Synthesis, microbiological study and X-ray structural characterisation of a tri-n-butylstannyl-2[4(diethylamino)arylazo]benzenecarboxylate

Article abstract of DOI:10.1016/S0022-328X(01)01350-X

Organostannyl carboxylates adopt an interesting range of structural variations leading to different structure-activity relationship. Organostanny1-2(arylazo)benzenecarboxylates, reported here, inhibit Gram-positive bacterial growth with an average MIC 10-

Full text of DOI:10.1016/S0022-328X(01)01350-X

Journal of Organometallic Chemistry 645 (2002) 33–38
www.elsevier.com/locate/jorganchem
Synthesis, microbiological study and X-ray structural
characterisation of a
tri-n-butylstannyl-2[4(diethylamino)arylazo]benzenecarboxylate
Sibani Chakraborty, Asim K. Bera, Suparna Bhattacharya, Sreya Ghosh, Asok K. Pal,
Soumen Ghosh, Asok Banerjee *
Biophysics Department, Bose Institute, P 1/12, C. I. T. Scheme VII M, Kolkata 700 054, India
Received 30 May 2001; received in revised form 1 October 2001; accepted 2 October 2001
Abstract
Organostannyl carboxylates adopt an interesting range of structural variations leading to different structure–activity relation-
ship. Organostannyl-2(arylazo)benzenecarboxylates, reported here, inhibit Gram-positive bacterial growth with an average MIC
10–20 mg ml−1, which is below the lethal dose. The discrete molecular units of this series of compounds function as an
anisobidentate chelating ligand, thus rendering the Sn atom five coordinated and adopt a polymeric form. The present work
reports the X-ray crystallographic structure of tri-n-butylstannyl-2[4(diethylamino)arylazo]benzenecarboxylate and microbial
studies in order to get insight into the mode of action of such compounds in biology. © 2002 Elsevier Science B.V. All rights
reserved.
Keywords: Crystal structures; Tributyltin analogs; Triorgano stannyl; Structure–activity
1. Introduction
conformational options and reduces the ambiguity in
stereochemical assignments for functional groups.
Organostannyl-2[4(diethylamino)arylazo]benzenecar-
boxylates have shown great promise in inhibiting the
growth of Gram-positive bacteria with an average MIC
10–20 mg ml−1 which is below the lethal dose.
Compounds of this series comprise discrete molecular
units, in which the carboxylato-group functions as an
anisobidentatate chelating ligand, thus rendering the tin
atom five coordinated and adopt a polymeric form [13].
In continuation of our earlier work [14] on the
structure–activity relationship (SAR) of a series of
organostannyl -2[ 4(diethylamino)arylazo]benzenecar-
boxylates, we extended our study with synthesis, micro-
biological activity, spectroscopic analysis, X-ray crystal-
lographic studies and computer modelling to correlate
their unique structural properties with their activities.
The present paper reports the full details of the X-ray
Organostannyl carboxylates are one of the most ex-
tensively investigated class of organometallics known
since early 1950s obviously for their biocidal properties
and unique structural features [1–4]. Organotin car-
boxylates are known to adopt an interesting range of
structural variations leading to different structure–ac-
tivity relationships (SAR), sometimes for compounds
with very similar chemical formulae [5]. When the
carboxylate residue contains additional potential donor
atoms, such as oxygen and nitrogen, other structural
possibilities arise. Several substituted organotin car-
boxylates are known to exhibit significant biological
activities [6,7]. Organotin compounds, diimine ligands
of diphenyltin dichloride [8] and diorganotin com-
pounds are known to possess significant antitumor
activity [9–12]. With this in view, we focussed attention
on molecules of the general formula (Fig. 1) containing
elements of structural rigidity, because rigidity restricts
crystallographic structure of
a
tri-n-butylstannyl-
2[4(diethylamino)arylazo]benzenecarboxylate and mi-
crobiological studies in order to get an insight into the
mode of action of such compounds in respect to biolog-
ical activity.
* Corresponding author. Fax: +91-33-334-3886.
E-mail address: ashoke@bic.boseinst.ernet.in (A. Banerjee).
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01350-X

34
S. Chakraborty et al. / Journal of Organometallic Chemistry 645 (2002) 33–38
2.2. Synthesis and spectroscopic studies
The title compound was prepared by stannylation of
2[4-(diethylamino)arylazo]benzenecarboxylic acid with
hexa-n-butyl-distannoxane in dry benzene at the reflux
temperature of the solvent (at 80 °C) for a period of 34
h, using 2:1 mole ratio of the substrate to reagent.
