Di- and tri-organotin(IV) complexes with 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone: Synthesis, characterization and in vitro antitumor activities

Article abstract of DOI:10.1016/j.jorganchem.2012.10.031

Series of new organotin(IV) complexes of the types R₂SnL, R is Me (1), Ph (2), o-Cl-C₆H₄CH₂ (3); and [R ₃SnL]_∞, R = n-Bu (4) (H₂L = 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone) have been synthesized and structurally characterized by means of elemental analysis, FT-IR, UV-vis spectroscopy, NMR (¹H, ¹³C and ¹¹⁹Sn) spectra and X-ray single crystal diffraction analyses. Structural analyses reveal that complexes 1-3 show similar monomeric structure, in which the tin center is coordinated with the enolic tridentate ligand (L) in the ONO chelate mode and exhibits five-coordinated trigonal bipyramidal geometry. Unexpectedly, complex 4 presents as a rare one-dimensional chain polymeric structure, in which the coordination of Sn is also five-coordinated trigonal bipyramidal geometry and the segment of tri-n-butyltin is bridged by the de-protonated phenolate O atom and the carbonyl O atom from the non-enolic Schiff base ligand. All compounds exhibit good in vitro antitumor activity toward human colon cancer cells (HCT-8), lung cancer cells (A549) and human promyelocyticfina leukemic cells (HL-60). The results indicate that both alkyl groups bound with tin centers and the structural of organotin compounds have significant effect on their in vitro antitumor activities. Among them, the polymeric tri-n-butyltin Schiff base complex 4 is the most active one, and the complex 3 shows high selectivity on the tumor cells HCT-8 and HL-60. For all of the title compounds, there was a good dose-effect relationship.

Full text of DOI:10.1016/j.jorganchem.2012.10.031

Accepted Manuscript
Di- and tri-organotin(IV) complexes with 2-hydroxy-1-naphthaldehyde 5-chloro-2-
hydroxybenzoylhydrazone: Synthesis, characterization and in vitro antitumor activities
Min Hong, Handong Yin, Xiuyun Zhang, Chuan Li, Caihong Yue, Shuang Cheng
PII:
S0022-328X(12)00620-1
10.1016/j.jorganchem.2012.10.031
JOM 17752
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 28 April 2012
Revised Date: 5 October 2012
Accepted Date: 17 October 2012
Please cite this article as: M. Hong, H. Yin, X. Zhang, C. Li, C. Yue, S. Cheng, Di- and tri-organotin(IV)
complexes with 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone: Synthesis,
characterization and in vitro antitumor activities, Journal of Organometallic Chemistry (2012), doi:
10.1016/j.jorganchem.2012.10.031.
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Graphical Abstract-Synopsis
Di-
and
tri-organotin(IV)
complexes
with
2-hydroxy-1-naphthaldehyde-5-chloro-2-hydroxybenzoylhydrazone:
Synthesis, characterization and in vitro cytotoxicity
Min Honga, Handong Yina , Xiuyun Zhanga, Chuan Lia, Caihong Yuea, Shuang
Chengb
a Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology,
School of Chemistry and Chemical Engineering; Liaocheng University, Liaocheng 252059,
China
b School of Agriculture, Liaocheng University, Liaocheng 252059, China
Synopsis
A
series
of
organotin(IV)
complexes
with
2-hydroxy-1-naphthaldehyde
5-chloro-2-hydroxybenzoylhydrazone have been synthesized and characterized. In vitro cytotoxic
activity against three human tumor cell lines is investigated. The results indicate that different
alkyl groups organotin(IV) complexes have different effects on cytotoxic activity and selectivity.
Corresponding author. Tel.:/Fax: +86 6358239121.
E-mail address: handongyin@163.com (H. Yin).

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Graphical Abstract-Pictogram
Di-
and
tri-organotin(IV)
complexes
with
2-hydroxy-1-naphthaldehyde-5-chloro-2-hydroxybenzoylhydrazone:
Synthesis, characterization and in vitro cytotoxicity
Min Honga, Handong Yina , Xiuyun Zhanga, Chuan Lia, Caihong Yuea, Shuang
Chengb
a Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology,
School of Chemistry and Chemical Engineering; Liaocheng University, Liaocheng 252059,
China
b School of Agriculture, Liaocheng University, Liaocheng 252059, China
Pictogram
Corresponding author. Tel.:/Fax: +86 6358239121.
E-mail address: handongyin@163.com (H. Yin).

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Highlights:
1. Series of new organotin(IV) complexes have been synthesized and characterized.
2. A novel one-dimensional chain polymeric compound with non-enolic Schiff base ligand was
obtained.
3. All compounds exhibit well in vitro cytotoxic activity.

