Homobimetallic organotin(IV) complexes with succinohydrazide Schiff base: Synthesis, spectroscopic characterization, and biological screening

Article abstract of DOI:10.1134/S1070363217030227

Six new bis-diorganotin(IV) complexes, [(Me₂Sn)₂L] (1), [(Et₂Sn)₂L] (2), [(n-Bu₂Sn)₂L] (3), [(Ph₂Sn)₂L] (4), [(n-Oct₂Sn)₂L] (5), and [(tert-C

Full text of DOI:10.1134/S1070363217030227

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 3, pp. 515–522. © Pleiades Publishing, Ltd., 2017.
Homobimetallic Organotin(IV) Complexes
with Succinohydrazide Schiff Base: Synthesis,
Spectroscopic Characterization, and Biological Screening1
S. Shujaha,c*, N. Khalidb, and S. Alic
a Department of Chemistry, Kohat University of Science and Technology, Kohat, 26000 Pakistan
*e-mail: shaukat.shujah@yahoo.com
b Chemistry Division, Pakistan Institute of Nuclear Science and Technology, PO Nilore, Islamabad, Pakistan
c Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320 Pakistan
Received December 17, 2015
Abstract—Six new bis-diorganotin(IV) complexes, [(Me2Sn)2L] (1), [(Et2Sn)2L] (2), [(n-Bu2Sn)2L] (3),
[(Ph2Sn)2L] (4), [(n-Oct2Sn)2L] (5), and [(tert-C4H9)2Sn)2L] (6), where L = N1',N4'-bis(2-oxidobenzylidene)-
succinohydrazide, were synthesized and characterized by elemental analysis, FT-IR, NMR (1H, 13C, and 119Sn)
and Mass spectra. Spectroscopic data authenticated the existence of two pentacoordinated tin centers in all
complexes, formed via coordination of bis-ONO donor sites with dialkyltin(IV) moieties. Biological screening
against selected pathogenic strains of bacteria and fungi revealed high activity of compound 3 against Bacillus
subtilis and Aspergillus flavis, it also exhibited highest cytotoxicity against Artemia salina.
Keywords: homobimetallic, bis-diorganotin(IV), Schiff base, antimicrobial, cytotoxicity
DOI: 10.1134/S1070363217030227
INTRODUCTION
bis-diorganotin(IV) complexes derived from ONO–
ONO donor ligands [16] and the mounting need for
developing more potent and efficient metal based
compounds that can inhibit growth of multidrug
resistant infection causing pathogens, we have carried
out synthesis, spectroscopic characterization and bio-
logical screening of six new homobimetallic diorgano-
tin(IV) derivatives of N1',N4'-bis(2-hydroxybenzyl-
idene)succinohydrazide. All synthesized compounds
were characterized by elemental analysis, FT–IR, multi-
nuclear NMR (1H, 13C and 119Sn) and Mass spectra,
and screened against selected pathogenic bacterial and
fungal strains. Cytotoxicity assessed by in vivo
lethality to brine shrimp nauplii is also reported.
Organotin(IV) Schiff bases constitute an important
class of compounds characterized by broad spectrum
of applications, ranging from antitumor activity to
catalytic and ion sensitive properties [1–7]. In
particular, substantial interest has been displayed in
metal complexes of diacylhydrazones, due to their
specific structural features and various biological and
pharmaceutical activities including antituberculosis,
antimalarial and antimicrobial [8–10]. The presence of
nitrogen and oxygen donor atoms in aroyl dihyd-
razones and their ability to act as monobasic bis-bi-
dentate or tridentate, dibasic bis-tridentate or tetrabasic
bis-tridentate chelators can lead to supramolecular
structures [11–13]. Recently some homobimetallic
organotin(IV) dithiocarbamates were studied for their
promising antileishmanial activity [14]. However, few
studies have been reported for the synthesis of dior-
ganotin(IV) complexes of bis-ONO donor diacyl-
hydrazones [15]. Presence of more than one metal
center can impart special pharmacological properties to
those compounds. Inspired by our previous studies on
EXPERIMENTAL
Diorganotin(IV) dichlorides, dioctyltin(IV) oxide,
butyltin(IV) chloride dihydroxide, succinic dihyd-
razide, and 2-hydroxybenzaldehyde were purchased
from Aldrich. Analytical grade solvents were freshly
dried before use adopting standard procedures [17].
