Synthesis and antimicrobial activities of sulfonohydrazide-substituted 8-hydroxyquinoline derivative and its oxinates

Article abstract of DOI:10.1002/aoc.1631

Looking at the pharmacological importance of 8-hydroxyquinolines and sulfonamides, in the present study, a novel bi-dentate ligand4-amino-N′- [(8-hydroxyquinoline-5-yl)methyl]benzenesulfonohydrazide(AHQMBSH) havingabovebothmoietieswithin a singlemolecular framework was synthesized by the reaction of N-acetamidobenzene sulfonohydrazide with 5-chloromethyl-8- hydroxyquinoline hydrochloride. Its metal(II) oxinates were also prepared with Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) salts. All the above compounds were investigated by physicochemical analyses, thermogravimetric analysis and spectroscopic techniques. Antimicrobial activities for the above prepared compounds were carried out using the agar-plate method against various strains of bacteria (Staphylococcus aureus, Bacillus subtillis, Pseudomonas aerugionsa, Escherichia coli) and fungi (Aspergillus niger and Aspergillus flavous). The results show a significant increase in antimicrobial and antifungal activities of AHQMBSH compared with the parent 8-hydroxyquinoline and sulfonamides. Copyright

Full text of DOI:10.1002/aoc.1631

Full Paper
Received: 1 December 2009
Revised: 1 January 2010
Accepted: 15 January 2010
Published online in Wiley Interscience: 24 February 2010
(www.interscience.com) DOI 10.1002/aoc.1631
Synthesis and antimicrobial activities
of sulfonohydrazide-substituted
8-hydroxyquinoline derivative and its oxinates
Ritu B. Dixita∗, Satish F. Vanpariab, Tarosh S. Patelb, Chandresh L. Jaganib,
Hiren V. Doshia and Bharat C. Dixitb
Looking at the pharmacological importance of 8-hydroxyquinolines and sulfonamides, in the present study, a novel bi-dentate
ligand4-amino-Nꢀ-[(8-hydroxyquinoline-5-yl)methyl]benzenesulfonohydrazide(AHQMBSH)havingabovebothmoietieswithin
a single molecular framework was synthesized by the reaction of N-acetamidobenzene sulfonohydrazide with 5-chloromethyl-
8-hydroxyquinoline hydrochloride. Its metal(II) oxinates were also prepared with Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)
salts. All the above compounds were investigated by physicochemical analyses, thermogravimetric analysis and spectroscopic
techniques. Antimicrobial activities for the above prepared compounds were carried out using the agar-plate method against
various strains of bacteria (Staphylococcus aureus, Bacillus subtillis, Pseudomonas aerugionsa, Escherichia coli) and fungi
(Aspergillus niger and Aspergillus flavous). The results show a significant increase in antimicrobial and antifungal activities of
c
AHQMBSH compared with the parent 8-hydroxyquinoline and sulfonamides. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: 8-hydroxyquinoline; sulfonylhydrazide; oxinates; antibacterial and antifungal activity
Introduction
Thus, looking at the promising biological activities of sulfon-
amides and 8-hydroxyquinolines, it was thought interesting to
bring these two biologically active moieties within a single molec-
ular framework with a view to studying their additive effects
on the chemical and biological properties. Hence, the present
study is enriched with progressive findings about the synthesis,
characterization and comparative biological study of 4-amino-Nꢁ-
[(8-hydroxyquinoline-5-yl)methyl]benzene sulfonohydrazide and
its M(II) oxinates.