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Di-
and
tri-organotin(IV)
complexes
with
2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone:
Synthesis, characterization and in vitro antitumor activities
Min Honga, Handong Yina , Xiuyun Zhanga, Chuan Lia, Caihong Yuea, Shuang
Chengb
a Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology,
School of Chemistry and Chemical Engineering; Liaocheng University, Liaocheng 252059,
China
b School of Agriculture, Liaocheng University, Liaocheng 252059, China
Abstract
Series of new organotin(IV) complexes of the types R2SnL, R is Me (1), Ph (2), o-Cl-C6H4CH2
(3);
and
[R3SnL]∞,
R
=
n-Bu
(4)
(H2L
=
2-hydroxy-1-naphthaldehyde
5-chloro-2-hydroxybenzoylhydrazone) have been synthesized and structurally characterized by
means of elemental analysis, FT-IR, UV–Vis spectroscopy, NMR (1H, 13C and 119Sn) spectra and
X-ray single crystal diffraction analyses. Structural analyses reveal that complexes 1-3 show
similar monomeric structure, in which the tin center is coordinated with the enolic tridentate
ligand (L) in the ONO chelate mode and exhibits five-coordinated trigonal bipyramidal geometry.
Unexpectedly, complex 4 presents as a rare one-dimensional chain polymeric structure, in which
the coordination of Sn is also five-coordinated trigonal bipyramidal geometry and the segment of
tri-n-butyltin is bridged by the de-protonated phenolate O atom and the carbonyl O atom from the
non-enolic Schiff base ligand. All compounds exhibit good in vitro antitumor activity toward
human colon cancer cells (HCT-8), lung cancer cells (A549) and human promyelocyticfina
leukemic cells (HL-60). The results indicate that alkyl groups bound with tin centers and the
structure of organotin compounds have significant effect on their in vitro antitumor activities.
Among them, the polymeric tri-n-butyltin Schiff base complex 4 is the most active one, and the
complex 3 shows high selectivity on the tumor cells HCT-8 and HL-60. For all of the title
Corresponding author. Tel.:/Fax: +86 6358239121.
E-mail address: handongyin@163.com (H. Yin).

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compounds, there was a good dose-effect relationship.
Keywords: Organotin(IV) complexes; Schiff base ligand; Crystal structure; In vitro antitumor
activity
1. Introduction
Organotin(IV) complexes have attracted much interest because of their bioactivities, in
particular as potential biocidal (e.g., antimicrobial, antifungal) [1] and anticancer agents [2].
Among main-group metal compounds, they appear to exhibit the most potent antitumor activities,
in some cases being more effective than cisplatin in vitro tests [3]. It is interesting to combine the
anticancer properties exhibited by the organotin(IV) complexes with the established biological
effects of hydrazone Schiff base. Organotin(IV) complexes with hydrazone Schiff base ligands
have received increasing attention owing to not only their potential applications in biotechnology
[4-8], but also their fascinating chemical behavior [9-13]. Structural analyses reveal that
hydrazone Schiff base ligands have strong coordination ability, a possibility of keto-enol
tautomerism and multi-coordination modes (scheme 1 A、B), and when reacting with organotin(IV)
moiety, which adopt an enolic tridentate chelate mode with monomeric or dimeric structure
(shown in scheme 2 I and II) [12].
In general, the biochemical activity of organotin(IV) complexes is influenced greatly by the
structure of the molecule and the coordination number of the tin atoms [14–16]. In addition, it is
well known that the biological activity of organotin complexes is related to the type of alkyl
groups attached to the organotin moiety. Usually, n-butyltin(IV) complexes display a larger array
of biological activity than their methyl-, phenyl- or benzyltin(IV) analogues [17-19]. Meanwhile,
as many of the typical antitumor agents, the efficiency and application of organotin derivatives
seem to be limited by their poor water solubility [20]. Therefore, the synthesis of organotin
complexes with higher water solubility has received particular attention [21–23]. In this context,
we design and synthesize a series of organotin(IV) complexes containing hydrophilic hydroxyl
ligands and involving different alkyl groups. Interestingly, a polymeric organotin(IV) compound
with novel non-enolic coordination mode for Schiff base ligand (shown in scheme 2 III) was

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obtained by the reaction of hydrazone ligand with bi(tri-n-butyltin) oxide. In order to compare
their activity with that of cisplatin, in vitro cytotoxic activity on human colon cancer cells
(HCT-8), lung cancer cells (A549) and human promyelocyticfina leukemic cells (HL-60), have
been tested in details. The dependence of the antitumor activity of the complexes on various
factors, namely the nuclearity, the organic ligand bound with tin and the coordination type are also
discussed.
2. Experimental
2.1. Materials and measurements
All reagents were commercially available and used without further purification. Schiff base
ligand and di-o-chlorobenzylltin chloride were prepared by the methods reported in the literature
[13,24,25]. All solvents used in the reaction were of AR grade and dried using standard literature
procedures.
FT-IR spectra were recorded on a Nicolet-460 spectrophotometer using KBr discs. 1H, 13C and
119Sn NMR spectra were recorded on a Mercury Plus-400 NMR spectrometer; chemical shifts
were given in ppm relative to Me4Si and Me4Sn in CDCl3 solvent. Elemental analyses were
performed with a PE-2400II elemental analyzer. UV-Vis was performed on a UV-2550 ultraviolet
spectrophotometer.
2.2 X-ray crystallography
Diffraction data for the title compounds were obtained on a Bruker Smart 1000 CCD
diffractometer (graphite monochromized Mo Kα radiation, λ = 0.71073 Å). All data were
corrected using SADABS method and the final refinement was performed by mull-matrix
least-square methods with anisotropic thermal parameters for non-hydrogen atoms on F2 using
SHELX-97 program [26]. The hydrogen atoms were added theoretically, riding on the concerned
atoms and refined with fixed thermal factors.
2.3 In vitro antitumor activity

