Diorganotin(IV) complexes of Schiff bases derived from salicylaldehyde and 2-amino-6-substituted benzothiazoles: synthesis, spectral studies, in vitro antimicrobial evaluation and QSAR studies

Article abstract of DOI:10.1007/s11164-018-3395-z

In the present work, Schiff base ligands (1–4) were prepared by condensation of 2-amino-6-substituted-benzothiazole and salicyaldehyde in a 1:1 molar ratio and were further treated with diorganotindichloride R’₂SnCl₂ leading to a series of organotin(IV) complexes (5–20) of type R’₂SnL^1?4Cl [R’ = Ph, Bu, Et, Me]. The prepared Schiff base ligands and the organotin(IV) complexes were characterized by various spectroscopic techniques (¹H, ¹³C, ¹¹⁹Sn NMR, FT-IR) and physical techniques. All the synthesized compounds were evaluated for in vitro antibacterial and antifungal activity against two Gram positive bacterial strains B. cereus, S. aureus, two Gram negative bacterial strains E. coli, P. aeruginosa and two fungal strains A. niger and A. flavus by serial dilution method. The spectral data revealed that the complexes were pentacoordinated with bidentate ligands coordinated through oxygen and nitrogen. The results of antimicrobial activity revealed that the synthesized complexes were more toxic towards Gram positive bacterial strains as compared to Gram negative bacterial strains. From the results of QSAR analysis, it was indicated that the antimicrobial activity of the synthesized compounds were controlled by topological parameters (molecular connectivity indices).

Full text of DOI:10.1007/s11164-018-3395-z

Res Chem Intermed
https://doi.org/10.1007/s11164-018-3395-z
Diorganotin(IV) complexes of Schiff bases derived
from salicylaldehyde and 2-amino-6-substituted
benzothiazoles: synthesis, spectral studies, in vitro
antimicrobial evaluation and QSAR studies
Aarti Ahlawat1 Priyanka Khatkar1 Vikramjeet Singh2
Sonika Asija1
•
•
•
Received: 4 January 2018 / Accepted: 15 March 2018
Ó Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract In the present work, Schiff base ligands (1–4) were prepared by con-
densation of 2-amino-6-substituted-benzothiazole and salicyaldehyde in a 1:1 molar
ratio and were further treated with diorganotindichloride R’2SnCl2 leading to a
series of organotin(IV) complexes (5–20) of type R’2SnL1-4Cl [R’ = Ph, Bu, Et,
Me]. The prepared Schiff base ligands and the organotin(IV) complexes were
characterized by various spectroscopic techniques (1H, 13C, 119Sn NMR, FT-IR) and
physical techniques. All the synthesized compounds were evaluated for in vitro
antibacterial and antifungal activity against two Gram positive bacterial strains B.
cereus, S. aureus, two Gram negative bacterial strains E. coli, P. aeruginosa and
two fungal strains A. niger and A. flavus by serial dilution method. The spectral data
revealed that the complexes were pentacoordinated with bidentate ligands coordi-
nated through oxygen and nitrogen. The results of antimicrobial activity revealed
that the synthesized complexes were more toxic towards Gram positive bacterial
strains as compared to Gram negative bacterial strains. From the results of QSAR
analysis, it was indicated that the antimicrobial activity of the synthesized com-
pounds were controlled by topological parameters (molecular connectivity indices).
Keywords Schiff base ligands Á Organotin(IV) complexes Á Benzothiazole
derivatives Á Antimicrobial activity Á QSAR studies
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11164-
018-3395-z) contains supplementary material, which is available to authorized users.
&
Sonika Asija
sc_ic2001@yahoo.co.in
1
2
Department of Chemistry, G.J. University of Science and Technology, Hisar, Haryana 125001,
India
Department of Pharmaceutical Sciences, G.J. University of Science and Technology, Hisar,
Haryana 125001, India
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A. Ahlawat et al.
Introduction
The need for pharmaceutical drugs is the core driving force for the extraordinary
growth in metal-based drug development studies. The optimistic results revealed by
tin complexes such as metallotherapeutics have inspired more precise research in
this area [1–3]. Organotin(IV) complexes show uniqueness at synthetic and
structural stages, and their application can be modified as a result of ligands attached
to the central tin metal [4, 5]. Moreover, organotin(IV) complexes demonstrate the
most assorted fragment of applications ranging from industrial, catalysis and
therapetics due to their wide range of fascinating structural potential [6–11]. Some
unique features of organotin(IV) complexes, such as thermodynamic and kinetic
characteristics, coordination number variations, geometries, and intrinsic properties
of the metal ion, have motivated research interest into finding use fore the varied
approaches in diverse fields including agricultural, industrialized, and biomedical
fields such as in wood preservatives, surface disinfectants, insecticides, antifouling
agents [12–14]. Schiff bases show promising chemotherapeutic applications such as
insecticidal, antibacterial, antifungal, anti-inflammatory and antitumor [15–17].
Nowadays, organotin(IV) complexes of Schiff bases are attractive scaffolds for
novel drug discovery as a result of their remarkable biological activities. Schiff
bases illustrate an expansive spectrum of applications owing to their ability to
cleave microorganism DNA [18]. They are enormously studied due to structural
varieties, flexibility, high thermal stability, and medical efficacy [19, 20].
Benzothiazoles are versatile fused heterocyclic scaffolds with extensive pharma-
ceutical applications. They are mainly found in bio-inorganic and medicinal
chemistry with wide applications in drug discovery. A large number of therapeutic
agents are synthesized with the help of a benzothiazole nucleus. In addition,
benzothiazoles act as the core nucleus in various drugs due to their various activities
and have attracted a great deal of interest due to their wide range of biological
activity such as anticancer, antitubercular, anti-HIV, cardiovascular, local anaes-
thetic, anti-inflammatory, anticonvulsant and anti-diabetic. The therapeutic prop-
erties of the benzothiazoles have encouraged medicinal chemists to synthesize a
large number of novel chemotherapeutic agents [21, 22]. Recently, substituted
2-arylbenzothiazoles have emerged as an imperative pharmacophore with a number
of remedial and analytical properties due to their synthetic accessibility [23].
In pursuit of this, the present study focused on the synthesis, spectroscopic
analysis, antimicrobial evaluation and QSAR studies of Schiff bases of 2-amino-6-
substituted-benzothiazole derivatives and their respective organotin(IV) complexes.
Experimental
Materials and physical measurements
All chemicals were purchased from Sigma Aldrich and were used without further
purification. All solvents were of analytical grade, received from Sigma Aldrich and
123

