Synthesis, characterization and cytotoxic activity of 5,10,15,20- tetrakis[4-(triorganostannyloxy)phenyl]porphyrins

Article abstract of DOI:10.1002/aoc.2971

5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins, (R ₃SnO)₄TPP [2, R = Cy (a), Ph (b), PhC(CH₃) ₂CH₂ (c)], have been synthesized by the condensation of 4-(triorganostannyloxy)benzaldehyde, 4-(R₃SnO)C₆H ₄CHO (1), with pyrrole in the presence of BF₃ followed by oxidation by p-chloranil and characterized by means of elemental analysis, IR, UV-visible and NMR (¹H, ¹³C and ¹¹⁹Sn) spectra. The results of X-ray single-crystal diffraction show that 1a and 1b possess a trans-C₃SnO₂ trigonal bipyramidal geometry with the axial positions occupied by the phenolate oxygen and formyl group oxygen of an adjacent molecule and form a one-dimensional zigzag chain. In 2a, the macrocyclic core of the porphyrin is coplanar and each tin atom possesses a distorted tetrahedral geometry. These compounds (1 and 2) have potent in vitro cytotoxic activity against two human tumor cell lines - CoLo205 and MCF-7 - and the activity decreases in the order Ph > Cy > PhC(CH₃) ₂CH₂ for the R group bound to tin. Copyright

Full text of DOI:10.1002/aoc.2971

Full Paper
Received: 19 November 2012
Revised: 1 January 2013
Accepted: 1 January 2013
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2971
Synthesis, characterization and cytotoxic
activity of 5,10,15,20-tetrakis
[4-(triorganostannyloxy)phenyl]porphyrins
Laijin Tiana*, Xianxian Caoa, Yanxiang Zhaoa, Jianzhuang Jiangb and
Xijie Liuc
5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins, (R3SnO)4TPP [2, R = Cy (a), Ph (b), PhC(CH3)2CH2 (c)], have been synthesized
by the condensation of 4-(triorganostannyloxy)benzaldehyde, 4-(R3SnO)C6H4CHO (1), with pyrrole in the presence of BF3
followed by oxidation by p-chloranil and characterized by means of elemental analysis, IR, UV–visible and NMR (1H, 13C and
119Sn) spectra. The results of X-ray single-crystal diffraction show that 1a and 1b possess a trans-C3SnO2 trigonal bipyramidal
geometry with the axial positions occupied by the phenolate oxygen and formyl group oxygen of an adjacent molecule and
form a one-dimensional zigzag chain. In 2a, the macrocyclic core of the porphyrin is coplanar and each tin atom possesses a
distorted tetrahedral geometry. These compounds (1 and 2) have potent in vitro cytotoxic activity against two human tumor
cell lines – CoLo205 and MCF-7 – and the activity decreases in the order Ph > Cy > PhC(CH3)2CH2 for the R group bound to tin.
Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: porphyrin; organotin complex; cytotoxic activity, crystal structure
Introduction
Experimental
Porphyrins are naturally occurring biological compounds. Their photo-
electric and biochemical properties open a wide field of applications in,
for example, electronic/electro-optical and nonlinear optics,[1] selective
catalysis[2] and material chemistry.[3] One of these applications is the
well-known use of porphyrins as photodynamic therapy agents for
cancer treatments in medicine. The curative effects of the photosensi-
tizers are dependent on their photosensitive ability and drug effects.[4]
To improve their functional properties, the structural modification of the
porphyrins is a efficient method.[5] Second-generation photosensitizers,
such as verteporfin (benzoporphyrin derivative monoacid ring A) and
rostaporfin (tin ethyl etiopurpurin), are good examples.[5] Organotin
compounds have found wide agricultural and industrial applications.[6]
Recent studies have shown their relatively high in vitro cytotoxicities.[6,7]
The organotin moiety and the ligand appear to play an important role
in determining their cytotoxicities.[7] Thus the porphyrin derivatives with
side chain containing organotin moieties can become the more efficient
cytotoxic/antitumor agents.[8,9] In the recent past, only a few papers
studied free-base porphyrin derivatives with organotin moieties.
Several groups[9] synthesized (R2Sn)2H2TPPC, (R3Sn)4H2TPPC,
(R2Sn)2H2TPPS, (R3Sn)4H2TPPS (R= Me, n-Bu, Ph), and n-Bu2Sn
(H2TPyPPC)2 by the reactions of organotin oxide or hydroxide with
H6TPPC [5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin], H6TPPS
[5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin] and H3TPyPPC
[5-p-(carboxylmethoxy)phenyl-10,15,20-trispyridinylporphyrin], re-
spectively, and reported their cytotoxic activity. In order to continue
to expand the chemistry and therapeutic potential of the porphy-
rin-organotin compounds,we synthesized 5,10,15,20-tetrakis[4-(trior-
ganostannyloxy)phenyl]porphyrins from 4-(triorganostannyloxy)
benzaldehyde and pyrrole by Lindsey’s method[10] (Scheme 1), and
determined their cytotoxic activity.
