New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates: Synthesis, spectroscopic characterization, X-ray structures and in vitro antimicrobial activities

Article abstract of DOI:10.1016/j.ica.2011.04.016

A new series of organotin(IV) complexes with 4-benzhydrylpiperazine-1- carbodithioate (L) were synthesised by the metathesis reactions of the ligand-salt with triorganotin(IV) chlorides and diorganotin(IV) dichlorides in the appropriate molar ratio. All the complexes were characterized by elemental analysis, Raman, IR, and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy. Solid-state studies (Raman, IR and X-ray analysis) confirmed the bidentate coordination of the ligand in all cases. Multinuclear NMR spectroscopy suggested that some tri- and diorganotin complexes reduce their geometry by one unit in solution. The τ values, 0.6 and 0.24 for chlorodibutyl- and chlorodiethyltin(IV) derivatives, respectively, authenticated the trigonal bipyramidal geometry for the first complex and distorted square-pyramidal geometry for the latter. The low τ value for the chlorodiethyltin(IV) complex is attributed to the additional Sn?Cl and Sn?S intermolecular interactions. The antimicrobial results indicated the compounds are active biologically.

Full text of DOI:10.1016/j.ica.2011.04.016

Inorganica Chimica Acta 373 (2011) 187–194
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates:
Synthesis, spectroscopic characterization, X-ray structures and in vitro
antimicrobial activities
c
Zia-ur-Rehman a,b, Niaz Muhammad a, Saqib Ali a, Ian S. Butler b, , Auke Meetsma
⇑
a Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
b Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec, Canada H3A2K6
c Crystal Structure Center, Chemical Physics, Zernike, Institute for Advanced Materials, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 May 2009
Received in revised form 6 April 2011
Accepted 9 April 2011
Available online 16 April 2011
A new series of organotin(IV) complexes with 4-benzhydrylpiperazine-1-carbodithioate (L) were syn-
thesised by the metathesis reactions of the ligand-salt with triorganotin(IV) chlorides and diorganotin(IV)
dichlorides in the appropriate molar ratio. All the complexes were characterized by elemental analysis,
Raman, IR, and multinuclear NMR (1H, 13C and 119Sn) spectroscopy. Solid-state studies (Raman, IR and
X-ray analysis) confirmed the bidentate coordination of the ligand in all cases. Multinuclear NMR spec-
troscopy suggested that some tri- and diorganotin complexes reduce their geometry by one unit in solu-
Keywords:
tion. The
authenticated the trigonal bipyramidal geometry for the first complex and distorted square-pyramidal
geometry for the latter. The low value for the chlorodiethyltin(IV) complex is attributed to the addi-
s values, 0.6 and 0.24 for chlorodibutyl- and chlorodiethyltin(IV) derivatives, respectively,
4-Benzhydrylpiperazine-1-carbodithioate
Organotin(IV) complexes
Trigonal bipyramidal and square-pyramidal
geometries
Molecular spectroscopy
Antimicrobial activity
s
tional SnꢀꢀꢀCl and SnꢀꢀꢀS intermolecular interactions. The antimicrobial results indicated the compounds
are active biologically.
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
ergosterol. Moreover, the significance of the presence of tin was
illustrated by the fact that all the organotin compounds investi-
Organotin(IV) compounds are amongst the most widely used
organometallic compounds owing to a variety of industrial and
agricultural applications, including their use as pesticides, fungi-
cides and anti-fouling agents [1]. For several decades since their
initial discovery, organotins, especially the triorganotins, are
remarkably persistent in the environment and the study of their
toxicology is a matter of some exigency [2]. It has been established,
however, that successive dealkylations of organotins yield ‘‘non-
toxic’’ Sn(II) species. Although the mechanism of organotin degra-
dation is not yet fully explored, it is generally acknowledged that
in vivo deactivation of R3Sn and R2Sn systems involves enzymes
with two sulfur donor sites [3]. Dithiocarboxylates merit special
attention because of their antitumor, antiviral and pesticidal activ-
ities. In addition, diethyldithiocarboxylate salts have applications
in chronic alcoholic therapy and the treatment of HIV-patients
[4]. The chemistry of organotin dithiocarboxylates has been a mat-
ter of interest because of their antimicrobial action. Menezes et al.
recently evaluated a series of organotin dithiocarboxylates for their
antifungal activity and discovered that the fungicidal action of
these compounds is due to the inhibition of the biosynthesis of
gated had activities greater than those exhibited by the uncoordi-
nated dithiocarboxylate ligand [5]. With respect to the
antibacterial activity of this class of compound, several attempts
have been made to replace the commercially available drugs but,
thus far, none of them has proven successful [6,7]. Nevertheless,
investigations are continuing in an effort to develop more potent
derivatives so as to overcome to the current and projected prob-
lems of organisms developing drug resistance. To be an active par-
ticipant in this field and as a continuation of our interest [8], a
series of new organotin(IV) 4-benzhydrylpiperazine-1-carbodi-
thioates has been synthesized (Scheme 1b) and the compounds
have been characterized and evaluated for their antibacterial and
antifungal activity. Some of these complexes revealed greater anti-
bacterial activity than the standard drug. This work is reported in
this paper.
