Synthesis, spectroscopic characterization, X-ray diffraction studies and in-vitro antibacterial activities of diorganotin(IV) derivatives with N-methyl-4-bromobenzohydroxamic acid

Article abstract of DOI:10.1016/j.ica.2017.09.035

Three new diorganotin(IV) complexes (CH₃)₂Sn(mbbha)₂ (2), (C₄H₉)₂Sn(mbbha)₂ (3), (C₆ H₅)₂Sn(mbbha)₂ (4), of N-methyl-4-bromobenzohydroxamic acid (Hmbbha) (1) have been synthesized by 2:1 condensation ratio of the parent hydroxamic acid with (CH₃)₂SnO, (C ₄H₉)₂SnO and (C₆H₅)₂SnO in toluene. Ligand has been synthesized by the reaction of 4-bromobenzoyl chloride and N-methylhydroxylamine hydrochloride. Elemental analysis, IR, multinuclear ¹H, ¹³C, ¹¹⁹Sn NMR spectroscopic techniques have been utilized to investigate the bonding and coordination modes of the ligand and its derivatives. It is found on the basis of spectroscopic and structural investigations that hydroxamate ligand acts as a bidentate chelator and coordinated to tin via carbonyl oxygen and deprotonated hydroxy group. The structures of complexes (3) and (4) have been deduced by X-ray crystallography which reveals octahedral geometry around tin in (C₄H₉)₂Sn(mbbha)₂ (3) and (C₆ H₅)₂Sn(mbbha)₂ (4) derivatives. The in-vitro antibacterial activities of ligand and its derivatives have been evaluated against one Gram positive and three Gram negative bacterial strains. The derivative (2) has displayed remarkable potency against both Gram positive and Gram negative strains. Anti-pathogenic results have been verified statistically.

Full text of DOI:10.1016/j.ica.2017.09.035

Accepted Manuscript
Research paper
Synthesis, spectroscopic characterization, X-ray diffraction studies and in-vi-
tro antibacterial activities of diorganotin(IV) derivatives with N-methyl-4-
bromobenzohydroxamic acid
Ali Irshad, Naqeebullah Khan, Yang Farina, Nizam Baloch, Samiullah, Akbar
Ali, Lo Kong Mun, Ghulam Murtaza, Attiq-ur-Rehman
PII:
S0020-1693(17)30964-7
http://dx.doi.org/10.1016/j.ica.2017.09.035
ICA 17894
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
19 June 2017
24 August 2017
13 September 2017
Please cite this article as: A. Irshad, N. Khan, Y. Farina, N. Baloch, Samiullah, A. Ali, L. Kong Mun, G. Murtaza,
Attiq-ur-Rehman, Synthesis, spectroscopic characterization, X-ray diffraction studies and in-vitro antibacterial
activities of diorganotin(IV) derivatives with N-methyl-4-bromobenzohydroxamic acid, Inorganica Chimica Acta
(2017), doi: http://dx.doi.org/10.1016/j.ica.2017.09.035
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Synthesis, spectroscopic characterization, X-ray diffraction
studies and in-vitro antibacterial activities of diorganotin(IV)
derivatives with N-methyl-4-bromobenzohydroxamic acid
Ali Irshada*, Naqeebullah Khana*, Yang Farinab, Nizam Balocha, Samiullaha, Akbar Alic,
Lo Kong Mund, Ghulam Murtazae, Attiq-ur-Rehmana.
aDepartment of Chemistry, Faculty of Basic Sciences, University of Balochistan, Sariab Road,
87300, Quetta, Pakistan
bSchool of Chemical Sciences And Food Technology, Faculty Of Science And Technology,
University Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan, Malaysia
cDepartment of Microbiology, Faculty of Biological Sciences, University of Balochistan, Sariab
Road, 87300, , Sariab Road, 87300, Quetta, Pakistan
dDepartment of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lampur,
Malaysia
eDepartment of Disaster Management, University of Balochsitan, Sariab Road, 87300,Quetta,
Pakistan.
* Corresponding authors. Address: Department of Chemistry, Faculty of Basic Sciences,
University of Balochistan, Sariab Road, 87300, Quetta, Pakistan. Tel: +92-0819211266 E-mail
address: irshad_uob@yahoo.com (A. Irshad) naqeebhmd2@gmail.com (N. Khan).
1

Abstract
Three new diorganotin(IV) complexes (CH3)2Sn(mbbha)2 (2), (C4H9)2Sn(mbbha)2 (3), (C6
H5)2Sn(mbbha)2 (4), of N-methyl-4-bromobenzohydroxamic acid (Hmbbha) (1) have been
synthesized by 2:1 condensation ratio of the parent hydroxamic acid with (CH3)2SnO, (C
4H9)2SnO and (C6H5)2SnO in toluene. Ligand has been synthesized by the reaction of 4-
bromobenzoyl chloride and N-methylhydroxylamine hydrochloride. Elemental analysis, IR,
multinuclear 1H, 13C, 119Sn NMR spectroscopic techniques have been utilized to investigate
the bonding and coordination modes of the ligand and its derivatives. It is found on the basis
of spectroscopic and structural investigations that hydroxamate ligand acts as a bidentate
chelator and coordinated to tin via carbonyl oxygen and deprotonated hydroxy group. The
structures of complexes (3) and (4) have been deduced by X-ray crystallography which
reveals octahedral geometry around tin in (C4H9)2Sn(mbbha)2 (3) and (C6 H5)2Sn(mbbha)2
(4) derivatives. The in-vitro antibacterial activities of ligand and its derivatives have been
evaluated against one Gram positive and three Gram negative bacterial strains. The
derivative (2) has displayed remarkable potency against both Gram positive and Gram
negative strains. Anti-pathogenic results have been verified statistically.
Keywords: Diorganotin(IV) hydroxamate; NMR; X-ray diffraction; antibacterial activity.
2