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The cell lines, human colon cancer cells (HCT-8), lung cancer cells (A549) and human
promyelocyticfina leukemic cells (HL-60) were used for screening. HCT-8 and A549 cell lines
were grown and maintained in Roswell park memorial institute 1640 (DMEM for HL-60)
supplemented with 10% fetal bovine serum (FBS), 1% an antibiotic (gentamycin), and were
incubated at 310 K in a 5% CO2 atmosphere.
Cell proliferation in compound-treated cultures was evaluated by using a system based on the
tetrazolium compound (MTT) [27]. All cell lines were seeded into 96 well plates at a
concentration of about 5000 cells/mL and were incubated in an atmosphere of 5% CO2 for 24 h.
Then, the samples (organotin complexes) were added and further incubation was carried out at
310 K for 48 h. The complexes were serially diluted with DMSO and added to cell incubation
medium at the final concentration of 0.5% DMSO in the medium. MTT was added to each well at
the final concentration of 10%. After 4 h incubation, the culture medium was removed, and 100 µl
DMSO was added to dissolve the insoluble blue formazan precipitates produced by MTT
reduction. The plate was shaken for 10 min on a plate shaker to ensure complete dissolution. The
optical density of each well was measured at 570 nm wavelength. The antitumor activity was
determined three times in independent experiments, using six replicate wells per toxicant
concentration (10, 5, 1, 0.5, 0.1 ꢀg/mL) and we obtained the mean optical densities for
drug-treated cells at each concentration.
2.4 Synthesis
2.4.1. Preparation of 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone
The Schiff base of 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone was
prepared with 5-chloro-2-hydroxybenzoylhydrazide and 2-hydroxy-1-naphthaldehyde in ethanol
solution. 2-hydroxy-1-naphthaldehyde (1.722g, 10.0mmol) was added slowly to an ethanol
solution containing 5-chloro-2-hydroxybenzoylhydrazide (1.866g, 10.0mmol) under stirring for 2
h. The yellow solid formed was filtered off, washed with water and ethanol in turn and dried in
vacuum. Yield 75%. M.p. >573K. Anal. Calc. for C18H13N2O3Cl: C, 63.44; H, 3.85; N, 8.22.
Found: C, 63.53; H, 3.91; N, 8.11%. IR (KBr, cm-1) v: 3185(s, N–H), 3440(m, O–H), 1736(s,
1
C=O), 1631(m, C=N). H NMR (400 MHz, CDCl3, 298 K): 9.49 (1H, s, CH), 3.30 (1H, s, NH),

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12.64 (1H, s, naphthalene–OH), 11.89 (1H, s, aromatic–OH). 13C NMR (101 MHz, CDCl3, 298 K):
163.72 (CH=N), 168.62 (CO-N), 113.63–138.90(aromatic carbons).
2.4.2. General procedure for synthesis of complexes
The ethanol solution (2 mL) of sodium ethoxide (0.0272 g, 0.4mmol) was added to 30 mL
methanol solution of 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone (0.0682
g, 0.2 mmol) with stirring at room temperature. When the solution changed from yellow solid to
clear, diorganotin(IV) dichloride (0.2 mmol) was added. The mixture was heated at reflux for ca. 8
h, and then filtered. The solvent was evaporated under vacuum to leave the yellow solid, which
was recrystallized from dichloromethane–petroleum ether (1:1) to give yellow crystal.
2.4.2.1. (CH3)2 SnC18H11N2O3Cl (1)
Yield 85%. Anal. Calc. for C20H17ClN2O3Sn: C, 49.27; H, 3.51; N, 5.75. Found: C, 49.38; H,
3.62; N, 5.63%. IR (KBr, cm-1) v: 1630(s, C=N), 1606(m, C=N–N=C), 620(m,Sn-O), 563(m,
Sn–C), 475(w, Sn–N).1H NMR (400 MHz, CDCl3, 298 K): 9.50 (1H, t, CH), 0.90 (6H, m, 2JSn-H
=
68 Hz, SnCH3), 11.84 (1H, s, aromatic–OH). 13C NMR (101 MHz, CDCl3, 298 K): 168.35
(CH=N), 169.51 (CO-N), 13.92 (1JSn-C = 520.4Hz, Sn-CH3), 107.10–158.17(aromatic carbons).
119Sn NMR (149 MHz, CDCl3, 298 K): -162.3 ppm.
2.4.2.2. (C6H5)2 SnC18H11N2O3Cl (2)
Yield 83%. Anal. Calc. for C30H21ClN2O3Sn: C, 58.90; H, 3.46; N, 4.58. Found: C, 58.98; H,
3.56; N, 4.45%. IR (KBr, cm-1) v: 1618(s, C=N), 1600(m, C=N–N=C), 616(m, Sn-O), 570(m,
1
Sn–C), 478(w, Sn–N). H NMR (400 MHz, CDCl3, 298 K): 9.52 (1H, s, CH), 11.79 (1H, s,
aromatic–OH). 13C NMR (101 MHz, CDCl3, 298 K): 168.43 (CH=N), 170.33 (CO-N),
107.42–158.17(aromatic carbons). 119Sn NMR (149 MHz, CDCl3, 298K): -341.4 ppm.
2.4.2.3 (o-ClC6H4CH2)2 SnC18H11N2O3Cl (3)
Yield 62%. Anal. Calc. for C32H23Cl3N2O3Sn: C, 54.24; H, 3.27; N, 3.95. Found: C, 54.46; H,
3.45; N, 3.63%. IR (KBr, cm-1) v: 1613(s, C=N), 1599(m, C=N–N=C), 617(m, Sn-O), 570(m,
1
Sn–C), 473(w, Sn–N). H NMR (400 MHz, CDCl3, 298 K): 9.49 (1H, s, CH), 11.76 (1H, s,
aromatic–OH). 13C NMR (101 MHz, CDCl3, 298 K): 168.47 (CH=N), 170.29 (CO-N), 33.60