Among the class of hydroxyquinolines, the chemistry of 8-
hydroxyquinolines (8HQs) has attracted special interest due
to their diverse biological properties[1,2] such as antiamebic,[3]
antiseptic and disinfectant,[4,5] antimalarial,[6] antituberculotic,[7]
antidiuretic,[8] anticancer,[9,10] antibacterial and antifungal.[11–13]
8HQ shows remarkable effects similar to the antibiotic, lomofugin,
whichrapidlyandselectivelyinhibitstheRNAsynthesisinyeast.[14]
Iron bound to the lipophilic chelator, 8HQ, causes substantial DNA
strand breakage of cultured human lung cells.[15]
8-Hydroxyquinoline-likebiologicalandpharmacologicalchelat-
ing agent-based ligands and chelates are in progress in coordi-
nation studies with increasing interest[16,17] and also in the field
of metal extraction.[18] 8HQs exert the above-mentioned activi-
ties, possibly due to their ability to chelate with the metal ions,
which essential for metabolism,[13] where the –OH group of
8HQ acts as an acid, dissociating to –O−. Bivalent cations are
bounded by the dissociated acid group and the lone pair of elec-
trons borne by the nitrogen atom. The metal chelates of 8HQs
(oxinates) have been reported biologically active due to their
lipid solubility and have comparable activity against bacteria and
fungi. The activity of oxinates was explained by assuming that
these complexes first penetrate the cell wall due to lipid solubil-
ity and at the site of action undergo dissociation to 1 : 1, 8HQ:
complex, which then becomes a toxic entity by combining with
the metal binding sites of enzymes as well as by blocking the
same.[19–22]
Experimental
Materials and Methods
All the chemicals used, including sulfanilamide, 4-
aminobenzenesulfonylhydrazide and 8-hydroxyquinoline, were
of analytical grade and were purchased from local markets. They
were purified by standard methods prior to use.[23] Nutrient-
agar and potato dextrose agar were purchased from Hi-media
Chemicals, India. Metal(II)-salts (chloride/nitrate/sulfate) of Mn(II),
Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) were used in their hydrated
form.
∗
Correspondence to: Ritu B. Dixit, Ashok and Rita Patel Institute of Integrated
Study and Research in Biotechnology and Allied Sciences, Chemistry, New
Vallabh Vidyanagar-388 121, India. E-mail: ritsdixit@yahoo.co.in
a
AshokandRitaPatelInstituteofIntegratedStudyandResearchinBiotechnology
and Allied Sciences, New Vallabh Vidyanagar-388 121, India
In addition to these, the synthetic antibacterial sulfonamides
have been well documented since 1935, due to their excellent
pharmacological activities, but toxicity and microbial resistance
mean that it cannot be used in the treatment of disease.[13]
b
ChemistryDepartment,V.P.&R.P.T.P.ScienceCollege,VallabhVidyanagar-388
120, India
c
Appl. Organometal. Chem. 2010, 24, 408–413
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Sulfonohydrazide-substituted 8-hydroxyquinoline derivative
Silica gel F254 thin-layer chromatographic plates of size
20 × 20 cm were purchased from the E. Merck (India) Limited,
Mumbai and used for purity evaluation. The elemental analyses
(C, H, N and S) were performed with a model Elemental Vario
EL C, H, N elemental analyzer. The infrared spectra (FT-IR) were
obtained from KBr pellets in the range 4000–400 cm−1 with a
Perkin Elmer spectrum GX spectrophotometer (FT–IR) instrument.
The 1H NMR and 13C NMR Attached Proton Test (APT) spectra
were recorded on a Bruker (400 MHz) instrument using DMSO-
d6 as solvent as well as an internal reference standard. The
mass (ESI-MS) spectrum of 4-amino-Nꢁ-[(8-hydroxyquinoline-5-
yl)methyl]benzenesulfonohydrazide (AHQMBSH) was recorded
on a Shimadzu LC-MS 2010 eV mass spectrophotometer in
acetonitrile. Diffuse electronic spectra were recorded on a
Beckman DK-2A spectrophotometer using MgO as a reference.
Magnetic moments were determined by the Gouy method
with mercury tetrathiocyaneto-cobaltate(II), [HgCo(NCS)4] as
calibrant (χg = 1644 × 10−6 cgs units at 20 ◦C), by Citizen
Balance (at room temperature). The diamagnetic correction
was made using Pascal’s constant.[24] The thermogravimetric
analyses studies were carried out with a model P◦erkin Elmer
thermogravimetry analyzer at a heating rate of 10 C min−1 in
air. The metal contents of the complexes were analyzed by
EDTA titration after decomposing the organic matter with HClO4,
H2SO4 and HNO3 (1 : 1.5 : 2.5) mixture.[25] The melting point of
AHQMBSH was checked by standard open capillary method and
is uncorrected.
The
chloromethyl-8-hydroxyquinoline
4-acetamidobenzenesulfonylhydrazide[26]
hydrochloride
and
5-
Scheme 1. Proposed route for the synthesis of AHQMBSH and
[M(AHQMBSH)2(H2O)2].