1. Introduction
Hydroxamic acids (R-CO-NH-OH) have received explosion of interest owing to their potent
biological activities. Hydroxamic acids usually act as mineral collectors, antibacterial agents,
growth factors, enzyme inhibitors, antimalarial drugs and fungicide agents due to their low
toxicity and high bioactivity [1-3]. Many of the chemotherapeutic entities such as histone
deacetylase (HDAC), matrix metalloproteinase (MMP) inhibitors and iron-based antibiotics
contain hydroxamic acids as a significant component [4-7]. The chelating ability of these ligands
with metal ions, particularly with transition metals enhances their bioactivities [8-9]. These
ligands frequently use the O, O donor sites to give bidentate chelates. Deportation of these acids
imparts two anionic forms; mono-deprotonated (hydroxamato) and di-deprotonated
(hydroximato). Hydroxamic acids are synthesized by a number of synthetic ways, which are well
depicted in literature [10], but some of these methods have been found pain staking, time
consuming and much costly. Hydroxmic acids are usually synthesized by the reaction of
hydroxylamines with esters or carboxylic acid salts [11]. The metal-organic framework has
gained considerable attraction owing to essential industrial, environmental and biological
applications [12-13]. In the area of organometallic chemistry, the organotin compounds have
gained extensive interest in industrial and basic research over the recent years. There is a
dramatic increase in the industrial utilization of organotin compounds due to their biocidal and
industrial applications [14-15]. Dioganotin(IV) complexes have displayed moderate antitumour
activity against human cell lines [16]. Tin exhibits a variety of coordination numbers and
geometries for both organometallic and inorganic complexes because of its rich coordination
chemistry [17-18]. The sulphur, nitrogen and oxygen donor ligands augment the bioactivity of
organotin moiety [19-20]. In view of the biological and structural diversity of organotin oxygen
donor ligands (hydroxamates), herein we are interested to report the synthesis, structural analyses
and antimicrobial activities of a new ligand N- methyl–4-bromobenzo-hydroxamic acid
(Hmbbha) and its three diorganotin(IV) complexes; Ph2Sn(mbbha)2, Bu2Sn(mbbha)2 and
Me2Sn(mbbha)2.
2. Experimental
2.1 Materials and methods
All materials were purchased from Sigma Aldrich and used without further purification.
All the chemicals were of analytical grade. TLC technique was used to assure the purity of the
3

ligand and its complexes. Uncorrected melting points were noted by open capillary method using
an electro-thermal 9300 digital melting point apparatus. Elemental analysis of C, H and N were
determined using Elemental Fison EA 1108 CHNS-O Analyzer. Estimation of tin was carried out
gravimetrically. Vibrational spectra of the compounds were obtained on KBr disc by pressed
pellet technique using Perkin-Elmer Spectrophotometer, in the range 4000-400 cm-1. 1H, 13C and
119Sn NMR spectra were recorded with a BRUKER FT-NMR 600 MHz Cryo-Prob
spectrophotometer. DMSO-d6 was used as a solvent, while TMS as an internal reference.
2.2 Synthesis of ligand
The preparation of ligand was carried out by adding N-methylhydroxylamine
hydrochloride (10 mmol) to a well stirred solution of sodium hydrogen carbonate (20 mmol) and
4-bromobenzoyl chloride (10 mmol). Sodium hydrogen carbonate was added as a catalyst.
Stirring was further continued for about 25 min below 4ºC. The solution was evaporated under
reduced pressure after filtration. Solid residue was purified by dissolving in a suitable solvent
and placed in a refrigerator to afford suitable crystals [21]. The synthesis of ligand is shown in
scheme 1.
2.3 Synthesis of complexes
Diorganotin (IV) complexes of ligand were obtained by refluxing 2:1 molar ratio of
ligand (2 mmol) and diorganotin (IV) oxide (1 mmol) in toluene, respectively. Refluxing was
continued for approximately 5-6 hours and the water formed during reaction was eliminated
using a Dean Stark Trap to drive the reaction in forward direction. After cooling and filtration,
the mother liquour was evaporated under reduced pressure. The solid residue was purified and
recrystallized in ethanol [22].Synthesis of complexes is shown in scheme 2.
2.4. X-ray crystallography
Suitable single crystals of dibutyltin(IV) N-methyl-4-bromobenzohydroxamate and
diphenyltin(IV) N-methyl-4-bromobenzohydroxamate were each fixed and placed on BRUKER
SMART 1000 CCD diffractometer, furnished with the radiation source (λ = 0.71073 Å).
SMART software was used to collect data and interpretation was made on SAINT. Empirical
absorption correction was performed by means of SADABS. Direct method was used to solve
the structure and F2 based full matrix least square procedure was used to refine, using
4

