Synthesis, crystal structures and in vitro antitumor activities of some arylantimony derivatives of analogues of demethylcantharimide

Article abstract of DOI:10.1016/j.jorganchem.2004.02.015

A series of novel arylantimony derivatives of analogues of demethylcantharimide with the formulae Ar_nSbL_(5-n) and Ar_nSbL^′_(5-n) (LH=N-hydroxy-demethyldehydrogencantharimide, L^′ H=N-hydroxy-demethylcantharimide, n=3, 4; Ar=C₆H₅, 4-CH₃C₆H₄, 3-CH₃C₆H₄, 2-CH₃C₆ H₄, 4-ClC₆H₄, 4-FC₆H₄) were synthesized and characterized by elemental analysis, IR, ¹H NMR and mass spectroscopy. The crystal structures of (C₆H₅)₄SbL, (4-CH₃C₆H₄)₃SbL₂ and (3-CH₃C₆H₄)₃ SbL^′₂ were determined by X-ray diffraction. The in vitro antitumor activities of all compounds against six cancer cells are reported.

Full text of DOI:10.1016/j.jorganchem.2004.02.015

Journal of Organometallic Chemistry 689 (2004) 1631–1638
www.elsevier.com/locate/jorganchem
Synthesis, crystal structures and in vitro antitumor
activities of some arylantimony derivatives
of analogues of demethylcantharimide
a
a
a
a,
b
Guo-Cang Wang , Jian Xiao , Lin Yu , Jin-Shan Li *, Jing-Rong Cui ,
b
Rui-Qing Wang , Fu-Xiang Ran
b
a
State Key Laboratory of Elemento-Organic Chemistry, School of Chemistry, Nankai University, Tianjin 300071, China
b
National Research Laboratories of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China
Received 25 December 2003; accepted 13 February 2004
Abstract
A series of novel arylantimony derivatives of analogues of demethylcantharimide with the formulae ArnSbLð5ꢀnÞ and
ArnSbL0ð5ꢀnÞ(LH ¼ N-hydroxy-demethyldehydrogencantharimide, L0H ¼ N-hydroxy-demethylcantharimide, n ¼ 3, 4; Ar@C6H5, 4-
CH3C6H4, 3-CH3C6H4, 2-CH3C6H4, 4-ClC6H4, 4-FC6H4) were synthesized and characterized by elemental analysis, IR, 1H NMR
and mass spectroscopy. The crystal structures of (C6H5)4SbL, (4-CH3C6H4)3SbL2 and (3-CH3C6H4)3SbL02 were determined by
X-ray diffraction. The in vitro antitumor activities of all compounds against six cancer cells are reported.
Ó 2004 Elsevier B.V. All rights reserved.
Keywords: Antimony; Demethylcantharimide; Crystal structures; Antitumor activity
1. Introduction
including antitumor activity [19–21]. In order to inves-
tigate whether including the analogues of demethyl-
cantharimide in organoantimony (V) derivatives can
improve their antitumor properties we have synthesized
a series of arylantimony derivatives of analogues of
demethylcantharimide. In addition, we are also inter-
ested in studying the nature of bonding and the structure
of these compounds.
A substantial number of references describing syn-
thesis and applications of ArnSbXð5ꢀnÞ (n ¼ 3, 4;
X ¼ halide, alkoxyl, carboxylate, sulphonate, oxime)
have appeared in the literature [1–14]. The use of anti-
mony in medicine has been reviewed by Tiekink [15].
Over the last several years, Silvestru co-workers [16–18]
reported that some organoantimony (III) derivatives
showed significant antitumor activity. In recent years we
have found that some organoantimony (V) derivatives
exhibit high in vitro antitumor activity [8,9], which is
associated with cytostatic activity similar to that of
cis-platin. However, demethylcantharimide {exo-7-oxa-
bicyclo[2,2,1]heptane-2,3-dicarboximide} and its ana-
logues have also a wide range of biological activity,
2. Results and discussion
2.1. Preparations
The title compounds are prepared under anhydrous
condition. All compounds are white crystals and stable
under ordinary conditions. They are soluble in organic
solvents such as dichloromethane, chloroform, acetone
and dimethyl sulfoxide, but not soluble in ether, hexane
and petroleum ether. The general reaction is shown as
follows:
* Corresponding author. Tel.: 00862223504230; fax: 0086222350-
3438.
