APPLICATION OF COMPUTATIONAL CHEMISTRY

METHOD TO STUDY THE RELATIVE ANTIOXIDANT

EFFICIENCY OF A LARGE SERIES OF CAROTENOIDS

Zaky Al-Fatony 1, Hanggara Sudrajat 2,*, Bongkot Pipoosananakaton 3,

Sudarath Veravong 3, and Nathaya Selphusit 3,4
1 Department of Chemistry, Faculty of Mathematics and Natural Sciences,
Gadjah Mada University, Bulaksumur Yogyakarta 55281, Indonesia
2 Austrian-Indonesian Centre for Computational Chemistry, Department of Chemistry, Faculty of
Mathematics and Natural Sciences, Gadjah Mada University,
Bulaksumur Yogyakarta 55281, Indonesia
3 Department of Chemistry, Faculty of Sciences,
Chulalongkorn University, Bangkok 10330, Thailand
4 Austrian-Thai Centre for Computational Chemistry, Department of Chemistry, Faculty of
Sciences, Chulalongkorn University, Bangkok 10330, Thailand
*Corresponding author. Tel : +6285868077123 ;
E-mail: angga_vanniveau@yahoo.co.id
Backgrounds Objectives Methodology Results Conclusion

Carotenoids (Car) are versatile organic molecules, which are of great relevance
to living systems. They serve multiple purposes for their producers as well as
for their consumers. Among their diverse functions [1], their free-radical-
scavenging antioxidant properties plays the most important role.

There are several mechanisms for carotenoids’ antioxidant activity.

Electron transfer: R•+ Car → R-+ Car•+ (I)
Adduct formation: R• + Car → [R-Car]• (II)
Hydrogen abstraction: R• + Car → RH + Car(-H)• (III)

work will focus on the electron-transfer (ET) processes

The antioxidant properties of carotenoids are related to their excellent ability

to deactivate excited states and to their high electron donation capability

there must be a relationship between the structure of carotenoids and their

reactivity toward free radicals
Backgrounds Objectives Methodology Results Conclusion

-Our goal :

To investigate which methods gives more reliable answers compared to

available data, and also to introduce the use of computational chemistry
methods for predicting antioxidant efficiency, expressed as electron
donating capability
Backgrounds Objectives Methodology Results Conclusion

- All of the electronic calculations were performed with the Gaussian 98 suite
of programs.

- For all of the modeled species, full geometry optimizations have been
carried out using the B3LYP hybrid density functional and the 6-31G(d,p)
basis set

-frequency calculations were performed at B3LYP/3-21G level of

theory for geometries previously optimized at the same level

- Unrestricted calculations were used for open-shell systems, and local minima were
identified by the number of imaginary frequencies (NIMAG = 0)

- Solvent effects were included by using the polarizable continuum

model (PCM) with water and benzene as the solvents for polar and
nonpolar environments

The Gibbs free energies of reaction for an aqueous environment

were calculated using a mixed discrete-continuum model with two
water molecules explicitly included, with a surrounding continuum
of bulk solvent for carotenoids + free radical reactions
Backgrounds Objectives Methodology Results Conclusion

- The corresponding energies were improved by single point (SP)

calculations at the B3LYP/6-311++G(d,p) level of theory.

- The energy associated with the completion of ET reactions

between carotenoid conjugated pairs has been computed as
the corresponding adiabatic Gibbs free energies of such
processes at 298 K

ΔG0ET = G(Car1•+, gn-1) + G(Car2, gn) - G(Car1, gn) - G(Car2•+, gn-1)

where gn represents the relaxed geometry of the neutral
carotenoid and gn-1 that of the radical cation.

- The adiabatic Gibbs free energies of electron-

transfer reactions between carotenoids and radicals
in nonpolar and polar environments have been
calculated as

ΔG0ET = G(Car1•+, gn-1) + G(Ox-, gn+1) - G(Car1, gn) - G(Ox•, gn)

where Ox represent the oxidant species, that is, free radicals.
Backgrounds Objectives Methodology Results Conclusion

Several Carotenoids Previously Studied by Experimental Techniques and also Modeled in the
Present Work
O

OH

C40H52O4 ASTA Astaxanthin

HO

C30H40O CHO APO β-apo-8'-carotenal

CAN Canthaxanthin
C40H52O2

O
OH

C40H56O2 LUT Lutein

HO

OH

C40H52O2
ZEA Zeaxanthin

HO

C40H56 BC All-trans-β-carotene

C40H56 LYC Lycopene

Backgrounds Objectives Methodology Results Conclusion
Several Carotenoids Modeled in the Present Work, with No Previous Data on Their Electron-Transfer
Reactions