The melting points were recorded on an electrothermal
melting point apparatus, model MP-D Mitamura
Rieken Kogyo (Japan). Element analyses were carried
1 The text was submitted by the authors in English.
515

516
SHUJAH et al.
out on a Leco CHNS 932 apparatus. IR spectra were
recorded on a Bio-Rad Excaliber FT–IR, model FTS
300 MX spectrophotometer (USA) in the frequency
range of 4000–400 cm–1 using KBr discs. Multinuclear
NMR (1H, 13C, and 119Sn) spectra were measured in
CDCl3 on a Bruker ARX 300 MHz FT–NMR and a
Bruker 400 MHz FT-NMR spectrometers. Mass spectra
were measured on a MAT-311A Finnigan (Germany).
(0.74 g, 3.0 mmol) and triethylamine (0.84 mL,
6.0 mmol) in a molar ratio 1 : 2 : 4. Yield 72 %, mp
104–108°C. FT–IR spectrum, ν, cm–1: 1612 (C=N),
1080 (N–N), 568 (Sn–O), 452 (Sn–N). 1H NMR
spectrum, δ, ppm: 1.26 t (12H, Hβ-SnEt, 3JH–H = 7.5 Hz),
1.41–1.51 m (8H, Hα-SnEt), 2.69 s (4H, 2CH2), 6.70 t
(2H, Ar-H, 3JH–H = 7.2 Hz), 6. 76 d (2H, Ar-H, 3JH–H
=
8.4 Hz), 7.12 d (2H, Ar-H, 3JH–H = 7.8 Hz), 7.31 t (2H,
Ar-H, 3JH–H = 7.0 Hz), 8.60 s [2H, CH=N, 3J(119Sn–1H) =
43 Hz]. 13C NMR spectrum, δ, ppm: 9.3 [Cβ-SnEt,
2J(119Sn–13C) = 44 Hz], 14.1 [Cα-SnEt, 1J(119/117Sn–13C) =
618, 592 Hz], 30.7 (CH2)2, 116.5 (Ar-C), 160.9 (CH=N),
175.0 (NCO). Found, %: C 44.39; H 4.90; N 7.91.
C26H34N4O4Sn2. Calculated, %: C 44.36; H 4.87; N
7.96. EI-MS, m/z: 706 [(C8H5N2O2)2C2H4Sn2(C2H5)4]+.
N1',N4'-Bis(2-hydroxybenzylidene)succinohydrazide
(H4L). 2-Hydroxybenzaldehyde 1.66 g (13.68 mmol)
and succinic dihydrazide 1.0 g (6.84 mmol) were mixed
in ethanol and refluxed upon stirring for 2 h. The
product was obtained as white solid, yield 78%, mp
214–216°C. FT–IR spectrum, ν, cm–1: 3455 (OHphenolic),
1
3178 (NH), 1669 (C=O), 1618 (C=N). H NMR spec-
Bis[di-n-butyltin(IV)] [N1',N4'-bis(2-oxidobenzyl-
idene)succinohydrazide] (3) was prepared similarly
to 1, using N1',N4'-bis(2-hydroxy-benzylidene)succino-
dihydrazide (0.53 g, 1.5 mmol), dibutyltin(IV) dichlo-
ride (0.91 g, 3.0 mmol) and TEA (0.84 mL, 6.0 mmol)