0022-328X/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.02.015

1632
G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
O
O
1725 cmꢀ1(strong) in the IR spectra of N-hydroxy-
demethylcantharimide [22]. In the IR spectra of the title
compounds the absorption vibration frequencies of five
membered ring imides are observed in the characteristic
regions: a strong absorption due to carbonyl group at
1706–1683 cmꢀ1 and a medium absorption due to imine
linkage at 1779–1765 cmꢀ1. The absorption vibration
frequencies at about 3300 cmꢀ1 [22] due to hydroxyl
group of free ligands disappeared, indicating the de-
protonation of hydroxyl group and formation of Sb–O
bond. In addition, the frequencies of Sb–C deformations
appear between 453 and 504 cmꢀ1, this is consistent with
the literature [1].
+ ArnSbBr(5-n)
OH
N
O
O
O
O
Et3N
O
SbArn
(5-n)
N
reflux
For compounds I: n ¼ 3, Ar@C6H5 (I1), 4-CH3C6H4
(I2), 3-CH3C6H4 (I3), 2-CH3C6H4 (I4), 4-ClC6H4 (I5);
n ¼ 4, Ar@C6H5 (I6), 4-ClC6H4 (I7).
O
O
+ ArnSbBr(5-n)
OH
N
1
2.3. H NMR
O
1
The H NMR data of the title compounds are listed
O
O
O
in Table 2. The chemical shifts of the protons of the
double-bonded carbons (CH@CH) appear between 6.28
and 6.37 ppm, and those of the protons of the single-
bonded carbons (CH2–CH2) appear between 1.31 and
1.73 ppm. The protons of Ar show a complex multiplet.
All the protons in the compounds have been identified
and the total number of protons calculated from the
integration curve tallies with what was expected from
the molecular formula.
Et3N
O
SbArn
(5-n)
N
reflux
For compounds II: n ¼ 3, Ar@C6H5 (II1), 4-CH3-
C6H4 (II2), 3-CH3C6H4 (II3), 2-CH3C6H4 (II4), 4-
ClC6H4 (II5), 4-FC6H4 (II6); n ¼ 4, Ar@C6H5 (II7),
4-ClC6H4 (II8).
2.2. IR
2.4. Mass spectra
The IR spectra of these compounds have been
recorded in the range of 4000–400 cmꢀ1. The ab-
sorption bands can be assigned on the basis of earlier
publications and the important data are listed in
Table 1.
The IR spectroscopic data provide further support
for the molecular constitution of the title compounds. A
characteristic feature of five membered ring imides is the
presence of bands at about 1785 cmꢀ1 (medium) and
The main mass spectra data of compound II3 are
listed in Table 3. In the mass spectra of compound II3
the molecular ion peak has never been observed, but the
fragment ions found (M–ONO3C8H8)þ (m/z 576, 578;
intensity 16.2%, 12.0%) and (ONO3C8H8)þ (m/z 182;
intensity 23.5%) are in agreement with the expected
structure of the compound. The breakdown of Sb–O
and Sb–C bonds are the main breakdown patterns for
the compound.
Table 1
IR data of the compounds (cmꢀ1
2.5. Crystal structure
)
Compound
m (C@O)
m (C–N–C)
m (Sb–C)
2.5.1. Crystal structure of compound I6
I1
1693 (s)
1702 (s)
1698 (s)
1702 (s)
1704 (s)
1683 (s)
1685 (s)
1699 (s)
1702 (s)
1702 (s)
1701 (s)
1706 (s)
1697 (s)
1686 (s)
1686 (s)
1768 (m)
1774 (m)
1775 (m)
1776 (m)
1774 (m)
1765 (m)
1770 (m)
1779 (m)
1773 (m)
1774 (m)
1776 (m)
1776 (m)
1778 (m)
1768 (m)
1765 (m)
457
483
467
504
490
461
490
453
485
468
486
489
473
458
491
The colorless crystals of compound I6 were obtained
from CH2Cl2-petroleum ether. One of the approximate
dimensions 0.20 ꢁ 0.18 ꢁ 0.14 mm was mounted in a
glass capillary and used for data collection. Fig. 1 shows
the molecular structure of the compound and gives the
atom numbering scheme. The selected bond distances
and angles are listed in Table 4.
