Structure, properties and cytostatic activity of tributyltin aminoarylcarboxylates

Article abstract of DOI:10.1016/S0020-1693(03)00475-4

Properties of butyltin complexes [Sn(C₄H₉-n) ₃{OOCC₆H₃(NH₂)₂-3,4}] _n (1), [Sn(C₄H₉-n)₃{OOCC ₆H₃(NH₂)<

Full text of DOI:10.1016/S0020-1693(03)00475-4

Inorganica Chimica Acta 356 (2003) 62ꢁ68
/
www.elsevier.com/locate/ica
Structure, properties and cytostatic activity of tributyltin
aminoarylcarboxylates
Florian P. Pruchnik a,*, Ma lgorzata Ban´bu la a, Zbigniew Ciunik a,
Ma lgorzata Latocha b, Barbara Skop b, Tadeusz Wilczok b
a Faculty of Chemistry, University of Wroclaw, ul. Joliot-Curie 14, 50-383 Wroclaw, Poland
b Department of Molecular Biology, Biochemistry and Biopharmacy, Medical University of Silesia, ul. Narcyzo´w 1, 41-200 Sosnowiec, Poland
Received 12 February 2003; accepted 14 July 2003
This article is dedicated to Professor J.J.R. Frau´sto de Silva
Abstract
Properties of butyltin complexes [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,4}]n (1), [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,5}] (2), [Sn(C4H9-
1
n)3{OOCC6H4NÄ
/
NC6H4N(CH3)2-4}] (3) and [Sn(C6H5)3{OOCC6H3(NH2)2-3,5}]n (4) have been investigated. H, 13C and 119Sn
NMR spectra indicate that the compounds in chloroform are distorted tetrahedral and in strongly coordinating solvents trigonal-
bipyramidal complexes. Structure of complex 3 has been determined by X-ray crystallography. This compound adopts trigonal
bipyramidal structure with bridging carboxylato ligand bound asymmetrically with tin atoms in axial positions. The complexes are
effective cytostatic agents.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Organotin complexes; Cytostatic agents; Antitumor activity; Crystal structures
1. Introduction
play high antitumor activities [5ꢁ14]. However, only few
/
tin carboxylates with amino groups have been investi-
gated. These complexes comprise pyridinocarboxylato
and aminosalicylato organotin compounds [5,6] and
Coordination and organometallic compounds are
among the very important antitumor agents [1,2].
Platinum and platinum metals complexes and other
transition metal compounds reveal promising antitumor
activity. However, many of them show severe toxicity.
This prompted a search for new drugs with high activity
and decreased side-effects. A number of organotin
compounds have been shown to be active against
various types of cancers. A series of organotin dipeptide
compounds and a number of diorganotin halides and
[(2-dimethylaminomethyl)phenyl]diphenyltin(IV)
[4?-(dimethylamino)phenyl]azobenzene-sulfonate
4-
and
[(2-dimethylaminomethyl)phenyl]diphenyltin(IV) 4-[4?-
(dimethylamino)phenyl]azobenzoate complexes [15].
Recently we have described 3,4-diaminobenzoato
and 3,5-diaminobenzoato [Sn4O2Bu8(OOCR)4] and
[Sn(CHꢀ
/
CH2)3)OOCR)]
compounds
and
[SnPh3{OOCC6H3(NH2)2-3,4}] complex and their cyto-
static activity [16,17]. However, tributyltin complexes
with these ligands and triphenyltin 3,5-diaminobenzoate
were not investigated. These compounds should show
high cytostatic activity and therefore it seemed interest-
ing to examine their properties. Thus, here we report the
synthesis, properties, structure and in vitro cytostatic
activity of tributyltin complexes with 3,4-diaminobenzo-
ate, 3,5-diaminobenzoate and 2-[4-(dimethylamino)phe-
nylazo]benzoate as well as triphenyltin 3,5-
diaminobenzoate.
pseudohalides [SnR2X2L2] (Lꢀamino ligand, e.g. py,
/
bpy, phen, en) have displayed modest antitumor activity
[3,4]. Many di-n-butyl, tri-n-butyl and triphenyltin
complexes with hydroxyarylcarboxylic, ketocarboxylic,
fluoroarylcarboxylic acids and many other oxygen and
nitrogen containing derivatives of carboxylic acids dis-
* Corresponding author. Tel./fax: ꢂ
/
48-71-3757-232.
