Synthesis, antibacterial evaluation and QSAR analysis of Schiff base complexes derived from [2,2′-(ethylenedioxy)bis(ethylamine)] and aromatic aldehydes

Article abstract of DOI:10.1039/c5md00554j

Two new Schiff bases derived from 1-hydroxy-2-naphthaldehyde/2-hydroxy benzaldehyde with 2,2′-(ethylenedioxy)bis(ethylamine) and their organosilicon and organotin complexes have been synthesized and characterized by spectroscopic techniques (UV-vis, IR an

Full text of DOI:10.1039/c5md00554j

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Synthesis, antibacterial evaluation and QSAR analysis of Schiff base complexes derived
from [2,2′ꢀ(ethylenedioxy)bis(ethylamine)] and aromatic aldehydes†
Jai Devia* • Suman Devia • Ashwani Kumarb
a
Department of Chemistry, Guru Jambheshwar University of Science and Technology
Hisarꢀ125001, Haryana, India
b
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and
Technology Hisarꢀ125001, Haryana, India
Email jaidevi_gju@yahoo.com
†The authors declare no competing interests.
Two new Schiff bases derived from 1ꢀhydroxyꢀ2ꢀnapthaldehyde/2ꢀhydroxy benzaldehyde with
2,2′ꢀ(ethylenedioxy)bis(ethylamine) and their organosilicon and organotin complexes have been
synthesized and characterized by spectroscopic techniques (UVꢀVis, IR and NMR) in
combination with elemental analyses. Spectral studies suggest bonding between central atom and
ligands in a penta and hexa coordinated fashion. Derived complexes and their corresponding
ligands were evaluated for their antibacterial activity against Gram positive bacteria viz.
Staphylococcus epidermidis, Staphylococcus hominis and Gram negative bacteria viz.
Pseudomonas aeruginosa and Klebsiella pneumonia and this study revealed that compounds 29,
30 and 34 exhibited antibacterial activities even better than standard drug ciprofloxacin. For most
of the complexes, higher activity was observed on coordination with silicon and tin atoms as
compared to their respective ligands. All these compounds were selected to execute QSAR
analysis in order to correlate antibacterial activity with significant structural parameters. Statistical
parameters used were Dipole, HOMO, CVolume and Total Energy.
Keywords: Organosilicon and organotin complexes, 2ꢀhydroxy benzaldehyde, antibacterial,
spectral studies, QSAR.
1. Introduction
The universal escalation in the rate of microbial resistance to various antibiotics is a terrifying
aspect, leading to reduction in the efficacy of treatments.1,2,3 So effective treatment and
implementation of improved drugs are the only way to overcome this exigency,4 which inspires
researchers to synthesize novel drugs with negligible microbial resistance. Schiff bases play key
role in the development of coordination chemistry to form stable complexes.5 Probably, Schiff
1

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base formation eases the absorption of the drugs. Schiff bases have been synthesized and widely
used because of their various significant properties like thermal stability, relevant biological
application, high flexibility and medicinal efficacy. Furthermore, it has also been reported that
Schiff base complexes of silicon and tin are known to possess immense chemotherapeutic
importance
as
antimicrobial,6ꢀ10
antimalarial,11
antiꢀinflammatory,12
antiviral,13
antihypertensive,14 anti HIV, antitubercular, anticonvulsant,15 anticancer16,17 and antifertility
agent.18 These are also used as herbicides, insecticides and plant growth regulators.19,20
Quantitative structure activity relationship (QSAR) is one of the most important areas in
chemometrics and is a significant tool to correlate biological activity with structural properties of
the compounds that helps in the process of development of new molecules and rational drug
designs. Numbers of structural descriptors are used to correlate the antibacterial activity of
compounds on the basis of QSAR model and best descriptors are deduced from the analysis.
Encouraged by the above findings and our interest in the field of silicon and tin complexes,
Schiff base ligands of amino ether [2,2′ꢀ(ethylenedioxy)bis(ethylamine)] and 1ꢀhydroxy
napthaldehyde/2ꢀhydroxy benzaldehyde and their organosilicon(IV) and organotin(IV)
complexes have been prepared and characterized with the help of conductance measurements,
elemental analyses, UVꢀVis, IR, and NMR (1H, 13C, 29Si, and 119Sn) spectroscopy. All the
synthesized compounds have been screened against several bacteria, and a comparative
description of their activities and quantitative structure–activity relationship studies have been
incorporated in the current results.
2. Results and discussion
2.1 Chemistry
The Schiff base ligands 1 [H2L1] and 18 [H2L2] were prepared by reaction of 2,2′ꢀ
(ethylenedioxy)bis(ethylamine) and 1ꢀhydroxy napthaldehyde/2ꢀhydroxy benzaldehyde (1:2
molar ratio) in ethanol (Scheme 1). The spectral data and elemental analysis of the synthesized
ligands and their complexes were in good agreement with their structure, indicating the purity of
all compounds. The analytical data of the complexes indicated a 1:1 and 2:1 metal to ligand
stoichiometry. Molar conductance values of 10ꢀ3 M solution of these compounds fall in the range
of 07ꢀ16 ohmꢀ1 cm2 molꢀ1 indicating non electrolytic nature.21 Low conductivity values are in
2

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good agreement with low solubility of complexes in ethanol, chloroform, acetone and most of
the organic solvents. All the complexes are soluble in DMSO and DMF.
OH
CHO
NH2
NH2
O
(CH2)2
O
(CH2)2
(CH2)2
+
Stirred
for 2h
EtOH
2:1 molar ratio
4
5
8
OH
1
10
9
6
7
3
8
a
b
c
2
9
O
N
7
N
O
c
a
2
b
1
OH
6
3
10
5
1
OH
CHO
+
NH2
NH2
(CH2)2
O
(CH2)2
O
(CH2)2
Stirred EtOH
for 2h
2:1 molar ratio
4
5
OH
1
3
2
O
O
N
6
5
N
6
1
OH
2
3
4
18
Scheme 1 Synthesis of ligands
2.2 IR spectra
In order to illustrate the binding mode of Schiff bases to the silicon and tin atom, IR spectrum of
free ligands was studied and compared with the spectra of complexes. The formation of Schiff
base ligands was confirmed by the absence of important stretching vibrations due to aldehyde
v
(CHO) and amino
v
(NH2) moiety and instead, a strong new band appeared at 1624 and 1618
(HꢀC=Nꢀ) group. In the spectra of complexes, (OꢀH)
cmꢀ1 corresponding to the azomethine
v
v
stretching modes at 3560ꢀ3041 cmꢀ1 of ligands22 disappeared in the complexes which revealed
the deprotonation of the hydroxyl OH group of H2L1 and H2L2. This showed that the proton of
the OH group was replaced by the metal ions in the formation of complexes. Similarly, band due
to the
v
(C=N) in the ligands, 23 was shifted to lower frequencies on coordination showing the
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involvement of azomethine group to form five and six membered chelate rings at Si and Sn
centers. The formation of the complexes was also supported by appearance of new bands at 419ꢀ
451 cmꢀ1 and 616ꢀ645 cmꢀ1 due to
v(SiꢀN)/(SnꢀN) and v(SiꢀO)/ν(SnꢀO) modes, respectively. The
spectral region for all the complexes is more or less similar due to similarity in coordination
modes of the ligands with metal centers.