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(Sn-CH2-Ph), 107.35–158.17 (aromatic carbons). 119Sn NMR (149 MHz, CDCl3, 298 K): -281.9
ppm.
2.4.2.4 Preparation of [(C4H9)3 Sn(C18H11N2O3Cl)]∞ (4)
2-Hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone (0.0682 g, 0.2 mmol) was
added to 50 ml flask containing 30 mL methanol solution with stirring for 30 minutes at room
temperature. After bis(tri-n-butyltin) oxide (0.0596g, 0.1mmol) was added to the reactor, the
reaction mixture was refluxed for 8 h more. The yellow solution with deposit thus obtained was
evaporated under vacuum to form a yellow solid and recrystallized in dichloromethane–petroleum
ether to give yellow crystal. Yield 89%. Anal.Calc. for C30H38N2O3ClSn: C, 57.30; H, 6.09; N,
4.46. Found: C, 57.63; H, 6.27; N, 4.23%. IR (KBr, cm-1) v:1617(s, C=N), 1742(s, C=O), 3181(s,
1
N–H), 3441(m, O–H), 601(m, Sn-O), 535(m, Sn–C). H NMR (400 MHz, CDCl3, 298 K): 9.46
(1H, t, CH), 3.65 (1H, s, NH), 0.88 (9H, t, –CH3), 1.35–1.68 (18H, m, SnCH2CH2CH2), 12.58 (1H,
s, naphthalene–OH). 13C NMR (101 MHz, CDCl3, 298 K): 168.54 (CH=N), 170.11 (CO-N),
107.04–158.17 (aromatic carbons), 27.96, 22.63, 16.97, 13.68 (Sn-Bu) ppm. 119Sn NMR (149
MHz, CDCl3, 298 K): -197.1 ppm.
3. Result and discussion
3.1 Syntheses
Complexes 1–3 were obtained by reaction of H2L/EtONa/R2SnCl2 in a 1:2:1 molar ratio in
methanol at 343 K, while complex 4 was obtained by reaction of H2L/(R3Sn)2O in a 1:1 molar
ratio in methanol at reflux. Moreover, when the reaction of 2-hydroxy-1-naphthaldehyde
5-chloro-2-hydroxybenzoylhydrazone with triphenyltin chloride was carried out, complex 2 was
also obtained. It is different from the former method of preparation. If like the polymeric structure
of complex 4, triphenyltin next to two large groups has relatively large steric and the formed
complex is not stabilizer than the diphenyltin compound. It is similar with the previous complexes
we have reported [9]. The synthetic procedures are shown in Scheme 3.
3.2 IR Spectra

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In IR spectra of the ligand, the vibration bands of ν(N-H), ν(O-H) and ν(C=O) were observed at
3185, 3440 and 1735 cm–1, respectively. In the complexes 1–3, there was no C=O characteristic
stretching vibration absorption, showing that the C=O has enolization and the oxygen atom has
coordinated to the tin atom. The strong bands appearing at 1613–1630 and 1598–1610 cm–1 in the
spectra indicate the presence of C=N and C=N–N=C group [28, 29]. Two new bands at 535–570
and 465–475 cm–1 are characteristic of Sn–O and Sn–N absorptions, respectively [10]. However,
the ν(C=O) band of complex 4 remains due to non-enolic Schiff base ligand and there is no
absorption to indicate the presence of C=N–N=C groups. There are only Sn-O bands absorptions
for complex 4. All these values are consistent with those detected in a number of organotin(IV)
derivatives [30,31]. And the characteristic absorptions of complexes 1–3 at 3370–3440 cm–1
indicate that the oxygen atoms of phenolic hydroxyl do not participate in the coordination to the
Sn atom.
3.3 NMR Spectra
All complexes gave good NMR spectra. In the spectra of ligand, single resonance is observed at
3.30 ppm, which is absent in the spectra of complexes 1-3, indicating deprotonation of–NHN=
group and confirming that the ligand coordinates to the tin in the enol form [32]. However, for
compound 4, the single resonance for the proton of –NHN= group remains at 3.6 ppm. The results
indicate that –NHN= group of the ligand does not coordinate to the Sn center in complex 4. It is
different from our previous reports [12]. In the 1H NMR spectra of complexes 1–3, there is no
signal resonance for naphthalenic OH group, and the single resonances of Ar–OH are observed at
11.76–11.84 ppm, which strongly suggests that the oxygen atoms of naphthalene nucleus
participate in coordination to the tin atom, but the phenolic oxygen atoms do not. While for
complex 4, the single resonance of Ar–OH is absent, and the naphthalenic OH group was
observed at 12.58 ppm [33].They are in accordance with X-ray single crystal diffraction structural
analysis.
The 119Sn chemical shift of tin complexes appears to depend not only on coordination number,
but is also very sensitive to the type of donor atoms bonded to the metal ion, so it is a useful tool
to determine the chemical environment of the tin atom. Holecek and coworkers studies result