Removal of solvent followed by crystallisation from
light petroleum afforded the desired product as beauti-
ful orange red needles, m.p. 102 °C. It was character-
ised by IR, UV–vis spectral data and elemental
analysis. The stannyl carboxylate asymmetric stretching
frequency which occurred at 1610 cm−1 in the solid
phase did not show a great change in solution phase
indicating thereby the existence of a typical five coordi-
nate stannyl carboxylate bridged structure (Fig. 2) in
the solid state.
Fig. 1. General schematic diagram of organostannylarylazobenzene-
carboxylates.
2. Experimental
2.3. Crystallography
2.1. Microbial studies
Suitable orange–red good needle shaped crystals of
tri-n-butyl-2[4(diethylamino)arylazo]benzenecarboxyl-
ate for X-ray study were obtained by slow evaporation
from petroleum ether (boiling range 333–353 K); di-
mensions 0.34×0.25×0.15 mm. Cell parameters were
obtained from least-squares refinement of setting angles
of 25 reflections.
A total of 1851 [1756 with I\2|(F)] unique reflec-
tions were collected in an Enraf–Nonius CAD4 diffrac-
tometer with Ni-filtered Cu–Ka radiation and ꢀ−2q
step scan mode. Ranges of h, k and l are −17 to 17, 0
to 12, and 0 to 13, respectively, and maximum 2q was
The microbiological activity of these compounds was
tested following the Agar-Cup bioassay method. Bacte-
rial suspension (1 ml) was mixed with sterilised NA
(nutrient agar) at 45 °C and plated. The plates were
chilled for 30 min and then with the aid of a sterile cork
borer, an 8 mm diameter cup was made. The same
volume of solution of the compound was added to each
cup and incubated at 37 °C for 24 h. The diameters of
the inhibition zones were recorded. All apparatus and
materials were sterilised where necessary using standard
procedures.
Fig. 2. The polymeric structure of tri-n-butyl 2[4(diethylamino)arylazo]benzenecarboxylate.

S. Chakraborty et al. / Journal of Organometallic Chemistry 645 (2002) 33–38
35
method. These compounds were found to exhibit con-
siderable activity against several Gram-positive bacteria
(Table 1). From the results, it was found that the nature
of the substituents (R%, R¦ and R§) at various positions
(Fig. 1) in the phenyl ring was found either to increase
or to decrease the biological activity of the organostan-
nyl-2-(arylazo)benzenecarboxylates. The results may be
explained as being due to the variation of electron
density environment on the b-azoic nitrogen brought
about by the substituents. These observations led us to
consider that the b-azoic nitrogen to be the active site
in organostannyl carboxylates under investigation. This
is not surprising, because the azoic nitrogen is capable
of forming a hydrogen bond which is established for
this series by IR, UV–vis and 1H-NMR spectral
studies.
The significant inhibition of bacterial growth by
organostannyl-2(arylazo)benzenecarboxylates in the
present study also proved the presence of the metal in
the reactive site of the substrate. The observed en-
hanced biological activity of the organostannyl car-
boxylates as compared to that of their corresponding
2(arylazo)benzenecarboxylic acids and the complete
loss of biological potency of the corresponding ethyl/
methylcarboxylates provide further support to this
view.
The unique structural feature of the organostannyl-
2(arylazo)benzenecarboxylates [1], which is involved in
complexation with solvents of variable nucleophilicity
as evident from UV–vis spectra (Table 2) and others
[10], can perhaps be successfully exploited in explaining
similar coordination with enzymatic protein molecules
also. The enzymatic proteins in their relatively rigid
planar peptide structures possess carbonyl group capa-
ble of forming metal–oxygen bond with the stannyl
groups of organostannyl carboxylate and the bond
formation is further augmented by the nearby b-azoic
nitrogen and stannyl carboxylate carbonyl oxygens
Fig. 3. ORTEP plot of the molecule with displacement ellipsoids at the
30% probability level.
156°. Three standard reflections measured for every 100
reflections showed 0.5% variation of intensity. The data
sets were corrected for Lorentz & Polarisation effects,
and for absorption. The crystal data are given in Table
3. The structure was solved by direct methods, SHELXS
-
86 [15] in the space group P21/m and refined by full-
matrix least-squares on F2o using SHELXL-93 [16]. The
refinement converged to R=0.0499 (wR=0.11237).