(CMHQ)[4]
were prepared and used as starting materials for the synthe-
sis of novel ligand AHQMBSH by slight modification of the
method reported in the literature[27] while metal(II) complexes
of AHQMBSH were synthesized by a subsequently reported
method.[28]
Synthesis of Metal(II) Oxinates: M(II)(AHQMBSH)2; M = Mn(II),
Fe(II), Co(II), Ni(II), Cu(II), Zn(II)
A warm solution of metal(II) salt (2.5 mmol) in 50% aqueous formic
acid (2.5 ml) was added drop by drop with continuous stirring
to previously warmed solution of AHQMBSH (5 mmol, 2 equivs)
in 20% aqueous formic acid solution (20 ml). With the proper
adjustment of the pH (∼8.5) with 50% NH4OH, the resultant
mixture was further digested in a water bath for 4–5 h and
centrifuged. The suspended solid complex was allowed to settle
and collected by filtration, washed with sufficient quantity of
distilled water and then with a little hot ethanol and acetonitrile,
thendriedinvacuumdesiccatorsoveranhydrouscalciumchloride.
The yield was 80–90%.
The outline of synthesis of AHQMBSH and its M(II) oxinates is
shown in Scheme 1. The physicochemical parameters of metal(II)
oxinates are summarized in Table 1.
Synthesis of ligand: AHQMBSH
To the mixture of 4-acetamidobenzenesulfonylhydrazide (5.87 g,
25.6 mmol) and triethylamine (8.18 g, 80.8 mmol) in dry pyridine
(40 ml), CMHQ (6.2 g, 26.9 mmol) was added with continuous
stirring. The contents were refluxed for 70 min. The completion of
the reaction was confirmed by TLC using CHCl3 : CH3OH (80 : 20)
mixture as the mobile phase (Rf 0.45). The excess of pyridine was
distilled off and the residue was poured into the ice-cold water
to yield a dark orange product which was filtered and washed
with hot water and ethyl acetate and then dried over a vacuum
desiccator (7.6 g).
It was further hydrolyzed by refluxing with 0.2 M hydrochloric
acid solution (50 ml) for 45 min. The reaction mixture was then
cooled, poured into ice-cold water and neutralized with saturated
Na2CO3 solution to yield a dark green product, which was filtered
off, washed with boiling water followed by ethyl acetate and
recrystallized from acetonitrile to afford dark green crystals, then
dried in a vacuum oven. The formation of the product was
confirmed by TLC using CHCl3 : CH3OH (80 : 20) mixture as the
mobile phase (Rf 0.53). Yield: 4.5 g, (51%). Decomposed at 241 ◦C;
ESI-MS: 344.02 m/z (M+ peak).
Results and Discussion
5-Chloromethyl-8-hydroxyquinoline hydrochloride was prepared
by chloromethylation of 8-hydroxyquinoline. Considerable dif-
ficulties were faced to obtain high purity of CMHQ even af-
ter washing the crude CMHQ with concentrated hydrochloric
acid and acetone. This might be due to incomplete removal
of 8-hydroxyquinoline. Another difficulty was the possibility
of substitution reaction during the crystallization with pro-
tic solvent. The use of inorganic base catalyst was avoided,
such as sodium/potassium bicarbonate, sodium/potassium hy-
drogen carbonate and sodium hydroxide, as it either leads to a
slow reaction or may give 5-hydroxymethyl-8-hydroxyquinoline
in quantitative yield.[4] To overcome these difficulties, triethy-
lamine (TEA) was used as scavenger while reacting CMHQ with
c
Appl. Organometal. Chem. 2010, 24, 408–413
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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R. B. Dixit et al.
