Important properties of sulfur-bonded organoboron (III) complexes with biologically potent ligands

Article abstract of DOI:10.1080/104265090509225

Important properties of sulfur/oxygen and nitrogen bonded organoboron (III) complexes with biologically potent ligands viz., semicarbazone, thiosemicarbazone, and dithiocarbazate having the donor groups ONX and NS have been studied. The unimolar and bimol

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Important Properties of
Sulfur–Bonded Organoboron (III)
Complexes with Biologically
Potent Ligands
a
a
R. V. Singh , Mukesh Kumar Biyala & Nighat Fahmi
a
a
Department of Chemistry, University of Rajasthan,
Jaipur, India
Published online: 21 Dec 2010.
To cite this article: R. V. Singh , Mukesh Kumar Biyala & Nighat Fahmi (2005)
Important Properties of Sulfur–Bonded Organoboron (III) Complexes with Biologically
Potent Ligands, Phosphorus, Sulfur, and Silicon and the Related Elements, 180:2,
425-434, DOI: 10.1080/104265090509225
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Phosphorus, Sulfur, and Silicon, 180:425–434, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090509225
Important Properties of Sulfur–Bonded Organoboron (III)
Complexes with Biologically Potent Ligands
R. V. Singh
Mukesh Kumar Biyala
Nighat Fahmi
Department of Chemistry, University of Rajasthan, Jaipur, India
Important properties of sulfur/oxygen and nitrogen bonded organoboron (III) com-
plexes with biologically potent ligands viz., semicarbazone, thiosemicarbazone, and
dithiocarbazate having the donor groups ONX and NS have been studied. The
unimolar and bimolar reactions of phenylboronic acid with monobasic bidentate
and dibasic tridentate ligands result in the formation of colored solids which have
been characterized by the elemental analysis, molecular weight determinations, and
1
13
11
conductance measurements. The UV, IR, and NMR ( H, C, and B) spectral
studies indicate tetracoordinated geometry for the resulting complexes. Both the
ligands and their complexes have been screened for their fungicidal and bacterici-
dal activities, and the results indicate that they exhibit significant antimicrobial
properties.
INTRODUCTION
The coordination complexes of the sulfur and nitrogen donor ligands
1
were investigated on their manifestation of novel structural features,
2
unique spectral and catalytic properties relevance to the biological
3
–5
6
process
and pest averting properties of sulfur. Tremendous work
has been done on non-transition metal complexes for their commercial
applications as ceramic precursors, heat stabilizers, disperse dyes , sol-
7
gel process, in polymerization of alkenes, nuclear applications, lubri-
8
cation technology, carbohydrate research, and in cosmetic preparation
due to their film forming properties, substantiality, and hydrophobic-
ity. Boron is an essential element for healthy plants. It is known to
be involved in nucleic acid synthesis which is possibly linked to ad-
equate provision of the pyrimidine nucleotides. Boron also plays an
Received May 11, 2004.
Address correspondence to R. V. Singh, Department of Chemistry, University of
Rajasthan, Jaipur-302004, India. E-mail: m-elgaby@hotmail.com
425