E-mail
address:
pruchnik@wchuwr.chem.uni.wroc.pl
(F.P.
Pruchnik).
0020-1693/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0020-1693(03)00475-4

F.P. Pruchnik et al. / Inorganica Chimica Acta 356 (2003) 62ꢁ
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63
2. Experimental
1338mw, 1300s ns(COO), 1280m, 1190s, 1150s, 1150w,
1075m, 1045vw, 1018vw, 997w, 990mw, 955w, 947m,
870m, 860m, 847m, 780s, 690m, 670s, 600m n(SnC),
508m, 492mw.
2.1. Materials and methods
2.1.1. Compounds
3,4-Diaminobenzoic acid and 3,5-diaminobenzoic
acid were obtained from Aldrich, 2-[4-(dimethylami-
no)phenylazo]benzoic acid from POCH (Poland), di-
phenyltin dichloride, triphenyltin chloride and
tributyltin chloride from Strem and used without further
purification. Diphenyltin oxide, triphenyltin oxide and
tributyltin oxide were prepared from diphenyltin
dichloride, triphenyltin chloride and tributyltin chloride
in reaction with sodium hydroxide in aqueous ethanol
solution. Syntheses were carried out in nitrogen atmo-
sphere. Infrared spectra (KBr pellets) were recorded on
a Bruker IFS 113v and 1H, 13C and 119Sn NMR spectra
were taken on a Bruker AMX 300 and a Bruker Avance
500. Carbon, hydrogen and nitrogen analyses were
2.2.3. [Sn(C4H9-n)3{OOCC6H4NÄ
4}] (3)
A mixture of {Sn(C4H9)3}2O (4.000 g, 6.71 mmol) and
NC6H4N(CH3)2-4 (3.614 g, 13.42
mmol) in ethanol (10 cm3) was refluxed with stirring
for 1 h. The dark-red solution was concentrated in
vacuo. Red solid complex 3 was filtered off, washed with
cold ethanol and dried in vacuo. Yield 6.158 g (82.2%).
Anal. Calc. for C27H41N3O2Sn: C, 58.08; H, 7.40; N,
7.53; Sn, 21.26. Found: C, 58.34; H, 7.53; N, 7.64; Sn,
21.41%. Single crystals for X-ray investigations were
/
NC6H4N(CH3)2-
HOOCC6H4NÄ
/
prepared by slow evaporation of tolueneꢁethanol solu-
/
tion of complex. IR (cmꢄ1) (KBr pellet): 3100vw n(CH),
3060vw n(CH), 2956s n(CH), 2920s n(CH), 2877m
n(CH), 2855m n(CH), 1600vs nas(COO), 1580m, 1565s,
1555s, 1520s, 1478w, 1464mw, 1455mw, 1440w, 1415m,
1404s, 1393s, 1370vs ns(COO), 1310m 1260mw, 1250m,
1237mw, 1144vs, 1090m, 1030vw, 117vw, 990vw, 945m,
878w, 865mw, 850w, 812s, 760s, 730vw, 696vw, 678mw,
665ms,632vw, 610mw n(SnC), 585w, 537m,515mw490w,
407m.
performed on a PerkinꢁElmer 2400 CHN analyzer,
/
and tin was determined using ICP-AES method on a
ARL 3410.
2.2. Synthesis of complexes
2.2.1. [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,4}] (1)
A suspension of {Sn(C4H9-n)3}2O (1,673 g, 2.81ꢃ
/
10ꢄ3 mol) and HOOCC6H3(NH2)2-3,4 (0.854 g, 5.62
mmol) in ethanol (20 cm3) was refluxed with stirring for
0.25 h. The pale-yellow solution was evaporated and
dried
in
vacuo.
