Synthesis and characterization of new macrocycles containing pendant groups

Article abstract of DOI:10.1081/SIM-120028305

The new ligands, 1,5,8,12-tetraaza-4-(1′,1′-dimethylethyl)-2- (1″,1″,2″, 2″,3″,3″,3″- heptafluoropropyl)-9,11-(dimethyl)-cyclotetradeca-1,4,8,11-tetraene (L ¹) and 1,5,9,13-tetraaza-4-(1′,1′-dimethylethyl)-2- (1″,1″,2″, 2″,3″,3″,3″- heptafluoropropyl)-10,12-(dimethyl)-cyclohexadeca-1,4,9,12-tetraene (L ²), have been prepared by the reaction of 1,1,2,2,3,3,3-heptafluoro- 7,7-dimethyl-4,6-octanedione with ethylenediamine and acetyl acetone (L ¹) and 1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione with 1,3-diaminopropane and acetylacetone (L²), respectively. Their complexes with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) ions have also been synthesized and characterized by elemental analyses, magnetic susceptibility measurements, molar conductance measurements, IR, EPR, ¹H NMR, and UV-Visible spectra. The molar conductance values show that the complexes of Fe(III) and Cr(III) are 1:1 electrolytes, the Ni(II) and Cu(II) complexes are 1:2 electrolytes while those of Mn(II), Co(II), and Zn(II) appear to be non-ionic. An octahedral structure has been proposed for all of these metal ions except for those of Cu(II) and Ni(II), which appear to be square-planar. The β values indicate a considerable orbital overlap in the metal-ligand bond. All of the compounds have been tested against gram-positive bacteria of Staphylococcus aureus and gram-negative bacteria of Escherichia coli. The results show that these compounds inhibit the growth of bacteria.