2.3 Electronic spectra
The nature of the ligand field around the central atom was assumed from the electronic spectra.
The spectra of ligands
1
[H2L1] and 18 [H2L2] exhibited a maxima at 391 and 393nm, which may
be due to the nꢀπ* transition of the azomethine group. 24 Blue shift in the complexes was due to
metalꢀligand interaction caused by polarization within the >C=N__ chromophore group, showing
the participation of azomethine nitrogen in coordination with silicon and tin atom. Occurrence of
s
ome medium intensity bands at 210ꢀ229 nm in Schiff base ligands indicated πꢀπ* transition of
benzene ring. These bands remain almost unchanged in the electronic spectra of complexes,
showing non involvement of benzene ring in bond formation.
2.4 1H NMR Spectra
1
The data obtained from H NMR spectral studies provide support to the binding mode of the
ligand’s coordinating sites discussed above in IR. The signals at
proton of and 18 disappeared in the complexes indicating the deprotonation of hydroxyl group
on complexation with central metal atom. The azomethine protons of ligands appeared at
9.00 and 10.83 and shifted in the complexes which suggested the participation of azomethine
group in bond formation. Aliphatic protons (Ha, Hb and Hc) of the ligands appeared at 2.32ꢀ
4.29 and aromatic protons resonated at 6.68ꢀ8.59, and these remains almost at the same
position in the spectra of the complexes showing non participation of these protons. However,
silicon and tin complexes showed additional signals at 0.07ꢀ1.65, 0.21ꢀ1.63, 0.62ꢀ1.55 and
δ 13.91 and δ 11.20 due to OH
1
25
δ
δ
δ
δ
δ
7.91ꢀ8.23 owing to the protons of the methyl, ethyl, butyl and phenyl groups respectively.
2.5 13C NMR Spectra
13C NMR chemical shifts of all the complexes were in the expected resonance. The appearance
of singlet at
δ 158.86 and δ 166.40 in the spectrum confirmed the presence of azomethine (–
CH=N–) carbon in the ligands26 and this shift towards higher value in the complexes suggested
again the participation of azomethine carbon in bond formation with central atom as observed in
1
IR and H NMR. The carbon attached to the hydroxyl group appeared at
δ 149.65ꢀ161.20 and
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this was shifted in the complexes suggesting its coordination. Aliphatic carbon atoms of ligands
appeared in the range of 16.10ꢀ70.57 and carbons of aromatic ring appeared at 110.05ꢀ143.77
δ
δ
that remained unchanged in the complexes, indicating their non participation in bond formation
with central atom. A considerable shift in the position of carbon atoms attached to the different
participating groups clearly shows the bonding of the azomethine nitrogen and hydroxyl oxygen
to the silicon and tin atoms. The signals due to carbon of methyl group attached to silicon and tin
atoms appeared at
δ
7.06ꢀ9.14, whereas signals due to the carbons of ethyl group appeared at
δ
δ
8.43ꢀ10.71 and 41.92ꢀ45.92. However, signals of carbons due to nꢀbutyl group appeared at
δ
8.04ꢀ9.89, 17.87ꢀ19.86, 25.78ꢀ27.89 and 44.01ꢀ46.70. The phenyl group carbons appeared in the
range of 127.66ꢀ138.07. This study further supports the mode of bonding as proved in IR and
1H NMR spectra.
29Si and 119Sn NMR spectra were recorded in CDCl3 and DMSOꢀd6. The spectra
δ
displayed one sharp singlet in each complex indicating the formation of a single species. The
chemical shift values of silicon complexes laid in the region δ ꢀ13.37 to ꢀ18.07 for penta and δ ꢀ
107.25 to ꢀ110.0627,28 for hexa coordinated complexes. 119Sn NMR chemical shifts of the
complexes were also in the range of penta and hexaꢀcoordinated environment, which appeared at δ
ꢀ151.01 to ꢀ156.89 and δ ꢀ300.00 to ꢀ315.76, respectively.29 Therefore, on the basis of
spectroscopic studies, penta and hexa coordinated geometries were assumed for all the synthesized
complexes (Scheme 2).
R
R
R
O
M
N
O
N
O
R
R
M
R
R3MCl
1:2 molar ratio
O
Dry MeOH
Reflux 2h
H2L2
O
O
R2MCl2
1:1 molar ratio
R M R
N
N
(H2C)2
(CH2)2
O
O
M= Sn and Si
(CH2)2
R=Me, Et, Bu and Ph
Scheme 2 Synthesis of complexes
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2.6 Xꢀray diffraction
Xꢀray powder diffraction of the compounds was recorded over the range 2θ = 10ꢀ80 degree and
average crystallite size dXRD was calculated to get insight about dynamics of the compounds. Xꢀ
ray diffraction study of compound
4 showed a clear crystalline peak with maxima at 2θ=19.14
and d = 4.63Ǻ (Fig. 1). Powder XRD of all the other compounds exhibited their crystalline
nature.
Fig. 1 XRD data for compound 4.
2.7 Antimicrobial Evaluation
The Schiff base ligands and their complexes were evaluated for their inhibitory effects on the
growth of Gramꢀpositive bacteria (Staphylococcus epidermidis
, Staphylococcus hominis) and
Gram negative bacteria (Pseudomonas aeruginosa Klebsiella pneumonia) using Agar well
,
diffusion method for determining zone of inhibition and MICs were calculated by micro dilution
technique and their results are summarized in Table 1, 2 and graphical representation for
compounds
1 to 34 is given in Fig. 2. Antibacterial activity was determined by measuring the
diameter of zone showing complete inhibition and minimum concentration that inhibited the
growth of bacteria. DMSO was used as negative control which produced no visible inhibitory
effect on any of the tested bacteria and ciprofloxacin was used as positive control.
Tested ligands
1 and 18 displayed zone of inhibition ranging from 8ꢀ16 mm and in
complexes it increased to 20 mm, showing higher activity of complexes than their respective
ligands. MICs of the synthesized compounds were also calculated which ranged from 0.021 to
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0.084 µmol/mL for ligands and 0.0017 to 0.072 µmol/mL for silicon and tin complexes.
Compound 30 was found to be most potent having maximum zone of inhibition and lowest MIC
against all the bacterial strains used. For Gram positive bacteria S.epidermidis and S.hominis,
compounds 29 (MIC=0.0020 µmol/mL), 34 (MIC=0.0021 µmol/mL), and for Gram negative
bacteria P.aeruginosa, K.Pneumonia compounds 29 (MIC=0.0040 µmol/mL) and 13 (0.0064
µmol/mL) were found to be more active (Table 2). Interestingly, some of the compounds (13
30 and 34) in the entire series were more active than the standard drug ciprofloxacin. However,
ligand
[H2L1] was found to be inactive against both Gram negative bacteria.