The
product
[Sn(C4H9-
2.2.4. [Sn(C6H5)3{OOCC6H3(NH2)2-3,5}] (4)
Method a: a mixture of Sn(C6H5)2O (0.610 g, 2.11
mmol) and HOOCC6H3(NH2)2-3,5 (0.321 g, 2.11 mmol)
n)3{OOCC6H3(NH2)2-3,4}] (1) was obtained in the
form of a yellow oil. Yield 1.928 g, 77.9%. Anal. Calc.
for C19H34N2O2Sn: C, 51.72; H, 7.77; N, 6.35. Found:
C, 51.97; H, 8.01; N, 6.11%. IR (cmꢄ1) (film on KBr):
3420sh n(NH2), 3356s n(NH2), 3260sh n(NH2), 2956vs
n(CH), 2928vs n(CH), 2872s n(CH), 2852s n(CH),
1615vs nas(COO), 1580vs nas(COO), 1516s, 1461ms,
1441s, 1416w, 1378s, 1357vs ns(COO), 1328vs ns(COO),
1244vs, 1180w, 1150s, 1110w, 1070m, 1045vw, 1018vw,
997vw,955w, 947m, 870m, 860m, 812m, 775s, 690m,
650s, 600m n(SnC), 560vw, 507vw, 485m, 445m.
in tolueneꢁ
ethanol (3/1) (10 cm3) was refluxed with
/
stirring for 4 h. The light-brown solid was filtered off.
The yellow filtrate was slowly concentrated giving
colorless crystals of complex 4. The solid was washed
with cold ethanol and dried in vacuo. Yield 0.52 g. Anal.
Calc. for C25H22N2O2Sn: C, 59.92; H, 4.42; N, 5.59; Sn,
23.69. Found: C, 60.24; H, 4.78; N, 5.32; Sn, 23.28%.
Method b: a mixture of {Sn(C6H5)3}2O (0.501 g, 0.70
mmol) and HOOCC6H3(NH2)2-3,5 (0.216 g, 1.42 mmol)
in ethanol (20 cm3) was refluxed with stirring for 0.5 h.
The pale-yellow solution was evaporated in vacuo. The
crude complex 4 was recrystallized from toluene (10
cm3) and washed with cold ethanol and dried in vacuo.
Yield 0.436 g (62%). Anal. Calc. for C25H22N2O2Sn: C,
59.92; H, 4.42; N, 5.59; Sn, 23.69. Found: C, 59.64; H,
4.50; N, 5.64; Sn, 24.11%. IR (cmꢄ1) (KBr pellet):
3452vs n(NH2), 3432vs n(NH2), 3352vs n(NH2), 3064
mw n(CHAr), 3048 w n(CHAr), 3020 vw n(CHAr),
2920vw n(CHAr), 1630sh vs nas(COO), 1590vs nas(COO),
1480 ms, 1420m, 1428s, 1372vs ns(COO), 1340m, 1294vs
ns(COO), 1270s, 1190s, 1076s, 996m, 948w, 870mw,
852mw, 788s, 780s, 730vs, 698vs, 660w, 550w, 540w,
518m, 500mw, 446ms.
2.2.2. [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,5}] (2)
A suspension of {Sn(C4H9-n)3}2O (1,673 g, 2.81ꢃ
/
10ꢄ3 mol) and HOOCC6H3(NH2)2-3,4 (0.854 g, 5.62
mmol) in ethanol (15 cm3) was refluxed with stirring for
0.25 h. The brown solution was evaporated and dried in
vacuo. The product [Sn(C4H9-n)3{OOCC6H3(NH2)2-
3,4}] (2) was obtained in the form of a light-brown oil.
Yield 2.03 g, 82.2. Anal. Calc. for C19H34N2O2Sn: C,
51.72; H, 7.77; N, 6.35. Found: C, 51.64; H, 8.02; N,
6.23%. IR (cmꢄ1) (film on KBr): 3460m n(NH2), 3360s
n(NH2), 3228mw n(NH2), 2956vs n(CH), 2924vs n(CH),
2872s n(CH), 2856s n(CH), 1620vs nas(COO), 1594vs
nas(COO), 1484w, 1464s, 1414w, 1374vs ns(COO),

64
F.P. Pruchnik et al. / Inorganica Chimica Acta 356 (2003) 62ꢁ68
/
2.3. X-ray crystallographic study
All measurements of crystal were performed on a
Kuma KM4CCD k-axis diffractometer with graphite-
monochromated Mo Ka radiation. The crystal was
positioned at 65 mm from the KM4CCD camera. 612
Frames were measured at 0.758 intervals with a counting
time of 15 s. The data were corrected for Lorentz and
polarization effects. Absorption correction were
omitted. Data reduction and analysis were carried out
with the Oxford Diffraction (Poland) (formerly Kuma
Diffraction Wroclaw, Poland) programs. The structure
was solved by the heavy atom method (program
SHELXS-97 [18]) and refined by the full-matrix least-
squares method on all F2 data using the SHELXL-97 [19]
programs. Non-hydrogen atoms were refined with
anisotropic thermal parameters; hydrogen atoms were
included from geometry of molecules and Dr maps but
were not refined. In studied crystals one butyl is
disorderd in 2:3 ratio.