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show that in the di- and tri-organotin the 119Sn NMR spectra can be used as an indicator of the
coordination number of the tin atom. In the range of +200 to -60, -90 to -190, -210 to -400, -440 to
-540 ppm, the coordinate number of the tin are four, five, six and seven [34-36]. The di-organotin
complexes of the present investigation exhibit the 119Sn spectra at -162.30 ppm, suggesting that
the tin atom is five-coordinate in the complex 1. However, diphenyltin complexes 2, 3 show the
119Sn spectra at -341.40, -281.86 ppm, indicating that the tin atoms are five-coordinate [32]. In the
tri-organotin, the signal of the 119Sn spectra appear at -197.08 ppm, indicating the tin atoms are
five-coordinate in the complex 4.
3.4 UV–Vis spectra
The UV-Vis absorption spectra of Sn(IV) complexes with multidentate Schiff base ligand
(shown in Fig 1) could also be good indicator of their geometry, which give some structural
information of organotin(IV) hydrazone Schiff base complexes and exhibit especially the
coordination mode of the ligand.
The dominant vibronic absorption peaks in ~325 and ~370 nm (for the free ligand and complex
4), and ~350 and ~440 nm (for complexes 1-3) can be ascribed to the ligand-centered (LC) π–π*
transitions. From the spectra data we can see that the absorption spectra of complexes 1-3 show
the obvious red-shift when compared with that of the free ligand, which should be the result of the
enolization of the Schiff base ligand as well as the coordination to the tin center. However, the
absorption peaks of complex 4 are almost the same as those of the Schiff base ligand, which
should be due to the main body of the Schiff base ligand in 4 having little changes, that is, the
phenomenon of enolization does not occur just like in complexes 1-3, and differently the carbonyl
and phenolate O atoms of the ligand bond to the tin atoms contributing to the formation of the
organotin(IV) polymer 4. All these values are consistent with their crystal structures.
3.5 Crystal structures
3.5.1. Crystal structures of complexes 1, 2 and 3
Complexes 1, 2 and 3 have similar molecular structures, as illustrated in Fig 2, 3a and 4a. From
the structure descriptions of the complexes, it can be seen that the Schiff base ligands coordinate

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to tin center in a tridentate fashion, an enolic O atom, a Schiff base group N atom and an O atom
of hydroxyl group of naphthalene nucleus. The tin atom is rendered five-coordinate with a
distorted trigonal bipyramidal geometry, surrounded axially by two O atoms from the Schiff base
ligand and equatorially by one N atom, two C atoms from the alkyl group. The Sn–O (amide)
bond lengths [between 2.121(2) and 2.138(2) Å] and the Sn–O (phenolate) bond lengths [between
2.062(2) and 2.078(2) Å] are in excellent agreement with other previously known acylhydrazone
diorganotin(IV) complexes in the literatures [37,38]. The Sn–O (amide) bond length is longer than
the Sn–O (phenolate) in the same complex. The Sn-O bond lengths are considerably shorter than
the sum of the Van der Waal’s radii (2.8 Å) and should be considered as bonding interactions,
indicating strong tin–oxygen interactions. The O-Sn-N (equatorial) and O-Sn-O (axial) angles
show a large deviation from the ideal values thus, confirming highly distorted trigonal bipyramidal
geometry. The distortion from the perfect trigonal bipyramidal geometry is mainly due to the
rigidity of the chelate rings and the large covalent radius of the tin(IV) atoms. There are five and
six membered Sn–N–N–C–O and Sn–N–C–C–C–O rings imposing the constraints. The dihedral
angles between the two rings are 0º for 1, 5.2º for 2 and 12.5º for 3. Due to the overall effect of
bulk and steric hindrance of the alkyl groups, the dihedral angles have obvious differences. Crystal
data and structure refinement parameters for all complexes are shown in Table 1. The selected
bond lengths and angles of complexes 1, 2, 3 are given in Table 2.
In complexes 1, 2 and 3, there also exist intra- and intermolecular hydrogen bonds, which are
listed in Table 3. These hydrogen bonds contribute to the crystal stability and compactness and
result in different supramolecular structures. For complex 1, there are intramolecular hydrogen
bond (O2-H2···N1) and intermolecular hydrogen bond [C4···O3#2 (x, y, z+1)], and the latter
aspect results in a one-dimensional chain arrangement. In complex 2, there are π···π stacking
interactions between the ring (C13-C18) and the ring (C1A,C2A,C3A,C4A,C9A,C10A) found in
the structure（shown in Fig 3b）, the distance between the ring centroids is 3.714 Å. As can be seen
from Fig 3b, the intermolecular hydrogen bond [C30···O2#1(-x+1, -y+1, -z)] and the π···π stacking
interactions between the aromatic rings link the molecules into centrosymmetric (symmetric
operation: 1-x, -y, -z) dimers. And the weak interactions (C-H···Cl) link the dimers into the
two-dimensional networks [Fig 3c]. For complex 3, through the intermolecular hydrogen bond