The presence of hydroxyl and azomethine groups in the Schiff bases plays vital role for
, 29,
1
biological activity which helps in transformation reaction in biological systems. The silicon and
tin complexes were found to be more active as compared to their parent Schiff base ligands
against the same microꢀorganism. The increase in biological activity of the metal complexes may
be due to the effect of silicon and tin atom on the normal cell process. A possible mode of
toxicity increase may be explained in the light of Tweedy’s chelation theory. 30ꢀ32 According to
this concept, on coordination the polarity of the metal atom decreases due to partial sharing of its
positive charge with the donor groups and possible π electron delocalization within the whole
chelate ring system created during coordination. Such chelating enhances the lipophilic character
of central atom, favoring its penetration through the lipid layer of the cell membrane thereby
deactivating respiration process in the microꢀorganism. Furthermore, the mode of action of the
compounds may involve the formation of hydrogen bonds between the azomethine nitrogen atom
and the active centers of cell constituents, which causes interference in the normal cell process.33ꢀ
35
Among all the complexes, phenyl derivatives were found to be more potent against
bacterial strains as compared to other derivatives. The order of activity for the compounds was
Ph>Bu>Et>Me. Phenyl group facilitates binding to biological molecules by π–π interactions and
increases lipophilic character, which in turn favors the permeation of the complexes through the
lipid layer of the cell membrane36 and also electron releasing ability of phenyl group increases
electron density over azomethine nitrogen which results in stronger interactions with active
centers of cell constituents. Further, all compounds were found to be more active against Gram
positive bacterial strains as compared to Gram negative because outer membrane of Gram
negative bacteria is more complex, containing lipopolysaccharide which protects the bacteria
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from EOs’ disruption and acts as a barrier to many environmental substances. The compounds
containing phenyl ring (ligand 18 and its complexes) were found to exhibit more efficacy as
compared to compounds with naphthyl ring (ligand
et al., 2005.37
1 and its complexes) as reported by Lukevics
Table 1 Zone of Inhibition of compounds (Agar well diffusion method)
Comp
No.
Compounds
Zone of Inhibition (mm)
S.hominis P.aeruginosa
Gram +ve bacteria
S.epidermidis
K.pneumonia
Gram ꢀve bacteria
1.
2.
3.
4.
5.
6.
7.
8.
H2L1
10
8
9
ꢀ
9
ꢀ
ꢀ
11
15
16
9
Me2Sn(L1)
Et2Sn(L1)
Bu2Sn(L1)
Ph2Sn(L1)
Me2Si(L1)
Et2Si(L1)
12
15
20
20
13
14
16
18
15
15
18
19
14
15
16
19
16
17
17
20
20
17
18
19
20
17
18
19
20
17
17
17
20
19
10
17
19
10
11
15
17
9
10
17
19
9
10
15
16
8
10
14
17
9
9
Bu2Si(L1)
Ph2Si(L1)
(Me3Sn)2L1
(Et3Sn)L1
(Bu3Sn)2L1
(Ph3Sn)2L1
(Me3Si)2L1
(Et3Si)2L1
(Bu3Si)2L1
(Ph3Si)2L1
H2L2
11
17
8
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
11
17
18
10
11
12
16
16
16
17
19
20
17
17
18
19
16
16
18
20
17
17
19
20
20
8
10
15
10
15
15
17
13
15
16
17
18
15
16
16
19
15
15
17
19
15
17
17
19
20
9
10
15
15
17
17
19
20
15
15
19
20
16
18
20
20
15
15
19
19
20
Me2Sn(L2)
Et2Sn(L2)
Bu2Sn(L2)
Ph2Sn(L2)
Me2Si(L2)
Et2Si(L2)
Bu2Si(L2)
Ph2Si(L2)
(Me3Sn)2L2
(Et3Sn)2L2
(Bu3Sn)2L2
(Ph3Sn)2L2
(Me3Si)2L2
(Et3Si)2L2
(Bu3Si)2L2
(Ph3Si)2L2
Ciprofloxacin
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Table 2 Minimum Inhibitory Concentrations (MICs) of compounds
Comp
No.
1.
Compounds
S.epidermidis
S.hominis
P.aeruginosa
K.pneumonia
Gram +ve bacteria
0.065
0.049
0.023
0.005
0.0051
0.060
0.027
0.012
0.011
0.019
0.017
0.0072
0.0067
0.049
Gram ꢀve bacteria
H2L1
0.065
0.049
0.023
0.0109
0.0103
0.0600
0.055
0.025
0.023
0.038
0.017
0.0072
0.0032
0.024
ꢀ
ꢀ
ꢀ
2.
3.
4.
5.
6.
7.
8.
9.
Me2Sn(L1)
Et2Sn(L1)
Bu2Sn(L1)
Ph2Sn(L1)
Me2Si(L1)
Et2Si(L1)
0.049
0.047
0.021
0.020
0.0600
0.027
0.025
0.023
0.038
0.017
0.0072
0.0129
0.049
0.043
0.017
0.015
0.042
0.029
0.028
0.025
0.011
0.036
0.034
0.030
0.013
0.021
0.0097
0.0040
0.0035
0.029
0.025
0.009
0.0042
0.045
0.047
0.021
0.0103
0.0600
0.055
0.025
0.023
0.038
0.034
0.014
0.0064
0.024
0.021
0.0087
0.0077
0.084
0.059
0.056
0.025
0.011
0.072
0.068
0.030
0.027
0.043
0.019
0.008
0.007
0.059
0.051
0.019
0.008
0.011
Bu2Si(L1)
Ph2Si(L1)
(Me3Sn)2L1
(Et3Sn)L1
(Bu3Sn)2L1
(Ph3Sn)2L1
(Me3Si)2L1
(Et3Si)2L1
(Bu3Si)2L1
(Ph3Si)2L1
H2L2
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
0.021
0.021
0.0087
0.0038
0.0210
0.0149
0.0141
0.0063
0.0029
0.0181
0.0170
0.0150
0.0069
0.0109
0.0048
0.0020
0.0017
0.0149
0.0127
0.0024
0.0021
0.022
0.0087
0.0077
0.021
0.0149
0.0141
0.0063
0.011
0.0181
0.0170
0.0075
0.0069
0.0109
0.0097
0.0040
0.0017
0.0149
0.0127
0.0049
0.0021
0.011
Me2Sn(L2)
Et2Sn(L2)
Bu2Sn(L2)
Ph2Sn(L2)
Me2Si(L2)
Et2Si(L2)
Bu2Si(L2)
Ph2Si(L2)
(Me3Sn)2L2
(Et3Sn)2L2
(Bu3Sn)2L2
(Ph3Sn)2L2
(Me3Si)2L2
(Et3Si)2L2
(Bu3Si)2L2
(Ph3Si)2L2
Ciprofloxacin
MIC value in µmol/mL
(ꢀ) compounds found inactive
DMSO was used as negative control
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S.epidermidis
S.hominis
0.1
0.08
0.06
0.04
0.02
P.aeruginora
K.pneumonia
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
Compounds
Fig. 2 Graphical representation of compounds (
2.8 QSAR studies
1ꢀ34) for antibacterial activity.