Full text of DOI:10.1081/SIM-120028305

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Synthesis and Reactivity in Inorganic and Metal-
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Synthesis and Characterization of New Macrocycles
Containing Pendant Groups
N. Nishat a , Rahis‐ud‐din a & M. M. Haq a
a Department of Chemistry , Jamia Millia Islamia , New Delhi, 110025, India
Published online: 16 Nov 2010.
To cite this article: N. Nishat , Rahis‐ud‐din & M. M. Haq (2004) Synthesis and Characterization of New Macrocycles
Containing Pendant Groups, Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 34:2, 335-351, DOI:
10.1081/SIM-120028305
To link to this article: http://dx.doi.org/10.1081/SIM-120028305
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SYNTHESIS AND REACTIVITY IN INORGANIC AND METAL-ORGANIC CHEMISTRY
Vol. 34, No. 2, pp. 335–351, 2004
Synthesis and Characterization of New
Macrocycles Containing Pendant Groups
*
N. Nishat, Rahis-ud-din, and M. M. Haq
Department of Chemistry, Jamia Millia Islamia, New Delhi, India
ABSTRACT
The new ligands, 1,5,8,12-tetraaza-4-(10,10-dimethylethyl)-2-(100,100,200,
200,300,300,300-heptafluoropropyl)-9,11-(dimethyl)-cyclotetradeca-1,4,8,11-
tetraene (L1) and 1,5,9,13-tetraaza-4-(10,10-dimethylethyl)-2-(100,100,200,
200,300,300,300-heptafluoropropyl)-10,12-(dimethyl)-cyclohexadeca-1,4,9,12-
tetraene (L2), have been prepared by the reaction of 1,1,2,2,3,3,3-
heptafluoro-7,7-dimethyl-4,6-octanedione with ethylenediamine and
acetyl acetone (L1) and 1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-
octanedione with 1,3-diaminopropane and acetylacetone (L2), respectively.
Their complexes with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), and
Zn(II) ions have also been synthesized and characterized by elemental
analyses, magnetic susceptibility measurements, molar conductance
1
measurements, IR, EPR, H NMR, and UV-Visible spectra. The molar
conductance values show that the complexes of Fe(III) and Cr(III) are
1 : 1 electrolytes, the Ni(II) and Cu(II) complexes are 1 : 2 electrolytes
*
Correspondence: N. Nishat, Department of Chemistry, Jamia Millia Islamia, New
Delhi 110025, India; E-mail: nishat_nchem03@yahoo.co.in.
335
DOI: 10.1081/SIM-120028305
0094-5714 (Print); 1532-2440 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Nishat, Rahis-ud-din, and Haq
while those of Mn(II), Co(II), and Zn(II) appear to be non-ionic. An
octahedral structure has been proposed for all of these metal ions except
for those of Cu(II) and Ni(II), which appear to be square-planar. The b
values indicate a considerable orbital overlap in the metal–ligand bond.
All of the compounds have been tested against gram-positive bacteria of
Staphylococcus aureus and gram-negative bacteria of Escherichia coli.
The results show that these compounds inhibit the growth of bacteria.
Key Words: L1; L2; Macrocycle; Pendant group.
INTRODUCTION
The coordination properties of macrocycles bearing pendant donor groups
have evoked much interest, which has produced a rapid advance in the field
of both biomimetic models and abiotic systems. A variety of metallated
macrocycles containing different functional groups on the periphery have been
reported. The syntheses and investigations of macrocyclic complexes are still
of burgeoning research interest and this area is reviewed regularly.[1–5] The
introduction of pendant groups in the macrocycle increases the stability of its
complexes.[6,7] Macrocycles have wide applications in medicine, metal ion
techniques, treatment of kidney stones, in cancer diagnosis, and in treatment of
malignant tumors,[8] they have proved useful as magnetic resonance imaging
(MRI) contrast agents.[9] 5-Fluorouracil has been found to be of immense use in
cancer chemotherapy and has high antitumor activity.[10] Some new copper(II)
complexes show antifungal activities[11] against phytopathogenic fungi.
Several compounds of transition metal ions act as effective antifungal
agents[12] against Aspergillus and Candida species. Metal complexes of diketones
have been used as metal extractants, substituted 1,4-dihydroquinozaline-2,3-dione
exhibit physiological and pharmacological activities, while pyrazolopyrimidine-
5,7-dione has been used as antibacterial agent. Because of the diverse application
of diketones and macrocycles in biological systems, it seemed appropriate to
synthesize macrocycles with pendant arms from diketones and to study their
interaction with metal ion.
In this paper, we report the syntheses of 14- and 16-membered N4
macrocycles, namely 1,5,8,12-tetraaza-4-(10,10-dimethylethyl)-2-(100,100,200,200,
300,300,300-heptafluoropropyl)-9,11-(dimethyl)-cyclotetradeca-1,4,8,11-tetraene
(L1), 1,5,9,13-tetraaza-4-(10,10-dimethyl-ethyl)-2-(100,100,200,200,300,300,300-hepta-
fluoropropyl)-10,12-(dimethyl)-cyclohexadeca-1,4,9,12-tetraene (L2), and
their transition metal complexes (Fig. 1). We are developing new pendant
armed macrocyles in which methyl and fluoro groups act as pendant groups.

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337
Figure 1. Structures of the macrocycles L1 and L2.
RESULTS AND DISCUSSION
The metal-free macrocycle L1 was prepared by the interaction of
1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione, ethylenediamine,
and acetylacetone in 2 : 1 : 1 ratio in ethanol, while there is the formation
of ligand L2 when 1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione
reacts with 1,3-diaminopropane and acetylacetone in 2 : 1 : 1 ratio. The
reactions for the formation of the ligands and their metal complexes
are shown below
C10H11F7O2 þ (CH3CO)2CH2 þ 2NH2(CH2)2NH2
EtOH, Stir, Reflux
ꢀ!C19H27F7N4
L1
C10H11F7O2 þ (CH3CO)2CH2 þ 2NH2(CH2)3NH2
EtOH, Stir, Reflux
ꢀ!C21H31F7N4
L2