4
26
R. V. Singh et al.
important role in the carbohydrate metabolism, hormone action, and
9
membrane formation. The structural study of the mononuclear boron
(
III) complexes of neobidentate thioimines has also been detected using
1
0
a wide range of analytical and spectroscopic techniques in our previ-
ous work. Boron complexes of semicarbazones, thiosemicarbazones, and
S-benzyldithiocarbazate have aroused considerable interest in view of
their industrial and biological importance.1 Many of these compounds
possess a wide spectrum of medicinal properties, including activity
1
against tuberculosis,12 leprosy, and bacterial and viral infections.
13
14
15
Their activity is frequently thought to be due to their ability to chelate
1
6
trace metals. Therefore, an attempt has been made to synthesize and
characterize some biologically active organoboron (III) complexes with
nitrogen and sulfur/oxygen donor ligands during these investigations.
The antibacterial and antifungal activities of the ligands along with
their boron derivatives also have been performed using conventional
fungicide, Bavistin, and bactericide Streptomycin as the standards for
the respective activities.
EXPERIMENTAL
The boron compound, [(Ph)B(OH)2], isatin, indol-3-acetic acid, and ace-
tophenone were purchased from Sisco, Lancaster, and Lobachemie and
as such. All the chemicals and solvents were dried and purified by stan-
dard methods. The reactions were carried out under strictly anhydrous
conditions.
Preparation of the Ligands
1
2
The ligands (L H2) and (L H2) were prepared by the condensation of
indol-3-acetic acid with thiosemicarbazide in 1:1 molar ratio and with
semicarbazide in presence of sodium acetate in 1:1 molar ratio, respec-
3
tively. The ligand (L H) was prepared by the reaction of isatin with
acetophenone in a 1:1 molar ratio, and then the resulted product con-
densed with S-benzyldithiocarbazate in absolute ethanol in unimolar
ratio. This reaction mixture was then refluxed over a water bath for
1
2
3
–4 h and allowed to stand overnight. The ligands (L H2, L H2, and
3
L H) separated out, were purified by recrystallization from the same
solvent, and analyzed before use. The parent ligands exist in the tau-
tomeric forms (Figure 1).
Preparation of the Complexes
Phenylboronic acid was dissolved in dry benzene in an 100-mL RB
flask and to this the requisite amount (1:2 molar ratio) of the ligands

Sulfur–Bonded Organoboron (III) Complexes
427
FIGURE 1
were added. The resulting mixture was refluxed for 12–24 hours. The
progress of the reaction was monitored by the liberation of water
azeotropically. The solid product was dried in vacuo. It was then washed
several times with dry cyclohexane and again dried in vacuo for 3–4 h.
The physical properties and analytical data of these complexes are en-
listed in Table I.
The purity of the compounds was checked by TLC on silica Gel-
G using anhydrous methanol and tetrahydrofuran (1:1) as a solvent.
Each of the compound moves as a single spot indicating the pres-
ence of only one component, hence their purity. Conductivity measure-
ments were made with a Systronic model 305 conductivity bridge in
dry dimethylformamide. Molecular weights were determined by the
Rast Camphor method. IR spectra of the solid samples were recorded
1
as KBr discs on a Nicolet Magna FT-IR 550 spectrophotometer. H,
1
3
11
C, and B NMR spectra were recorded on a Hitachi Perkin Elmer
spectrometer in DMSO-d6 and THF as a solvent at Delhi Univer-
sity, New Delhi. Nitrogen and sulfur were estimated by the Kjeldahl’s
and Messanger’s methods, respectively. Boron was estimated as boric
acid in the presence of mannitol using phenolphthalein as an indi-
cator. Carbon and hydrogen analyses were performed at the CDRI,
Lucknow.