SHELXTL, based on SHELX 97. The particulars of structure solution, data collection and
crystallographic information are summarized in Table 5.
2.5. Antibacterial activity
Agar well method were used for the determination of antibacterial effects of the
synthesized compounds against different pathogenic bacterial strains including Salmonella typhi,
Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Moller Hinton Agar were
prepared following the manufacturer’s instructions and sterilized at 15 lbs. (121°C) pressure for
15 minutes. After sterilization, the molten medium was spreaded on 100 mm (millimeter) petri
plates. Petri plates containing 25 mL of medium were seeded with fresh (24 hours) culture of
bacterial strains. Wells (6mm) were made in the medium with sterilized borers and 100 µL of
stock solutions (4mg/mL in DMSO) of compounds were poured in each well. Pure DMSO and
antimicrobial drug Doxycycline (DO 30µg) were employed as negative and positive controls,
respectively. The petri plates were then incubated for 24 hours at 37 0C. Antibacterial activities
of the compounds were assayed by measuring the inhibition zone diameter in mm around each
well [23-24].
3. Results and Discussion
3.1. Synthesis of ligand
The preparation of N-methyl-4-bromobenzohydroxamic acid was carried out by reacting
N-methylhydroxylamine hydrochloride with 4-bromobenzoyl chloride. Sodium hydrogen
carbonate was used as catalyst. Purity of the synthesized ligand and its organotin complexes was
assured by TLC, and silica gel-G was used as a stationary phase. The physical properties and
analytical data of ligand and its complexes are given in Table 1. The calculated values are found
close to the experimental ones.
3.2 Infra-Red Spectroscopy
Vibrational spectra of ligand N-methyl-4-bromobenzohydroxamic acid and its
diorganotin(IV) complexes have been recorded in solid state in the range 4000-370 cm1-. The
key stretching absorptions are given in Table 2. In free hydroxamic acid, the main stretching
vibrations are ν(O-H), ν(C=O), ν(N-C) and ν(N-O). The ν(C=O) absorption is observed at 1600
cm-1, lower than the simple carbonyl group ν(C=O) positioned at 1700 cm-1. The location of
ν(O-H) stretching frequency at 3123 cm-1 as a broad peak indicates the presence of
5

intramolecular hydrogen bonding between the proton of hydroxy group and lone pair of carbonyl
oxygen. The presence of carbonyl peak at lower value along with the broad ν(O-H) peak is a
strong evidence of formation of hydroxamic acid. The sharp spectral bands at 1398 and 915 cm-1
indicate the presence of ν(N-C) and ν(N-O) bonds, respectively [25]. In IR spectra of
hydroxamate complexes, the absence of the hydroxyl ν(O-H) frequency and shifting of carbonyl
group absorption to lower frequencies are main characteristic peaks. The absence of ν(O-H) peak
in the spectra of complexes implies the replacement of (OH) proton by tin and existence of
ligand in deprotonated form in complexes [26]. The carbonyl group absorptions shift to the lower
value range (1600-1584 cm-1) in spectra of organotin derivatives, which confirm the formation of
complexes. This shifting of stretching frequency of carbonyl group to lower value range and the
absence of ν(O-H) vibrational frequency indicates the existence of hydroxamic acid as a
bidentate chelating ligand in complexes. Furthermore, the shifting of ν(N-O) stretching
frequencies to higher values in spectra of complexes, excludes the ligation of hydroxamic acid
through nitrogen atom. The frequencies of ν(Sn-C) and ν(Sn-O) are observed in the range (573-
521 cm-1) and (458-443 cm-1), respectively [27].
3.3. NMR Spectroscopy
The ligand and its organotin complexes are dissolved in DMSO at room temperature to
record their 1H NMR spectra. 1H NMR spectral values of ligand and its complexes are
documented in Table 3. The low field absorption of OH proton at 10.34 ppm in 1H-NMR
spectrum of free ligand supports the presence of intramolecular hydrogen bonding between the
hydroxy proton and oxygen of carbonyl group. The complete disappearance of OH absorption in
the spectra of complexes implies occurrence of ligand in deprotonated form in organotin(IV)
derivatives. The protons of methyl group attached to nitrogen atom in the ligand appear in the
region 3.22 ppm in spectra of complexes and their unaffected position strongly indicates the non-
involvement of nitrogen atom in complex formation. The resonance frequency of methyl protons
bonded with tin atom in dimethyltin(IV) complex is observed as a singlet in the range 0.32 ppm
accompanied with tin satellites. The value of two bond heteronuclear coupling constant 2J(119Sn-
1H) = 85.2 Hz has been calculated from tin satellites present in the 1H NMR spectrum of
dimethyltin(IV) complex which lies in the range of hexa-coordinated complexes [28]. Methyl
and methylene protons of dibutyl group occur as a triplet and multiplet in the regions 0.82 ppm
and 1.24-1.30 ppm, respectively [29]. Aromatic protons of the free ligand appear as a multiplet
6