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Nishat, Rahis-ud-din, and Haq
HCl, Reflux
L1 þ MCl2ꢀ![ML1Cl2]
HCl, Reflux
L1 þ M0Cl2ꢀ![M0L1]Cl2
HCl, Reflux
L1 þ M00Cl3ꢀ![M00L1Cl2]Cl
HCl, Reflux
L2 þ MCl2ꢀ![ML2Cl2]
HCl, Reflux
L2 þ M0Cl2ꢀ![M0L2]Cl2
HCl, Reflux
L2 þ M00Cl3ꢀ![M00L2Cl2]Cl
where M ¼ Mn(II), Co(II), Zn(II), M0 ¼ Ni(II), Cu(II), and M00 ¼ Cr(III),
Fe(III).
The colors, melting points, and analytical data of the new macrocycles
and their first row transition metal complexes are given in Table 1.
The elemental analyses suggest 1 : 1 (metal–ligand) stoichiometry and
correspond to the composition of the type [ML1Cl2], [ML2Cl2], where M ¼ Mn(II),
Co(II), Zn(II); [M0L1]Cl2, [M0L2]Cl2, where M ¼ Ni(II), Cu(II); and [M00L1Cl2]Cl,
[M00L2Cl2]Cl, where M00 ¼ Cr(III), Fe(III). All the complexes are thermally stable.
The molar conductance of the Mn(II), Co(lI), and Zn(II) complexes of the ligands
L1 and L2 in 1023 M DMSO exhibited low molar conductivity values in the
10–34 ohm21 cm2 mol21 range, suggesting that they are non-electrolytes. While the
complexes of the trivalent metal ions Fe(III) and Cr(III) have molar conductivities
(55–70 ohm21 cm2 mol21) in the range reported for 1 : 1 electrolytes. For the
[NiL1]Cl2, [CuL1]Cl2, and [NiL2]Cl2, [CuL2]Cl2 complexes the molar conductance
falls in the 132–146 ohm21 cm2 mol21 range showing 1 : 2 electrolytes.[13]
IR Spectra
The preliminary identification of the macrocyclic complexes was done from
the IR spectra (Table 2). In 1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octane-
dione, the carbonyl stretching frequencies appear at 1660cm21, however, the
macrocyclic ligands gave no bands assignable to the v(C55O) stretching mode,
because v(C55O) of keto group has been replaced by the v(C55N) vibration. In
the ligand L1, the v(C55N) vibration is observed at 1605cm21, while in the
ligand L2 the v(C55N) vibration is found to appear at 1610cm21
.
A comparison of the IR spectra of free macrocycles with those of their
transition metal complexes indicated a substantial shift in the v(C55N)
(1565–1595 cm21) wave number region.[14] The decrease in the C55N

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339

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Nishat, Rahis-ud-din, and Haq

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341
Table 2. IR spectra bands (cm21) of the ligands and their complexes.
n(C55N)
(m)
n(C–N)
(s)
n(C–C)
(w)
n(M–N)
(s)
n(M–Cl)
(m)
Compounds
Ligand [L1]
[CrL1CL2]Cl
[MnL1Cl2]
[FeL1Cl2]Cl
CoL1Cl2]
1605
1565
1580
1585
1570
1580
1575
1570
1610
1580
1595
1585
1570
1575
1580
1570
1410
1390
1385
1385
1390
1390
1387
1385
1410
1388
1390
1385
1385
1390
1385
1387
1060
1060
1060
1060
1060
1060
1060
1060
1060
1055
1060
1060
1055
1055
1060
1060
—
—
380
310
395
350
360
345
340
—
280
260
275
250
270
250
275
—
[NiL1]Cl2
[CuL1]Cl2
[ZnL1Cl2]
Ligand [L2]
[CrL2Cl2]Cl
[MnL2Cl2]
[FeL2Cl2]Cl
CoL2Cl2]
[NiL2]Cl2
[CuL2]Cl2
[ZnL2Cl2]
385
320
400
325
350
345
335
295
300
270
275
260
280
275
stretching frequencies has been attributed to the coordination of the metal ion via
the nitrogen atom. The presence of a sharp band in the region 310–360 cm21 for
all the complexes can be assigned to v(M–N), supporting the involvement of
nitrogen in coordination. The metal to nitrogen bond is further confirmed by
the decrease in the v(C–N) stretching frequency by 20–25cm21 in all
the complexes. The strong bands in trivalent metal ion Cr(III) and Fe(III)
are observed in the 380–400 cm21 region, due to greater coupling of
chromium(III) and iron(III) with the ligand, which can be attributed to v(M–N)
vibration. The medium intensity bands of v(M–Cl) have been observed
at 250–300 cm21 in all the complexes confirming the metal to chlorine
coordination.
Electronic Spectra and Magnetic Moments
The magnetic moment values and electronic spectral bands are
represented in Table 3. For the chromium(III) ion three spin-allowed
4
transitions are expected from the A2g ground state to three excited quartet
states. In the Cr(III) complexes of the ligands L1 and L2 the three bands
4
4
4
observed (Table 3) are assigned to T1g(P) ꢀ A2g(F), T1g(F) ꢀ A2g(F),

