing
a little distortion from the ideal value of 360°. The Sn–C bond
lengths [Sn(1)–C(9) 2.12, Sn(1)–C(10) 2.13 Å] are similar with
those reported in the literature [31]. The Sn–Cl bond length
[Sn(1) Cl(1) 2.49 Å] lies in a range of the covalent radii of Sn–Cl,
2.37–2.60 Å [32].
The insecticidal activity of the compounds (1–9) was deter-
mined by direct contact application using filter paper [33]. The
compounds were tested against Tribolium castaneum, Callosobru-
chus analis, Sitophilus oryzae, and Rhyzopartha dominica. Permethrin
(235.71 l
g/cm2) was used as a reference insecticide (Table 5). All
compounds were found active but the mortality rate is less than
reference insecticidal drug.
4.4. Cytotoxic activity
The cytotoxic studies were taken by brine-shrimp bioassay
lethality method [34,35] and the results are summarized in Table
6. The LD50 data depicts the toxicity of all the tested compounds

Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
1531
Table 3
Antibacterial activitya,b of organotin(IV) derivatives (1–9) of ‘‘S” donor ligands.
Name of bacterium
Clinical implication
Zone of inhibition (mm)
Ref. drug
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Escherichia coli
Bacillus subtilis
Shigella flexenari
Pseudomonas aeruginosa
Staphylococcus aureus
Salmonella typhi
Infection of wounds, urinary tract and dysentery
Food poisoning
Blood diarrhea with fever and severe prostration
Infection of wounds, eyes, septicemia
Food poisoning, scaled skin syndrome, endocarditis
Typhoid fever, food poisoning, localized infection
37
48
54
47
–
57
44
34
68
–
17
12
24
20
–
22
24
23
20
20
18
30
24
25
25
22
24
26
28
22
26
20
14
20
23
21
22
20
20
23
21
18
19
17
21
18
24
21
–
16
–
35
38
32
38
29
28
42
12
21
a
In vitro, agar well diffusion method, conc. 3 mg/mL of DMSO.
Reference drug = Imipenum.
b
Table 4
Antifungal activitya,b,c data of organotin(IV) derivatives (1–9) of ‘‘S” donor ligand.
Name of Fungus
Percent inhibition
Standard drug
Percentage inhibition
MIC (lg/mL)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Trichophyton longifusus
Candida albicans
Aspergillus flavus
Microsporum canis
Fusarium solani
21
29
73
64
34
18
24
36
80
80
41
20
35
47
90
90
46
38
–
–
–
40
–
64
80
45
50
–
90
62
36
56
80
–
–
–
43
–
65
44
20
38
50
50
44
59
80
80
80
75
30
80
Miconazole
Miconazole
Amphotericin-B
Miconazole
Miconazole
Miconazole
100
100
100
100
100
100
70
110.8
20
98.4
73.25
110.8
Candida glaberata
–
–
a
b
c
Concentration: 100 l
g/cm3 of DMSO.
MIC: minimum inhibitory concentration.
Percent inhibition (standard drug) = 100.
Table 5
Insecticidal bioassaya–c of organotin(IV) derivatives (1–9) of ‘‘S” donor ligand.
Table 7
Insecticidal bioassaya–c of organotin(IV) derivatives (1–9) of ‘‘S” donor ligand.
Insects
% Mortality
Compound
% Age inhibition S.E.Ma
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
1
2
3
4
5
6
7
8
9
65.8% 0.43
45.02% 0.35
87.15% 0.26
71.46% 0.14
45.23% 0.16
81.54% 0.24
84.34% 0.41
48.32% 0.12
75.43% 0.16
Tribolium castaneum
Sitophilus oryzae
Rhyzopertha dominica
Callosbruchus analis
3
4
5
–
12
5
2
10
5
3
5
–
8
5
2
7
4
7
3
4
6
7
2
3
7
9
6
–
4
6
7
3
7
8
8
7
a
b
c
+ve control = 100%.
+ve control = 0%.
Reference drug = Permethrin.
a
b
c
Standard error of mean.
Standard drug Thiourea.
% Inhibition 100.
Table 6
Brine shrimp lethality bioassay of organotin(IV) derivatives (1–9) of ‘‘S” donor ligand.
tion in activity in case of tri-n-butyltin (2), chlorodi-n-butyltin
(5) and di-n-butyltin (6) derivatives is presumably due to the pres-
ence of bulky butyl group that hinder such kind of interaction of
the ligand moiety with enzyme.
The triphenyltin (3), chlorodiphenyltin(6) and diphenyltin (9)
derivatives were also found very good inhibitor against this
enzyme.
Compound no.
LD50 g/mL)
1
2
3
4
5
6
7
8
9
(l
1.10 0.75 1.25 0.25 0.62
–
0.75 2.45 4.6
Against brine-shrimps (in vitro).
Standard drug Etoposide LD50 7.46
l
g/mL.
with LD50 values in the range 0–4.6
lg/mL in comparison to LD50
value (7.46 g/mL) of the reference drug, Etoposide. Among these
organotins, di-n-butyltin(IV)- and diphenyltin(IV) derivatives (8
l
5. Conclusions
and 9) emerged as most toxic compounds.
A series of organotin(IV) derivatives (1–9) of 4-ethoxycarbonyl-
piperazine-1-carbodithioate ligand has been synthesized and fully
characterized by different analytical techniques. The results indi-
cate the diverse structural motifs for these compounds (tetrahe-
dral, square-pyramidal, trigonal-bipyramidal and octahedral
geometries) depending upon the mode of coordination of ligand
as well as the presence or absence of intermolecular Sꢁ ꢁ ꢁSn interac-
tions (in case of five-coordinated Sn). The X-ray structure con-
firmed supramolecular design for compounds 3 and 4 owing to
the presence of non-covalent secondary interactions between the
neighboring molecules. The good antimicrobial, insecticidal and
antiurease activity of these compounds can be attributed to their
4.5. Urease inhibition activity
All compounds (1–9) were tested for their antiurease activity
according to literature protocol [36]. Thiourea was used as stan-
dard inhibitor and results are given in Table 7. All the tested com-
pounds demonstrated fairly good inhibition even at micromolar
level. Methyltin(IV) derivatives (1, 4 and 7) and phenyl derivatives
(3, 6 and 9) demonstrated interesting activity. This can be attrib-
uted to the ability of these compounds to establish secondary
interactions with the active site of enzyme i.e. nickel. The reduc-

1532
Aziz-ur-Rehman et al. / Journal of Organometallic Chemistry 695 (2010) 1526–1532
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with the cell constituents (as evident in Figs. 2 and 3, packing dia-
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pounds can be monitored by two factors: its ease of diffuse (low
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Acknowledgements
We thank the Higher Education Commission of Pakistan for
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Appendix A. Supplementary material
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