4
28
R. V. Singh et al.
TABLE I Analytical Data and Physical Properties of the Ligands and
Their Complexes
Analysis found
Mol. Wt.
(
Calcd.) (%)
M.pt.
( C)
Found
(Calcd.)
◦
Compound
Colour
Grey
B
C
H
N
S
1
L H2
126
132
158
152
161
174
192
—
53.02
4.24
22.22
12.24
246
(53.20) (4.87) (22.56) (12.91) (248.30)
2
L H2
Dark
Brown
—
—
56.96
(56.88) (5.20) (24.12)
67.02 4.24 9.64
5.46
24.43
—
235
(232.24)
428
3
L H
Coke
Brown
Dim
14.67
(67.10) (4.45) (9.78) (14.92) (429.55)
C17H15N4OSB
C17H15N4O2B
3.14
60.84 4.32 16.26 9.32 333
(
3.23) (61.09) (4.52) (16.76) (9.59) (334.20)
3.24
(3.39) (64.18) (4.75) (17.61)
2.59 67.74 4.24 12.32
2.02) (67.54) (4.53) (12.01) (2.02) (533.46)
1.24 68.99 4.22 8.99 13.92 946
(1.14) (68.63) (4.36) (8.89) (13.57) (944.95)
64.02
4.64
17.47
—
317
(318.13)
535
Brown
C30H24N3O2S2B Grey
2.17
(
C54H41N6O2S4 B Dark
Brown
RESULTS AND DISCUSSION
The reactions of phenylboronic acid with dibasic tridentate,
thiosemicarbazone, semicarbazone and monobasic bidentate, and S-
benzyldithiocarbazate in different molar ratios yielded products accord-
ing to the general Eq. (1)–(3).
1
:1
[
[
[
(Ph)B(OH)2] + HONXH → [(Ph)B(ONX)] + 2H2O
(1)
(2)
(3)
1:1
(Ph)B(OH)2] + NSH → [(Ph)B(OH)(NS)] + H2O
1:1
(Ph)B(OH)2] + 2NSH → [(Ph)B(NS)2] + 2H2O
(
Where, ONX and NS are the donor systems of the ligands and X = S
or O).
These reactions are quite facile and could be completed within 12–
4 h of refluxing in benzene. The resulting products are colored solids
2
and insoluble in common organic solvents but soluble in DMSO, THF,
and DMF. Boron complexes are quite stable. The molecular weight de-
terminations indicate their monomeric nature. The low molar conduc-
−
1
2
−1
tance values (8–12 ohm cm mol ) of these derivatives in DMF at
−
3
10
M concentrations show them to be nonelectrolytes.

Sulfur–Bonded Organoboron (III) Complexes
429
Electronic Spectra
1
2
3
The electronic spectra of the ligands L H2, L H2, L H, and their
boron complexes were recorded in DMF. The bands at ca 264 nm
∗
and 328 nm in the case of free moieties were assigned to π-π elec-
tronic transitions within the benzene ring. These bands remain al-
most unchanged in the spectra of the complexes. Another band ob-
∗
served at ca 370 nm in the spectra of the moieties is due to the n-π
transitions of the azomethine (>C N) group. However, in the spec-
tra of the compounds this band appears in the region 359–334 nm
due to the polarization within the >C N chromophore resulting after
chelation.
Infrared Spectra
The IR spectra of the free ligands and their complexes were scanned
in the form of KBr pellets. IR spectra of the free ligands show a
−1
medium intensity band at 3395–3100 cm due to υNH/υOH vibra-
tions, which are absent in the spectra of the complexes. The bands due
to υ(C O) and υ(C S) modes in the spectra of the ligands are observed
−
1
−1
17
at 1690–1710 cm and 1030–1040 cm , respectively. These bands
disappeared in the spectra of the organoboron compounds, suggesting
the enolization and thioenolization of the ligands and their chelation
through the amido oxygen and thiolic sulfur, respectively. This fact gets
support by the observation of the bands due to υ(C O) and υ(C S)
modes at lower frequencies in the spectra of the boron compounds. The
−1
18
absorption at ca 1615 cm characteristic of the azomethine (>C N)
group in the spectra of the ligands, gets split into two sharp bands at
ca 1610 cm and 1630 cm in 1:2 complexes. This splitting of bands
−
1
−1
suggests that the azomethine group is in different chemical environ-
−
1
ments. The shifting of bands at ca 1630 cm (higher wave number
side) suggest the coordination of the azomethine nitrogen to the boron
−1
atom, whereas the band at ca 1610 cm is assigned to the uncoor-
dinated azomethine group. The υOH band in case of 1:1 boron com-
−
1
plexes appears at ca 3450 cm . There are no changes in the υsym and
υasym modes of the NH2 group19 appearing at ca 3360 and 3460 cm
−1
,
respectively, indicating the noninvolvement of this amino group in
chelation.
The coordination through the azomethine nitrogen atom and the
enolic oxygen/thiolo sulfur is further substantiated by the appearance
−
1
−1
of new bands in the region of 1350–1360 cm , 830–870 cm , 1520–
−1
−1
1
540 cm , and 1230–1250 cm in the boron complexes due to υ(B-O),
υ(B-S), υ(B← N) and υ(Ph-B) frequencies, respectively.
2
0
21
22