Fig. 1. Molecular structure of complex 3, [Sn(C4H9)3{OOC-2-
NC6H4N(CH3)2-4}] with crystallographic numbering. The
open lines indicate a minor component of disorderd butyl group.
C6H4NÄ
/
2.4. Cytostatic activity in vitro.
Table 1
Crystal data and structure refinement for complex [Sn(C4H9)3{OOC-2-
Human cell line A549 (lung adenocarcinoma) was
used for the proliferation assay. The experiments were
repeated in triplicate for each tested Sn compound
concentration. Statistical significance was tested using
C6H4NÄNC6H4N(CH3)2-4}] (3)
/
Empirical formula
Formula weight
Temperature (K)
C27H41N3O2Sn
558.32
100(2)
Student’s t-test (p B
significant). The in vitro tests against all cell lines were
performed as described previously [17,20ꢁ22]. The stock
/0.05 was considered statistically
˚
Wavelength (A)
0.71073
monoclinic
P21/n
Crystal system
Space group
Unit cell dimensions
/
solutions of the organotin compounds at a concentra-
tion of 10ꢄ4 M were prepared in 70% ethanol. The
control cells culture was performed in standard media
enriched with adequate dilution of 70% ethanol. The
results of cytotoxic activity in vitro were expressed as
˚
a (A)
10.1993(6)
10.9261(7)
25.4534(16)
97.498(5)
2812.2(3)
4
˚
b (A)
˚
c (A)
b (8)
3
V (A )
˚
ID50*the dose of compound that inhibits proliferation
/
Z
Dcalc (Mg mꢄ3
)
1.319
0.934
1160
rate of the tumor cells by 50% as compared to control
untreated cells.
Absorption coefficient (mmꢄ1
F(000)
)
Crystal size (mm3)
Diffractometer
0.16ꢃ
Kuma KM4CCD
3.48ꢁ28.47
13]13, ꢄ
/0.12ꢃ0.12
/
3. Results and discussion
u Range (8)
Ranges of h,k,l
/
ꢄ/
/
/
14]
/
9, ꢄ
/
33]
/
33
17871
Complexes 1, 2, 3 and 4 are soluble in ethanol,
methanol, acetone, chloroform, dichloromethane and in
other polar organic solvents and slightly soluble in
Reflections collected
Independent reflections (Rint
Data/parameters
Goodness-of-fit (F2)
)
6538 (0.0367)
6538/322
1.228
aqueous ethanol (50%). The complexes 1ꢁ3 have been
/
obtained in reactions between {Sn(C4H9)3}2O and
appropriate acid in ethanol while the complex 4 has
been prepared in reactions of SnO(C6H5)2 or
{Sn(C6H5)3}2O with 3,5-diaminobenzoic acid. The
structure of complex 3 is shown in Fig. 1. The crystal-
lographic data, selected bond distances and angles are
given in Tables 1 and 2. The compound [Sn(C4H9-
Final R1/wR2 indices (I ꢀ
Largest difference peak and hole (e
Aꢄ3
/
2s(I))
0.0434/0.0841
1.447/ꢄ0.925
/
)
this polymeric structure exist in distorted trigonal
bipyramidal environment. The three n-butyl groups
define the trigonal planes with the very nearly planar
SnC3 groups. The Cꢁ