C40H58 DIH 7,7' Dihydro-β-

carotene
O

C40H54O ECH Echinenone

OH

C40H56O4
NOS
HO
OH Nostoxanthin
HO OCH3

C41H54O2 O OKE Okenone

C40H56O2
SAP Saproxanthin
OH
HO

C40H54
TOR Torulene
OH

OH
C40H56O3
CSAN
O
Capsanthin
HO

C40H56O4 O
O CRUB Capsorubin

OH
Backgrounds Objectives Methodology Results Conclusion

OH

C40H56O2 O
CRY Cryptocapsin

HO

C40H56O4 C
NEO Neoxanthin
O

HO OH

C40H56O4 O VIO Violaxanthin

OH

HO

OH O

C40H52O4 MIT Mytiloxanthinone

HO O
Backgrounds Objectives Methodology Results Conclusion

Figure 1. Correlation between vertical and adiabatic ionization potentials with Koopman’s IP, for polar and nonpolar media.
Backgrounds Objectives Methodology Results Conclusion
Ionization Potentials (eV) of carotenoids in Nonpolar and Polar Environments

solvent = benzene solvent = water

Koopman vertical adiabatic Koopman vertical adiabatic

ASTA 4.808 5.165 5.038 4.701 4.559 4.438

APO 4.676 5.083 4.914 4.687 4.553 4.406
CAN 4.707 5.069 4.942 4.658 4.518 4.412
LUT 4.493 4.882 4.736 4.495 4.366 4.243
ZEA 4.458 4.836 4.681 4.474 4.346 4.213
BC 4.414 4.790 4.629 4.455 4.328 4.186
LYC 4.321 4.672 4.522 4.388 4.251 4.105
DIH 4.491 4.938 4.779 4.548 4.425 4.271
ECH 4.563 4.922 4.770 4.550 4.415 4.282
NOS 4.472 4.849 4.680 4.489 4.360 4.206
OKE 4.593 4.937 4.790 4.572 4.431 4.300
SAP 4.375 4.721 4.577 4.408 4.276 4.158
TOR 4.313 4.641 4.495 4.361 4.230 4.094
CSAN 4.685 5.064 4.902 4.646 4.511 4.368
CRUB 4.886 5.269 5.142 4.850 4.706 4.600
CRY 4.625 5.003 4.853 4.627 4.491 4.364
NEO 4.444 4.842 4.689 4.509 4.380 4.242
VIO 4.516 4.917 4.778 4.558 4.429 4.310
MYT 4.741 5.124 4.990 4.723 4.590 4.471
Backgrounds Objectives Methodology Results Conclusion

Relative order of carotenoids in terms of the ease of oxidation for

LYC, BC, ZEA, LUT, ECH, CAN, APO, ASTA

adiabatic IPs is LYC > BC > ZEA > LUT > ECH > APO > CAN > ASTA,
vertical IPs, is LYC > BC > ZEA > LUT > ECH > CAN > APO > ASTA

vertical IPs is in
perfect agreement with
the experimental
findings

LYC > BC > ZEA > LUT > ECH > CAN > ASTA [12]*
LYC > BC > ZEA > LUT > CAN > APO > ASTA [13]*

* 12. Mortensen, A. and Skibsted, L. H., 1997, J. Agric. Food Chem., 45, 2970.
* 13. Edge, R., Land, E. J., McGarvey, D., Mulroy, L. and Truscott, T. G., 1998, J. Am. Chem. Soc., 120, 4087
Backgrounds Objectives Methodology Results Conclusion
More easier to oxidate

Figure 2. Relative order of carotenoids in terms of oxidation potentials in nonpolar and polar solvents;
■ ref 12, □ ref 13
standing for the order of the ease of electron transfer

TOR is expected to repair other damaged carotenoids through

redox reactions between pairs Car2/Car1•+, regardless of the
environment’s polarity.
Backgrounds Objectives Methodology Results Conclusion
Table 4. Gibbs Free Energies of Reaction (kcal/mol) for Electron Transfer between Pairs of
Carotenoids with Respect to BC, LYC, and TOR

