Synthesis, characterization and cytotoxic activity of new diorganotin(IV) complexes of N-(3,5-dibromosalicylidene)tryptophane

Article abstract of DOI:10.1002/aoc.1758

Four new diorganotin(IV) complexes of N-(3,5-dibromosalicylidene) tryptophane, R₂Sn[3,5-Br₂-2-OC₆H ₂CH-NCH(CH₂Ind)COO] [Ind = 3-indolyl; R = Et (1); n-Bu (2); Cy (3); Ph (4)], were synthesized and cha

Full text of DOI:10.1002/aoc.1758

Full Paper
Received: 15 July 2010
Revised: 28 October 2010
Accepted: 28 October 2010
Published online in Wiley Online Library: 21 January 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1758
Synthesis, characterization and cytotoxic
activity of new diorganotin(IV) complexes
of N-(3,5-dibromosalicylidene)tryptophane
Laijin Tiana∗, Xicheng Liua, Xiaoliang Zhengb,Yuxi Suna, Dongmei Yanb
and Linglan Tub
Four new diorganotin(IV) complexes of N-(3,5-dibromosalicylidene)tryptophane, R2Sn[3,5-Br2-2-OC6H2CH NCH(CH2Ind)COO]
[Ind = 3-indolyl; R = Et (1); n-Bu (2); Cy (3); Ph (4)], were synthesized and characterized by elemental analysis and IR, NMR (1H,
13C and 119Sn) spectra. The crystal structures of complexes 1–3 were determined by X-ray single crystal diffraction. The tin
atom is five-coordinated and its coordination geometry is best described as an intermediate between trigonal bipyramidal and
square pyramidal. Intermolecular weak interactions in the complexes 1–3 connect molecules into a one-dimensional helical
chain and a two-dimensional array. The dibutyltin complex 2 has potent in vitro cytotoxic activity against two human tumor cell
c
lines, CoLo205 and Bcap37, while the diethyltin complex 1 displays weak cytotoxic activity. Copyright ꢀ 2011 John Wiley &
Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: organotin complex; tryptophane; cytotoxic activity; crystal structure
Introduction
Experimental
Materials and Physical Measurements
In recent years, a considerable interest in organotin carboxylates
has emerged due to their structural diversity[1,2] and biological
properties, particularly cytotoxicity activity.[3–5] N-Salicylidene-α-
amino acid derived from salicylaldehyde and amino acid is a
very versatile ligand having a variety of coordination modes
and its metal complexes have been extensively studied.[6,7]
Some organotin complexes of the ligand have been reported
by several groups.[8–14] Structural studies have shown that the
diorganotin complexes adopt isolated monomeric structures
with the tin atom in a distorted trigonal bipyramid and the
dimeric, trimeric and polymeric structures with the tin atom
in a distorted octahedron or a distorted pentagonal bipyramid
in solid state.[8–14] Bioassay studies showed that the diorgan-
otin complexes possess significant cytotoxic activity against
some human tumor cell lines.[10,11,14] In general, the toxicity
of organotin compounds seems to increase with the chain
length of the organic alkyl groups, which are often more ac-
tive than aryl ones. The organotin moiety, the ligand and
the number of tin atoms appear to play an important role
in determining their cytotoxicity activity.[3–5] In order to con-
tinue to expand the chemistry and therapeutic potential of the
diorganotin(IV) complexes of the ligands, recently we synthe-
sized and characterized some diorganotin(IV) complexes with
N-(halosalicylidene)-α-amino acid.[15–18] As a continuation of our
work,hereweselectedN-(3,5-dibromosalicylidene)tryptophaneas
a ligand, synthesized four new diorganotin complexes, R2Sn[3,5-
Br2-2-OC6H2CH NCH(CH2Ind)COO] [Ind = 3-indolyl; R = Et (1);
n-Bu (2); Cy (3); Ph (4); Scheme 1], and determined their cytotoxic
activity.
The chemicals were of reagent grade and were used without
further purification. Carbon, hydrogen and nitrogen analyses were
obtained using a Perkin Elmer 2400 Series II elemental analyzer.
The melting points were measured on a WRS-1A digital melting
point apparatus. IR spectra were recorded on a Nicolet 470 FT-IR
spectrophotometer using KBr disks in the range 4000–400 cm−1
.
1Hand13CNMRspectraldatawerecollectedusingaBrukerAvance
DMX500 FT-NMR spectrometer with CDCl3 or D2O as solvent and
TMS as internal standard. 119Sn NMR spectra were recorded in
CDCl3 on a Varian Mercury Vx300 spectrometer using Me4Sn
external reference.
Synthesis of Potassium N-(3,5-dibromosalicylidene)
tryptophanate
At room temperature, potassium hydroxide (0.11 g, 2 mmol) and
L-tryptophane (0.41 g, 2 mmol) were added in methanol (60 ml),
and a methanolic solution (20 ml) of 3,5-dibromosalicylaldehyde
(0.56 g, 2 mmol) was added dropwise under stirring. The stirring
was continued for 30 min at 60 ◦C. The yellow solution obtained
was concentrated to about 15 ml under reduced pressure, and
∗
Correspondence to: Laijin Tian, Department of Chemistry, Qufu Normal
University, Qufu 273165, China. E-mail: laijintian@163.com
a
Department of Chemistry, Qufu Normal University, Qufu 273165, China.
b
Institute of Materia Medica, Zhejiang Academy of Medical Science, Hangzhou
310013, China
c
Appl. Organometal. Chem. 2011, 25, 298–304
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

New diorganotin(IV) complexes of N-(3,5-dibromosalicylidene)tryptophane
Scheme 1. Synthetic route of compounds 1–4.
