Abstract
We investigated the conformational structure of eugenol and eugenyl acetate under torsional angle effect by performing semiempirical calculations using AM1 and PM3 methods. From these calculations, we have evaluated the strain energy of conformational interconversion. To provide a better estimate of stable conformations, we have plotted the strain energy versus dihedral angle. So, we have determined five geometries of eugenol (three energy minima and two transition states) and three geometries of eugenyl acetate (two energy minima and one transition state). From the molecular orbital calculations, we deduce that the optimized trans form by AM1 method is more reactive than under PM3 method. We can conclude that both methods are efficient. The AM1 method allows us to determine the reactivity and PM3 method to verify the stability.
1. Introduction
Eugenol (4-allyl-2-methoxyphenol) is a phenylpropene, an allyl chain-substituted guaiacol. It is the main phenolic compound extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, basil, and bay leaf [1–14]. Eugenol is a phenol derivative used in many areas such as perfumes, flavorings agent, and dental materials. It is used as an antiseptic, analgesic, fungicide, bactericide, insecticide, anticarcinogenic, antiallergic, antioxidant, anti-inflammatory, and so forth [15–17]. As derivative, the eugenyl acetate was characterized and its structural properties have investigated by Dos Santos et al. [18, 19].
To our knowledge, a study of the conformational structure as a function of the dihedral angle was not reported. In the present paper, we investigated the conformational structure of eugenol and eugenyl acetate under torsional angle effect by performing semiempirical calculations using AM1 and PM3 methods. From these calculations, we have evaluated the strain energy of conformational interconversion to provide a better estimate of stable conformations. These results can be used to make future applications possible (Figure 1).
2. Methodology
Molecular modeling of the optimized eugenol and eugenyl acetate was carried out with the use of an efficient program for molecular mechanics (MM). Calculations are performed for all optimized geometries using AM1 and PM3 methods. The main molecular properties to characterize the geometry structures and the molecular orbital of the eugenyl acetate were calculated and compared. For each method, the geometry of the compound was optimized by using the Polak-Ribiere conjugate gradient algorithm with a gradient of 0.01 Kcal/mol (RMS). The following quantum chemical results are considered: heat of formation (Δ), total energy (), minimum energy of conformation (), strain energy of conformational interconversion (), energy of highest occupied molecular orbital (HOMO), energy of lowest unoccupied molecular orbital (LUMO), and HOMO-LUMO energy gaps (EG).
3. Results and Discussion
Molecular geometries of eugenol and eugenyl acetate were optimized by semiempirical molecular orbital method (AM1 and PM3). The semiempirical simulations results for structure optimization of eugenol and eugenyl acetate are given in Table 1. The conformational interconversion energy-minimum of eugenyl acetate and eugenol was investigated in detail by changing different torsional angles. From these studies, we have determined five geometries of eugenol (three energy minima and two transition states) and three geometries of eugenyl acetate (two energy minima and one transition state). These geometries are important in the description of the conformational properties of our systems (Figure 2).
(a)
(b)
We have obtained the curves plotted in Figure 2 from the simulated data using the nonlinear fitting process based on the Levenberg-Marquardt algorithm implemented in the Origin v. 6.0. Software [20].
The dihedral angle for rotation about C4–C10 bond in eugenol has several stationary points. A/A′, C, C′, and E/E′ are minima and B, B′ and D, D′ are maxima. Only the structures at the minima represent stable species and of these, the syn conformation is more stable than the anti. The gauche and the eclipsed represent the transition states. In eugenyl acetate, the stationary points A/A′, B/B′, C/C′, E/E′, F/F′, and G/G′ are minima and D, D′ are maxima. The anti conformation represents the transition state while the syn, gauche, and eclipsed conformations are stable species. So, the deformation around C4–C13 in eugenyl acetate remains unchanged and is not influenced by torsional angle effect.