119.54(16)ꢁ120.47(16)8. The axial positions are occu-
pied by bridging carboxylate ligands forming different
/
SnꢁC angles lie in the range
/
n)3{OOCC6H4NÄ
chain polymer associating via bridging carboxylate
ligands with anti ꢁsyn configuration. The Sn atoms in
/
NC6H4N(CH3)2-4}] (3) is a zigzag
/
/

F.P. Pruchnik et al. / Inorganica Chimica Acta 356 (2003) 62ꢁ
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65
Table 2
Bond lengths (A) and bond angles (8) for complex [Sn(C4H9)3{OOC-2-
C6H4NÄNC6H4N(CH3)2-4}] (3)
respectively (Fig. 2). This distinctive and recurring
zipperlike motif is observed only in the bc planes. The
consecutive chains along the [100] direction form a weak
˚
/
attractive interactions between the C2ꢁC7 aromatic ring
/
Bond lengths
Sn(1)ꢁ
Sn(1)ꢁ
Sn(1)ꢁ
Sn(1)ꢁ
Sn(1)ꢁ
/
C(41)
C(21)
C(31)
O(2i)
O(1)
2.124(4)
2.134(3)
2.142(3)
2.226(2)
2.365(2)
1.244(4)
1.275(4)
2.226(2)
1.508(4)
C(2)ꢁ
C(2)ꢁ
C(5)ꢁ
C(6)ꢁ
N(1)ꢁ
N(2)ꢁ
N(3)ꢁ
N(3)ꢁ
N(3)ꢁ
/
C(3)
C(7)
C(6)
C(7)
1.392(4)
1.392(4)
1.383(5)
1.401(4)
1.427(4)
1.410(4)
1.368(4)
1.444(4)
1.451(4)
of the first chain and the methyl group (C15) of the
second one (Fig. 3). The CÁ Á ÁPh(centroid) distance of
/
/
/
/
˚
3.53 A suggests the presence of the Cꢁ
/
HÁ Á ÁPh weak
/
/
interaction between both groups. It was found that the
weak hydrogen bonding can be important for crystal-
lization of compounds [25,26].
/
/
C(7)
O(1)ꢁ
O(2)ꢁ
O(2)ꢁ
C(1)ꢁ
/
C(1)
C(1)
/
C(8)
/
/
C(11)
C(14)
C(15)
/
Sn(1ii)
/
Infrared spectra of all investigated complexes are
consistent with X-ray data for compound 3. The
/C(2)
/
Bond angles
C(41)ꢁSn(1)ꢁ
C(41)ꢁSn(1)ꢁ
C(21)ꢁSn(1)ꢁ
C(41)ꢁSn(1)ꢁ
C(21)ꢁSn(1)ꢁ
C(31)ꢁSn(1)ꢁ
C(41)ꢁSn(1)ꢁ
presence of nas(COO) and ns(COO) in the range 1580ꢁ
1630 and 1330ꢁ
1374 cmꢄ1, respectively, and therefore
nsCOO values are consistent with the
/
/
/
C(21) 119.54(16) C(21)ꢁ
C(31) 119.86(16) C(31)ꢁ
C(31) 120.47(12) O(2)#1ꢁ
/
Sn(1)ꢁ
/
O(1)
94.99(10)
87.20(11)
/
/
/
/
Sn(1)ꢁ
/O(1)
as
COO
/
/
/Sn(1)ꢁO(1) 168.97(8)
/
large Dnꢀ
/n
ꢁ
/
/
/
O(2i)
O(2i)
O(2i)
O(1)
85.68(11) C(1)ꢁ
93.99(10) C(1)ꢁ
93.75(11) O(1)ꢁ
84.33(11)
/
O(1)ꢁ
O(2)ꢁ
C(1)ꢁ
/
Sn(1)
Sn(1ii)
O(2)
136.6(2)
130.2(2)
124.9(3)
presence in the complexes 1, 2, 3 and 4 asymmetrically
coordinated carboxylato group. These differences are
larger for complexes 1, 2 and 4 in comparison with
compound 3. This suggests that corboxylato groups in
the former complexes are coordinated more asymme-
trically than in the latter. This is consistent with
/
/
/
/
/
/
/
/
/
/
Symmetry transformations used to generate equivalent atoms: i: ꢄ
/
xꢂ1/2, yꢂ1/2, ꢄzꢂ1/2; ii: ꢄxꢂ1/2, yꢄ1/2, ꢄzꢂ1/2.