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(C32···O1#1), two complexes 3 molecules bind together with each other into a centrosymmetric
(symmetric operation: -x+2, -y+1, -z) conformation (shown in Fig 4b).
3.5.2. Crystal structures of complex 4
When the reaction of 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone ligand
with bis(tri-n-butyltin) oxide was carried out, a rare one-dimensional chain polymeric structure
complex 4 was obtained (shown in Fig 5b). The molecular structure of the complex 4 is shown in
Fig 5a. The selected bond lengths and angles are given in Table 2. The molecular structure is
different from the former complexes. In complex 4, the tin atom is five-coordinate in a distorted
trigonal-bipyramid geometry, but the Schiff base ligand coordinated to the tin atom as a bidentate
ligand. The central tin atom is surrounded axis by an non-enolic O(3) atom of the carbonyl group
and O(2)#1 from the phenolic hydroxyl of the Schiff base, and the equatorial position were
occupied by three C atoms from the n-butyl group. The Sn(1)–O(2)#1 bond length is 2.169(3) Å
and Sn(1)–O(3) bond length is 2.446 Å, which are much less than the sum of the Vander Waals
radii for Sn–O (2.8 Å ), indicating the significant contacts with the Sn(1) atom. Meanwhile, these
Sn–O bond lengths contribute to the angle of O(2)#1–Sn(1)–O(3) which is 174.37(12)º and cause
the angle deviated from linear 180º. The packing of the molecules of complex 4 show that the
de-protonated phenolate O atom and the carbonyl O atom from the non-enolic Schiff base ligand
played as a bridge on forming the unexpected one-dimensional chain polymeric structure. The
Schiff base ligand did not follow the traditional way of dehydrocarbylation [11] to coordinate with
the tin atom in a tridentate mode. Unexpectedly, the carbonyl O atom chelated to the tin. The
explanation of phenomenon may be that the chelation capacity is larger than the ability of
dehydroxylation . In other words, the chelation is not enough to destroy the alkyl group. It is
different from the previously reported complexes that are obtained by the way of destroying the
alkyl group and forming the stable seven-coordinated complexes [9]. In summary, examples of
triorganotin Schiff base structure of similar compound 4 are reported less. This result provides the
impetus for further exploration of this class of compounds as potential molecular precursors.
3.6 Antitumor activity in vitro
The antitumor activity in vitro of complexes 1-4 against human promyelocyticfina leukemic cell

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line (HL-60), a human colon cancer cells (HCT-8) and lung cancer cells (A549) were determined
by MTT-based assays. This study has been carried out in order to understand the possible
relationship between the different tin moieties (bearing methyl, butyl, phenyl or benzyl groups),
the coordination geometry and the antitumor activity.
Comparison of inhibition between complexes 1, 2, 3 and 4 are shown in Fig 6, 7 and 8. The IC50
values, calculated from the dose-survival curves, obtained after 48 h of drug treatment in the MTT
test, are summarized in Table 4.
The results of in vitro cytotoxic effects of compounds 1-4 demonstrate these compounds are
active against three tumor cell lines (A549, HCT-8 and HL-60) that are either sensitive to or have
acquired resistance to cisplatin, the clinically used drug. From Fig 6, 7 and 8, we can also see that
there was a good dose-effect relationship for all complexes, the percentage inhibition grows with
the increasing of the concentration of organotin(IV) complexes. n-Butyltin(IV) complex 4 exhibits
a greater activity than complexes 1, 2 and 3 against three cancer cells examined, which is well
consistent with the results reported in the literature [39-41]. As for the identical coordination
geometry, the IC50 values of complexes 1, 2 and 3 (shown in Table 4) follow different trends for
three cancer cell line, that is 1 > 3 > 2 for A549 and HCT-8, but 3 > 1 > 2 for HL-60. Also, the
data analysis reveals that different complexes demonstrate different anticancer activities against
the same cell line, and the inhibitory potencies of the same complex against three different tumor
cells exhibit a high selectivity. For example, di-o-chlorobenzyltin(IV) complex 3 demonstrates
significant activities for tumor cells HL-60 and HCT-8, while exhibits no activity for tumor cell
A549.
Therefore, possible structure-activity relationships could be recognized as follows: (i) with the
increasing concentration, the inhibition of cancer cells was also increased; (ii) the polymeric
complex 4 with the long carbon chain butyl ligand is the most active one, in comparison with
other organotin(IV) complexes; (iii) the organic ligand R plays an important role, the dimethyl
complexes exhibiting a stronger antitumor activity than the diphenyl analogues, while the effects
of the benzyltin complexes on different tumor cells are different. The results indicate that
complexes act against cells selectively and the type of alkyl groups attached to the organotin
moiety has effects on antitumor activity; (iv) the contribution from coordination geometry to tin
atom in the present compounds towards the cytotoxic effects may not be rules out.