The antimony atom of the compound is five-coordi-
nate, the coordination geometry of antimony can be
described as a distorted trigonal bipyramid. The three
equatorial positions are occupied by the carbon atoms
(C(9), C(15) and C(21)) of the three phenyl groups,
while the atoms C(27) and O(1) occupy the axial posi-
I2
I3
I4
I5
I6
I7
II1
II2
II3
II4
II5
II6
II7
II8

G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
1633
Table 2
1H NMR data of the compounds
Compound
OCCH
CH–O
CH@CH
CH–CH
Ar
I1
I2
1.94 (4H, s)
1.89 (4H, s)
4.92 (4H, s)
4.93 (4H, s)
6.29 (4H, s)
6.28 (4H, s)
7.50–8.21 (15H, m)
7.28–8.05 (12H, m)
2.35 (9H, s)
I3
I4
1.91 (4H, s)
2.00 (4H, s)
4.91 (4H, s)
4.90 (4H, s)
6.28 (4H, s)
6.28 (4H, s)
7.32–8.03 (12H, m)
2.39 (9H, s)
7.35–8.44 (12H, m)
2.57 (9H, s)
I5
2.10 (4H, s)
1.94 (2H, s)
2.24 (2H, s)
1.97 (4H, s)
4.91 (4H, s)
4.95 (2H, s)
6.32 (4H, s)
6.31 (2H, s)
6.37 (2H, s)
7.44–8.12 (12H, m)
7.42–7.72 (20H, m)
7.37–7.53 (16H, m)
7.54–8.26 (15H, m)
I6
I7
II1
4.96 (2H, s)
4.55–4.57 (4H, t)
1.36–1.40 (4H, m)
1.69–1.72 (4H, m)
1.32–1.36 (4H, m)
1.65 (4H, m)
II2
II3
II4
II5
II6
II7
II8
1.96 (4H, s)
1.98 (4H, s)
2.08 (4H, s)
2.18 (4H, s)
2.16 (4H, s)
2.04 (2H, s)
2.34 (2H, s)
4.52–4.54 (4H, t)
4.51–4.52 (4H, t)
4.48–4.50 (4H, t)
4.50 (4H, t)
7.28–8.07 (12H, m)
2.38 (9H, s)
1.31–1.37 (4H, m)
1.66–1.69 (4H, m)
1.31–1.37 (4H, m)
1.65–1.67 (4H, m)
1.38–1.41 (4H, m)
1.68–1.73 (4H, m)
1.35–1.42 (4H, m)
1.68–1.71 (4H, m)
1.36–1.41 (2H, m)
1.69–1.71 (2H, m)
1.44–1.46 (2H, m)
1.74–1.77 (2H, m)
7.30–8.01 (12H, m)
2.40 (9H, s)
7.29–8.03 (12H, m)
2.57 (9H, s)
7.44–8.10 (12H, m)
4.49–4.50 (4H, t)
4.56–4.57 (2H, t)
4.56–4.57 (2H, t)
7.17–8.21 (12H, m)
7.40–7.71 (20H, m)
7.36–7.50 (16H, m)
Table 3
Fragment ions observed for compound II3
m/z
Fragment
Intensity (%)
m/z
Fragment
Intensity (%)
578
576
396
394
305
[(3-CH3C6H4)3Sb(ONO3H8C8)]þ
[(3-CH3C6H4)3Sb(ONO3H8C8)]þ
(3-CH3C6H4)3Sbþ
12.0
16.2
2.0
303
214
212
182
91
(3-CH3C6H4)2 Sbþ
(3-CH3C6H4)Sbþ
(3-CH3C6H4)Sbþ
(ONO3H8C8)þ
17.4
14.4
17.6
23.5
28.0
(3-CH3C6H4)3Sbþ
3.4
10.5
(3-CH3C6H4)2Sbþ
(3-CH3C6H4)þ
ꢀ
tions. The apical Sb(1)–C(27) distance [2.179(6) A] is
slightly longer than the equatorial Sb(1)–C(9), Sb(1)–
C(15) and Sb(1)–C(21) distances [2.118(7), 2.112(6) and
ꢀ
2.124(6) A, respectively]. The Sb(1)–O(1) distance
ꢀ
[2.223(4) A] is longer than the corresponding distance in
ꢀ
Ph4SbOMe [2.061(7) A] [4], but slightly shorter than
ꢀ
that in Ph4Sb[ON@C(CN)C(O)NH2] [2.259(1) A] [13].