in a molar ratio 1 : 2 : 4. Yield 78 %, paste. FT–IR
spectrum, ν, cm–1: 1610 (C=N), 1075 (N–N), 570 (Sn–O),
trum, δ, ppm: 2.58 s (4H, 2CH2), 6.89 t (2H, Ar-H,
3
3JH–H = 7.1 Hz), 6.90 d (2H, Ar-H, JH–H = 7.1 Hz),
3
7.27 t (2H, Ar-H, JH–H = 7.8 Hz), 7.49 d (2H, Ar-H,
3JH–H = 8.1 Hz), 8.28 s (2H, CH=N). 13C NMR spec-
trum, δ, ppm: 29.4 [(CH2)2], 116.6 (Ar-C), 147.0
(CH=N), 168.2 (NCO). Found, %: C 61.06; H 5.14; N
15.79. C18H18N4O4. Calculated, %: C 61.01; H 5.12; N
15.81. EI-MS, m/z: 354 [C18H18N4O4]+.
1
458 (Sn–N). H NMR spectrum, δ, ppm: 0.87 t (12H,
Hδ-SnBu, 3JH–H = 7.2 Hz), 1.30–1.41 m (8H, Hγ-SnBu),
Bis[dimethyltin(IV)] [N1',N4'-bis(2-oxidobenzyl-
idene)succinohydrazide] (1). N1',N4'-bis(2-Hydroxy-
benzylidene)succinohydrazide H4L (0.53 g, 1.5 mmol)
and TEA (0.84 mL, 6.0 mmol) were mixed and stirred
for 15 min in dry toluene. Dimethyltin(IV) dichloride
(0.66 g, 3.0 mmol) was added and the mixture was
stirred for 5 h at room temperature. White precipitate
of Et3NHCl formed was filtered off. Upon evaporation
under reduced pressure the filtrate gave yellow solid.
The product was recrystallized from chloroform : n-
hexane (4 : 1) (Scheme 1b). Yield 75 %, mp 233–235°C.
FT–IR spectrum, ν, cm–1: 1609 (C=N), 1077 (N–N),
1.46–1.54 m (8H, Hβ-SnBu), 1.60–1.67 m (8H, Hα-
3
SnBu), 2.67 s (4H, 2CH2), 6.70 t (2H, Ar-H, JH–H
=
3
7.8 Hz), 6. 76 d (2H, Ar-H, JH–H = 8.4 Hz), 7.12 d
3
3
(2H, Ar-H, JH–H = 7.8 Hz), 7.31 t (2H, Ar-H, JH–H
=
7.0 Hz), 8.58 s [2H, CH=N, 3J(119Sn–1H) = 43 Hz]. 13C
NMR spectrum, δ, ppm: 13.6 (Cδ-SnBu), 22.0 (Cα-
SnBu), 26.4 [Cγ-SnBu, 3J(119/117Sn–13C) = 89 Hz], 26.8
[Cβ-SnBu, J(119/117Sn–13C) = 18 Hz], 30.8 (CH2)2,
2
116.5 (Ar-C), 160.8 (CH=N), 174.9 (NCO). 119Sn NMR
spectrum, δ, ppm: –194.0. Found, %: C 49.98; H 6.20; N
6.84. C34H50N4O4Sn2. Calculated, %: C 50.03; H 6.17; N
6.86. EI-MS, m/z: 761 [(C8H5N2O2)2C2H4Sn2(C4H9)3]+.
1
563 (Sn–O), 457 (Sn–N). H NMR spectrum, δ, ppm:
2
0.88 s [12H, Hα-SnMe, J(119/117Sn–1H) = 78, 76 Hz],
Bis(diphenyltin(IV)] [N1',N4'-bis(2-oxidobenzyl-
idene)succinohydrazide] (4) was prepared similarly
to 1, using N1',N4'-bis(2-hydroxybenzylidene)succino-
hydrazide (0.53 g, 1.5 mmol), diphenyltin(IV) dichlo-
ride (1.03 g, 3.0 mmol) and TEA (0.84 mL, 6.0 mmol)
in a molar ratio 1 : 2 : 4. Yield 78 %, mp 236–238°C.
IR spectrum, ν, cm–1: 1608 (C=N), 1070 (N–N), 568
3
2.58 s (4H, 2CH2), 6.74 d (2H, Ar-H, JH–H = 8.0 Hz),
3
6.72 t (2H, Ar-H, JH–H = 8.1 Hz), 7.14 d (2H, Ar-H,
3
3JH–H = 7.5 Hz), 7.32 t (2H, Ar-H, JH–H = 7.6), 8.58 s
3
[2H, CH=N, J(119Sn–1H) = 46 Hz]. 13C NMR spec-
trum, δ, ppm: 30.6 (CH2)2, 116.2 (Ar-C), 156.2
(CH=N), 174.1 (NCO). 119Sn NMR spectrum, δ, ppm:
–158.1. Found, %: C 40.81; H 4.01; N 8.68.