Diorganotin(IV) complexes of Schiff bases derived from…
used after drying with standard procedures. IR spectra were recorded using a
.
Shimadzu IR Affinity-I 8000 FT-IR spectrometer in the range 4000–400 cm-1
NMR spectra of the compounds were recorded on 400 MHz using Bruker Avance II
1
400 MHz NMR spectrometer. H, 13C NMR and 119Sn NMR were recorded using
tetramethylsilane and tetramethyltin, respectively, as internal standard in DMSO-d6.
Tin was gravimetrically estimated as SnO2 after decomposition with concentrated
HNO3 [24]. The melting points were recorded on an electrical heating coil apparatus
and were uncorrected. The elemental analysis of the compounds was done using a
Perkin Elmer 2400 instrument.
The compounds were assessed for in vitro antimicrobial activity against bacterial
and fungal strains using serial dilution to evaluate MIC (minimum inhibitory
concentration) [25]. Sabouraud dextrose broth and nutrient broth were used as
growth media for fungal and bacterial strains, respectively, and test tubes with 1 mL
of nutrient medium were autoclaved for 30 min at 121 °C. The stock solutions of
compounds with a concentration of 100 lg/mL were prepared in DMSO and further
diluted to concentrations of 50, 25, 12.5, 6.25, 3.12 and 1.56 lg/mL. One hundred
microliters of freshly cultured strain in normal saline was transferred to each test
tube for inoculation and incubated at 25 °C for 7 days for fungal strains and 37 °C
for 24 h for bacterial strains. Each sample was assayed in triplicate, and the
concordant MIC values were reported.
Pre-optimization of the structures of compounds 1–20 was done by the Molecular
Mechanics Force Field (MM) process of Hyperchem 6.03 [26], and the resulting
geometries were further developed by means of the semiempirical method
Parametric Method-3 (PM-3). Geometric optimization was done by a gradient
norm limit of 0.01 kcal/A°. The minimum energy structure of each molecule was
used for the calculating physicochemical parameters using TSAR 3.3 software for
Windows [27]. Regression analysis was done using the SPSS software package [28].
Synthesis of Schiff base ligands (1–4)
The methanolic solution of salicylaldehyde (5 mmol), 2-amino-6-substituted
benzothiazoles (5 mmol), 2–3 drops of glacial acetic acid were refluxed together
(30 mL) for about 5–6 h at room temperature. The solid obtained was dried,
purified, washed with methanol and recrystallised with the mixture of methanol and
chloroform (1:1, v/v). The purity of the compound was checked regularly with thin
layer chromatography (TLC).
[1] (2-((6-ethoxybenzo[d]thiazol-2-ylimino)methyl)phenol) Yield: 82%; yellow
solid; melting point: 180–182 °C; (Mol. Wt. 298.08); Anal. Calcd for C16H14N2O2S
(%): C, 64.41; H, 4.73; N, 9.39; O, 10.72; S, 10.75. Found: C, 64.03; H, 4.52; N,
9.04; O, 10.56; S, 10.49; IR (KBr pellets, cm-1): 3430 (s, mO–H), 1618 (s, mC=N),
1
other bands (1204 s, 1036w, 969 s). H NMR (DMSO-d6, dH, ppm, 400 MHz):
11.72 (1H, s, O–H), 9.33 (1H, s, HC=N), 7.85 (1H, d, Ar–H, J = 8 Hz), 7.80 (1H, d,
Ar–H, J = 8 Hz), 7.48 (1H, d, Ar–H), 7.07 (1H, d, Ar–H, J = 8 Hz), 7.02 (1H, t,
Ar–H, J = 8 Hz), 7.00 (1H, t, Ar–H, J = 8 Hz), 6.95 (1H, s, Ar–H, J = 8 Hz), 4.14–
4.08 (2H, q, OCH2), 1.43–1.39 (3H, t, CH3). 13C NMR (DMSO-d6, dC, ppm,
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A. Ahlawat et al.
100 MHz): 184.30, 171.00, 161.05, 145.34 (C=N), 135.52 126.65, 124.77, 123.97,
123.38, 122.94, 120.57, 115.65, 113.44, 112.56, 111.09 (s, Ar–C), 62.12 (s, C–
OCH2), 12.87 (s, C–CH3).
[2] (2-((6-nitrobenzo[d]thiazol-2-ylimino)methyl)phenol) Yield: 84%; yellow
solid; melting point: 168–170 °C; (Mol. Wt. 299.04); Anal. Calcd for C14H9N3O3S
(%): C, 56.18; H, 3.03; N, 14.04; O, 16.04; S, 10.71. Found: C, 55.96; H, 2.94; N,
13.96; O, 15.87; S, 10.35; IR (KBr pellets, cm-1): 3338 (s, mO–H), 1617 (s, mC=N),
1
other bands (1209 s, 1035w, 975 s). H NMR (DMSO-d6, dH, ppm, 400 MHz):
11.64 (1H, s, O–H), 9.24 (1H, s, HC=N), 7.76 (1H, d, Ar–H, J = 8 Hz), 7.71 (1H, d,
Ar–H, J = 8 Hz), 7.41 (1H, d, Ar–H, J = 8 Hz), 7.37 (1H, d, Ar–H, J = 8 Hz), 6.98
(1H, t, Ar–H, J = 8H), 6.91 (1H, t, Ar–H, J = 8 Hz), 6.88 (1H, s, Ar–H). 13C NMR
(DMSO-d6, dC, ppm, 100 MHz): 182.12, 172.51, 158.87, 143.16 (C=N), 133.34,
124.47, 122.98, 122.59, 121.79, 121.20, 120.76, 118.39, 113.47, 111.29, 110.38 (s,
Ar–C).
[3] (2-((6-methoxybenzo[d]thiazol-2-ylimino)methyl)phenol) Yield: 81%; yellow
solid; melting point: 112–114 °C; (Mol. Wt. 284.06); Anal. Calcd for C15H12N2O2S
(%): C, 63.36; H, 4.25; N, 9.85; O, 11.25; S, 11.28. Found: C, 63.03; H, 3.96; N,
9.63; O, 10.97; S, 11.09. IR (KBr pellets, cm-1): 3397 (s, mO–H), 1618 (s, mC=N),
1
other bands (1222 s, 1035w, 951 s). H NMR (DMSO-d6, dH, ppm, 400 MHz):
11.69 (1H, s, O–H), 9.29 (1H, s, HC=N), 7.81 (1H, d, Ar–H, J = 8 Hz), 7.76 (1H, d,
Ar–H, J = 8 Hz), 7.47–7.41 (1H, m, Ar–H), 7.04 (1H, d, Ar–H, J = 8 Hz), 7.00
(1H, t, Ar–H, J = 8 Hz), 6.94 (1H, t, Ar–H, J = 8 Hz), 6.91 (1H, s, Ar–H), 4.08
(3H, s, OCH3). 13C NMR (DMSO-d6, dC, ppm, 100 MHz): 185.58, 162.63, 158.87,
146.92 (C=N), 137.10, 128.23, 126.74, 126.34, 125.55, 124.96, 124.52, 122.15,
117.23, 115.02, 114.14 (s, Ar–C), 61.82 (s, C–OCH3).
[4] (2-((6-methylbenzo[d]thiazol-2-ylimino)methyl)phenol) Yield: 83%; yellow
solid; melting point: 154–156 °C; (Mol. Wt. 268.07); Anal. Calcd for C15H12N2OS
(%): C, 67.14; H, 4.51; N, 10.44; O, 5.96; S, 11.95. Found: C, 66.95; H, 4.38; N,
10.09; O, 5.65; S, 11.86. IR (KBr pellets, cm-1): 3400 (s, mO–H), 1617 (s, mC=N),
1
other bands (1221 s, 1042w, 976 s). H NMR (DMSO-d6, dH, ppm, 400 MHz):
11.77 (1H, s, O–H), 9.37 (1H, s, HC=N), 7.90 (1H, d, Ar–H, J = 8 Hz), 7.85 (1H, d,
Ar–H, J = 8 Hz), 7.54 (1H, m, Ar–H), 7.50 (1H, m, Ar–H), 7.12 (1H, t, Ar–H,
J = 4 Hz), 7.04 (1H, t, Ar–H, J = 4 Hz), 7.01 (1H, s, Ar–H), 1.46 (3H, s, CH3). 13
C
NMR (DMSO-d6, dC, ppm, 100 MHz): 186.17, 162.93, 147.21, 137.40 (C=N),
128.53, 127.04, 126.64, 125.84, 125.26, 124.81, 122.45, 117.52, 115.31, 114.44 (s,
Ar–C), 18.17 (s, CH3).
Synthesis of complexes (5–20)
Diorganotin(IV) complexes were synthesized by reaction of corresponding Schiff
base ligands (R = –OC2H5, –NO2, –OCH3, –CH3) and the corresponding dialkl/
aryltindichlorides (R’ = Ph, Bu, Et, Me). A weighed amount of sodium (5 mmol)
was added to the methanolic solution of prepared Schiff base ligands (5 mmol), and
the reaction mixture was refluxed for 2 h to afford the sodium salts of the
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Diorganotin(IV) complexes of Schiff bases derived from…
corresponding Schiff bases. Dialkyl/aryltindichloride (5 mmol) was added to this
sodium salt, and the reaction mixture was again refluxed for 9–10 h. Finally, after
the solid salt separated out, it was filtered, washed with methanol and then collected.
The excess solvent was evaporated over a rotary evaporator under reduced pressure
to separate out the solid which was collected and washed with dry n-hexane. The
collected solid was recrystallized with mixture of chloroform and diethylether (1:1,
v/v).
[5] N-(2-(chlorodiphenylstannyloxy)benzylidene)-6-ethoxybenzo[d]thiazol-2-amine
Yield: 79%; Yellow solid; melting point: 209–211 °C; (Mol. Wt. 606.02); Anal.
Calc. for C28H23ClN2O2SSn (%): C, 55.52; H, 3.83; Cl, 5.85; N, 4.62; O, 4.88; Sn,
19.60. Found: C, 55.34; H, 3.75; Cl, 5.56; N, 4.47; O, 4.89; Sn, 19.43. IR (KBr
pellets, cm-1): 1589 (s, mC=N), 636 (m, mSn-N), 520 (m, mSn–C), 425 (w, mSn–O), other
bands (1222 s, 1027w, 982 s). 1H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.68 (1H,
s, HC=N), 8.09 (1H, s), 8.03 (1H, d, J = 8 Hz), 7.99 (1H, d, J = 8 Hz), 7.40–7.44
(10H, m), 7.39 (1H, d, J = 8 Hz), 7.35 (1H, d, J = 8 Hz), 7.32 (1H, d, J = 8 Hz),
7.22 (1H, d, J = 8 Hz), 4.12 (2H, q, OCH2), 1.24 (3H, t, CH3). 13C NMR (DMSO-
d6, dC, ppm, 100 MHz): 184.97, 172.88, 161.72, 150.98 (C=N), 145.96, 136.19,
133.65, 130.54, 127.42, 127.00, 125.84, 125.55, 124.64, 124.05, 123.61, 121.45,
119
117.39, 116.10, 112.05 (s, Ar–C), 66.56 (s, C–OCH2), 13.55 (s, C–CH3).
NMR (DMSO-d6, dSn, ppm, 149 MHz): - 326.35.
Sn
[6] N-(2-(dibutylchlorostannyloxy)benzylidene)-6-ethoxybenzo[d]thiazol-2-amine
Yield: 76%; yellow solid; melting point: 201–203 °C; (Mol. Wt. 566.08); Anal.
Calc. for C24H31ClN2O2SSn (%): C, 50.95; H, 5.52; Cl, 6.27; N, 4.95; Sn, 20.98.
Found: C, 50.65; H, 5.45; Cl, 6.01; N, 4.78; Sn, 20.72. IR (KBr pellets, cm-1): 1601
(s, mC=N), 621 (m, mSn-N), 559 (m, mSn–C), 436 (w, mSn–O),other bands (1222 s,
1
1029w, 998 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.66 (1H, s, HC=N),
8.11 (1H, s), 8.03 (1H, d, J = 8 Hz), 7.86 (1H, d, J = 8 Hz), 7.82 (1H, d, J = 8 Hz),
7.65 (1H, d, J = 8 Hz), 7.45 (1H, d, J = 8 Hz), 7.35 (1H, d, J = 8 Hz), 4.12 (2H, q,
OCH2), 3.99 (4H, m, Bu), 3.56 (4H, m, Bu), 1.42 (3H, s, CH3), 1.34 (4H, m), 0.89
(6H, t, Bu). 13C NMR (DMSO-d6, dC, ppm, 100 MHz): 180.84, 168.75, 157.85,
146.85 (C=N), 141.82, 129.51, 126.40, 123.28, 121.41, 119.48, 119.48, 117.31,
113.26, 111.97, 107.92 (s, Ar–C), 62.43 (s, C–OCH2), 33.50 (s, Bu–C), 23.20 (s,
Bu–C), 19.42 (s, C–CH3), 15.37 (s, Bu–C), 9.41 (s, Bu–C). 119Sn NMR (DMSO-d6,
dSn, ppm, 149 MHz): - 267.14.
[7] N-(2-(chlorodimethylstannyloxy)benzylidene)-6-ethoxybenzo[d]thiazol-2-amine
Yield: 77%; yellow brown; melting point: 214–216 °C; (Mol. Wt. 481.99); Anal.
Calc. for C18H19ClN2O2SSn (%): C, 44.89; H, 3.98; Cl, 7.36; N, 5.82; Sn, 24.65.
Found: C, 44.76; H, 3.73; Cl, 7.09; N, 5.65; Sn, 24.21. IR (KBr pellets, cm-1): 1591 (s,
m
C=N), 608 (mSn-N), 528 (mSn–C), 457 (mSn–O), other bands (1227 s, 1023w, 939 s). 1H
NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.83, (1H, s, HC=N), 8.19 (1H, s), 8.11 (1H, d,
J = 8 Hz), 7.93 (1H, d, J = 8 Hz), 7.89 (1H, d, J = 8 Hz), 7.70 (1H, d, J = 8 Hz), 7.50
(1H, d, J = 8 Hz), 7.30 (1H, d, J = 8 Hz, 4.05 (2H, q, OCH2), 1.42 (3H, t, CH3), 0.86
(6H, s, Me). 13C NMR (DMSO-d6, dC, ppm, 100 MHz): 187.16, 175.07, 163.91,
153.17 (C=N), 148.14, 140.58, 138.83, 132.72, 129.60, 127.74, 125.80, 123.34,
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A. Ahlawat et al.
119.58, 114.24, 108.88, 106.71,, (s, Ar–C), 63.71 (s, C–OCH2), 29.52 (s, Me-C), 10.11
(s, C–CH3). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz): - 142.09.
[8] N-(2-(chlorodiethylstannyloxy)benzylidene)-6-ethoxybenzo[d]thiazol-2-amine
Yield: 78%; yellow; melting point: 198–200 °C; (Mol. Wt. 510.02); Anal. Calc.
for C20H23ClN2O2SSn (%): C, 47.13; H, 4.55; Cl, 6.96; N, 4.95; Sn, 23.29. Found:
C, 46.98; H, 4.24; Cl, 6.73; N, 5.32; Sn, 23.02. IR (KBr pellets, cm-1): 1597 (s,
m
C=N), 603 (m, mSn-N), 534 (m, mSn–C), 457 (w, mSn–O), other bands (1216 s, 1024w,
1
924 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 8.89 (1H, s, HC=N), 8.11 (1H,
s), 8.07 (1H, d, J = 8 Hz), 7.86 (1H, d, J = 8 Hz), 7.82 (1H, d, J = 8 Hz), 7.64 (1H,
d, J = 8 Hz), 7.44 (1H, d, J = 8 Hz), 7.22 (1H, d, J = 8 Hz), 4.11 (2H, q, OCH2),
1.42 (4H, t, CH3), 1.08 (4H, t, Et), 0.90 (6H, m, Et). 13C NMR (DMSO-d6, dC, ppm,
100 MHz): 184.59, 172.51, 161.35, 150.61 (C=N), 145.58, 133.27, 130.16, 127.04,
125.17, 123.24, 121.07, 117.02, 115.72, 111.68 (s, Ar–C), 63.31 (s, C–OCH2), 26.96
(s, C–CH3), 21.00 (s, Et-C), 15.91 (s, Et-C). 119Sn NMR (DMSO-d6, dSn, ppm,
149 MHz): - 172.95.
[9] N-(2-(chlorodiphenylstannyloxy)benzylidene)-6-nitrobenzo[d]thiazol-2-amine
Yield: 78%, yellow solid; melting point: 189–191 °C; (Mol. Wt. 606.98); Anal.
Calc. for C26H18ClN3O3SSn (%): C, 51.47; H, 2.99; Cl, 5.84; N, 6.93; Sn, 19.57.
Found: C, 51.21; H, 2.76; Cl, 5.49; N, 6.93; Sn, 19.31. IR (KBr pellets, cm-1): 1580
(s, mC=N), 606 (m, mSn-N), 528 (m, mSn–C), 455 (w, mSn–O),other bands (1216 s,
1023w, 914 s) 1H NMR (DMSO-d6, dH, ppm, 400 MHz): 9.81 (1H, s, HC=N), 8.54
(1H, s), 8.15 (1H, d, J = 8 Hz), 8.09–8.00 (10H, m), 7.98 (1H, d, J = 8 Hz), 7.84
(1H, t, J = 8 Hz), 7.61 (1H, d, J = 8 Hz), 7.58 (1H, d, J = 8 Hz), 7.27 (1H, d,
J = 8 Hz) 7.22 (1H, d, J = 8 Hz). 13C NMR (DMSO-d6, dC, ppm, 100 MHz):
184.00, 171.91, 160.75, 150.01 (C=N), 135.22, 132.67, 129.56, 126.44, 126.03,
124.86, 124.57, 123.08, 122.64, 120.47, 116.42, 115.13, 111.08 (s, Ar–C). 119Sn
NMR (DMSO-d6, dSn, ppm, 149 MHz): - 322.35.
[10] N-(2-(dibutylchlorostannyloxy)benzylidene)-6-nitrobenzo[d]thiazol-2-amine
Yield: 76%; yellow solid; melting point: 198–200 °C; (Mol. Wt. 567.04); Anal.
Calc. for C22H26ClN3O3SSn (%): C, 46.63; H, 4.62; Cl, 6.26; N, 7.42; Sn, 20.95.
Found: C, 46.45; H, 4.34; Cl, 6.01; N, 7.26; Sn, 20.71. IR (KBr pellets, cm-1): 1586
(s, mC=N), 618 (m, mSn-N), 593 (m, mSn–C), 453 (w, mSn–O), other bands (1216 s,
1
1026w, 917 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 10.06 (1H, s, HC=N),
8.07 (1H, s), 7.89 (1H, d, J = 8 Hz), 7.85 (1H, d, J = 8 Hz), 7.69 (1H, d, J = 8 Hz),
7.66 (1H, d, J = 8 Hz), 7.48 (1H, s, J = 8 Hz), 7.36 (1H, t, J = 8 Hz), 1.46 (4H, m),
1.38 (4H, m), 1.27 (4H, m), 0.91 (6H, t). 13C NMR (DMSO-d6, dC, ppm, 100 MHz):
182.72, 170.63, 159.48, 148.73 (C=N), 143.71, 131.40, 128.29, 125.17, 123.30,
121.36, 119.20, 115.14, 113.80, 109.81(s, Ar–C), 33.89, 24.79, 19.13, 14.72 (s, Bu–
C). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz): - 280.75.
[11] N-(2-(chlorodimethylstannyloxy)benzylidene)-6-nitrobenzo[d]thiazol-2-amine
Yield: 77%; brown solid; melting point: 192–194 °C; (Mol. Wt. 482.95); Anal.
Calc. for C16H14ClN3O3SSn (%): C, 39.83; H, 2.92; Cl, 7.35; N, 8.71; Sn, 24.60.
123