in the range 7.51-7.61 ppm. However, arromatic protons of ligand and diphenyltin(IV) moiety
occur as a complex multiplet in the region 7.31-7.69 ppm.
13C NMR studies have been carried out in DMSO-d6. The carbonyl C=O absorption is the
main characteristic peak in 13C NMR spectra of ligand and its complexes. In ligand spectrum,
carbonyl group resonates at 168.3 ppm. In spectra of complexes, carbonyl signal exists in the
range 161.1-161.7 ppm. This upfield shift of the carbonyl resonance frequency in
diorganotin(IV) complexes is due to increase in shielding at carbon and substantially indicates
the coordination of carbonyl group with tin via oxygen atom of carbonyl group [30]. The singlet
of methyl carbon attached to nitrogen atom fall in the range 39.08-39.2 ppm and its unaltered
position on complexation is in conformity with 1H NMR spectral interpretation. In 13C NMR
spectrum of dimethyltin(IV) derivative, the carbons of methyl group attached to tin atom
resonate at 6.57 ppm. The chemical shifts of dibutyl carbons bonded to tin atom fall in the
range 7.3-28.2 ppm.
119Sn NMR studies have been carried out in DMSO-d6 at room temperature in decoupling
mode. 119Sn NMR is one of the sensitive techniques to determine the coordination geometry
around tin [31]. Substituent effects, coordination number around tin, oxidation state of tin and
isotope effect mainly influence the chemical shift of 119Sn NMR. 119Sn NMR resonating
frequencies of diorganotin(IV) complexes are found in the range -405 to -407 ppm which
substantially reflects octahedral geometry around tin in solution for the reported complexes [32].
This larger upfield shift of 119Sn NMR in spectra of complexes as compared to simple analogues;
Me2SnCl2 (+137 ppm) and Ph2SnCl2 (-32 ppm) is due to higher coordination number of tin and
increase in shielding at tin centre [33]. 13C and 119Sn NMR data for ligand and diorganotin(IV)
complexes are documented in Table 4.
3.4. X-ray crystallography
The suitable quality single crystals of complexes (3) and (4) were each fixed and placed
on the BRUKER SMART 1000 CCD diffractometer, furnished with the radiation source (λ =
0.71073 Å). The ranges 2.67-25.50 for (2) and 2.78-25.98 for (3) were selected for data
collection. SHELXTL-97 program system was used to perform the calculations. The refining
parameters and data collection are reported in Table 5. The molecular structures of complexes
(3) and (4) are shown in Fig 1 and 3, respectively. Selected bond distances and bond angles of
the compounds are recorded in the Tables 6 and 7, respectively. The crystal structures of (3) and
7

(4) organotin(IV) complexes exhibit that two N-methyl-4-bromobenzohydroxamate ligands are
bonded to tin as a chelator through oxygens of carbonyl and deprotonated hydroxy groups. The
molecular structures of (3) and (4) have shown similar crystal characteristics where tin atom is
coordinated with two ligands in a complex through two oxygen atoms and two carbon atoms of
butyl or phenyl moieties imparting a six-coordinated tin structure. N-methyl-4-bromo-
benzohydroxamate ligand acts as a bidentate ligand. The selected bond lengths of Sn(1)−O(1),
Sn(1)−O(2), Sn(1)−O(3) Sn(1)−O(4) are 2.110(2), 2.193(2)Å, 2.110(2) Å and 2.217(2) Å, for
the complex (3), Sn1−O1 Sn1−O2 Sn1−O3, Sn1−O4 are 2.105(2)Å, 2.363(2) Å, 2.121(2)Å and
2.398(3) Å, respectively, which are in consistent with the bond distances of identical compounds
reported in literature [34]. The shorter bond length of tin and oxygen is measured very close to
sum of their covalent radii (2.098(6)Å) [35], while the longer bond length 2.398(3) Å is found
much shorter as compared to van der Waals radii (4.00 Å). This is substantial indication of
strong bond formation between tin and oxygens of carbonyl and deprotonated hydroxy group of
ligand, as speculated by infrared and NMR spectral interpretation. The complex Bu2Sn(mbbha)2
(3) crystalizes as colourless block shaped crystal in triclinic space group P-1, while
Ph2Sn(mbbha)2 (4) crystallizes as block shaped crystal in orthorhombic space group.
3.5. Antibacterial activity
The in-vitro antibacterial activities of ligand (Hmbbha), its complexes; Me2Sn(mbbha)2,
Bu2Sn(mbbha)2, Ph2Sn(mbbha)2 and doxycycline (a standard drug) have been assayed by agar-
well and disc diffusion methods against four different pathogenic bacterial strains; Gram positive
(Staphylococcus aureus) and Gram negative (Escherichia coli, Salmonella typhi, Klebsiella
pneumoniae) [36]. The inhibition zone values for tested agents are recorded in mm and presented
in Table 8. Zone inhibitions of diameter less than 10 mm are referred as weak; 10-16 mm are
considered moderate and higher than 16 mm are active [37]. Ligand (Hmbbha) exhibits
moderate activity against Salmonella typhi and significant activity against three other strains.
The potent biological effectiveness of hydroxamic acid (ligand) is attributed to the presence of
OH and CO groups. Although, hydroxamic acids inhibit the activity of enzymes essential for
bacterial growth but probably their antibacterial activity is due to interaction with deoxyribose
nucleic acid (DNA) of bacteria. The greater potency of hydroxamic aicds may also be related
with their hydrophobicity [38-40].The results of antimicrobial screening of compounds reveal
8