then 60 ml anhydrous diethylether was slowly added. The yellow
precipitates afforded were filtered out and recrystallized from
anhydrous ethanol. The yield of product was 0.70 g (69.4%) after
drying for 24 h in vacuum. M.p. 196 ◦C (dec.). Anal. calcd for
C18H13Br2KN2O3: C 42.88, H 2.60, N 5.56; found: C 42.62, H 2.69, N
5.45%. IR (KBr) cm−1: 3407 (broad, O–H), 3219 (broad, N–H), 1633
[broad, (COO)as + C N], 1357 [(COO)s], 1212 (Ph–O). 1H NMR
(D2O) δ: 2.90 (dd, 3J = 10.0 Hz, 2J = 14.2 Hz, 1H, Ha-10), 3.71 (dd,
3J = 3.2 Hz, 2J = 14.2 Hz, 1H, Hb-10), 4.06 (dd, 3J = 3.2, 10.0 Hz,
1H, H-2), 6.60 (d, 4J = 2.4 Hz, 1H, H-9), 6.77 (s, 1H, H-12), 6.89 (s, 1H,
H-3), 7.05 (dd, 3J = 7.5, 8.0 Hz, 1H, H-16), 7.19 (dd, 3J = 7.5, 8.0 Hz,
1H, H-15), 7.38 (d, 3J = 8.0 Hz, 1H, H-14), 7.62 (d, 3J = 8.0 Hz, 1H,
H-17), 7.72 (d, 4J = 2.4 Hz, 1H, H-7), 8.36 (s, 1H, NH), 12.39 (s, 1H,
OH) ppm.
n-Bu2Sn[3,5-Br2-2-OC6H2CH NCH(CH2Ind)COO] (2)
Yield 65%, m.p. 205–206 ◦C, Anal. calcd for C26H30Br2N2O3Sn: C
44.80, H 4.34, N 4.02; found: C 44.82, H 4.19, N 3.86%. IR (KBr) cm−1
:
3240 (N–H), 1664 [(COO)as], 1610 (C N), 1344 [(COO)s], 1293
(Ph–O), 558 (Sn–O). 1H NMR (CDCl3) δ: 0.82 (t, 3J = 7.3 Hz,
3H, CH3), 0.96 (t, 3J = 7.3 Hz, 3H, CH3), 1.24–1.74 (m, 12H,
2CH2CH2CH2Sn), 3.01 (dd, 3J = 10.0 Hz, 2J = 14.7 Hz, 1H, Ha-10),
3.81 (dd, 3J = 3.1 Hz, 2J = 14.7 Hz, 1H, Hb-10), 4.24 [dd, 3J = 3.1,
3
4
10.0 Hz, J(119Sn–1H) = 36 Hz, 1H, H-2], 6.63 (d, J = 2.4 Hz, 1H,
H-9), 6.87 (s, 1H, H-12), 7.08 [s, 3J(119Sn–1H) = 47 Hz, 1H, H-3], 7.11
(dd, 3J = 7.5, 8.0 Hz, 1H, H-16), 7.23 (dd, 3J = 7.5, 8.0 Hz, 1H, H-15),
7.43 (d, 3J = 8.0 Hz, 1H, H-14), 7.61 (d, 3J = 8.0 Hz, 1H, H-17),
4
7.74 (d, J = 2.4 Hz, 1H, H-7), 8.51 (s, 1H, NH) ppm. 119Sn NMR
(CDCl3) δ: −196.2 ppm. 13C NMR (CDCl3) δ: 173.77 (C-1), 170.70
(C-3), 163.47 (C-5), 141.66 (C-7), 136.77 (C-13), 135.89 (C-9), 126.61
(C-18), 124.95 (C-12), 123.01 (C-15), 120.47 (C-16), 118.65 (C-4),
118.14 (C-6), 118.12 (C-17), 112.04 (C-14), 108.87 (C-11), 107.22 (C-
8), 69.26 (C-2), 32.58 (C-10), 27.03 [2J(119Sn–13C) = 26 Hz, CH2-β],
26.84[2J(119Sn–13C)=24 Hz,CH2-β],26.79[3J(119Sn–13C)=96 Hz,
CH2-γ ], 26.70 [3J(119Sn–13C) = 90 Hz, CH2-γ ], 22.56 [1J(119Sn–13C)
= 605 Hz, CH2-α], 22.36 [1J(119Sn–13C) = 589 Hz, CH2-α], 13.83
(CH3), 13.65 (CH3) ppm.
Synthesis of the Complexes 1–4
Amethanolsolution(15 ml)ofdiorganotindichloride(2 mmol)and
Et3N (0.20 g, 2 mmol) was added drop-wise to a methanol solution
(25 ml) of potassium N-(3,5-dibromosalicylidene)tryptophanate
(1.08 g, 2 mmol) under stirring. The reaction mixture was heated
under reflux for 2 h, and the solvent was then removed
using a rotary evaporator. The residues was redissolved in
trichloromethane and filtered after washed by using hot hexane. A
yellow product was obtained by removal of solvent under reduced
pressure, and recrystallized from methanol and dried in vacuum.