Diorganotin(IV) complexes of Schiff bases derived from…
Found: C, 39.57; H, 2.78; Cl, 7.13; N, 8.71; Sn, 24.34. IR (KBr pellets, cm-1): 1597
(s, mC=N), 603 (mSn-N), 534 (mSn–C), 457 (mSn–O), other bands (1216 s, 1024w, 924 s).
1H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.70 (1H, s, HC=N), 8.22 (1H, s), 8.15
(1H, d, J = 8 Hz), 7.97 (1H, d, J = 8 Hz), 7.93 (1H, d, J = 8 Hz), 7.76 (1H, d,
J = 8 Hz), 7.54 (1H, d, J = 8 Hz), 7.33 (1H, d, J = 8 Hz), 0.89 (6H, s, Me). 13C
NMR (DMSO-d6, dC, ppm, 100 MHz): 182.72, 170.63, 159.45, 148.73 (C=N),
143.71, 131.40, 128.29, 125.17, 123.30, 121.36, 119.20, 115.14, 113.85, 109.81 (s,
Ar–C), 11.30 (s, Me-C). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz): - 125.24.
[12] N-(2-(chlorodiethylstannyloxy)benzylidene)-6-nitrobenzo[d]thiazol-2-amine
Yield: 79%; yellow solid; melting point: 187–189 °C; (Mol. Wt. 510.98); Anal.
Calc. for C18H18ClN3O3SSn (%): C, 42.34; H, 3.55; Cl, 6.94; N, 8.23; Sn, 23.25.
Found: C, 42.06; H, 3.26; Cl, 6.76; N, 8.01; Sn, 23.01. IR (KBr pellets, cm-1): 1580
(s, mC=N), 606 (mSn-N), 528 (mSn–C), 455 (mSn–O), other bands (1216 s, 1023w, 914 s).
1H NMR: (DMSO-d6, dH, ppm, 400 MHz): 10.10 (1H, s, HC=N), 8.10 (1H, s), 8.11
(1H, d, J = 8 Hz), 7.93 (1H, d, J = 8 Hz), 7.89 (1H, d, J = 8 Hz), 7.71 (1H, d,
J = 8 Hz), 7.50 (1H, d, J = 8 Hz), 7.30 (1H, d, J = 8 Hz), 1.16 (4H, q, Et), 0.97
(6H, t, Et). 13C NMR (DMSO-d6, dC, ppm, 100 MHz): 183.70, 171.16, 160.45,
149.71 (C=N), 144.69, 132.38, 129.27, 126.15, 124.28, 122.34, 120.17, 116.12,
114.83, 110.78 (s, Ar–C), 24.69, 14.72 (s, Et-C). 119Sn NMR (DMSO-d6, dSn, ppm,
149 MHz): - 179.85.
[13] N-(2-(chlorodiphenylstannyloxy)benzylidene)-6-methoxybenzo[d]thiazol-2-
amine Yield: 78%; yellow solid; melting point: 182–183 °C; (Mol. Wt. 592.00);
Anal. Calc. for C27H21ClN2O2SSn(%): C, 54.81; H, 3.58; Cl, 5.99; N, 4.73; Sn,
20.06. Found: C, 54.72; H, 3.32; Cl, 5.78; N, 4.53; Sn, 19.89. IR (KBr pellets,
cm-1): 1600 (s, mC=N), 604 (m, mSn-N), 517 (m, mSn–C), 412 (w, mSn–O) other bands
1
(1203 s, 1014w, 975 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.81 (1H, s,
C=N), 8.09 (1H, s), 7.99 (1H, d, J = 8 Hz), 7.97–7.85 (10H, m), 7.61 (1H, d,
J = 8 Hz), 7.59 (1H, d, J = 8 Hz), 7.27 (1H, d, J = 12 Hz), 7.22 (1H, t, J = 12 Hz),
7.11 (1H, d, J = 8 Hz), 4.04 (3H, s, OCH3). 13C NMR (DMSO-d6, dC, ppm,
100 MHz): 186.17, 174.08, 162.93, 152.18 (C=N), 147.16, 137.40, 134.85, 131.74,
128.62, 128.20, 127.04, 126.75, 125.84, 125.26, 124.81, 122.65, 118.59, 117.30,
113.26 (s, Ar–C), 62.11 (s, C–OCH3). 119Sn NMR (DMSO-d6, dSn, ppm,
149 MHz): - 304.11.
[14] N-(2-(dibutylchlorostannyloxy)benzylidene)-6-methoxybenzo[d]thiazol-2-amine
Yield: 76%, yellow solid; melting point: 197–199 °C; (Mol. Wt. 552.07); Anal.
Calc. for C23H29ClN2O2SSn (%): C, 50.07; H, 5.30; Cl, 6.43; N, 5.08; Sn, 21.52.
Found: C, 49.94; H, 5.03; Cl, 6.23; N, 5.08; Sn, 21.41. IR (KBr pellets, cm-1): 1604
(s, mC=N), 607 (m, mSn-N), 513 (m, mSn–C), 419 (w, mSn–O). other bands (1207 s,
1
1018w, 976 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 10.43 (1H, s, HC=N),
8.19 (1H, s), 8.05 (1H, d, J = 8 Hz), 7.87 (1H, d, J = 8 Hz), 7.83 (1H, d, J = 8 Hz),
7.64 (1H, t, J = 1 2 Hz), 7.46 (1H, t, J = 12 Hz), 7.36 (1H, d, J = 8 Hz), 4.12 (3H,
s, OCH3), 3.61 (4H, m), 3.55 (4H, m), 1.42 (4H, m), 1.35 (6H, t). 13C NMR
(DMSO-d6, dC, ppm, 100 MHz): 182.61, 170.31, 159.15, 148.41 (C=N), 143.38,
131.08, 127.96, 124.85, 122.98, 121.04, 118.87, 114.82, 113.53, 109.43 (s, Ar–C),
123

