Evaluation of DPPH radical scavenging activity of 2-(furan-2′-yl)-3-hydroxy-4H-chromen-4-one and their derivatives

Article abstract of DOI:10.14233/ajchem.2016.19809

The 2-(furan-2′-yl)-3-hydroxy-4H-chromen-4-one and their substituted derivatives with electron donating and electron withdrawing groups have been synthesized. Free radical scavenging activity has been studied using 2,2′-diphenyl-1-picrylhydrazine (DPPH).

Full text of DOI:10.14233/ajchem.2016.19809

Asian Journal of Chemistry; Vol. 28, No. 9 (2016), 1921-1924
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19809
Evaluation of DPPH Radical Scavenging Activity of
2-(Furan-2'-yl)-3-hydroxy-4H-chromen-4-one and Their Derivatives
*
RANBIR KAUR, KULVIR KAUR and MANISHA BANSAL
Department of Chemistry, Punjabi University, Patiala-147 002, India
Corresponding author: E-mail: jindal_manisha@yahoo.co.in
Received: 31 December 2015; Accepted: 4 April 2016;
*
Published online: 1 June 2016;
AJC-17917
The 2-(furan-2'-yl)-3-hydroxy-4H-chromen-4-one and their substituted derivatives with electron donating and electron withdrawing
groups have been synthesized. Free radical scavenging activity has been studied using 2,2'-diphenyl-1-picrylhydrazine (DPPH). The
kinetic studies and co-relation of excited state intramolecular proton transfer (ESIPT) with electron donating and electron withdrawing
group explains the effect of these groups on percentage scavenging activity.
Keywords: 2-(Furan-2'-yl)-3-hydroxy-4H-chromen-4-one, Free radical scavenging activity, Kinetic studies, DPPH.
the result. This results in the formation of the colourless 2,2'-
diphenyl-1-picrylhydrazine. Reduction of the DPPH radicals
can be estimated quantitatively by measuring the decrease in
the absorption at 517 nm. Percentage scavenging has been
calculated from the following equation [11]:
INTRODUCTION
Flavonoids are a group of naturally occurring compounds,
widely distributed as secondary metabolites in the plant kingdom.
They have been well documented as having interesting medicinal
properties, such as anti-inflammatory, antiviral, antibacterial
and anti-tumor activities [1,2]. Flavonoids have also been
reported to possess antioxidant and antiradical properties [3-5].
Antioxidants are the free radical scavengers which inhibits
the activity of the free radicals generated in the body, which
cause damage to all organs, muscles, etc. Phytochemicals like
flavonoids are widely accepted class of naturally occurring
plants compounds which are intensively been used as anti-
oxidants [6-8]. Further, out of wide range of flavonoids
Absorption of blank–Absorption of test
Scavenging (%) =
×100
Absorption of blank
The aim of present work to evaluate the percentage free
radical scavenging activity using 2,2’-diphenyl-1-picryl-
hydrazine (DPPH).
EXPERIMENTAL
Methanol of spectroscopic grade was purchased from S.D.
Fine chemicals. 3-Hydroxyflavone, DPPH and the reagents
used for the preparation of 2-furyl-3-hydroxychromone deriva-
tives were purchased from Sigma Aldrich (USA).
3
-hydroxyflavones have attracted many researchers due to its
antioxidant activity.
In this family, polyhydroxyflavones such as quercetin,
morin, myricetin and kempferol are a subgroup of well-known
natural antioxidant molecules [9]. Quercetin is most exclusively
studied 3-hydroxy flavones. Its electron donating hydroxyl
groups at position 3,5,7,3',4' may play a crucial role in increased
antioxidant activity as compared to 3-hydroxy flavone [10].
Antioxidant activity can be evaluated using DPPH in vitro.
DPPH is a stable free radical that can accept an electron or
hydrogen radical to become a stable diamagnetic molecule.
Due to its odd electron, the methanolic solution of DPPH shows
a strong absorption band at 517 nm. DPPH radical react with
various electron donating molecules (antioxidants). When
electrons become paired off, bleaching of DPPH solution is
Melting points of the synthesized compounds were deter-
mined in open capillary. IR spectra were recorded with FTIR
1
Spectrophotometer (Perkin Elmer, RZX) and H NMR on
BrukerAvance 400 NMR Spectrophotometer with TMS as an
internal standard. Double beam UV-visible spectrophotometer
(UV-1800 Shimadzu) equipped with UV-probe software has
been employed for recording the UV-visible spectra.
Preparation, purificationandcharacterizationofvariously
substituted 2-(furan-2'-yl)-3-hydroxy-4H-chromen-4-one:
2-(Furan-2'-yl)-3-hydroxy-4H-chromen-4-one (FHC) and its
derivatives have been synthesized by two step synthesis scheme
already reported [12]. First step is preparation of chalcone