C22H26N4O4Sn2. Calculated, %: C 40.78; H 4.04; N
8.65 EI-MS, m/z: 650 [(C8H5N2O2)2C2H4Sn2(CH3)4]+.
1
(Sn–O), 451 (Sn–N). H NMR spectrum, δ, ppm: 2.97
s (4H, 2CH2), 6.78 t (2H, Ar-H, 3JH–H = 7.5 Hz), 7.10 d
3
3
(2H, Ar-H, JH–H = 8.4 Hz), 7.15 d (2H, Ar-H, JH–H
=
Bis[diethyltin(IV)]
[N1',N4'-bis(2-oxidobenzyl-
7.8 Hz), 7.37–7.42 m (2H, Ar-H), 7.81–7.87 m (4H,
3
idene)succinohydrazide] (2) was prepared similarly
to 1, using N1',N4'-bis(2-hydroxybenzylidene)succino-
hydrazide (0.53 g, 1.5 mmol), diethyltin(IV) dichloride
Hβ-SnPh), 8.55 s[(2H, CH=N, J(119Sn–1H) = 52 Hz].
13C NMR spectrum, δ, ppm: 30.7 (CH2)2, 116.6 (Ar-C),
2
136.2 [Cb-SnBu, J(119/117Sn–13C) = 54 Hz], 128.8
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HOMOBIMETALLIC ORGANOTIN(IV) COMPLEXES
517
Scheme 1. Synthesis of N1',N4'-bis(2-hydroxybenzylidene)succinohydrazide (a) and bis[diorganotin(IV)] derivatives (b–c).
Numbering scheme of alkyl groups bonded to tin atom in bis[dialkyltin(IV)] derivatives (d).
(a)
O
O
H
H
H2N
N
2
+
N
NH2
H
OH
HO
O
HO
OH
O
H
N
N
N
N
N
N
Ethanol
2 h reflux
N
N
H
+ 2H2O
HO
OH
Iminol form
O
OH
OH
(b)
Amido form
O
H
N
N
+ 2R2SnCl2 + 4(C2H5)3N
N
N
H
O
OH
R
R
Sn
O
O
N
N
N
O
N
Toluene
+ 4(C2H5)3NHCl
O
Sn
R
R
R = CH3 (1), C2H5 (2), C4H9 (3), C6H5 (4), tert-C4H9 (6).
(c)
HO
O
H
N
N
+ 2R2SnO
N
N
H
O
OH
R
R
Sn
O
O
N
N
N
N
Toluene
+ 2H2O
O
O
Sn
R
R
R = C8H17 (5).
(d)
β
γ
β
CH3
α C
H2
H2
H2
H2
α
H2
H2
H2
α
β
β
β'
δ
β
δ'
CH3
β
δ
C
C
C
C
C
δ
CH3,
C
C
,
,
,
,
CH3
CH3
α'
γ
α
γ'
γ
α
C
C
C
α
C
CH3
CH3
H2
H2
H2
H2
γ'
β'
β
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

518
SHUJAH et al.
3
[Cγ-SnBu, J(119/117Sn–13C) = 88], 130.5 [Cδ-SnBu,
Calculated, %: C 50.03; H 6.17; N 6.86. EI-MS, m/z:
4J(119/117Sn–13C)
=
17 Hz], 139.0 [Cα-SnBu,
[(C8H5N2O2)2C2H4Sn2(C4H9)3]+ 761.
1J(119/117Sn–13C) = 592 Hz], 161.2 (CH=N), 174.6
(NCO). 119Sn NMR spectrum, δ, ppm: –342.0. Found,
%: C 56.31; H 3.79; N 6.21. C42H34N4O4Sn2. Cal-
culated, %: C 56.29; H 3.82; N 6.25. EI-MS, m/z: 463
[(C8H5N2O2)C2H4Sn(C6H5)2]+.