ꢀ
The Sb(1)–N(1) distance (3.097(8) A) is obviously
ꢀ
shorter than the sum (3.74 A) of the van der Waals’ radii
ꢀ
of antimony and nitrogen atoms (2.2 and 1.54 A, re-
spectively) [23]. This indicates that there is a weak co-
ordination interaction between the no-bonded nitrogen
atom and antimony atom, which leads to a small vari-
ation of the three equatorial angles of compound I6, the
C(9)–Sb(l)–C(15) angle is increased to 125.4(3)°, while
the C(9)–Sb(l)–C(21) and C(15)–Sb(l)–C(21) angles are
decreased to 119.0(3)° and 113.3(2)°, respectively. The
ꢀ
Fig. 1. The molecular structure of compound I6.
atom Sb(l) is displaced by 0.0674 A towards C(27) from

1634
G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
Table 4
Selected bond distances and bond angles of compound I6
ꢀ
Bond
Sb(1)–C(21) 2.112(6)
Sb(1)–C(9) 2.118(7)
Distance (A)
Bond
Angle (°)
C(9)–Sb(1)–C(21)
C(15)–Sb(1)–C(21)
C(9)–Sb(1)–C(15)
C(21)–Sb(1)–C(27)
C(9)–Sb(1)–C(27)
C(15)–Sb(1)–C(27)
O(1)–Sb(1)–C(21)
O(1)–Sb(1)–C(9)
O(1)–Sb(1)–C(15)
O(1)–Sb(1)–C(27)
O(1)–N(1)–C(1)
O(1)–N(1)–C(8)
C(1)–N(1)–C(8)
N(1)–O(1)–Sb(1)
C(3)–O(4)–C(6)
119.0(3)
113.3(2)
125.4(3)
96.4(2)
93.5(2)
94.8(2)
87.1(2)
81.2(2)
87.4(2)
174.6(2)
122.3(5)
122.9(5)
114.7(5)
118.0(3)
95.7(6)
Sb(1)–C(15) 2.124(6)
Sb(1)–C(27) 2.179(6)
Sb(1)–O(1)
Sb(1)–N(1)
N(1)–O(1)
N(1)–C(1)
N(1)–C(8)
O(2)–C(1)
O(3)–C(8)
O(4)–C(3)
O(4)–C(6)
C(2)–C(7)
C(4)–C(5)
C(1)–C(2)
C(7)–C(8)
C(2)–C(3)
C(6)–C(7)
C(3)–C(4)
C(5)–C(6)
2.223(4)
3.097(8)
1.351(6)
1.381(8)
1.396(8)
1.197(8)
1.180(8)
1.416(10)
1.442(9)
1.543(10)
1.303(14)
1.496(9)
1.494(9)
1.555(10)
1.549(9)
1.469(12)
1.496(13)
Fig. 3. The molecular structure of compound II3.
ꢀ
2.109(3), 2.111(4) and 2.113(3) A in compound II3] are
approximately equal to those in Ph3Sb[ON@
ꢀ
C(Me)C5H4N-2]2 [2.098(2) and 2.120(3) A] [11]. The Sb–
Table 5
Selected bond distances and bond angles of compound I2
ꢀ
Distance (A)
Bond
Bond
Angle (°)
the plane defined by the equatorial carbon atoms C(9),
C(15) and C(21).