Materials and Physical Measurements
Pyrrole was distilled over CaH2 under reduced pressure before use.
CH2Cl2 was distilled from potassium carbonate and stored over 4 A
molecular sieves. Tris(2-methyl-2-phenylpropyl)tin hydroxide was
prepared according to the literature procedure.[11] Other chemicals
were of reagent grade and were used without further purification.
The melting points were measured on a WRS-1A digital melting point
apparatus. Carbon, hydrogen and nitrogen analyses were obtained
using a PerkinElmer 2400 Series II elemental analyzer. IR spectra were
recorded on a Nicolet 470 FT-IR spectrophotometer using KBr discs in
the range 4000–400 cmꢀ1. NMR spectral data were collected using a
Bruker Avance DPX300 NMR spectrometer with CDCl3 as solvent and
tetramethylsilane as internal standard for 1H and 13C, and SnMe4 as
external standard for 119Sn. UV–visible spectra were obtained on an
Agilent 8453 spectrophotometer.
*
Correspondence to: Laijin Tian, Key Laboratory of Natural Products and
Pharmaceutical Intermediates, Qufu Normal University, Qufu 273165, China.
E-mail: laijintian@163.com
a Key Laboratory of Natural Products and Pharmaceutical Intermediates, Qufu
Normal University, Qufu 273165, China
b School of Chemistry and Biological Engineering, University of Science and
Technology Beijing, Beijing 100083, China
c
Beijing Centaurus BioPharma Technology Co. Ltd, Beijing 100089, China
Appl. Organometal. Chem. 2013, 27, 191–197
Copyright © 2013 John Wiley & Sons, Ltd.

L. Tian et al.
Scheme 1. Synthetic route of compounds.
Synthesis of 4-(Triorganostannyloxy)benzaldehydes (1a–1c)
115.87 (C-3), 37.86 (Ph-C), 33.96 (1J(119/117Sn-13C)= 348/332 Hz,
CH2Sn), 32.87 (3J(119Sn-13C)= 44 Hz, CH3). 119Sn NMR d: 114.5.
To a suspension of triorganotin hydroxide (5 mmol) in 60 ml toluene
was added 4-hydroxybenzaldehyde (0.61 g, 5 mmol). The reaction
mixtures were heated under reflux for 6 h with a Dean–Stark
separator, and then allowed to cool to room temperature. The
solution was filtered and the solvent was removed under reduced
pressure. The resulting white solid was recrystallized from
chloroform–hexane (1:2). The yield, melting point and spectral data
for compounds 1a–1c were as follows.
Synthesis of 5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]
porphyrins (2a–2c)
Pyrrole (0.201 g, 3 mmol) and 4-(triorganostannyloxy)benzaldehyde
(3 mmol) were added to dichloromethane (300 ml) purged with
argon for 30 min. The mixture was stirred and purged with argon
for a further 10 min, after which a BF3 etherate (0.142 g, 1 mmol) in
methylene chloride was added. This reaction mixture was stirred
for 2 h at room temperature. p-Chloranil (0.553 g, 2.25 mmol) was
added, and then the mixture was stirred under reflux for 1 h. The
solvent was evaporated to dryness, and the product was purified
by silica gel column chromatography (CH2Cl2–n-C6H14, 4:3). The yield
and spectral data for compounds 2a–2c were as follows.
4-(Tricyclohexylstannyloxy)benzaldehyde, 4-(Cy3SnO)C6H4CHO (1a)
Yield 86%; m.p. 84.8–85.6ꢁC. Anal. Calcd for C25H38O2Sn (%):
C 61.37, H 7.83. Found: C 61.43, H 7.71. IR cmꢀ1: 1644
(C¼O), 1316 (C-O), 528 (Sn-O). 1H NMR d: 9.79 (s, 1H, CHO),
7.72 (d, 2H, J = 8.4 Hz, H-2 of C6H4), 6.73 (d, 2H, J = 8.4 Hz,
H-3 of C6H4), 2.00–1.30 (33H, m, Cy). 13C NMR d: 191.06
(C¼O), 163.84 (C-4), 132.05 (C-2), 129.94 (C-1), 115.62 (C-3),
33.97 (1J(119/117Sn-13C)= 334/320 Hz, C-a), 31.32 (2J(119Sn-13C)= 15
Hz, C-b), 29.19 (3J(119Sn-13C)= 64 Hz, C-g), 27.16 ppm (C-d). 119Sn
NMR d: 12.3.