A group of linear models consisting of dissimilar sets of parameters with different performances
was obtained by the application of Multiple Linear Regression method. However the models
with good fitting ability, predictive power, robustness, stability and generalizability were
retained for further study. Different outliers were detected for different activities and those were
not used for the model development. Statistically significant linear models were developed for
activity against S. hominis
, P. aeruginosa, and K. pneumonia. However, no statistically
significant QSAR model was found for activity against S. epidermidis
.
The best QSAR model for activity against S. hominis was a multiparametric model
containing three descriptors as shown in equation (1) below.
pMICsh = + 0.0719 (± 0.0479) Dipole – 0.9546 (± 0.3558) HOMO + 0.0013 (± 0.0005)
CVolume –7.2027 (± 3.1034)
(1)
Ntr = 24; Npred = 6; R2 = 0.7682; R2 = 0.7334; R2–R2 = 0.0348; s = 0.195; CCCtr = 0.8689;
adj
adj
RMSEtr = 0.1776; F = 22.092; Q2LOO = 0.678; Q2LMO = 0.5801; R2Yscr = 0.1276;
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RMSEcv = 0.2092; Q2 = 0.7160; Q2F2 = 0.7020; Q2F3 = 0.7016.
F1
Ntr is number of compounds in training set and Npred is number of compounds in prediction set.
The sign of coefficients of parameters shows that Dipole and CVolume are directly
correlated with the activity while HOMO is negatively correlated with the activity. The
standardized coefficients of Dipole, HOMO and CVolume are 0.5409, ꢀ0.7412, and 0.7603
respectively which indicates that CVolume and HOMO are more almost equally contributing
towards activity but more than Dipole. CVolume represents the cosmo volume of the molecules
related to the bulkiness of molecular framework. Generally, the compounds with large descriptor
value have higher activity e.g. compounds 30 and 34. HOMO tells about the nucleophilicity of
the molecules. Some compounds with higher nucleophilicity are less active e.g. compounds
2, 3,
6
and . Dipole is related to the polarity of the compounds. Four compounds namely 18, 21
7
1
,
and 33 were found to be outliers in this model. As compound 33 was outlier in this model, hence
compound 29 was taken in prediction set.
The QSAR model for activity against P. aeruginosa is given in equation (2).
pMICpa = 0.0017(± 0.0007) HF + 0.0474 (± 0.0302) Dipole – 0.631 (± 0.2298) HOMO + 0.0011
(± 0.0004) CVolume – 4.3119 (± 1.9747)
Ntr = 22; Npred = 6; R2 = 0.8782; R2adj = 0.8496; R2–R2adj = 0.0286; s = 0.1204; CCCtr = 0.9352;
RMSEtr = 0.1059; F = 30.6543; Q2 = 0.8138; Q2 = 0.6628; R2Yscr = 0.1903;
(2)
LOO
LMO
RMSEcv = 0.1380; Q2 = 0.7268; Q2F2 = 0.7205; Q2F3 = 0.8479.
F1
Positive signs of coefficients of HF, Dipole and CVolume show that these descriptors are
in direct correlation with the activity while negative coefficient of HOMO indicates its indirect
correlation. Standardized coefficients of HF, Dipole, HOMO and CVolume are 0.4346, 0.4337, –
0.6267, and 0.6233 respectively. This illustrates that role of HOMO and CVolume descriptors in
activity determination is almost equal and opposite but more than that of HF and Dipole which in
turn are also equally contributing. In general compounds with higher values of CVolume and low
values of HOMO possess higher activities e.g. compounds 30
18 and 29 were found to be outliers for this QSAR model.
, 33 and 34. Compounds 12, 13, 17,
The antimicrobial activity against K. pneumonia was explained by total energy (TE) of
the molecules. The monoparametric QSAR model developed is depicted in equation (3).
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pMICkp = –0.0002 TE + 0.3495 (± 0.2405)
(3)
Ntr = 24; Npred = 6; R2 = 0.8509; R2adj = 0.8441; R2–R2adj = 0.0068; s = 0.1428; CCCtr = 0.9195;
RMSEtr = 0.1367; F = 125.5682; Q2 = 0.8286; Q2 = 0.7899; R2Yscr = 0.0432;
LOO
LMO
RMSEcv = 0.1466; Q2 = 0.7466; Q2F2 = 0.6174; Q2F3 = 0.8841.
F1
Negative sign of coefficient of TE shows that it is indirectly correlated with the activity.
It can be observed from the table 3 as the value of TE decreases, activity increases e.g. TE value
for compounds 10
, 11, 12, 13 decreases in the same order (–6501.05, ꢀ7399.93, ꢀ9199.33, ꢀ
10344.67) and their activity increases in the same order (1.420, 1.469, 1.854, 2.194). This shows
that more stable molecules are more active. Compounds
this model.
5 and 22 were detected to be outliers in
Calculated statistical parameters of all these models indicate that above discussed models
are statistically sound models. From the correlation table 4 it can be observed that the descriptors
used in multiparametric model are poorly correlated with each other which attest that the built
models are free from the problem of colinearity.
Table 3 Calculated properties of the compounds
Comp.