Sb(1)–O(1)
Sb(1)–O(5)
Sb(1)–C(31)
Sb(1)–C(24)
Sb(1)–C(17)
Sb(1)–N(1)
Sb(1)–N(2)
O(1)–N(1)
O(5)–N(2)
N(1)–C(8)
N(1)–C(1)
C(4)–C(5)
2.108(4)
2.119(4)
2.104(4)
2.101(5)
2.110(4)
3.017(5)
3.050(4)
1.365(4)
1.357(4)
1.377(4)
1.382(4)
1.306(5)
O(1)–Sb(1)–O(5)
O(1)–Sb(1)–C(24)
O(1)–Sb(1)–C(31)
O(1)–Sb(1)–C(17)
O(5)–Sb(1)–C(24)
O(5)–Sb(1)–C(31)
O(5)–Sb(1)–C(17)
C(17)–Sb(1)–C(24)
C(17)–Sb(1)–C(31)
C(24)–Sb(1)–C(31)
N(1)–O(1)–Sb(1)
N(2)–O(5)–Sb(1)
176.17(9)
93.89(14)
92.46(15)
86.66(13)
89.93(14)
85.74(14)
91.04(13)
129.00(15)
114.92(17)
116.00(14)
119.06(18)
121.2(2)
2.5.2. Crystal structures of compounds I2 and II3
Both colorless crystals were obtained from CH2Cl2-
petroleum ether solution. The molecular structures of
compounds I2 and II3 with the atom numbering scheme
are depicted in Figs. 2 and 3, respectively. The selected
bond distances and angles of the two compounds are
listed in Tables 5 and 6, respectively.
The antimony atoms in compounds I2 and II3 are all
five-coordinate, and their geometries are represented as a
distorted trigonal bipyramid. The Sb–C bond distances
C(12)–C(13) 1.308(6)
C(20)–C(21) 1.507(5)
C(27)–C(28) 1.528(6)
C(34)–C(35) 1.507(5)
ꢀ
[2.101(5), 2.104(4) and 2.110(4) A in compound I2,
Table 6
Selected bond distances and bond angles of compound II3
ꢀ
Distance (A) Bond
Bond
Angle (°)
Sb(1)–O(1)
Sb(1)–O(5)
Sb(1)–C(8)
Sb(1)–C(15)
Sb(1)–C(1)
Sb(1)–N(1)
Sb(1)–N(2)
N(1)–O(1)
N(1)–C(29)
N(1)–C(22)
N(2)–O(5)
2.106(2)
2.094(2)
2.109(3)
2.111(4)
2.113(3)
3.028(5)
3.027(6)
1.362(3)
1.372(4)
1.373(5)
1.368(3)
O(1)–Sb(1)–O(5)
176.16(9)
90.46(13)
89.74(11)
86.91(12)
93.54(11)
93.40(12)
85.87(13)
131.49(14)
116.38(14)
112.07(14)
120.12(19)
120.48(19)
O(1)–Sb(1)–C(15)
O(1)–Sb(1)–C(8)
O(1)–Sb(1)–C(1)
O(5)–Sb(1)–C(8)
O(5)–Sb(1)–C(1)
O(5)–Sb(1)–C(15)
C(8)–Sb(1)–C(15)
C(1)–Sb(1)–C(8)
C(1)–Sb(1)–C(15)
N(1)–O(1)–Sb(1)
N(2)–O(5)–Sb(1)
C(25)–C(26) 1.544(7)
C(33)–C(34) 1.537(6)
C(3)–C(7)
1.515(6)
C(10)–C(14) 1.514(7)
C(17)–C(21) 1.507(7)
Fig. 2. The molecular structure of compound I2.

G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
1635
ꢀ
O bond distances [2.108(4) and 2.119(4) A in compound
ꢀ
I2, 2.106(2) and 2.094(2) A in compound II3] are both
derivatives of analogues of demethylcantharimide.
When comparing with cisplatin, the tetraarylantimony
derivatives of analogues of demethylcantharimide,
namely compounds I6, I7, II7 and II8, have very high
antitumor activity against some cancer cells. The anti-
tumor activities are also affected by the nature of the
aryl at Sb. When Ar is 4-ClC6H4 compounds I7 and II8
have relatively higher antitumor activity.
longer than the corresponding distances in Ph3Sb
ꢀ
[ON@C(Me)C5H4N-2]2 [both 2.068(1) A]. The Sb–N
ꢀ
distances [3.017(5) and 3.050(4) A in compound I2,
ꢀ
3.027(5) and 3.028(6) A in compound II3] are markedly
ꢀ
shorter than the sum (3.74 A) of the van der Waals’ radii
of antimony atom and nitrogen atom [23], therefore,
there are also weak interactions between Sb(l) and the
nitrogen atoms [N(1) and N(2)] in compounds I2 and II3.
