International Conference on Food Science and Technology, 2008

APPLICATION OF COMPUTATIONAL CHEMISTRY METHOD

TO STUDY THE ANTIOXIDANT ACTIVITY OF CURCUMIN

Syahrul Khairi1, Hanggara Sudrajat2,*, Pranyong Dongdee3,

Nathaya Selphusit3,4, and Mongkol Sukwattanasinitt3,4

1Department of Chemistry, Faculty of Mathematics and Natural Sciences,

Gadjah Mada University, Bulaksumur Yogyakarta 55281, Indonesia
2Austrian-Indonesian Centre for Computational Chemistry, Department of Chemistry,

Faculty of Mathematics and Natural Sciences, Gadjah Mada University,

Bulaksumur Yogyakarta 55281, Indonesia
3Austrian-Thai Centre for Computational Chemistry, Department of Chemistry,

Faculty of Sciences, Chulalongkorn University, Bangkok 10330, Thailand

4Department of Chemistry, Faculty of Sciences, Chulalongkorn University,

Bangkok 10330, Thailand

 International Conference on Food Science and Technology, 2008

BACKGROUND
Free Radical

Antioxidant
accelerate the selection
of Antioxidant

Natural Antioxidant Design a Novel Antioxidant

Related compound Synthesize

of natural Antioxidant

CURCUMIN
 International Conference on Food Science and Technology, 2008

BACKGROUND

β-diketone
heptadione

O O

HO OH

H H
H3CO Curcumin in cis-diketone form OCH3

Hydrogen bond

Orthomethoxylated phenol
 International Conference on Food Science and Technology, 2008

OBJECTIVES

1. Curcumin structure optimization to investigate the

stable form

2. O-H Bond Dissociation Energy (BDE) calculation to

predict antioxidant activity

3. Rationally design of new compound based on

Curcumin structure
 International Conference on Food Science and Technology, 2008

METHODOLOGY

1. Curcumin structure optimization with B3LYP/6-31G(d,p)

using PCM model

2. O-H Bond Dissociation Energy (BDE) calculation with

(RO) B3LYP/6-311+G (2d,2p)//AM1/AM1

3. Rationally design of new compound based on Curcumin

structure
 International Conference on Food Science and Technology, 2008
O O
RESULT
HO OH

H H
H3CO Curcumin in cis-diketone form OCH3
O
H
HO

O OH
H3CO

Curcumin in trans-diketone form OCH3

H
O O

HO OH

H
H3CO Curcumin in enol-diketone form OCH3
 International Conference on Food Science and Technology, 2008

RESULT
 International Conference on Food Science and Technology, 2008

RESULT

Table 1. Bond dissociation enthalpies (BDEs) of curcumin and relevant antioxidants

Cucumin 3,4-
Half- Ferulic Dihydroxy- Designed
Antioxidant trans-
curcumin acid cinnamic molecule
Diketone Enol form
acid
form

TEp -1263.962 -1263.970 -652.248 -688.181 -648.874 -1224.652

TER -1263.318 -1263.328 -651.605 -687.350 -648.240 -1224.020

ECp 0.407 0.380 0.212 0.190 0.174 0.350

ECR 0.391 0.364 0.198 0.176 0.160 0.337

BDE 82.322 80.603 83.10 84.88 77.09 76.01

104.623a

Activityh 0.371 ndb nd 0.666 0.281 nd

 International Conference on Food Science and Technology, 2008

RESULT
OH OH OH

OCH3 OCH3 OH

HC CHCOCH3 HC CHCOOH HC CHCOOH

Half curcumin Ferulic acid 3,4-Dihydroxycinnamic acid
O O

HO OCH3
C
H2

HO Designed molecule OH
 International Conference on Food Science and Technology, 2008

RESULT

Table 2. Ionization potentials (IPs) for curcumin and designed molecule

Antioxidant Curcumin Designed molecule

TEp -1263.555 -1224.248

TEc -1263.306 -1223.995

ZPEp 0.379 0.350

ZPEc 0.376 0.347

IPe 154.033 156.802

 International Conference on Food Science and Technology, 2008

CONCLUSION

The enol form of curcumin is more stable than the diketo form. This is
due to the intramolecular hydrogen bond formed in the enol with the
extended conjugation in the enol chain. According to the phenolic O-H
BDE, curcumin in its most stable form can be suggested to be a
relatively good antioxidant. In order to avoid overcoming H-bond
interaction and to improve the antioxidant activity of curcumin, a
catechol moiety was incorporated into curcumin and a novel
antioxidant was designed. It is found that the designed molecule is
much more efficient to scavenge radical than curcumin. Moreover, the
IP of the designed molecule is similar to that of curcumin.