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Nishat, Rahis-ud-din, and Haq
b

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343

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Nishat, Rahis-ud-din, and Haq
4
4
and T2g(F) ꢀ A2g(F) transitions, respectively. The observed magnetic
moment values are slightly lower (3.50–3.72 B.M.) than that calculated value
for three unpaired electrons. However, these studies are indicative of an
octahedral geometry[15] for Cr(III) ion.
The macrocyclic manganese(II) complexes showed effective magnetic
moment values in the range 5.6–5.8 B.M., correspond to a high-spin state and
are very close to the calculated values. The electronic spectra of the Mn(II)
complexes of L1 and L2 in DMSO gave three bands at 24,390, 22,220, and
16,666 cm21 for L1 and at 23,530, 21,740, and 16,390 cm21 for L2, which can
6
4
6
4
6
be assigned to 4Eg(G) ꢀ A1, T2g(G) ꢀ A1g, and T1g (G) ꢀ A1g
transitions, respectively, suggesting an octahedral environment[16] around the
Mn(II) ion.
The iron(III) macrocyles displayed three main d–d bands (Table 3), these
4
4
6
6
bands are attributed to the transitions Eg(G) ꢀ A1, T2g(G) ꢀ A1g, and
6
4T1g(G) ꢀ A1g, respectively. The meff values observed are 5.90 B.M. for
L1 and 5.82 B.M. for L2. On the basis of the magnetic moment values and
the electronic spectral bands, an octahedral geometry for the iron(III) is
proposed.
The observed magnetic moment values of the cobalt(II) complexes are in
the range expected for three unpaired electrons. The electronic spectra showed
three bands at around 20,408, 15,873, and 12,195 cm21 for the [CoL1Cl2]
complex and 19,608, 15,500, and 12,050 cm21 for the [CoL2Cl2] complex, which
4
4
4
can be reasonably assigned to the T1g(P) ꢀ T1g(F),4 A2g(F) ꢀ T1g(F),
4
4
and T2g(F) ꢀ T1g(F) transitions, respectively. These transitions are char-
acteristic of compounds with an octahedral stereochemistry of the Co(II) ion, a
fact that is confirmed by the values of the effective magnetic moment. The
three bands observed for each of the [NiL1]Cl2 and [NiL2]Cl2 complexes at
22,222, 20,000, 18,607 as well as 23,255, 19,420, 18,690 cm21. The former
bands are at 22,222 and 23,255 cm21 due to the charge transfer while the last
two bands can be assigned to the transitions arising from the 1A1g ground state
1
1
to the B1g and A2g excited states, respectively. This study showed square-
planar geometry[17] around Ni(II) ion.
The electronic absorption spectra of the copper(II) complexes exhibit three
bands. The bands at 27,027cm21 for [CuL1]Cl2 and at 26,880cm21 for
[CuL2]Cl2 can be attributed to charge transfer. The other bands found at 18,518,
15,115cm21 for [CuL1]Cl2 and at 18,348, 15,037cm21 for [CuL2]Cl2 are
2
2
2
assigned as (2A1g ꢀ B1g, Eg ꢀ B1g). These are characteristic of square-
planar geometry around the copper(II) ion. The observed magnetic moment
values of these compounds of the ligands L1 and L2 are 1.80 and 1.72B.M.,
repectively, suggesting the square-planar[18] environment for Cu(II).
The 10 Dq values for the complexes follow the order Cr(III) . Mn(II) .
Co(II) . Fe(III).