The C(17)–Sb(l)–C(24) angle in compound I2, which
is affected by adjacent N(1) and N(2), is increased to
129.00(15)°, while the C(24)–Sb(l)–C(31) and C(17)–
Sb(l)–C(31) angles are decreased to 116.00(14)° and
114.92(17)°, respectively. Correspondingly, the C(8)–
Sb(l)–C(15) angle in compound II3, which is also af-
fected by adjacent N(1) and N(2), is increased to
131.49(14)°, while the C(1)–Sb(l)–C(8) and C(1)–Sb(l)–
C(15) angles are decreased to 116.38(14)° and
112.07(14)°, respectively. The atoms Sb(l), C(17), C(24)
3. Experimental
Elemental analyses were determined on a Yanaco
CHN Corder MT-3 elemental analyzer. IR spectra were
recorded on a Bruker Equinox 55 spectrometer in KBr
discs. 1H NMR spectra were measured on a Bruker AC-
200 spectrometer in CDCl3 solution with TMS as in-
ternal standard. Mass spectra were recorded on a VG
ZAB-HS mass spectrometer (FAB). All the reactions
involving metal halides were carried out under anhy-
drous. Solvents were purified, dried, and stored by lit-
erature methods.
ꢀ
and C(31) in compound I2 are coplanar within 0.0130 A,
while the corresponding atoms Sb(l), C(1), C(8) and
ꢀ
C(15) in compound II3 are coplanar within 0.0115 A.
3.1. Reagents
2.6. Antitumor activity
The analogues of demethylcantharimide were syn-
thesized via the following reaction [24,25]. Ar3SbBr2 was
prepared by the method reported by Lile and Menzies
[2], and the solid product was recrystallized from tolu-
ene–petroleum ether mixture. To prepare Ar4SbBr, an
adaptation of the method of McEwen et al. [5] was used.
The antitumor activities of all compounds are listed
in Table 7. The results of bioassay showed that the
tetraarylantimony derivatives of analogues of demeth-
ylcantharimide have relatively higher antitumor activity
against the six cancer cells than the triarylantimony
Table 7
Antitumor activity of all compounds in vitro
Inhibition ratio (%) (10 lg/ml)a
Compound
HL-60
PC-3MIE8
BGC-823
MDA-MB-435
Bel-7402
Hela
I1
12.1
17.0
15.3
7.6
)1.5
)0.6
)2.2
)6.5
26.2
0.6
1.5
8.2
7.3
10.3
8.0
10.8
6.4
I2
I3
4.2
1.5
6.8
9.1
3.2
7.1
6.8
5.4
I4
I5
18.5
74.5
87.7
)1.7
10.4
)6.7
8.8
23.8
65.7
95.8
23.7
3.8
3.3
13.3
58.6
97.3
1.1
14.0
6.9
I6
57.0
84.8
17.5
94.8
5.5
I7
II1
91.1
)18.8
10.8
)7.0
)1.4
)0.7
)11.4
38.6
33.6
)3.5
)2.1
)3.5
77.7
)20.0
)1.7
4.9
II2
II3
6.0
12.6
11.1
6.2
22.3
16.3
25.3
11.2
83.8
90.7
20.2
18.6
20.4
90.6
17.4
)3.4
)9.7
24.6
43.7
91.3
)0.4
0.4
II4
II5
)18.2
)15.0
6.9
26.8
6.1
11.2
1.5
II6
II7
87.6
84.4
25.4
19.3
21.7
45.4
83.2
71.2
69.6
92.2
)2.2
6.3
II8
A
)16.3
)11.4
)8.2
76.0
B
C
Cisplatin
1.9
57.5
14.3
33.4
A: N-hydroxy-demethyldehydrogencantharimide, B: N-hydroxy-demethylcantharimide, C: Ph3SbBr2.
a Inhibition ratio (%) ¼ (A1 ꢀ A2Þ=A1 ꢁ 100%. A1: the mean optical densities of untreated cells, A2: the mean optical densities of drug-treated cells.

1636
G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
O
O
O
O
O
ether
O
N
OH
+
O
O
O
O
.
O
HCl NH OH
2
Ranny Ni
O
H
2
NaOCH
HOCH
3
3
O
O
O
O
N OH
O
O
3.2. Synthesis of the title compounds
by a full-matrix least square procedure based on F 2.