/
/
/
/
/
/
/
/
/
relatively small difference between Sn(1)ꢁ
/
O(1) and
Snꢁ
/
O distances. The shorter Sn(1)ꢁ
/
O(2A) bond is equal
O(1) distance is
2.365(2) A. The difference between these bonds (0.139
Sn(1)ꢁO(2i) distances. The intense ns(NH2) vibrations
/
˚
to 2.226(2) A and the longer Sn(1)ꢁ
/
are observed at relatively low frequencies and are
broadened, suggesting that strong hydrogen bonding is
pronounced in the 1, 2 and 4 compounds, while in
compound 3 crystal structure is controlled by weak
hydrogen bonding and stacking of phenyl rings of the
˚
˚
A) is relatively small. In the case of many analogous
˚
0.5 A [23,24]. It is
compounds this difference is 0.2ꢁ
˚
equal to 0.325 A in the complex [SnBu3(OOCC9H8N)]
/
[24]. The O(1)ꢁSn(1)ꢁO(2A) angle is 168.97(8)8 and
/
/
ligands. The n(SnC) bands for butyl compounds (1ꢁ
are observed in the range 600ꢁ
610 cmꢄ1, thus at values
similar to other bytyl Sn(IV) compounds.[27].
/3)
belongs to the lowest values found in the single strand
[SnR3(OOCR?)]n polymers [23,24]. The polymeric zigzag
chains are located along the [001] direction. The crystal
structure of compound 3 is stabilized by intermolecular
/
stacking interaction between parallel C(8)ꢁ/C(13) phenyl
rings of the two neighbor molecules. The distance
˚
between these rings and offset are 3.50 A and 1.43 A,
˚
Fig. 2. Molecular packing along the [100] direction showing the
stacking of the OOC-C6H4NÄ
/
NC6H4N(CH3)2 ligand domains of 3
Fig. 3. Weak hydrogen bonding between consecutive polymeric
chains.
within the lattice. The hydrogen atoms are omitted for clarity.

Table 3
1H, 13C and 119Sn NMR spectra of complexes [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,4}] (1), [Sn(C4H9-n)3{OOCC6H3(NH2)2-3,5}] (2), [Sn(C4H9-n)3{OOCC6H4NÄ
[(C6H5)3Sn{OOCC6H3(NH2)2-3,5}] (4)
/NC6H4N(CH3)24}] (3) and
Complex, sol- 1H NMR ppm (Hz)
vent
13C NMR ppm (Hz)
119Sn NMR
ppm (Hz)
1, CDCl3
CH2-a, 1.57ꢁ
7.4); H6, 7.43 (dd, 3J(H6,H5)ꢀ
NH2, 3.94 (s), 3.70 (s)
1, (CD3)2SO CH2-a, 1.51ꢁ1.63, (m); CH2-b 1.19ꢁ
3J(HꢁH) 7.3); H2, 7.11 (s); H6, 7.05 (d, 3J(H5,H6)ꢀ
3.94 (s), 3.70 (s)
CH2-a, 1.57ꢁ1.65 (m); CH2-bꢂ
7.4); H2, H6, 6.71 (s); H4, 6.17 (s); 3,5ꢁ
/
1.65, (m); CH2-bꢂ
/
CH2-g, 1.24ꢁ
/
1.35 (m); CH3-d, 0.87 (t, 3J(Hꢁ
1.7); H5, 6.57 (d); 3,4- C-g, 26.81 (3J(13Cꢁ119/117
132.80; C6 123.41; C1 122.53; C2 118.70; C5 114.59
Sn)ꢀ
496.9/480.0); C-b, 27.6 (2J(13Cꢁ119/117
79.6); C-d, 13.66; (COO) 168.04; C4 139.45; C3
/
H) C-a, 16.30 (1J(13Cꢁ119/117
/
Sn)ꢀ
/
361.5/344.7); C-b, 27.67 (2J(13Cꢁ119/117
/
Sn)ꢀ20.2); 104.4
/
/
8.1); H2, 7.37 (d, 4J(H2,H6)ꢀ
/
/
Sn)ꢀ
/
63.9); C-d, 13.44; (COO) 171.87; C4 139.49; C3
