Diorganotin Complexes with N(4)-Phenylthiosemicarbazones: Synthesis, Spectroscopic Characterization, and Antibacterial Activity

Article abstract of DOI:10.1080/10426507.2013.777727

The organotin(IV) complexes, SnPh₂L^a (1), SnMe ₂L^a (2), SnBu₂L^a (3), SnPh ₂L^b (4), SnMe₂L^b (5), SnPh ₂L^c (6), SnMe₂

Full text of DOI:10.1080/10426507.2013.777727

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DIORGANOTIN COMPLEXES WITH N(4)-
PHENYLTHIOSEMICARBAZONES: SYNTHESIS,
SPECTROSCOPIC CHARACTERIZATION AND
ANTIBACTERIAL ACTIVITY
Tahereh Sedaghat a , Azam Golalzadeh a & Hossein Motamedi b
a Department of Chemistry, College of Sciences, Shahid Chamran University, Ahvaz, Iran
b Department of Biology, College of Sciences, Shahid Chamran University, Ahvaz, Iran
Accepted author version posted online: 05 Apr 2013.
To cite this article: Phosphorus, Sulfur, and Silicon and the Related Elements (2013): DIORGANOTIN COMPLEXES WITH N(4)-
PHENYLTHIOSEMICARBAZONES: SYNTHESIS, SPECTROSCOPIC CHARACTERIZATION AND ANTIBACTERIAL ACTIVITY, Phosphorus,
Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2013.777727
To link to this article: http://dx.doi.org/10.1080/10426507.2013.777727
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DIORGANOTIN COMPLEXES WITH N(4)-PHENYLTHIOSEMICARBAZONES:
SYNTHESIS, SPECTROSCOPIC CHARACTERIZATION AND ANTIBACTERIAL
ACTIVITY
Tahereh Sedaghat1*, Azam Golalzadeh1, Hossein Motamedi2
aDepartment of Chemistry, College of Sciences, Shahid Chamran University, Ahvaz, Iran
bDepartment of Biology, College of Sciences, Shahid Chamran University, Ahvaz, Iran
*corresponding author: tsedaghat@scu.ac.ir , Fax: 98 611 3331042
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Abstract
Z
Y
N
NHPh
N
Sn
S
O
R
R
X
The organotin(IV) complexes, SnPh2La (1), SnMe2La (2) and SnBu2La (3), SnPh2Lb (4), SnMe2Lb
(5), SnPh2Lc (6), SnMe2Lc (7) and SnBu2Lc (8) were obtained by reaction of SnR2Cl2 (R= Ph,
Me, Bu) with 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide (H2La), 1-((2-
hydroxynaphthalen-1-yl)methylene)-4-phenylthiosemicarbazide (H2Lb) and 1-(2-hydroxy-3-
methoxybenzylidene)-4-phenylthiosemicarbazide (H2Lc). The synthesized complexes have been
1
investigated by elemental analysis, IR, H NMR, and 119Sn NMR spectroscopy. The data show
that the thiosemicarbazone acts as a tridentate dianionic ligand and coordinates via the thiol
group, imine nitrogen, and phenolic oxygen. The coordination number of tin is five. The in vitro
antibacterial activities of the ligands and their complexes have been evaluated against Gram-
positive (B. subtilis and S. aureus) and Gram-negative (E. coli) bacteria and compared with the
standard antibacterial drugs.
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Keywords: Thiosemicarbazones; Organotin; Antibacterial activity; 119Sn NMR
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following
free supplemental files: Additional text, figures and tables.]