A. Ahlawat et al.
61.80 (s, OCH3), 33.57, 24.47, 18.80, 14.39 (s, Bu–C). 119Sn NMR (DMSO-d6, dSn,
ppm, 149 MHz): - 249.49.
[15] N-(2-(chlorodimethylstannyloxy)benzylidene)-6-methoxybenzo[d]thiazol-2-
amine Yield: 75%; yellow solid; melting point: 178–180 °C; (Mol. Wt. 467.97);
Anal. Calc. for C17H17ClN2O2SSn (%): C, 43.67; H, 3.66; Cl, 7.58; N, 5.99; Sn,
25.39. Found: C, 43.42; H, 3.32; Cl, 7.21; N, 5.71; Sn, 25.12. IR (KBr pellets,
cm-1): 1596 (s, mC=N), 612 (m, mSn-N), 517 (m, mSn–C), 415 (w, mSn–O) other bands
1
(1202 s, 1015w, 972 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.54 (1H, s,
HC=N), 8.11 (1H, s), 7.86 (1H, d, J = 8 Hz), 7.82 (1H, d, J = 8 Hz), 7.65 (1H, d,
J = 8 Hz), 7.43 (1H, t, J = 12 Hz), 7.22 (1H, t, J = 12 Hz), 7.09 (1H, d, J = 8 Hz),
4.11 (3H, s, OCH3), 1.38 (6H, s, Me). 13C NMR (DMSO-d6, dC, ppm, 100 MHz):
185.99, 173.50, 162.34, 151.60 (C=N), 146.57, 139.01, 136.81, 134.26, 131.15,
128.03, 126.17, 124.23, 122.06, 121.77, 118.01, 112.67, 107.31, 105.14 (s, Ar–C),
61.53 (s, C–OCH3), 8.54 (s, Me-C). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz):
- 140.11.
[16] N-(2-(chlorodiethylstannyloxy)benzylidene)-6-methoxybenzo[d]thiazol-2-amine
Yield: 78%; yellow solid; melting point: 195–197 °C; (Mol. Wt. 496.00); Anal.
Calc. for C19H21ClN2O2SSn (%): C, 46.04; H, 4.27; Cl, 67.15; N, 5.65; Sn, 23.95.
Found: C, 45.89; H, 4.04; Cl, 7.02; N, 5.31; Sn, 23.72. IR (KBr pellets, cm-1): 1602
(s, mC=N), 605 (m, mSn-N), 520 (m, mSn–C), 409 (w, mSn–O) other bands (1207 s,
1
1018w, 976 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.59 (1H, s, HC=N),
8.21 (1H, s), 8.02 (1H, d, J = 8 Hz), 7.89 (1H, d, J = 8 Hz), 7.84 (1H, d, J = 8 Hz),
7.69 (1H, t, J = 12 Hz), 7.39 (1H, t, J = 12 Hz), 7.25 (1H, d, J = 8 Hz), 4.11 (3H, s,
OCH3), 1.29 (4H, q), 0.92 (6H, t). 13C NMR (DMSO-d6, dC, ppm, 100 MHz):
183.70, 171.61, 160.45, 149.71 (C=N), 144.69, 132.38, 129.27, 126.15, 124.28,
122.34, 120.17, 116.12, 114.83, 110.78 (s, Ar–C), 62.42 (s, C–OCH3) 26.06, 15.02
(s, Et-C). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz): - 176.09.
[17] N-(2-(chlorodiphenylstannyloxy)benzylidene)-6-methylbenzo[d]thiazol-2-amine
Yield: 77%; yellow solid; melting point: 177–179 °C; (Mol. Wt. 576.01); Anal.
Calc. for C27H21ClN2OSSn (%): C, 56.33; H, 3.68; Cl, 6.16; N, 4.87; Sn, 20.62.
Found: C, 56.12; H, 3.42; Cl, 5.97; N, 4.56; Sn, 20.34. IR (KBr pellets, cm-1): 1594
(s, mC=N), 610 (m, mSn-N), 504 (m, mSn–C), 425 (w, mSn–O),other bands (1211 s,
1019w, 974 s) 1H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.42 (1H, s, HC=N), 8.12
(1H, s), 8.01 (1H, d, J = 8 Hz), 7.93–7.87 (10H, m), 7.65 (1H, d, J = 8 Hz), 7.61
(1H, d, J = 8 Hz), 7.29 (1H, d, J = 12 Hz), 7.21 (1H, t, J = 12 Hz), 7.14 (1H, d,
J = 8 Hz), 1.35 (3H, s, CH3) ppm. 13C NMR (DMSO-d6, dC, ppm, 100 MHz)
185.88, 173.79, 162.63, 151.89 (C=N), 146.86, 137.10, 134.56, 131.44, 128.32,
127.91, 126.74, 125.55, 124.96, 124.52, 122.35, 118.30, 117.01, 112.96 (s, Ar–H),
11.89 (s, C–CH3). 119Sn NMR (DMSO-d6, dSn, ppm, 149 MHz): - 300.75.
[18] N-(2-(dibutylchlorostannyloxy)benzylidene)-6-methylbenzo[d]thiazol-2-amine
Yield: 78%; yellow solid; melting point: 165–167 °C; (Mol. Wt. 536.07); Anal.
Calc. for C23H29ClN2OSSn (%): C, 51.57; H, 5.46; Cl, 6.62; N, 5.46; Sn, 22.16.
Found: C, 51.32; H, 5.35; Cl, 6.45; N, 5.04; Sn, 21.98. IR (KBr pellets, cm-1): 1603
123