5,10,15,20-Tetrakis[4-(tricyclohexylstannyloxy)phenyl]porphyrin (2a)
Yield 16%. Anal. Calcd for C116H158N4O4Sn4 (%): C 64.88, H 7.42,
N 2.61. Found: C 64.46, H 7.27, N 2.49. IR cmꢀ1: 3316 (N-H), 1598,
1499, 1469, 1443, 1347 (¼C-N), 1248 (C-O), 1106, 989, 840, 802,
735, 627, 540 (Sn-O). 1H NMR d: 8.90 (s, 8H, b-H of pyrrole), 8.11 (d,
J= 8.0 Hz, 8H, m-H of OC6H4), 7.30 (d, J=8.0 Hz, 8H, o-H of OC6H4),
2.08-1.34 (132H, m, Cy), ꢀ2.79 (s, 2H, NH). 13C NMR d: 156.90 (C-i
of OC6H4), 146.06 (C-a of pyrrole), 137.24 (C-p of OC6H4), 135.10
(C-m of OC6H4), 131.61 (C-b of pyrrole), 119.74 (C-meso),
115.56 (C-o of OC6H4), 34.23 (1J(119Sn-13C) = 328 Hz, C-a), 31.33
(C-b), 29.16 (C-g), 27.14 (C-d). 119Sn NMR d: 9.6.
4-(Triphenylstannyloxy)benzaldehyde, 4-(Ph3SnO)C6H4CHO (1b)
Yield 86%; m.p. 142.1–142.8ꢁC. Anal. Calcd for C25H20O2Sn (%):
C 63.73, H 4.28. Found: C 63.67, H 4.13. IR cmꢀ1: 1649 (C¼O),
1301 (C-O), 536 (Sn-O). 1H NMR d: 9.73 (s, 1H, CHO), 7.69–7.66
(m, 6H, 3J(119Sn–H) = 54.0 Hz, o-H of Ph), 7.61(d, 2H, J = 8.0
Hz, H-2 of C6H4), 7.25–7.49 (m, 9H, m- and p-H of Ph), 6.82 (d, 2H,
J= 8.0 Hz, H-3 of C6H4). 13C NMR d: 190.70 (C¼O), 164.63(C-4),
138.17 (1J(119/117Sn-13C) = 640/612 Hz, C-i of PhSn), 137.43 (2J
(
119Sn-13C) = 48 Hz, C-o of PhSn), 131.93 (C-2), 130.44 (4J(119Sn-13C) =
5,10,15,20-Tetrakis[4-(triphenylstannyloxy)phenyl]porphyrin (2b)
14 Hz, C-p of PhSn), 129.97 (C-1), 128.97 (3J(119Sn-13C) = 64 Hz, C-m
of PhSn), 114.86 (C-3). 119Sn NMR d: ꢀ104.4.
Yield 12%. Anal. Calcd for C116H86N4O4Sn4 (%): C 67.15, H 4.18, N
2.70. Found: C 67.24, H 4.07, N 2.67. IR cmꢀ1: 3323 (N-H), 1604,
1586, 1506, 1467, 1432, 1346 (¼C-N), 1224 (C-O), 1168, 1071,
966, 803, 730, 532 (Sn-O). 1H NMR d: 8.86 (s, 8H, b-H of
pyrrole), 8.06 (d, J = 8.0 Hz, 8H, m-H of OC6H4), 7.68–7.64
(m, 24H, 3J(119Sn-H) = 54.6 Hz, o-H of Ph), 7.50–7.23 (m, 44H,
o-H of OC6H4 and m- and p-H of Ph), ꢀ2.80 (s, 2H, NH). 13C
NMR d: 157.03 (C-i of OC6H4), 146.26 (C-a of pyrrole), 137.86
(1J(119Sn-13C) = 632 Hz, C-i of PhSn), 137.56 (C-p of OC6H4),
137.19 (2J(119Sn-13C) = 44 Hz, C-o of PhSn), 135.29 (C-m of
OC6H4), 131.47 (C-b of pyrrole), 130.13 (C-p of PhSn), 128.76 (C-m
of PhSn), 119.67 (C-meso), 115.34 (C-o of OC6H4). 119Sn
NMR d: ꢀ108.6.
4-[Tris(2-methyl-2-phenylpropyl)stannyloxy]benzaldehyde, 4-[(PhC(CH3)2CH2)3SnO]
C6H4CHO (1c)
Yield 84%; m.p. 66.6–67.6ꢁC. Anal. Calcd for C37H44O2Sn (%):
C 69.50, H 6.94. Found: C 69.40, H 6.79. IR cmꢀ1: 1673 (C¼O),
1
1298 (C-O), 541 (Sn-O). H NMR d: 9.82 (s, 1H, CHO), 7.72 (d, 2H,
J = 8.8 Hz, H-2 of C6H4), 7.30 (dd, 6H, J =7.4, 7.4, m-H of Ph), 7.23
(t, 3H, J = 7.4, p-H of Ph), 7.06 (d, 6H, J = 7.4, o-H of Ph), 6.63
(d, 2H, J = 8.8 Hz, H-3 of C6H4), 1.19 (s, 18H, CH3), 1.11 (s,
6H, 2J(119Sn-H) = 50.6 Hz, CH2Sn). 13C NMR d: 190.46
(C¼O), 163.89 (C-4), 151.04 (C-i of Ph), 131.96 (C-2), 129.98
(C-1), 128.55 (C-m of Ph), 126.07 (C-p of Ph), 125.50 (C-o of Ph),
wileyonlinelibrary.com/journal/aoc
Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 191–197

5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins
5,10,15,20-Tetrakis[4-(tris(2-methyl-2-phenylpropyl)stannyloxy)phenyl]
porphyrin (2c)
the relative high R-value. Crystallographic parameters and refine-
ments of 1a, 1b and 2a are listed in Table 1.