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that will be available on-line only.</AQ>
INTRODUCTION
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Thiosemicarbazones have a long history and broad spectrum of biological efficacy
including antibacterial, antiviral, antifungal, antimalarial and antitumor activity.1-3 They are an
important group of multidentate ligands with potential binding hard-soft donor sites available for
both transition and main group of metallic ions, forming many structurally different
complexes.4,5 The coordinating ability of thiosemicarbazones to a wide range of metallic ions is
attributed to the extended delocalization of electron density over the –NH-C(S)-NH-N= system,
which is enhanced by substitution at the N(4) position, also higher activity is incorporated with
substitution at the N(4) position.6,7 In many cases the metal complexes of thiosemicarbazones
show greater biological activity than the free ligands and some side effects may decrease upon
complexation.5 This observation further encouraged detailed studies on coordination chemistry
involving thiosemicarbazones. One of the interesting work in this field is structural and
biological studies of organotin(IV) complexes of thiosemicarbazones. Interest to the chemistry of
these complexes has stemmed from the wide range of biomedical and commercial applications of
organotin compounds, including in vitro and in vivo antitumor activity.8,9 In addition, they
present an interesting variety of structural possibilities, so that a remarkable diversity in structure
may be observed even when only a small change in the chemistry occurs. It has also been
observed that a small structural change, such as the change of a substituent in the ligand may
lead to enhanced biological activity of both free ligand and complex.10 In general, the
biochemical activity of organotin compounds is influenced by the structure of complex,
coordination number of tin and the organic group and donor ligand bound to tin. It has been
revealed that a judicious choice of the ligand coordinated to the organotin fragment can modulate
the activity of the complex and minimize its drawback.11 Up to now; considerable efforts have
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been made to synthesize and characterize organotin compounds of different ligands having
heterodonor atoms (O, N, S). They have a variety of structures and different applications and
stabilities depending on the number, type and arrangement of ligands about the tin center, and
many studies have been focused on their structure–activity correlations.12-15 The recognition of
the importance of Sn-S bond for the biological properties of organotin compounds have spurred
on the study of thiosemicarbazone complexes with tin.5 As a part our studies on organotin(IV)
complexes of Schiff bases,16-19 and in order to investigate the role of organic group and
coordinated ligand on biological activity, herein we report the spectral and biological
perspectives of diorganotin(IV) complexes with three phenylthiosemicarbazone derivatives: 1-
(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide (H2La), 1-((2-hydroxynaphthalen-
1-yl)methylene)-4-phenylthiosemicarbazide (H2Lb) and 1-(2-hydroxy-3-methoxybenzylidene)-
4-phenylthiosemicarbazide (H2Lc), Fig. 1. The molecular variations through electron releasing
and electron withdrawing substituents were centered in the salicylaldehyde moiety to track the
resulting responses in biological activities.
[Insert Figure 1]
RESULTS AND DISCUSSION
The ligands, H2La, H2Lb and H2Lc, were prepared by condensation of N(4)-
phenythiosemicarbazide with 5-bromosalicylaldehyde, 2-hydroxy-1-naphthaldehyde and 3-
methoxysalicylaldehyde, respectively, (Figure 2). This type of molecules may exist in four
tautomeric forms, thione/thiol and ketoamine/phenolimine, (Figure 3). The previous studies
exhibited a phenol-thione tautomeric form in both solid state and solution.20,21 We have also
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predicted from spectral data the phenol-thione tautomeric form for these molecules. The
organotin complexes 1-8 were prepared by reaction of R2SnCl2 (R = Ph, Me or Bu) with
corresponding ligands in methanol in the presence of NEt3 in a 1 : 1 : 2 ratio with a slight excess
of NEt3.
[Insert Figures 2, 3]
Spectroscopic studies
In the IR spectra of ligands the absence of (S-H) at 2800-2550 cm-1 region reveals the
presence of only the thione tautomer in the solid state. The IR spectra of complexes lack bands
located at 3150 and 2998 cm-1, attributed to (NN-H) and (O-H) in free ligands. It is a result of
double deprotonation of the ligand during coordination. The (C=N) band at 1606-1617 cm-1 for
ligands is shifted towards lower frequency in the spectra of complexes, indicating coordination
of the azomethine nitrogen to the tin. The band at 829-856 cm-1 in the spectrum of ligand
assigned to the thiocarbonyl group is shifted to lower energies after complexation, indicating
coordination via the thiolate sulfur. The appearance of new bands in the IR spectra of complexes
assigned to (Sn–N), ν(Sn–O) and ν(Sn–S) supports the bonding of nitrogen, oxygen and sulfur
to tin.