2. Experimental
2.1. Materials and methods
The reagents, organotin(IV) chlorides and 4-benzhydrylpiper-
azine, were obtained from Aldrich, while CS2 was purchased from
Riedal-de Haën; methanol was dried before use by the literature
⇑
Corresponding author. Tel.: +1 514 398 6910; fax: +1 514 398 3797.
E-mail address: ian.butler@mcgill.ca (I.S. Butler).
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.04.016

188
Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
a
b
3
2
S
1
2a
3a
N
N
N
4
S
H2N
3'
2'
4a
3a'
2a'
γ
β
β
γ
δ
β
α
γ
β
α
CH3
α
α
α
δ
δ
CH2 CH3
CH3
H2C
,
,
,
,
S
N
a) MeOH
Ar
N
NH
Ar
N
+ CS2
b) 4 h stirring
SH
c) 0 oC
Ar
N
NH
..
Dry MeOH
6 h reflux
R3SnCl
R
S
S
R
Ar
Sn
R
N
N
Ar
N
N
S
-Salt
S
Ar
H2N
N
R = n-C4H9, C6H11, C6H5
-Salt
Dry MeOH
6 h reflux
Dry MeOH
6 h reflux
R2SnCl2
-Salt
1/2R2SnCl2
R
S
Sn
S
R
R
S
S
N
N Ar
Sn
Cl
Ar
N
N
Ar
N
N
S
S
R
R = n-C4H9, C2H5, CH3
R = n-C4H9, C2H5, CH3
Ar
Ar =
Salt =
N
NH2Cl
,
Scheme 1. (a) Numbering scheme of ligand-salt and organic moiety of tin; (b) Synthesis of ligand-salt and complexes 1-9.
procedure [9]. Microanalyses were done using a Leco CHNS 932
apparatus. Infrared spectra were recorded as KBr pellets in the
range from 4000–400 cmꢁ1 using a Bio-Rad Excaliber FT-IR, model
FTS 300 MX spectrometer (USA). Raman spectra ( 1 cmꢁ1) were
measured with an InVia Renishaw spectrometer, using argon-ion
(514.5 nm) and near-infrared diode (785 nm) lasers. WiRE 2.0 soft-
ware was used for the data acquisition and spectra manipulations.
NMR spectra (DMSO-d6) were obtained with Varian Mercury
300 MHz spectrometer (1H and 13C) and a Varian Unity 500-MHz
instrument [119Sn; SnMe4 (ext) ref].
2.2.1. 4-Benzhydrylpiperazinium 4-benzhydrylpiperazine-1-
carbodithioate ( -salt)
L
Dropwise addition of CS2 (in excess) in methanol (50 mL) to 4-
benzhydrylpiperazine (6 g, 23.79 mmol) in methanol (50 mL) fol-
lowed by stirring for 6 h at 0 °C gave a white precipitate. The prod-
uct was filtered off and washed with diethyl ether (Yield: 11.03 g,
80%). M.p. 191–193 °C. Anal. Calc. for C35H40N4S2: C, 72.37; H, 6.94;
N, 9.65; S, 11.04. Found: C, 72.11; H, 6.69; N, 9.45; S, 10.87%. Ra-
man (cmꢁ1): 650
m
(C–S), 1045
m(C@S), 1460 m
(C–N). IR (cmꢁ1):
1035
m(C–S), 1450 m
(C–N). 1H NMR (ppm): 2.62, 2.46 (bs, 8H,
0
0
0
0
0
H
2,2 ,2a,2 a), 4.40, 3.32 (bs, 8H, H3,3 ,3a,3 a), 4.28 (s, 2H, H4,4 ), 7.48–
7.17 (m, 10H, Ar-H), 8.1 (s, 2H, NH2). 13C NMR (ppm): 209.6 (C-
1), 49.6, 44.8 (C-2, 20, 2a, 20a), 52.4, 50.8 (C-3, 30, 3a, 30a), 69.8 (C-
4), 142.5, 142.0, 128.9, 128.8, 128.1, 127.9, 127.6, 127.4 (Ar-C).
2.2. Syntheses
The syntheses and Raman, IR and mass spectral data of the li-
gand-salt and the new organotin(IV) complexes, together with
the 1H and 13C NMR data of ligand-salt are presented in this sec-
tion. For the complexes, 1H NMR are given in Table 1, whereas
13C and 119Sn NMR are listed in Table 2. The assignments of the
1H and 13C NMR spectra of the ligand and the organic groups at-
tached to Sn were made according to Scheme 1a.