/
/
1.32, CH2-g, 1.00ꢁ
/
1.35 (m); CH3-d, 0.81 (t, C-a, 19.33 (1J(13Cꢁ119/117
8.2); H5, 6.47 (d); 3,4-NH2, C-g, 26.61 (3J(13Cꢁ119/117
Sn)ꢀ
133.65; C6 120.40 C1 119.05; C2 115.35; C5 112.66
Sn)ꢀ
C-a, 16.36 (1J(13Cꢁ119/117 358.9/343.9); C-b, 27.66 (2J(13Cꢁ119/117
Sn)ꢀ
C-g, 26.83 (3J(13Cꢁ119/117 64.7); C-d, 13.45; (COO), 171.77; C3, C5 147.21; C1
133.69; C2, C6 107.40; C4 105.02
1.08 (m); CH3-d, 0.81 (t, C-a, 19.13 (1J(13Cꢁ119/117
Sn)ꢀ505.5/482.8); C-b, 27.61; C-g, 26.60
Sn)ꢀ
(3J(13Cꢁ119/117 80.9); C-d, 13.60; (COO), 168.39; C3, C5 149.13; C1 131.67; C2,
C6 104.06; C4 103.51
C-a, 16.5 (1J(13Cꢁ119/117
Sn)ꢀ24.3); 77.9
/
/
/
Sn)ꢀ
/
27.8);
/
/
/
/
3
2, CDCl3
/
/
CH2-g, 1.24ꢁ
/
1.35 (m); CH3-d, 0.87 (t, J(H,H)ꢀ
/
/
/
/
Sn)ꢀ20.2); 110.7
/
/NH2 3.78 (s)
/
/
2, (CD3)2SO CH2-a, 1.51ꢁ
/
1.62 (m); CH2-b 1.18ꢁ
/
1.32; CH2-g, 1.00ꢁ
/
/
/
3J(H,H)ꢀ7.3); H2, H6, 6.40 (s); H4, 5.98 (s)
/
/
/
3
3,
CD3COCD3
CH2-a, 1.63ꢁ
7.3); H2?, H6?, 7.83 (m, 3J(H2?,H3?)ꢀ
3J(H3,H4)ꢀ7.7); H4, 7.48 (dt, 3J(H4,H5)ꢀ
4J(H3,H5)ꢀ1.5); H3?, H5?, 6.83 (m, 3J(H5?,H6?)ꢀ
Ho, 7.76ꢁ7.83 (m, 3J(1Hꢁ119/117 62.1); Hm, Hp, 7.40ꢁ
Sn)ꢀ
(d, 4J(H2,H6)ꢀ2.0); H4 6.09 (t); 3,5-NH2 ꢁ
3.59 (s)
/
1.71 (m); CH2-bꢂ
/
CH2-g, 1.28ꢁ
9.4); H6, 7.68 (d 3J(H5,H6)ꢀ
7.6, 4J(H4,H6)ꢀ1.5), H5, 7.39 (dt,
9.4); CH3, 3.08 (s)
/
1.38 (m); CH3-d, 0.66 (t, J(H,H)ꢀ
/
/
Sn)ꢀ
Sn)ꢀ
/
390.7/373.6); C-b, 27.55 (2J(13Cꢁ119/117
/
/
/
/
7.6); H3, 7.52 (d, C-g, 26.59 (3J(13Cꢁ119/117
/
/
70.2); C-d, 12.86; (COO) 172.09; C2 152.53; C4?
/
/
/
151.50; C1? 143.58; C1 133.19; C4 129.65; C6 128.76; C5 127.87; C2?, C6? 124.82; C3
116.86; C3?, C5? 111.04; CH3 39.20
/
/
4, CDCl3
/
/
/
/
7.50 (m); H2, H6 6.88 Ci 140.69; Co, 137.65, (2J(13Cꢁ119/117
63.5); Cp, 130.02 (4J(13Cꢁ119/117
Sn)ꢀ
132.13; C2, C6 107.91; C4 105.56
/
Snꢀ
/
47.5); Cm,128.82 (3J(13Cꢁ119/117
/
Sn)ꢀ
/
ꢄ/112.0
/
/
/
/
13.2); (COO) 173.21; C3, C5 147.33; C1

F.P. Pruchnik et al. / Inorganica Chimica Acta 356 (2003) 62ꢁ
/68
67
1
The H NMR data of complexes 1ꢁ4 are given in
/
Table 4
Inhibition doses ID50 of complexes 1ꢁ
Table 3. The proton chemical shifts of the Sn(C4H9)3
moiety are similar to those of other [Sn(C4H9)3X]
/4 against A549 cancer cells
Compound ID50 (mmol
Compound
ID50 (mmol
complexes [7,28ꢁ
are multiplets both in CDCl3 and (CD3)2SO, therefore
the determination of nJ(119/117Snꢁ1
H) coupling con-
/
32]. All CH2 signals of n-butyl groups
dmꢄ3
)
dmꢄ3
)
/
1
0.25
HOOCC6H4NÄ
/
N
84.29
1
C6H4NMe2-4
HOOCC6H3(NH2)2-3,4
HOOCC6H3(NH2)2-3,5
stants was not possible. The H chemical shift of the
phenyl and carboxylato ligands were deduced from
2
3
4
0.57
1.80
0.30
i.