1
922 Kaur et al.
Asian J. Chem.
from 0.03 mole of furan-2-carboxaldehyde and 0.03 mol of
'-hydroxyacetophenone in the presence of 0.09 mol of sodium
0.46
2
hydroxide in ethanol at 10 ± 0.5 ꢀC.
The chalcone obtained was subjected to Algar-Flynn-
Oymada (A.F.O.) reaction conditions in sodium hydroxide and
0.44
ethanol at 10 ± 0.5 ꢀC with dropwise addition of 30 % (w/v) H
O
2 2
over 1 h. The compounds were crystallized and characterized
by IR and H NMR spectral data are given in Table-1.
2
R = 0.998
1
0.42
0.40
TABLE-1
CHARACTERIZATION DATA OF VARIOUSLY SUBSTITUTED
2
-(FURAN-2-YL)-3-HYDROXY-4H-CHROMEN-4-ONE
m.p.
IR (KBr,
ꢀC)
1
Compd.
H NMR
-
1
(
νmax, cm )
1
3
616 (C=O),
258 (OH)
Ar 7H (m, 7.64-7.35),
OH, 1H, 6.88
1
2
178
0
.38
0
20
40
60
Ar 1H (d, 9.54), Ar 5H (m,
8-7) OH, 1H (s, 6.68), CH3,
Time (min)
1601 (C=O),
198
3
225 (OH)
0.18
3H (s, 2.55)
1
3
620 (C=O),
324 (OH)
Ar 5H (m, 7.83-7.21), 6-OH,
1H (s, 9.70), 3-OH, (s, 6.67)
3
4
5
202
112
167
0.16
1
(
618 (C=O), 3227 Ar 7H (m, 7.0-8.55), OH, 1H
OH), 1344 (NO2) (s, 6.98)
2
R = 0.981
1628 (C=O),
Ar 6H (m, 8.32-7.13), OH,
1H, (s, 6.88)
0.14
3
452 (OH)
For evaluation of percentage scavenging activity equal
volume of 50 µM solution of DPPH and 20 µM solution of 3-
hydroxyflavone and variously substituted 2-(furan-2'-yl)-3-
hydroxy-4H-chromen-4-one (1-5) as shown in Scheme-I was
prepared in methanol:water (80:20) and absor-bance at 517
nm was measured after different time intervals.
0
.12
.10
0
0
50
100
150
Time (min)
Fig. 1. Decrease in absorbance versus time for equal volumes of DPPH
with 3-hydroxy flavone and FHC respectively
OH
OH
(
i) NaOH/EtOH
(10 ± 5 °C)
O
acts as antioxidants. The percentage scavenging activity was
calculated using equation as given earlier.
Fig. 2 increase in percentage scavenging activity value
with time for both 3-hydroxy flavone and FHC. From the value
of percentage scavenging activity value, it was estimated that
FHC is better antioxidant as compared to 3-hydroxy flavone.
H
O
CH
3
+
R'
ii) dil. HCl R'
(
O
O
O
2
'-hydroxyacetophenone Furan-2-carbaldehyde
Chalcone
R'=H=1
R'=CH =2
R'=OH=3
R'=NO =4
R'= Cl=5
3
2
2
-(Furan-2'-yl)-3-hydroxy-4H-chromen-4-one is better
antioxidant than 3-hydroxy flavone. As discussed in previous
data [12] it was observed that in excited state intramolecular
proton transfer (ESIPT), substitution at 2- position, in 3-hydroxy
flavones plays a crucial role. In FHC the oxygen atom belonging
to furan ring undergo conjugation to increase the electron
density of 4-carbonyl group in addition to the only conjugation
from oxygen atom of the benzopyran ring to 4-carbonyl in 3-
hydroxy flavone. Proton transfer in excited state in such
compounds depends upon number of factors like electron
density, polarity, charge transfer, solvent polarity, etc. Out of
these excited state intra-molecular charge transfer (ESICT)
plays a vital role in increasing ESIPT interactions. The electron
donor substitutents undergo conjugation to increase the charge
density at 4-carbonyl group. So, in FHC better ESIPT is observed.
The contribution of phenyl ring at the 2- position to ESICT
effect on 4-carbonyl, is little due to its non-planarity and non-
conjugation [13,14]. In FHC, furyl, which replaces phenyl is
the major contributor as electron donor in the molecule because
planarity due to small size increases conjugation in the molecule
4
'
3
'
1
8
5'
7
9
O
2
2
' O
1'
6
3
R'
10
OH
4
5
O
FHC and their derivatives
Scheme-I: Synthetic scheme for the preparation of FHC and their derivatives
RESULTS AND DISCUSSION
As already been discussed 3-hydroxy flavone shows low
antioxidant activity as compared to quercetin. In order to
resolve the problem that whether electron donating substitution
plays a role in increasing the antioxidant activity. We have
replaced the 6-membered ring (phenyl) with 5-membered ring
furan) at the 2-position of 3-hydroxy flavone. The representative
polynomial (Fig. 1) with regression factor (R ) 0.998 and 0.991
for 3-hydroxy flavone and FHC respectively shows decrease
at 517 nm. The decrease in the absorbance shows that both
(
2