2.2.2. General procedure for synthesis of complexes
Triorganotin(IV) chloride or diorganotin(IV) dichloride in meth-
anol (30 mL) was added dropwise to the ligand-salt in methanol
(50 mL) in the appropriate molar ratio and the mixture was re-
fluxed for 6–8 h with constant stirring. The solvent was rotary

Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
189
Table 1
1H NMR dataa, of complexes 1–9.
b
1H
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
2,20
2.65
(bs)
3.15
(bs)
7.40–7.15
(m)
4.23
2.48–2.45
(m)
4.20–4.17
(m)
7.42–7.17
(m)
4.26
2.57
(bs)
3.07
(bs)
7.37–7.18
(m)
3.22
(bs)
3.97
(bs)
7.41–7.16
(m)
4.29
3.22
(bs)
3.97
(bs)
7.41–7.16
(m)
4.29
2.63
(bs)
3.15–3.12
(m)
7.40–7.14
(m)
2.63
(bs)
3.15–3.12
(m)
7.40–7.14
(m)
2.54–2.51
(m)
3.96–3.93
(m)
7.42–7.18
(m)
4.29
2.49–2.46
(m)
4.10–4.05
(m)
7.42–7.17
(m)
4.26
3,30
Ar-H
4
4.27
(s)
4.29
(s)
4.29
(s)
(s)
(s)
(s)
(s)
(s)
(s)
a
1.62–1.26
(m)
2.00–1.28
(m)
–
1.85–1.35
(m)
1.85–1.35
(m)
1.81
(q), (7.5)
1.81
(q), (7.5)
1.28
(s)
1.48
(s)
[75,73]
–
[85, 82]
–
b
c
d
1.62–1.26
(m)
1.62–1.26
(m)
0.89
(t), (7)
2.00–1.28
(m)
2.00–1.28
(m)
2.00–1.28
(m)
7.70–7.66
(m)
7.44–7.36
(m)
7.44–7.36
(m)
1.85–1.35
(m)
1.85–1.35
(m)
0.94
(t), (7.5)
1.85–1.35
(m)
1.85–1.35
(m)
0.94
(t), (7.5)
1.46
(t),(7.5)
–
1.46
(t),(7.5)
–
–
–
–
–
–
–
aChemical shifts (d) in ppm. 2J[119Sn, 1H], 3J(1H, 1H) in Hz are listed in square brackets and parenthesis, respectively. Multiplicity is given as s = singlet, d = doublet,
m = muliplet, bs = broad signal.
bNumbering in accordance with Scheme 1a.
Table 2
13C and 119Sn NMR dataa,b of complexes 1–9.
13C
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
1
198.4
52.0
51.6
199.3
52.0
51.6
196.9
52.7
51.4
196.6
52.0
51.2
198.1
52.0
51.2
196.5
52.1
51.2
202.4
51.9
51.2
195.9
52.1
51.1
199.1
51.4
44.4
2,20
3,30
Ar-C (i, o, 141.7, 127.8,
m, p) 129.0, 127.6
141.7, 127.8,
129.0, 127.6
75.8
142.0, 127.9,
128.9, 127.5
75.7
141.7, 127.8,
129.0, 127.7
75.7
141.7, 127.8,
129.0, 127.7
141.7, 127.9,
129.0, 127.7
75.6
141.8, 127.9,
129.0, 127.6
75.6
141.7, 128.0,
129.0, 127.7
75.6
142.1, 128.0,
128.9, 127.5
75.8
4
75.8
a
17.9
[340, 321]
29.1
35.5
[335,318]
32.1
142.6
[791]
136.4
[48]
26.5
[595]
28
[18]
26.6
[605]
34.1
[19]
21.4
[532,509]
10.5
21.4
[620,595]
10.5
10.3
[570,545]
–
15.1
[675, 660]
–
b
[16]
[17]
[38]
[48.5,44.7]
c
27.3
[67]
13.9
29.6
[68]
27.4
129.3
[62]
130.5
[12.8]
ꢁ185.4
27.3
[65]
13.8
28.8
[65]
13.9
–
–
–
–
d
–
–
–
–
119Sn
27.6
ꢁ26.9
ꢁ195.1
ꢁ194.9
ꢁ188.5
ꢁ188.1
ꢁ194.3
ꢁ331.1
a
Chemical shifts (d) in ppm. nJ[119Sn, 13C] in Hz are listed in square brackets.
Number in accordance with Scheme 1a.
b
evaporated off and the product obtained was recrystallized from
chloroform–ethanol mixture (Scheme 1b).
1480
1469
m
(C–N), 268
m(Sn–C), 392 m m(C–S),
(Sn–S). IR (cmꢁ1): 985
m(C–N).
2.2.6. Chlorodibutyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate
(4)
2.2.3. Tributyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate (1)
Yield: 0.73 g, 69%. M.p. 77–79 °C. Anal. Cacl. for C30H46N2S2Sn: C,
58.35; H, 7.51; N, 4.54; S, 10.38. Found: C, 58.23; H, 7.43; N, 4.50; S,
Yield: 0.87 g, 85%. M.p. 211–216 °C. Anal. Calc. for C26H37
N2S2SnCl: C, 52.41; H, 6.26; N, 4.70; S, 10.76. Found: C, 52.30; H,
10.31%. Raman (cmꢁ1): 644
(Sn–C), 371
m
(C–S), 1026
m
(C@S), 1462
m(C–N), 590
6.18; N, 4.66; S, 10.70%. Raman (cmꢁ1): 617
m
(C–S), 1029
m(C@S),
m
m
(Sn–S). IR (cmꢁ1): 955
m(C–S), 1460 m
(C–N).