4
30
R. V. Singh et al.
1H NMR Spectra
1
The H NMR spectra of the ligands and their complexes have been
1
recorded in DMSO–d6-using TMS as an internal standard. The H NMR
−
spectra of the free ligands show signals due to NH of the indol ring at
−
δ 11.92–11.96 ppm and NH of the remaining ligand unit disappears
indicating deprotonation and a simultaneous covalent bond formation
between enolic oxygen and thiolo sulfur and the boron atom. The NH2
proton signal remains almost unchanged, which shows the noninvolve-
ment of this group in the complexation. The phenyl protons are observed
at ∼δ 6.70–8.24 ppm in the boron complexes, which were absent in the
spectra of the ligands. The resonance due to the SCH2 and aromatic
protons in the complexes appears in almost the same positions as in
−
1
the respective free ligands. The OH proton signal of the ligands, L H2
2
and L H2, were observed at δ 4.94 and δ 4.92 ppm, respectively. The
OH proton signal in 1:1 complex is observed at δ 4.20 ppm. Chemical
−
shift values of all the complexes are listed in Table II.
13C NMR Spectra
The 13C NMR spectral data also support the authenticity of the pro-
posed structures. The considerable shifts in the positions of carbon
atoms adjacent to the azomethine nitrogen (δ 158.26–162.72 ppm), thi-
olic sulfur/enolic oxygen (δ 164.34–176.84 ppm) support the proposed
coordination in the complexes. Thus the shifts in the position of carbon
atoms adjacent to the coordinating atoms clearly indicate the bonding
of the azomethine nitrogen and amido oxygen to the boron atom.
11B NMR Spectra
The 11B NMR spectra of the boron complexes have signals in DMSO-
d6 at δ 2.0–5.0 ppm, which unequivocally suggests a tetracoordinated
TABLE II 1H NMR Spectral Data (δ ppm) of the Ligands and Their
Complexes
Compound
NH2
NH(1)
NH(2)
SCH2
OH Aromatic protons
1
L H2
3.40
3.42
—
3.42
3.44
—
11.26
11.28
11.24
—
—
—
11.94
11.92
11.96
11.92
11.96
11.94
11.93
—
—
4.56
—
—
4.78
4.82
4.94
4.92
—
—
—
6.81–8.24
6.72–8.18
6.79–8.24
6.76–8.20
6.70–8.22
6.74–8.26
6.70–8.24
2
L H2
3
L H
C17H15N4 OSB
C17H15N4O2B
C30H24N3O2S2B
C54H41N6O2S4B
4.20
-
—
—