To provide a better estimate of conformations, we should search the conformational space in reasonable computing time. So, we run the simulations; then we run a geometry optimization on each structure. Thus, we have grouped the resulting structures in Figure 3. First, we observe that all geometries from cis conformations obtained after optimization present deformation mainly on branching allyl. The torsional angle value varies around 136°. This situation is due to methylene group (sp3 hybridization) which gives a noncoplanar final geometry. Then, the -bond of branching allyl is situated in the same side that acetate group. Second, we note that the geometry in anti conformations stays unchanged after optimization. All the substituents of aromatic ring, acetate and methoxy groups then branching allyl, are situated in the same plane (trans: 180°).
From our molecular orbital calculations, we want to deduce the structure-reactivity relationship depending on different conformations. First, AM1 and PM3 calculations show that the cis forms are favored (Table 1, entry 7, EG: 9.075, 9.110 ev). On the other hand, the same calculations show that the most active site of the nucleophilic reaction is located on the oxygens of the acetate group and methoxy, and the most active site of the electrophilic reaction is C8 position of eugenyl acetate.
The AM1 and PM3 calculations show that the trans form is most active (Table 1, entry 7, EG: 8.852; 8.881 ev). Thus, these results reveal that the instability is caused by the high activity of methylene group in the strand allyl which provides to the aromatic ring another nucleophilic reaction site. This one is stabilized by resonance with the double bonds of the aromatic ring and the allylic radical (Figure 4). So, we note that the value of the strain energy obtained with AM1 method (Table 1, entry 4, Es: 9.180 ev) is higher than that obtained by PM3 calculation (Table 1, entry 4, Es: 5.600 ev). Consequently, we deduce that the optimized trans form by AM1 method is more reactive than under PM3 method. We can conclude that the efficient method for the eugenyl acetate is the semiempirical method AM1.
These observations remain the same for eugenol, except for the energy gaps. From Figure 2(a), we note that the trans form (C or C′) is near the transition states B and D, respectively, B′ and D′. This situation is clearer when the eugenol is optimized by PM3 (Table 1, entries 5 and 6, PM3: HOMO −8.599, LUMO 0.327 ev; AM1: HOMO −8.670, LUMO 0.254 ev). So, this trans form (C or C′) corresponds to the reaction intermediate present in eugenol and absent in eugenyl acetate (AM1: HOMO −8.606, LUMO 0.343; PM3: HOMO −8.702, LUMO 0.260 ev).
Furthermore, we also see that the HOMO is located at the oxygen sites whereas for the molecule the Homo is distributed along the aromatic cycle site (Figure 4, Table 2). This clearly shows the high reactivity of eugenol compared to its corresponding acetate. This reactivity is due to mobility of hydrogen and the nucleophilicity on the aromatic ring.
From calculating wave functions, we observe that the charge distributions are mainly located on electrowithdrawing oxygen atoms in each molecule. They also are situated on aromatic ring and the strand allyl. The charge density is much higher under AM1 than under PM3. So, these results are in accordance with their energy properties (see Table 1) and the electronic properties of each substituent. The acetate group is an electron withdrawing type which reduces the aromatic cycle charge while hydroxyl group is an electron donor type that can provide its charge to the aromatic ring and thus increases its nucleophilic effect (Table 2).
4. Conclusion
In the present work, we have studied the conformational structure of eugenol and eugenyl acetate under torsional angle effect by performing semiempirical calculations using AM1 and PM3 methods. From quantum calculations, we have evaluated the strain energy of conformational interconversion. To provide a better estimate of stable conformations, we have plotted the strain energy versus dihedral angle. So, we have determined five geometries of eugenol (three energy minima and two transition states) and three geometries of eugenyl acetate (two energy minima and one transition state). We have verified the presence of the intermediate form of eugenol which corresponds to the trans form (C or C′).
From the molecular orbital calculations, we deduce that the optimized trans form by AM1 method is more reactive than under PM3 method. We note that the charge distributions are mainly located on the aromatic ring and the strand allyl in each molecule. We can conclude that both methods are efficient. The AM1 method allows us to determine the reactivity and PM3 method to verify the stability.
Conflict of Interests
The author declares that there is no conflict of interest regarding the publication of this paper.