Yield 13%. Anal. Calcd for C164H182N4O4Sn4 (%): C 71.68, H 6.68,
N 2.04. Found: C 71.42, H 6.37, N 1.96. IR cmꢀ1: 3317 (N-H), 1596,
1496, 1468, 1442, 1360 (¼C-N), 1264 (C-O), 1166, 1071, 964,
841, 803, 768, 741, 698, 627, 554 (Sn-O). 1H NMR d: 8.86 (s, 8H, b-H
of pyrrole), 8.13 (d, 8H, J = 8.4 Hz, m-H of OC6H4), 7.36–7.21
(m, 44H, o-H of OC6H4 and m- and p-H of Ph), 7.06 (d, 24H,
J = 7.4, o-H of Ph), 1.24 (s, 24H, 2J(119Sn-H) = 50.4 Hz, CH2Sn),
1.13 (s, 72H, CH3), ꢀ2.77 (s, 2H, NH). 13C NMR d: 156.36 (C-i of
OC6H4), 150.83 (C-i of Ph), 146.31 (C-a of pyrrole), 137.46 (C-p
of OC6H4), 135.27 (C-m of OC6H4), 131.17 (C-b of pyrrole),
128.53 (C-m of Ph), 126.14 (C-p of Ph), 125.45 (C-o of Ph),
119.32 (C-meso), 115.13 (C-o of OC6H4), 37.84 (Ph-C), 34.01 (1J
In Vitro Cytotoxicity
Cytotoxic activity was assayed against two human tumor cell lines:
CoLo 205 (colon carcinoma cell) and MCF-7 (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 <0.1% (the concentra-
tion used was found to be non-cytotoxic against tumor cells.). In
vitro cytotoxic activity of the compounds was measured by the
MTT assay according to the literature.[13] All cells were cultured in
Dulbecco’s Modified Eagle Medium (DMEM) supplemented with
10% heat-inactivated new-born calf serum at 37ꢁC in a humidified
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 of cell
proliferation was measured. The experiments were repeated three
times for each test. Statistical significance was tested using
Student’s t-test (p < 0.05 was considered statistically significant).
The dose causing 50% inhibition of cell growth (IC50) was calculated
as previously described.[14]
(
119Sn-13C) = 340 Hz, CH2Sn), 32.76 (CH3). 119Sn NMR d: 109.7.
X-Ray Crystallography
Single crystals of compounds 1a, 1b and 2a 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-Ka radiation (0.71073 Å) using the ’ and o scan technique.
The structures were solved by direct methods and refined by a full-
matrix least squares procedure based on F2 using SHELX-97.[12] The
non-hydrogen atoms were refined anisotropically and hydrogen
atoms were placed at calculated positions in the riding model
approximation. In 1a, the C atoms of a cyclohexyl group were
disordered over two positions, and their site occupancies were
refined to 0.55(5):0.45(5). For 2a, the low single crystallinity and small
size made it difficult to obtain good intensity data, which resulted in
Results and Discussion
Synthesis
5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins (2) were
prepared according to the general route outlined in Scheme 1. 4-(Trior-
ganostannyloxy)benzaldehydes (1) were synthesized from triorganotin
Table 1. Crystallographic and refinement data for 1a, 1b and 2a
Compound
1a
1b
2a
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C
25H38O2Sn
C25H20O2Sn
471.10
C116H158N4O4Sn4
2147.22
489.24
Monoclinic
P21/n
Monoclinic
P21/c
Triclinic
P-1
10.351(2)
14.797(3)
16.241(3)
90
8.6082(16)
18.137(3)
13.247(2)
90
11.831(3)
13.252(3)
17.965(4)
79.247(4)
87.249(5)
80.049(4)
2725.1(11)
1
b (Å)
c (Å)
a (ꢁ)
b (ꢁ)
93.669(2)
90
99.528(2)
90
g (ꢁ)
Volume (Å3)
2482.5(8)
4
2039.6(7)
4
Z
Dc (g cmꢀ3
)
1.309
1.534
1.308
m (mmꢀ1
F(000)
)
1.045
1.270
0.957
1016
944
1114
Crystal size (mm)
Total reflections
Unique reflections
Reflections with I > 2s(I)
GOF on F2
0.20 ꢂ 0.30 ꢂ 0.44
18 089
0.10 ꢂ 0.26 ꢂ 0.38
14 209
0.01 ꢂ 0.02 ꢂ 0.12
11 641
4 725 (Rint = 0.032)
3 206
3 755 (Rint = 0.025)
3 300
8 930 (Rint = 0.087)
1 910
1.02
1.05
0.87
R indices [I > 2s(I)]
R indices (all data)
R = 0.053, wR = 0.147
R = 0.081, wR = 0.170
ꢀ0.44, 1.16
911366
R = 0.026, wR = 0.060
R = 0.031, wR = 0.062
ꢀ0.42, 0.75
911367
R = 0.096, wR = 0.234
R = 0.357, wR = 0.373
ꢀ0.43, 0.53
911368
Δrmin, Δrmax (e Åꢀ3
)
CCDC deposition no.
