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

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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-OC6 H2 CH NCH(CH2 Ind)COO]
[Ind = 3-indolyl; R = Et (1); n-Bu (2); Cy (3); Ph (4)], were synthesized and characterized by elemental analysis and IR, NMR (1 H,
13
C and 119 Sn) 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 2011 John Wiley &
lines, CoLo205 and Bcap37, while the diethyltin complex 1 displays weak cytotoxic activity. Copyright Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: organotin complex; tryptophane; cytotoxic activity; crystal structure
Introduction
298
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-αamino 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 diorganotin 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 active 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 continue to expand the chemistry and therapeutic potential of the
diorganotin(IV) complexes of the ligands, recently we synthesized and characterized some diorganotin(IV) complexes with
N-(halosalicylidene)-α-amino acid.[15 – 18] As a continuation of our
work, here we selected N-(3,5-dibromosalicylidene)tryptophane as
a ligand, synthesized four new diorganotin complexes, R2 Sn[3,5Br2 -2-OC6 H2 CH NCH(CH2 Ind)COO] [Ind = 3-indolyl; R = Et (1);
n-Bu (2); Cy (3); Ph (4); Scheme 1], and determined their cytotoxic
activity.
Appl. Organometal. Chem. 2011, 25, 298–304
Experimental
Materials and Physical Measurements
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 .
1 H and 13 C NMR spectral data were collected using a Bruker Avance
DMX500 FT-NMR spectrometer with CDCl3 or D2 O as solvent and
TMS as internal standard. 119 Sn NMR spectra were recorded in
CDCl3 on a Varian Mercury Vx300 spectrometer using Me4 Sn
external reference.
Synthesis of Potassium N-(3,5-dibromosalicylidene)
tryptophanate
At room temperature, potassium hydroxide (0.11 g, 2 mmol) and
(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
L-tryptophane
∗
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 2011 John Wiley & Sons, Ltd.
Copyright 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
C18 H13 Br2 KN2 O3 : 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). 1 H NMR
(D2 O) δ: 2.90 (dd, 3 J = 10.0 Hz, 2 J = 14.2 Hz, 1H, Ha -10), 3.71 (dd,
3 J = 3.2 Hz, 2 J = 14.2 Hz, 1H, H -10), 4.06 (dd, 3 J = 3.2, 10.0 Hz,
b
1H, H-2), 6.60 (d, 4 J = 2.4 Hz, 1H, H-9), 6.77 (s, 1H, H-12), 6.89 (s, 1H,
H-3), 7.05 (dd, 3 J = 7.5, 8.0 Hz, 1H, H-16), 7.19 (dd, 3 J = 7.5, 8.0 Hz,
1H, H-15), 7.38 (d, 3 J = 8.0 Hz, 1H, H-14), 7.62 (d, 3 J = 8.0 Hz, 1H,
H-17), 7.72 (d, 4 J = 2.4 Hz, 1H, H-7), 8.36 (s, 1H, NH), 12.39 (s, 1H,
OH) ppm.
Synthesis of the Complexes 1–4
A methanol solution (15 ml) of diorganotin dichloride (2 mmol) and
Et3 N (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.
Et2 Sn[3,5-Br2 -2-OC6 H2 CH NCH(CH2 Ind)COO] (1)
Appl. Organometal. Chem. 2011, 25, 298–304
Yield 65%, m.p. 205–206 ◦ C, Anal. calcd for C26 H30 Br2 N2 O3 Sn: 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). 1 H NMR (CDCl3 ) δ: 0.82 (t, 3 J = 7.3 Hz,
3H, CH3 ), 0.96 (t, 3 J = 7.3 Hz, 3H, CH3 ), 1.24–1.74 (m, 12H,
2CH2 CH2 CH2 Sn), 3.01 (dd, 3 J = 10.0 Hz, 2 J = 14.7 Hz, 1H, Ha -10),
3.81 (dd, 3 J = 3.1 Hz, 2 J = 14.7 Hz, 1H, Hb -10), 4.24 [dd, 3 J = 3.1,
10.0 Hz, 3 J(119 Sn– 1 H) = 36 Hz, 1H, H-2], 6.63 (d, 4 J = 2.4 Hz, 1H,
H-9), 6.87 (s, 1H, H-12), 7.08 [s, 3 J(119 Sn– 1 H) = 47 Hz, 1H, H-3], 7.11
(dd, 3 J = 7.5, 8.0 Hz, 1H, H-16), 7.23 (dd, 3 J = 7.5, 8.0 Hz, 1H, H-15),
7.43 (d, 3 J = 8.0 Hz, 1H, H-14), 7.61 (d, 3 J = 8.0 Hz, 1H, H-17),
7.74 (d, 4 J = 2.4 Hz, 1H, H-7), 8.51 (s, 1H, NH) ppm. 119 Sn NMR
(CDCl3 ) δ: −196.2 ppm. 13 C 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 (C8), 69.26 (C-2), 32.58 (C-10), 27.03 [2 J(119 Sn– 13 C) = 26 Hz, CH2 -β],
26.84 [2 J(119 Sn– 13 C) = 24 Hz, CH2 -β], 26.79 [3 J(119 Sn– 13 C) = 96 Hz,
CH2 -γ ], 26.70 [3 J(119 Sn– 13 C) = 90 Hz, CH2 -γ ], 22.56 [1 J(119 Sn– 13 C)
= 605 Hz, CH2 -α], 22.36 [1 J(119 Sn– 13 C) = 589 Hz, CH2 -α], 13.83
(CH3 ), 13.65 (CH3 ) ppm.