Cy2Sn[3,5-Br2-2-OC6H2CH NCH(CH2Ind)COO] (3)
Yield 74%, m.p. 237.3–238.2 ◦C. Anal. calcd for C30H34Br2N2O3Sn:
C 48.10, H 4.57, N 3.74; found: C 48.01, H 4.36, N 3.62%. IR (KBr)
cm−1: 3240 (N–H), 1656 [(COO)as], 1619 (C N), 1352 [(COO)s],
1
1301 (Ph–O), 540 (Sn–O). H NMR (CDCl3) δ: 1.28–2.13 (m, 22H,
Et2Sn[3,5-Br2-2-OC6H2CH NCH(CH2Ind)COO] (1)
3
2
2Cy), 3.00 (dd, J = 10.0 Hz, J = 14.7 Hz, 1H, Ha-10), 3.83 (dd,
3J = 3.2 Hz, 2J = 14.7 Hz, 1H, Hb-10), 4.23 (dd, 3J = 3.2, 10.0 Hz,
3J (119Sn–1H) = 39 Hz, 1H, H-2), 6.57 (d, 4J = 2.4 Hz, 1H, H-9),
6.85 (s, 1H, H-12), 7.02 [s, 3J(119Sn–1H) = 41 Hz, 1H, H-3], 7.12 (dd,
Yield 63%, m.p. 222–224 ◦C. Anal. calcd for C22H22Br2N2O3Sn: C
41.23, H 3.46, N 4.37; found: C 41.02, H 3.39, N 4.34%. IR (KBr)
cm−1: 3234 (N–H), 1658 [(COO)as], 1606 (C N), 1351 [(COO)s],
1301 (Ph–O), 559 (Sn–O). 1H NMR (CDCl3) δ: 1.08 [t, 3J = 8.0 Hz,
3J(119Sn–1H) = 133 Hz, 3H, CH3], 1.28–1.40 (m, 7H, CH3 +2CH2Sn),
2.93 (dd, 3J = 10.0 Hz, 2J = 14.4 Hz, 1H, Ha-10), 3.77 (dd,
3J = 3.0 Hz, 2J = 14.4 Hz, 1H, Hb-10), 4.18 [dd, 3J = 3.0, 10.0 Hz,
3J(119Sn–1H) = 44 Hz, 1H, H-2], 6.55 (d, 4J = 2.4 Hz, 1H, H-9), 6.81
(s, 1H, H-12), 6.99 [s, 3J(119Sn–1H) = 46 Hz, 1H, H-3], 7.07 (dd,
3
3J = 7.5, 7.9 Hz, 1H, H-16), 7.24 (dd, J = 7.5, 8.1 Hz, 1H, H-15),
7.43 (d, 3J = 8.1 Hz, 1H, H-14), 7.62 (d, 3J = 7.9 Hz, 1H, H-17),
7.74 (d, 4J = 2.4 Hz, 1H, H-7), 8.39 (s, 1H, NH). 119Sn NMR (CDCl3)
δ: −265.2 ppm. 13C NMR (CDCl3) δ: 173.72 (C-1), 170.67 (C-3),
163.69 (C-5), 141.88 (C-7), 136.28 (C-13), 135.86 (C-9), 126.67 (C-
18), 124.88 (C-12), 122.99 (C-15), 120.45 (C-16), 118.80 (C-4), 118.54
(C-6), 118.42 (C-17), 112.06 (C-14), 108.89 (C-11), 107.58 (C-8), 69.21
(C-2), 41.58 [1J(119Sn–13C) = 562 Hz, CH-α], 39.94 [1J(119Sn–13C)
= 554 Hz, CH-α], 32.52 (C-10), 30.34 [2J(119Sn–13C) = 20 Hz, CH2-
β], 30.18 [2J(119Sn–13C) = 21 Hz, CH2-β], 28.84 [3J(119Sn–13C) =
88 Hz, CH2-γ ], 28.62 [3J(119Sn–13C) = 87 Hz, CH2-γ ], 26.74 (CH2-δ),
26.56 (CH2-δ) ppm.
3
3J = 7.5, 8.0 Hz, 1H, H-16), 7.20 (dd, J = 7.5, 8.0 Hz, 1H, H-15),
7.36 (d, 3J = 8.0 Hz, 1H, H-14), 7.59 (d, 3J = 8.0 Hz, 1H, H-17), 7.69
(d, 4J = 2.4 Hz, 1H, H-7), 8.14 (s, 1H, NH) ppm. 119Sn NMR (CDCl3)
δ: −192.8 ppm. 13C NMR (CDCl3) δ: 173.45 (C-1), 170.62 (C-3),
163.49 (C-5), 141.54 (C-7), 136.55 (C-13), 135.72 (C-9), 126.39 (C-
18), 124.71 (C-12), 122.89 (C-15), 120.42 (C-16), 118.55 (C-4), 118.14
(C-6), 117.95 (C-17), 111.78 (C-14), 108.88 (C-11), 107.06 (C-8), 68.99
(C-2), 32.37 (C-10), 14.36 [1J(119Sn–13C) = 600 Hz, CH2Sn], 14.05
[1J(119Sn–13C)=590 Hz,CH2Sn],9.55[2J(119Sn–13C)=30 Hz,CH3],
9.25 [2J(119Sn–13C) = 29 Hz, CH3] ppm.
Ph2Sn[3,5-Br2-2-OC6H2CH NCH(CH2Ind)COO] (4)
Yield 68%, m.p. 226.6–227.3 ◦C. Anal. calcd for C30H22Br2N2O3Sn:
C 48.89, H 3.01, N 3.80; found: C 48.66, H 2.93, N 3.56%. IR (KBr)
c
Appl. Organometal. Chem. 2011, 25, 298–304
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Tian et al.
Table 1. Crystallographic and refinement data for 1, 2 and 3
Compound
1
2
3
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C45H48Br4N4O7Sn2
C26H30Br2N3O3Sn
697.03
C30H34Br2N2O3Sn
749.10
1313.89
Orthorhombic
Monoclinic
P21/c
Monoclinic
C/2c
P212121
12.240(6)
17.8130(12)
10.2490(8)
17.9830(10)
115.425(2)
2965.1(3)
4
34.237(2)
10.7326(12)
18.0908(17)
105.114(2)
6417.6(10)
8
b (Å)
14.301(6)
c (Å)
27.549(12)
β (deg)
Volume (Å3)
90
4822(4)
Z
4
Dc (g cm−3
)
1.810
1.561
1.551
µ (mm−1
)
4.402
3.584
3.317
F(000)
2568
1376
2976
Crystal size (mm)
Total reflections
0.42 × 0.39 × 0.33
0.17 × 0.12 × 0.02
27 691
0.40 × 0.20 × 0.10
22 762
37 816
Unique reflections
Reflections with I > 2σ(I)
GOF on F2
9467
5508
5812
6827
2441
2707
0.973
0.961
1.016
R indices [I > 2σ(I)]
R indices (all data)
CCDC deposition no.