Table 1. Physicochemical parameter of the AHQMBSH ligand and M(II)(AHQMBSH)2 complexes
Elemental analysis, % found (required)
Compounds
(empirical formula)
Molecular
weight
Yield m.p.a
(%)
(◦C)
µeff B.M. Ea (kcal
Color
C
H
N
S
Metal (calcd) mol−1
)
AHQMBSH (C16H16N4O3S)
344.39
777.73
778.64
781.72
781.48
768.32
788.20
Dark green 63.5
241 55.82
4.66
16.31
9.33
–
–
12
(55.80) (4.68) (16.27) (9.31)
>300 49.40 4.43 14.38 8.28
[Mn(AHQMBSH)2(H2O)2] (C32H34MnN8O8S2)
[Fe(AHQMBSH)2(H2O)2] (C32H34FeN8O8S2)
[Co(AHQMBSH)2(H2O)2] (C32H34CoN8O8S2)
[Ni(AHQMBSH)2(H2O)2] (C32H34NiN8O8S2)
[Cu(AHQMBSH)2(H2O)] (C32H32CuN8O7S2)
[Zn(AHQMBSH)2(H2O)2] (C32H34ZnN8O8S2)
Brown
87
7.14
5.58
(5.92)
5.28
7.5
8.6
8.5
8.9
8.4
8.8
(49.42) (4.41) (14.41) (8.25) (7.06)
>300 49.39 4.39 14.41 8.21 7.08
(49.36) (4.40) (14.39) (8.24) (7.17)
>300 49.14 4.41 14.30 8.23 7.48
(49.17) (4.38) (14.33) (8.20) (7.54)
287 49.21 4.37 14.37 8.18 7.64
(49.18) (4.39) (14.34) (8.21) (7.51)
>300 49.99 4.18 14.61 8.33 8.30
(50.02) (4.20) (14.58) (8.35) (8.27)
>300 48.79 4.32 14.26 8.13 8.42
(48.76) (4.35) (14.22) (8.14) (8.30)
Dark brown 84
Dark green 88
(4.90)
4.86
(3.87)
3.27
Dark red
91
(2.83)
1.86
Dark green 89
Dark yellow 82
(1.73)
D
a Melting points (◦C) are uncorrected; D = diamagnetic.
4-acetamidobenzenesulfonylhydrazide to afford intermediate in
good yield, which upon acid hydrolysis gave AHQMBSH in moder-
ate yield.
the presence of –SO2 –group.[30] The N–H stretching vibrations
appeared near about 3200 cm−1, while N–H and C–N bending
vibrationsappearedat1659and1260 cm−1, respectively, showing
the presence of an amino group. The band observed at 1036 cm−1
shows the presence of the –HN–NH–group.
The synthesized novel 4-amino-Nꢁ-[(8-hydroxyquinoline-5-
yl)methyl]benzene sulfonohydrazide (AHQMBSH) appears as dark
greencrystals.Ithaspartialsolubilityinacetone,methanol,ethanol
and acetonitrile, while being soluble in polar aprotic solvents like
dimethylformamide (DMF), dimethylsulfoxide (DMSO), organic
acids and pyridine. All the metal(II) oxinates, M(II)(AHQMBSH)2
had characteristic color, are stable in air and practically insoluble
in water, ethanol, methanol, chloroform and hexane, while low
solubility was observed in DMF as well as in DMSO.
However, comparisons of FT-IR spectra of ligand (AHQMBSH)
and its metal(II)-coordinated oxinates showed some important
characteristic differences.[31] One of the significant differences to
be expected was the presence of a more broadened band in the
region of 2700–3400 cm−1 for the chelates, as the oxygen of the
–OH group of the ligand forms a coordination bond with the
metal ions. It also explains the presence of coordinated water
molecules.[32] Another noticeable difference is that the band due
to the C N stretching vibration of 8HQ at around 1600 cm−1
in the IR spectrum of AHQMBSH was shifted to lower frequency,
whereas the band at 1400 cm−1 in the IR spectrum of AHQMBSH
assigned to in-plane –OH deformation was shifted towards higher
frequency in the spectra of the chelates due to the formation
of the M–O bond.[33] This was further confirmed by a weak
band at 1100 cm−1 corresponding to C–O–M stretching, while
bands around ∼730 and ∼545 cm−1 correspond to the M → N
vibration.[34] The bands due to the –HN–NH–group appear to be
the same as in the spectrum of AHQMBSH. These characteristic
features of the IR studies suggest the formation of AHQMBSH and
its metal(II) oxinates.
Characterizations
The formation of the AHQMBSH was apparent from the dark blue
and yellow spots by visualizing in long- and short-wavelength
UV light respectively on the TLC. The mass spectrum (ESI-MS) of
AHQMBSHwasrecordedinacetonitrileandthemolecularionpeak
observed at m/z 344.02 confirmed the proposed formula.