that Me2Sn(mbbha)2 has displayed significant effectiveness against both Gram positive and
Gram negative tested strains in comparison to ligand and other complexes [41]. This significant
activity of Me2Sn(mbbha)2 is associated with its lower molecular weight than other organotin
compounds, because of which it has greater rate of diffusion across the membrane [42- 43]. It
may also attribute to the ligand’s role, which adds in transportation of organotin moiety to the
site of action [44-45]. Fig 3 shows the inhibition zone of Me2Sn(mbbha)2 complex.
Bu2Sn(mbbha)2 complex possesses strong activity against all the tested pathogens as compared
to other compounds except Me2Sn(mbbha)2. The lower potency of Bu2Sn(mbbha)2 complex in
comparison to Me2Sn(mbbha)2 may be ascribed to its lower permeability through the bacterial
cell membrane owing to its greater molecular weight and increase in carbon chain length [46-
47]. Ph2Sn(mbbha)2 has displayed moderate activity against all the pathogens but found least
active as compared to other tested compounds. In general, the bioactivity of organotin(IV)
complexes is influenced both by nature and number of organic groups on tin centre and the donor
ligand. Furthermore, the permeability of compound through the bacterial cell is essential for the
effectiveness of a bactericidal agent. Thus, each factor which adds in passage of the compound
through microorganism membrane may increase the activity [48]. The current work is also in
consistent with the decreasing order of antibacterial activity of diorganotins; dimethyltin ˃
dibutyltin ˃ diphenyltin as reported earlier [49-50]. As a whole, the dimethyltin(IV) complex has
been observed as a promising agent which is strongly active against both Gram positive and
Gram negative tested strains as represented in Fig 4. Nevertheless, the lack of data on
antimicrobial activity of oranotin(IV) hydroxamtes has prevented us to establish a rational
comparison of the similar compounds.
3.6. Statistical analysis
The statistical information have been generated by IBM SPSS Statistics 20. Important
statistical values including mean, standard deviation and confidence interval with variables are
given in the summary Table 9. The results of ANOVA analysis are shown in Table 10. The
ANOVA table F (4, 15), 8.349, p=0.005) exhibits that there are statistically significant difference
between the activity of assayed compounds which may be argued owing to the various organotin
moieties in each compound. The existence of significance value (p=0.005), reasonably below
0.05, confirms the rejection of null hypothesis (H0). The results of Tukey’s multiple studies are
given in Table 11. The Tukey post hoc analysis displays that the activity of Me2Sn(mbbha)2
9

(29.25 2.217, p = 0.002) complex is significantly high as compared to other assayed
compounds including ligand (21.25 5.737, p = .084), Bu2Sn(mbbha)2 (22.25 2.217, p =
0.154), and Ph2Sn(mbbha)2 (15.50 2.082, p = 0.002) and the standard (Doxycycline) (22.75
5.852, p = 0.025).
4. Conclusion
The new ligand and its dioranotin(IV) derivatives have been synthesized and
characterized successfully. Infrared data show the disappearance of the ν(O-H) stretching
frequency, lowering of the carbonyl frequency and shifting of the ν(N-O) absorption to higher
frequency on chelation indicate that the hydroxamic acid is a bidentate chelator. The new
absorption bands appeared in the spectra of complexes are assigned to ν(Sn-O) and ν(Sn-C). 1H
NMR spectral data confirm the presence of ligand in deprotonated form in complexes. 13C
spectra illustrate minor upfield shift in the position of carbonyl absorption on complexation. Up-
field shift of 119Sn NMR absorptions reflects six coordination number for tin in the derivatives.
The X-ray diffraction studies confirm the speculated six-coordination environment around tin in
(3) and (4) derivatives. Compound (2) has exhibited strong antimicrobial activity against all
tested strains as compared to other compounds and its further investigation is proposed as an
antibacterial agent.
.
ACKNOWLEDGMENT
The support and financial assistance for this work by Chemistry Department, Faculty of
Basic Sciences, University of Balochistan, Quetta, Pakistan, Department of Microbiology,
Faculty of Biological Sciences, University of Balochistan, Quetta, Pakistan and School of
Chemical Sciences and Food Technology, University of Kebangsaan Malaysia is greatly
acknowledged.
Supplementary material
Crystallographic data for structure analysis of compound (3) and (4) have been deposited with
the Cambridge Crystallographic Data Centre, CCDC reference numbers 4171 for (3) and 4244
for (4). The provided information can be obtained free of charge from the Director, CCDC, 12
10

Union Road, Cambridge, CB2 1EZ, UK (fax: +44-1223-336033; e-
mail:deposit@ccdc.cam.ac.uk; website: http://www.ccdc.cam.ac.uk).
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13

O
C
O
C
OH
N
Cl
CH3
NaHCO3
+
H3CNHOH.HCl
CH3OH/ 0oC
N-Methyl-hydroxylamine
hydrochloride
Br
Br
4-Bromobenzoyl chloride
N-Methyl-4-bromobenzohydroxamic acid
(Hmbbha)
Scheme 1 Reaction of Hydroxylamine with Acid Chloride
R
H3C
O
O
Reflux
C
Br
N
R2SnO
2Hmbbha
Sn
Toluene/ 6hr
N
Br
C
O
O
CH3
R
R = CH3, C4H9, C6H5
Scheme 2 Reaction of free Ligand with Diorganotin(IV) oxide
14