1443
935
m
(C–N), 588
m
(Sn–C), 382
m(Sn–S), 272 m
(Sn–Cl). IR (cmꢁ1):
m
(C–S), 1470
m(C–N).
2.2.4. Tricyclohexyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate
(2)
2.2.7. Dibutyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate] (5)
Yield: 0.65 g, 85%. M.p. 207–209 °C. Anal. Calc. for C44H56
N4S4Sn: C, 59.52; H, 6.36; N, 6.31; S, 14.45. Found: C, 59.44; H,
Yield: 0.78 g, 65%. M.p. 164–166 °C. Anal. Calc. for C36H52
N2S2Sn: C, 62.16; H, 7.53; N, 4.03; S, 9.22. Found: C, 62.01; H,
7.45; N, 4.01; S, 9.17%. Raman (cmꢁ1): 635
m
(C–S), 1024 (C@S),
m
6.29; N, 6.27; S, 14.38%. Raman (cmꢁ1): 617
m
(C–S), 1025 (C@S),
m
(Sn–S). IR (cmꢁ1): 937
m(C–S),
1437
1460
m
(C–N), 646
m
(Sn–C), 376
m
(Sn–S). IR (cmꢁ1): 960
m(C–S),
1443
1456
m
(C–N), 587
m(Sn–C), 384
m
m
(C–N).
m(C–N).
2.2.5. Triphenyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate (3)
Yield: 0.87 g, 75%. M.p. 140–142 °C. Anal. Calc. for C36H34
N2S2Sn: C, 63.82; H, 5.06; N, 4.13; S, 9.47. Found: C, 63.71; H,
2.2.8. Chlorodiethyltin(IV) 4-benzhydrylpiperazine-1-carbodithioate
(6)
Yield: 0.75 g, 81%. M.p. 133–134 °C. Anal. Calc. for C44H56
N4S4Sn: C, 48.95; H, 5.42; N, 5.19; S, 11.88. Found: C, 48.84; H,
5.01; N, 4.11; S, 9.41%. Raman (cmꢁ1): 652
m(C–S), 1022 m(C@S),

190
Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
5.38; N, 5.16; S, 11.81%. Raman (cmꢁ1): 592
m
(C–S), 1024
m(C@S),
Table 3
1484
945
m
(C–N), 490
m
(Sn–C), 387
m(Sn–S), 259 m
(Sn–Cl). IR (cmꢁ1):
(C–Sn–C) angles (°) based on NMR parameters of selected of complexes 1–9.
Compounds number 1J(119Sn, 13C) (Hz) 2J(119Sn, 1H) (Hz) Angle (°)
m
(C–S), 1470
m(C–N).
1J
2J
2.2.9. Diethyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate] (7)
Yield: 0.51 g, 71%. M.p. 153–154 °C. Anal. Calc. for
C44H56N4S4Sn: C, 57.76; H, 5.82; N, 6.74; S, 15.42. Found: C,
1
2
3
4
5
6
7
8
9
340
335
–
–
–
532
620
570
675
–
–
791
595
605
–
106.6
106.1
125.4
–
–
–
57.66; H, 5.73; N, 6.71; S, 15.36%. Raman (cmꢁ1): 621
m
(C–S),
128
129.8
–
–
1031
955
m
(C@S), 1464
m(C–N), 492 m(Sn–C), 385 m
(Sn–S). IR (cmꢁ1):
123.4
131.1
126.7 121.5
m
(C–S), 1460 (C–N).
m
75
85
135.9 130.3
2.2.10. Chlorodimethyltin(IV) 4-benzhydrylpiperazine-1-
carbodithioate (8)
Yield: 0.71 g, 81%. M.p. 166–167 °C. Anal. Calc. for
C44H56N4S4Sn: C, 46.94; H, 4.92; N, 5.47; S, 12.53. Found: C,
geometry of the methyltin derivatives was predicted from the val-
ues of the 2J [119Sn, 1H] coupling constants. The CSnC angles, calcu-
lated from Lockhart’s equation (h = 0.0105 [2J]2 ꢁ 0.799 [2J] +
122.4) shown in Table 3, are in agreement with trigonal bipyrami-
dal and octahedral geometry for compounds 8 and 9, respectively.
Owing to the complex peak patterns observed for the organic
groups attached to Sn, in the case of the butyl-, cyclohexyl, phenyl
and ethyltin derivatives, no tin-proton satellites were observed
and hence assignment of the geometry is not possible. The geom-
etry of the triphenyltin compound was confirmed by the difference
of the ortho protons compared to those of the meta- and para pro-
tons and corresponded to a five-coordinate Sn atom [12].