R = 0.047, wR = 0.086
R = 0.080, wR = 0.097
784 287
R = 0.065, wR = 0.172
R = 0.145, wR = 0.214
784 288
R = 0.070, wR = 0.184
R = 0.121, wR = 0.234
784 289
cm−1: 3215 (N–H), 1671 [(COO)as], 1605 (C N), 1350 [(COO)s],
1299 (Ph–O), 565 (Sn–O). 1H NMR (CDCl3) δ: 2.82 (dd, 3J = 10.5 Hz,
2J = 14.6 Hz, 1H, Ha-10), 3.72 (dd, 3J = 3.2 Hz, 2J = 14.6 Hz, 1H,
Hb-10), 4.28 [dd, 3J = 3.2, 10.5 Hz, 3J (119Sn–1H) = 46 Hz, 1H, H-2],
6.54(d, 4J = 2.3 Hz, 1H, H-9), 6.77(s, 1H, H-12), 6.93[s, 3J(119Sn–1H)
placed at calculated positions in the riding model approximation.
The absolute structure of complex 1 was determined from the
configuration of the ligand L-tryptophane and confirmed by the
X-ray study with 4207 Friedel pairs.[21] The Flack parameter is
−0.001(10). In the complex 1, the C(2A) and C(4A) atoms of two
ethyl groups are disordered over two positions, and their site
occupancies were refined to 0.804(14):0.196(14) for C(2A)/C(2Aꢁ)
and 0.551(12):0.449(12) for C(4A)/C(4Aꢁ). In the complex 2, the
two n-butyl groups are disordered over two positions, and their
site occupancies were refined to 0.557(16):0.443(16) for C(2)-
C(4) and 0.710(13):0.290(13) for C(6)-C(8). In addition, these C
atoms are refined using the pseudo-isotropic ‘ISOR’ restraint as
the free refinement gave unrealistic anisotropic displacement
parameters. For the structure of the complex 3, one cyclohexyl
group [C(7)–C(12)] is also treated similarly and the site occupancy
factorsoftwopartsis0.507(17)and0.493(17). Inaddition, owingto
serious disorder problems of the solvent molecules, we were not
abletowelldefinethem. Therefore, aSQUEEZE/PLATONtechnique
was applied.[22] The estimated volume of the void per unit cell
is 125.0 Å3. Molecular graphics of the compounds were drawn
with the program package XP.[19] Crystallographic parameters and
refinements of the complexes 1–3 are listed in Table 1.
3
= 58 Hz, 1H, H-3], 7.04 (dd, J = 7.5, 7.9 Hz, 1H, H-16), 7.16 (dd,
3J = 7.5,8.2 Hz,1H,H-15),7.29(d,3J = 8.2 Hz,1H,H-14),7.36–7.38
(m, 3H, m- and p-H in Ph), 7.45 (d, 3J = 7.9 Hz, 1H, H-17), 7.50–7.53
(m, 3H, m- and p-H in Ph), 7.80–7.82 [m, 2H, 3J (119Sn–1H) = 88 Hz,
o-H in Ph], 7.83 (d, 4J = 2.3 Hz, 1H, H-7), 7.99–8.01 [m, 2H, 3J
(
119Sn–1H) = 87 Hz, o-H in Ph], 8.14 (s, 1H, NH) ppm. 119Sn NMR
(CDCl3) δ: −335.7 ppm. 13C NMR (CDCl3) δ: 172.74 (C-1), 171.59
(C-3), 163.67 (C-5), 142.36 (C-7), 137.46 [1J(119Sn–13C) = 986 Hz,
i-C], 137.39 [1J(119Sn–13C) = 978 Hz, i-C], 136.87 [2J(119Sn–13C)
= 58 Hz, o-C], 136.72 (C-13), 136.51 [2J(119Sn–13C) = 59 Hz,
o-C], 136.36 (C-9), 131.31 [4J(119Sn–13C) = 18 Hz, p-C], 131.16
[4J(119Sn–13C) = 16 Hz, p-C], 129.36 [3J(119Sn–13C) = 90 Hz, m-C],
129.27 [3J(119Sn–13C) = 86 Hz, m-C], 126.71 (C-18), 124.87 (C-12),
122.96 (C-15), 120.45 (C-16), 118.90 (C-4), 118.80 (C-6), 118.67 (C-
17), 112.01 (C-14), 109.12 (C-11), 108.61 (C-8), 69.31 (C-2), 32.80
(C-10) ppm.
X-ray Crystallography
In Vitro Cytotoxicity
Yellow single crystals of complexes 1, 2 and 3 were obtained
from the slow evaporation of methanol solution of the respective
compounds. Intensity data for the crystals were measured at
295(2) K on a Bruker Smart Apex area-detector fitted with graphite
monochromatized Mo-Kα radiation (0.71073 Å) using the ϕ and
ω scan technique. The data reductions were performed using
SAINT program and empirical corrections for absorption effects
were made using the SADABS program.[19] The structures were
solved by direct-methods and refined by a full-matrix least squares
procedure based on F2 using SHELX-97.[20] The non-hydrogen
atoms were refined anisotropically and hydrogen atoms were
Cytotoxic activity was assayed against two human tumor cell lines,
CoLo205(coloncarcinomacell)andBcap37(mammarytumorcell).
