Synthesis, characterization and antimicrobial screening of 1,3-dione with their metal complexes

Article abstract of DOI:10.14233/ajchem.2018.21041

1-(5-Bromo-2-hydroxyphenyl)-3-(thiophen-2-yl)-propane-1,3-dione and its metal complexes has been synthesized. The functionalized 1,3-dione potentially acts as bidentate ligand and coordinate with the transition metal ions through β-diketo system. The synthesized diketone and their transition metal complexes have been screened for in vitro antibacterial and antifungal activity using Resazurin 96 well plate method. The transition metal complexes showed moderate to excellent antimicrobial activity against all tested bacteria and fungi which constitutes a new group of compounds that can be used as potential metal derived drugs.

Full text of DOI:10.14233/ajchem.2018.21041

Asian Journal of Chemistry; Vol. 30, No. 2 (2018), 398-402
ASIAN JOURNAL OF CHEMISTRY
https://doi.org/10.14233/ajchem.2018.21041
Synthesis, Characterization and Antimicrobial Screening of 1,3-Dione with their Metal Complexes
1
2
3
3,*
SANDEEP N. SAMPAL , SHAILENDRASINGH V. THAKUR , ANJALI S. RAJBHOJ and SURESH T. GAIKWAD
1Department of Chemistry, Kalikadevi Arts, Commerce and Science College, Shirur (Kasar), Beed-413 249, India
2Department of Chemistry, Milliya Arts, Science and Management Science College, Beed-431 122, India
3Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-431 004 India
*Corresponding author: E-mail: gaikwadsuresh12@gmail.com
Received: 13 September 2017;
Accepted: 28 November 2017;
Published online: 31 December 2017;
AJC-18713
1-(5-Bromo-2-hydroxyphenyl)-3-(thiophen-2-yl)-propane-1,3-dione and its metal complexes has been synthesized. The functionalized
1,3-dione potentially acts as bidentate ligand and coordinate with the transition metal ions through β-diketo system. The synthesized
diketone and their transition metal complexes have been screened for in vitro antibacterial and antifungal activity using Resazurin 96 well
plate method. The transition metal complexes showed moderate to excellent antimicrobial activity against all tested bacteria and fungi
which constitutes a new group of compounds that can be used as potential metal derived drugs.
Keywords: 1,3-Dione, Metal complexes, Magnetic susceptibility, XRD, TGA, Antimicrobial activity.
In the present work, we have synthesized, characterized
INTRODUCTION
and screened for in vitro antibacterial and antifungal activities
The research on various 1,3-dione and its metal complexes
of the ligand, 1-(5-bromo-2-hydroxyphenyl)-3-(thiophen-2-
has wide scope in pharmaceutical industries. The functionalized
yl)propane-1,3-dione and its metal complexes.
1,3-diones are potential antibacterial [1], antiviral [2], insectitial
[3], antioxidant [4], antisunscreen activity [5], antitumor [6],
EXPERIMENTAL
HIV-1 Integrase (IN) inhibitors [7]. 1,3-Dione are key inter-
mediate for the synthesis various heterocyclic compounds [8-
10]. It is well known that the simplest form of 1,3-dione is
pentane 2,4-dione or acetyl acetone in which two carbonyl
group at 1, 3 position shows keto-enol tautomerism. The equili-
brium in 1,3-dione is strongly shifted towards the enol form
since formation of six membered stable ring and intramolecular
hydrogen bonding. The enol form plays a vital role in formation
of metal complexes with 1,3-diones.
All the chemical were used of analytical grade. All metal
salts were used as nitrate (S.D. Fine). 5-Bromo-2-hydroxy-
aceto-phenone (Himedia), 2-thiophenecarboxylic acid (Sigma
Aldrich), dry pyridine (Spectrochem) were purchased and used
without further purification. Distilled ethanol was used for
recrystallization and synthesis of metal-complexes. Infrared
spectra were recorded on Perkin Elmer spectrometer. The C,
H and N analyses were carried out using a Euro-E 3000. The
1H and 13C NMR spectra were recorded in CDCl3 using TMS
as internal standard on a BrukerAvance DPX-400 spectrometer.
The magnetic susceptibility was measured at room temperature
using Guoy balance.
H
O
O
Synthesis of 2-acetyl-4-bromophenyl thiophene-2-
carboxylate (3): To the mixture of 5-bromo-2-hydroxyaceto-
phenone (2.150 g, 0.01 mol) and 2-thiophene carboxylic acid
(1.281 g, 0.01 mol), dry pyridine (20 mL) and POCl3 (1 mL)
were added drop wise with constant stirring at 0 °C. The reaction
mixture was then continually stirred for 5-6 h.After completion
of the reaction (monitored by TLC), the reaction mixture was
poured into HCl (1 M) containing of crushed ice. The solid
obtained was filtered and washed with ice-cold methanol and
R1
R2
General structure of enol form of 1,3-diones
1,3-Dione metal complexes are used as catalyst in reaction
of olefin oxidation and epoxidation [11,12]. Europium(III)-
diketonates have excellent luminescent property [13]. It is also
used as chelating agent [14] and extractants for lanthanide
ions [15].