In the 1H NMR spectra of complexes the absence of both phenolic and hydrazinic signals
suggests deprotonation and coordination of dianionic ligand to tin. The singlet at 10.04-10.60
ppm assigned to PhN-H in ligands is shifted upfield, probably because the intramolecular
hydrogen bond interaction involving this proton in the free ligands disappears after
complexation. The signal attributable to imine proton of the free ligands is shifted downfield and
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accompanied by satellites in complexes due to 3J(119Sn-H) coupling. This is an indication that the
imine nitrogen atom is coordinated to tin(IV). Therefore ligands are coordinated to tin(IV) via
phenolic oxygen, thiolic sulfur and imine nitrogen (Figure 4). The 1H NMR spectra of dimethyl
complexes shows a singlet at low frequency for SnMe2 protons accompanied by satellites
2
because of 119Sn-1H coupling. J(119Sn-1H) for these complexes is larger than uncomplexed
Me2SnCl2 (68.7 Hz). Generally, on complexation the magnitude of J(119Sn-1H) increases and
varies depending on the stereochemistry at the tin atom and the nature of the ligand. The larger
coupling constant indicates a higher co-ordination number of tin.22 Substitution of this coupling
constant in the Lockhart–Manders equation23 gives the values 134.75, 133.84 and 133.94 for the
1
Me-Sn-Me angle in 2, 5 and 7, respectively. The H NMR spectrum of diphenyl complexes
shows a multiplet peak for the Hortho of SnPh2 moiety. This signal has 119Sn satellites but
3J(119Sn-1H) can not be extracted accurately. The 119Sn satellites for dibutyl complex were not
2
observed and the J(119Sn-1H) value cannot be extracted from the spectrum because of the
complexity of the methylene multiplets.
[Insert Figure 4]
The 119Sn{1H}NMR spectra of all complexes show one sharp singlet significantly at
lower frequency than that of the original SnPh2Cl2 (-32 ppm), SnBu2Cl2 (+122 ppm) and
SnMe2Cl2 (+137 ppm). 119Sn NMR chemical shift is strongly dependent on the coordination
number of tin, and an increase in coordination number produces a large upfield shift. On the
basis of the chemical shift ranges proposed empirically for organotin(IV) derivatives,24-26 the
coordination number of tin is five for dimethyl and dibutyl complexes. The 119Sn NMR
measurement was obtained in noncoordinating (CDCl3) and coordinating (DMSO-d6) solvents
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for 6. The chemical shift -242, in CDCl3, is indicative of pentacoordinated tin atom. For
experiments in DMSO-d6, the chemical shifts were observed at -352.2, -320.8 and -333.8 ppm
for 1, 4 and 6, respectively, since the solvent molecules coordinate to tin, shifting the signal to
the region corresponding to hexacoordinated species.27
Biological studies
The in vitro antibacterial activities of all Schiff bases and their organotin(IV) complexes were
studied along with four standard antibacterial drugs, viz, Vancomycin, Colistin, Nalidixic acid
and Erythromycin. The microorganisms used in this work include Bacillus subtilis and
Staphylococcus aureus (as Gram-positive bacteria) and Escherichia coli (as Gram-negative
bacteria). The results are presented in Table S 1 (Supplemental Materials). An inhibition zone
diameter over 7 mm indicates that the test compound is active against the bacteria under
investigation.28 The antibacterial activity and inhibition zone around tested compounds can be
caused by their bactericidal effect that is due to killing of bacteria or from their bacteriostatic
effect that inhibits bacterial growth and colony formation through blocking of active sites on
surface or inside bacterial cell. Based on the results, among the ligands, only H2La shows
moderate activity towards the bacteria, this confirms the previous findings that compounds
having halogens show good inhibitory effects.29 The investigation of antibacterial screening data
reveals that the organotin complexes show similar or more inhibitory effects relative to ligand.