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345
1H NMR Spectra
The 1H NMR spectra of the ligands L1 and L2 in DMSO-d6 show a peak at
1.79–1.84 ppm due to the three terminal CH3 groups. A triplet in the
1.82–1.86 ppm range may be assigned unambiguously to imine methyl
(CH3C55N–, 6H) protons and two singlets at d3.77 ppm and d3.80 ppm can be
ascribed to the two methylene groups (–C–CH2–C–, 2H). The peaks for –CH2–
adjacent to the N-atom appear at 3.49 and at 3.47 ppm as triplets in the
ligands L1 and L2, respectively. However, in the case of L2 an additional –CH2–
peak of the 1,3-propanediamine ring system appears at 3.82–3.91 ppm as a
triplet.[19] The [NiL1]Cl2 and [NiL2]Cl2 complexes exhibit high d values of CH2
groups adjacent to nitrogen atom due the low electron density upon complex
formation.
EPR Spectra
The EPR spectra of the polycrystalline Cu(II) complexes were recorded
at room temperature. The [CuL1] and [CuL2]Cl2 complexes show gII ¼ 2.16–2.19
and g ¼ 2.01–2.07, which support that the dx22y2 orbitals may be the
?
ground state. No hyperfine splitting is observed due to nuclear interaction of other
nuclei. The values are in agreement with the square-planar geometry around the
Cu(II) ion.
On the basis of above studies the structures in Fig. 2 has been proposed
for the macrocyclic metal complexes [M ¼ Mn(II), Co(II), and Zn(II);
M0 ¼ Ni(II) and Cu(II)].
Antibacterial Activity
The screening results are recorded in Table 4. A comparative study of the
ligands, their complexes, and metal salts indicate that the metal complexes
show higher antibacterial activity than the free ligands, gentamicin the
standard drug and metal(II) and (III) chlorides. In general, the metal complexes
were found to have higher activities than those of the test compounds against
the bacteria strains. It may be concluded that the compounds inhibit the growth
of bacteria to a greater extent as the concentration is increased due to the effect
of the metal ion on the normal cell process.
EXPERIMENTAL
1,1,2,2,3,3,3-Heptafluoro-7,7-dimethyl-4,6-octanedione(SCM),ethylene-
diamine (CDH), 1,3-diaminopropane, (E. Merck), acetylacetone (BDH),

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Nishat, Rahis-ud-din, and Haq
Figure 2. Suggested structures of the metal complexes of L1 and L2. Key: M00 ¼
Cr(III) and Fe(III).
transition metal(II) and metal(III) cholrides (S.D. Fine Chem.) were used as
received.
Elemental analyses (C, H, N) were carried out with a Carlo Erba 1106
Thomas and Coleman analyzer. The IR spectra (4000–200 cm21) were
recorded on a model 621 Perkin Elmer spectrophotometer. The UV-Visible
spectra of the metal complexes in DMSO were recorded on a Lambda

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347
Table 4. Antibacterial activity of ligands and complexes (zone formation in mm).
S. aureus E. coli
0.5 mg/mL
Compounds
0.5 mg/mL
1.0 mg/mL
1.0 mg/mL
Gentamicina
Ligand L1
Ligand L2
[CrL1Cl2]Cl
[MnL1Cl2]
[FeL1Cl2]Cl
[CoL1Cl2]
[NiL1]Cl2
[CuL1]Cl2
[ZnL1Cl2]
[CrL2Cl2]Cl
[MnL2Cl2]
[FeL2Cl2]Cl
[CoL2Cl2]
[NiL2]Cl2
[CuL2]Cl2
[ZnL2Cl2]
CrCl3
7
8
8
10
13
15
16
17
19
16
15
15
17
17
19
21
15
16
20
11
10
11
9
6
9
8
12
14
13
17
16
19
14
16
16
18
17
20
22
15
17
18
10
11
9
12
12
12
15
12
13
12
12
13
14
14
15
11
14
14
9
12
11
10
14
12
10
14
12
12
13
13
14
11
13
11
7
MnCl2
FeCl3
8
7
9
8
CoCl2
NiCl2
8
7
10
8
7
8
6
CuCl2
ZnCl2
7
9
8
9
10
6
8
8
aUsed as standard.
EZ201 Perkin–Elmer spectrophotometer and magnetic susceptibility
measurements were done with a model 155 Allied Research vibration
sample magnetometer at room temperature. The conductivity measurements
were carried out on a CM-82T Elico conductivity bridge in DMSO.
The EPR spectra were recorded on
a Bruker Scientific X-band
1
spectrometer (ESP-300). The H NMR spectra of the macrocyclic ligands
were run in DMSO-d6 on a JOEL-FX-100 spectrometer. Chlorine was
determined gravimetrically[20] and the metals were determined by EDTA
titration.[21] The solvents were distilled and dried by conventional methods
before use.