Appl. Organometal. Chem. 2013, 27, 191–197
Copyright © 2013 John Wiley & Sons, Ltd.
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L. Tian et al.
1
hydroxides and 4-hydroxybenzaldehyde in toluene by azeotropic
dehydration in ~85% yields. These compounds are white crystals
and soluble in common organic solvents such as benzene, trichloro-
methane, acetone and methanol. The porphyrins 2a–2c were
synthesized following Lindsey’s method.[10] This procedure (Scheme 1)
consists of the condensation of 4-(triorganostannyloxy)benzaldehyde
with pyrrole in the presence of BF3 etherate, followed by oxidation
by p-chloranil to afford 2a–2c in 12–16% yields. 2a–2c are purple
crystals and soluble in benzene, dichloromethane, methanol, tetrahy-
drofuran and ethyl acetate.
The H NMR spectra of these compounds showed the expected
resonances and integration. In 1a–1c, the signals assigned to CHO
proton appear in the range 9.73–9.82 ppm, and the signals of phenyl
ring (C6H4) protons appear as doublets at ~7.70 and ~6.60 ppm,
respectively. In 2a–2c, single resonances of CHO proton are not
observed, and NH and b-H of pyrrole rings appear as single peaks
at ꢀ2.80 and 8.90 ppm, respectively, which confirms the presence
of the porphyrin ring. The 13C chemical shifts of the carbonyl carbon
of aldehydes in 1a–1c are at ~190 ppm. In 2a–2c, the resonance
signals of the meso carbons, a and b pyrrolic carbons appear at
~119, 131 and 146 ppm, respectively. In compounds 1 and 2,
coupling between tin nuclei and carbon can be observed, and the
1J(119Sn-13C) is at ~330 Hz in 1a and 2a, ~630 Hz in 1b and 2b, and
~340 Hz in 1c and 2c. The 119Sn NMR chemical shift and 1J
Spectroscopic characterization
The infrared spectra of three 4-(triorganostannyloxy)benzaldehydes do
not show a strong band at ~3200 cmꢀ1 assigned to n(OH), indicting
the deprotonation of the phenolic oxygen of 4-hydroxybenzaldehyde
upon complexation with tin atom.[15] It has further been confirmed by
the appearance of a sharp band at ~540 cmꢀ1 assignable to the Sn-O
stretching vibration.[15,16] The stretching vibrations of phenolic C-O and
C¼O appear at 1298–1316 and 1644–1673 cm-1, respectively.
Compared with 4-hydroxybenzaldehyde (1670 cmꢀ1), the n(C¼O)
bands of 1a (1644 cmꢀ1) and 1b (1649 cmꢀ1) undergo a shift to
lower frequency by ~20 cmꢀ1, while that of 1c (1673 cmꢀ1) shows
almost no change. This indicates that in 1a and 1b there is carbonyl
oxygen atom coordination to tin atom,[17] but in 1c this is not the
case. The C¼O ! Sn coordination decreases the double bond char-
acteristic and vibration frequency of C¼O. Thus it may be suggested
that the tin atom in compounds 1a and 1b is five-coordinated and
in 1c is four-coordinated in the solid. In 2, the disappearance of the
n(C¼O) band and the appearance of the bands at 1465, 1350, and
965 cmꢀ1, assigned to the porphyrin skeletal modes,[18,19] indicate
the formation of prophyrin rings. The absorption bands at ~3320
and ~1440 cmꢀ1 are assigned to N-H stretching vibrations and
the C-H bending vibrations of pyrrole, respectively.[19,20] The
n(C-O) and n(Sn-O) are in agreement with those of 1a–1c.
Figure 1 shows the UV–visible absorption of 2a–2c. The porphyrin
derivatives synthesized in this work show typical electronic spectra,
with a Soret band near 420 nm and four less intense visible bands
Q near 520, 550, 590, and 650 nm in CH2Cl2.[21] The absorption
spectra of 2a–2c are quite similar, indicating that the differences in
substituting groups R3Sn do not affect obviously the absorption
properties.