The ORTEP diagram is shown in Fig. 3.
3. Results and discussion
The organotin carboxylates were obtained in good
yield via the stannylation of 2-[4(diethylamino)-
arylazo]benzenecarboxylic acid with hexa-n-butyl-di-
stannoxane in dry benzene.
Organostannyl-2(arylazo)benzenecarboxylates under
investigation were screened in vivo for their biological
activity against several microorganisms using Agar-Cup
Table 1
Antimicrobial activities of organostannyl-2(arylazo)benzenecarboxylates
Compound
R
R%
R¦
R§
S. a
B. m
S. l
B. p
M. f
B. s
1
2
3
4
5
6
7
8
9
Ph
n-Bu
Ph
n-Bu
Ph
n-Bu
Ph
n-Bu
Ph
n-Bu
Ph
H
H
H
H
Me
Me
Me
Me
Et
Et
Et
Et
Me
Me
Me
Me
Me
Me
Me
Me
Et
3-Cl
3-Cl
3-Me
3-Me
2-Cl
2-Cl
2-Br
2-Br
H
15.0
15.0
15.0
15.0
15.0
16.0
16.0
19.0
19.0
19.0
20.0
20.0
15.0
15.0
15.0
16.0
15.0
16.0
17.0
19.0
18.0
19.0
19.0
20.0
13.0
15.0
15.0
15.0
16.0
16.0
18.0
19.0
18.0
20.0
20.0
21.0
15.0
15.0
15.0
16.0
16.0
17.0
17.0
19.0
19.0
19.0
19.0
19.0
15.0
15.0
15.0
15.0
16.0
17.0
17.0
19.0
19.0
19.0
19.0
20.0
14.0
15.0
15.0
15.0
15.0
16.0
18.0
18.0
19.0
19.0
20.0
21.0
10
11
12
Et
Et
Et
H
2-Me
2-Me
n-Bu
S. a: Staphylococcus aureus; B. m: Bacillus cereus var. mycoides; S. l: Sarcina lutea; B. p: Bacillus pumilus; M. f: Micrococcus fla6us; B. s: Basillus
subtilis.

36
S. Chakraborty et al. / Journal of Organometallic Chemistry 645 (2002) 33–38
Table 2
UV–vis spectra of organostannyl-2(arylazo)benzenecarboxylates in different nucleophilic solvents [u (nm)]
Compound
R
R%
R¦
R§
MeOH
Pyridine
DMSO
1
2
3
4
5
Ph
n-Bu
Ph
n-Bu
Ph
H
H
H
H
Me
Me
Me
Me
Me
3-Cl
3-Cl
3-Me
3-Me
2-Cl
391
395
400
402
407
498
412
500
410
510
410
512
412
510
415
512
397
395
405
400
415
398
401
410
407
421
Me
6
7
n-Bu
Ph
Me
Me
Me
Et
Me
Me
Me
Et
2-Cl
2-Br
2-Br
H
412
417
420
416
418
421
422
420
8
n-Bu
Ph
9
432
518
432
510
10
n-Bu
Et
Et
H
which form bifurcated hydrogen bonds with the peptide
NH groups [14] thus enhancing the electron density of
the peptide oxygen. This binding through peptide
bonds is not unusual since the affinity of the stannyl
group for oxygen coordination [17] is believed to be
greater than that of the peptide nitrogen. This complex-
ation results in ceasing the bacterial growth. Spectral
evidence also supports the fact by a rapid change in
umax and m-values in the UV–vis spectroscopy in differ-
ent solvent [14].
On thorough examination it was observed that while
these organostannyl carboxylates are active against
Gram-positive bacteria, none possess any activity
against Gram-negative bacteria and pathogenic fungi.
Gram-negative bacteria are resistant to this group of
organostannyl carboxylates possibly due to the inability
of these larger polar molecules to cross the outer mem-
brane and reach the target site.