The samples were prepared by dissolving the test compounds in
DMSO, and by diluting the resultant solutions with water. In the
assays, the final concentration of DMSO was less than 0.1% (the
concentration used was found to be non-cytotoxic against tumor
cells.). In vitro cytotoxic activity of the compounds were measured
by the MTT assay according to the literature.[23] All cells cultured in
DMEM (Dulbecco’s modified Eagle medium) supplemented with
10% heat-inactivated new-born calf serum at 37 ◦C in a humidified
c
wileyonlinelibrary.com/journal/aoc
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 298–304

New diorganotin(IV) complexes of N-(3,5-dibromosalicylidene)tryptophane
5% CO2 incubator and were seeded into each well of 96-well plate
Table 2. Selected bond lengths (Å) and angles (deg) for 1,2 and 3
andwerefixedfor24 h. Thefollowingday, differentconcentrations
of the test compounds were added. After incubation with various
concentrations of test compounds for 72 h, the inhibition on cell
proliferation was measured. The experiments were conducted in
triplicate for each tested concentration. The dose causing 50%
inhibition of cell growth (IC50) was calculated by NDST software as
previously described.[24]
1A
1B
2
3
Bond lengths
Sn(1)–C(1)
2.118(8)
2.114(7)
2.142(5)
2.191(5)
2.197(6)
2.114(7)
2.092(8)
2.099(5)
2.240(5)
2.232(6)
2.112(13)
2.17(2)
Sn(1)–C(a)a
2.095(11) 2.178(17)
Sn(1)–O(1)
2.071(6)
2.150(8)
2.158(6)
2.103(12)
2.151(12)
2.176(13)
Sn(1)–O(2)
Sn(1)–N(1)
Bond angles
Results and Discussion
C(a)–Sn(1)–O(1)
C(a)–Sn(1)–C(1)
O(1)–Sn(1)–C(1)
C(a)–Sn(1)–N(1)
O(1)–Sn(1)–N(1)
C(1)–Sn(1)–N(1)
C(a)–Sn(1)–O(2)
89.2(3)
141.8(3)
93.5(3)
96.0(3)
146.9(3)
97.0(2)
95.1(5)
130.1(5)
97.3(5)
117.6(4)
83.7(2)
111.7(5)
88.0(5)
157.5(3)
97.6(5)
75.1(2)
93.4(8)
136.8(8)
94.7(6)
107.4(7)
83.6(5)
115.6(5)
98.2(8)
158.1(5)
89.5(6)
75.2(4)
The complexes 1–4 were prepared by the reaction of diorgan-
otin dichloride with potassium N-(3,5-dibromosalicylidene)
tryptophanate formed from condensation of 3,5-dibromosali-
cylaldehyde and L-tryptophane in the presence of KOH in good
yield (Scheme 1). The complexes are yellow crystalline solids that
are soluble in common organic solvents such as benzene, chloro-
form, methanol, acetone and tetrahydrofuran.
111.6(3)
79.11(19)
106.3(3)
97.2(3)
104.0(3)
81.36(19)
108.0(2)
89.0(3)
O(1)–Sn(1)–O(2) 151.72(19) 153.70(19)
C(1)–Sn(1)–O(2)
N(1)–Sn(1)–O(2)
98.1(3)
92.6(3)
72.91(19)
72.39(19)
IR Spectra
a a = 3, 5 and 7 for 1, 2 and 3, respectively.
The complexes 1–4 did not show the ν (OH) band at
3300–3500 cm−1, indicating the deprotonation of the pheno-
lic oxygens of the ligand due to the formation of the oxygen tin
bond. This is further proved by the appearance of a sharp band at
∼560 cm−1, assignable to the Sn–O stretching vibration.[11,25] The
NH stretching vibration of indolyl in the tryptophane fragment as
a medium strong band lies in the range of 3215–3240 cm−1. In all
complexes, the ν (C N) absorption, appearing as a strong band
at ∼1610 cm−1, is shifted towards lower frequencies with respect
to that of the free ligand (1633 cm−1), confirming the coordina-
tion of the azomethine nitrogen to diorganotin moiety (C N →
Sn).[8,26] The stretching frequencies of carboxylate have been used
to distinguish the coordination mode of the carboxylate group
and to identify the nature of bonding[27,28] as the ν [νas(CO2)
− νs(CO2)]valueisbelow200 cm−1 forbidentatecoordinationand
above 200 cm−1 for the unidentate coordination. The difference
between the νas(CO2) and νs(CO2) bands in the complexes 1–4
is in the range of 304–321 cm−1, indicating an unidentate car-
boxylate moiety. Thus, it is concluded that the compounds feature
five-coordinated tin in the solid, consistent with the below X-ray
structural analysis.
imine carbon (C-3) are at ca 174 and 171 ppm, respectively, and
the singles of C-5 appear at ∼163 ppm due to phenolic O–Sn
bond formation.
In the complexes 1–4, the coupling between tin nuclear and
carbon can be observed, and the 1J(119Sn–13C) is in the range
605–554 Hz in the complexes 1–3 and 986 and 978 Hz in 4.