Cy2 Sn[3,5-Br2 -2-OC6 H2 CH NCH(CH2 Ind)COO] (3)
Yield 74%, m.p. 237.3–238.2 ◦ C. Anal. calcd for C30 H34 Br2 N2 O3 Sn:
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 ],
1301 (Ph–O), 540 (Sn–O). 1 H NMR (CDCl3 ) δ: 1.28–2.13 (m, 22H,
2Cy), 3.00 (dd, 3 J = 10.0 Hz, 2 J = 14.7 Hz, 1H, Ha -10), 3.83 (dd,
3 J = 3.2 Hz, 2 J = 14.7 Hz, 1H, H -10), 4.23 (dd, 3 J = 3.2, 10.0 Hz,
b
3 J (119 Sn– 1 H) = 39 Hz, 1H, H-2), 6.57 (d, 4 J = 2.4 Hz, 1H, H-9),
6.85 (s, 1H, H-12), 7.02 [s, 3 J(119 Sn– 1 H) = 41 Hz, 1H, H-3], 7.12 (dd,
3 J = 7.5, 7.9 Hz, 1H, H-16), 7.24 (dd, 3 J = 7.5, 8.1 Hz, 1H, H-15),
7.43 (d, 3 J = 8.1 Hz, 1H, H-14), 7.62 (d, 3 J = 7.9 Hz, 1H, H-17),
7.74 (d, 4 J = 2.4 Hz, 1H, H-7), 8.39 (s, 1H, NH). 119 Sn NMR (CDCl3 )
δ: −265.2 ppm. 13 C 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 (C18), 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 [1 J(119 Sn– 13 C) = 562 Hz, CH-α], 39.94 [1 J(119 Sn– 13 C)
= 554 Hz, CH-α], 32.52 (C-10), 30.34 [2 J(119 Sn– 13 C) = 20 Hz, CH2 β], 30.18 [2 J(119 Sn– 13 C) = 21 Hz, CH2 -β], 28.84 [3 J(119 Sn– 13 C) =
88 Hz, CH2 -γ ], 28.62 [3 J(119 Sn– 13 C) = 87 Hz, CH2 -γ ], 26.74 (CH2 -δ),
26.56 (CH2 -δ) ppm.
Ph2 Sn[3,5-Br2 -2-OC6 H2 CH NCH(CH2 Ind)COO] (4)
Yield 68%, m.p. 226.6–227.3 ◦ C. Anal. calcd for C30 H22 Br2 N2 O3 Sn:
C 48.89, H 3.01, N 3.80; found: C 48.66, H 2.93, N 3.56%. IR (KBr)
c 2011 John Wiley & Sons, Ltd.