46.85; H, 4.86; N, 5.44; S, 12.48%. Raman (cmꢁ1): 561
m(C–S),
1026
m
(C@S), 1462
m
(C–N), 518
m
(Sn–C), 389
m(Sn–S), 261 m(Sn–
Cl). IR (cmꢁ1): 995
m
(C–S), 1466
m(C–N).
2.2.11. Dimethyltin(IV) bis[4-benzhydrylpiperazine-1-carbodithioate]
(9)
Yield: 0.51 g, 74%. M.p. 216–218 °C. Anal. Calc. for
C44H56N4S4Sn: C, 56.78; H, 5.52; N, 6.97; S, 15.96. Found: C,
56.69; H, 5.46; N, 6.93; S, 15.90%. Raman (cmꢁ1): 558
m
(C–S),
1026
991
m
(C@S), 1475
m(C–N), 509 m(Sn–C), 376 m
(Sn–S). IR (cmꢁ1):
m
(C–S), 1457 (C–N).
m
The 13C NMR data exhibited explicitly the resonances of all the
distinct carbon atoms present in the compounds. The assignment
of the carbon resonances associated with the organotin moieties
was made on the basis of the nJ [119Sn, 13C] coupling constant(s)
and signal intensities, as illustrated earlier [13]. The resonances
in CS2 for the complexes were shifted slightly upfield thus suggest-
ing coordination of the metal to the ligand. The 1J [119Sn, 13C] cou-
pling constants observed in some compounds were exploited to
obtain geometry information. For compounds 1 and 2, the 1J
3. Results and discussion
3.1. Vibrational spectra
The appearance of a new Sn–S stretching vibration in the Ra-
man spectra indicated the formation of complexes. A band in the
490–646 cmꢁ1 region, which can be assigned to a Sn–C stretch,
was identified in all the organotin(IV) derivatives except for the tri-
phenyltin(IV) compound (a weak vibration at 267 cmꢁ1). In the
chlorodiorganotin(IV) derivatives, the peak associated with m(Sn–
Cl) was also observed, which pointed to substitution of one chlo-
ride by a ligand moiety.
[
119Sn, 13C] coupling constants correspond to tetrahedral geometry,
while for compounds 6 and 8, the values obtained match well with
a pentacoordinated environment about the Sn centre [14a,b]. A
characteristic feature for triphenyltin derivatives is the observation
of the 13C chemical shift of the ipso-carbon at about 142.6 ppm,
which is attributed to a five-coordinated Sn atom [15].
In the IR spectra, the m(C–S) mode, which appears in the region
ꢂ1000 cmꢁ1, is of prime importance in deciding the mode of coor-
dination of the dithiocarboxylate ligand. The presence of single
peak in this region indicates bidentate coordination, while splitting
into a doublet signifies monodentate coordination [10]. A single
sharp band at 1035 cmꢁ1 was observed in the ligand-salt, which
was shifted to lower energy in the complexes, thus suggesting
The appearance of a single peak in the 119Sn NMR spectra of all
the complexes signified the formation of single species. The 119Sn
chemical shifts for compounds 1 and 2 are in accord with tetrahe-
dral geometry. Complex 9 exhibited a 119Sn peak corresponding to
an octahedral environment about the Sn atom. The 119Sn values ob-
served for compounds 3–8 were indicative of a five-coordinated Sn
atom [16]. These results indicate that in solution the diorganotin
derivatives change their solid-state octahedral geometry to a trigo-
bidentate coordination of the ligand via the CSS moiety. The m(N–
CSS) mode was observed between the ranges reported for a C–N
single bond (1250–1360 cmꢁ1) and a C@N double bond (1640–
1690 cmꢁ1), indicative of the partial double bond character in the
C–N bond [11]. On passing from the ligand-salt to the complexes,
R
R
the
m
(N–CSS) mode is shifted to higher energies, showing an in-
(N–CSS) band appeared
S
S
S
S
S
S
crease in C–N double bond character. The
m
Sn
R
Sn
R
R
R
R
R
at higher energy in the chlorodiorganotin(IV) derivatives than in
the counterparts without a chloride substituent, because the elec-
tron-withdrawing capacity of the chloride leads to a higher posi-
tive charge on the nitrogen atom.
S
S
b
a
3.2. Multinuclear NMR spectra
R
S
S
The 1H NMR spectra were recorded for compounds 1–10 in
DMSO-d6. The characteristic chemical shifts were recognized by
their intensity and multiplicity patterns. The total numbers of pro-
tons, calculated from the integration curves, were in agreement
with the proposed molecular structure of the compounds. The
Sn
R
R
S
S
R
c
Scheme 2. (a) Solid-state structure; (b and c) solution structures.

Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
191
Fig. 1. ORTEP drawing of molecule 1 (top) and molecule 2 (lower) of the 4 with atomic numbering scheme.