Vol. 30, No. 2 (2018)
Synthesis, Characterization and Antimicrobial Screening of 1,3-Dione with their Metal Complexes 399
then with distilled water. It was recrystallized from ethanol.
Yield: 69 %.
distilled water. In this method, the microbial growth detected
by small volumes of solution in microtitre plates without the
use of a spectrophotometer. The medium was used for this
assay isosensitest [19]. Using aseptic techniques single colony
was transferred into a 100 mL bottle containing isosensitest
broth, capped and placed in incubator overnight at 35 °C. after
that using aseptic preparation and centrifuge, a clean sample
of bacteria was prepared. The broth was settled down using
centrifuge at 4000 rpm for 5-6 min. The supernatant was separate
out in waste beaker. Using 20 mL of sterile saline the pellet
was re-suspended by centrifuge at 4000 rpm for 5-6 min. The
pellet was suspended in 20 mL of sterile saline and it is labeled.
The optical density of labeled was recorded at 500 nm and
serial dilutions were carried out by aseptic techniques upto
0.5-1.0 range of optical density. By using viability graph, the
actual number of colony forming units was calculated. The
plates were prepared in triplicate and placed in an incubator
set at 37 °C for 18-24 h. The colour changes from purple to pink
or colourless were recorded as positive. MIC values taken as
colour change occur at lowest concentration. The average of
three values of MIC for the test material and bacterial strain
has been considered.
Synthesis of 1-(5-bromo-2-hydroxyphenyl)-3-(thiophen-
2-yl)propane-1,3-dione (4): Compound 3 (3.251 g, 0.01 mol)
was dissolved in dry pyridine (15 mL). To this powdered KOH
(1.12 g, 0.02 mol) was added and the reaction mixture was
continually stirred for 3-4 h. After completion of the reaction
(monitored by TLC), the mixture was poured on ice cold water
and acidified with 1 M of HCl. The yellow colour solid product
obtained was filtered off and recrystallized from absolute
ethanol [16,17].Yield: 72 %; m.p.: 93 °C; LC-MS: 324.8 (M+)
elemental analysis: calculated C, 48.02, H, 2.79. Found C,
48.31; H, 2.84; 1H NMR: 15.59 δ (s, 1H, enolic-OH), 11.93 δ
(s, 1H, phenolic -OH), 7.6 δ (s, 1H, =C-H ethylene); 6.81-7.81
δ (m, 6H, Ar-H); IR νmax, cm-1: 1618 ν(C=O) ketonic, 1220
ν(C-O) enolic.
Bis-[1-(5-bromo-2-hydroxyphenyl)-3-(thiophen-2-yl)-
propane-1,3-dionate]-Fe(III) complex: A mixture of com-
pound 4 (5 mmol) and 2.5 mmol of appropriate ferric nitrate
added in anhydrous 30 mL ethanol and the resulting mixture
was refluxed at 60-65 °C for 1-2 h where upon the complex
precipitation occurs after the addition of alcoholic ammonia.
The precipitated coloured solid complex washed with ethanol
and crystallized by using dichloromethane (Scheme-I).Yield
67 %, m.p.: 348 °C, elemental analysis: calculated C, 42.19,
H, 2.72 found C, 42.02, H, 2.85.
RESULTS AND DISCUSSION
The synthesized ligand and its transition metal complexes
of 1-(5-bromo-2-hydroxyphenyl)-3-(thiophen-2-yl)propane-
1,3-dione are stable at room temperature in the solid state.
The ligand is soluble in all organic solvents but its metal comp-
lexes are highly soluble in dimethyl sulfoxide and dimethyl
formamide. The synthesized metal complexes have 1:2 stoi-
chiometric ratio of metal-ligand. Spectral analysis data shows
the confirmation of 1,3-dione and its metal complexes.
Magnetic susceptibility and molar conductance: The
magnetic susceptibility observed at room temperature.All the
metal complexes paramagnetic in nature except Zn-complex
show diamagnetic in nature. Molar conductance (ΛM) values
of metal complexes were obtained at room temperature at 1 ×
10-3 M DMSO solution. The studies show negligible molar
conductance values of metal complexes in range 0.008-0.012
ohm-1 cm2 mol-1 results showed in Table-1 clear that all the
metal complexes are non-electrolytic in nature [20].
Similarly, the complexes of cobalt, nickel, copper and zinc
were prepared by the same method.
O
O
Br
Br
CH
CH
O
3
3
Pyridine, 0°C
OH
S
OH
O
S
POCl
3
O
2
3
1
Pyridine,
KOH
O
OH
Br
O
O
Br
S
OH
S
4
OH
Ferric nitrate
Ethanol
60-65 °C
1-2 h
IR spectra: The characteristic infrared spectral data of
ligand (L) and their metal complexes are reported in Table-1.
The carbonyl group (>C=O) of ligand (L) stretching frequency
appearance at 1618 cm-1. The appearance of frequency at 1587
cm-1 due to (-C=C-) double bond and the bond (C-O) appear
at 1220 cm-1. The metal complexes shows IR frequency of
carbonyl group (>C=O) at 1596-1615 cm-1 which were lower
than IR frequency of ligand (L) 1618 cm-1. This lowering
stretching frequency indicates that the ligand (L) coordinated
with the transition metal ion. In addition, new band at 519-
527 cm-1 observed due to metal-oxygen (M-O) bond vibrations
in metal complexes which were absent in ligand 4. This
confirms of metals coordinate with ligand via oxygen.
OH
O
S
Br
O
H O
H O
2
2
Fe
O
O
Br
S
OH
5
Scheme-I: Synthetic route of 1,3-dione and its metal complexes
Antimicrobial activities: The antimicrobial activity carried
out by Resazurin method which is developed by Drummond
andWaigh [18]. This method is simple, sensitive, rapid, reliable
and achieves more accurate minimum inhibitory concentration
(MIC). In this method Resazurin used as an indicator and it
was prepared by dissolving 270 mg tablet in 40 mL of sterile
Electronic absorption spectra: UV spectra were taken
at 1 × 10-3 M DMSO solution. Electronic absorption spectra
studies reveals that only charge transfer transitions were
observed in all metal complexes therefore geometry of the

