Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV) complexes of Schiff bases derived from 2-(3-methylbutanoyl)-1H-indene-1,3(2H)-dione and 4-substituted anilines

Article abstract of DOI:10.1007/s00706-018-2308-6

Abstract: A series of some new diorganotin(IV) complexes [R₂SnLCl] was synthesized by the reaction of 2-(3-methylbutanoyl)-1H-indene-1,3(2H)-dione and 4-substituted anilines (p-OCH₃, p-NO₂, p-CH₃, p-Cl) with R₂SnCl₂, (R=Me, Et, n-Bu, Ph) in 1:1 molar ratio. The structure of the Schiff bases and their complexes were characterized by IR, ¹³C, ¹H, ¹¹⁹Sn NMR, and mass spectral techniques. The synthesized ligands and derived organotin complexes were evaluated in vitro against some bacterial strains, viz., Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus and fungal strains, viz., Aspergillus flavus, Aspergillus niger, and Candida albicans by serial dilution method. The antimicrobial results revealed that organotin complexes showed a distinct escalation in biocidal activity. Phenyl and butyl complexes were found to be more intoxicating. Furthermore, we performed QSAR studies which explained the different factors affecting the enhancement in the bioactivity of the complexes.

Full text of DOI:10.1007/s00706-018-2308-6

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-018-2308-6
ORIGINAL PAPER
Synthesis, characterization, in vitro antimicrobial and QSAR
studies of diorganotin(IV) complexes of Schiꢀ bases derived
from 2‑(3‑methylbutanoyl)‑1H‑indene‑1,3(2H)‑dione
and 4‑substituted anilines
1
1
1
2
Priyanka Khatkar · Sonika Asija · Aarti Ahlawat · Vikramjeet Singh
Received: 10 January 2018 / Accepted: 1 October 2018
©
Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract
A series of some new diorganotin(IV) complexes [R SnLCl] was synthesized by the reaction of 2-(3-methylbutanoyl)-
2
1
H-indene-1,3(2H)-dione and 4-substituted anilines (p-OCH , p-NO , p-CH , p-Cl) with R SnCl , (R=Me, Et, n-Bu, Ph)
3 2 3 2 2
1
3
1
119
in 1:1 molar ratio. The structure of the Schiꢀ bases and their complexes were characterized by IR, C, H, Sn NMR, and
mass spectral techniques. The synthesized ligands and derived organotin complexes were evaluated in vitro against some
bacterial strains, viz., Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus and fungal strains,
viz., Aspergillus favus, Aspergillus niger, and Candida albicans by serial dilution method. The antimicrobial results revealed
that organotin complexes showed a distinct escalation in biocidal activity. Phenyl and butyl complexes were found to be more
intoxicating. Furthermore, we performed QSAR studies which explained the diꢀerent factors aꢀecting the enhancement in
the bioactivity of the complexes.
Graphical abstract
2
2
2
2
2
1
1
.4
.3
.2
.1
.0
.9
.8
1
1
.7
.6
1
.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
2.4
Observed pMICpa
Keywords Schiꢀ bases · Diorganotin(IV) complexes · 2-(3-Methylbutanoyl)-1H-indene-1,3(2H)-dione · Antibacterial
activity · Antifungal activity · QSAR studies
Introduction
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-018-2308-6) contains
Since the last few years, the major problem has arisen due
supplementary material, which is available to authorized users.
to the expression of resistance by microorganisms against
the marketed drugs; therefore, there is a great need for
the discovery of innovative eꢁcacious therapeutic drugs
with better and new mechanisms against microbes [1–3].
To develop potential drugs, eꢀorts have been done by sci-
entists in various ꢂelds. In particular, Schiꢀ bases play an
essential role in biological ꢂelds as they are broadly used in
various chemical, biological, and photochemical reactions.
*
Sonika Asija
Sonika_ic2001@yohoo.co.in
1
2
Department of Chemistry, Guru Jambheshwar University
of Science and Technology, Hisar, Haryana 125001, India
Department of Pharmaceutical Sciences, Guru
Jambheshwar University of Science and Technology, Hisar,
Haryana 125001, India
Vol.:(0
1
123456789)
3

P. Khatkar et al.
In recent times, the Schiꢀ bases coordinated with the met-
als have been studied extensively in bioinorganic chemistry.
The Schiꢀ bases metal complexes are of great importance as
they act as potential drugs which possess a wide spectrum
of potential activity such as antimicrobial [4, 5], anticancer
Hence, these types of moieties are getting attraction due to
immense clinical importance [36, 37]. Therefore, based on
the facts discussed above and continuing our research work,
the synthesis, spectral characterization, in vitro antimicro-
bial potential and QSAR studies of diorganotin(IV) com-
plexes of Schiꢀ bases derived from, 2-(3-methylbutanoyl)-
1H-indene-1,3(2H)-dione with 4-substituted anilines are
discussed in this section.
[
6, 7], anti-inꢃammatory [8], antiparasitic [9], and antivi-
ral [10]. From the detailed literature survey on condensed
heterocyclic ring systems, it is evident that indenopyra-
zoles have also played a signiꢂcant role due to their wide
biological activities, viz., analgesics, antitubercular, anti-
inꢃammatory agents, etc. An huge literature revealed that
organotin(IV) complexes appeared as biologically potent
moieties having antitumor [11, 12], antitubercular [13–15],
antifertility [16, 17], antimicrobial [18–20], antiviral [21],
antinematicidal, antiinsecticidal [22], antilieshmanial [23],
anti-inꢃammatory [24], antidiabetic [25], antihypertensive
Chemistry
The starting triketone required for the synthesis of Schiꢀ
bases, i.e., 2-(3-methylbutanoyl)-1H-indene-1,3(2H)-dione
is synthesized by Claisen condensation of diethyl phthlate
and 4-methylpentan-2-one in the presence of sodium meth-
oxide as described in the literature [38, 39] (Scheme 1). The
purity of the compound was conꢂrmed by TLC and its melt-
ing point.
[
26], antioxidant [27], antimalarial [28] activity, etc. The
bioactive metal complexes have enormous chemotherapeutic
importance due to their ability to bind and degrade DNA
of the microorganisms [29–33]. By considering the above
facts and in continuation of our work towards the synthesis
of bioactive compounds, we report herein the convenient
synthesis, characterization, biological evaluation, and QSAR
studies of Schiꢀ bases containing oxygen and nitrogen donor
atoms and their organotin (IV) complexes.
Further, the triketone 2-(3-methylbutanoyl)-1H-indene-
1,3(2H)-dione was condensed with 4-substituted anilines
(p-methoxyaniline, p-nitroaniline, p-methylaniline, and
p-chloroaniline) in methanol in an equimolar ratio which
gave the desired Schiꢀ bases in excellent yield. The con-
densation took place on side chain as reported in the lit-
erature. These Schiff bases were subsequently treated
with dialkyl/aryltin(IV) dichloride to give respective
diorganotin(IV) complexes in good yields. The synthetic
protocol of Schiꢀ bases derived from 2-(3-methylbutanoyl)-
Results and discussion
1
H-indene-1,3(2H)-dione with 4-substituted anilines and
The prior knowledge available for condensed heterocyclic
ring systems indicated that indenopyrazoles have attained
signiꢂcant attention because of their synthetic utility and
enormous biological potential. Indenopyrazoles have been
found to be potent analgesics, antitubercular and anti-inꢃam-
matory agents, etc. Indenopyrazoles consist of indanedione
moiety which may be responsible for their biological activi-
ties [34, 35]. The Schiꢀ bases have also been reported to be
good complexing agents. The Schiꢀ base scaꢀolds play a
vital role in the synthetic and medicinal chemistry as they
are the core structure of numerous bioactive compounds.
their diorganotin(IV) complexes is given in Scheme 2. All
the diorganotin(IV) complexes were colored solids, stable,
and soluble in CDCl , DMSO, and MeOH. The Schiꢀ base
3
ligands and their diorganotin(IV) complexes were well char-
1
13
acterized by elemental analysis, molar conductance, H, C,
1
19
Sn NMR, and mass spectral studies. The ligands behaved
as monobasic bidentate (O–/N–) and coordinated to the cen-
tral tin atom with the oxygen atom of enol form. The molar
conductance of these complexes was found in the range
−
1
2
−1
10–17 Ω cm mol in DMSO, signifying the nonelec-
trolytic nature of complexes. The derived compounds were
Scheme 1
1
3

Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV)…
Scheme 2
subjected to evaluation of their in vitro antimicrobial poten-
tial by serial dilution method. Quantitative structure–activity
relationship (QSAR) analysis was performed using the linear
free energy relationship model (LFER).
NMR spectra
The binding sites (O–/N–) of Schiꢀ bases were further con-
1
13
ꢂrmed by comparing the H and C NMR spectra of ligands
and complexes. The NMR spectra were recorded in CDCl
3
FT‑IR spectra
and DMSO-d . The spectral data are described in “Experi-
6
mental” section.
The FT-IR spectra of all the synthesized compounds were
recorded using KBr. The IR spectral data are given in the
experimental section. The IR spectra of the Schiꢀ bases dis-
played characteristic sharp absorption bands at 1720–1710
1H NMR
−
1
1
and 1597–1587 cm due to C=O and C=N, respectively.
By comparing the IR spectra of ligands and complexes,
the coordination sites of the ligands were assigned. In the
IR spectra of the complexes, absorption band due to C=N
In the H NMR spectra of the ligands, the signal due to
enolic proton of the ꢂve membered ring of 1,3-indan-
edione moiety of Schiff base appeared as a singlet at
δ = 12.47–12.28 ppm. The disappearance of this signal
−
1
1
was shifted to lower frequency by 10–25 cm , which
showed coordination through the azomethine nitrogen.
The appearance of new band in the spectra of complexes at
in the H NMR spectra of the complexes suggested the
coordination mode of the carbonyl oxygen with central
1
tin atom through enolization. In the H NMR spectra of
−
1
1
243–1069 cm was due to C–O stretching conꢂrmed that
ligands and complexes, isobutyl group exhibited a doublet
the coordination had occurred through the carbonyl oxygen
to the tin after deprotonation. The new absorption bands in
the complexes due to Sn–C, Sn–O, and Sn–N at 723–627,
in the region 3.41–2.96 ppm due to CH protons, a multi-
2
plet in the region 2.27–1.82 ppm due to CH proton, and a
doublet for six protons of CH groups at 1.04–0.83 ppm.
3
−
1
1
5
53–531, and 475–451 cm , respectively, also conꢂrmed
In the ligand H L and its complexes, a singlet was
1
the formation of the complexes [40, 41].
observed due to three protons of OCH at 3.94–3.86 ppm
3
3
due to electronegative oxygen atom, in ligand H L and
1
its complexes, three protons of CH appeared as a sin-
3
glet in the region 2.32–2.30 ppm. The other aromatic
1
3

P. Khatkar et al.
protons appeared in the expected region. However, in the
diorganotin(IV) complexes, some new signals appeared
in the region 8.08–6.93 ppm due to phenyl group,
Mass spectra
The ESI-mass spectra of all the synthesized compounds fur-
ther conꢂrmed the formation of the compounds as the data
were found to be in good agreement with their molecular for-
mula (vide experimental). The fragmentation patterns were
2
.78–0.74 ppm due to butyl group, 1.75–0.83 ppm due to
ethyl group, and 1.71–1.66 ppm due to methyl groups as
expected [42].
+
analysed and base peaks were found due to [L] and the peak
+
due to [M+H] ion of the diorganotin(IV) complexes was
found with very low abundance in some cases. In the mass
spectra of the complexes, the fragment ions were observed
13C NMR
+
+
+
+
+
due to the [M+H] , [R′ SnL] , [L] , [R′SnL] , [SnL] ,
2
1
3
+
The C NMR spectral data of all the synthesized com-
pounds were found to be in the expected regions and fur-
[Sn] which were in accordance with literature [46]. The
1
molecular ion and base peaks of Ph SnClL were appeared
2
1
+
+
ther supported the data obtained from IR and H NMR. The
at m/z=644.50 and 336.00 due to [M+H] and [L] , respec-
tively, which were found in agreement with the theoretical
values. The ESI-mass spectrum of diorganotin(IV) complex
1 is shown in Fig. 1.
characteristic signals in ligands due to carbonyl carbons and
azomethine carbon were appeared at δ=194.01–170.63 ppm
and 159.02–148.66 ppm, respectively. The signal due to the
C–H carbon of the ꢂve membered ring of 1,3-indanedione
moiety of Schiꢀ bases appeared at 103.69–100.83 ppm for
ligands and complexes supporting the tautomerization of the
In vitro antimicrobial activity
13
proton attached to the carbon. In C NMR spectra of ligands
and complexes signals due to carbons of OCH and CH
The Schiꢀ bases derived from 2-(3-methylbutanoyl)-1H-in-
dene-1,3(2H)-dione with 4-substituted anilines and their
diorganotin(IV) complexes were tested for their potential
against Gram-positive bacterial strains, viz., Staphylococ-
cus aureus, Bacillus cereus, Gram-negative bacterial strains,
viz., Escherichia coli, Pseudomonas aeruginosa, and fungal
strains, viz., Aspergillus favus, Aspergillus niger, and Can-
dida albicans using serial dilution technique and ciproꢃoxa-
cin and ꢃuconazole as standard drugs. The potential regard-
ing the antibacterial and antifungal activity is presented in
Table 1 and Fig. 2. The presence of C=N group in the Schiꢀ
bases and central tin atom plays a vital role in biological
activity. Among the tested compounds, most of the com-
plexes were found more potent against microbial strains as
the R′, group increases the lipophilicity of the complexes as
they can easily bind with biological molecules by π–π inter-
actions which boost up their bioactivity. The diorganotin(IV)
complexes were found to be more potent as compared to the
Schiꢀ base ligands against the same strains as explained by
the chelation theory [47], which is responsible for the aug-
mentation of the biocidal activity. The compounds penetrate
through the cell wall and bind with the DNA of the microor-
ganism which leads to deactivate the respiration process of
the microorganisms. The hydrogen bond formation between
oxygen and nitrogen atom with active centers of cell con-
stituents may alter the mode of action at cell processes [48,
49]. Further, the derived compounds had higher potential
against Gram-positive bacterial strains as compared to Gram
negative due to the presence of outer complex cell mem-
brane, containing lipopolysaccharides. The data revealed
3
3
were observed at 57.35–55.54 ppm and 39.63–34.72 ppm,
respectively. The three signals of isobutyl moiety appeared in
the range 38.96–35.45, 29.09–22.96, and 22.69–21.23 ppm
can be assigned to CH , CH, CH carbons, respectively. The
2
3
signals due to carbonyl carbon, azomethine carbon and the
carbon directly attached to the central metal were shifted
downꢂeld on complexation owing to decrease in electron
density on these groups and electropositive nature of tin
metal. The data supported the coordination modes through
13
azomethine nitrogen and carbonyl carbon. In the C spectra
of the complexes, the new signals due to carbon of methyl,
ethyl, butyl, and phenyl group directly attached to central tin
atom appeared in the expected region [43].
119Sn NMR
The pentacoordinated environment of the diorganotin(IV)
1
19
119
complexes was conꢂrmed by Sn NMR spectra. In Sn
spectra of complexes, a sharp singlet was observed indi-
1
19
cating the formation of a single tin species. In Sn NMR
spectra signal in the range δ = − 397.48 to − 378.32 ppm,
−
−
298.21 to −273.18 ppm, −233.60 to −203.17 ppm, and
189.66 to −178.30 ppm was due to phenyl, butyl, ethyl,
and methyl complexes which were in accordance with the
literature and supported the pentacoordinated environment
and distorted trigonal bipyramidal geometry around the tin
atom [44, 45].
3
that the complexes 13 (MIC 0.0048 µmol/cm ) against
3
E. coli and 1 (MIC 0.0024 µmol/cm ) against P. aerugi-
3
nosa, 5 (MIC 0.0047 µmol/cm ) against B. cereus, 1 (MIC
1
3

Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV)…
Fig. 1 ESI-mass spectrum of diorganotin(IV) complex 1
3
0
.0024 µmol/cm ) against S. aureus, 1 (MIC 0.0024 µmol/
diꢀerent parameters, i.e., molecular descriptors. The active inter-
relationship was observed between zero-order molecular con-
3
3
cm ) against A. favus, 5 (MIC 0.0024 µmol/cm ) against
3
0
A. niger and 1 (MIC 0.0024 µmol/cm ) against C. albicans
nectivity index, χ and electronic energy (r=0.999), nuclear
3
(
MIC 0.0024 µmol/cm ) were ꢀound to be most potent.
repulsion energy, and zero-order molecular connectivity index,
0
χ (r=0.998), and least interrelationship was found between Bala-
QSAR studies
ban index (J), and dipole moment, μ (r=0.007) and third-order
3
molecular connectivity index, χ and energy of highest occupied
1
In the present study, data set of twenty compounds (H L –H
molecular orbital, HOMO (r=0.009). The correlation matrix
pointed the role of kappa shape indices, Randic parameter, and
molecular connectivity indices in the expression of antibacterial
and antifungal activity by the synthesized complexes [50, 51].
The assessment of antimicrobial potential of synthesized
compounds against P. aeruginosa revealed that topological
1
4
L and diorganotin(IV) complexes 1–16) was submitted for the
1
regression analysis to correlate the molecular descriptors of these
compounds with the observed in vitro antimicrobial activities.
During the regression analysis study, it was observed that the
results of the two compounds, viz., 1 and 16 were outside the
limits of whole data set and being outliers were not included in the
regression analysis for the generation of mathematical models for
the prediction of antimicrobial activities. The relationship between
molecular descriptors and biological potential was accessed by
regression analysis and correlation matrix constructed for anti-
bacterial activity against P. aeruginosa is presented in Table 2
descriptor ꢂrst-order kappa shape index (κ ) was eꢀectively
1
controlling the antibacterial activity (Eq. 1).
QSAR model for antibacterial activity against P. aerugi-
nosa is
pMICpa = 0.0623ꢀ + 0.518,
1
(1)
(
supplementary section). The interrelationship of various struc-
2
n = 18, r = 0.963, r = 0.928, q = 0.910,
2
tural descriptors with antimicrobial potential is presented in
Table 3 (supplementary section). In general, going through the
whole data set, high colinearity (r>0.8) was observed between
s = 0.065, F = 205.616,
1
3

P. Khatkar et al.
Table 1 The in vitro
Minimum inhibitory concentration (MIC)/µmol/cm3
Compounds
antibacterial and antifungal
activity of Schiꢀ bases derived
from 2-(3-methylbutanoyl)-
Gram-negative bacteria
Gram-positive bacteria Fungi
E. coli P. aeruginosa B. cereus S. aureus A. niger A. favus C. albicans
1
4
H-indene-1,3(2H)-dione with
-substituted anilines and their
1
H1L
H1L
H1L
H1L
0.0186 0.0186
0.0357 0.0178
0.0783 0.0196
0.0368 0.0184
0.0097 0.0024
0.0104 0.0052
0.0229 0.0114
0.0241 0.0121
0.0095 0.0047
0.0101 0.0050
0.0223 0.0111
0.0234 0.0117
0.0050 0.0050
0.0107 0.0053
0.0118 0.0118
0.0373
0.0178
0.0391
0.0184
0.0097
0.0104
0.0114
0.0121
0.0047
0.0101
0.0111
0.0117
0.0050
0.0053
0.0236
0.0249
0.0048
0.0103
0.0227
0.012
0.0373
0.0178
0.0391
0.0368
0.0024
0.0052
0.0057
0.0060
0.0011
0.0051
0.0111
0.0058
0.0100
0.0107
0.0118
0.0031
0.0097
0.0051
0.0113
0.006
0.0093
0.0089
0.0196
0.0046
0.0097
0.0052
0.0114
0.0121
0.0024
0.0051
0.0111
0.0117
0.0025
0.0053
0.0118
0.0124
0.0048
0.0051
0.0113
0.012
0.0093
0.0045
0.0098
0.0092
0.0024
0.0026
0.0114
0.006
0.0095
0.0051
0.0111
0.0058
0.0050
0.0053
0.0118
0.0062
0.0048
0.0051
0.0057
0.006
0.0186
0.0089
0.0196
0.0092
0.0024
0.0052
0.0114
0.0121
0.0047
0.0101
0.0056
0.0058
0.0050
0.0053
0.0118
0.0124
0.0048
0.0103
0.0113
0.0120
–
diorganotin(IV) complexes
2
3
4
1
Ph SnClL (1)
2
2
1
Bu SnClL (2)
1
Et SnClL (3)
2
1
Me SnClL (4)
2
2
Ph SnClL (5)
2
2
Bu SnClL (6)
2
2
Et SnClL (7)
2
2
Me SnClL (8)
2
3
Ph SnClL (9)
2
3
Bu SnClL (10)
2
3
Et SnClL (11)
2
3
Me SnClL (12) 0.0124 0.0124
2
4
Ph SnClL (13)
0.0048 0.0048
0.0103 0.0051
0.0227 0.0113
2
4
Bu SnClL (14)
2
4
Et SnClL (15)
2
4
Me SnClL (16) 0.0239 0.0060
2
Ciproꢃoxacin
Fluconazole
0.0047 0.0047
0.0047
–
0.0047
–
–
–
–
0.0102
0.0102
0.0102
2
2
2
2
2
1
1
.4
.3
.2
.1
.0
.9
.8
The QSAR model for antibacterial activity against P. aer-
uginosa (Eq. 1) demonstrated the role of ꢂrst-order Kappa
shape indices (κ ) in modulating the activity. According to
1
Kier, “the shape of a molecule may be partitioned into attrib-
utes, each described by the count of bonds of various path
lengths. The basis for devising a relative index of shape is
given by the relationship of the number of path of length
l
l in the molecule i, P , to some reference values based on
i
molecules with a given number of atoms, n, in which the
l
l
l
values of P are maximum and minimum, P
and P
.
min
max
The ꢂrst-order shape attribute, κ , is given by the following
1
1
1
.7
.6
expression”:
2
1
2
= n(n − 1) ∕( P ) .
ꢀ1
i
1
.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
2.4
It can be seen from the results of antimicrobial activity
Observed pMICpa
in Table 4 (supplementary section) that compounds 1 and 5
have the highest antibacterial potential against P. aeruginosa
Fig. 2 Plot of observed pMICpa against the predicted pMICpa for the
QSAR model developed by Eq. (1)
and they have high κ values (Table 5, supplementary sec-
1
tion) which are in concordance with the model expressed by
Eq. (1) in which there is a positive correlation between anti-
bacterial potential of synthesized compounds and topologi-
where r is the correlation coeꢁcient, n is the number of
2
2
cal descriptors κ . The best use of QSAR models is in their
data points, r is the squared correlation coeꢁcient, q is the
1
2
ability to predict the activity potential of similar compounds
cross-validated r obtained by leave one out method, s is the
and this assessing potential is measured by testing the validity
standard error of the estimate and F is the Fischer statistics.
1
3

Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV)…
of derived QSAR models. The validity of the models was
QSAR model for antifungal activity against A. niger is
2
measured by the leave one out (LOO) method and q value
pMICan = 0.119ꢀ + 0.957,
2
(4)
was found to be 0.910. The QSAR model is valid if value of
2
q >0.5; hence, the model represented by Eq. (1) was consid-
2
n = 16, r = 0.907, r = 0.822,
ered as a valid one. Further, the mathematical model (Eq. 1)
was also tested for its predictability and the results of predicted
antibacterial activity are presented in Table 6 (supplementary
section).
2
q = 0.771, s = 0.083, F = 64.505.
QSAR model for antibacterial activity against B. cereus
is
The comparison of in vitro observed and predicted antibac-
terial activity indicated that the model represented by Eq. (1)
was valid as it gave low residual values, hence supporting the
validity of the derived model. Further, to conꢂrm the predict-
ability and validity of derived QSAR model a plot of observed
and predicted antibacterial activity against P. aeruginosa was
drawn which also supported the validity of model represented
by Eq. (1) (Fig. 2). The plot of observed antibacterial activity
1
pMICbc = 0.099 ꢀ + 0.414,
(5)
2
n = 16, r = 0.899, r = 0.809,
2
q = 0.749, s = 0.127, F = 59.121.
QSAR model for antibacterial activity against S. aureus
is
2
pMIC = 0.142 ꢀ + 0.007,
against residual antibacterial activity (pMIC ) demonstrated
(6)
pa
sa
the nonexistence of systematic errors in development of QSAR
2
n = 16, r = 0.862, r = 0.743,
model (Fig. 3) [52].
The other important QSAR models derived are as repre-
sented below.
2
q = 0.636, s = 0.191, F = 40.93.
QSAR model for antifungal activity against C. albicans
QSAR model for antibacterial activity against E. coli is
is
1
pMICec = 0.112 ꢀ + 0.103,
(2)
2
pMICca = 0.083 ꢀ + 0.869,
(7)
2
n = 16, r = 0.913, r = 0.833,
2
n = 16, r = 0.847, r = 0.717,
2
q = 0.767, s = 0.115, F = 69.621.
2
q = 0.639, s = 0.118, F = 35.509.
QSAR model for antibacterial activity against E. coli is
pMICec = 0.112R + 0.103,
The above models have been discussed in detail in the
supplementary section.
(3)
2
n = 16, r = 0.913, r = 0.833,
2
q = 0.767, s = 0.115, F = 69.621.
Conclusion
Diorganotin(IV) complexes were obtained by the reac-
tion of 2-(3-methylbutanoyl)-1H-indene-1,3(2H)-dione
and 4-substituted anilines (p-OCH , p-NO , p-CH , p-Cl)
.
.
2
1
3
2
3
with R SnCl , (R=Me, Et, n-Bu, Ph). The synthesized
2
2
complexes have been characterized by diꢀerent spectro-
1
13
119
scopic ( H, C, Sn NMR, IR, mass) and other physi-
cal techniques. The Schiꢀ base ligands were found to be
bidentate coordinated with tin metal with (N–/O–) donor
sites having pentacoordinated tin(IV) complexes. These
compounds were further screened for their in vitro anti-
microbial activity against diꢀerent bacterial and fungal
strains. The activity varies with the substitution on the tin
atom, and the phenyl complexes were found to be more
potent than other compounds. The presence of chlorine
atom showed superior biocidal activity. Furthermore, the
QSAR analysis revealed that the antimicrobial activity was
controlled by topological indices which indicated that the
complexes were more proliꢂc than the parent ligands.
0
.0
-
-
.1
.2
1
.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
2.4
Observed pMICpa
Fig. 3 Plot of residual pMICpa against the observed pMICpa for the
QSAR model developed by Eq. (1)
1
3

P. Khatkar et al.
Experimental
(E)‑2‑[3‑Methyl‑1‑(4‑nitrophenylimino)butyl]‑1H‑in‑
2
dene‑1,3(2H)‑dione (H L , C H N O ) White solid; yield:
1
20 18 2 4
All the reactions were carried under inert atmosphere.
The starting materials, i.e., dimethyltin(IV) dichloride,
diethyltin(IV) dichloride, di-n-butyltin(IV) dichloride, and
diphenyltin(IV) dichloride were of analytical grade supplied
by Sigma-Aldrich and used as such without any further puri-
ꢂcation. The elemental analysis (C, H, and N) was carried
on a Perkin-Elmer 2400 instrument and the measured data
were found to be in accordance with the calculated data. The
89%; m.p.: 178–181 °C; IR (KBr): ̄ꢀ = 1720 (C=O), 1590
−
1 1
(C=N) cm ; H NMR (CDCl3): δ = 12.61 (s, 1H), 8.07
(d, 2H), 7.84 (d, 2H, J = 8 Hz), 7.41 (d, 2H, J = 8 Hz),
6.63 (d, 2H, J = 8 Hz), 2.86 (d, 2H, J = 8 Hz), 2.27–2.18
1
3
(m, 1H), 1.04 (d, 6H, J = 8 Hz) ppm; C NMR (CDCl3):
δ=191.4, 189.4, 157.7, 148.9, 142.6, 134.6, 132.3, 126.3,