Non-hydrogen atoms were refined with anisotropic
thermal parameters. Crystal data are summarised in
Table 9.
The title compounds were synthesized by more con-
venient method. Ar3SbBr2 (0.5 mmol) or Ar4SbBr (1
mmol) was added to a solution of N-hydroxy-dem-
ethyl(dehydrogen)cantharimide (1 mmol) in 30 ml THF
and 0.6 ml Et3N. The reaction mixture was refluxed for
8 h, cooled and filtered. The filtrate was evaporated in
vacuo. The obtained solid was recrystallized from
CH2Cl2-petroleum ether. The yields, melting points and
elemental analysis of the prepared compounds are given
in Table 8.
3.4. Antitumor activities
All cell lines were derived in the National Research
Laboratories of Natural and Biomimetic Drugs of Pe-
king University and grown in RPMI 1640 medium with
10% fetal bovine serum, in 5% CO2 atmosphere.
The antitumor activity was assayed by the MTT or
SRB methods [26,27]. The cell lines, human immature
granulocyte leukemia (HL-60), human prostatic
carcinoma (PC-3MIE8), human gastric carcinoma
(BGC-823), human mammary gland carcinoma (MDA-
MB-435), human hepatocellular carcinoma (Bel-7402)
and human hela carcinoma (Hela) were used for the
screening. All cell lines were seeded into 96 well plates
at a concentration of about 50 000 cells/ml and were
incubated in 5% CO2 atmosphere at 37 °C for 24 h.
Then 20 ll of the sample (organoantimony complex)
were added and further incubation was carried out at
3.3. Crystal structure determination
Diffraction measurements of compounds I2, I6 and
II3 were carried out at 293 K on a Bruker Smart 1000
diffractometer (graphite-monochromatized Mo Ka ra-
ꢀ
diation, k ¼ 0:71073 A). The crystal class, orientation
matrix and accurate unit-cell parameters were deter-
mined by standard procedures. The intensities were
corrected for absorption using SADABS program. The
structure was solved by heavy atom method and refined
Table 8
Yields and elemental analyses of the compounds
Compound
Yield (%)
M.p. (°C)
Elemental analysis: Found (Calc.) (%)
C
H
N
Formula for Calc.
I1
59.2
72.9
58.3
51.7
63.7
68.9
69.5
77.1
60.2
80.4
42.5
88.9
55.8
68.6
78.7
196 dec
204 dec
192–193
210 dec
170 dec
197 dec
184 dec
240 dec
274
57.33(57.25)
54.02(54.31)
58.70(58.83)
51.15(50.62)
50.15(50.00)
62.96(62.97)
51.22(51.38)
57.04(56.92)
58.05(58.51)
58.37(58.51)
58.48(58.51)
49.76(49.76)
53.01(52.94)
62.64(62.77)
47.55(47.47)
3.84(3.82)
3.90(4.20)
4.60(4.40)
3.81(4.03)
3.02(2.96)
4.39(4.29)
2.95(2.96)
4.30(4.36)
4.61(4.91)
4.78(4.91)
4.90(4.91)
3.53(3.44)
3.79(3.66)
4.46(4.61)
2.92(3.14)
3.74(3.93)
3.66(3.33)
3.75(3.71)
2.93(3.03)
3.49(3.43)
2.40(2.30)
1.96(1.87)
4.02(3.90)
4.00(3.69)
3.70(3.69)
3.64(3.69)
3.44(3.41)
3.78(3.63)
2.33(2.29)
1.99(1.68)
C34H27N2O8Sb
C37H33N2O8Sb ꢂ CH2Cl2
C37H33N2O8Sb
I2
I3
I4
C37H33N2O8Sb ꢂ 2CH2Cl2
C34H24Cl3N2O8Sb
C32H26NO4Sb
I5
I6
I7
C32H22Cl4NO4Sb
C34H31N2O8Sb
C37H37N2O8Sb
II1
II2
II3
II4
II5
II6
II7
II8
258–259
280 dec
288
C37H37N2O8Sb
C37H37N2O8Sb
C34H28Cl3N2O8Sb
C34H28F3N2O8Sb
C32H28NO4Sb
272 dec
200 dec
220
C32H24Cl4NO4Sb ꢂ CH2Cl2