Table 3
Crystal data and structure refinement parameters for tri-n-butylstan-
nyl[2(4diethylaminoarylazo)]benzenecarboxylate
Colour/shape
Orange–red/needle shaped
C29H43N3O2Sn
586.068
293(2)
Cu–Ka
1.54182
Monoclinic
P21/m
Empirical formula
Formula weight
Temperature (K)
Radiation
Wavelength (A)
Crystal system
Space group
,
Unit cell dimensions
,
a (A)
14.135(2)
10.252(3)
10.802(2)
90
99.93(2)
90
1541.9(6)
4
2.526
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
V (A )
Z
Dcalc (g cm−3
)
Absorption coefficient (mm−1
F(000)
)
13.584
1224
3.1. Crystal structure
Crystal size (mm)
Theta range for data collection (°) 3.17–78.01
Index ranges
0.34×0.25×0.15
The structure of tri-n-butylstannyl-2[4(diethylamino)-
arylazo]benzenecarboxylate is shown in Fig. 2 (see
Table 3 for crystal data), and selected interatomic
parameters are listed in Table 4. The structure reported
here for tri-n-butylstannyl-2[4(diethylamino)arylazo]-
benzenecarboxylate is in agreement with that reported
earlier by us [1] and others [18]. The crystallographic
asymmetric unit comprises one centrosymmetric
molecule about a symmetric plane, which associate as a
result of mutual intermolecular Sn“O contacts, af-
forded by bidentate bridging carboxylate groups as
shown in Fig. 2. The resultant structure is therefore
polymeric, that is the crystals of the compound com-
−175h517, 05k512,
05l513
1851
1756 [Rint=0.0288]
Full-matrix least-squares on
Fo2
1756/0/316
1.088
Reflections collected
Independent reflections
Refinement method
Data/restraints/parameters
Goodness-of-fit on Fo2
Final R indices [I\2|(I)]
R indices (all data)
R1=0.0494, wR2=0.1232
R1=0.0499, wR2=0.1237
0.00037(6)
Extinction coefficient
Largest differential peak and hole 0.954 and −0.632
−3
,
(e A
)

S. Chakraborty et al. / Journal of Organometallic Chemistry 645 (2002) 33–38
37
Table 4
atom. The SnꢀC bond in the second axial site trans to
,
Selected bond lengths (A) and bond angles (°) for tri-n-butylstan-
nyl[2(4diethylaminoarylazo)]benzenecarboxylate
,
the coordinate SnꢀO bond is marginally longer (A),
whilst the sum of the equatorial angle at Sn is 345.7°.
The CꢀSnꢀC angles are opened up [122(4)°, 115(2)° and
122(4)°] due to the proximity of the carbonyl oxygen
atom O2, whereas the OꢀSnꢀC angles are compressed
[95(1)°, 89(2)° and 97(2)°], as obtained also in other
structures [13]. In this structure the aromatic ring and
the carboxylate group are twisted by 79° which is
similar to that found in the case of polymeric
triphenyltin 2-chlorobenzoate [19]. The two CꢀO bond
distances of the carbonyl group are unequal as ex-
pected, with the longer CꢀO distance being associated
with the shorter SnꢀO bond, and vice versa. The aryl
azobenzenecarboxylate unit exhibits a trans geometry at
the NꢁN (C3ꢀNꢀN2ꢀC8=179.4(1)° linkage, with the
ligand apparently held in a quite rigid conformation by
hydrogen bonds. Atom O1 forms bifurcated hydrogen
Bond lengths
Bond angles
SnꢀC30
SnꢀC20
SnꢀC40
SnꢀO1
2.14(3)
2.13(4)
2.14(3)
2.20(2)
C30ꢀSnꢀC20
C30ꢀSnꢀC40
C20ꢀSnꢀC40
C30ꢀSnꢀO1
C20ꢀSnꢀO1
C40ꢀSnꢀO1
C1ꢀO1ꢀSn
O2ꢀC1ꢀO1
O2ꢀC1ꢀC2
O1ꢀC1ꢀC2
C7ꢀC2ꢀC3
C7ꢀC2ꢀC1
C3ꢀC2ꢀC1
C4ꢀC3ꢀN1
C4ꢀC3ꢀC2
N1ꢀC3ꢀC2
C3ꢀC4ꢀC5
C4ꢀC5ꢀC6
C7ꢀC6ꢀC5
121.9(1)
115.0(2)
122.1(1)
96.8(1)
94.6(1)
88.9(1)
O1ꢀC1
C1ꢀO2
C1ꢀC2
1.27(4)
1.17(4)
1.55(5)
120.0(3)
126.0(4)
121.0(4)
113.0(3)
119.0(4)
124.0(4)
117.0(3)
127.0(4)
117.0(4)
116.0(4)
124.0(4)
118.0(3)
121.0(3)
121.0(4)
108.0(3)
112.0(3)
126.0(3)
118.0(4)
116.0(4)
122.0(3)
121.0(3)
126.0(3)
116.0(3)
118.0(3)
122.0(3)
121.0(4)
124.0(3)
118.0(3)
118.0(2)
111.0(3)
113.0(2)
116.0(2)
112.0(3)
115.0(3)
113.0(2)
127.0(2)
124.0(2)
122.0(3)
120.0(3)
118.0(4)
C2ꢀC7
1.33(5)
C2ꢀC3
C3ꢀC4
1.50(6)
1.35(5)
C3ꢀN1
C4ꢀC5
C5ꢀC6
C6ꢀC7
1.50(5)
1.35(5)
1.44(5)
1.36(5)
,
bond to C41 and C42 by 2.125 and 2.696 A, respec-
tively, for self-stabilisation while N1 and N3 atoms
,
form intermolecular hydrogen bond with C40 (2.698 A)
C6ꢀC7ꢀC2
,
and C17 (2.543 A), respectively.