HF
TE
EE
CCR
Dipole HOMO LUMO CArea CVolume
1
2
ꢀ46.6356 ꢀ5368.76 ꢀ41606.6 36237.8 1.60068 ꢀ8.696
ꢀ67.9826 ꢀ5758.75 ꢀ60951.9 55193.16 7.2269 ꢀ7.753
ꢀ0.726
512.1
555.18
612.82
655.21
746.8
ꢀ0.323 446.47
ꢀ0.343 467.71
ꢀ0.476 546.13
ꢀ0.518 523.65
ꢀ0.747 423.46
ꢀ0.686 443.37
ꢀ0.709 507.68
ꢀ0.907 505.08
3
ꢀ72.8112 ꢀ6058.36 ꢀ67447.4 61389.04 7.11534 ꢀ7.754
ꢀ95.0603 ꢀ6658.24 ꢀ79146.6 72488.4 4.78975 ꢀ7.909
ꢀ6.69817 ꢀ7039.91 ꢀ86085.3 79045.35 6.98592 ꢀ7.914
ꢀ124.569 ꢀ5772.67 ꢀ62576.9 56804.26 6.43661 ꢀ7.838
4
5
749.78
607.99
652.54
740.56
737.43
784.31
926.43
1172.32
1200.46
751.58
882.42
1172.61
6
7
ꢀ133.198 ꢀ6072.38
ꢀ69677
63604.62 6.72499 ꢀ7.789
8
ꢀ154.085 ꢀ6672.15 ꢀ82405.2 75733.08 6.60143 ꢀ7.806
ꢀ78.3892 ꢀ7054.49 ꢀ88190.5 81135.99 7.25406 ꢀ7.831
ꢀ58.1441 ꢀ6501.05 ꢀ63039.8 56538.76 0.94166 ꢀ8.078
ꢀ72.8677 ꢀ7399.93 ꢀ82244.5 74844.59 1.41499 ꢀ8.033
9
10
11
12
13
14
15
16
ꢀ0.52
646.44
ꢀ0.568 714.93
ꢀ0.589 891.31
ꢀ0.735 905.33
ꢀ135.46
ꢀ9199.33 ꢀ122060 112860.6 1.20566 ꢀ8.101
132.4914 ꢀ10344.7 ꢀ138101 127756.2 1.59597 ꢀ8.244
ꢀ164.514 ꢀ6528.73 ꢀ66318.1 59789.36 3.40601 ꢀ7.991
ꢀ0.66
608.59
ꢀ188.192 ꢀ7428.02 ꢀ83490.1 76062.12 1.0861
ꢀ8.233
ꢀ0.582 685.76
ꢀ0.596 863.35
ꢀ264.698 ꢀ9377.59 ꢀ132888 123510.1 0.68802 ꢀ8.305
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17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
ꢀ29.4285 ꢀ10374.2 ꢀ157191 146817.1 2.36954
ꢀ80.5082 ꢀ4332.28 ꢀ29628.6 25296.32 1.71612
ꢀ8.21
ꢀ9.27
ꢀ0.78
792.56
1165.75
440.98
505.48
544.74
641.55
640.22
490.95
535.32
617.58
622.42
670.31
808.33
1056.9
1083.84
631.71
788.79
1079.73
1061.13
ꢀ0.422 422.47
ꢀ0.371 387.32
ꢀ0.395 411.01
ꢀ0.375 478.92
ꢀ0.581 469.14
ꢀ0.711 365.31
ꢀ89.1741 ꢀ4721.9 ꢀ43472.3 38750.37 5.99407 ꢀ8.048
ꢀ93.4193 ꢀ5021.49 ꢀ49111.4 44089.89 5.93089 ꢀ8.03
ꢀ117.448 ꢀ5621.42 ꢀ60162.6 54541.14 7.24447 ꢀ7.965
ꢀ25.7499 ꢀ6003.05 ꢀ65404.2 59401.18 6.03541 ꢀ8.216
ꢀ153.332 ꢀ4736.16 ꢀ45180.3 40444.1 8.45846 ꢀ8.157
ꢀ160.897 ꢀ5035.89 ꢀ50963.7 45927.77 7.89096 ꢀ8.144
ꢀ0.696
ꢀ0.734
388.8
456
ꢀ182.516 ꢀ5635.71
ꢀ62085
56449.25 8.2242
ꢀ8.165
ꢀ105.305 ꢀ6017.9 ꢀ67825.8 61807.88 7.93307 ꢀ8.303
ꢀ92.0227 ꢀ5464.52 ꢀ51706.4 46241.92 1.57426 ꢀ8.333
ꢀ111.084 ꢀ6363.55 ꢀ70291.6 63928.07 5.59495 ꢀ8.256
ꢀ167.563 ꢀ8162.49 ꢀ112439 104276.3 1.48496 ꢀ8.325
ꢀ0.846 437.86
ꢀ0.425
ꢀ0.194
531.7
590.1
ꢀ0.331 737.06
ꢀ0.706 836.03
ꢀ0.527 538.51
ꢀ0.456 615.55
ꢀ0.139 721.77
ꢀ0.764 785.45
107.0921 ꢀ9307.95 ꢀ118467
ꢀ191.225 ꢀ5492.02 ꢀ49257.4 43765.37 0.19887 ꢀ8.704
ꢀ220.902 ꢀ6391.57 ꢀ65784 59392.41 3.88302 ꢀ8.529
ꢀ305.638 ꢀ8341.26 ꢀ117451 109110 2.96163 ꢀ8.913
ꢀ54.1935 ꢀ9337.77 ꢀ124699 115361.5 0.3915 ꢀ8.939
109159
2.4156
ꢀ8.567
Table 4 Correlation table
HF
TE
EE
CCR
Dipole
HOMO
LUMO
C Area C Volume pMICse pMICsh pMICpa pMICkp
HF
TE
1
ꢀ0.2227
ꢀ0.1549
0.1510
ꢀ0.0371
0.0855
ꢀ0.2748
0.1406
0.0930
0.1665
0.1944
0.2326
0.3542
1
EE
0.9828
1
CCR
ꢀ0.9809 ꢀ0.9999
1
Dipole
HOMO
LUMO
C Area
C Volume
pMICse
pMICsh
pMICpa
pMICkp
0.5205
0.1218
0.2097
0.4142
0.0732
0.1907
ꢀ0.4079
ꢀ0.0704
1
0.5758
1
ꢀ0.1895 ꢀ0.0759 ꢀ0.1087
1
ꢀ0.7380 ꢀ0.2744 ꢀ0.0601
ꢀ0.5950 ꢀ0.1644 ꢀ0.0577 0.9678
ꢀ0.9296 ꢀ0.8672
ꢀ0.9743 ꢀ0.9520
ꢀ0.5786 ꢀ0.6226
ꢀ0.6053 ꢀ0.6167
ꢀ0.6543 ꢀ0.6598
ꢀ0.8626 ꢀ0.8629
0.8629
0.9498
0.6244
0.6168
0.6595
0.8621
1
1
ꢀ0.1913 ꢀ0.3050
ꢀ0.2647 ꢀ0.3956
ꢀ0.3782 ꢀ0.4029
0.1288
0.0423
0.0019
0.5035
0.5862
0.6396
0.5894
0.6178
0.6814
0.8231
1
0.8766
0.8990
0.7534
1
0.8395
0.7125
1
ꢀ0.3625 ꢀ0.0943 ꢀ0.1484 0.7668
0.7443
1
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The value of coefficient of determination R2 is more than 0.75 and the difference between
R2 and R2adj is very less proving that R2adj is very near to coefficient of determination.
Furthermore, the value of CCC is more than 0.85 which is recommended for a good QSAR
model. All these particulars verify the good fitting ability of the developed models. High values
of Q2LOO and Q2LMO show that models have good internal predictive ability and stability. The plot
of Q2
and KXY (the intercorrelation between descriptors and response) (Fig. 3) shows that
LMO
values of Q2
are very close to the value of model Q2. This confirms the robustness and
LMO
stability of the developed models.
(a)
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(b)
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(c)
Fig. 3 Scatter plot of LMO models compared to the QSAR model Q2 for (a) S. hominis (b) P.
aeruginosa (c) K. pneumonia.
Further to ascertain the happenstance of the built models, Y scrambling procedure was
performed. It can be seen that values of R2Yscr are very less as compared to model R2 values
establishing that the developed models were not obtained by chance. Closeness of RMSEtr and
RMSEcv confirms that the demonstrated models have enough generalizability.38
The true predictive power of the QSAR models is ascertained by predicting the
compounds not used in the model creation process because prediction of external chemicals is
most important for practical use of a QSAR model. Therefore the developed models were used to
predict the activity of the compounds not used in model development (20% of the total dataset).