400 Sampal et al.
Asian J. Chem.
TABLE-1
MAGNETIC, CONDUCTANCE, INFRARED AND ELECTRONIC SPECTRA
IR (cm-1)
Magnetic
Molar
conductance
ν (cm-1)
Compound
moment
ν(OH) coordinated
µeff (BM) (ohm-1 cm2 mol-1)
ν(C=O)
ν(C=C) ν(C-O)
ν(M-O)
H2O molecule
Ligand
–
5.86
3.49
2.45
1.39
–
1618
1610
1606
1615
1596
1597
1587
1572
1580
1585
1596
1597
1220
1227
1230
1241
1210
1229
–
3672
3679
3564
3584
3351
–
25873, 38535
26212, 31347, 38314
25641, 38461
24420, 25706, 38535
25873, 38240
24183, 27397, 38461
Fe(III) complex
Co(II) complex
Ni(II) complex
Cu(II) complex
Zn(II) complex
0.012
0.008
0.012
0.011
0.010
525
525
527
519
522
Diamag.
complexes is octahedral geometry with center of symmetry
which is Laporte forbidden transition therefore weak d-d transi-
tions were not observed only charge transfer transitions occurs
in metal complexes. Wavenumber of electronic absorption
spectra as shown in Table-1.
(Fig. 1).Also, the value of unit cell dimension of Zn(II) complex
were a = 6.847 Å, b = 8.310 Å, c = 24.12 Å and α = 90°, β =
90°, γ = 120°. Unit cell volume = 932.54 (Fig. 2).
Thermogravimetric analysis of metal complexes:Thermal
decomposition of selected metal complexes was carried out at
a heating rate of 10 °C min-1 under nitrogen atmosphere over
the temperature range 28-1000 °C. Thermogravimetric analysis
of cobalt complex shows some loss of weight between 60 and
185 °C indicating that surface and coordinated water molecules
are present in the complexes [21,22]. A sudden weight loss
from 200 to 300 °C due to loss of one phenyl ring with two
hydroxy and one carbonyl group. Further, the weight loss from
377 to 420 °C corresponds to the decomposition of two phenyl
ring and a propane-1,3-dione moiety. On further heating up to
600 °C, the weight remaining corresponds to that of cobalt
oxide (Fig. 2).
Thermogravimetric analysis of zinc(II) complexes shows
some loss of weight between 70 and 233 °C indicating that
coordinated water molecules are present in the complexes. A
sudden weight loss from 357 to 450 °C due to loss of one phenyl
ring with two hydroxyl and one carbonyl group. Further, the
weight loss from 450 to 520 °C corresponds to the decompo-
sition of two phenyl ring and a propane-1,3-dione moiety. On
further heating up to 600 °C the weight remaining corresponds
to that of zinc oxide (Fig. 2).
1H NMR and 13C NMR spectra: The 1H NMR spectral
data of the 1-(5-bromo-2-hydroxyphenyl)-3-(thiophen-2-yl)
propane-1,3- dione (L) shows singlet at δ 15.59 ppm due to enolic
proton, a singlet at δ 11.93 ppm due to phenolic proton adjacent
to the carbonyl group which confirms the formation of β-diketone.
In the 13C NMR of ligand 4, peak appeared at δ 193.33 ppm
corresponds to carbonyl carbon (C=O) and enolic carbon (C-O)
at δ 173.62 ppm. The signal at δ 91.67 ppm appeared shows
methine linkage.
Powder X-ray diffraction: The XRD study was perfor-
med with Cu as anode material, Kα (Å) = 1.540598 and the
generator settings 30 mA, 40 KV in the range 10-80°. The high
intensity peaks of the diffraction pattern were indexed and
analyzed by the powder-X software. The XRD pattern of L-
Co and L-Zn complexes shows monoclinic crystal system. The
average crystallite size for the above mentioned complexes was
found to be 15.6 and 9.01 nm, respectively. The value of unit
cell dimension of Co(II) complex were a = 8.818 Å, b = 7.585
Å, c = 19.26 Å and α = 90°, β = 90°, γ = 120°. Unit cell volume
= 1114.13.
The powder X-ray diffraction analysis of Zn(II) complex
exhibited some sharp peaks while no sharp peaks were
observed for Co-complex indicating their amorphous nature
The antimicrobial activity data shows that ligand and its
transition metal complexes shows considerable antimicrobial
activity compared with standard drug (Table-2).
7000
8000
7000
Zn-complex
Co-complxe
6000
6000
5000
4000
3000
2000
1000
0
5000
4000
3000
0
10
20
30
40
50
(°)
60
70
80
90
0
10
20
30
40
50
(°)
60
70
80
90
2
θ
2θ
Fig. 1. Powder XRD patterns of Co-complex and Zn-complex (using Origin Software)