The enhanced antibacterial activity of the ligand on complexation may be due to electron
delocalization over the whole chelate ring increases the lipophilic character which favors the
permeation of the complexes through the lipid layer of the cell membrane (chelation theory)28,30-
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32
and also because of the intrinsic biological activity effects of organotin moiety. Among the
complexes, SnBu2La against S. aureus and SnMe2Lc towards B. Subtilis, show better inhibition
than others. The variation in the effectiveness of the biocide compounds against different
microorganisms depends on, among things, the permeability across the bacterial cell wall.27 In
general biological activity of organotin complexes is determined both by donor ligand and by the
number and nature of the organic groups bound to tin.
CONCLUSION
On the basis of above discussion, thiosemicarbazones are completely deprotonated and
act as tridentate ligands through thiol group, imine nitrogen, and phenolic oxygen. Therefore
coordination number of tin is five. The synthesized organotin complexes show different activities
against studied Gram-positive (B. subtilis and S. aureus) and Gram-negative (E. coli) bacterial
species. This research shows that both the nature of organic groups (R) bound to tin and the
substituents in the donor ligand (L) can change the biological activity of R2SnL derivatives.
EXPERIMENTAL
Materials and methods
All starting materials were purchased from Merck, diphenyltin dichloride was supplied
from Acros Company and were all used as received. All solvents were of reagent grade and used
without further purification. IR spectra were obtained using a FT IR BOMEM MB102
1
spectrophotometer. The H and 119Sn NMR spectra were recorded with a Bruker Avance (400
1
MHz) Ultrashield spectrometer using TMS and SnMe4 as references, respectively. Selected H
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and 119Sn NMR spectra for 1, 6, 7 and 8 are presented in the Supplemental Materials (Figures S 1
– S 8)
Synthesis of ligands
H2La, H2Lb and H2Lc have been prepared according to a modified procedure described in
the literature20 equimolar amounts of N(4)-phenythiosemicarbazide and corresponding aldehyde
in presence of a few drops of acetic acid were refluxed in methanol for 1-2 h.
1
H2La: Yield: 68%; m.p. 174-175C. FT-IR (KBr, cm-1): ν(C=N), 1606, ν(C=S), 829. HNMR
(DMSO): δ = 11.82 (s, H5), 10.34 (s, br, H4), 10.19 (s, OH), 8.42 (CH=N), 8.34 (d, J = 1.9 Hz,
H7), 7.51 (d, J=7.6 Hz, H1), 7.37 (m, H2, H8), 7.22 (t, J=7.3 Hz, H3), 6.84 (d, J = 8.7 Hz, H9).
H2Lb: Yield: 40%; m.p. 199-201 C. FT-IR (KBr, cm-1): ν(C=N), 1622, ν(C=S), 856. 1HNMR
(DMSO): δ = 11.77 (s, H5), 10.60 (s, br, H4), 10.08 (s, OH), 9.16 (CH=N), 8.49 (s, br, H12), 7.91
(d, J = 8.9 Hz, H7), 7.87 (d, J = 8.0 Hz, H9), 7.58 (m, H1, H11), 7.39 (m, H2, H10), 7.20 (m, H3,
H8).
H2Lc: Yield: 79%; m.p. 192-195 C. FT-IR (KBr, cm-1): ν(C=N), 1617, ν(C=S), 831. 1HNMR
(DMSO): δ = 11.81 (s, H5), 10.04 (s, H4) , 9.27 (s, OH), 8.51 (CH=N), 7.71 (d, J = 7.7 Hz, H7),
7.56 (d, J = 7.6 Hz, H1), 7.36 (t, J = 7.8 Hz, H2), 7.19 (t, J = 7.4 Hz, H3), 6.98 (dd, J = 8.0, 1.2
Hz, H9), 6.79 (t, J = 8.0 Hz, H8), 3.82 (s, OCH3).