Vol. 28, No. 9 (2016)
DPPH Radical Scavenging Activity of 2-(Furan-2'-yl)-3-hydroxy-4H-chromen-4-one and Their Derivatives 1923
7
6
6
5
5
4
4
7
0
5
0
5
0
5
0
4
70
6
0
0
5
2
R = 0.962
2
40
R = 0.986
30
0
20
40
60
80
100
120
140
70
60
50
40
30
20
10
0
0
50
100
150
72
70
68
66
64
2
R = 0.996
0
Fig. 3. Increase in % scavenging activity versus time for equal volumes of
DPPH with 6-OHFHC and 6-CH FHC respectively
50
100
150
2
R = 0.981
3
40
30
20
0
50
100
150
Fig. 2. Increase in % scavenging activity versus time for equal volumes of
DPPH with 3-hydroxy flavone and FHC respectively
2
and is also richer in electron as compare to phenyl ring. Due
to enhancement in electron density at the ring ‘C’ hydrogen
radical for DPPH is easily available, which cause increase in
R = 0.973
•
10
antioxidant activity. When we compared the % scavenging
activity approximately after 18 min the activity value is 11.39
for 3-hydroxy flavone and 64.55 for FHC, which is almost 6
times greater than 3-hydroxy flavone. More is the value of %
scavenging better is the antioxidant. So, it shows that FHC is
better antioxidant than 3-hydroxy flavone.
0
0
50
100
150
70
Substitution at the 6- position electron donor –CH
3
, -OH,
electron withdrawing –NO and +M and –I effect –Cl group
2
alter the antioxidant activity. The substitution at 6- position
also effect the ESIPT process by changing the electron density
and dipole moment of the molecule due to which change in
overall polarity has been reported. Behaviour at 6-position is
different from that of substitution at 2-position. The electromeric
effect of this kind of substitution on 2-3 double bond in the
60
2
R = 0.986
5
0
0
‘
C’ ring is similar but the effect on the double bond of 4-
carbonyl is opposite [15]. In case –CH and –OH substitution
3
at 6-position, % scavenging activity increases with time and
the value is more as compare to 3-hydroxy flavone. After 2 h,
%
scavenging activity value is 59.07 for both 6-CH
3
FHC and
4
6
-OHFHC in Fig. 3. After 40 min, dramatic decrease was
0
50
100
150
observed in % scaven-ging activity value behind which reason
is not known yet.
Fig. 4. Increase in % scavenging activity versus time for equal volumes of
DPPH with 6-NO FHC and 6-ClFHC, respectively
2

1
924 Kaur et al.
Asian J. Chem.
In electron withdrawing group –NO
2
substitution cause
ships under “MANF” and UGC-BSR. We are also thankful
SAIF/CIL, Punjab University, Chandigarh for providing us
H NMR and IR data of the synthesized flavonols.
decrease in electron density at ring ‘C’due to which % scaven-
ging value of 6-NO FHC is much lower than FHC and is almost
nearly comparable with 3-hydroxy flavone. Fig. 4 represents
the % scavenging activity of 6-NO FHC with time.
1
2
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ACKNOWLEDGEMENTS
Two of the authors gratefully acknowledge the University
Grants Commission (UGC), New Delhi for awarding fellow-