The results of elemental analyses (C, H, N, S) of ligand AHQMBSH
and its metal(II) oxinates are given in Table 1 and were in good
agreement with their predicted molecular formula, showing that
the oxinates have 1 : 2 metal–ligand ratio.
FT-IR Spectra
Diffuse Electronic Spectral and Magnetic Properties Data
TheFT-IRspectrumofAHQMBSHandallofitsoxinatesshowsallthe
important stretching and bending vibrations in the appropriate
region.[29] In the spectrum of AHQMBSH, the band appeared
at 3379 cm−1 due to O–H stretching vibration and a strong
band at 1400 cm−1 was due to O–H bending vibration and
C–O stretching vibration.[29] The –CH2 –shows C–H stretching
vibration at 2964 cm−1. The IR spectrum of AHQMBSH also
shows the important bands at 1598 cm−1 of C N, 1500 cm−1
of C C and 1475 cm−1 of C–C, assigned to the aromatic skeletal
stretching vibrations of the parent heterocyclic ring.[29] Further,
two strong bands of S O appeared at 1318 and 1144 cm−1 due
to asymmetric and symmetric stretching vibrations, suggesting
The diffuse electronic spectra of [Cu(AHQMBSH)2(H2O)] exhibited
two bands at 26 235 cm−1 due to charge transfer and a broad
band having maxima at 15 576 cm−1 due to the 2Eg
→
2T2g
transition. The broadening of the signal might be due to
Jahn–Teller distortion. The absorption bands of the diffuse
electronic spectra and the value of their magnetic moment favor a
tetragonally distorted octahedral geometry around Cu(II) ion.[35,36]
[Ni(AHQMBSH)2(H2O)2] showed three weak absorption bands at
9981, 16 025 and 24 470 cm−1 corresponding to the characteristic
3
3
transitions A2g
→
3T2g
,
3A2g
→
3T1g(F), A2g
→
3T1g(P).
[Co(AHQMBSH)2(H2O)2] exhibited three absorption bands at
c
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Appl. Organometal. Chem. 2010, 24, 408–413

Sulfonohydrazide-substituted 8-hydroxyquinoline derivative
Figure 1. Thermogravimetric curve of AHQMBSH and its oxinates.
9830, 15490 and 22115 cm−1, respectively, due to T1g(F) →
in the range of 125–180 ◦C might be attributed to the metal-
coordinated two water molecules.[40] This also satisfies the six
coordination sites of the metal ions of metal(II) oxinates. For
metal(II) oxinates maximum weight loss (74.64, 75.30, 75.55, 74.40,
73.32 and 73.40%) was observed in the temperature range of
210–900 ◦C, and the remaining weights of 18.85 (878 ◦C), 18.80
(779 ◦C), 18.35 (697 ◦C), 19.40 (664 ◦C), 21.00 (631 ◦C) and 19.70
(784 ◦C) correspond to a mixture of metal oxide and some ashes
as the ultimate pyrolysis products.