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Nishat, Rahis-ud-din, and Haq
Synthesis of the Ligand 1,5,8,12-Tetraaza-4-(10,10-
dimethylethyl)-2-(100,100,200,200,300,300,300-heptafluoropropyl)-
9,11-(dimethyl)-cyclotetradeca-1,4,8,11-tetraene (L1)
To a solution of 1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione
(20 mmol, 4.6 mL) in ethanol (75 mL) were added acetylacetone (20 mmol,
2.0 mL) and ethylenediamine (40 mmol, 2.6 mL) continuously and drop-wise
within 2 hr, in a 250 mL round bottom flask. The resulting mixture was
refluxed for 7 hr, then cooled at 08C and kept in a refrigerator for 4 days. An
orange product was removed by filtration, washed with diethyl ether and
hexane (1 : 1), and dried in vacuo. It was recrystallized in methanol. Yield,
5.5 g (60%).
Synthesis of the Ligand 1,5,9,13-Tetraaza-4-(10,10-
dimethylethyl)-2-(100,100,200,200,300,300,300-heptafluoro propyl)-
10,12-(dimethyl)-cyclohexadeca-1,4,9,12-tetraene (L2)
The ligand L2 was synthesized by adding an ethanol (50 mL) solution of
1,1,2,2,3,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione (20 mmol, 4.6 mL),
acetylacetone (20 mmol, 2.0 mL), and 1,3-diaminopropane (40 mmol,
3.2 mL) simultaneously very, very slowly drop-wise within 1 hr to a 250 mL
round bottom flask. The mixture then was refluxed with stirring for 8 hr and
then cooled at 0 8C. It was kept in a refrigerator for 5 days. The formed light-
red product was filtered, washed with dry diethyl ether, and dried in vacuo.
It was recrystallized in methanol. Yield, 5.5 g (56%).
Synthesis of Complexes of the Ligands L1 and L2
L1 (10 mmol, 4.4 g) was dissolved in a mixture of methanol (40 mL) and
conc. HCl mixture (1 mL) and nickel(II) chloride (10 mmol, 2.4 g) in methanol
(25 mL) was added. The solution was refluxed for 3–4 hr. The light-red
precipitate that formed was filtered, washed with hexane and dry diethyl ether
(1 : 1) and dried in vacuo. Yield, 3.6 g (54%).
The nickel(II) complex of the ligand L2 was synthesized by a similar
method. The light-brown product that formed was filtered, washed with
hexane, and dried in vacuo. Yield, 3.4 g (48%).
Similar procedures were employed for the synthesis of the Mn(II), Co(II),
Cu(II), Zn(II) complexes of L1. Yields, 50–64%.
To L1 (10 mmol, 4.4 g) in methanol (40 mL) and conc. HCl (1 mL), a
ferric(III) chloride (10 mmol, 1.6 g) solution in methanol (25 mL) was added.

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349
The mixture was refluxed with stirring for 12 hr, yielding a brown solid
product. The precipitate was filtered, washed with dry diethyl ether, and dried
in vacuo. Yield, 3.7 g (52%).
The chromium(III) complex was synthesized by the similar above
procedure. The light green precipitate was filtered, washed with dry diethyl
ether, and dried in vacuo. Yield, 3.5 g (58%).
The complexes of the ligand L2 were synthesized by the similar procedure
as applied for the ligand L1 complexes. Yields, 47–58%.
Bacterial Screening
The antibacterial activity of the ligands and their complexes were
evaluated by the filter paper disc method.[22] In this method the sterile discs
(5 mm diameter) of filter paper (Whatman No. 4) were dipped into the solution
of the test compounds of 0.5–1.0 mg/ml concentrations in DMSO, placed
over the seeded plates, left for diffusion and incubated at 37 8C for 24 hr. The
compound diffusing into the nutrient agar plate prevents the growth of
bacterium in a zone around the disc. Control plates for the solvent, gentamicin
as the standard drug, and metal(II) and (III) chlorides were compared with the
test compound.
ACKNOWLEDGMENTS
The authors thank the Third World Academy of Sciences, Italy, for
financial support through research grant No. 00-047 RG/CHE/AS and also to
Dr. Syed Farooq for antimicrobial activity measurements at the Microbiology
Laboratory, Himalya Drugs Co. Najafgarh Road, New Delhi, India.
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Received April 30, 2003
Accepted October 22, 2003
Referee I: D. T. Esterline
Referee II: H. N. Po

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