Antibacterial activity. The synthesized ligand (H4L)
and bis-diorganotin(IV) complexes were evaluated for
antibacterial activity against Escherichia coli ATCC
11229, Bacillus subtilis ATCC 11774, Shigella
flexneri ATCC 10782, Staphylococcus aureus ATCC
25923, Pseudomonas aeruginosa ATCC 10245 and
Salmonella typhi ATCC 10749 using the agar well
diffusion method [18]. Imipenum was used as еру
standard drug and 6 mm diameter wells were dug in
the media with the help of a sterile metallic borer. In
8 h old bacterial inoculums containing ca 104–106
colony forming units (CFU)/mL were spread on the
surface of nutrient agar with the help of a sterile cotton
swab. The recommended concentration of the test
sample (2 mg/mL in DMSO) was introduced into the
respective wells. Other wells supplemented with
DMSO and reference antibacterial drug served as
negative and positive controls, respectively. The plates
were incubated immediately at 37 °C for 20 h. Activity
was determined by measuring diameter of the
inhibition zone in mm. Growth inhibition was
calculated with reference to the positive control.
Bis[di-n-octyltin(IV)][N1',N4'-bis(2-oxidobenzyl-
idene)succinohydrazide] (5) was prepared by re-
fluxing N1',N4'-bis(2-hydroxybenzylidene)succinohyd-
razide (0.53 g, 1.5 mmol) and dioctyltin(IV) oxide
(1.09 g, 3.0 mmol) in 100 mL of dry toluene, molar
ratio 1 : 2. The accumulated water was removed by a
Dean-Stark apparatus. The yellow solution obtained
was evaporated under reduced pressure. The solid
product was recrystallized from chloroform n-hexane
(4 : 1) (Scheme 1c). Yield 72%, paste. FT–IR spec-
trum, ν, cm–1: 1612 (C=N), 1070 (N–N), 564 (Sn–O),
1
458 (Sn–N). H NMR spectrum, δ, ppm: 0.87 t (12H,
3
Hδ'-SnOct, JH–H = 6.9 Hz), 1.22–1.36 br.s (32H, Hγ-γ'-
SnOct), 1.44–1.48 m (8H, Hβ-SnOct), 1.63–1.67 m
(8H, Hα-SnOct), 2.66 s (4H, 2CH2), 6.70 t (2H, Ar-H,
3JH–H = 7.2 Hz), 6.75 d (2H, Ar-H, JH–H = 8.4 Hz),
3
3
7.11 d (2H, Ar-H, JH–H = 7.2 Hz), 7.30 t (2H, Ar-H,
3JH–H = 7.2 Hz), 8.57 s [2H, CH=N, J(119Sn–1H) =
3
43 Hz]. 13C NMR spectrum, δ, ppm: 14.1 (Cδ-SnOct),
Antifungal activity. The in vitro antifungal activity
of synthesized compounds was investigated against six
fungal strains [Trichophyton longifusus ATCC 22397,
Candida albicans ATCC 2192, Aspergillus flavus
ATCC 1030, Microsporum canis ATCC 9865,
Fusarium solani ATCC 11712, Candida glabrata
ATCC 90030] using the agar tube dilution test [19].
Miconazole and Amphotericin B were used as the
standard drugs. Stock solutions of pure compounds
(200 mg/mL) were prepared in sterilized DMSO.
Sabouraud dextrose agar was prepared by mixing
Sabouraud (32.5 g), glucose agar (4%) and agar-agar
(20 g) in 500 mL of distilled water followed by
dissolution at 90–95°C. The media (4 mL) was
dispensed into screw-capped tubes and autoclaved at
121 °C for 15 min. Known amounts of test compounds
were added from the stock solution to non-solidified
Sabouraud agar media (50 °C). The contents of the
tubes were then solidified at room temperature and
inoculated with 4 mm diameter portion of inoculums
derived from a 7 days old respective fungal culture.