There was a remarkable difference in the mode of thermal
degradation for AHQMBSH and its oxinates. Oxinates have shown
fast decomposition patterns as compared with AHQMBSH. These
results of thermal behavior can be explained by the fact that the
decomposition of chelates was catalytically induced by the metal
ions.[41]
4
4T2g(F), 4T1g(F) → A2g(F) and 4T1g(F) → T1g(P) transitions. The
absorption bands of the diffuse electronic spectra and values of
their magnetic moments show an octahedral geometry around
Ni(II) and Co(II) ions.[37,38] The spectra of [Mn(AHQMBSH)2(H2O)2]
showed weak bands at 16 798, 18 435 and 23 816 cm−1 assigned
4
4
to the 6A1g → T1g,6A1g → T2g,6A1g → A1g,4Eg transitions and
their magnetic moment values suggest an octahedral geometry
for the Mn(II) ion. The spectrum for [Fe(AHQMBSH)2(H2O)2] shows
4
4
4
bands at 18 985 and 36 738 cm−1 assigned to the 5T2g → Eg and
3
5T2g
→
3T1g transitions, respectively, suggesting its octahedral
structure in support of the magnetic moment value around the
Fe(II) ion. As the spectrum of [Zn(AHQMBSH)2(H2O)2] was not well
resolved, it was not well interpreted, but its magnetic moment
value shows that it is diamagnetic in nature, as expected.[28]
The results of the magnetic moment value (Table 1) were shown
to have octahedral geometry for all the M(II) oxinates. Hence,
the observed values of magnetic moments and the electronic
spectra of M(II) oxinates supported octahedral geometry for all the
structures.[39]
The energy of activation (Ea) for thermal decomposition of
AHQMBSH and its oxinates was estimated by the reported method
using following equation:[42]
ln[ln(1/y)] = (Ea/RT + 1) ln T + constant
The energy of activation (Ea) was computed from the slope
(−Ea/R)oftheplotofln[ln(1/y)]vs(lnT),andisnotedinTable 1.The
Thermogravimetric Analysis
energy of activation for AHQMBSH was found to be 12 kcal mol−1
,
while the activation energy observed for oxinates was between
Thermogravimetric analysis (TGA) for the AHQMBSH and its
oxinates◦ was carried out within the temperature range of
40–900 C in air at the heating rate of 10 ◦C min−1 to establish
their compositional differences and to ascertain the nature of
associated water molecules. The thermogravimetric curves of
all the compounds are presented in Fig. 1. The determined
temperature ranges and corresponding percentage mass losses
accompanying the changes on heating revealed the following
findings.
Securitization of this data envisages that AHQMBSH follows
single-step thermal decomposition. The initial weight loss of 1%
might be due to loosely held solvent in AHQMBSH. The weight
loss commences in the range of 150–550 ◦C up to 74% and further
slower degradation takes place up to 900 ◦C.
8.8 and 10.9 kcal mol−1
.
1H NMR Spectra
The 1H NMR spectrum of ligand exhibited a broad singlet at
δ 9.99 ppm due to the –OH proton.[43,44] Disappearance of this
signal in the spectrum of Zn(II) complex suggested that this proton
had been lost due to coordination of oxygen atom to the metal
ion.[45] The signal due to H2 of Zn(II) complex appeared at very
low magnetic field compared with that of ligand, suggesting the
involvement of N1 in the formation of complex. The protons of
N(1) and N(2) in AHQMBSH and its Zn(II) complex resonated as a
singlet at δ 10.74, δ 12.48 and δ 10.71, δ 12.47 ppm respectively.
This suggested that neither of the nitrogen atoms participated
in the complex formation as the chemical shifts remained almost
unchanged both in ligand as well as in complex. The N(3)H2
protons appeared as singlet at δ 6.14 in ligand shifted to downfield
in Zn(II) complex (δ 6.19). All the quinoline protons shifted slightly
downfield, except H7, which shifted slightly upfield.[45,46]
Similarly, securitizations of the TGA data of oxinates of
corresponding Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) have
shown two-step decomposition. The initial weight loss occurring
might be due to the solvent molecules or loosely held moisture
trapped inside the oxinates, whereas the weight loss observed
c
Appl. Organometal. Chem. 2010, 24, 408–413
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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R. B. Dixit et al.
Table 2. Antimicrobial activity of all the compounds
Zone of inhibition (mm)a
Sample no.
Compounds
Sulfanilamide
S. aureus
B. subtilis
E. coli
P. aeruginosa
A. niger
A. flavus
1
18
16
24
34
16
22
17
18
19.5
13
14
15
22
35
13
19.5
15
16
22
15
20
17
26
31
13
21
16
14
21
11
19
21
22
28
14
19
17
19
20
12
24
22
21
37
12
23
13.5
17
20
12
22
20
19
32
11
21
18
15
19.5
15
2
Sulfahydrazone
3
8HQ
4
AHQMBSH
5
[Mn(AHQMBSH)2(H2O)2]
[Fe(AHQMBSH)2(H2O)2]
[Co(AHQMBSH)2(H2O)2]
[Ni(AHQMBSH)2(H2O)2]
[Cu(AHQMBSH)2(H2O)]
[Zn(AHQMBSH)2(H2O)2]
6
7
8
9
10
a Zone of inhibition (mm) obtained upon subtraction of control (DMSO) ≈11.