124.5, 101.5, 38.9, 24.4, 22.7 ppm; ESI–MS: m/z calcd. for
+
C20H18N2O4 ([M+H] ) 351.3, found 351.60.
−
1
Fourier transform infrared (FTIR) spectra (4000–400 cm )
were recorded on a Perkin-Elmer spectrum RX1 instrument.
The NMR spectra were recorded on a Bruker Avance II
( E) ‑ 2 ‑ [ 3 ‑ M e t h y l ‑ 1 ‑ ( p‑ t o l y l i m i n o ) b u t y l ] ‑ 1 H‑ i n ‑
3
dene‑1,3(2H)‑dione (H1L , C21H21NO2) White solid; yield:
4
00 MHz NMR spectrometer in CDCl or DMSO-d using
87%; m.p.: 201–203 °C; IR (KBr): ̄ꢀ = 1718 (C=O), 1595
3
6
−
1 1
tetramethylsilane (TMS) as an internal standard. The mass
spectra were recorded on an LCMS MS 6410 Agilent Tech-
nologies spectrometer with an electron impact quadropole
(C=N) cm ; H NMR (CDCl3): δ=12.47 (s, 1H), 7.87 (d,
2H), 7.62 (d, 2H, J=8 Hz), 7.33 (d, 2H, J=8 Hz), 7.15 (d,
2H, J=8 Hz), 2.31 (s, 3H), 2.96 (d, 2H, J=8 Hz), 1.93–1.82
1
3
analyzer. Tin was estimated gravimetrically as SnO .
(m, 1H), 0.91 (d, 6H, J = 8 Hz) ppm; C NMR (CDCl3):
δ=193.7, 188.3 (C=O), 153.6 (C=N), 140.2, 134.5, 132.4,
128.6, 127.8, 126.7, 100.8, 39.6, 30.7, 22.9, 21.5 ppm; ESI–
2
General procedure for the synthesis of Schiꢀ base
1
4
+
ligands H L –H L
MS: m/z calcd. for C21H21NO2 ([M+H] ) 320.17, found
1
1
3
20.20.
The 2-(3-methylbutanoyl)-1H-indene-1,3(2H)-dione needed
for the synthesis was prepared by the Claisen condensation
of diethyl phthlate and 4-methylpentan-2-one in the presence
of sodium methoxide as described in the literature. procedure
(E)‑2‑[1‑(4‑Chlorophenylimino)‑3‑methylbutyl]‑1H‑in‑
4
dene‑1,3(2H)‑dione (H1L , C20H18ClNO2) White solid; yield:
91%; m.p.: 191–193 °C; IR (KBr): ̄ꢀ = 1710 (C=O), 1597
1
4
−1 1
[
38, 39]. Schiꢀ base ligands H L –H L were prepared in
(C=N) cm ; H NMR (CDCl3): δ=12.31 (s, 1H), 7.73 (m,
2H), 7.61 (m, 2H, J = 8 Hz), 7.23–7.13 (m, 4H), 2.97 (d,
2H, J = 8 Hz), 1.98–1.89 (m, 1H), 0.86 (d, 6H, J= 8 Hz)
1
1
good yield by the reaction of 1.151 g 2-(3-methylbutanoyl)-
H-indene-1,3(2H)-dione (5 mmol) and 0.615 g p-meth-
1
1
3
oxyaniline (5 mmol) or 0.690 g p-nitroaniline (5 mmol) or
ppm; C NMR (CDCl3): δ = 192.6, 189.6, 156.7 (C=N),
0
.535 g p-methylaniline (5 mmol) or 0.637 g p-chloroaniline
145.5, 132.8, 130.3, 129.7, 128.8, 127.4, 101.3, 35.5, 23.6,
3
+
(
5 mmol) in 1:1 molar ratio in 30 cm methanol by adding
22.4 ppm; ESI–MS: m/z calcd. for C20H18ClNO2 ([M+H] )
3
–4 drops of glacial acetic acid. The progress of reaction
340.11, found 340.20.
was monitored by TLC analysis of the reaction mixture
withdrawn at diꢀerent interval of time. The reaction mix-
ture was reꢃuxed for 6–7 h and after the completion of reac-
tion, contents were allowed to cool and stand overnight at
room temperature. The products thus obtained were ꢂltered,
washed with methanol, and recrystallized from methanol and
chloroform solution to furnish the pure products.
General procedure for the synthesis
of diorganotin(IV) complexes 1–16
For the synthesis of diorganotin(IV) complexes firstly
1
sodium salt of the ligands by the reaction of 1.67 g H1L ,
2
3
4
1.75 g H1L , 1.59 g H1L , or 1.69 g H1L (5 mmol each)
3
and 0.23 g sodium metal (5 mmol) in 20 cm dry metha-
(
E)‑2‑[1‑(4‑Methoxyphenylimino)‑3‑methylbutyl]‑1H‑in‑
nol was prepared. To the reaction mixture, the metha-
nolic solution of 1.71 g diphenyltin(IV) dichloride, 1.51 g
dibutyltin(IV) dichloride, 1.23 g diethyltin(IV) dichloride,
or 1.09 g dimethyltin(IV) dichloride was added dropwise
with constant stirring and then reꢃuxed at 40–50 °C for
6–7 h. Thereafter, the reaction mixture was cooled and kept
overnight at room temperature. Then, the reaction mixture
was ꢂltered to remove sodium chloride salt thus formed.
Consequently, the excess solvent was evaporated over rotary
evaporator under reduced pressure to separate out the solid.
The solid thus obtained was washed with dry hexane and
1
dene‑1,3(2H)‑dione (H L , C H NO) White solid; yield:
1
21 21
9
3%; m.p.: 174–176 °C; IR (KBr): ̄ꢀ = 1716 (C=O), 1587
−
1 1
(
C=N) cm ; H NMR (CDCl ): δ=12.28 (s, 1H), 7.72 (d,
3
2
H), 7.59 (d, 2H, J=8 Hz), 7.14 (d, 2H, J=8 Hz), 6.95 (d,
H, J=8 Hz), 3.86 (s, 3H), 2.97 (d, 2H, J=8 Hz), 2.00–1.90
2
1
3
(
m, 1H), 0.86 (d, 6H, J = 4 Hz) ppm; C NMR (CDCl ):
3
δ=195.0, 190.4, 166.0, 158.9, 139.9, 138.9, 133.2, 132.8,
1
2
3
29.1, 127.7, 121.4, 120.9, 114.6, 103.6, 55.5, 35.5, 29.0,
+
2.4 ppm; ESI–MS: m/z calcd. for C H NO ([M+H] )
2
1
21
36.16, found 336.10.
1
3

Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV)…
recrystallized with methanol and chloroform mixture to get
the pure products.
δ=−189.66 ppm; ESI–MS: m/z calcd. for C H ClNO Sn
2
3
26
3
+
([M+H] ) 520.07, found 520.60.
(
E)‑3‑[(Chlorodiphenylstannyl)oxy]‑2‑[1‑(4‑methox
yphenylimino)‑3‑methylbutyl]‑1H‑inden‑1‑one (1,
C H ClNO Sn) Yellow solid; yield: 76%; m.p.: 187–189 °C;
(
E)‑3‑[(Chlorodiphenylstannyl)oxy]‑2‑[3‑methyl‑1‑(4‑nitro‑
p h e n y l i m i n o ) b u t y l ] ‑ 1 H ‑ i n d e n ‑ 1 ‑ o n e ( 5 ,
C H ClN O Sn) Yellow solid; yield: 90%; m.p.: 172 °C;
33
30
3
3
2
27
2 4
IR (KBr): ̄ꢀ=1708 (C=O), 1568 (C=N), 1172 (C–O), 692
IR (KBr): ̄ꢀ=1716 (C=O), 1577 (C=N), 1191 (C–O), 701
−
1 1
(
Sn–C), 541 (Sn–O), 471 (Sn–N) cm ; H NMR (CDCl ):
−1 1
3
(Sn–C), 546 (Sn–O), 474 (Sn–N) cm ; H NMR (CDCl ):
3
δ=7.90–6.99 (m, 18H), 3.87 (s, 3H), 2.97 (d, 2H, J=8 Hz),
δ=8.08 (d, 2H, J=8 Hz), 7.81–6.93 (m, 16H), 2.96 (d, 2H,
1
3
1
.98–1.91 (m, 1H), 0.86 (d, 6H) ppm; C NMR (CDCl ):
3
J=8 Hz), 1.92–1.87 (m, 1H), 0.83 (d, 6H, J =8 Hz) ppm;
δ=195.0, 190.4, 169.0, 158.0, 139.8, 138.9, 136.1, 133.2,
13
C NMR (CDCl ): δ = 193.5, 189.0, 162.9, 147.2, 139.4,
3
1
2
32.8, 129.1, 127.7, 121.4, 121.0, 114.6, 103.6, 55.6, 35.4,
1
38.3, 137.8, 136.2, 133.0, 132.2, 129.1, 127.9, 122.6,
1
19
9.0, 22.4 ppm; Sn NMR (CDCl ): δ = − 379.47 ppm;
119
3
116.7, 101.0, 35.7, 27.8, 22.1 ppm; Sn NMR (CDCl ):
3
+
ESI–MS: m/z calcd. for C H ClNO Sn ([M+H] ) 644.10,
3
3
30
3
δ=−393.89 ppm; ESI–MS: m/z calcd. for C H ClN O Sn
32
27
2
4
found 644.40.
+
(
[M+H] ) 659.08, found 659.40.
(
E)‑3‑[(Dibutylchlorostannyl)oxy]‑2‑[1‑(4‑methoxyphenylimi
(
E)‑3‑[(Dibutylchlorostannyl)oxy]‑2‑[3‑methyl‑1‑(4‑nitrophe‑
no)‑3‑methylbutyl]‑1H‑inden‑1‑one (2, C H ClNO Sn) Yel-
29
38
3
nylimino)butyl]‑1H‑inden‑1‑one (6, C H ClN O Sn) Yellow
28
35
2 4
low solid; yield: 78%; m.p.: 182–183 °C; IR (KBr): ̄ꢀ=1718
solid; yield: 82%; m.p.: 198–200 °C; IR (KBr): ̄ꢀ = 1719
(
C=O), 1571 (C=N), 1109 (C–O), 627 (Sn–C), 537 (Sn–O),
(
C=O), 1572 (C=N), 1088 (C–O), 665 (Sn–C), 544 (Sn–
−
1 1
4
62 (Sn–N) cm ; H NMR (CDCl ): δ=7.57 (d, 2H), 7.31 (d,
−1 1
3
O), 468 (Sn–N) cm ; H NMR (CDCl ): δ=8.06 (d, 2H,
3
2
H, J=8 Hz), 7.09 (d, 2H, J=8 Hz), 6.92 (d, 2H, J=8 Hz), 3.91
J = 8 Hz), 7.87 (d, 2H, J = 8 Hz), 7.42 (d, 2H, J = 8 Hz),
(
s, 3H), 3.41 (d, 2H, J=8 Hz), 2.78–2.47 (m, 6H), 2.11–2.03
6
.73 (d, 2H, J=8 Hz), 3.31 (d, 2H, J=8 Hz), 2.51–2.48 (m,
13
(
m, 1H, CH), 1.48–0.83 (m, 18H) ppm; C NMR (CDCl ):
13
3
3H), 1.52–0.84 (m, 21H) ppm; C NMR (CDCl ): δ=192.8,
3
δ=194.0, 189.6, 168.6, 157.7, 139.4, 137.1, 135.6, 133.3, 131.3,
1
1
88.2, 159.0, 146.9, 139.1, 137.4, 135.6, 133.4, 132.4,
1
29.2, 101.0, 56.5, 35.4, 30.1, 26.7, 25.5, 23.1, 22.7, 15.9 ppm;
29.0, 100.0, 36.5, 28.1, 25.2, 22.1, 21.7, 20.1, 13.3 ppm;
1
19
Sn NMR (CDCl ): δ=-287.19 ppm; ESI–MS: m/z calcd. for
119
3
Sn NMR (CDCl ): δ=−273.18 ppm; ESI–MS: m/z calcd.
3
+
C H ClNO Sn ([M+H] ) 604.16, found 604.40.
+
29
38
3
for C H ClN O Sn ([M+H] ) 619.14, found 619.60.
28 35 2 4
(
E)‑3‑[(Diethylchlorostannyl)oxy]‑2‑[1‑(4‑methoxyphenylimino)‑3
(
E)‑3‑[(Chlorodiethylstannyl)oxy]‑2‑[3‑methyl‑1‑(4‑nitrophe‑
‑
methylbutyl]‑1H‑inden‑1‑one (3, C H ClNO Sn) Yellow solid;
25
30
3
nylimino)butyl]‑1H‑inden‑1‑one (7, C H ClN O Sn) Yellow
24
27
2 4
yield: 72%; m.p.: 189–191 °C; IR (KBr): ̄ꢀ=1709 (C=O), 1573
solid; yield: 90%; m.p.: 172 °C; IR (KBr): ̄ꢀ=1714 (C=O),
−1
(
C=N), 1075 (C–O), 671 (Sn–C), 539 (Sn–O), 473 (Sn–N) cm ;
1
568 (C=N), 1092 (C–O), 688 (Sn–C), 531 (Sn–O), 460
1
H NMR (CDCl ): δ=7.79 (d, 2H, J=8 Hz), 7.71–7.63 (m, 2H),
−1 1
3
(Sn–N) cm ; H NMR (CDCl ): δ=8.07 (d, 2H, J=8 Hz),
3
7
.19 (d, 2H), 7.05 (d, 2H, J=8 Hz), 3.93 (s, 3H), 2.94 (d, 2H,
7
2
.79 (d, 2H, J=8 Hz), 7.41 (d, 2H), 6.93 (d, 2H, J=8 Hz),
J=8 Hz), 2.13–2.02 (m, 1H), 1.73–1.63 (m, 4H), 1.21–0.83 (m,
.99 (d, 2H, J = 8 Hz), 2.07–1.98 (m, 1H), 1.75–1.68
1
3
1
2H) ppm; C NMR (CDCl ): δ=193.1, 189.0, 168.8, 158.6,
13
3
(m, 4H), 1.23–0.88 (m, 12H) ppm; C NMR (CDCl ):
3
1
41.0, 137.7, 133.5, 131.4, 130.2, 129.7, 102.8, 56.7, 36.1, 29.6,
δ=194.4, 190.6, 158.6, 147.5, 141.9, 139.2, 137.1, 133.3,
119
2
5.3, 21.5, 15.2 ppm; Sn NMR (CDCl ): δ=−203.17 ppm;
119
3
131.2, 128.4, 100.2, 35.7, 28.8, 26.1, 21.7, 15.5 ppm; Sn
+
ESI–MS: m/z calcd. for C H ClNO Sn ([M+H] ) 548.10,
25
30
3
NMR (CDCl ): δ=−213.70 ppm; ESI–MS: m/z calcd. for
3
found 548.90.
+
C H ClN O Sn ([M+H] ) 563.08, found 563.10.
2
4
27
2
4
(
E)‑3‑[(Chlorodimethylstannyl)oxy]‑2‑[1‑(4‑methox
yphenylimino)‑3‑methylbutyl]‑1H‑inden‑1‑one (4,
C H ClNO Sn) Yellow solid; yield: 78%; m.p.: 185–
(
E)‑3‑[(Chlorodimethylstannyl)oxy]‑2‑[3‑methyl‑1‑(4‑nitro‑
p h e n y l i m i n o ) b u t y l ] ‑ 1 H ‑ i n d e n ‑ 1 ‑ o n e ( 8 ,
C H ClN O Sn) Yellow solid; yield: 81%; m.p.: 191–
2
3
26
3
2
2
23
2 4
1
87 °C; IR (KBr): ̄ꢀ = 1721 (C=O), 1572 (C=N), 1069
1
93 °C; IR (KBr): ̄ꢀ = 1711(C=O), 1573 (C=N), 1093
−
1 1
(
C–O), 679 (Sn–C), 538 (Sn–O), 469 (Sn–N) cm ; H
−1 1
(
C–O), 657 (Sn–C), 538 (Sn–O), 475 (Sn–N) cm ; H
NMR (CDCl ): δ=7.80 (m, 2H), 7.70–7.65 (m, 2H), 7.22
3
NMR (CDCl ): δ = 8.03 (d, 2H, J = 8 Hz), 7.86 (d, 2H,
3
(
d, 2H, J=8 Hz), 7.03 (d, 2H, J=8 Hz), 3.94 (s, 3H), 3.05
J = 8 Hz), 7.44 (d, 2H, J = 8 Hz), 6.83 (d, 2H, J = 8 Hz),
(
d, 2H, J=8 Hz), 2.07–2.00 (m, 1H), 1.66 (s, 6H), 0.94 (d,
3
.01 (d, 2H, J=8 Hz), 2.08–1.99 (m, 1H), 1.68 (s, 6H), 0.93
1
3
6
1
5
H, J=8 Hz) ppm; C NMR (CDCl ): δ=194.39, 190.0,
13
3
(d, 6H, J=8 Hz) ppm; C NMR (CDCl ): δ=193.4, 189.7,
3
71.7, 157.0, 140.8, 138.3, 134.4, 132.1, 131.7, 129.1, 99.2,
1
58.4, 146.0, 140.8, 139.2, 138.6, 134.4, 133.4, 129.5,
1
19
7.3, 35.5, 26.7, 21.2, 15.2 ppm; Sn NMR (CDCl ):
119
3
99.9, 36.2, 29.7, 23.3, 14.5 ppm; Sn NMR (CDCl ):
3
1
3