For non-mycelial growth an agar surface streak was
employed. The tubes were incubated at 27–29°C for 7–
10 days and growth in the compound containing media
was determined by measuring the linear growth in mm.
22.4 [Cα-SnOct, J(119/117Sn–13C) = 602 Hz], 22.7 (Cδ-γ'-
1
SnOct), 24.7 [Cb-SnOct, J(119/117Sn–13C) = 35 Hz],
2
30.8 (CH2)2, 33.4 [Cγ-SnOct, 3J(119/117Sn–13C) = 79 Hz],
116.6 (Ar-C), 160.7 (CH=N), 174.9 (NCO). 119Sn NMR
spectrum, δ, ppm: –198. Found, %: C 57.68; H 7.97; N
5.40. C50H82N4O4Sn2. Calculated, %: C 57.71; H 7.94;
N 5.38. EI-MS, m/z: 929 [(C8H5N2O2)2C2H4Sn2(C8H17)3]+.
Bis[di-tert-butyltin(IV)] [N1',N4'-bis(2-oxidobenzyl-
idene)succinohydrazide] (6) was prepared similarly
to 1, using N1',N4'-bis(2-hydroxybenzylidene)succino-
hydrazide (0.53 g, 1.5 mmol), di-tert-butyltin(IV)
dichloride (0.91 g, 3.0 mmol) and TEA 0.84 mL
(6.0 mmol) in a molar ratio 1 : 2 : 4. Yield 70 %, mp
128–133°C. FT–IR spectrum, ν, cm–1: 1607 (C=N),
1071 (N–N), 559 (Sn–O), 452 (Sn–N). 1H NMR
spectrum, δ, ppm: 1.31 s [18H, Hβ-Sn-tert-Bu,
3J(119/117Sn-1H) = 109, 105 Hz], 2.72 s (4H, 2CH2),
3
6.67 t (2H, Ar-H, JH–H = 7.5 Hz), 6.81 d (2H, Ar-H,
3JH–H = 8.1 Hz), 7.10 d (2H, Ar-H, JH–H = 7.8 Hz),
3
3
7.30 t (2H, Ar-H, JH–H = 7.6), 8.58 s (2H, CH=N,
3J(119Sn–1H) = 39 Hz)]. 13C NMR spectrum, δ, ppm:
29.6 (Cβ-Sn-tert-Bu), 30.4 (CH2)2, 40.4 (Cα-Sn-tert-
Bu), 116.4 (Ar-C), 160.5 (CH=N), 175.0 (NCO).
Found, %: C 49.98; H 6.21; N 6.84. C34H50N4O4Sn2.
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HOMOBIMETALLIC ORGANOTIN(IV) COMPLEXES
519
Cytotoxicity. Cytotoxicity of the compounds was
studied by the Brine shrimp lethality bioassay [19].
Brine shrimps (Artemia salina) were hatched using
brine shrimp eggs in a vessel, filled with sterile
simulated seawater (prepared using sea salt 38 g/L and
adjusted to pH 8.5 using 1 M NaOH) at 22–29°C with
constant aeration for two days. After hatching, thirty
active nauplii were drawn through a glass capillary and
placed in a vial containing 4.5 mL of brine solution
and a drop of yeast suspension. In each experiment,
0.5 mL of the test solution was added to the vial and
maintained at ambient temperature for 24 h, the
surviving larvae were counted. All experiments with
different concentrations (1, 10, 100 mg/mL) of the test
substances were conducted in triplicate and compared
with the control. Data were analyzed with Finney’s
probit analysis to determine the LD50 [20]. Etoposide
was used as the standard drug.
indicated formation of the Sn–O and Sn–N bonds,
respectively [21–23].