Table 4
Crystal data and structure refinement parameters for compounds 4 and 6.
Table 5
Selected bond lengths (Å) and bond angles (°) for compound 4.
4
6
x = 1
x = 2
Empirical formula
Formula mass
Crystal system
Space group
a (Å)
C
26H37N2S2SnCl
C22H29N2S2SnCl
539.77
monoclinic
C2/c
29.612(15)
9.609(5)
18.082(10)
–
117.844(10)
–
Snx–Clx
2.446(2)
2.754(2)
2.125(11)
1.716(6)
2.4721(13)
2.7849(13)
2.145(6)
595.89
triclinic
P1
Snx–Sx2
Snx–Cx23
Sx2–Cx18
ꢀ
1.705(4)
9.9510(10)
13.3727(14)
21.113(2)
100.6968(14)
91.2796(14)
92.3442(14)
2757.1(5)
4 (2)
Clx–Snx–Sx1
88.07(6)
95.4(2)
68.55(5)
119.7(4)
96.8(3)
90.9(2)
117.3(3)
138.5(11)
85.52(4)
99.27(16)
68.31(4)
114.57(16)
91.83(14)
91.58(14)
117.7(2)
115.8(4)
b (Å)
c (Å)
Clx–Snx–Cx19
Sx1–Snx–Sx2
Sx1–Snx–Cx23
Sx2–Snx–Cx23
Snx–Sx1–Cx18
Sx1–Cx18–Sx2
Snx–Cx23–Cx24
a
(°)
b (°)
c
(°)
V (Å3)
4549(4)
8 (1)
Z
Crystal size (mm)
Temperature (K)
Total reflections
Independent reflections
All
0.49 ꢃ 0.23 ꢃ 0.14 0.32 ꢃ 0.28 ꢃ 0.16
Snx–Sx1
Snx–Cx19
Sx1–Cx18
2.4705(15)
2.208(8)
1.740(6)
2.4688(13)
2.137(6)
1.756(4)
100(1)
20874
10225
100(1)
3682
3682
Clx–Snx–Sx2
156.57(7)
96.2(4)
115.3(2)
93.4(2)
124.0(5)
82.3(2)
115.9(6)
153.84(4)
99.55(14)
116.18(17)
92.43(16)
126.8(2)
For Fo P 4.0
r
(Fo)
7585
0.0528
2448
0.0716
Clx–Snx–Cx23
Sx1–Snx–Cx19
Sx2–Snx–Cx19
Cx19–Snx–Cx23
Snx–Sx2–Cx18
Snx–Cx19–Cx20
P
P
R(F) = (||Fo| ꢁ |Fc||)/ |Fo|
For Fo > 4.0
r(Fo)
P
wR(F2) = [ [w(Fo2 ꢁ F2c )2]/
0.1302
0.2084
P
[w(F2o )2]]1/2
82.45(14)
113.3(4)
R indices (all data)
Final R indices [I > 2
0.0528
0.1302
0.0716
0.2084
r(I)]
Goodness-of-fit (GOF)
1.034
1.138
h Range for data collections (°)
Data/restraints/parameters
2.51–25.68
10225/0/581
2.77–25.03
3682/0/256
3.3. Crystal structures of compounds 4 and 6
The asymmetric unit for compound 4 contains two different mol-
ecules, each having a slightly different geometry. Fig. 1 shows ORTEP
diagrams for both molecules together with the atom numbering
Scheme. Crystal data and selected interatomic parameters are
nal bipyramidal one, most probably by the mechanism shown in
Scheme 2.

192
Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
Fig. 4. Supramolecular chain in the structure of
secondary SnꢀꢀꢀS interactions.
6
mediated by SnꢀꢀꢀCl and
Fig. 2. Supramolecular chain structure of compound 4.
occupy exactly the position trans to Cl and the Cl1–Sn1–S12 and
Cl2–Sn2–S22 angles are 156.57(7)° and 153.84 (4)°. Thus, the dithio-
carboxylate groups in both molecules are asymmetrically coordi-
nated, as shown by Snx–Sx2(ax) [2.754 (2) Å and 2.7849 (13) Å]
and Sn–Sx2(eq), [2.4705(15) Å and 2.4688(13) Å] bond lengths.
The S–C bond lengths [(Sx1–Cx18 = 1.740(6) Å and 1.756 (4) Å)
and (Sx2–Cx18 = 1.716(6) Å and 1.705 (4) Å)] also show the asym-
metric nature of the dithiocarboxylate group in each molecule. The
packing of molecules to form a supramolecular chain is shown in
Fig. 2, which indicates no intermolecular SnꢀꢀꢀS and SnꢀꢀꢀCl interac-
Table 6
Selected bond lengths (Å) and bond angles (°) for compound 6.