(
119Sn-13C) values may be used to give tentative indications of the
environment around the tin atoms.[22–24] Holecek and co-workers[22]
have suggested that the 119Sn chemical shifts and the coupling
constants 1J(119Sn-13C) for the four-coordinated triphenyltin
compounds are in the range ꢀ40 to ꢀ120 ppm and 550–660 Hz,
respectively. The 119Sn NMR and J(119Sn-13C) values observed in
1
1b and 2b are ꢀ104.4 ppm, 640 Hz and ꢀ108.6 ppm, 632 Hz,
respectively, indicating that 1b and 2b are four-coordinated in CDCl3
solution. For the four-coordinated trialkyltin compounds, the 1J
(13C-119Sn) values in CDCl3 solution are in the range 295–390
Hz.[23,24] The 119Sn NMR resonances and J(119Sn-13C) of 1a (12.3
1
ppm, 334 Hz), 1c (114.5 ppm, 348 Hz), 2a (9.6 ppm, 328 Hz)
and 2c (109.7 ppm, 340 Hz) are close to those of the
corresponding four-coordinated triorganotin compounds,[23–26]
suggesting that the tin atoms in these compounds are also
four-coordinated in non-coordinating solvents.
X-Ray Structures of 1a, 1b and 2a
The structures of 1a, 1b and 2a are shown in Figs (2–4) and the
selected geometric parameters are given in Table 2. Compound 1a
(Fig. 2a) is a zigzag chain polymer associating via phenolate O(1)
and formyl group O(2) in the ligand with a distance of 10.118(2) Å
between two tin atoms (Fig. 3a). The Sn atoms in this polymeric
structure exist in a distorted trans-C3SnO2 trigonal bipyramidal
environment with the trigonal plane defined by the three cyclohexyl
groups. The C-Sn-C angles are in the range 115.2(4)–123.1(3)ꢁ. The
axial positions are occupied by the phenolate O(1) and formyl group
O(2)#1 (symmetry code #1: xꢀ 1/2, ꢀy+3/2, z+ 1/2) of the ligand of
an adjacent molecule with an O(1)-Sn(1)-O(2)#1 angle of 178.20(17)ꢁ.
The Sn(1)-O(2)#1 (2.712(5) Å) bond is significantly longer than the Sn
(1)-O(1) (2.071(4) Å) bond, so that the Sn atom is displaced out of the
C3 trigonal plane of the trans-C3SnO2 trigonal bipyramidal
polyhedron in the direction of the O(1) atom by 0.286(2) Å and the
O(1)-Sn(1)-C angles (92.3(3)–101.7(3)ꢁ) are greater than the
ideal 90ꢁ. There are few examples of triorganotin systems
having ArCH¼O ! Sn; two examples are triphenyltin salicylal-
dehydate[17] and tribenzyltin 5-nitrovanillinate,[27] which
feature the long O ! Sn bond (2.459(5) and 2.494(1) Å,
respectively). The O ! Sn bond length in 1a is longer than that
in the two compounds mentioned above, which may be due to
the bulky cyclohexyl groups bound on the tin. The Sn-C lengths
from 2.110(7) to 2.139(8) Å are similar to those found in the
five-coordinated chain tricyclohexyltin compounds such as
[28]
Cy3SnN(SO2CH3)2
and Cy3SnOCOCH2CH2CH3.[29]
Compound 1b (Fig. 2b) is also a zigzag chain polymer similar to 1a
in which the tin atom adopts a distorted trans-C3SnO2 trigonal
bipyramidal geometry and the distance between two tin atoms is
Figure 1. UV–visible absorption of 2a–2c in CH2Cl2.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 191–197

5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins
example of structural characterized free-base porphyrin derivatives
with a side chain of organotin moieties. The macrocyclic core of
the porphyrin is coplanar and the displacement of each atom in
the equatorial mean plane is within ꢃ0.073 Å. The dihedral angle
between the benzene rings at the meso positions of porphyrin ring
is 86.12(75)ꢁ, and the dihedral angles between the porphyrin ring
and the benzene ring are 85.06(52)ꢁ and 87.67(48)ꢁ, respectively.
The closest distance between two porphyrin plane centroids in the
lattices is 11.831(45) Å, with a plane dihedral angle of 89.31(42)ꢁ,
indicating the lack of any p–p overlapping between these porphyrin
rings. The C-C and C-N bond lengths of the porphyrin ring in 2a are in
agreement with those reported in other free-base porphyrin
compounds such as tetrakis(4-methoxyphenyl)porphyrin,[30] tetrakis
(4-pentyloxyphenyl)porphyrin[31] and tetrakis[4-(carboxymethyle-
neoxy)phenyl]porphyrin.[32] Compound 2a contains four tin atoms
in which each tin atom possesses a distorted tetrahedral geometry.