i.
resonance
nJ(119/117Snꢁ1
shifts and coupling constants for complexes 1ꢁ
well with data found for [Sn(C4H9)3(OOCR)],
[Sn(C6H5)3(OOCC6H5)] [7,28ꢁ32],
[Sn(C6H5)3(OOCC6H4NH2)] and other triphenyltin(IV)
compounds [30ꢁ32] and with spectra of 3,4-diamino-
intensities
H) coupling constants. Both chemical
4 agree
and
nJ(1Hꢁ1
/
H)
and
/
i., inactive.
/
/
constants for complexes 1 and 2 in (CD3)2SO (496.9 and
505.5 Hz) are typical of the five-coordinate organotin
/
compounds with trigonal-bipyramidal structure [29ꢁ
The estimated CꢁSnꢁC angles for 1 and 2 in DMSO are
approximately 118 and 1198, respectively.
/32].
benzoic and 2-(4-dimethylaminophenylazo)benzoic
acids and their metal salts. The 119Sn chemical shifts
are higher for four-coordinate compounds than for the
five-coordinate complexes. They depend strongly also
on the number and nature of alkyl or aryl groups as well
as on electronegativity of inorganic ligand coordinated
with tin central atom. The values of the d(119Sn) for the
/
/
The complexes 1, 2, 3 and 4 belong to the very
efficient cytostatic agents (Table 4). Compounds are
very active against A547 cells (ID50ꢀ
dmꢄ3). Activity of the compounds against this cell line
decreases in the series 1]4]2ꢀ3. It is noteworthy
that the complexes are active in ethanol solutions. Thus
these compounds are promising cytostatic agents in
vitro.
/
0.25ꢁ1.80 mmol
/
/
/
/
complexes 1, 2 and 4 in CDCl3 are 104.4, 110.7 and ꢄ
/
112.0 ppm respectively and for compound 3 in
(CD3)2CO, 77.9 ppm. They are in the range found for
[Sn(C4H9)3(OOCR)] and Sn(C6H5)3(OOCR)] com-
plexes. The higher values of the d(119Sn) for complexes
1 and 2 in comparison with that for compound 3
indicate that electronegativity of 3,4-diaminobenzoate
and 3,5-diaminobenzoate ligands is higher than that of
2-(4-dimethylaminophenylazo)benzoate. The assign-
ment of the 13C resonances of the tri-n-butyl part
4. Supplementary material
Crystallographic data (excluding structure factors) for
the structural analysis have been deposited with the
Cambridge Crystallographic Data Centre, CCDC No.
204437. Copies of this information may be obtained free
of charge from The Director, CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK (fax: ꢂ44-1223-336-033; e-
mail: deposit@ccdc.cam.ac.uk or www: http://
www.ccdc.cam.ac.uk).
follows from the nJ(119/117Snꢁ3
and the aromatic resonances of triphenyltin moiety from
both the nJ(119/117Snꢁ13
C) coupling constants and signal
intensities. It is known that J(119/117Snꢁ13
/
C) coupling constants
/
/
n
/
C) coupling
constants depend on properties of ligands in organotin
compounds and increase with increasing of coordination
number of tin atom [29ꢁ
/
32]. They decrease in the order:
C)ꢀ2J(119/117Snꢁ13
13C) and are considerably larger for phenyl tin com-
1J(119/117Snꢁ13C)ꢁ3J(119/117Snꢁ13
/
/
/
/
/
References
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1J(119/117Snꢁ13
C) coupling constants for complexes 1
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in chloroform these compounds are monomeric with
/
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