Diorganotin(IV) complexes of Schiff bases derived from…
(s, mC=N), 610 (m, mSn-N), 519 (m, mSn–C), 410 (w, mSn–O), other bands (1213 s,
1
1021w, 973 s). H NMR: (DMSO-d6, dH, ppm, 400 MHz): 9.75 (1H, s, HC=N),
8.21 (1H, s), 8.07 (1H, d, J = 8 Hz), 7.86 (1H, d, J = 8 Hz), 7.81 (1H, d, J = 8 Hz),
7.68 (1H, t, J = 1 2 Hz), 7.48 (1H, t, J = 12 Hz), 7.38 (1H, d, J = 8 Hz), 4.05 (4H,
m, Bu), 3.64 (4H, m, Bu), 1.49 (4H, m, Bu), 1.41 (6H, t, Bu), 1.28 (3H, s, CH3). 13
C
NMR (DMSO-d6, dC, ppm, 100 MHz): 181.81, 169.72, 158.57, 147.82 (C=N),
142.80, 130.49, 127.38, 124.26, 122.39, 120.45, 118.29, 114.23, 112.94, 108.90 (s,
Ar–C), 32.98, 23.88, 18.22, 13.81, 9.73 (s, C–CH3). 119Sn NMR (DMSO-d6, dSn,
ppm, 149 MHz): - 252.95.
[19] N-(2-(chlorodimethylstannyloxy)benzylidene)-6-methylbenzo[d]thiazol-2-amine
Yield: 79%, yellow solid; melting point: 172–174 °C; (Mol. Wt. 451.98); Anal.
Calc. for C17H17ClN2OSSn (%): C, 45.22; H, 3.79; Cl, 7.85; N, 6.20; Sn, 26.29.
Found: C, 44.10; H, 3.61; Cl, 7.68; N, 6.01; Sn, 25.96. IR (KBr pellets, cm-1): 1602
(s, mC=N), 608 (m, mSn-N), 508 (m, mSn–C), 413 (w, mSn–O), other bands (1220 s,
1025w, 976 s). 1H NMR (DMSO-d6, dH, ppm, 400 MHz): 9.75 (1H, s, HC=N), 8.14
(1H, s), 7.87 (1H, d, J = 8 Hz), 7.83 (1H, d, J = 8 Hz), 7.67 (1H, d, J = 8 Hz), 7.45
(1H, t, J = 12 Hz), 7.25 (1H, t, J = 12 Hz), 7.11 (1H, d, J = 8 Hz), 1.37 (3H, s,
CH3), 0.86 (6H, s, Me). 13C NMR (DMSO-d6, dC ppm, 100 MHz): 182.40, 172.31,
159.15, 148.41 (C=N), 143.38, 131.08, 127.96, 124.85, 122.98, 121.04, 118.87,
114.82, 113.53, 109.48 (s, Ar–H), 18.80 (s, C–CH3), 10.97 (s, Me-C). 119Sn NMR
(DMSO-d6, dSn, ppm, 149 MHz): - 126.09.
[20] N-(2-(chlorodiethylstannyloxy)benzylidene)-6-methylbenzo[d]thiazol-2-amine
Yield: 76%, yellow solid; melting point: 186–188 °C; (Mol. Wt. 480.01); Anal.
Calc. for C19H21ClN2OSSn (%): C, 47.58; H, 4.41; Cl, 6.69; N, 5.58; Sn, 24.75.
Found: C, 47.32; H, 4.23; Cl, 6.34; N, 5.34; Sn, 24.54. IR (KBr pellets, cm-1): 1610
(s, mC=N), 619 (m, mSn-N), 504 (m, mSn–C), 409 (w, mSn–O), other bands (1218 s,
1024w, 975 s). 1H NMR (DMSO-d6, dH, ppm, 400 MHz): 9.89 (1H, s, HC=N), 8.25
(1H, s), 8.05 (1H, d, J = 8 Hz), 7.92 (1H, d, J = 8 Hz), 7.87 (1H, d, J = 8 Hz), 7.71
(1H, t, J = 12 Hz), 7.42 (1H, t, J = 12 Hz), 7.27 (1H, d, J = 8 Hz), 1.43 (3H, s,
CH3), 1.12 (4H, q, Et), 0.91 (6H, t, Et). 13C NMR (DMSO-d6, dC ppm, 100 MHz):
183.09, 171.00, 159.84, 149.10 (C=N), 144.07, 131.77, 128.65, 125.67, 123.67,
121.73, 119.56, 115.51, 114.22, 110.17 (Ar–C), 25.15 (s, C–CH3), 15.08, 8.81 (s,
Et-C). 119Sn NMR (DMSO-d6, dSn ppm, 149 MHz): - 175.24.
Results and discussion
Synthetic aspects
The reaction of salicylaldehyde with 2-amino-6-substituted-benzothiazole (where
R = –OC2H5, –NO2, –OCH3, –CH3) leads to the formation of (1-[(6-substituted-
benzothiazol-2-ylimino)-methyl]-naphthalen-2-ol) (1–4). The sodium salt of the
Schiff base ligands was prepared using Na metal, which was then reacted with
R2SnCl2, yielding complexes 5–20. These were isolated as coloured compounds that
123