According to the equation, 1J(119Sn–13C) = 9.99 ( 0.73) θ − 746
( 100)[31] and 1J(119Sn–13C) = 15.56 ( 0.84) θ − 1160 ( 101),[32]
the calculated value of the C–Sn–C angle (θ) from 1J(119Sn–13C)
is 137.9–130.1◦ for the complexes 1–4, suggesting that the tin
atom has a distorted trigonal bipyramid geometry in the non-
coordinating solvents, this behavior is in agreement with the
values reported for pentacoodinated tin compounds.[12,31,32] The
complexes 1–4 display two sets of 1H and 13C NMR signals from
the Sn–R groups (R = Et, n-Bu, Cy, and Ph) indicating that the two R
groups experience different environments on the NMR time scale
due to the presence of a stereogenic carbon in the ligand.[12,14]
The 119Sn chemical shifts primarily depend on the coordination
number and the nature of the donor atom directly bonded to the
central tin atom.[33] The 119Sn chemical shifts of the complexes
1–4 are at −192.8, −196.2, −265.2 and −335.7 ppm, further
confirming a five-coordinated tin structure in solution.[12,31–33]
NMR Spectra
The 1H and 13C chemical shift assignments of the compounds
are straightforward from the multiplicity patterns and resonance
intensities, and are consistent with the literature.[12,29,30] The NH
proton of the indole ring appears as a broad singlet in the range
of δ 8.14–8.51 ppm. The signals assigned to azomethine proton
Crystal Structures of Complexes 1–3
The molecular structures of complexes 1–3 are shown in Figs 1, 3
and 4, respectively, and the selected geometric parameters are
given in Table 2. Complex 1 crystallizes in orthorhombic chiral
spacegroup P212121. Theasymmetricunitcontainstwomolecules
of the mononuclear organotin complex which are labeled as
molecules 1A and 1B, respectively, and one solvent CH3OH
molecule (Fig. 1). In the complex 1, the tin atom is five-coordinated
and the five coordination atoms come from two carbons [C(1) and
C(3)]ofethylgroups, anN(1)atom, aphenolicO(1)andacarboxylic
O(2)atomoftheligand.Itscoordinationgeometryisbestdescribed
as an intermediate geometry[34] between trigonal bipyramidal
and square pyramidal with the bond angles O(1)–Sn(1)–O(2)
of 151.72(19) and 153.70(19)◦. This is quantified by the value
N
CH(H-3)andaromaticprotonH-9lieintherange6.93–7.08and
6.54–6.63 ppm, respectively, which is shifted to lower frequencies
compared with the general chemical shift value of N CH proton
(δ ∼ 8.25) and aromatic proton (δ ∼ 7.35) owing to the shielding
effect of the phenyl ring in the indole on the H-3 and H-9.[12,16] The
appearanceofspin-spincouplingbetweentheazomethineproton
and the tin nucleus [3J(119Sn–1H) = 41–58 Hz] further confirms
the presence of nitrogen-tin coordination in all complexes. The
CH–N (H-2) proton exhibits a doublet of doublets at about δ
4.23 ppm and the 3J(119Sn–1H) coupling constants for H-2 are in
the range 36–46 Hz. The signals of the carboxyl carbon (C-1) and
c
Appl. Organometal. Chem. 2011, 25, 298–304
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Tian et al.
Figure 1. The molecular structure of 1; hydrogen atoms are omitted for clarity.
· · ·
· · ·
· · ·
Figure 2. The helical chain formed by the intermolecular N–H O and O–H O hydrogen-bonding interactions and Sn O interactions between
adjacent molecules. Ethyl group on the tin and all hydrogen atoms except those involved in hydrogen bonding have been omitted for clarity.
of τ (τ = 0.17 for 1A and 0.11 for 1B), which compares with
τ = 0.00 for an ideal square pyramid and τ = 1.00 for an ideal
trigonal bipyramid.[34] Tin atom forms a five-membered and a six-
membered chelate ring with the tridentate ligand. The two chelate
rings both are non-planar. The five-membered rings formed by the
N(1)–C(12)–C(13)–O(2)–Sn(1) fragments in 1A and 1B have the
C(12) atoms out of the mean planes by 0.215(7) and 0.172 (7) Å,
respectively. With respect to the six-membered rings defined by
the N(1)–C(11)–C(10)–C(5)–O(1)–Sn(1) fragments, the maximum
deviations from the mean planes at C(10) atoms are 0.472(7) and
0.303(7) Å, respectively.
tances are considerably longer than a normal O → Sn coordination
bond (∼2.40 Å),[10] but much shorter than the sum of the van
der Waals radii of these atoms (3.77 Å).[35] It is shown that the
carboxylate O(2) atoms make weak contacts with the Sn(1)
atom between 1A and 1B and there is a weak contact between
O(4) atom of methanol and Sn(1B) of 1B. 1A and 1B form a
· · ·
weak-bridged dimer through these Sn O weak interactions and
· · ·
· · ·
· · ·
O(4)–H(4) O(3A) [O(4) O(3A) 2.662(9) Å, O(4)–H(4) O(3A)
139.3◦] hydrogen bonds involving the methanol O–H and
carbonyl O atom of 1A. The major stereochemical role of the
O(2A), O(2B) and O(4) atoms are to distort the trigonal bipyramid
geometry by opening up the C(1)–Sn(1)–C(3) angle [141.8(3) and
146.9(3)◦] with concomitant reduction of the C(1)–Sn(1)–N(1)
[106.3(3) and 108.0(2)◦] and C(3)–Sn(1)–N(1) [111.6(3) and
104.0(3)◦] angles. The weak-bridged dimer is further connected
The Sn(1)–O(1) (2.142(5) and 2.099(5) Å) and Sn(1)–O(2)
(2.191(5) and 2.240(5) Å) bond distances are consistent with
those found in the analogs Bu2Sn[OC6H4CH NCH(CH2Ind)
COO]
[2.093(3)
and
2.162(3) Å]
and
Et2Sn[5-Cl-2-
OC6H3CH NCH(CH2Ind)COO][2.1022(16)and2.1754(15) Å].[13,18]
intoinfinitehelicalchainbytheintermolecularN–H Ohydrogen
· · ·
The bond angles O(1)–Sn(1)–O(2) [151.72(19) and 153.70(19)◦] in
bonds involving the indolyl N(2A)–H(2A) of 1A and carbonyl
O(3B)#1 atom (symmetry code #1: −x + 2, y − 1/2, −z + 1/2) of
the complex 1 are slightly smaller than those of above two analogs
◦
[158.75(11)◦ and 158.33(6) ]. The Sn(1A) O(2B) [2.889(5) Å],
the adjacent 1B [N(2A) O(3B) 2.81(1) Å, N(2A)-H(2A) O(3B)
#1
#1
· · ·
· · ·
· · ·
Sn(1B) O(2A) [3.114(5) Å] and Sn(1A) O(4) [3.004(8) Å] dis-
162.2◦] (Fig. 2).