Fig. 1 Thermal ellipsoid plot of C24H32Br2N2O4Sn. Displacement ellipsoids are drawn at the 50%
probability level, and H atoms are shown as spheres of arbitrary radii
15

Fig. 2 Thermal ellipsoid plot of C28H24Br2N2O4Sn. Displacement ellipsoids are drawn at the 50%
probability level, and H atoms are shown as spheres of arbitrary radii.
Fig. 3 A representation of inhibition zones of various bacterial strains.
16

Fig. 4 Boxplot graph of antimicrobial activity of compounds (1-6) against various bacteria.
17

Table 1 Physical data for the prepared ligand and the complexes.
Compound
Colour
Yield (%)
Found
C
(Calc.) %
H
M.P.(ºC)
N
Sn
(Hmbbha)
Colourless 82
104-105
118-119
38.83
3.88
5.90
(41.76)
36.53
(3.48)
2.48
(6.09)
4.48
Me2Sn(mbbha)2 White
85
17.38
(35.59)
(3.32)
(4.61)
(19.60)
Bu2Sn(mbbha)2 Colourless 76
154-155
151-152
41.63
4.66
3.79
15.82
(41.68)
(4.66)
(4.05)
(17.22)
White
Ph2Sn(mbbha)2
71
45.46
3.11
3.28
15.01
(45.97)
(3.31)
(3.83)
(16.28)
Table 2: Infrared spectral data for the ligand and its complexes
Compound
?? (O-H) ?? (C=O) ?? (C-N) ?? (N-O) ?? (Sn-C) ?? (Sn-O)
cm1
cm1
cm-1
cm1
915
934
937
946
cm-1
cm1-
(Hmbbha)2
3123
1600
1584
1586
1590
1436
1496
1497
1492
-
-
Me2Sn(mbbha)2
Bu2Sn(mbbha)2
Ph2Sn(mbbha)2
-
-
-
524
521
573
443
447
458
18

1
Table 3 H NMR data for free ligand and diorganotin(IV) complexes (ppm)
No
Compound
OH
H(Aromatic)
H(Aliphatic)
(Hmbbha)
10.34
(H)
-
7.51-7.61m
(4H)
N-CH3: 3.22 s
1
(3H)
Me2Sn(mbbha)2
Bu2Sn(mbbha)2
7.11-7.44m
2(4H)
N-CH3: 3.41s 2(3H)
Sn-(CH3)2: 0.32
N-CH3: 3.38s 2(3H)
1.24-1.30m 2(6H)
-(CH3):0.82t 2(3H)
N-CH3:3.46s 2(3H)
2
-
-
7.56-7.70m
2(4H)
3
Ph2Sn(mbbha)2
7.31-7.69m
2(9H)
4
Table 4 13C and 119Sn NMR data for free ligand and diorganotin(IV) complexes (ppm)
No
Compound
C=O
Aromatic
Aliphatic
119Sn-R
(Hmbbha)
168.3
161.3
161.5
114- 134
124-131
115-142
124-135
39.0
-
1
2
3
4
Me2Sn(mbbha)2
Bu2Sn(mbbha)2
Ph2Sn(mbbha)2
39.2, 6.5
39.2, 7.3-28.2
39.2
-404
-407
-405
161.7
19

Table 5 Crystal data of the complexes studied
Compound
(3)
(4)
Gross formula
C28 H24 Br2 N2 O4 Sn
731
C24 H32 Br2 N2 O4 Sn
691.06
M
Crystal system, space group
Triclinic, P-1
Block
Orthorhombic, P21/n
Block
Crystal shape
Colour
Colourless
9.0565(6)
12.4799(8)
14.0288(9)
66.8960(10)
84.8720(10)
80.9240(10)
1439.50(16)
2
Colourless
14.151(6)
11.692(5)
17.404(7)
90.00
a, Ǻ
b, Ǻ
c, Ǻ
ꢀ, deg
106.109(6)
90.00
ꢁ, deg
ꢂ, deg
V, Ǻ 3
2766.5(19)
4
Z
1.686
1.608
dc, g/cm
ꢃ (Mo Kꢀ)cm-1
3.698
3.840
100(2)
100(2)
T , K
0.2, 0.9, 0.12
17150
0.33, 0.25, 0.36
32004
Crystal size, mm
measured reflections
independent reflections
reflections with I > 2ꢄ(I)
Rint
5945
5726
4771
4238
0.0416
0.0475
26.50º
26.50º
θ max
1.88º
2.13º
θ min
-11 11
-15 15
-17 17
-17 17
-14 14
-21 21
h
k
l
20