P. Khatkar et al.
δ=−182.36 ppm; ESI–MS: m/z calcd. for C H ClN O Sn
138.6, 136.7, 133.4, 130.4, 128.7, 100.9, 34.7, 28.8, 24.3,
22
23
2
4
+
119
(
[M+H] ) 535.04, found 535.60.
21.6, 15.0 ppm; Sn NMR (CDCl ): δ = − 183.06 ppm;
3
+
ESI–MS: m/z calcd. for C H ClNO Sn ([M+H] ) 504.08,
2
3
26
2
(
E)‑3‑[(Chlorodiphenylstannyl)oxy]‑2‑[3‑methyl‑1‑(p‑tol‑
found 504.90.
ylimino)butyl]‑1H‑inden‑1‑one (9, C H ClNO Sn) Yellow
3
3
30
2
solid; yield: 90%; m.p.: 197–199 °C, IR (KBr): ̄ꢀ = 1721
(E)‑3‑[(Chlorodiphenylstannyl)oxy]‑2‑[1‑(4‑chlorophenylimino)‑
3‑methylbutyl]‑1H‑inden‑1‑one (13, C H Cl NO Sn) Yel-
(
C=O), 1582 (C=N), 1171 (C–O), 723 (Sn–C), 542 (Sn–
3
2
27
2
2
−
1 1
O), 461 (Sn–N) cm ; H NMR (CDCl ): δ = 7.79–6.97
low solid; yield: 85%; m.p.: 232–234 °C; IR (KBr): ̄ꢀ=1722
3
(
(
m, 18H), 2.94 (d, 2H, J= 8 Hz), 2.32 (s, 3H), 1.90–1.79
(C=O), 1577 (C=N), 1196 (C–O), 683 (Sn–C), 535 (Sn–O),
1
3
−1 1
m, 1H), 0.89 (d, 6H, J = 8 Hz) ppm; C NMR (CDCl ):
458 (Sn–N) cm ; H NMR (CDCl ): δ = 7.63–7.12 (m,
3
3
δ=194.7, 189.3, 162.0, 142.9, 137.5, 136.4, 133.1, 132.2,
18H), 2.96 (d, 2H, J=8 Hz), 1.91–1.82 (m, 1H), 0.81 (d, 6H,
13
1
2
30.9, 129.7, 128.3, 127.3, 122.1, 115.47, 100.6, 36.9, 31.1,
J=8 Hz) ppm; C NMR (CDCl ): δ=193.8, 189.0, 158.5,
3
1
19
2.3, 21.2 ppm; Sn NMR (CDCl ): δ = − 397.48 ppm;
144.0, 139.9, 136.1, 133.7, 133.2, 129.3, 128.9, 128.5, 125.6,
3
+
119
ESI–MS: m/z calcd. for C H ClNO Sn ([M+H] ) 628.11,
122.4, 117.4, 100.9, 35.7, 29.2, 22.3 ppm; Sn NMR (CDCl ):
3
3
30
2
3
found 628.40.
δ=−391.47 ppm; ESI–MS: m/z calcd. for C H Cl NO Sn
32
27
2
2
+
(
[M+H] ) 648.05, found 648.40.
(
E)‑3‑[(Dibutylchlorostannyl)oxy]‑2‑[3‑methyl‑1‑(p‑tolylim‑
ino)butyl]‑1H‑inden‑1‑one (10, C H ClNO Sn) Yellow
(E)‑2‑[1‑(4‑Chlorophenylimino)‑3‑methylbutyl]‑3‑[(dibutylch
lorostannyl)oxy]‑1H‑inden‑1‑one (14, C H Cl NO Sn) Yel-
2
9
38
2
solid; yield: 89%; m.p.: 210–212 °C; IR (KBr): ̄ꢀ = 1699
2
8
35
2
2
(
C=O), 1578 (C=N), 1243 (C–O), 705 (Sn–C), 553 (Sn–
low solid; yield: 76%; m.p.: 211–213 °C; IR (KBr): ̄ꢀ=1718
−
1 1
O), 467 (Sn–N) cm ; H NMR (CDCl ): δ=7.73 (d, 2H,
(C=O), 1568 (C=N), 1201 (C–O), 678 (Sn–C), 543 (Sn–O),
3
−
1 1
J = 8 Hz), 7.64 (d, 2H, J = 8 Hz), 7.31 (d, 2H, J = 8 Hz),
472 (Sn–N) cm ; H NMR (CDCl ): δ=7.64–7.42 (m, 5H),
3
7
5
.18 (d, 2H, J=8 Hz), 3.37 (d, 2H, J=8 Hz), 2.48–2.38 (m,
7.31–7.13 (m, 2H), 6.88–6.78 (m, 1H), 3.19–2.94 (m, 7H),
H), 2.31 (s, 3H), 2.11–2.01 (m, 1H), 1.42–0.81 (m, 19H)
2.71 (d, 2H, J = 8 Hz), 2.13–2.04 (m, 1H), 1.82–0.74 (m,
1
3
13
ppm; C NMR (CDCl ): δ = 194.3, 188.7, 159.4, 140.0,
17H) ppm; C NMR (CDCl ): δ = 193.7, 188.3, 159.6,
3
3
1
2
38.2, 135.5, 133.6, 131.9, 130.5, 128.9, 100.0, 38.7, 30.2,
145.0, 137.2, 136.5, 133.2, 132.1, 130.9, 129.4, 98.0, 37.7,
119
119
7.1, 25.7, 23.6, 22.5, 21.1, 14.1 ppm; Sn NMR (CDCl ):
28.7, 26.8, 25.4, 21.5, 20.4, 13.8 ppm; Sn NMR (CDCl ):
3
3
δ=−298.21 ppm; ESI–MS: m/z calcd. for C H ClNO Sn
δ = − 273.46; ESI–MS: m/z calcd. for C H Cl NO Sn
2
9
38
2
28 35
2
2
+
+
(
[M+H] ) 588.17, found 588.40.
([M+H] ) 608.11, found 608.60.
(
E)‑3‑[(Chlorodiethylstannyl)oxy]‑2‑[3‑methyl‑1‑(p‑tolylim‑
(E)‑3‑[(Chlorodiethylstannyl)oxy]‑2‑[1‑(4‑chlorophenylimino)‑
3‑methylbutyl]‑1H‑inden‑1‑one (15, C H Cl NO Sn) Yel-
ino)butyl]‑1H‑inden‑1‑one (11, C H ClNO Sn) Yellow
2
5
30
2
24 27
2
2
solid; yield: 82%; m.p.: 198–200 °C; IR (KBr): ̄ꢀ = 1712
low solid; yield: 86%; m.p.: 202–204 °C; IR (KBr): ̄ꢀ=1720
(
C=O), 1587 (C=N), 1108 (C–O), 692 (Sn–C), 548 (Sn–
(C=O), 1567 (C=N), 1166 (C–O), 702 (Sn–C), 543 (Sn–O),
−
1
1
−1 1
O), 471 (Sn–N) cm ; H NMR (CDCl ): δ=7.78 (d, 2H,
461 (Sn–N) cm ; H NMR (CDCl ): δ=7.61–7.39 (m, 4H),
3
3
J=8 Hz), 7.66 (d, 2H, J=8 Hz), 7.33 (d, 2H), 7.24 (d, 2H,
J = 8 Hz), 2.99 (d, 2H, J = 8 Hz), 2.32 (s, 3H), 2.15–2.04
7.22 (d, 2H, J=8 Hz), 6.90 (d, 2H, J=8 Hz), 2.97 (d, 2H,
J=8 Hz), 2.27–2.19 (d, 2H), 2.09–1.74 (m, 1H), 1.64–1.52
1
3
13
(
m, 1H), 1.77–1.69 (m, 4H), 1.32–0.91 (m, 12H) ppm;
C
(m, 4H), 1.30–0.90 (m, 12H) ppm; C NMR (CDCl ):
3
NMR (CDCl ): δ=193.4, 189.3, 158.6, 141.2, 138.2, 136.7,
δ=192.4, 187.5, 157.1, 144.0, 139.2, 138.5, 134.1, 133.4,
3
119
1
2
33.3, 130.1, 126.7, 129.4, 100.2, 35.3, 27.6, 25.4, 22.1,
129.3, 125.7, 100.8, 35.9, 29.6, 25.2, 21.6, 15.4 ppm; Sn
1
19
1.5, 15.5 ppm; Sn NMR (CDCl ): δ = − 233.60 ppm;
NMR (CDCl ): δ=−203.38 ppm; ESI–MS: m/z calcd. for
3
3
+
+
ESI–MS: m/z calcd. for C H ClNO Sn ([M+H] ) 532.11,
C H Cl NO Sn ([M+H] ) 552.05, found 552.70.
2
5
30
2
24 27
2
2
found 532.70.
(E)‑3‑[(Chlorodimethylstannyl)oxy]‑2‑[1‑(4‑chlorophenylimino)‑
(
E)‑3‑[(Chlorodimethylstannyl)oxy]‑2‑[3‑methyl‑1‑(p‑tol‑
3‑methylbutyl]‑1H‑inden‑1‑one (16, C H Cl NO Sn) Yel-
2
2
23
2
2
ylimino)butyl]‑1H‑inden‑1‑one (12, C H ClNO Sn) Yellow
low solid; yield: 82%; m.p.: 189–191 °C; IR (KBr): ̄ꢀ=1709
23
26
2
solid; yield: 90%; m.p.: 201–203 °C; IR (KBr): ̄ꢀ = 1709
(C=O), 1562 (C=N), 1189 (C–O), 697 (Sn–C), 552 (Sn–O),
−
1 1
(
C=O), 1588 (C=N), 1073 (C–O), 689 (Sn–C), 543 (Sn–
451 (Sn–N) cm ; H NMR (CDCl ): δ = 7.62–7.38 (m,
3
−
1 1
O), 463 (Sn–N) cm ; H NMR (CDCl ): δ=7.79 (d, 2H,
4H), 7.22 (d, 2H, J=8 Hz), 6.89 (d, 2H, J=8 Hz), 2.96 (d,
3
J = 8 Hz), 7.68 (d, 2H, J = 8 Hz), 7.34 (d, 2H, J = 8 Hz),
2H, J=8 Hz), 2.01–1.91 (m, 1H), 1.71 (s, 6H), 0.93 (d, 6H,
13
7
.21 (d, 2H, J=8 Hz), 2.98 (d, 2H, J=8 Hz), 2.30 (s, 3H),
.11–2.01 (m, 1H), 1.69 (s, 3H), 0.87 (d, 6H, J=8 Hz) ppm;
J=8 Hz) ppm; C NMR (CDCl ): δ=194.3, 189.1, 159.9,
3
2
140.2, 139.0, 136.1, 133.6, 131.5, 128.2, 126.1, 102.1, 35.9,
1
3
119
C NMR (CDCl ): δ = 195.1, 189.8, 159.4, 140.8, 139.2,
25.1, 21.7, 16.3 ppm; Sn NMR (CDCl ): δ=−178.30 ppm;
3
3
1
3