Synthesis of Complexes
Synthesis of SnPh2La (1)
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H2La (0.350 g, 1 mmol) was dissolved in MeOH (35 mL) at 40-50 C and in the presence
of NEt3 (2.5mmol). The solution was stirred for 15 min and then SnPh2Cl2 (0.344 g, 1 mmol) in
MeOH (5 mL) was added. The solution was stirred for 1 h. During this time an orange
precipitate gradually formed. The product was collected and washed with methanol and dried
over CaCl2.Yield: 0.510 g (83 %); m.p. 186-188 C; Anal. Calcd. for C26H20BrN3OSSn: C, 50.3;
H, 3.2; N, 6.8 %. Found: C, 50.6; H, 3.7; N, 6.7 %. FT-IR (KBr, cm-1): ν(C=N), 1594, ν(CS),
820, ν(Sn-O), 501, ν(Sn-N), 449, ν(Sn-S), 418. 1H NMR (DMSO): δ = 9.60 (s, 1H, H4), 8.68 [s,
3
1H, CH=N, J(119Sn-H) = 40.8Hz], 7.75 (d, J = 7.7 Hz, 1H, H1), 7.63 (d, J = 1.5 Hz, 1H, H7),
7.61 (m, 4H, Ho in SnPh2), 7.37 (dd, J = 8.9, 2.6 Hz, H8), 7.30-7.25 (m, 7H, Hm,p in SnPh2, H2),
6.99 (t, J = 7.3 Hz, 1H, H3), 6.8 (d, J = 8.8 Hz, 1H, H9).119Sn{1H}NMR (DMSO): δ= -352.2.
Synthesis of SnMe2La (2)
H2La (0.175 g, 0.5 mmol) was dissolved in MeOH (12 mL) at 40-50 C and in presence
of NEt3 (1.25 mmol). The solution was stirred for 15 min and then SnMe2Cl2 (0.110 g, 0.5
mmol) in MeOH (5 mL) was added. The solution was refluxed for 3 h. The yellow product was
obtained after reducing the solution volume at room temperature. The solid was filtered off and
washed with methanol and dried over CaCl2.Yield: 0.052 g (31 %); m.p. 128-131 C; Anal.
Calcd. for C16H16BrN3OSSn: C, 38.6; H, 3.2; N, 8.4 %. Found: C, 38.9; H,3.7; N, 8.4%. FT-IR
(KBr, cm-1): ν(C=N), 1591, ν(CS), 821, νas(Sn-C), 630, νs(Sn-C), 586, ν(Sn-O), 521, ν(Sn-N),
3
496, ν(Sn-S), 425. 1H NMR (DMSO): δ = 9.43 (s, 1H, H4), 8.72 [s, 1H, CH=N, J(119Sn-1H) =
29.2Hz], 7.71 (d, J = 7.7 Hz, 1H, H1), 7.60 (d, J = 2.6 Hz, 1H, H7), 7.34 (dd, J = 8.9, 2.7 Hz, H8),
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7.26 (t, J = 7.8 Hz, 1H, H2), 6.96 (t, J = 7.3 Hz, 1H, H3), 6.59 (d, J = 8.8 Hz, 1H, H9), 0.77 [s,
6H, 2J(119Sn-1H) = 83 Hz, CH3 in SnMe2]. 119Sn{1H}NMR (CDCl3): δ = -112.7.
Synthesis of SnBu2La (3)
Complex 3 was synthesized as described for compound 2 from SnBu2Cl2 (0.152 g, 0.5
mmol). Yield: 0.180 g (62 %); m.p. 72-74 C; Anal. Calcd. for C22H28BrN3OSSn: C, 45.4; H,
4.8; N, 7.2 %. Found: C, 45.0; H, 5.3; N, 6.7 %. FT-IR (KBr, cm-1): ν(C=N), 1592, ν(CS), 818,
ν(Sn-O), 506, ν(Sn-N), 446, ν(Sn-S), 416. 1H NMR (DMSO): δ = 9.44 (s, 1H, H4), 8.81 [s, 1H,
3
CH=N, J(119Sn-1H) = 30 Hz], 7.71 (d, J = 8.02 Hz, 1H, H1), 7.59 (d, J = 2.6 Hz, 1H, H7), 7.35
(dd, J = 8.9,2.6 Hz, H8), 7.26 (t, J = 7.5 , 8.1Hz, 1H, H2), 6.96 (t, J = 7.3 Hz, 1H, H3), 6.60 (d, J
= 8.9 Hz, 1H, H9), 0.79 (t, J = 8 Hz, 6H, Hδ), 1.24 (m, 4H, Hγ), 1.45 (m, 4H, Hβ), 1.55 (t, 4H,
Hα). 119Sn{1H}NMR (DMSO): δ = -131.8.