1
NMR spectra. Signals of OH and NH in H NMR
spectrum of the ligand disappeared in the spectra of bis-
diorgnaotin(IV) complexes 1–6 suggesting deprotona-
tion and enolization of the ligand in the course of
complex formation [24]. Aromatic protons of the
ligand and methylene protons of the alkyl linker were
recorded by signals in the regions 6.90–7.49 and
2.58 ppm, respectively. These groups were not
involved in bonding and their signals remained
unaffected in the NMR spectra of bis-diorganotin(IV)
by complexes formation. The signal at 8.28 ppm was
assigned to the noncoordinated azomethine (CH=N)
proton. Upon coordination its downfield shift to 8.55–
3
8.60 ppm with J(119Sn–1H) = 39–52 Hz indicated
shifting of electrons density from azomethine nitrogen
to Sn atom, thus, affirming the presence of Sn–N bond
in a solution. The chemical shifts and coupling con-
stants were consistent with reported diorganotin(IV)
complexes of bis-ONO donor type ligands [25].
RESULTS AND DISCUSSION
All synthesized compounds were stable in the air.
Efforts to obtain single crystal were not successful.
The CH3 protons in complex 1 resonated as a
singlet at 0.88 ppm with Sn satellites corresponding to
2J(119Sn–1H) coupling constant of 78 Hz. Substitution
into the Lockhart–Manders equation, θ = 0.016|2J|2 –
1.32|2J| + 133.4, gave C–Sn–C angle of 128.4° indicat-
ing a pentacoordinated Sn atom in a solution [26].
Mass spectra. MS data for the fragmented ions
were in good agreement with structureы of the
compounds. The molecular ion peaks M+ were
observed only for H4L compounds 1 and 2. Primary
fragmentation took place by loss of the R group. Loss
of the ligand in a subsequent step led to the formation
of [RSn]+. [Sn]+ fragment was formed by elimination
of R radical. The [C4H9]+ and [CH3]+ ions were also
observed with significant intensities.
Complexation induced a shift of the electron
density from the ligand to diorganotin(IV) moieties and,
hence, a downfield shift of 13C signals of the ligand. In
organotin(IV) compounds, the 1J (119Sn, 13C) value was
an important parameter used to establish the coordina-
tion around tin in solution. The calculated coupling
constants for compounds 1, 2, 4, and 5 were in the
range of 592–649 Hz indicating pentacoordination
around the Sn atom in a solution [27]. The calculated
C–Sn–C angles (deg) based on NMR parameters
(1J and 2J) are presented in Table 1.
119Sn NMR spectra were used to ascertain the
coordination geometry of Sn atom. All complexes
exhibited a single sharp resonance indicating similar
coordination environment around each Sn atom. The
119Sn NMR signals for dimethyl, dibutyl and dioctyl
complexes were observed at –158, –194, and
–198 ppm, respectively. For the diphenyl complex the
anisotropic shielding effects and pi interactions caused
the signal to appear at –342 ppm. The chemical shift
data accumulated for complexes in CDCl3 suggested
that in noncoordinating solvents each Sn atom was
FT-IR spectra. Comparison of IR spectra of
complexes with that of ligand provided evidence for
the binding sites involved in chelation. Absorption
bands observed in the solid state IR spectrum of ligand
at 3455, 3178, and 1669 cm–1 have been assigned to
the stretching vibrations of OH, NH, and C=O groups,
all bands disappearув in the IR spectra of bis-
diorganotin(IV) complexes, suggesting tautomeric
shift followed by deprotonation and coordination of
phenolic and enolic oxygens to the diroganotin(IV)
moieties. The shift of stretching vibrations of C=N to
lower frequencies provided evidence for the interaction
of azomethine nitrogen with Sn atom. The band
assigned to N–N was shifted to higher frequencies
(1070–1080 cm–1) in the spectra of organotin(IV)
complexes due to the decrease in repulsion of the lone
pairs of electrons on nitrogen atoms. Appearance of
new bands in the regions of 559–570 and 451–458 cm–1
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520
SHUJAH et al.
Table 1. C–Sn–C angles (deg) based on NMR parameters of
selected bis-diorganotin(IV) complexes
penetration of complexes into the cell easily. On the
other hand, Gram-negative bacterial cell with a bilayer
phospholipid structure protected the inner cytoplasmic
membrane to a greater degree against the inhibitory
action of the organotin(IV) complex. All synthesized
compounds were inactive against S. typhi. Highest
activity was demonstrated by 3 against B. subtilis.