Sn–Cl
2.462(4)
2.784(4)
2.113(15)
1.707(17)
Sn–S1
Sn–C19
S1–C18
2.457(4)
2.120(14)
1.724(15)
Sn–S2
Sn–C21
S2–C18
Cl–Sn–S1
85.43(12)
97.1(4)
67.87(12)
110.5(4)
92.6(4)
Cl–Sn–S2
153.29(12)
97.6(4)
108.9(4)
91.1(4)
138.9(6)
82.0(5)
Cl–Sn–C19
S1–Sn–S2
S1–Sn–C21
S2–Sn–C21
Sn–S1–C18
S1–C18–S2
Cl–Sn–C21
S1–Sn–C19
S2–Sn–C19
C19–Sn–C21
Sn–S2–C18
tions, however, the molecules are linked together via
interactions.
pꢀꢀꢀH
92.3(5)
117.8(8)
For compound 6, the pertinent crystallographic parameters, se-
lected bond lengths and bond angles are given in Tables 4 and 6,
respectively. An ORTEP view of compound 7, together with atomic
numbering Scheme, is presented in Fig. 3. The asymmetric unit
contains a single SnEt2 moiety connected to a chloride and to a
dithiocarboxylate ligand via two Sn–S bonds. The Sn–S2 [2.784
(4) Å] distance for the bond approximately trans- to the chloride
is longer than is the other Sn–S1 [2.457(4) Å] distance. The coordi-
nation geometry is almost intermediate between square-pyrami-
dal and trigonal bipyramidal with a slight bias towards the
collected in Tables 4 and 5, respectively. The configuration about the
tin atom is five-coordinate with a distorted trigonal–bipyramidal
geometry at the central Sn atom. The sums of the equatorial angles
involving the two
(x1): 359°: 357.5°, show little deviation from the ideal angle of
360°. The values, 0.6 and 0.62, for both molecules agree well with
a-carbons of the butyl groups and an S atom,
s
the distorted trigonal bipyramidal structure. For each molecule, the
Cl atom occupies one of the apical positions of the trigonal-bipyra-
mid with Cl1–Sn1–S11 and Cl2–Sn2–S21 angles of 88.07(6)° and
85.52(4)°, respectively. The quasi-axial S11 and S12 atoms cannot
former, based on the
s value (0.24), and is consistent with 0.29 va-
lue for (MeO(O@)CCH2CH2)2Sn (S2CNMe2)Cl [17]. More tangible
explanations are available for the deviation of the coordination
geometries towards square pyramidal. In complex 7, there are
Fig. 3. ORTEP drawing of 6 with atomic numbering scheme.

Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
193
Table 7
Antibacterial activity data
a,b
of ligand-salt and organotin(IV) derivatives 1–9.
Bacterium
Clinical implication
Zone of Inhibition (mm)
Reference drug
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
L
-salt
Escherichia coli
Salmonella typhi
Pseudomonas aeruginosa
Staphlococcus aureus
Streptococcus
Infection of wounds, urinary tract and dysentery
Typhoid fever, localized infection
Infection of wounds, eyes, septicemia
Food poisoning, scaled skin syndrome, endocarditic
Strep throat
20
21
0
0
12
25
0
13
0
13
0
0
0
13
21
25
0
0
0
22
35
12
14
13
18
22
0
13
0
26
32
13
18
20
19
0
12
13
20
0
17
0
12
12
0
11
0
0
13
34
31
24
38
38
0
a
In vitro, agar well diffusion method, conc. 1 mg/mL of DMSO.
Reference drug, streptomycin.
b
Table 8
Antifungal activitya of ligand-salt and organotin(IV) derivatives 1–9.
Sample
Tested fungi
Aspergillus nigar
Aspergillus flavus
Helminthosporium solani
Alternia solani
Fusarium sp.
Linear
%
Linear
%
Linear
%
Linear
%
Linear
%
growth
Inhibition
growth
Inhibition
growth
Inhibition
growth
Inhibition
growth
Inhibition
Control
85
68
86
70.0
87
74.0
90
68.0
70
62
20.0
18.6
14.9
24.4
11.4
L
-salt
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
80
78
74
66
78
66
83
80
80
5.9
8.2
12.9
22.4
8.2
22.4
2.4
5.9
81.0
78.0
78.0
78.0
78.0
72.0
82.0
83.0
78.0
52
5.8
9.3
9.3
9.3
9.3
16.3
4.7
3.5
9.3
39.5
78.0
74.0
72.0
76.0
73.0
73.0
76.0
80.0
68.0
51
10.3
14.9
17.2
12.6
16.1
16.1
12.6
8.0
74.0
80.0
80.0
70.0
74.0
66.0
73.0
78.0
64.0
48
17.8
11.1
11.1
22.2
17.8
26.7
18.9
13.3
28.9
46.7
70
70
70
68
68
60
70
68
61
44
0
0
0
2.8
2.8
14.2
0
2.8
12.8
37.1
5.9
29.4
21.8
41.4
Clotrimazole 60
a
Concentration: 200
lg/mL of DMSO.