The values of Q2 , Q2 , Q2F3 are high and rather similar confirming the good external predictive
F1
F2
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ability of the created models. Besides, the Williams plot, standardized residuals vs. diagonal
HAT elements, (Fig. 4) was used for prediction and to find out the applicability domain of the
discussed models. It can be seen that all (1ꢀ34) compounds except 33 in QSAR model 2, are
present in the applicability domain with leverage values lesser than the warning h*. The
compounds present in the prediction set were well predicted except 33 in QSAR model 2 which
is present beyond the warning leverage value h* which shows that it is outside the domain of the
model and is wrongly predicted. This compound is also response outlier in case of model 1.
(a)
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(b)
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(c)
Fig. 4 Williams plot of diagonal hat elements vs. standardized residual predictions for QSAR
models against (a) S. hominis (b) P. aeruginosa (c) K. pneumonia. Warning h* is given in
each graph.
The scatter plots of observed versus predicted activity for all models are shown in Fig. 5.
It can be observed that all compounds lie close to the line y = x which means that compounds
were predicted very well. The plots of experimental activity versus residuals are shown in Fig. 5.
Spreading of residuals of both sides of the zero line in random fashion proves that the developed
models are free from propagation as well as systematic errors. The values of predicted activities
along with residuals are shown in Table 5.
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(a)
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(b)
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(c)
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(d)
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(e)
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(f)
Fig. 5 Scatter plots of expermental (Exp. endpoint) vs. predicted activities (a,c,e) and residual
plots (b,d,f) for QSAR models against S. hominis, P. aeruginosa and K. pneumonia
respectively.
Table 5 Experimental and predicted activities of compounds along with residuals
pMICsh
pMICpa
Pred. Residuals Exp.
pMICkp
Pred. Residuals
Comp. Exp.a Pred.b Residuals Exp.
d
1
2
oc
o
o
*
*
*
*
*
*
*
*
*
1.3098 1.4936 0.1838 1.3098 1.4594 0.1496
1.6383 1.5401 ꢀ0.0981 1.3279 1.4916 0.1637 1.3279 1.4477 0.1198
1.9626 1.6368 ꢀ0.3258 1.6778 1.5388 ꢀ0.1390 1.6778 1.5565 ꢀ0.1213
3pe
4
5
1.9872 1.8032 ꢀ0.1839
1.699 1.7988 0.0998
ꢀ
ꢀ
ꢀ
6
7p
8
1.2218 1.5118 0.2899 1.2218 1.3746 0.1528 1.2218 1.3959 0.1741
1.2596 1.5421 0.2825 1.5686 1.3901 ꢀ0.1785 1.2596 1.4503 0.1906
1.6021 1.6608 0.0588 1.6021 1.4532 ꢀ0.1489 1.6021 1.559
1.6383 1.7276 0.0894 1.6383 1.6247 ꢀ0.0136 1.6383 1.6283 ꢀ0.0100
1.4202 1.5689 0.1487 1.4202 1.5654 0.1452 1.4202 1.528 0.1078
1.7696 1.7398 ꢀ0.0297 1.7696 1.6856 ꢀ0.0840 1.4685 1.6909 0.2224
2.1427 2.1008 ꢀ0.0419 1.8539 2.0171 0.1633
ꢀ0.0431
9
10
11
12
o
o
o
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13
14
15p
16
2.4949 2.3009 ꢀ0.1939
1.6198 1.6216 0.0018 1.3098 1.4125 0.1027 1.6198 1.533
1.6778 1.8514 0.1736 1.3665 1.5542 0.1877 1.6778 1.696
o
o
o
2.1938 2.2248 0.0309
ꢀ0.0868
0.0183
2.0605 2.2587 0.1982 1.7696 1.7597 ꢀ0.0099 2.0605 2.0495 ꢀ0.0110
17
18
2.1135 2.2802 0.1667
o
o
o
o
o
o
2.1135 2.2301 0.1166
1.0757 1.1348 0.0591
o
o
o
19
20p
21
1.8268 1.5508 ꢀ0.2760 1.5376 1.4371 ꢀ0.1005 1.2291 1.2055 ꢀ0.0237
1.8508 1.5787 ꢀ0.2721 1.5528 1.4573 ꢀ0.0955 1.2518 1.2598 0.0080
o
o
o
1.6021 1.5408 ꢀ0.0613 1.6021 1.3685 ꢀ0.2335
22
23
24
1.9586 1.8846 ꢀ0.0740 1.9586 1.7956 ꢀ0.1630
1.7423 1.8136 0.0713 1.4437 1.4987 0.0550 1.1427 1.208
1.7696 1.8165 0.0470 1.4685 1.498
o
o
O
0.0654
0.0294 1.1675 1.2624 0.0949
25
26p
27
2.1249 1.9646 ꢀ0.1603 1.5229 1.5778 0.0550 1.5229 1.3711 ꢀ0.1518
2.1612 2.0815 ꢀ0.0796 1.8861 1.7869 ꢀ0.0991 1.5686 1.4404 ꢀ0.1282
1.9626 1.7136 ꢀ0.2490 1.6778 1.5778 ꢀ0.1000 1.3665 1.3401 ꢀ0.0264
2.0132 2.1038 0.0906 2.0132 1.8342 ꢀ0.1790 1.7212 1.5031 ꢀ0.2182
28
29p
30
31
2.3979 2.1887 ꢀ0.2093
o
o
o
2.0969 1.8292 ꢀ0.2677
2.7696 2.5207 ꢀ0.2489 2.4559 2.5418 0.0859 2.1549 2.0368 ꢀ0.1181
1.8268 1.9201 0.0933 1.5376 1.5378 0.0002 1.2291 1.3451 0.1159
1.8962 2.2166 0.3204 1.6021 1.7187 0.1167 1.2924 1.5081 0.2157
32
33p
34
o
o
o
2.0458 2.0831 0.0374 1.7212 1.8616 0.1403
2.6778 2.7015 0.0238 2.3768 2.3835 0.0068 2.0969 2.0422 ꢀ0.0547
a Exp. is experimental endpoint or observed activity.
b Pred. is predicted activity by model equation.
c o denotes outliers.
d * denotes compounds not tested.
e p denotes compounds used in prediction set.
3. Conclusions
In this work, two new Schiff bases and their organotin(IV) and organosilicon(IV) complexes has
been prepared successfully. The bi and tetradentate nature of Schiff bases were established on
the basis of different spectral and analytical techniques. The in vitro antibacterial activity of the
synthesized compounds was evaluated against Gram positive and Gram negative bacteria.
Complexes displayed enhanced antibacterial activity then their respective ligands. QSAR model
developed had good fitting ability and predictive power. Among the synthesized compounds, 29,
30 and 34 possessed the most prominent and consistent activity and compound 30 was most
potent antibacterial agent. Therefore, such compounds can be used for the development of a new
class of antibacterial agents.
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4. Experimental
4.1 Materials and methods
All the chemicals were of reagent grade (supplied by SigmaꢀAldrich and Qualigen) and used as
received without any further purification. All the reactions were carried out under dry nitrogen.
