4TH International Congress on Technology - Engineering & SCIENCE - Kuala Lumpur - Malaysia (2017-08-05)

Theoretical Study Of Hydrogen Atom Transfer Mechanism In Tetrahydrocurcumin
Tetrahydrocurcumin (THC) is a major metabolite of curcumin and the most active compound found in rhizome of turmeric [1]. Recently, THC has been proposed as a new anticancer agent for human leukemia[2], a chemopreventive agent for human breast cancer [3], and as an antioxidant due to its ability to scavenge Reactive Oxygen Species (ROS) [4]. In performing as an antioxidant, THC must be able to transfer its hydrogen atom toward ROS. This mechanism is known as hydrogen atom transfer (HAT) and occurs according to the following reaction [5]: R. + THC-H  THC. + RH (1) where R. is ROS that is lack of hydrogen atom, THC-H stands for THC molecule prior to hydrogen transfer, THC. is a THC molecule that has transferred its hydrogen atom to ROS and RH stands for ROS that has received one hydrogen atom. In order for this scavenging activity to occur, THC must be able to break its hydrogen bond. Experimental results has confirmed THC’s ability to transfer hydrogen atom toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical [1]. To explain how this phenomenon occurs in molecular level, we utilize density-functional theory (DFT). We use DFT framework to calculate Bond Dissociation Enthalpy (BDE) of an X-H bond. The objective of this study is to explain THC’s antioxidant ability through HAT mechanism by evaluating BDE value. In our calculation, we use MO5-2X exchange functional [6] and 6-31++G(d,p) basis set implemented in Gaussian 09 suite program[7]. Molecular geometries were optimized with two kinds of DFT methods, RMO5-2X/6-31++G(d,p) and UMO5-2X/6-31++G(d,p) in gas phase. RMO5-2X and UMO5-2X refer to restricted open shell calculation for neutral THC and unrestricted open shell calculation for THC., respectively. To create a THC., hydrogen atom is abstracted from three different sites, which are C20, O5 and O6. Thermodynamic corrections at 298.15 K were included in calculations. Geometry optimization is then repeated in water solvents to represent polar environment (see figure 1). To add the solvent effect we used polarized continuum model (PCM), where the solvent is modelled as cavity that interact electrostatically with solute placed within the cavity [8]. The X-H BDE is calculated as follow [9]: BDE = Hr + Hh - Hn (2) where Hr is the enthalpy of THC., Hh is the enthalpy of hydrogen atom (0.4962 Hartree) and Hn is the enthalpy of neutral molecule. Our results suggest that hydrogen atom bonded to a carbon atom has the highest BDE value compare to other sites. This means C-H bonds barely can transfer its hydrogen atom regardless of the environment. However, two O-H sites in THC are competing in transferring their hydrogen atom. The differences in BDE values at site O5 and O6 is less than 1 kcal/mol in both of the environment. This suggests that the presence of water solvents does not change the active site of THC. Our result shows the same trend as the one from previous calculation [10]. We predict that two O-H sites in THC compete in transferring a hydrogen atom in HAT mechanism
Keywords: Antioxidant, Bond dissociation enthalpy, Density-functional theory, Tetrahydrocurcumin
Lusia Silfia Pulo Boli, Adhitya G. Saputro, Mohammad K. Agusta, Febdian Rusydi, Heni Rachmawati