The four coordination atoms of the tin atom come from three carbon
atoms of the cyclohexyl groups and a phenolate oxygen atom. The
geometry parameters around tin atoms in the molecule do not differ
from each other significantly. The ranges of the Sn(1)-C and Sn(2)-C
bond distances and C-Sn(1)-C and C-Sn(2)-C bond angles are 2.13
(5)–2.15(3) and 2.07(3)–2.11(3) Å, and 113(2)–121.5(14) and 115.2
(19)–118.6(18)ꢁ, respectively, which are similar to those found in
the tetrahedral Cy3SnOCOCH2CH(C6H5)Ge(C6H4Me-4)3.[33]
In Vitro Cytotoxicity
Colon carcinoma and mammary cancers are common malignant
tumors. In order to evaluate the cytotoxicity of the synthesized
4-(triorganostannyloxy)benzaldehyde and tetrakis[4-(triorganos-
tannyloxy)phenyl]porphyrins, we tested the activity of all com-
pounds against two human tumor cell lines: CoLo 205 and MCF-7.
The results of the cytotoxic assay are shown in Table 3. These
compounds are active and their cytotoxic activities are higher than
those of the clinically widely used cisplatin, an anticancer metal-drug.
The data from Table 3 also reveal that the porphyrin–organotin com-
pounds 2 are more active than the triorganotin compounds 1, which
may be due to the differences of the numbers of tin atoms and the
ligand. The ligand tetrakis(4-hydroxyphenyl)porphyrin accumulated
preferentially in neoplastic tissues,[5,9] and enhanced the activity of
compounds 2 in the cancer cells. The triphenyltin derivatives are
the most active against the two cell lines and the activity decreases
in the order Ph > Cy > PhC(CH3)2CH2 for the R group bound to
tin, which is consistent with our previous results on the triorganotin
2-phenyl-1,2,3-triazole-4-carboxylates, 2-PhC2N3CO2SnR3.[34] Gielen
et al.[35] found that the di- and triorganotin steroid carboxylates,
crown ether carboxylates and fluorine-substituted carboxylates
Figure 2. Coordination geometry of the tin atom in 1a (a) and 1b (b);
symmetry code A: x ꢀ 1/2, ꢀy + 3/2, z + 1/2 for 1a and x + 1, ꢀy + 1/2,
z + 1/2 for 1b; hydrogen atoms are omitted for clarity.
10.459(2) Å (Fig. 3b). The three C-Sn-C angles in the equatorial plane
are 115.02(10), 117.70(10) and 123.18(9)ꢁ, respectively, which
are consistent with those in 1a, and the axial O(1)-Sn(1)-O
(2)#2 (symmetry code #2: x + 1, ꢀy + 1/2, z + 1/2) angle (168.82
(8)ꢁ) is significantly smaller than that of 1a (178.20(17)ꢁ). The
tin atom is 0.249(2) Å away from the C3 trigonal plane in the
direction of the more tightly held O(1) atom. The Sn(1)-C
(2.114(2)-2.124(2) Å) and Sn(1)-O(2) (2.0741(19) Å) bond
lengths are compared with those (2.105(7), ꢀ2.134(6) and
2.087(5) Å) of the reported analogue, triphenyltin salicylaldehy-
date.[17] However, the Sn(1)-O(2)#2 distance (2.601(2) Å) is
longer than that of triphenyltin salicylaldehydate (2.459(5) Å).
In compound 2a (Fig. 4), the porphyrin entity is located about a
center of inversion. To the best of our knowledge, this is the first
Figure 3. 1D zigzag chain formed in 1a (a) and 1b (b). The phenyl and cyclohexyl groups on the tin and all hydrogen atoms have been omitted for clarity.
Appl. Organometal. Chem. 2013, 27, 191–197
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Tian et al.
Figure 4. Molecular structure of 2a; the molecule is centrosymmetric and only the asymmetric unit is labeled. Hydrogen atoms are omitted for clarity.