13C NMR (APT) Spectra
to the AHQMBSH and oxinates attributed less activity. Thus, it was
suggestedthatAHQMBSHexertsitsbiologicalactivitiessimilarlyto
8HQ as a membrane-active agent through metal-ion chelation.[48]
The biological activity of the above compounds also depends
on the nature of the ligand, concentration, lipophilicity, nature of
metal ion, coordinating sites and geometry of the complex. All
the M(II) oxinates have also shown moderate or less activity as
compared with AHQMBSH, as the mechanisms of inhibition are
different. The activity of oxinates against bacteria and fungi was
explained by assuming that these complexes first penetrate the
cell-wall due to lipid solubility and at the site of action undergo
dissociation to 1 : 1, 8HQ : complex which then becomes a toxic
entity by combining with the metal binding sites of enzymes as
well as by blocking the same.[22]
The13CNMR(APT)spectraoftheAHQMBSHandZn(II)(AHQMBSH)2
were in acceptable patterns.[44,45] In the 13C NMR spectrum of
AHQMBSH all the aromatic carbon peaks were observed in be-
tween δ 110.04–153.99 ppm and a peak of C11 appeared at
δ 58.27. C2, C5 signals at δ 148.13, 116.40 ppm, respectively, in
AHQMBSH significantly shifted upfield at δ 144.68, 112.32 ppm, re-
spectively, in the complex. The C8, C10 signal (δ 153.99, 138.53 ppm
respectively) underwent a downfield shift (δ 161.86, 143.69 ppm
respectively) in Zn(II)(AHQMBSH)2, indicating coordination of Zn
with N1 and oxygen attached to C8 of quinoline ring.
Antimicrobial Activity
The synthesized novel ligand AHQMBSH and its oxinates,
M(II)(AHQMBSH)2, were subjected to in vitro antimicrobial ac-
tivity against the Gram-positive bacteria Staphylococcus aureus
and Bacillus subtillis and the Gram-negative bacteria Pseu-
domonas aerugionsa and Escherichia coli, using agar nutrient as
medium, and fungi Aspergillus niger and Aspergillus flavous, using
potato dextrose agar as medium. A stock solution of 25 ppm
was prepared by dissolving compounds in 20% DMSO solu-
tion. The antimicrobial and antifungal activity was performed
at a concentration 25 µg ml−1, using the agar-cup method,[47]
and using DMSO as a control for comparisons of antibacte-
rial and antifungal activity with parent 8HQ, sulfanilamide and
4-aminobenzenesulfonylhydrazide. The results of the measured
zone of inhibition (in millimetres) of comparative biological
study for AHQMBSH and its oxinates against each of species
are shown in Table 2. This suggested that AHQMBSH ligand
exhibited higher activity than parent moieties sulfanilamide,
4-aminobenzenesulfonylhydrazide and 8HQ, while oxinates
showed less bioactivity as compared with AHQMBSH.
Conclusion
In the present investigation novel AHQMBSH and its octahedral
metal(II) oxinates (1 : 2 metal-ligand ratio) were synthesized and
characterized, and showed good antibacterial and antifungal
activities compared with the parent moieties 8-hydroxyquinoline
and sulfonamides. Among the oxinates, Fe(II) and Cu(II) chelates
showed better activity, but were found to be less active than
AHQMBSH.
Acknowledgments
The authors gratefully acknowledge the financial support of this
work by the TWAS (UNESCO FR: 08-025RG/CHE/AS), Italy. We
are also thankful to C.V.M. and Director, ARIBAS, New Vallabh
Vidyangar for providing necessary research facilities.
Supporting information
AHQBMSH was found to be more active. The enhancement
in the activity of AHQMBSH might be due to the synergistic[13]
Supporting information may be found in the online version of this
article.
effect of sulfonamide and 8HQ moieties within a single molecular
framework. AHQMBSH is similar to sulfonamides that, having
the heterocyclic tail of that 8HQs, involve chelation with metal
ions to form lipophilic chelates, which rapidly transfer the metal
across the intact plasma membrane of endothelial cells of Gram-
positive bacteria and increase their sensitivity to oxidants. The
outer membrane of the Gram-negative bacteria might serve as a
selective barrier that hinders the passage in the cell in comparison
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