two intermolecular interactions responsible for lowering the
s
va-
data for both complexes indicate that the Sn–Cl bond is compara-
tively longer in chlorodiethyltin complex than in the chlorodibu-
tyltin derivative and hence it is more easily hydrolysed. The
possible inhibitory action of the complexes may be attributable
to their inhibition of DNA replication by interacting with the en-
zyme prosthetic group. These compounds are quite active due to
their membrane penetrating ability. The reduced activities in some
cases can, however, be attributed to the inability of hydrogen bond
formation with the cell constituents [19].
lue, a SnꢀꢀꢀCl and a secondary SnꢀꢀꢀS interaction, which lead to the
formation of a supramolecular chain structure (Fig. 4). The Cl atom
occupies one of the apical positions of the highly distorted trigo-
nal-bipyramid with a Cl–Sn–S1 angle of 85.43(12)°. The quasi-axial
S2 atom again cannot occupy exactly the position trans to Cl and
Cl–Sn–S2 is 153.29(12)°. Thus, the 4-benzhydrylpiperazine-1-car-
bodithioate ligand chelates the Sn atom via its two sulfur atoms
in anisobidentate fashion, forming a four-membered ring with
S1–Sn–S2 bond angle of 67.87(12)°. The S–C bond lengths [S1–
C18 = 1.724(15) Å and S2–C18 = 1.707(17) Å] also demonstrate
the asymmetric nature of the ligand.
3.5. Antifungal activity
The agar tube dilution protocol method was employed to test
the antifungal activities of the synthesized compounds against five
different strains of fungi, namely Aspergillus nigar, Aspergillus flavus,
Helminthosporium solani, Alternia solani, Fusarium sp. The results
are shown in Table 8. The inhibition of fungal growth, expressed
in percentage terms, was determined using the Vincent equation
[20]:
3.4. Antibacterial activity
The antibacterial activities of DMSO solutions of the new com-
pounds were tested against five bacterial strains by the agar well
diffusion method. The activities were compared with that of the
reference antibiotic, streptomycin, and the results are given in Ta-
ble 7. The complexes have activities comparable to that of the ref-
erence drug in some cases. The higher activities observed for the
chlorodiorganotin(IV) complexes are most probably due to the
presence of the more labile chloride group the presence of which
make these complexes easily hydrolysable [18]. Among the chlo-
rodiorganotin compounds, the low activity of complex 9, confirms
the notion that activity increases with increasing alkyl chain
length. This situation arises because increasing chain length en-
hances the lipophilicity of the molecules, so that they can pene-
trate faster to produce a cytotoxic effect. The higher activity of
the chlorodiethyltin complex compared to that of the chlorodibu-
tyltin species indicates that lipophilicity is not the sole factor
responsible for cytotoxic action. The ease of detachment of the la-
bile group must also play a significant role. The crystal structural
Inhibition % ¼ 100ðC ꢁ TÞ=C
ð1Þ
where C is the diameter of fungal growth for a control and T is the
diameter of fungal growth for the sample.
The complexes inhibit the fungal growth to a medium extent;
however, the zone of inhibition of complexes 5 and 7 is comparable
with those of a standard fungicide, especially against the A. nigar
and A. solani fungi.
4. Conclusion
Nine new organotin(IV) 4-benzhydrylpiperazine-1-carbodithio-
ates have been synthesised and characterized by various spectros-
copy techniques. X-ray single crystal study proved supramolecular

194
Zia-ur-Rehman et al. / Inorganica Chimica Acta 373 (2011) 187–194
(b) M. Gielen, E.R.T. Tiekink, Metallotherapeutic Drugs and Metal-Based
Diagnostic Agents: The Use of Metals in Medicine, Wiley, 2005;
(c) K.E. Appel, Drug Metab. Rev. 36 (2004) 763.
molecular structure for complexes 4 and 9 with a distorted trigonal
bipyramidal and a distorted square-pyramidal geometry, respec-
tively. The square-pyramidal geometry is of particular interest be-
cause geometry of such kind is scantly available in the literature
for organotins. The different geometry of 9 than 4 can be attributed
to the intermolecular SnꢀꢀꢀCl interactions in the former. The antimi-
crobial activities of the complexes are, in broad terms, excellent
and far exceed the level for the free ligand. The influence of the me-
tal is clearly visible in the antibacterial activity. The antibacterial
activity maximizes for complexes 4 and 6, although the activity
of all the organotin complexes is reasonable.
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Acknowledgements
We thank the Higher Education Commission of Pakistan and the
NSERC (Canada) for financial support.
Appendix A. Supplementary material
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J. Organomet. Chem. 633 (2001) 7.
CCDC 733924 and 733923 contain the supplementary crystallo-
graphic data for complexes 4 and 6, respectively. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.ica.2011.04.016.
[16] A. Tarassoli, T. Sedaghat, B. Neumüller, M. Ghassemzadeh, Inorg. Chim. Acta
318 (2001) 15.
[17] O.S. Jung, J.H. Jeong, Y.S. Sohn, Organometallics 10 (1991) 2217.
[18] E.R.T. Tiekink, Appl. Organomet. Chem. 22 (2008) 533.
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