Table 2. Selected bond lengths (Å) and angles (ꢁ) for 1a, 1b and 2a
1a
Sn(1)-C(1)
2.132(7)
2.110(7)
92.3(3)
Sn(1)-C(13)
2.139(8)
2.071(4)
116.4(4)
123.1(3)
178.20(17)
85.9(3)
Sn(1)-O(2)#1
2.712(5)
1.307(6)
82.3(3)
Sn(1)-C(7)
Sn(1)-O(1)
O(1)-C(19)
O(1)-Sn(1)-C(7)
O(1)-Sn(1)-C(1)
C(7)-Sn(1)-C(1)
O(1)-Sn(1)-C(13)
1b
C(7)-Sn(1)-C(13)
C(1)-Sn(1)-C(13)
O(1)-Sn(1)-O(2)#1
C(7)-Sn(1)-O(2)#1
C(1)-Sn(1)O(1)-Sn(1)-C(13)O(2)#1
C(13)-Sn(1)-O(2)#1
C(19)-O(1)-Sn(1)
C(2)-C(1)-Sn(1)
98.7(3)
78.9(3)
115.2(4)
101.7(3)
133.6(4)
115.7(5)
Sn(1)-C(1)
2.114(2)
2.122(3)
90.39(8)
101.03(9)
123.18(9)
99.05(9)
Sn(1)-O(1)
2.0741(19)
2.124(2)
Sn(1)-O(2)#2
2.601(2)
1.317(3)
78.41(8)
91.19(9)
131.85(7)
124.7(2)
Sn(1)-C(7)
Sn(1)-C(13)
O(1)-C(19)
O(1)-Sn(1)-C(1)
O(1)-Sn(1)-C(7)
C(1)-Sn(1)-C(7)
O(1)-Sn(1)-C(13)
2a
C(1)-Sn(1)-C(13)
C(7)-Sn(1)-C(13)
O(1)-Sn(1)-O(2)#2
C(1)-Sn(1)-O(2)#2
117.70(10)
115.02(10)
168.82(8)
80.81(8)
C(7)-Sn(1)-O(2)#2
C(13)-Sn(1)-O(2)#2
C(19)-O(1)-Sn(1)
C(2)-C(1)-Sn(1)
Sn(1)-O(1)
1.978(13)
2.15(3)
Sn(2)-C(41)
2.11(3)
N(2)-C(6)
N(2)-C(9)
O(1)-C(14)
O(2)-C(20)
1.362(19)
1.359(19)
1.35(2)
Sn(1)-C(23)
Sn(2)-C(56)
2.10(3)
Sn(1)-C(29)
2.15(3)
Sn(2)-C(68)
2.07(3)
Sn(1)-C(35)
2.13(5)
N(1)-C(1)
1.36(2)
1.34(2)
Sn(2)-O(2)
1.967(15)
103(2)
N(1)-C(4)
1.354(19)
105.1(17)
104.4(12)
115.2(19)
94.1(12)
118.6(18)
115.1(17)
O(1)-Sn(1)-C(35)
O(1)-Sn(1)-C(29)
C(35)-Sn(1)-C(29)
O(1)-Sn(1)-C(23)
C(35)-Sn(1)-C(23)
C(29)-Sn(1)-C(23)
O(2)-Sn(2)-C(68)
O(2)-Sn(2)-C(56)
C(68)-Sn(2)-C(56)
O(2)-Sn(2)-C(41)
C(68)-Sn(2)-C(41)
C(56)-Sn(2)-C(41)
C(4)-N(1)-C(1)
C(9)-N(2)-C(6)
C(20)-O(1)-Sn(1)
C(14)-O(2)-Sn(2)
C(6)-C(5)-C(4)
109.8(15)
108.2(14)
124.4(12)
129.5(14)
123.7(17)
124.7(17)
103.1(9)
113(2)
97.4(10)
114.8(19)
121.5(14)
C(9)-C(10)-C(1)#3
Symmetry code: #1 x ꢀ 1/2, ꢀy + 3/2, z + 1/2; #2 x + 1, ꢀy + 1/2, z + 1/2; #3 ꢀ x + 1, ꢀy + 1, ꢀz.
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Appl. Organometal. Chem. 2013, 27, 191–197

5,10,15,20-Tetrakis[4-(triorganostannyloxy)phenyl]porphyrins
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Table 3. Cytotoxic activity [IC50 (mmol lꢀ1)] of compoundsa
Compound
CoLo 205
MCF-7
1a
0.92 ꢃ 0.06
0.46 ꢃ 0.08
4.19 ꢃ 0.12
0.27 ꢃ 0.12
0.042 ꢃ 0.011
2.13 ꢃ 0.08
13.94 ꢃ 0.47
0.97 ꢃ 0.13
0.33 ꢃ 0.04
2.06 ꢃ 0.04
0.18 ꢃ 0.08
0.019 ꢃ 0.004
0.84 ꢃ 0.06
18.73 ꢃ 0.60
1b
1c
2a
2b
2c
Cisplatin
aThe data represent mean ꢃ standard deviation; p < 0.01 versus
cisplatin in each cell line.
exhibited quite potent cytotoxicities against many human tumor
cell lines, such as MCF-7, EVSAT, WiDr, IGROV, MI9, A498 and
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In summary, three novel tetrakis[4-(triorganostannyloxy)phenyl]-
porphyrins have been synthesized from 4-(triorganostannyloxy)
benzaldehyde and pyrrole by Lindsey’s method and characterization.
In solid state, compounds 1a and 1b possess a trans-C3SnO2 trigonal
bipyramidal geometry and form an infinite zigzag chain by the
coordination of formyl group oxygen to the tin atom of an adjacent
molecule, while the tin atoms in 1c and 2a–2c adopt a distorted
tetrahedral geometry. In the non-coordination solvent, these
compounds exist as a monomeric structure with the four-coordinate
tin atoms. These compounds have potent in vitro cytotoxic activity
against two human tumor cell lines – CoLo205 and MCF-7 – and
can be considered as excellent antitumor compounds for further
study.
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Acknowledgments
This work was supported by Shandong Provincial Natural Science
Foundation, China (ZR2010BL012) and the National Natural Science
Foundation of China (20931001; 21173126).
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