Synthesis of SnPh2Lb (4)
H2Lb (0.058 g, 0.2 mmol) was dissolved in MeOH (14 mL) at 40-50 C and in presence
of NEt3 (0.5 mmol). The solution was stirred for 15 min and then SnPh2Cl2 (0.068 g, 0.2 mmol)
in MeOH (3 mL) was added. The solution was stirred for 15 min then under reflux for 1 h. The
dark yellow products were separated on slow evaporation of solvent for 3 days. The product was
collected and washed with methanol and dried over CaCl2. Yield: 0.093 g (79 %); m.p. 177-178
C; Anal. Calcd. for C30H23N3OSSn: C, 60.8; H, 3.9; N, 7.1 %. Found: C, 61.1; H, 4.2; N, 7.1%.
1
FT-IR (KBr, cm-1): ν(C=N), 1596, ν(CS), 827, ν(Sn-O), 516, ν(Sn-N), 449, ν(Sn-S), 418. H
3
NMR (DMSO): δ = 9.57 (s, 1H, H4), 9.5 [s, 1H, CH=N, J(119Sn-1H) = 48 Hz], 8.19 (d, J = 8.6
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Hz, 1H, H12), 7.90 (d, J = 9.0 Hz, 1H, H7), 7.85 (d, J = 7.7 Hz, 1H, H1), 7.79 (d, J = 8.0 Hz, 1H,
H9), 7.74 [dd, 4H, Ho in SnPh2, 3J(119Sn-1H) = 77 Hz], 7.50 (t, H11), 7.37-7.29 (m, 8H, Hm,p in
SnPh2, H2, H10), 7.17 (d, J = 9.0 Hz, 1H, H8), 6.99 (t, 1H, H3). 119Sn{1H}NMR (DMSO): δ = -
320.8.
Synthesis of SnMe2Lb (5)
Complex 5 was synthesized as described for compound 2 from H2Lb (0.146 g, 0.5 mmol).
Yield: 0.122 g (48 %); m.p. 179-180 C; Anal. Calcd. for C20H19N3OSSn: C, 51.3; H, 4.1; N,
8.9%. Found: C, 51.2; H, 4.5; N, 8.8 %. FT-IR (KBr, cm-1): ν(C=N), 1594, ν(CS), 825, νas(Sn-C),
592, νs(Sn-C), 547, ν(Sn-O), 522, ν(Sn-N), 476, ν(Sn-S), 413. 1H NMR (DMSO): δ = 9.40 (s,
1H, H4), 9.36 [s, 1H, CH=N, 3J(119Sn-1H) = 26.3 Hz], 8.12 (d, J = 8.5 Hz, 1H, H12), 7.84 (d, J =
9.1 Hz, 1H, H7), 7.81 (dd, J = 8.9, 1.0 Hz, H1), 7.77 (dd, J = 8.0, 1.0 Hz, 1H, H9), 7.50 (m, 1H,
2
H11), 7.3 (m, 2H, H10, 2), 6.96 (t, J = 7.3 Hz, H3), 6.91 (d, J = 9.0Hz, H8), 0.81 [s, 6H, J(119Sn-
1H) = 82.3 Hz, CH3 in SnMe2]. 119Sn{1H}NMR (CDCl3): δ = -177.3.