· · ·
· · ·
c
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc
Appl. Organometal. Chem. 2011, 25, 298–304

New diorganotin(IV) complexes of N-(3,5-dibromosalicylidene)tryptophane
In Vitro Cytotoxicity
The results of the cytotoxic assay against CoLo205 and Bcap37
are shown in Table 3. The dibutyltin complex 2 displayed the
potent in vitro activity, while the diethyltin complex 1 has low
activity. The cytotoxicity against the two cell lines of complex 2
is similar to those of our previous reported dibutyltin analogs
Bu2Sn[5-Cl-2-OC6H3CH NCH(CH2Ind)COO] and Bu2Sn[5-Br-2-
OC6H3CH NCH(CH2Ind)COO].[18] The dibutyltin complex of (2-
hydroxynaphthalidene)glycine, Bu2Sn(2-OC10H6CH NCH2COO),
reported by Nath et al.,[11] showed quite promising cytotox-
icity – the IC50 values against cancer cell lines MCF-7, EVSA-
T, WiDr, IGROV and MI9 are 0.075, 0.035, 0.480, 0.075,
and 0.090 µg ml−1, respectively. More recently, R2Sn[5-MeO-2-
OC6H3CH NCH(CH2Ph)COO] (R = Bu, Ph) also exhibits a high
activity against MCF-7 (IC50 0.0700 and 0.0512 µg ml−1). Thus,
further structure modification of diorganotin compounds of the
Schiff base derived from α-amino acid are valuable for enhancing
cytotoxicity.
Figure 3. The molecular structure of 2; hydrogen atoms are omitted for
clarity.
Conclusions
As shown in Figs 3 and 4, the tin atoms of complexes 2 and
3 are five-coordinated and the coordination geometry is also an
intermediate geometry between trigonal bipyramidal and square
pyramidal with the τ = 0.46 for 2 and τ = 0.36 for 3.[34] The
bond angles and bond distances around tin atom are comparable
to those observed in the related dibutyltin and dicyclohexyltin
complexes such as Bu2Sn[OC6H4CH NCH(CH2Ind)COO],[13] and
Cy2Sn[3,5-Br2-2-OC6H4CH NCH(CH2Ph)COO].[17] However, the
C–Sn–C angles are different from that of complex 1 (Table 2)
since there are no intermolecular Sn and O weak interactions in
the complexes 2 and 3. Complexes 2 and 3 are linked into two-
In summary, four new diorganotin(IV) complexes of N-(3,5-
dibromosalicylidene)tryptophane have been synthesized by
the reaction of diorganotin dichloride with potassium N-(3,5-
dibromosalicylidene)tryptophanate derived from condensation
of 3,5-dibromosalicylaldehyde and L-tryptophane in the presence
of KOH in good yield. The X-ray single crystal diffraction analysis
reveals that intermolecular weak interactions in the complexes
1–3 link molecules into a one-dimensional helical chain and a
two-dimensional array, respectively. The dibutyltin complex 2 has
potent in vitro cytotoxic activity against two human tumor cell
lines, CoLo205 and Bcap37, while the diethyltin complex 1 dis-
plays weak cytotoxic activity. Further structure modification and
optimization of these diorganotin complexes are necessary.
· · ·
dimensional arrays through intermolecular N–H O hydrogen
bonds involving the hydrogen atom on N(2) of indolyl and O(3)#1
#1
#1
· · ·
· · ·
atom◦ of carbonyl [N(2) O(3) 2.77(1) Å, N(2)–H(2) O(3)
◦
155.9 for 2 and N(2) O(3) 2.79(2) Å, N(2)–H(2) O(3)#1 155.9
for 3, symmetry code #1: x, 11/2 − y, 1/2 + z] and π –π stacking
interactions between phenyl rings from indolyl and salicylidene
with the centroid-centroid separations of 3.690 (2) Å in 2 and
3.805(2) Å in 3 (Fig. 5).
#1
· · ·
· · ·
Supporting information
Supporting information may be found in the online version of this
article.
C15
Br1
Br2
C16
C2
C14
C13
C3
C17
C18
C1
O1
C4
C19
Sn1
O2
C26
C27
C12
N1
N2
C25
C30
C5
C6
C24
C11
C20
C28
C10
C9
C7
C29
C8
C23
C21
C22
O3
Figure 4. The molecular structure of 3; hydrogen atoms are omitted for clarity.
c
Appl. Organometal. Chem. 2011, 25, 298–304
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Tian et al.
· · ·
Figure 5. The 2D array formed by intermolecular N–H O hydrogen bonds and π –π stacking interactions between phenyl rings; hydrogen atoms
except H2 are omitted for clarity.
[11] M. Nath, R. Yadav, M. Gielen, H. Dalil, D. de Vos, G. Eng, Appl.
Table 3. Cytotoxic activity [IC50 (µg ml−1)] of compounds
Organomet. Chem. 1997, 11, 727.