A. Ahlawat et al.
are soluble in DMSO and less soluble in chloroform. The purity of the compounds
was checked by TLC. The synthetic protocol of the Schiff base ligands and their
diorganotin(IV) complexes is shown in Scheme 1.
IR spectra
FT-IR spectra of all the ligands and the complexes were recorded using KBr pellets.
The coordination sites of the ligands were assigned by comparing IR spectra of the
corresponding Schiff bases with their corresponding diorganotin(IV) complexes.
The presence of a hydroxyl group in the Schiff base ligands was confirmed by the
appearance of a broad absorption band at 3316–3287 cm-1 due to m (OH). The
absorption band of medium intensity with stretching frequency at 1623–1612 cm-1
was attributed to the m (C=N) of azomethine group in the ligands. The broad
absorption band of the hydroxyl group disappeared due to the deprotonation of
phenolic group in the complexes suggesting bonding of oxygen atom to the central
tin atom. The absorption band for the azomethine group was shifted by 10–24 cm-1
towards lower frequencies with medium intensity in complexes suggesting
coordination of nitrogen atom to the tin atom. The other bands appeared at their
usual positions. The absorption bands were observed in the ranges 619–602, 521–
504, 425–403 cm-1 attributed to m (Sn–C), m (Sn–O), m (Sn–N) vibrations
respectively, and suggesting coordination of carbon, oxygen and nitrogen to the
central tin atom [29, 30].
Scheme 1 Scheme for the synthesis of Schiff base ligands and organotin(IV) complexes
123

Diorganotin(IV) complexes of Schiff bases derived from…
NMR spectroscopy
1H NMR
The 1H, 13C, 119Sn NMR spectra of the ligands and the complexes were recorded in
1
DMSO. The H NMR spectra of the compounds are based on integration values,
coupling constants and chemical shifts. The signal in the range d 11.77–11.64 ppm
was assigned to phenolic proton in Schiff base ligands. A signal in the range d 9.37–
9.24 ppm revealed the presence of azomethine protons in the ligands, confirming
the condensation of benzothiazole derivatives with salicylaldehyde. The signals at d
7.89–6.88 ppm were assigned to the aryl protons of the ligands and the signals due
to aliphatic protons appeared in the range d 4.14–1.39 ppm due to the presence of
1
strong electron withdrawing groups in the compounds. The H NMR spectra of the
complexes were compared with that of the ligands on the basis of coupling
constants, integration and chemical shift values. All the diorganotin(IV) complexes
showed the absence of signal due to phenolic proton suggesting the deprotonation of
the phenolic proton and coordination to the tin atom. The proton signals of
azomethine group were slightly shifted which may be due to the coordination of
nitrogen atom of imino moeity to the tin atom leading to a significant deshielding
effect. The signals of aryl and alkyl groups were observed in the expected regions as
reported earlier [31–33].
13C NMR
In the 13C NMR spectra of the ligands, the signal due to carbon attached to the
phenolic group was observed at d 186.17–182.12 ppm. The carbons attached to
thiazole group appeared at d 162.93–143.16 ppm due to presence of nitrogen and
sulfur. The carbon attached to the azomethine group was appeared in the range d
137.40–133.34 ppm. The carbons attached to the aromatic ring were appeared in the
expected region in the range d 128.53–110.38 ppm in ligands. The chemical shift
values of carbon attached to aliphatic group appeared in the region from d 62.12–
12.87 ppm in ligands. In the 13C NMR spectra of the complexes, the signal due to
phenolic groups was shifted due to bonding of oxygen to the central tin atom
indicating formation of complexes. The carbons attached to thiazole group were
shifted because of deshielding effect due to presence of nearby azomethine nitrogen.
The azomethine carbon was shifted downfield on complexation indicating
involvement of nitrogen atom in coordination to the central tin atom. The aromatic
and aliphatic carbons were appeared at their usual positions [34–36].
119Sn NMR
A sharp singlet appeared in the 119Sn spectra of the compounds in the range d
- 326.35 to - 300.75 ppm for phenyl, d - 280.75 to - 249.49 ppm for butyl, d
- 179.85 to - 170.76 ppm for ethyl, and d - 142.09 to - 125.24 ppm for methyl
complexes. These chemical shifts revealed the formation of pentacoordinated tin
123

A. Ahlawat et al.
centres in the complexes. The phenyltin complexes showed high field chemical shift
values due to anisotropic shielding effects, as well as the pi interactions [34–37].
In vitro antimicrobial activity
The in vitro antimicrobial activity of all synthesized compounds was evaluated
against Gram negative bacteria, E. coli, P. aeruginosa, Gram positive bacteria, B.
cereus, S. aureus, and fungi, A. niger, A. flavus. Ciprofloxacin and fluconazole were
used as standard drugs for antibacterial and antifungal activity, respectively. The
serial dilution method was used for the evaluation of antimicrobial activity. The
results of antimicrobial activity in terms of MIC (minimum inhibitory concentration
in lM/mL) are presented in Table 1. The results of antibacterial and antifungal
activity revealed that the compound 5 was found to be the most active against all
microbial strains. The ligands were found to be least active. The order of
antimicrobial activity was found Ph [ Bu [ Et [ Me. From the observed results, it
Table 1 In vitro antimicrobial activity of Schiff bases derived from 2-amino-6-substituted benzothia-
zoles with salicylaldehyde and their diorganotin(IV) complexes
Compound
MIC (lM/mL)
E.coli
P.aeruginosa
B.cereus
S. aureus
A. niger
A. flavus
1
0.0419
0.0209
0.0220
0.0233
0.0101
0.0110
0.0245
0.0130
0.0103
0.0220
0.0122
0.0129
0.0211
0.0113
0.0126
0.0267
0.0108
0.0116
0.0253
0.0276
0.0047
–
0.0209
0.0209
0.0220
0.0233
0.0048
0.0055
0.0061
0.0065
0.0051
0.0055
0.0061
0.0064
0.0052
0.0056
0.0126
0.0134
0.0054
0.0058
0.0063
0.0069
0.0047
–
0.0419
0.0418
0.0440
0.0465
0.0048
0.0055
0.0122
0.0130
0.0051
0.0055
0.0122
0.0129
0.0052
0.0056
0.0126
0.0134
0.0054
0.0058
0.01263
0.0138
0.0047
–
0.0209
0.0209
0.0220
0.0233
0.0024
0.0057
0.0123
0.0130
0.0026
0.0027
0.0063
0.0067
0.0026
0.0059
0.0126
0.0134
0.0027
0.0060
0.0126
0.0138
0.0047
–
0.0104
0.0104
0.0110
0.0116
0.0024
0.0027
0.0061
0.0065
0.0026
0.0027
0.0061
0.0064
0.0026
0.0113
0.0031
0.0034
0.0027
0.0029
0.0063
0.0069
–
0.0209
0.0209
0.0220
0.0233
0.0048
0.0055
0.0061
0.0065
0.0051
0.0055
0.0061
0.0064
0.0053
0.0056
0.0063
0.0067
0.0054
0.0058
0.0063
0.0069
–
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Ciprofloxacin
Fluconazole
0.0102
0.0102
123

Diorganotin(IV) complexes of Schiff bases derived from…
was observed that there was a remarkable boost in the activity of complexes than the
ligands. The increase in the antimicrobial activity of synthesized complexes may be
due to chelation, as it tends to formulate ligands to operate as more influential and
better antimicrobial agents [38–40].
QSAR analysis
QSAR analysis for the in vitro antimicrobial activity and structural descriptors
coding for various molecular properties of the diorganotin(IV) complexes of Schiff
bases derived from 2-amino-6-substituted-benzothiazoles described by Hansch and
Fujita [41] using the linear free energy relationship model (LFER). The pMIC (–log
MIC), i.e. the negative logarithm of observed antimicrobial activity (MIC, Table 2)
was taken for QSAR study. The structural descriptors were calculated for
diorganotin(IV) complexes of Schiff bases derived from 2-amino-6-substituted
benzothiazoles and salicylaldehyde are presented in Table 3 [42–48].
In the present study, a dataset of synthesized compounds was subjected to linear
regression analysis to correlate antimicrobial activity with structural quantifiers, i.e.
molecular descriptors. The inter-relationship between structural quantifiers and
Table 2 In vitro antimicrobial activity (pMIC) values of Schiff bases derived from 2-amino-6-substi-
tuted benzothiazoles with salicylaldehyde and their diorganotin(IV) complexes
Compounds
pMICec
PMICpa
pMICbc
pMICsa
pMICan
pMICaf
1
1.378
1.680
1.658
1.633
1.986
1.957
1.610
1.887
1.987
1.656
1.912
1.888
1.675
1.946
1.899
1.573
1.964
1.933
1.597
1.558
2.610
1.679
1.680
1.658
1.633
2.288
2.258
2.213
2.189
2.289
2.259
2.214
2.189
2.278
2.248
1.899
1.874
2.266
2.235
2.200
2.161
2.610
1.378
1.379
1.357
1.332
2.288
2.258
1.911
1.887
2.289
2.259
1.912
1.888
2.278
2.248
1.899
1.874
2.266
2.235
1.898
1.859
2.610
1.679
1.680
1.658
1.633
2.589
2.241
1.911
1.887
2.590
2.560
2.196
2.172
2.579
2.230
1.899
1.874
2.567
2.217
1.898
1.859
2.610
1.981
1.982
1.960
1.935
2.589
2.559
2.213
2.189
2.590
2.560
2.214
2.189
2.579
1.946
2.502
2.477
2.567
2.536
2.200
2.161
2.640
1.679
1.680
1.658
1.633
2.288
2.258
2.213
2.189
2.289
2.259
2.214
2.189
2.278
2.248
2.201
2.176
2.266
2.235
2.200
2.161
2.640
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Std.
123