Information about the exact mechanism was meager
and is yet to be fully explored. However, the enhanced
activity of complexes can be rationalized on the basis
of Overtone’s concept and Tweedy’s chelation theory,
which demands enhanced lipophilicity for antimicro-
bial action [33–35]. None of the synthesized com-
pounds was more active than the standard drug.
Angle, deg
Comp.
1J(119Sn, 13C),
2J(119Sn, 1H),
2J,
Hz
1J, Hz
no.
Hz
Hz
1
2
4
5
649
618
592
602
78
–
133.7 128.4
131.0
134.1
135.1
–
–
–
–
–
pentacoordinated with trigonal bipyramidal geometry
[28–31].
Antifungal activity. The in vitro antifungal activity
of ligand H4L and bis[diorganotin(IV)] complexes 1–6
was tested against six human pathogenic fungal strains
including yeasts (Candida albicans, Candida glabrata),
dermatophytes (Microsporum canis, Trichophyton
longifusus) and opportunistic molds (Aspergillus
flavus, Fusarium solani) using the agar tube dilution
Antibacterial activity. The corresponding data
(Table 2) demonstrated an increase in the antibacterial
activity upon complexation with the diorganotin(IV)
[32]. The synthesized bis-diorganotin(IV) complexes
1–6 exhibited elevated inhibitory activity against gram
positive bacteria (B. subtilis, S. aureus) which had a
loosely packed polyglycane outer layer making the
Table 2. Antibacterial activity of bis-diorganotin(IV) derivatives of N1',N4'-bis(2-hydroxybenzylidene)succinohydrazidea,b
Inhibition zone diameter, mm
Bacteria (ATCC no.)
H4L
1
2
3
4
5
–
–
6
reference drugc
Escherichia coli (11229)
–
12
–
12 14
–
30
37
36
26
32
30
Bacillus subtilis (11774)
–
11 12 16 14
14
Shigella flexnari (10782)
Staphlococcus aureus (25923)
Pseudomonas aeruginosa (10145)
Salmonella typhi (10749)
–
14
–
–
–
–
–
–
11 12
–
12 10 12
–
–
–
12
–
–
11
-
–
–
–
–
–
–
a Concentration 1 mg/mL of DMSO. b Reference drug, imipenum. c (–) Insignificant activity.
Table 3. Antifungal activity of bis-diorganotin(IV) derivatives of N1',N4'-bis(2-hydroxybenzylidene)succinohydrazidea,b
Inhibition, %
Fungi (ATCC no.)
H4L
–
1
–
–
–
–
2
3
4
–
5
–
–
–
–
–
–
6
10
–
standard drugc
Trichophyton longifusus (22397)
Candida albicans (2192)
Aspergillus flavis (1030)
Microsporum canis (9865)
Fusarium solani (11712)
Candida glaberata (90030)
10 20
100
100
100
100
100
100
30
40
–
–
–
–
–
70
–
–
–
30
–
–
45
–
30 35
-
70
–
–
–
–
–
–
a Concentration 400 μg/mL of DMSO. b Standard drug: amphotericin-B, miconazole. c (–) No inhibition.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

HOMOBIMETALLIC ORGANOTIN(IV) COMPLEXES
521
formation of compounds 1–6. 1H and 13C NMR spectra
indicated five-coordinated structure of Sn (1–6) in a
solution. The complexes exhibited high antimicrobial
activity as compared to ligand indicating the role of Sn
in their antimicrobial action. Compound 3 exhibited
the highest activity against Bacillus subtilis and
Aspergillus flavis. The highest cytotoxicity was demon-
strated by compound 3 (LD50 32.11 μg/mL).
Table 4. Brine Shrimp (Artemia salina) lethality bioassay
data of bis-diorganotin(IV) derivatives of N1',N4'-bis(2-hyd-
roxybenzylidene)succinohydrazidea
Comp. no.
LD50, μg/mL
H4L
1
–
–
2
–
3
32.11
ACKNOWLEDGMENTS
4
–
–
–
We thank the Higher Education Commission of
Pakistan for the financial support.
5
6
a Standard drug: etoposide, LD50 = 7.46 μg/mL.
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