R[F2 > 2ꢄ(F2)]
wR(F2)
0.0322
0.0705
1.012
5945
336
0.0321
0.0648
1.057
5726
306
S
reflections
parameters
restraints
∆ꢅmax e Ǻ-3
∆ꢅmin e Ǻ-3
0
24
1.670
-1.215
0.509
-0.698
Table 6 Selected bond lengths of the compounds
(3)
(4)
Sn1 O3 2.110(2)
Sn1 O1 2.110(2)
Sn1 C7 2.148(4)
Sn1 C1 2.152(3)
Sn1 O2 2.193(2)
Sn1 O4 2.217(2)
Br1 C18 1.905(3)
Br2 C26 1.897(4)
N1 C13 1.318(4)
N1 O1 1.375(3)
N1 C14 1.451(4)
N2 C21 1.314(4)
C5 C6 1.380(5)
Sn1 O1 2.105(2)
C19 C20 1.384(5)
C19 C24 1.390(5)
C19 C17 1.494(5)
C22 C21 1.370(5)
C22 C23 1.375(5)
C9 C11 1.498(5)
C11 C12 1.388(5)
C11 C16 1.382(5)
C15 C16 1.382(5)
C1 C2 1.500(6)
C7 C12 1.390(5)
C7 C8 1.395(5)
Sn1 O3 2.121(2)
Sn1 C1 2.123(4)
Sn1 C5 2.131(5)
Sn1 O2 2.363(2)
Sn1 O4 2.398(3)
Br2 C22 1.900(3)
Br1 C14 1.895(3)
O1 N1 1.384(3)
N1 C9 1.316(4)
N1 C10 1.451(4)
O4 C17 1.254(4)
C8 C9 1.390(5)
C9 C10 1.384(6)
C10 C11 1.382(6)
C11 C12 1.395(6)
C13 C15 1.472(5)
C15 C16 1.398(5)
C15 C20 1.398(5)
C16 C17 1.378(5)
C17 C18 1.376(5)
C24 C23 1.380(5)
C21 C20 1.374(5)
21

N2 O3 1.373(3)
N2 C22 1.455(4)
O2 C13 1.283(4)
O4 C21 1.276(4)
C1 C2 1.396(5)
C1 C6 1.396(5)
C2 C3 1.384(5)
C3 C4 1.385(5)
C4 C5 1.381(5)
C18 C19 1.384(5)
C19 C20 1.383(5)
C21 C23 1.486(5)
C23 C28 1.384(5)
C23 C24 1.386(5)
C24 C25 1.380(5)
C25 C26 1.387(5)
C26 C27 1.381(5)
C27 C28 1.385(5)
O3 N2 1.377(3)
O2 C9 1.263(4)
N2 C17 1.321(4)
N2 C18 1.451(4)
C14 C15 1.372(5)
C14 C13 1.379(5)
C12 C13 1.379(5)
C5 C6 1.502(6)
C2 C3 1.527(8)
C3 C4 1.264(11)
C6 C7 1.549(7)
C7 C8 1.429(8)
Table 7 Selected bond angles of the compounds
(3)
(4)
O1 Sn1 O3 73.99(9)
O3 Sn1 O1 157.92(9)
O3 Sn1 C7 87.99(11)
C12 C7 C8 117.3(3)
C12 C7 Sn1 126.4(3)
C21 C22 C23 121.5(3)
O1 Sn1 C1 107.09(13) C21 C22 Br2 119.3(3)
O3 Sn1 C1 101.40(14) C23 C22 Br2 119.2(3)
O1 Sn1 C5 103.49(15) O2 C9 N1 120.7(3)
O3 Sn1 C5 103.68(15) O2 C9 C11 119.3(3)
C1 Sn1 C5 144.68(18) N1 C9 C11 120.0(3)
O1 Sn1 C7 105.37(12) C8 C7 Sn1 116.2(3)
O3 Sn1 C1 104.41(11) C9 C8 C7 122.1(4)
O1 Sn1 C1 89.23(11)
C10 C9 C8 119.4(4)
C7 Sn1 C1 105.16(13) C11 C10 C9 119.8(4)
O3 Sn1 O2 88.72(9)
O1 Sn1 O2 73.59(9)
C7 Sn1 O2 91.94(11)
C10 C11 C12 120.3(4)
C7 C12 C11 121.1(4)
O2 C13 N1 118.8(3)
O1 Sn1 O2 72.08(9)
O3 Sn1 O2 145.98(8)
C1 Sn1 O2 86.18(13)
C12 C11 C16 118.9(3)
C12 C11 C9 122.4(3)
C16 C11 C9 118.5(3)
22