A. Ahlawat et al.
123

Diorganotin(IV) complexes of Schiff bases derived from…
antimicrobial activities was analyzed on the basis of regression analysis and
correlation matrix constructed for antifungal activity of synthesized compounds
against A. flavus is presented in Table 4. The correlation of different molecular
descriptors with antimicrobial activities is presented in Table 5. An overview of the
entire dataset demonstrated high colinearity (r [ 0.8) between structural quantifiers.
The high correlation was observed between first order molecular connectivity index,
1v and Randic parameter, R (r = 1.000), zero order molecular connectivity index, 0v
and lectronic energy, Ele.E (r = 0.997), zero order molecular connectivity index, 0v
and nuclear repulsion energy, Nu.E (r = 0.997), and least inter-relationship was
0
observed between valence zero order molecular connectivity index, vv and dipole
moment, l (r = 0.008), first order molecular connectivity index, 1v and dipole
moment, l (r = 0.008) and Randic parameter, R and dipole moment, l (r = 0.008).
The correlation matrix highlighted the role of various molecular connectivity
indices (Topological descriptors) in modulation of antibacterial and antifungal
activity of the synthesized complexes.
The QSAR model for antifungal potential of synthesized compounds against A.
flavus depicted that structural descriptors, valence first order molecular connectivity
index (1vv) is responsible for the control of antifungal activity (Eq. 1)
QSAR model for antifungal activity against A. flavus
pMICaf ¼ 0:0451vv þ 1:350
ð1Þ
n = 20 r = 0.990 r2 = 0.980 q2 = 0.977 s = 0.034 F = 881.67
Topological indices are numerical quantifiers of molecular topology and are
sensitive to bonding pattern, symmetry, heteroatom content, as well as degree of
complexity of atomic neighborhoods. The first-order molecular connectivity
topological index (2v) represents the molecules with branched structure [49]. The
QSAR model represented by Eq. 1 for antifungal activity against A. flavus has high
r, r2, q2 and F values and a low s value, which indicates that the results of the
predicted antifungal activity will be reliable. The validity of the QSAR model was
examined by leave-one-out (LOO) method, which states that the mathematical
models are valid if they have q2 value greater than 0.5, and both of these models
meet this criterion [50]. The statistical significance of the validity of Eq. 1 was also
assessed by drawing two plots, one between observed and predicted antifungal
activity (Fig. 1) and the other between the observed and residual antifungal activity
(Fig. 2), and both of these plots support the validity of the QSAR model represented
by Eq. 1.
QSAR model for antibacterial activity against B. cereus
pMICbc ¼ 0:0800vv þ 0:405
ð2Þ
n = 20 r = 0.989 r2 = 0.977 q2 = 0.973 s = 0.053 F = 774.243
QSAR model for antibacterial activity against S. aureus
pMICsa ¼ 0:1572v þ 0:240
ð3Þ
n = 20 r = 0.963 r2 = 0.926 q2 = 0.913 s = 0.096 F = 226.314
123

A. Ahlawat et al.
123

Diorganotin(IV) complexes of Schiff bases derived from…
Table 5 Correlation of molecular descriptors with antimicrobial activity of Schiff bases derived from
2-amino-6-substituted benzothiazoles with salicylaldehyde and their diorganotin(IV) complexes
pMICec
pMICpa
pMICbc
pMICsa
pMICan
pMICaf
0v
0vv
1v
0.641
0.615
0.855
0.923
0.957
0.989
0.953
0.859
0.795
0.785
0.836
0.952
0.621
0.803
0.923
0.952
0.787
0.773
1vv
2v
0.536
0.911
0.906
0.691
0.693
0.990
0.628
0.850
0.935
0.962
0.805
0.832
2vv
3v
0.477
0.866
0.826
0.580
0.620
0.968
0.348
0.687
0.583
0.427
0.453
0.780
3vv
0.255
0.612
0.510
0.257
0.365
0.740
j1
0.643
0.863
0.966
0.932
0.780
0.847
j2
0.616
0.800
0.929
0.885
0.729
0.768
j3
0.590
0.841
0.925
0.779
0.667
0.833
R
0.621
0.803
0.923
0.952
0.787
0.773
J
- 0.159
0.615
- 0.085
0.777
- 0.174
0.903
- 0.450
0.953
- 0.326
0.775
- 0.019
0.736
W
Te
- 0.647
- 0.639
0.637
- 0.844
- 0.849
0.848
- 0.935
- 0.960
0.961
- 0.947
- 0.942
0.940
- 0.775
- 0.787
0.787
- 0.831
- 0.831
0.830
Ele.E
NuE
LUMO
HOMO
L
- 0.425
0.053
- 0.467
0.259
- 0.417
0.333
- 0.615
0.105
- 0.384
0.240
- 0.420
0.327
0.000
0.126
0.051
0.167
0.121
0.138
QSAR model for antibacterial activity against P. aeruginosa
pMICpa ¼ 0:0540vv þ 1:064
n = 20 r = 0.923 r2 = 0.852 q2 = 0.833 s = 0.097 F = 103.509
ð4Þ
QSAR model for antifungal activity against A. niger
pMICan ¼ 0:0972v þ 1:148
ð5Þ
n = 20 r = 0.805 r2 = 0.648 q2 = 0.601 s = 0.155 F = 33.198
In the case of antibacterial activity of synthesized compounds against B. cereus,
the QSAR model represented by Eq. 2 was obtained, which pointed out the
involvement of valence zero order molecular connectivity index (0vv) in deciding
the pattern of antibacterial activity against B. cereus. This model (Eq. 2) also has
high r, r2, q2 and F values and low s values, which suggests the high prediction
reliability of this model. The coefficient of valence zero order molecular index (0vv)
is positive which indicated that antibacterial potential (Table 3) of synthesized
0
compounds will increase with increase in values of vv (Table 4) and the same can
be confirmed from the results that compounds 5 and 9 with high 0vv values (23.688
and 22.836, respectively) have high antibacterial activity (2.288 and 2.289 lM/mL,
123

A. Ahlawat et al.
2.4
2.3
2.2
2.1
2.0
1.9
1.8
1.7
1.6
1.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
Observed pMICaf
Fig. 1 Plot of observed pMICaf against the predicted pMICaf for the linear regression model developed
by Eq. 1
.08
.06
.04
.02
0.00
-.02
-.04
-.06
1.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
Observed pMICaf
Fig. 2 Plot of residual pMICaf against the observed pMICaf for the linear regression model developed by
Eq. 1
0
respectively), and compounds 3, 4 and 19 with low vv values (11.660, 11.251 and
17.799, respectively) have low antibacterial activity.
The QSAR model for antibacterial activity of synthesized compounds against S.
aureus revealed the importance of second-order molecular connectivity index (2v)
in altering the antibacterial activity (Eq. 3). The coefficient of molecular descriptors
123