[12] H. I. Beltran, L. S. Zamudio-Rivera, T. Mancilla, R. Santillan, N. Farfan,
Compound
CoLo205
Bcap37
Chem. Eur. J. 2003, 9, 2291.
[13] H. Yin, Q. Wang, S. Xue, J. Organomet. Chem. 2004, 689, 2480.
[14] N. Kobakhidze, N. Farfan, M. Romero, J. M. Mendez-Stivalet,
M. G. Ballinas-Lopez, H. Garcia-Ortega, O. Dominguez, R. Santillan,
F. Sanchez-Bartez, I. Gracia-Mora, J. Organomet. Chem. 2010, 695,
1189.
1
>10
7.61 1.75
0.22 0.09
1.02 0.10
1.78 0.25
2
0.51 0.05
2.69 0.69
4.12 0.12
4
cis-Platin
[15] L. Tian, B. Qian, Y. Sun, X. Zheng, M. Yang, H. Li, X. Liu, Appl.
Organomet. Chem. 2005, 19, 980.
[16] L. Tian, Z. Shang, X. Zheng, Y. Sun, Y. Yu, B. Qian, X. Liu, Appl.
Organomet. Chem. 2006, 20, 74.
[17] L. Tian, Y. Sun, X. Zheng, X. Liu, Y. Yu, X. Liu, B. Qian, Chin. J. Chem.
2007, 25, 312.
[18] L. Tian, H. Yang, X. Zheng, Z. Ni, D. Yan. L. Tu, J. Jiang, Appl.
Organomet. Chem. 2009, 23, 24.
[19] Bruker, SAINT, SADABS and XP. Bruker AXS Inc., Madison, WI, 2002.
[20] G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112.
[21] H. D. Flack, Acta Crystallogr. 1983, A39, 876.
[22] A. L. Spek, J. Appl. Crystallogr. 2003, 36, 7.
[23] F. Denizot, R. Lang, J. Immunol. Meth. 1986, 89, 271.
[24] X.-L. Zheng, H.-X. Sun, X.-L. Liu, Y.-X. Chen, B.-C. Qian, Acta
Pharmacol. Sin. 2004, 25, 109.
[25] V. G. Kumar Das, N. S. Weng, P. J. Smith, Inorg. Chim. Acta 1982, 49,
149.
[26] S. G. Teoh, G. Y. Yeap, C. C. Loh, L. W. Foong, S. B. Teo, H. K. Fun,
Polyhedron 1997, 16, 2213.
Acknowledgments
This work was supported by Shandong Provincial Natural Science
Foundation, China (ZR2010BL012), the Post-Doctor Innovation
Project of Shandong Province (200702021) and the National
Natural Science Foundation of China (20701027).
References
[1] a) E. R. T. Tiekink, Appl. Organomet. Chem. 1991, 5, 1;
b) E. R. T. Tiekink, Trends Organomet. Chem. 1994, 1, 71.
[2] V. Chandrasekhar, S. Nagendran, V. Baskar, Coord. Chem. Rev. 2002,
235, 1.
[3] M. Gielen, M. Biesemans, R. Willem, Appl. Organomet. Chem. 2005,
19, 440.
[4] M. Gielen, E. R. T. Tiekink, Metallotherapeutic Drug and Metal-based
Diagnostic Agents: The Use of Metals in Medicine, Wiley: New York,
2005, p. 421.
[5] S. K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev. 2009, 253, 235.
[6] W. E. Estes, W. E. Hatfield, Inorg. Chem. 1978, 17, 3226.
[7] D. Point, W. Davis, C. Clay, J. Steven, M. B. Ellisor, R. S. Pugh,
P. R. Becker, O. F. X. Donard, B. J. Porter, S. A. Wise, Anal. Bioanal.
Chem. 2007, 387, 2343.
[27] B. Y. K. Ho, J. J. Zuckerman, Inorg. Chem. 1973, 12, 1552.
[28] G. B. Deacon, R. J. Phillips, Coord. Chem. Rev. 1980, 33, 227.
[29] M. S. Morales-Rios, P. Joseph-Nathan, J. Heterocyclic. Chem. 1986,
23, 1617.
[30] K. Bernardo, S. Leppard, A. Robert, G. Commenges, F. Dahan,
B. Meunier, Inorg. Chem. 1996, 35, 387.
[31] J. Holecek, M. Nadvornik, K. Handlir, J. Organomet. Chem. 1986, 315,
299.
[32] J. Holecek, K. Handlir, M. Nadvornik, A. Lycka, Z. Chem. 1990, 30,
265.
[33] A. G. Davies, M. Gielen, K.H. Pannell, E.R.T. Tiekink, Tin Chemistry:
Fundamentals, Frontiers, and Applications. John Wiley & Sons:
Chichester, 2008, p. 17.
[8] D. Dakternieks,
T. S. Basu
Baul,
S. Dutta,
E. R. T. Tiekink,
Organometallics 1998, 17, 3058.
[9] J. M. Rivera, H. Reyes, A. Cortes, R. Santillan, Chem. Mater. 2006, 18,
1174.
[10] a) T. S. Basu Baul, C. Masharing, R. Willem, M. Biesemans,
M. Holcapek, R. Jirasko, A. Linden, J. Organomet. Chem. 2005,
690, 3080; b) T. S. Basu Baul, C. Masharing, G. Ruisi, R. Jirasko,
M. Holcapek, D. de Vos, D. Wolstenholme, A. Linden, J. Organomet.
Chem. 2007, 692, 4849.
[34] A. W. Addison, T. N. Rao, J. Reedijk, J. van Rijn, G. C. Verschoor,
J. Chem. Soc. Dalton Trans. 1984, 1349.
[35] A. Bondi, J. Phys. Chem. 1964, 68, 441.
c
wileyonlinelibrary.com/journal/aoc
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 298–304