G.-C. Wang et al. / Journal of Organometallic Chemistry 689 (2004) 1631–1638
1637
Table 9
Crystallographic data for compounds I2, I6 and II3
Compound
I2
I6
II3
Formula
Temperature (K)
ꢀ
Wavelength (A)
C37H33N2O8Sb
293(2)
0.71073
C32H26NO4Sb
293(2)
0.71073
C37H37N2O8Sb
293(2)
0.71073
Crystal system
Space group
Unit cell dimensions
Triclinic
ꢁ
Monoclinic
P21=n
Triclinic
ꢁ
P1
P1
ꢀ
a (A)
9.186(15)
10.946(18)
9.602(3)
12.388(4)
10.307(4)
11.461(4)
ꢀ
b (A)
ꢀ
c (A)
20.44(4)
77.42(3)
25.259(7)
90
18.335(6)
75.405(5)
a (°)
b (°)
c (°)
80.88(3)
70.56(3)
1883(6)
93.178(5)
90(6)
2999.8(15)
89.257(5)
79.731(6)
3
ꢀ
Volume (A )
2061.1(12)
2
1.497
Z
2
1.482
4
1.445
Density (Mg mꢀ3
Absorption coefficient (mmꢀ1
)
)
0.928
852
1.045
1316
0.981
944
F ð000Þ
Crystal size (mm)
h Range for data collection (°)
Limiting indices
0.24 ꢁ 0.20 ꢁ 0.18
1.03–25.03
0.20 ꢁ 0.18 ꢁ 0.14
1.82–26.42
0.34 ꢁ 0.22 ꢁ 0.20
1.15–26.41
ꢀ12 6 h 6 12, ꢀ14 6 k 6 8,
ꢀ22 6 l 6 22
11 918
ꢀ10 6 h 6 10, ꢀ9 6 k 6 13,
ꢀ24 6 l 6 22
ꢀ10 6 h 6 12, ꢀ15 6 k 6 14,
ꢀ20 6 l 6 31
Reflections collected
Independent reflections
Completeness to h
Absorption correction
Refinement method
Goodness-of-fit on F 2
Final R indices [I > 2rðIÞ]
R indices (all data)
7835
6589 (Rint ¼ 0:0244)
16 930
6151 (Rint ¼ 0:0205)
26.42° (99.7%)
Semi-empirical from equivalents
Full-matrix least-squares on F 2
1.150
8353 (Rint ¼ 0:0205)
25.03° (99.4%)
26.41° (98.7%)
Semi-empirical from equivalents
Full-matrix least-squares on F 2
1.007
Semi-empirical from equivalents
Full-matrix least-squares on F 2
1.019
R1 ¼ 0:0353; wR2 ¼ 0:0717
R1 ¼ 0:0540; wR2 ¼ 0:0801
R1 ¼ 0:0567; wR2 ¼ 0:1418
R1 ¼ 0:0970; wR2 ¼ 0:1628
1.333 and )0.973
R1 ¼ 0:0412; wR2 ¼ 0:0978
R1 ¼ 0:0586; wR2 ¼ 0:1065,
0.626 and )0.852
Largest differential peak and hole 0.468 and )0.419
ꢀ3
ꢀ
(e A
)
37 °C for 48 h. 50 ll of 0.1% MTT or SRB (Sigma)
was added to each well. After 4 h incubation, the
culture medium was removed, and 150 ll of isopro-
panol was added to dissolve the insoluble blue
formazan precipitates produced by MTT reduction.
The plate was shaken for 20 min on a plate shaker to
ensure complete dissolution. The optical density of
each well was measured at 570 nm (MTT) or 540 nm
(SRB) wavelength. The antitumor activity was deter-
mined three times in independent experiments, using
three replicate wells per toxicant concentration (10, 1,
0.1 lg/ml) and obtained the mean optical densities for
drug-treated cells at each concentration as a percentage
of that of untreated cells.
Director, CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK (fax: +44-1223-336033; e-mail: deposit@
ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Acknowledgements
We thank that Professor Honggeng Wang and as-
sistant Professor Haibin Song for their support of the
Crystallographic study. We are also grateful to profes-
sor Kui Wang of National Research Laboratories of
Natural and Biomimetic Drugs of Beijing Medical
University for testing antitumor activity.
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