C1 Sn1 O2 158.58(11) O2 C13 C15 119.3(3)
C5 Sn1 O2 86.76(14)
O1 Sn1 O4 144.34(9)
O3 Sn1 O4 70.60(9)
C1 Sn1 O4 84.24(14)
C5 Sn1 O4 81.11(15)
O2 Sn1 O4 143.42(8)
C14 C15 C16 119.4(4)
C14 C15 H15 120.3
C16 C15 H15 120.3
C2 C1 Sn1 115.9(3)
Sn1 C1 H1A 108.3
Sn1 C1 H1B 108.3
O3 Sn1 O4 73.10(9)
O1 Sn1 O4 90.37(9)
N1 C13 C15 121.8(3)
C16 C15 C20 118.8(3)
C7 Sn1 O4 159.23(11) C16 C15 C13 122.8(3)
C1 Sn1 O4 88.21(11)
O2 Sn1 O4 79.39(9)
C13 N1 O1 117.6(3)
C20 C15 C13 118.3(3)
C17 C16 C15 120.2(3)
C18 C17 C16 119.7(3)
N1 O1 Sn1 116.71(17) O4 C17 N2 119.7(3)
C13 N1 C14 130.2(3) C17 C18 C19 121.6(3)
C9 N1 O1 119.0(3)
C9 N1 C10 129.3(3)
O1 N1 C10 111.5(3)
C17 O4 Sn1 112.4(2)
O4 C17 C19 119.7(3)
N2 C17 C19 120.5(3)
C23 C24 C19 120.0(3)
C15 C16 C11 120.6(3)
O1 N1 C14 111.7(3)
C21 N2 O3 117.7(3)
C17 C18 Br1 119.2(3)
C19 C18 Br1 119.2(3)
C21 N2 C22 129.5(3) C20 C19 C18 118.5(3)
O3 N2 C22 112.6(3) C19 C20 C15 121.0(3)
N1 O1 Sn1 112.86(17) O4 C21 N2 119.3(3)
C13 O2 Sn1 113.5(2) O4 C21 C23 119.1(3)
N2 O3 Sn1 113.88(18) N2 C21 C23 121.6(3)
N2 O3 Sn1 117.78(17) C20 C21 C22 118.5(3)
C9 O2 Sn1 111.3(2)
C17 N2 O3 119.4(3)
C17 N2 C18 128.3(3)
O3 N2 C18 111.3(3)
C21 C20 C19 121.6(3)
C22 C23 C24 119.5(3)
C13 C12 C11 121.0(4)
C14 C13 C12 118.8(3)
C21 O4 Sn1 113.4(2)
C2 C1 C6 117.2(3)
C2 C1 Sn1 120.0(3)
C6 C1 Sn1 122.8(3)
C3 C2 C1 121.3(3)
C2 C3 C4 120.3(3)
C28 C23 C24 119.7(3)
C28 C23 C21 121.6(3)
C24 C23 C21 118.6(3)
C25 C24 C23 120.8(3)
C24 C25 C26 118.5(4)
C27 C26 C25 121.8(4)
C15 C14 C13 121.3(3) C6 C5 Sn1 117.4(3)
C15 C14 Br1 119.4(3) C1 C2 C3 116.2(5)
C13 C14 Br1 119.4(3) C4 C3 C2 116.4(11)
C20 C19 C24 118.7(3) C5 C6 C7 115.9(5)
C20 C19 C17 122.4(3) C8 C7 C6 115.6(5)
23

C5 C4 C3 119.4(3)
C6 C5 C4 120.1(3)
C5 C6 C1 121.7(3)
C27 C26 Br2 118.6(3)
C25 C26 Br2 119.6(3)
C26 C27 C28 118.8(4)
C23 C28 C27 120.4(3)
C24 C19 C17 118.6(3)
Table 8 Antibacterial activity of the ligand and its organotin(IV) derivatives
Compound
Inhibition zone (mm)
E. coli
22
K. pneumoniae S. typhi
S. aureus
Hmbbha (1)
26
32
25
18
21
13
27
21
15
16
24
28
23
13
13
Me2Sn(mbbha)2 (2)
Bu2Sn(mbbha)2 (3)
Ph2Sn(mbbha)2 (4)
Doxycycline (5)
30
20
16
24
Note: E. coli = Escherichia coli, K. pneumoniae = Klebsiella pneumoniae, S. typhi = Salmonella
typhi, S. aureus = Staphylococcus aureus
Table 9 Summary statistics of statistical analysis
Compounds
N
Mean
Std. Deviation Std. Error
95% Confidence Interval for Mean
Minimum Maximum
Lower Bound
Upper Bound
(Hmbbha)
4
4
4
4
4
21.25
29.25
22.25
15.50
22.75
5.737
2.217
2.217
2.082
5.852
5.745
2.869
1.109
1.109
1.041
2.926
1.285
12.12
25.72
18.72
12.19
13.44
19.51
30.38
32.78
25.78
18.81
32.06
24.89
13
27
20
13
16
13
26
32
25
18
30
32
Me2Sn(mbbha)2
Bu2Sn(mbbha)2
Ph2Sn(mbbha)2
Doxycycline
Total
20 22.20
24

Table 10 ANOVA
Sum of Squares df
Mean Square
F
Sig.
Between Groups
Within Groups
Total
383.200
244.000
627.200
4
95.800
16.267
5.889
.005
15
19
Table 11 Tukey’s multiple comparative test results
Compound (Hmbbha) Me2Sn(mbbha)2 Bu2Sn(mbbha)2 Ph2Sn(mbbha)2 Doxycycline
Mean
21.25a 29.25b 22.25ab 15.50a 22.75ab
Note: Distinct letters in superscripts show statistically significant difference
25

Graphical Abstract
Synthesis, spectroscopic characterization, X-ray diffraction studies and in-vitro antibacterial
activities of diorganotin(IV) derivatives with N-methyl-4-bromobenzohydroxamic acid.
OH
O
N
Ligand
Br
+
Reflux
Toulene/6hrs
Sn
O
Organotin salt
Diorganotin(IV) complex
26

HIGHLIGHTS
• The compounds were characterized by CHN, IR, NMR and X-ray methods.
• The ligand in diorganotin(IV) complexes is bidentate.
• The geometry around tin in diorganotin(IV) complexes is octahedral.
•
The dimethyltin(IV) complex has exhibited significant antibacterial activity
27