Sulfur–Bonded Organoboron (III) Complexes
431
environment around the boron atom and the presence of a B←N coor-
2
3,24
dinate bond.
The driving force for the formation of this coordinate
bond is the ability of trivalent PhB(OH)2 to accept a pair of electrons
from a suitable donor atom.
MICROBIAL ASSAY
Antimicrobial Screening
The synthesized ligandss and their complexes were tested for the
in vitro growth inhibitory activity against pathogenic fungi, Alternaria
cymopsidis and Macrophomina phaseolina and bacteria Escherichia
coli (−) and Staphylococcus aureus (+). The proper temperature, nec-
essary nutrients and growth media were employed for the preparation
2
5
of cultures of the fungi and bacteria using aseptic technique.
Antifungal Screening
The antifungal activity of the boron (III) complexes has been eval-
uated against Alternaria cymopsidis and Macrophomina phaseolina.
The Radial Growth Method26 using Czapek‘s agar medium having the
composition glucose 20 g, starch 20 g, agar–agar-20 g and distilled
water 1000 mL was employed to measure fungicidal activity. The com-
pounds were mixed directly with the medium in different concentra-
tions. Spores of the fungi were placed on the medium with the help of
an inoculum needle. The petri dishes were wrapped in polythene bags
containing a few drops of alcohol and were placed in an incubator at
◦
3
0 ± 1 C. Controls were also run and three replicates were used in each
case. The linear growth of the fungus was obtained by measuring the
fungal colony diameter after 4 days. The amount of growth inhibition
in each of the replicates was calculated by the equation (C-T) 100 C
−
1
,
where C is the diameter of the fungal colony on the control plate and
T is the diameter of the fungal colony on the test plate.
Antibacterial Screening
Antibacterial activity was evaluated by the Paper Disc Plate method.27
For this purpose, pure cultures of the organisms were dissolved in
peptone-water (1:1) and then uniformly seeded on the nutrient agar
plates having the composition peptone 5 g, beaf extract 5 g, NaCl 5 g,
agar-agar 20 g, and distilled water 1000 mL. The compounds were dis-
solved in 500- and 1000-ppm concentrations. Paper discs of Whatman
No. 1 with a diameter of 5 mm were soaked in different solutions of

4
32
R. V. Singh et al.
the compounds. These discs were placed on the medium previously
seeded with the organisms in the petri dishes at suitable distances.
◦
The petri dishes were stored in an incubator at 30 ± 2 C for 24 h. The
zone of inhibition thus formed around each disc containing the test
compound was measured accurately in mm. The organisms used in the
present investigations included Escherichia coli (−) and Staphylococcus
aureus (+).
Mode of Action
The ligands and their corresponding boron complexes were screened
against the selected pathogenic fungi and bacteria to examine their
growth-inhibiting potential towards the test organism. The results
show that these compounds exhibit antimicrobial properties. Boron
complexes show more inhibitory effects than the parent ligands
(
Tables III and IV). The ligand with sulfur and nitrogen donor sys-
tem might have inhibited enzyme productions since enzymes, which
require reactive groups for their activity, appear to be especially sus-
ceptible to deactivation by the complexes. The complexes facilitate their
diffusion through the lipid layer of the spore membrane to the site of
action, ultimately killing them by combining with the reactive groups
of certain cell enzymes. The results show that the activity is enhanced
by undergoing chelation.28 It is a well known fact that the concentra-
tion plays a vital role in increasing the degree of inhibition. As the
concentration increases, the activity increases. The fungicidal activity
was better when compared to the bactericidal activity. It is interesting to
TABLE III Fungicidal Screening Data of the
Ligands and Their Complexes (Average %
Inhibition after 96 h, Concentration in ppm)
Alternaria
cymopsidis
Macrophomina
phaseolina
Compound
100 ppm
200 ppm 100 ppm 200 ppm
1
L H2
38
32
49
44
40
52
56
86
51
48
59
54
52
63
67
100
37
33
48
42
41
51
55
82
52
47
57
55
53
62
68
100
2
L H2
3
L H
C17H15N4OSB
C17H15N4O2B
C30H24N3O2S2B
C54H41N6O2S4B
Bavistin

Sulfur–Bonded Organoboron (III) Complexes
433
TABLE IV Antibacterial Activity of the Ligands and
Their Complexes (Diameter of Inhibition Zone after
30 h, Concentration in ppm)
Escherichia coli (−)
Staphylococcus aureus (+)
Compound
500 ppm
1000 ppm
500 ppm
1000 ppm
1
L H2
7
9
9
10
8
12
11
17
9
7
7
6
10
11
9
13
14
15
10
9
2
L H2
3
L H
12
13
11
14
15
18
13
12
11
15
16
17
C17H15N4OSB
C17H15N4O2B
C30H24N3O2S2B
C54H41N6O2S4B
Streptomycin
note that the synthesized boron complexes with thiosemicarbazone and
S-benzyldithiocarbazate have more activity than the semicarbazone.
This may be due to the presence of the sulfur atoms in such ligands.
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