Copyright wileyonlinelibrary.com/journal/aoc
299
Yield 63%, m.p. 222–224 ◦ C. Anal. calcd for C22 H22 Br2 N2 O3 Sn: 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). 1 H NMR (CDCl3 ) δ: 1.08 [t, 3 J = 8.0 Hz,
3 119
J( Sn– 1 H) = 133 Hz, 3H, CH3 ], 1.28–1.40 (m, 7H, CH3 + 2CH2 Sn),
2.93 (dd, 3 J = 10.0 Hz, 2 J = 14.4 Hz, 1H, Ha -10), 3.77 (dd,
3 J = 3.0 Hz, 2 J = 14.4 Hz, 1H, H -10), 4.18 [dd, 3 J = 3.0, 10.0 Hz,
b
3 119
J( Sn– 1 H) = 44 Hz, 1H, H-2], 6.55 (d, 4 J = 2.4 Hz, 1H, H-9), 6.81
(s, 1H, H-12), 6.99 [s, 3 J(119 Sn– 1 H) = 46 Hz, 1H, H-3], 7.07 (dd,
3 J = 7.5, 8.0 Hz, 1H, H-16), 7.20 (dd, 3 J = 7.5, 8.0 Hz, 1H, H-15),
7.36 (d, 3 J = 8.0 Hz, 1H, H-14), 7.59 (d, 3 J = 8.0 Hz, 1H, H-17), 7.69
(d, 4 J = 2.4 Hz, 1H, H-7), 8.14 (s, 1H, NH) ppm. 119 Sn NMR (CDCl3 )
δ: −192.8 ppm. 13 C 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 (C18), 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 [1 J(119 Sn– 13 C) = 600 Hz, CH2 Sn], 14.05
[1 J(119 Sn– 13 C) = 590 Hz, CH2 Sn], 9.55 [2 J(119 Sn– 13 C) = 30 Hz, CH3 ],
9.25 [2 J(119 Sn– 13 C) = 29 Hz, CH3 ] ppm.
n-Bu2 Sn[3,5-Br2 -2-OC6 H2 CH NCH(CH2 Ind)COO] (2)
L. Tian et al.
Table 1. Crystallographic and refinement data for 1, 2 and 3
Compound
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
b (Å)
c (Å)
β (deg)
Volume (Å 3 )
Z
Dc (g cm−3 )
µ (mm−1 )
F(000)
Crystal size (mm)
Total reflections
Unique reflections
Reflections with I > 2σ (I)
GOF on F 2
R indices [I > 2σ (I)]
R indices (all data)
CCDC deposition no.
1
2
3
C45 H48 Br4 N4 O7 Sn2
1313.89
Orthorhombic
P21 21 21
12.240(6)
14.301(6)
27.549(12)
90
4822(4)
4
1.810
4.402
2568
0.42 × 0.39 × 0.33
37 816
9467
6827
0.973
R = 0.047, wR = 0.086
R = 0.080, wR = 0.097
784 287
C26 H30 Br2 N3 O3 Sn
697.03
Monoclinic
P21 /c
17.8130(12)
10.2490(8)
17.9830(10)
115.425(2)
2965.1(3)
4
1.561
3.584
1376
0.17 × 0.12 × 0.02
27 691
5508
2441
0.961
R = 0.065, wR = 0.172
R = 0.145, wR = 0.214
784 288
C30 H34 Br2 N2 O3 Sn
749.10
Monoclinic
C/2c
34.237(2)
10.7326(12)
18.0908(17)
105.114(2)
6417.6(10)
8
1.551
3.317
2976
0.40 × 0.20 × 0.10
22 762
5812
2707
1.016
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). 1 H NMR (CDCl3 ) δ: 2.82 (dd, 3 J = 10.5 Hz,
2 J = 14.6 Hz, 1H, H -10), 3.72 (dd, 3 J = 3.2 Hz, 2 J = 14.6 Hz, 1H,
a
Hb -10), 4.28 [dd, 3 J = 3.2, 10.5 Hz, 3 J (119 Sn– 1 H) = 46 Hz, 1H, H-2],
6.54 (d, 4 J = 2.3 Hz, 1H, H-9), 6.77 (s, 1H, H-12), 6.93 [s, 3 J(119 Sn– 1 H)
= 58 Hz, 1H, H-3], 7.04 (dd, 3 J = 7.5, 7.9 Hz, 1H, H-16), 7.16 (dd,
3
J = 7.5, 8.2 Hz, 1H, H-15), 7.29 (d, 3 J = 8.2 Hz, 1H, H-14), 7.36–7.38
(m, 3H, m- and p-H in Ph), 7.45 (d, 3 J = 7.9 Hz, 1H, H-17), 7.50–7.53
(m, 3H, m- and p-H in Ph), 7.80–7.82 [m, 2H, 3 J (119 Sn– 1 H) = 88 Hz,
o-H in Ph], 7.83 (d, 4 J = 2.3 Hz, 1H, H-7), 7.99–8.01 [m, 2H, 3 J
(119 Sn– 1 H) = 87 Hz, o-H in Ph], 8.14 (s, 1H, NH) ppm. 119 Sn NMR
(CDCl3 ) δ: −335.7 ppm. 13 C NMR (CDCl3 ) δ: 172.74 (C-1), 171.59
(C-3), 163.67 (C-5), 142.36 (C-7), 137.46 [1 J(119 Sn– 13 C) = 986 Hz,
i-C], 137.39 [1 J(119 Sn– 13 C) = 978 Hz, i-C], 136.87 [2 J(119 Sn– 13 C)
= 58 Hz, o-C], 136.72 (C-13), 136.51 [2 J(119 Sn– 13 C) = 59 Hz,
o-C], 136.36 (C-9), 131.31 [4 J(119 Sn– 13 C) = 18 Hz, p-C], 131.16
[4 J(119 Sn– 13 C) = 16 Hz, p-C], 129.36 [3 J(119 Sn– 13 C) = 90 Hz, m-C],
129.27 [3 J(119 Sn– 13 C) = 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 (C17), 112.01 (C-14), 109.12 (C-11), 108.61 (C-8), 69.31 (C-2), 32.80
(C-10) ppm.