Vol. 30, No. 2 (2018)
Synthesis, Characterization and Antimicrobial Screening of 1,3-Dione with their Metal Complexes 401
120
120
Co-complex
Zn-complex
3.987%
(0.1612mg)
184.87°C
26.78°C
28.65°C
7.079%
(0.2494mg)
100
80
60
40
20
0
100
80
60
40
20
0
357.73°C
101.28°C
232.63°C
19.08%
(0.7716mg)
377.06°C
299.73°C
56.09%
(1.976mg)
32.16%
(1.300mg)
445.30°C
419.71°C
449.85°C
18.84%
(0.7616mg)
539.69°C
498.18°C
0
100
200
300
Temperature (°C)
400
500
600
0
100
200
300
Temperature (°C)
400
500
600
Fig. 2. TGA of Co(II) complex and Zn(II) complex
TABLE-2
MIC (µg/mL) VALUES DETERMINATION USING MODIFIED RESAZURIN ASSAY
Antibacterial activity
Antifungal activity
Compounds
Gram-positive
B. subtilis
Gram-negative
P. aeruginosa
C. albicans
S. cerevisiae
S. aureus
< 50
< 50
< 50
< 50
< 50
< 50
1
E. coli
100
100
100
100
100
100
4
L
L-Fe
L-Co
L-Ni
L-Cu
50
100
< 50
100
50
50
2
-
50
50
50
100
100
50
1
100
200
100
150
150
100
-
100
100
50
150
100
150
-
L-Zn
Tetracycline
Amphotericin B
-
-
-
1.25
1.25
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Conclusion
In the present work, we have synthesized a new ligand
and its metal complexes by conventional method. The synthe-
sized compounds were characterized by various analytical
techniques. The synthesized β-diketone ligand coordinate with
the metal ions by oxygen atom as donor sites. Magnetic studies
revealed the paramagnetic nature of complexes.
ACKNOWLEDGEMENTS
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The authors are thankful to the Head, Department of
Chemistry, Dr. BabasahebAmbedkar Marathwada University,
Aurangabad and Principal, KalikadeviArts, Commerce & Science
College, Shirur (ka), India for providing the laboratory facilities.
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