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4. Conclusions
Four new organotin(IV) complexes were obtained by the reaction of
2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone Schiff base ligand and
organotin(IV) salts in methanol. Complexes 1-3, characterized by X-ray analysis, showed the
structure with tridentate chelate ligand through the oxygen of deprotonated phenolic and enolic
hydroxyl group and the nitrogen atoms. In complex 4, a novel non-enolic bidentate
O,O-coordination of Schiff base ligand in synthesized tri-n-butyltin(IV) complex was documented
for the first time.
Moreover, the results of in vitro antitumor activity screening also indicate that n-butyltin(IV)
complex 4 shows better antitumor activity on three cancer cell lines than the methyl-, phenyl- or
benzyltin(IV) derivatives. Otherwise, benzyltin(IV) complex 3 show high selectivity between
cancer cell lines HCT-8, HL-60 and A549.
Acknowledgement
We acknowledge the National Natural Foundation of China (21105042), the National Basic
Research Program (No. 2010CB234601), the Natural Science Foundation of Shandong Province
(ZR2011BM007, ZR2010BQ021) for financial support. And this work was supported by
Shandong “Tai–Shan Scholar Research Fund”.
Appendix A. Supplementary data
CCDC-836674 (for 1), -836672 (for 2), -836675 (for 3), and -836673 (for 4), contain the
supplementary crystallographic data for this paper. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/data_request/cif, or from the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk.
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Fig 1. Absorption spectra of L1 (a) and complex 1 (c), 2 (e), 3 (d), 4 (b) at 298 K in methanol.
Fig 2. Molecular structure of 1 with 30% probability ellipsoids. All H atoms are omitted for clarity.
Fig 3. Molecular structure of 2 with 30% probability ellipsoids (a). The view of the dimer via the
intermolecular hydrogen bond and π···π stacking interactions (b). A perspective view of the 2D
supramolecular structures via the intermolecular hydrogen bond, π···π stacking interactions and
C-H···Cl interactions (c).
Fig 4. Molecular structure of 3 with 30% probability ellipsoids (a). The dimer structure by
intermolecular hydrogen bond interactions (b).
Fig 5. Structure of segments of the 1D chain of complex 4. (a). A perspective view of the
one-dimensional chain polymeric structure (b).
Fig 6. In vitro antitumor activity against A549 (human lung cancer cell line). Inhibition vs CVOL
(Inhibition = (A0-A)/A; A0 and A represent the optical density of each well in the absence and
presence of the sample, respectively; CVOL relates to the concentration of the sample). From left to
right, CVOL = 0.1, 0.5, 1, 5, 10 ꢀg/mL.
Fig 7. In vitro antitumor activity against HCT-8 (human colon cancer cells).
Fig 8. In vitro antitumor activity against HL-60 (human promyelocyticfina leukemic cell line).
Table 1. Crystal data and structure refinement parameters for complexes 1, 2, 3 and 4
Table 2. Selected bond lengths (Å) and angles (º) for complexes 1, 2, 3 and 4
Table 3. Hydrogen bonding geometries for complexes 1, 2, 3 and 4
Table 4. In vitro cytotoxicity assay for complexes 1-4 against tumor cell lines
Scheme 1. Different coordination sites of the Schiff base group.
Scheme 2. Different modes of the Schiff base group.
Scheme 3. Synthetic routes to complexes 1-4.

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Table 1. Crystal data and structure refinement parameters for complexes 1, 2, 3 and 4
Complexes
EmpiricalFormula
Formula mass
Crystal system
Space group
a [Å]
1
C20H17ClN2O3Sn
487.50
Orthorhombic
Pnma
2
C30H21ClN2O3Sn
611.63
3
C32H23Cl3N2O3Sn
708.56
4
C30H38ClN2O3Sn
628.76
Monoclinic
P2(1)/c
9.3991(8)
11.1000(10)
26.143(2)
90
Triclinic
P-1
Monoclinic
P2(1)/c
9.7397(8)
16.3895(15)
18.6474(17)
90
24.265(2)
7.2450(8)
10.8311(11)
90
8.1570(8)
13.3971(12)
13.9919(13)
91.2830(10)
104.414(2)
98.1300(10)
1463.4(2)
2
b [Å]
c [Å]
α[°]
β[°]
90
108.9920(10)
90
93.289
γ[°]
V [Å3]
90
90
1904.1(3)
4
2579.0(4)
4
2971.8(5)
4
Z
F(000)
968
1224
708
1292
Dcalcd. [g·cm-3]
θ range [°]
Number of Reflections
Number of Parameters
Final R indices [I > 2σ(I)]
wR2 [I > 2σ(I)]
Goodness of fit on F2
1.701
1.575
1.608
1.405
3.14 - 25.02
7336
2.47 - 25.02
12592
2.66 - 25.02
7587
2.44 - 25.02
14705
163
335
371
338
0.0264
0.0623
1.011
0.0335
0.0317
0.0379
0.0686
0.0716
0.0839
1.062
1.086
1.118
Table 2. Selected bond lengths (Å) and angles (º) for complexes 1, 2, 3 and 4
Complex 1
Sn1-O3
2.068(3)
2.096(3)
N1-C1
N1-N2
1.309(4)
1.388(4)
Sn1-C20
Sn1-C20#1
Sn1-O1
2.096(3)
2.121(3)
2.149(3)
95.55(10)
95.55(10)
N2-C8
1.312(5)
1.296(4)
1.357(5)
82.41(12)
118.72(9)
O1-C1
Sn1-N2
O2-C3
O3-Sn1-C20
O3-Sn1-C20#1
O3-Sn1-N2
C20-Sn1-N2
C20-Sn1-C20#1
O3-Sn1-O1
122.40(19)
155.96(10)
95.96(9)
C20#1-Sn1-N2
O1-Sn1-N2
118.72(9)
73.56(10)
95.96(9)
C20-Sn1-O1
Complex 2
Sn1-O1
C20#1-Sn1-O1
2.062(2)
2.111(4)
2.158(3)
N2-C12
N1-C11
O3-C12
1.317(4)
1.300(4)
1.290(4)
Sn1-C19
Sn1-N1
Sn1-O3
2.121(2)
2.111(4)
N1-N2
O1-C1
1.399(4)
1.307(4)
Sn1-C25