The IR spectra were recorded using a Spectrum BX Series FTꢀIR spectrophotometer in the range
400ꢀ4000 cmꢀ1, using KBr pellets. The NMR (1H, 13C, 29Si and 119Sn) spectra were recorded on
a Bruker Avance II 300 MHz NMR Spectrometer and all chemical shifts (δ) were reported in
parts per million (ppm) downfield from the internal standard tetramethylsilane (TMS) in CDCl3
and DMSOꢀd6. The electronic spectra were recorded in methanol and DMF on a UVꢀVisꢀNIR
Varian Caryꢀ5000 spectrometer. Elemental analyses were carried out on a Perkin Elmer 2400
analyzer. Molar conductance was measured with conductivity bridge type modelꢀ306 Systronics in
DMSO solvent. Powder XRD was carried out on RigakuꢀminiflexꢀII with a source of radiation Cuꢀ
Ka (1.54 Ǻ).
4.2 Synthesis
4.2.1 Schiff base ligand H2L1 (
1). It was synthesized by condensation of 1.46 mL (10 mmol) of
2,2′ꢀ(ethylenedioxy)bis(ethylamine) and 3.44 g (20 mmol) of 1ꢀhydroxyꢀnaphthaldehyde [1:2
molar ratio] in dry ethanol with continuous stirrng for 2h (Scheme 1). Yellow colored crystalline
product obtained was recrystallized from ethanol and dried in vacuum. Progress of reaction was
monitored by thin layer chromatography.
2ꢀ{[2ꢀ(2ꢀ{2ꢀ[(1ꢀHydroxyꢀ1,5ꢀdienylmethylene)ꢀamino]ꢀethoxy}ꢀethoxy)ꢀethylimino]ꢀmethyl}ꢀ
dinapthalene. Yield: (90%). Anal. Calcd. for C28H28N2O4: C, 73.66; H, 6.18; N, 6.14. Found: C,
73.63; H, 6.15; N, 6.17%. 1H NMR [300 MHz, DMSO, δ(ppm)]: 13.91 (s, 1H, OH), 9.00 (s, 1H,ꢀ
N=CꢀH), 7.98ꢀ8.01 (d, Hꢀ8), 7.68ꢀ7.71 (d, Hꢀ3), 7.59ꢀ7.62 (d, Hꢀ5), 7.36ꢀ7.41 (m, Hꢀ7), 7.14ꢀ
7.18 (m, Hꢀ6), 6.68ꢀ6.71 (d, Hꢀ4), 3.72ꢀ3.74 (t, 2H, Hb), 3.66ꢀ3.68 (t, 2H, Ha), 3.60 (s, 2H, Hc).
13C NMR [300 MHz, DMSO, δ(ppm)]: 158.86 (HC=N), 149.65 (CꢀOH), 143.77 (Cꢀ10), 142.90
(Cꢀ5), 138.03 (Cꢀ6), 134.93 (Cꢀ3 and Cꢀ7), 129.66 (Cꢀ9), 127.54 (Cꢀ8), 119.27 (Cꢀ4), 110.05 (Cꢀ
2), 60.05 (Cꢀb), 45.35 (Cꢀc), 16.10 (Cꢀa). FTꢀIR (v, cmꢀ1): 3560 (br), 1624 (m).
4.2.2 Schiff base ligand H2L2 (18). 1.46 mL of (10 mmol) 2,2′ꢀ(ethylenedioxy)bis(ethylamine)
was added to 2.44 g (20 mmol) of 2ꢀhydroxyꢀbenzaldehyde [1:2 molar ratio] in dry ethanol and
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stirred for 2h. Yellow colored crystalline product obtained was recrystallized from ethanol and
dried under vacuum.
2ꢀ{[2ꢀ(2ꢀ{2ꢀ[(2ꢀHydroxyꢀ1,5ꢀdienylmethylene)ꢀamino]ꢀethoxy}ꢀethoxy)ꢀethylimino]ꢀmethyl}ꢀ
diphenol. Yield: (88%). Anal. Calcd. for C28H28N2O4: C 67.40; H 6.79; N 6.86. Found: C, 67.38;
1
H, 6.77; N, 6.86%. H NMR [300 MHz, DMSO, δ(ppm)]: 11.20 (s,1H, OH), 10.83 (s,1H,ꢀN=Cꢀ
H), 8.57ꢀ8.59 (d, Hꢀ6), 8.02ꢀ8.11 (m, Hꢀ4), 7.81ꢀ7.86 (m, Hꢀ5), 7.38ꢀ7.43 (d, Hꢀ3), 4.21ꢀ4.29 (t,
13
2H, Hb), 2.49ꢀ2.52 (t, 2H, Ha), 2.32 (s, 2H, Hc). C NMR [300 MHz, DMSO δ (ppm)]:
δ =
166.40 (HC=N), 161.20 (CꢀOH), 138.03 (Cꢀ5), 134.93 (Cꢀ3), 129.66 (Cꢀ2), 127.54 (Cꢀ4), 119.27
(Cꢀ6), 70.57 (Cꢀb), 66.84 (Cꢀc), 59.07 (Cꢀa). FTꢀIR (v, cmꢀ1): 3041 (br), 1618 (m).
Complexes of H2L1 in 1:1molar ratio
4.2.3 Me2Sn(L1) (
2). The sodium salt of Schiff base ligand was prepared by reacting 4.56 g (10
mmol) of H2L1 and 0.45 g (20 mmol) of sodium metal in 20 mL dry methanol in 1:2 molar ratio.
To the sodium salt of Schiff base, 2.19 g (10 mmol) of Me2SnCl2was added slowly in 1:1 molar
ratio and reaction mixture was refluxed for 4h. The precipitated NaCl was filtered and solvent
was evaporated on rotary evaporator under reduced pressure. The final product obtained was
recrystallized from dry methanol and hexane and finally dried under reduced pressure. The other
tin and silicon complexes were synthesized by reacting the appropriate amount of ligands,
H2L1/H2L2 with appropriate amount of R2SnCl2/R3SnCl/R2SiCl2/R3SiCl in 1:1 and 1:2 molar
ratios according to the above described procedure.
Me2Sn(L1)
.
Yield: (65%). Anal. Calcd. for C30H32N2O4Sn: C, 59.73; H, 5.35; N, 6.64; Sn, 19.68.
1
Found: C, 59.70; H, 5.37; N, 6.65; Sn, 19.65%. H NMR [300 MHz, CDCl3, δ(ppm)]: 8.37 (s,
1H, ꢀN=CꢀH), 8.01ꢀ8.03 (d, Hꢀ8), 7.82ꢀ7.84 (d, Hꢀ3), 7.68ꢀ7.71 (m, Hꢀ7), 7.63ꢀ7.65 (d, Hꢀ5),
7.45ꢀ7.50 (m, Hꢀ6), 7.16ꢀ7.18 (d, Hꢀ4), 3.47ꢀ3.53 (t, 2H, Hb), 3.14ꢀ3.17 (t, 2H, Ha), 1.40 (s, 2H,
13
Hc), 1.03 (s, 6H, Me). C NMR [300 MHz, CDCl3. δ(ppm)]: 177.00 (HC=N), 157.14 (CꢀOH),
137.51 (Cꢀ10), 133.06 (Cꢀ5), 129.91 (Cꢀ6), 128.17 (Cꢀ3), 126.67 (Cꢀ7), 125.53 (Cꢀ9), 123.97 (Cꢀ
8), 117.38 (Cꢀ4), 106.44 (Cꢀ2), 65.08 (Cꢀb), 64.27 (Cꢀc), 48.09 (Cꢀa), 7.06 (Me). 119Sn NMR
[300 MHz, CDCl3, δ(ppm)]: −307. FTꢀIR (v, cmꢀ1): 1606 (m), 446 (SnꢀN), 636 (SnꢀO).