solvent = benzene solvent = water

BC LYC TOR BC LYC TOR
ASTA -8.21 -11.65 -12.50 -4.57 -7.42 -7.91
APO -5.32 -8.76 -9.61 -3.81 -6.66 -7.15
CAN -6.17 -9.60 -10.46 -4.16 -7.00 -7.49
LUT -2.35 -5.79 -6.64 -1.20 -4.05 -4.54
ZEA 0.08 -3.36 -4.21 0.65 -2.20 -2.68
BC -3.44 -4.29 -2.85 -3.34
LYC 3.44 -0.85 2.85 -0.49
DIH -2.60 -6.04 -6.89 -1.08 -3.93 -4.41
ECH -1.87 -5.31 -6.16 -0.82 -3.66 -4.15
NOS -1.18 -4.62 -5.47 -0.46 -3.30 -3.79
OKE -2.50 -5.94 -6.79 -1.42 -4.27 -4.76
SAP 1.64 -1.79 -2.65 1.10 -1.75 -2.24
TOR 4.29 0.85 3.34 0.49
CSAN -6.08 -9.52 -10.37 -4.00 -6.85 -7.33
CRUB -11.31 -14.74 -15.60 -9.03 -11.87 -12.35
CRY -4.97 -8.41 -9.26 -3.90 -6.75 -7.24
NEO -0.18 -3.62 -4.47 -0.09 -2.93 -3.42
VIO -2.42 -5.85 -6.71 -1.84 -4.69 -5.18
MYT -6.83 -10.26 -11.12 -5.06 -7.91 -8.40
Backgrounds Objectives Methodology Results Conclusion

Table 5. Gibbs Free Energies (kcal/mol)a of Carotenoidsa Electron-Transfer Reactions with Different Radicals
in a Polar Environment (Solvent = Water)

R1 R2 R3 R4 R5 R6 R7 R8 R9
(R1)= hydrogen peroxyl
ASTA 9.26 1.55 -10.84 4.11 2.71 -14.46 -11.03 -20.69 -14.50 HOO•
APO 8.73 1.02 -11.37 3.58 2.18 -14.99 -11.56 -21.22 -15.03
CAN 9.02 1.31 -11.08 3.86 2.46 -14.71 -11.27 -20.93 -14.75
(R2)= methyl peroxyl
CH3OO•
LUT 5.78 -1.92 -14.32 0.63 -0.77 -17.94 -14.51 -24.17 -17.98
ZEA 3.96 -3.75 -16.14 -1.20 -2.59 -19.77 -16.33 -25.99 -19.81 (R3)= methoxyl
BC 4.48 -3.23 -15.62 -0.67 -2.07 -19.24 -15.81 -25.47 -19.28
CH3O•

LYC 2.07 -5.64 -18.03 -3.08 -4.48 -21.65 -18.22 -27.88 -21.69 (R4)= benzyl peroxyl
DIH 5.59 -2.11 -14.51 0.44 -0.96 -18.13 -14.70 -24.36 -18.17 C6H5CH2OO•
ECH 5.81 -1.90 -14.29 0.66 -0.74 -17.91 -14.48 -24.14 -17.95
(R5)= phenoxyl
NOS 5.69 -2.01 -14.40 0.54 -0.86 -18.03 -14.60 -24.25 -18.07 C6H5O•
OKE 6.31 -1.40 -13.79 1.16 -0.24 -17.41 -13.98 -23.64 -17.45
(R6)= acyl peroxyl
SAP 3.96 -3.75 -16.14 -1.20 -2.59 -19.77 -16.33 -25.99 -19.81
CH3C(O)OO•
TOR 1.52 -6.19 -18.58 -3.64 -5.03 -22.21 -18.77 -28.43 -22.25
CSAN 8.84 1.13 -11.26 3.69 2.29 -14.88 -11.45 -21.11 -14.92 (R7)= phenylacetyl
peroxyl C6H5C(O)OO•
CRUB 14.03 6.32 -6.07 8.87 7.47 -9.70 -6.26 -15.92 -9.74
CRY 8.42 0.71 -11.68 3.26 1.87 -15.30 -11.87 -21.53 -15.34 (R8)= trichloromethyl
NEO 4.98 -2.73 -15.12 -0.18 -1.58 -18.75 -15.32 -24.97 -18.79 peroxyl CCl3OO
VIO 6.38 -1.33 -13.72 1.23 -0.17 -17.34 -13.91 -23.57 -17.38
(R9)= nitrite NO2•
MYT 9.92 2.21 -10.18 4.76 3.37 13.80 --10.37 -20.03 -13.84

aEnergies: SP/B3LYP/6-311++G(d,p); geometries: B3LYP/6-31G(d,p); thermodynamic corrections: B3LYP/3-21G.

Backgrounds Objectives Methodology Results Conclusion

- Ionization potentials seem to be capable of predicting the correct

relative ease of oxidation in a series of carotenoids at a low
computational cost

- TOR is predicted as the carotenoid with the highest antioxidant

efficiency from the modeled set, expressed as the electron donating
capability, in polar and nonpolar media and in Car + free radical
reactions as well as in carotenoid pair redox reactions.