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O1-Sn1-C25
O1-Sn1-C19
C25-Sn1-C19
93.72(13)
99.36(13)
126.38(14)
C19-Sn1-O3
O1-Sn1-N1
C25-Sn1-N1
96.24(13)
82.26(10)
122.72(13)
O1-Sn1-O3
154.67(10)
92.92(13)
C19-Sn1-N1
O3-Sn1-N1
110.53(13)
73.61(10)
C25-Sn1-O3
Complex 3
Sn1-N2
2.167(3)
O3-C25
1.324(4)
1.321(4)
1.394(4)
1.296(4)
1.309(4)
92.49(12)
81.68(10)
101.29(12)
133.44(12)
73.04(9)
Sn1-C26
2.137(3)
C1-N1
Sn1-O2
2.138(2)
N1-N2
Sn1-C8
2.137(3)
C1-O2
Sn1-O3
2.078(2)
C15-N2
O3-Sn1-C26
O3-Sn1-C8
C26-Sn1-C8
O3-Sn1-O2
C26-Sn1-O2
101.90(12)
92.18(12)
125.02(14)
149.09(10)
100.28(11)
C8-Sn1-O2
O3-Sn1-N2
C26-Sn1-N2
C8-Sn1-N2
O2-Sn1-N2
Complex 4
Sn1-C27
2.130(5)
2.146(5)
2.169(3)
2.136(5)
2.446(3)
131.9(2)
116.1(2)
92.23(17)
85.11(16)
91.51(16)
125.7(3)
O2-Sn1#2
O3-C7
2.169(3)
1.239(5)
1.354(6)
1.389(5)
1.2886
Sn1-C23
Sn1-O2#1
N2-C7
Sn1-C19
N1-N2
Sn1-O3
N1-C8
C27-Sn1-C19
C19-Sn1-C23
C19-Sn1-O2#1
C27-Sn1-O3
C23-Sn1-O3
C4-O2-Sn1#2
C27-Sn1-C23
C27-Sn1-O2#1
C23-Sn1-O2#1
C19-Sn1-O3
O2#1-Sn1-O3
110.5(2)
97.00(17)
92.63(16)
82.51(17)
174.37(12)
Symmetry transformations used to generate equivalent atoms: Complex 1: #1 x, -y+1/2, z;
Complex 4: #1 -x+2, y+1/2, -z+1/2, #2 -x+2, y-1/2, -z+1/2
Table 3. Hydrogen bonding geometries for complexes 1, 2, 3 and 4
D-H...A
D-H
H...A
D...A
D-H...A
Complex 1
C(4)-H(4)...O(3)#2
O(2)-H(2)...N(1)
C(7)-H(7)...O(1)
Complex 2
0.93
0.82
0.93
2.43
1.86
2.46
3.359(5)
2.576(4)
2.774(5)
175.3
145.6
99.8
C(30)-H(30)...O(2)#1
O(2)-H(2)...N(2)
C(18)-H(18)...O(3)
C(30)-H(30)...O(1)
0.93
0.82
0.93
0.93
2.58
1.92
2.40
2.57
3.332(5)
2.638(4)
2.728(4)
3.120(5)
138.7
145.9
100.5
118.4

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Complex 3
O(1)-H(1)...N(1)
C(32)-H(32)...O(1)#1
Complex 4
0.82
0.93
1.86
2.46
2.576(4)
3.215(4)
144.8
138.4
C(2)-H(2)...O(3)
O(1)-H(1)...N(1)
0.93
0.82
2.42
1.89
2.748(6)
2.609(5)
100.6
146.3
Symmetry transformations used to generate equivalent atoms:complex 1: #2 x, y, z+1
complex 2: #1 -x+1, -y+1, -z; complex 3: #1 -x+2, -y+1, -z
Table 4. In vitro cytotoxicity assay for complexes 1-4, organotin(IV) chlorides and H2L against tumor cell lines.
IC50(ꢀg/mL)
Complex
A549
0.9 ±0.14
>10
HCT-8
HL-60
9.3±0.82
>10
1
0.5±0.13
4.1±0.25
3.9±0.05
0.5±0.13
2
3
4
>10
0.6±0.04
0.4±0.06
0.09±0.03
>10
Me2SnCl2
Ph2SnCl2
(o-ClC6H4CH2)2 SnCl2
n-Bu3SnCl
H2L
4.23±0.46
0.48±0.12
0.81±0.21
0.95±0.06
2.1±0.44
cisplatin
0.9±0.26
0.7±0.23

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