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(2A )
and 0.551(12):0.449(12) for C(4A)/C(4A ). 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
factors of two parts is 0.507(17) and 0.493(17). In addition, owing to
serious disorder problems of the solvent molecules, we were not
able to well define them. Therefore, a SQUEEZE/PLATON technique
was applied.[22] The estimated volume of the void per unit cell
is 125.0 Å 3 . 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.
X-ray Crystallography
300
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 F 2 using SHELX-97.[20] The non-hydrogen
atoms were refined anisotropically and hydrogen atoms were
wileyonlinelibrary.com/journal/aoc
In Vitro Cytotoxicity
Cytotoxic activity was assayed against two human tumor cell lines,
CoLo 205 (colon carcinoma cell) and Bcap37 (mammary tumor cell).
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 2011 John Wiley & Sons, Ltd.
Copyright 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
and were fixed for 24 h. The following day, different concentrations
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]
Results and Discussion
The complexes 1–4 were prepared by the reaction of diorganotin dichloride with potassium N-(3,5-dibromosalicylidene)
tryptophanate formed from condensation of 3,5-dibromosalicylaldehyde 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, chloroform, methanol, acetone and tetrahydrofuran.
IR Spectra
Table 2. Selected bond lengths (Å) and angles (deg) for 1,2 and 3
Bond lengths
Sn(1)–C(1)
Sn(1)–C(a)a
Sn(1)–O(1)
Sn(1)–O(2)
Sn(1)–N(1)
Bond angles
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)
O(1)–Sn(1)–O(2)
C(1)–Sn(1)–O(2)
N(1)–Sn(1)–O(2)
a
The complexes 1–4 did not show the ν (OH) band at
3300–3500 cm−1 , indicating the deprotonation of the phenolic 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 coordination 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 )] value is below 200 cm−1 for bidentate coordination and
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 carboxylate moiety. Thus, it is concluded that the compounds feature
five-coordinated tin in the solid, consistent with the below X-ray
structural analysis.
NMR Spectra
Appl. Organometal. Chem. 2011, 25, 298–304
1B
2
3
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)
2.095(11)
2.071(6)
2.150(8)
2.158(6)
2.17(2)
2.178(17)
2.103(12)
2.151(12)
2.176(13)
89.2(3)
141.8(3)
93.5(3)
111.6(3)
79.11(19)
106.3(3)
97.2(3)
151.72(19)
98.1(3)
72.91(19)
96.0(3)
146.9(3)
97.0(2)
104.0(3)
81.36(19)
108.0(2)
89.0(3)
153.70(19)
92.6(3)
72.39(19)
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)
a = 3, 5 and 7 for 1, 2 and 3, respectively.
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 1 J(119 Sn– 13 C) is in the range
605–554 Hz in the complexes 1–3 and 986 and 978 Hz in 4.
According to the equation, 1 J(119 Sn– 13 C) = 9.99 (±0.73) θ − 746
(±100)[31] and 1 J(119 Sn– 13 C) = 15.56 (±0.84) θ − 1160 (±101),[32]
the calculated value of the C–Sn–C angle (θ ) from 1 J(119 Sn– 13 C)
is 137.9–130.1◦ for the complexes 1–4, suggesting that the tin
atom has a distorted trigonal bipyramid geometry in the noncoordinating 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 1 H and 13 C 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 119 Sn chemical shifts primarily depend on the coordination
number and the nature of the donor atom directly bonded to the
central tin atom.[33] The 119 Sn 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]
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
space group P21 21 21 . The asymmetric unit contains two molecules
of the mononuclear organotin complex which are labeled as
molecules 1A and 1B, respectively, and one solvent CH3 OH
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)] of ethyl groups, an N(1) atom, a phenolic O(1) and a carboxylic
O(2) atom of the ligand. Its coordination geometry is best described
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
c 2011 John Wiley & Sons, Ltd.