Diorganotin(IV) complexes of Schiff bases derived from…
123

A. Ahlawat et al.
(2v) in Eq. 3 is positive, which indicates that antibacterial activity will increase with
increasing values of 2v and vice versa, and the same can be verified from the results
presented in Tables 3 and 4.
In the case of antibacterial potential of synthesized compounds against P.
aeruginosa, the computational model represented by Eq. 4 was obtained, and this
model emphasized that valence zero-order molecular connectivity index (0vv) was
the determinant factor for the antibacterial activity of the synthesized compounds.
The antifungal activity of synthesized compounds against A. niger was governed by
second-order molecular connectivity index (2v) and positive coefficient of 2v
signifies that the antifungal activity against A. niger will increase with increase in 2v
values. No statistically valid model was obtained for antibacterial potential of
synthesized compounds against E. coli. Similar to the QSAR model represented by
Eqs. 1, 2–5 have high r, r2, q2 and F values and low s values, and the comparison of
observed and predicted antimicrobial potential of synthesized compounds (Table 6)
revealed that they have low residual values, thus confirming the statistical validity
of these models [51–53].
Acknowledgements The authors are grateful to the CIL, Guru Jambheshwar University of Science and
Technology, Hisar and SAIF, Punjab University, Chandigarh for providing IR and NMR facilities. One of
the authors, Ms. Aarti Ahlawat, is thankful to UGC, New Delhi for providing financial assistance. The
authors are thankful to Dr. Namita Singh, Department of Bio and Nanotechnology, Guru Jambheshwar
University of Science and technology, Hisar for providing microbial strains.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
References
1. M.A. Salam, M.A. Hussein, I. Ramli, M.S. Islam, J. Organomet. Chem. 813, 71 (2016)
2. L. Xu, M. Hong, Y. Yang, J. Cui, C. Li, J. Coord. Chem. 69(17), 2598 (2016)
3. R.A. Haque, M.A. Salam, M.A. Arafath, J. Coord. Chem. 68(16), 2953 (2015)
4. Y.Y. Zhang, R.F. Zhang, S.L. Zhang, S. Cheng, Q.L. Li, C.L. Ma, Dalton Trans. 45(20), 8412 (2016)
5. M. Hong, H. Yin, X. Zhang, C. Li, C. Yue, S. Cheng, J. Organomet. Chem. 724, 23 (2013)
6. G.M. Treich, S. Nasreen, A. Mannodi Kanakkithodi, R. Ma, M. Tefferi, J. Flynn, Y. Cao, R.
Ramprasad, G.A. Sotzing, ACS Appl. Mater. Interfaces 8(33), 21270 (2016)
´
´
´
´
7. M.C. Garcıa-Lopez, B.M. Munoz-Flores, R. Chan-Navarro, V.M. Jimenez-Perez, I. Moggio, E.
´
Arias, A. Rodrıguez-Ortega, M.E. Ochoa, J. Organomet. Chem. 806, 68 (2016)
8. A. Tyagi, G. Kedarnath, A. Wadawale, V.K. Jain, M. Kumar, B. Vishwanadh, RSC Adv. 5(77),
62882 (2015)
9. T.A. Grusenmeyer, A.W. King, J.T. Mague, J.J. Rack, R.H. Schmehl, Dalton Trans. 43(47), 17754
(2014)
10. F.A. Shah, S. Sabir, K. Fatima, S. Ali, I. Qadri, C. Rizzoli, Dalton Trans. 44(22), 10467 (2015)
11. M. Roy, S. Roy, K.S. Singh, J. Kalita, S.S. Singh, New J. Chem. 40(2), 1471 (2016)
12. A.D. Garnovskii, I.S. Vasilchenko, D.A. Garnovskii, B.I. Kharisov, J. Coord. Chem. 62(2), 151
(2009)
13. A. Chilwal, P. Malhotra, A.K. Narula, Phosphorus Sulfur Silicon Relat. Elem. 189, 410 (2014)
14. H.L. Siddiqui, A. Iqbal, S. Ahmad, G.W. Weaver, Molecules 11, 206 (2006)
15. M. Nath, P.K. Saini, A. Kumar, Appl. Organometal. Chem. 23, 434 (2009)
123

Diorganotin(IV) complexes of Schiff bases derived from…
´
16. T.S. Basu Baul, W. Rynjah, E. Rivarola, A. Lycka, M. Holcapek, R. Jirasko, D. de Vos, J.B.L.A. Ray,
J. Organomet. Chem. 691, 4850 (2006)
17. W. Rehman, M.K. Baloch, A. Badshah, Eur. J. Med. Chem. 43, 2380 (2008)
18. H.L. Singh, J. Singh, Bioinorg. Chem. Appl. 2014, 1 (2014)
19. J. Devi, S. Devi, A. Kumar, Heteroat. Chem. 27(6), 361 (2016)
20. A.A.R. Despaigne, G.L. Parrilha, J.B. Izidoro, P.R. da Costa, R.G. Santos, O.G. Piro, E.E. Castellano,
W.R. Rocha, H. Beraldo, Eur. J. Med. Chem. 50, 163 (2012)
21. A. Kamal, M.A.H. Syed, S.M. Mohammed, Expert Opin. Ther. Pat. 25(3), 335 (2015)
22. S. Seth, Anti-Inflamm. Anti-Allergy Agents Med. Chem. 14(2), 98 (2015)
23. A.A. Weekes, A.D. Westwell, Curr. Med. Chem. 16(19), 2430 (2009)
24. A.K. Sonika, O.P. Narula, H.K. Vermani, A.S. Sharma, J. Sarpal, Organometal. Chem. 470(1–2), 67
(1994)
25. D.F. Spooner, G. Sykes, Methods in Microbiology (Academic Press, London, 1972)
26. Hyperchem 6.0, Hypercube Inc., Gainesville (1993)
27. TSAR 3D Version 3.3, Oxford Molecular Limited (2000)
28. SPSS for Windows, version 10.05, SPSS Inc Bangalore, India (1999)
29. M.K. Rauf, M.A. Saeed, M. Imtiaz-ud-Din, A. Bolte, B.Mirza Badshah, J. Organomet. Chem.
693(18), 3043 (2008)
30. M.A. Abdellah, S.K. Hadjikakou, N. Hadjiliadis, M. Kubicki, T. Bakas, N. Kourkoumelis, Y.V.
Simos, S. Karkabounas, M.M. Barsan, I.S. Butler, Bioinorg. Chem. Appl. 2009, 1 (2009)
31. Sonika Nidhi, R. Malhotra, Phosphorus Sulfur Silicon Relat. Elem. 186, 1449 (2011)
32. S. Asija, N. Malhotra, R. Malhotra, Phosphorus Sulfur Silicon Relat. Elem. 187, 1510 (2012)
33. K. Singh, Y. Kumar, R.K. Pundir, Synth. React. Inorg. Met. Org. Chem. 40, 836 (2010)
34. A. Ahlawat, V. Singh, S. Asija, Chem. Pap. 71, 2195 (2017)
35. P. Khatkar, S. Asija, Phosphorus Sulfur Silicon Relat. Elem. 192, 446 (2017)
36. P. Khatkar, S. Asija, N. Singh, J. Serb. Chem. Soc. 82, 13 (2017)
37. R. Malhotra, A. Ravesh, V. Singh, Phosphorus Sulfur Silicon Relat. Elem. 192, 73 (2017)
38. J. Devi, S. Devi, A. Kumar, Monatsh. Chem. 147, 2195 (2016)
39. L.C. Dias, G.M. Lima, J.A. Takahashi, J.D. Ardisson, Appl. Organomet. Chem. 29, 305 (2015)
40. L. Czympiel, J.M. Lekeu, C. Hegemann, S. Mathur, Inorg. Chim. Acta 455, 197 (2017)
41. C. Hansch, T. Fujita, J. Am. Chem. Soc. 86, 1616 (1964)
42. C. Hansch, A. Leo, S.H. Unger, K.H. Kim, D. Nikaitani, E.J. Lien, J. Med. Chem. 16(11), 1207
(1973)
43. L.B. Kier, L.H. Hall, Molecular Connectivity in Chemistry and Drug Research (Academic Press,
New York, 1976)
44. M. Randic, J. Am. Chem. Soc. 97, 6609 (1975)
45. A.T. Balaban, Chem. Phys. Lett. 89, 399 (1982)
46. H. Wiener, J. Am. Chem. Soc. 69, 17 (1947)
47. M. Randic, Croat. Chem. Acta 66, 289 (1993)
48. V. Lather, A.K. Madan, Bioorg. Med. Chem. 13, 1599 (2005)
49. A. Golbraikh, A. Tropsha, J. Mol. Graph. Model. 20, 269 (2002)
50. A. Kumar, B. Narasimhan, D. Kumar, Bioorg. Med. Chem. 15, 4113 (2007)
51. V. Judge, B. Narasimhan, M. Ahuja, Med. Chem. Res. 21(3), 1363 (2012)
52. L.B. Kier, L.H. Hall, in Topological Indices and Related Descriptors in QSAR and QSPR, ed. by J.
Devillers, A.T. Balaban (Gordon and Breach Science Publishers, Amsterdam, 1999), p. 455
53. M. Karelson, V.S. Lobanov, A.R. Katritzky, Chem. Rev. 96(3), 1027 (1996)
123