Synthesis, characterization, in vitro antimicrobial and QSAR studies of diorganotin(IV)…
+
ESI–MS: m/z calcd. for C H Cl NO Sn ([M+H] ) 524.02,
7. Shpakovsky DB, Banti CN, Mukhatova EM, Gracheva YA, Osi-
22
23
2
2
pova VP, Berberova NT, Albov DV, Antonenko TA, Aslanov LA,
Milaeva ER, Hadjikakou SK (2014) Dalton Trans 43:6880
Bekhit AA, Fahmy HT, Rostom SA, Baraka AM (2003) Eur J Med
Chem 38:27
found 524.70.
8
9
.
.
Pharmacology
Rathelot P, Azas N, El-Kashef H, Delmas F, Di Giorgio C, Timon-
David P, Maldonado J, Vanelle P (2002) Eur J Med Chem 37:671
All the newly synthesized compounds were assessed for
their in vitro antimicrobial activity against Gram positive
bacterial strains, viz., B. cereus (MTCC 10072), S. aureus
10. Chavan SP, Sivappa R (2004) Tetrahedron Lett 45:3941
1
1. de Oliveira KN, Andermark V, Onambele LA, Dahl G, Prokop A,
Ott I (2014) Eur J Med Chem 87:794
1
2. Ge R, Wang YJ, Tang L, Cheng JM, Han LG, Li YL, Li QS (2014)
Appl Organomet Chem 28:204
(
NCIM 2901) and Gram negative bacterial strains, viz., E.
coli (MTCC 732), P. aeruginosa (MTCC 424), and fungal
strains, viz., A. favus (ATCC 76801), A. niger (MTCC
13. Iqbal H, Ali S, Shahzadi S (2015) Cogent Chem 1:1029039
1
4. Dokorou V, Kovala-Demertzi D, Jasinski JP, Galani A, Demertzis
MA (2004) Helv Chim Acta 87:1940
9
933), and C. albicans (MTCC 227) at diꢀerent concentra-
1
5. Kovala-Demertzi D, Dokorou V, Primikiri A, Vargas R, Silvestru
C, Russo U, Demertzis MA (2009) J Inorg Biochem 103:738
tions under the standard set of conditions. Minimum inhibi-
3
tory concentration (MIC, µmol/cm ) was calculated by serial
16. Singh RV, Chaudhary P, Chauhan S, Swami M (2009) Spectro-
chim Acta Part A 72:260
dilution method.
1
7. Chaudhary A, Agarwal M, Singh RV (2006) Appl Organomet
Chem 20:295
1
8. Sharma A, Jain A, Saxena S (2015) Appl Organomet Chem
QSAR studies of the Schiꢀ bases and their
diorganotin(IV) complexes
2
9:499
1
2
9. Chauhan HPS, Shaik NM (2005) J Inorg Biochem 99:538
0. Bhatra P, Sharma J, Sharma RA, Singh Y (2017) Appl Organomet
Chem 31:e3639
For QSAR study a data set of synthesized compounds with
diꢀerent antimicrobial activities excluding outliers were
2
2
1. Shah FA, Sabir S, Fatima K, Ali S, Qadri I, Rizzoli C (2015)
Dalton Trans 44:10467
used. The antimicrobial activity was calculated in MIC
2. Jain M, Gaur S, Diwedi SC, Joshi SC, Singh RV, Bansal A (2004)
Phosphorus. Sulfur Silicon Relat Elem 179:1517
3
(
µmol/cm ) and it was converted into the corresponding
pMIC (− logMIC). The structures of the molecules were
optimized by using Marvin Sketch. The molecular param-
eters including one-, two-, and three-dimensional descrip-
tors were calculated. The pre-optimization of the structures
of test compound was performed by molecular mechanics
force ꢂeld (MM) process of Hyperchem 6.03 [53] and the
resultant geometries were further developed by means of
the semiempirical method PM3 (Parametric Method 3). A
gradient norm limit of 0.01 kcal/Ǻ was used for the geom-
etry optimization. The minimum energy structure of every
molecule was taken for the calculation of physicochemical
parameters using TSAR 3.3 software for Windows [54].
The regression analysis was done using the SPSS software
package [55]. Predictive power and model’s corpulence were
23. Sirajuddin M, Ali S, McKee V, Sohail M, Pasha H (2014) Eur J
Med Chem 84:343
2
2
2
4. Nath M, Vats M, Roy P (2013) Eur J Med Chem 59:310
5. Watanabe M, Watanabe K (2002) Vet Hum Toxicol 44:140
6. Jankovics H, Pettinari C, Marchetti F, Kamu E, Nagy L, Troyanov
S, Pellerito L (2003) J Inorg Biochem 97:370
2
2
7. Danish M, Raza MA, Ilyas T, Sharif A, Anjum N (2015) Med
Chem 5:373
8. Awang N, Kamaludin NF, Hamid A, Mokhtar NWN, Rajab NF
(
2012) Pak J Biol Sci 15:833
29. Yang Y, Hong M, Xu L, Cui J, Chang G, Li D, Li C (2016) J
Organomet Chem 804:48
3
3
3
3
3
0. Nath M, Yadav R, Gielen M, Dalil H, Vos DD, Eng G (1997) Appl
Organomet Chem 11:727
1. Yin HD, Hong M, Li G, Wang DQ (2005) J Organomet Chem
690:3714
2. Prasad KS, Kumar LS, Prasad M, Revanasiddappa HD (2010)
Bioinorg Chem Appl 2010:1
2
assessed by means of cross-validation coeꢁcient q .
3. Tabassuma S, Khan RA, Arjmand F, Sen S, Kayal J, Juvekar AS,
Zingde SM (2011) J Organomet Chem 696:1600
4. Kumar D, Singh VK, Khiwar SS, Saxena N (2014) J Drug Deliv
Ther 4:73
References
35. Kumar D, Singh VK, Khiwar SS, Saxena N (2014) J Biomed
Pharm Res 3:30
3
3
3
6. Dawara L, Singh RV (2011) App Organomet Chem 25:643
7. Jayabalakrishnan C, Natarajan K (2002) Trans Met Chem 27:75
8. Dhawan SN, Dasgupta S, Mor S, Gupta SC (1993) Ind J Hetero-
cycl Chem 2:155
1
2
3
.
.
.
Thumar NJ, Patel MP (2012) Med Chem Res 21:1751
Peto J (2011) Nature 411:390
Chopra I, Schoꢂeld C, Everett M, O’Neill A, Miller K, Wilcox M,
Frere JM, Dawson M, Czapleavski L, Courvalin P (2008) Lancet
Infect Dis 8:133
3
4
4
9. Mor S, Nagoria S (2015) Chem Biol Interface 5:389
0. Malhotra R, Mehta J, Puri JK (2007) Cent Eur J Chem 5:858
1. Srinivas P, Suresh T, Revanasiddappa M, Khasim S (2008) J
Chem 5:627
4
.
Zamudio-Rivera LS, George-Tellez R, López-Mendoza G,
Morales-Pacheco A, Flores E, Höpꢃ H, Barba V, Fernandez FJ,
Cabirol N, Beltrán HI (2005) Inorg Chem 44:5370
Gaur S, Fahmi N, Singh RV (2007) Phosphorus. Sulfur Silicon
Relat Elem 182:853
4
4
2. Nath M, Yadav R (1997) Bull Chem Soc Jpn 70:1331
3. Kapoor R, Gupta A, Kapoor P, Venugopalan P (2003) Appl Orga-
nomet Chem 17:607
5
6
.
.
Khan RA, Yadav S, Hussain Z, Arjmand F, Tabassum S (2014)
Dalton Trans 43:2534
1
3

P. Khatkar et al.
4
4
4. Buntine MA, Kosovel FJ, Tiekink ER (2003) Cryst Eng Commun
:331
5. Dakternieks D, Duthie A, Smyth DR, Stapleton CP, Tiekink ER
50. Hansch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lien EJ
(1973) J Med Chem 16:1207
5
51. Kier LB, Hall LH (1976) Molecular connectivity in chemistry and
drug research. Academic Press, New York
(
2003) Organometallics 22:4599
4
4
6. Dubey RK, Baranwal P, Jha AK (2012) J Coord Chem 65:2645
7. Czympiel L, Lekeu JM, Hegemann C, Mathur S (2017) Inorg
Chim Acta 455:197
52. Kumar A, Narasimhan B, Kumar D (2007) Bioorg Med Chem
15:4113
53. Hyperchem 6.0 (1993) Hypercube Inc, Gainesville
54. TSAR 3D Version 3.3 (2000) Oxford Molecular Limited
55. SPSS for Windows, version 10.05 (1999) SPSS Inc, Bangalore
4
4
8. Kashar TI (2014) Eur Chem Bull 3:878
9. Sallam SA, Orabi AS, El-Shetary BA, Lentz A (2002) Trans Metal
Chem 27:447
1
3