4.2.4 Et2Sn(L1) (
3). Light yellow colored solid product obtained from hexane and methanol
mixture. Yield: 69 (%). Anal. Calcd. for C32H36N2O4Sn: C, 60.88; H, 5.75; N, 4.44; Sn, 18.80.
28

Page 29 of 43
MedChemComm
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DOI: 10.1039/C5MD00554J
1
Found: C, 60.86; H, 5.76; N, 4.45; Sn, 18.78%. H NMR [300 MHz, CDCl3, δ(ppm)]: 8.65 (s,
1H, ꢀN=CꢀH), 7.78ꢀ7.80 (d, Hꢀ8), 7.64ꢀ7.66 (d, Hꢀ3), 7.56ꢀ7.58 (d, Hꢀ5), 7.36ꢀ7.40 (m, Hꢀ7),
7.18ꢀ 7.22 (m, Hꢀ6), 6.88ꢀ6.90 (d, Hꢀ4), 3.68ꢀ3.70 (t, 2H, Hb), 3.64 (s, 2H, Hc), 3.07ꢀ3.12 (t, 2H,
Ha), 1.60ꢀ1.61 (t, 6H, Me), 1.39ꢀ1.43 (m, 4H, Me). 13C NMR [300 MHz, CDCl3, δ(ppm)]:
177.75 (HC=N), 158.91 (CꢀOH), 137.49 (Cꢀ10), 133.97 (Cꢀ5), 129.04 (Cꢀ6), 127.78 (Cꢀ3),
125.91 (Cꢀ7), 125.33 (Cꢀ9), 122.49 (Cꢀ8), 117.88 (Cꢀ4), 106.68 (Cꢀ2), 70.95 (Cꢀb), 69.97 (Cꢀc),
51.93 (Cꢀa), 8.43 (Et), 45.71 (Et). 119Sn NMR [300 MHz, CDCl3, δ(ppm)]: −300. FTꢀIR (v, cmꢀ1):
1608 (m), 450(SnꢀN), 638(SnꢀO).
4.2.5 Bu2Sn(L1) (
4). Light yellow colored product obtained from hexane. Yield: (68%). Anal.
Calcd. for C36H44N2O4Sn: C, 62.90; H, 6.45; N, 4.07; Sn, 17.27. Found: C, 62.91; H, 6.44; N,
1
4.04; Sn, 17.30%. H NMR [300 MHz, CDCl3, δ(ppm)]: 8.60 (s, 1H, ꢀN=CꢀH), 7.72ꢀ7.75 (d, Hꢀ
8), 7.63ꢀ7.66 (d, Hꢀ3), 7.50ꢀ7.54 (d, Hꢀ5), 7.40ꢀ7.46 (m, Hꢀ7), 7.17ꢀ7.22 (m, Hꢀ6), 6.88ꢀ6.91 (d,
Hꢀ4), 3.69ꢀ3.72 (t, 2H, Hb), 3.50ꢀ3.54 (t, 2H, Ha), 3.47 (s, 2H, Hc), 1.49ꢀ1.53 (t, 4H, Bu), 0.93ꢀ
0.97 (m, 8H, Bu), 0.66ꢀ0.69 (t, 6H, Bu). 13C NMR [300 MHz, CDCl3, δ(ppm)]: 176.60 (HC=N),
158.04 (CꢀOH), 138.50 (Cꢀ10), 133.87 (Cꢀ5), 129.35 (Cꢀ6), 128.08 (Cꢀ3), 126.98 (Cꢀ7), 126.23
(Cꢀ9), 123.41 (Cꢀ8), 117.89 (Cꢀ4), 107.64 (Cꢀ2), 65.91 (Cꢀb), 61.87 (Cꢀc), 48.93 (Cꢀa), 45.00
(Bu), 26.39 (Bu), 17.87 (Bu), 8.98 (Bu). 119Sn NMR [300 MHz, CDCl3, δ(ppm)]: −310. FTꢀIR (v,
cmꢀ1): 1606 (m), 449 (SnꢀN), 640 (SnꢀO).
4.2.6 Ph2Sn(L1) (
5). Brown colored compound was obtained from a mixture of hexane and
methanol. Yield: (65%). Anal. Calcd. for C40H36N2O4Sn: C, 66.04; H, 4.99; N, 3.85; Sn, 16.32.
1
Found: C, 66.07; H, 4.97; N, 3.84; Sn, 16.35%. H NMR [300 MHz, CDCl3, δ(ppm)]: 8.68 (s,
1H,ꢀN=CꢀH), 8.01ꢀ8.07 (m, 10H, Ph), 7.71ꢀ7.75 (d, Hꢀ8), 7.64ꢀ7.68 (d, Hꢀ3), 7.53ꢀ7.59 (d, Hꢀ5),
7.39ꢀ7.44 (m, Hꢀ7), 7.19ꢀ7.25 (m, Hꢀ6), 6.87ꢀ6.91 (d, Hꢀ4), 3.70ꢀ3.73 (t, 2H, Hb), 3.65ꢀ3.68 (t,
13
2H, Ha), 3.61 (s, 2H, Hc). C NMR [300 MHz, CDCl3, δ(ppm)]: 175.62 (HC=N), 158.18 (Cꢀ
OH), 138.69 (Cꢀ10), 137.87 (Ph), 136.03 (Ph), 135.46 (Ph), 134.77 (Ph), 133.05 (Cꢀ5), 129.65
(Cꢀ6), 127.18 (Cꢀ3), 126.98 (Cꢀ7), 126.18 (Cꢀ9), 123.03 (Cꢀ8), 118.88 (Cꢀ4), 106.45 (Cꢀ2), 66.01
(Cꢀb), 65.97 (Cꢀc), 49.93 (Cꢀa). 119Sn NMR [300 MHz, CDCl3, δ(ppm)]: −315. FTꢀIR (v, cmꢀ1):
1603 (m), 450 (SnꢀN), 645 (SnꢀO).
4.2.7 Me2Si(L1) (
6). Yield: (61%). Anal. Calcd. for C30H32N2O4Si: C, 70.28; H, 6.29; N, 5.46; Si,
5.48. Found: C, 70.31; H, 6.27; N, 5.47; Si, 5.50%. 1H NMR [300 MHz, CDCl3, δ(ppm)]: 8.69 (s,
29