N1ꢀN2
1.23(5)
N2ꢀN1ꢀC3
N1ꢀN2ꢀC8
C9ꢀC8ꢀN2
It is interesting to note that, in spite of the n-butyl
group attached to Sn and the very large steric demands
of the arylazobenzoato group which prevent inter-
molecular bridging, the carboxyl group prefers to func-
tion as a chelating ligand giving the five coordinated
structure, rather than as a unidentate ligand.
N2ꢀC8
C8ꢀC9
C8ꢀC13
C9ꢀC10
C10ꢀC11
C11ꢀC12
C11ꢀN3
1.39(5)
1.35(5)
1.39(5)
1.37(5)
1.43(5)
1.36(5)
1.40(4)
C9ꢀC8ꢀC13
N2ꢀC8ꢀC13
C8ꢀC9ꢀC10
C9ꢀC10ꢀC11
C12ꢀC11ꢀN3
C12ꢀC11ꢀC10
N3ꢀC11ꢀC10
C11ꢀC12ꢀC13
C12ꢀC13ꢀC8
C11ꢀN3ꢀC15
C11ꢀN3ꢀC14
C15ꢀN3ꢀC14
C16ꢀC14ꢀN3
N3ꢀC15ꢀC17
C21ꢀC20ꢀSn
C20ꢀC21ꢀC22
C23ꢀC22ꢀC21
C31ꢀC30ꢀSn
C32ꢀC31ꢀC30
C31ꢀC32ꢀC33
C41ꢀC40ꢀSn
C42ꢀC41ꢀC40
C41ꢀC42ꢀC43
C12ꢀC13
1.36(5)
4. Supplementary material
N3ꢀC15
N3ꢀC14
1.43(4)
1.49(4)
Crystallographic data for the structural analysis
have been deposited with the Cambridge Crystallo-
graphic Data Centre, CCDC no. 163010 for com-
pound tri-n-butyl-[2(4diethylamino)arylazo]benzenecar-
boxylate. Copies of this information may be obtained
free of charge from The Director, CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (Fax: +44-1223-
336033; e-mail: deposit@ccdc.cam.ac.uk or
C14ꢀC16
C15ꢀC17
C20ꢀC21
C21ꢀC22
C22ꢀC23
C30ꢀC31
C31ꢀC32
C32ꢀC33
C40ꢀC41
C41ꢀC42
C42ꢀC43
1.49(4)
1.46(4)
1.49(5)
1.57(5)
1.48(5)
1.54(4)
1.28(3)
1.41(4)
1.45(6)
1.36(6)
1.57(5)
www: http://www.ccdc.cam.ac.uk).
Acknowledgements
We are thankful to Dr Kanai Lal Ghatak, Govern-
ment College Durgapur, W.B & Dr B. Maji for helpful
discussion and DBT, Govt. of India for financial
support.
prise discrete molecular units, in which the carboxylato-
group functions as an anisobidentate chelating ligands
,
,
(SnꢀO=2.21 A and SnꢀO=2.4 A), thus rendering five
coordination to tin atom (Fig. 2). Each of the tin atom
exists in a distorted trigonal bipyramidal geometry with
the axial positions occupied by the oxygen atoms and
the equatorial plane is defined by trigonal plane of
three n-butyl carbon atoms. The axial carboxylate oxy-
gen atoms are organised in the weakly syn–anti bridged
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