Synthesis of SnPh2Lc (6)
Complex 6 was synthesized as described for compound 4 from H2Lc (0.060 g, 0.2 mmol)
but was refluxed for 4 h. Yield: 0.065 g (58 %); m.p. 139-143 C; Anal. Calcd. for
C27H23N3OSSn: C, 56.7; H, 4.0; N, 7.3 %. Found: C, 57.2; H, 4.5; N, 7.4 %. FT-IR (KBr, cm-1):
1
ν(C=N), 1597, ν(CS), 825, ν(Sn-O), 503, ν(Sn-N), 452, ν(Sn-S), 430. H NMR (DMSO): δ =
3
9.52 (s, 1H, H4), 8.71 [s, 1H, CH=N, J(119Sn-1H) = 42.4 Hz], 7.75 (d, J = 7.7 Hz, 1H, H1), 7.7
(d, 4H, Ho in SnPh2), 7.35-7.25 (m, 7H, Hm,p in SnPh2, H2), 7.00-6.95 (m, 3H, H3,7,9), 6.63 (t, J =
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7.8 Hz, 1H, H8), 3.81 (s, OCH3). 119Sn{1H}NMR (DMSO): δ = -333.8, 119Sn{1H}NMR (CDCl3):
δ = -242.9.
Synthesis of SnMe2Lc (7)
Complex 7 was synthesized as described for compound 2 from H2Lc but was refluxed for
2 h. Yield: 61%; m.p. 172-176C; Anal. Calcd. for C17H16N3O2SSn: C, 45.6; H, 4.3; N, 9.4 %.
Found: C, 46; H, 4.7; N, 9.4 %. FT-IR (KBr, cm-1): ν(C=N), 1600, ν(CS), 823, νas(Sn-C), 591,
νs(Sn-C), 555, ν(Sn-O), 518, ν(Sn-N), 504, ν(Sn-S), 422. 1H NMR (DMSO): δ = 9.32 (s, 1H, H4),
8.74 [s, 1H, CH=N, 3J(119Sn-1H) = 31.8Hz], 7.74 (d, J = 7.7 Hz, 1H, H1), 7.26 (t, J = 8.0 Hz, 1H,
H2), 6.98 (dd, J = 8.9, 1.4 Hz, H7, 9), 6.93 (t, J = 7.6 Hz, 1H, H3), 6.59 (t, 1H, J = 7.9 Hz, H8),
3.72 (s, OCH3), 0.78 [s, 6H, 2J(119Sn-1H) = 82.4 Hz, CH3 in SnMe2]. 119Sn{1H}NMR (DMSO): δ
= -174.4.
Synthesis of SnBu2Lc (8)
The method used for 8 was the same as in 3 but from H2Lc (0.150 g, 0.5 mmol). Yield:
0.194 g (73%); m.p. 111-114 C; Anal. Calcd. for C23H31N3O2SSn: C, 51.9; H, 5.8; N, 7.9 %.
Found: C, 52; H, 6.1; N, 7.9 %. FT-IR (KBr, cm-1): ν(C=N), 1602, ν(CS), 824, ν(Sn-O), 506,
1
ν(Sn-N), 452, ν(Sn-S), 418. H NMR (DMSO): δ = 9.34 (s, 1H, H4), 8.78 [s, 1H, CH=N,
3J(119Sn-1H) = 31.4 Hz], 7.72 (d, J = 7.7 Hz, 1H, H1), 7.26 (t, J = 8.0 Hz, 1H, H2), 6.98–6.93 (m,
H3,7,9), 6.59 (t, J = 7.8 Hz, 1H, H8), 0.78 (t, J = 7.3 Hz, 6H, Hδ), 1.25 (m, 4H, Hγ), 1.44 (m, 4H,
Hβ), 1.56 (m, 4H, Hα). 119Sn{1H}NMR (DMSO): δ = -165.5.
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Antibacterial tests
The in vitro antibacterial activity of ligands and their corresponding organotin(IV)
complexes was investigated against the standard strains of two Gram-positive (Bacillus subtilis
ATCC 12711 and Staphylococcus aureus ATCC 6538) and one Gram-negative (Escherichia coli
ATCC 11303) bacteria. In order to compare the results, Vancomycin, Colistin, Nalidixic acid
and Erythromycin were used as standard antibacterial drugs. Determination of the antibacterial
activity was carried out by paper-disc diffusion method33 described in S1.