Copyright wileyonlinelibrary.com/journal/aoc
301
The 1 H and 13 C 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
N CH (H-3) and aromatic proton H-9 lie in the range 6.93–7.08 and
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
appearance of spin-spin coupling between the azomethine proton
and the tin nucleus [3 J(119 Sn– 1 H) = 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 3 J(119 Sn– 1 H) coupling constants for H-2 are in
the range 36–46 Hz. The signals of the carboxyl carbon (C-1) and
1A
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.
302
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 sixmembered 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.
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 Bu2 Sn[OC6 H4 CH NCH(CH2 Ind)
COO]
[2.093(3)
and
2.162(3) Å]
and
Et2 Sn[5-Cl-2OC6 H3 CH NCH(CH2 Ind)COO] [2.1022(16) and 2.1754(15) Å].[13,18]
The bond angles O(1)–Sn(1)–O(2) [151.72(19) and 153.70(19)◦ ] in
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],
Sn(1B)· · ·O(2A) [3.114(5) Å] and Sn(1A)· · ·O(4) [3.004(8) Å] dis-
wileyonlinelibrary.com/journal/aoc
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
into infinite helical chain by the intermolecular N–H· · ·O hydrogen
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 adjacent 1B [N(2A)· · ·O(3B)#1 2.81(1) Å, N(2A)-H(2A)· · ·O(3B)#1
162.2◦ ] (Fig. 2).
c 2011 John Wiley & Sons, Ltd.
Copyright 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
Bu2 Sn[5-Cl-2-OC6 H3 CH NCH(CH2 Ind)COO] and Bu2 Sn[5-Br-2OC6 H3 CH NCH(CH2 Ind)COO].[18] The dibutyltin complex of (2hydroxynaphthalidene)glycine, Bu2 Sn(2-OC10 H6 CH NCH2 COO),
reported by Nath et al.,[11] showed quite promising cytotoxicity – the IC50 values against cancer cell lines MCF-7, EVSAT, WiDr, IGROV and MI9 are 0.075, 0.035, 0.480, 0.075,
and 0.090 µg ml−1 , respectively. More recently, R2 Sn[5-MeO-2OC6 H3 CH NCH(CH2 Ph)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 Bu2 Sn[OC6 H4 CH NCH(CH2 Ind)COO],[13] and
Cy2 Sn[3,5-Br2 -2-OC6 H4 CH NCH(CH2 Ph)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 twodimensional arrays through intermolecular N–H· · ·O hydrogen
bonds involving the hydrogen atom on N(2) of indolyl and O(3)#1
atom of carbonyl [N(2)· · ·O(3)#1 2.77(1) Å, N(2)–H(2)· · ·O(3)#1
155.9◦ for 2 and N(2)· · ·O(3)#1 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).
In summary, four new diorganotin(IV) complexes of N-(3,5dibromosalicylidene)tryptophane have been synthesized by
the reaction of diorganotin dichloride with potassium N-(3,5dibromosalicylidene)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 displays weak cytotoxic activity. Further structure modification and
optimization of these diorganotin complexes are necessary.
Supporting information
Supporting information may be found in the online version of this
article.
C15
Br1
Br2
C16
C2
C14
C3
C13
C17
C18
O1
C1
C4
C19
C27
Sn1
C26
C25
C12
N1
N2
C6
C24
C5
C11
C20
C28
C29
C30
C10
C7
C23
C21
C22
O2
C8
C9
O3
303
Figure 4. The molecular structure of 3; hydrogen atoms are omitted for clarity.
Appl. Organometal. Chem. 2011, 25, 298–304
c 2011 John Wiley & Sons, Ltd.
Copyright 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.
Table 3. Cytotoxic activity [IC50 (µg ml−1 )] of compounds
Compound
1
2
4
cis-Platin
CoLo205
Bcap37
>10
0.51 ± 0.05
2.69 ± 0.69
4.12 ± 0.12
7.61 ± 1.75
0.22 ± 0.09
1.02 ± 0.10
1.78 ± 0.25
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).
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