Supplemental Materials
Figure S 1: 1H NMR of 1
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Figure S 2: 119Sn NMR of 1
Figure S 3: 1H NMR of 6
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Figure S 4: 119Sn NMR of 6
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Figure S 5: 1H NMR of 7
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Figure S 6: 119Sn NMR of 7
Figure S 7: 1H NMR of 8
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Figure S 8: 119Sn NMR of 8
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Biological Activity
Experimental
Antibacterial tests
The in vitro antibacterial activity of ligands and their corresponding organotin(IV)
complexes was investigated against the standard strains of two Gram-positive (Bacillus subtilis
ATCC 12711 and Staphylococcus aureus ATCC 6538) and one Gram-negative (Escherichia coli
ATCC 11303) bacteria. In order to compare the results, Vancomycin (30 mg/disc), Colistin (2
mg/disc), Nalidixic acid (30 mg/disc) and Erythromycin (15 mg/disc) were used as standard
antibacterial drugs. Determination of the antibacterial activity was carried out by paper-disc
diffusion method. The compounds were dissolved in DMSO at 5 and 50 mg/ml concentration.
Muller Hinton broth was used for preparing basal media for the bioassay of the organisms. A
lawn culture from 0.5 MacFarland suspension of each strain was prepared on Muller Hinton
agar. Blank paper discs (6.4 mm diameter) were saturated with a solution of test compounds (40
L) and placed on the surface of the agar plates. On one paper disc only DMSO was poured as a
control. The plates were incubated at 37 C for 24 h. The inhibition zone diameters around each
disc were measured in mm (Table S 1).
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Table S 1: Antibacterial activity data of ligands and their organotin(IV) complexes
Compound
Conc.
Inhibition zone (mm)
(mg/mL)
E. Coli S. aureus
B.
subtilis
11
13
13
13
13
15
8
H2La
5
50
5
50
5
50
5
50
5
50
5
50
5
50
5
50
5
9
13
n.a.
n.a.
n.a.
n.a.
9
11
9
9
12
15
n.a.
n.a.
8
11
9
16
9
8
8
H2Lb
n.a.
n.a.
n.a.
n.a.
n.a.
8
11
13
13
21
H2Lc
SnPh2La
SnMe2La
SnBu2La
SnPh2Lb
SnMe2Lb
SnPh2Lc
SnMe2Lc
SnBu2Lc
12
9
12
13
16
n.a.
13
11
13
11
12
20
20
13
14
24
30
28
30
n.a.
21
7
10
n.a.
n.a.
10
50
5
50
5
14
12
15
18
12
28
20
13
n.a.
n.a.
18
28
16
50
Vancomycin
Colistin
Nalidixic acid
Erythromycine
28
n.a. = no activity
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Acknowledgment
Support of this work by Shahid Chamran University, Ahvaz, Iran is gratefully acknowledged.
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Figure 1: Structure of ligands with numbering for NMR assignments
Z
Z
H
Y
CHO
OH
Y
N
NHPh
H
N
N
NHPh
SnR2Cl2 (R= Me, Ph or Bu)
SnR2L + 2NEt3HCl
Reflux
MeOH
+
H2N
2NEt3
S
OH
S
X
X
H2La: X = H, Y = Br, Z = H
H2Lb: X =H, Y, Z =
H2Lc: X =OMe, Y = H, Z = H
Figure 2: Synthesis pathway of ligands and complexes
Figure 3: Tautomeric forms of ligands (X, Y and Z have been defined in Figure 2)
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Z
Z
H
Y
N
NHPh
Y
N
NHPh
N
N
X, Y, Z
R
Ph
Me
Bu
SH
S
H, Br, H
1
OH
OH
H, Br, H
2
H, Br, H
3
X
X
Z
H,
H,
Ph
4
Z
5
Me
H
N
Y
NHPh
Y
N
NHPh
OMe, H, H
Ph
Me
6
7
8
N
H
N
OMe, H, H
H
OMe, H, H
Bu
S
SH
O
O
X
X
Z
Y
N
R
NHPh
N
Sn
S
O
R
X
Fig. 4 Suggested structure of complexes
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