Theoretical calculation on a compound formed by methyl alcohol and simmondsin

Etheric oil results from the esterification reactions of oil acids with alcohols. In these reactions, one molecule water (H2O) is composed of H protons from oil acids and OH groups which separated from alcohol. Etheric oil is commonly used in food industry, perfume industry and medicine. From this perspective, we need to know physical properties of etheric oil as well as chemical properties. In this study, the highest occupied molecular orbital (HOMO) energies, the lowest unoccupied molecular orbital (LUMO) energies, the electronic properties (total energy, electronegativity, chemical hardness and softness), NBO analysis and thermodynamic parameters of a compound formed by methyl alcohol and simmondsin have been performed by using Gaussian 09W program. The structural and spectroscopic data of the molecule in the ground state have been calculated by using density functional method (DFT/B3LYP) with the 6-31++G(d,p) basis set.


Introduction
Simmondsin is a flavan-3-ol, a type of natural phenol and antioxidant.It is a plant secondary metabolite.It belongs to the group of flavan-3-ols (or simply flavanols (phenols)), part of the chemical family of flavonoids.In organic chemistry; phenols sometimes called phenolics are the class of chemical compounds consisting of a hydroxyl group ( -OH) bonded directly to an aromatic hydrocarbon group.Phenolic compounds are classified as simple phenols or polyphenols which are based on the number of phenol units in the molecule [1][2][3].
Simmondsin is an extract of jojoba seeds (Simmondsia chinensis), it was traditionally thought to be a toxic substance due to jojoba seed meal which causing weight loss in animals.
Although it has been researched as a potential treatment for reducing appetite of obese individuals by helping to reduce craving for food.Several mechanisms of action are thought to be involved in the appetite suppressant effect [4][5][6].
Etheric oil results from the esterification reactions of oil acids with alcohols.Etheric oil is commonly used in food industry, perfume industry and medicine.From this perspective, we need to know physical properties of etheric oil as well as chemical properties.It is also important to understand the properties of the coalescence of simmondsin to develop new molecules.
Calculations using large basis sets are more accurate because they are less restrictive on the location of the electrons.Such calculations are also more expensive because they require computing more integrals.DFT methods account for electron correlation by estimating the interaction of an electron with the total electron density.DFT orbitals are formed from basis functions like those used in SCF or MP2.Most popular DFT method is B3LYP (Becke3-Parameter method for calculating that part of the molecular energy due to overlapping orbitals, plus the Lee-Yang-Parr method of accounting for correlation).In this regard, we optimized the methyl alcohol and simmondsin by using B3LYP method and 6-31++G(d,p) basis set.
In this study, we investigated theoretically the electronic structure using HOMO-LUMO energies, electron delocalizations using NBO analysis and thermodynamic parameters at different temperatures using B3LYP/6-31++G(d,p) level of a compound formed by methyl alcohol and simmondsin.

Calculation
The electronic and thermal properties of the compound are theoretically examined by means of B3LYP method with 6-31++G(d,p) basis set.All the calculations were performed by using Gaussian 09.Revision C1 program and GaussView 5.0.8 was used for the visualization of the structure and simulation [7].Gaussian09 package, approximates orbital shapes and orbital energies of a given molecular geometry using a model chemistry consisting of two parts: a basis set and a method.Methanol, also known as methyl alcohol, is a chemical with the formula CH3OH (often abbreviated MeOH).The new simmondsin form (S2 form) comprise by the reaction of methanol and simmondsin (Figure 1).

C16H25NO9 + CH3OH
C17H27NO9 + H2O In these reactions, one molecule water (H2O) is composed of H protons from oil acids and OH -groups which separated from alcohol.After the optimization of the new simmondsin form we determined that the methyl alcohol added to the nucleophilic region of the simmondsin (Figure 3).formed by methyl alcohol and simmondsin.

Electronic Properties
In quantum chemistry, HOMO and LUMO energies are very important parameters.LUMO as an electron acceptor represents the ability to obtain an electron, whereas HOMO represents the ability to donate an electron [8].The HOMO and LUMO energies of the compounds (S1 and S2 form) are calculated by using B3LYP/6-31++G(d,p) level in gas phase and these energies are presented in Table 1.Energy gap (ΔE) between HOMO and LUMO characterizes the molecular chemical stability and electron conductivity.The following parameters can be calculated using HOMO and LUMO energy values: Ionization potential (I=-EHOMO) is the minimum energy required to remove an electron from a molecule in gas phase.Electron affinity (A= -ELUMO) is the amount of energy increasing when added an electron to a molecule in the gas phase.Electronegativity (χ = (I + A)/2) represents the electron attraction of atom in a molecule.Chemical hardness (η=(I-A)/2) is a measure of the inhibition of the charge transfer to the molecule.If the value of chemical hardness of a molecule is high, the charge transfer can be less or charge transfer could not take place.Chemical softness is S=1/η [9,10].The HOMO-LUMO energy gap values of the S1 and S2 form of the molecule are 5.09 and 5.14 eV, respectively.An electronic system with a larger HOMO-LUMO energy gap should be less reactive than one having a smaller gap [11].The high HOMO-LUMO energy gap value indicates that there is very little or no charge transfer in the molecule.As seen from Fig. 2, the positive phase is symbolized with red and the negative phase green.

Molecular electrostatic potential (MEP)
MEPs, also known as electrostatic potential maps, show that the molecules have three dimensional charge distributions.In this case the knowledge of charge distribution can be used for determination of molecule interactions.The red color represents the low potential areas and rich electron regions, while blue color represents the high potential areas and poor electron regions and green color represents the regions of zero potential on the map (red < orange < yellow < green < blue).MEP values are calculated by using the following equation where ZA is the charge on nucleus A, located at RA and (r) is the electronic density function of the molecule, and r is the dummy integration variable [12].MEPs map of the title compound is represented using B3LYP/6-31++ G (d,p) level of theory and are given in Figure 3.As can be seen from Fig. 3, map color range is between from -0.06606 (deepest red region) to +0.06606 (deepest blue region).In the S1 form the red regions are around the OH and N so the methyl alcohol attached the nucleophilic region.The deepest blue regions both in S1 and S2 forms are the electrophilic regions waiting for attract the positive ions.

Thermodynamic Properties
The heat formation is one of the most important parameter of thermochemical properties of the molecule.The heat formation values of many organic compounds are not known.The importance of the quantum chemical calculations are increased by the heat effect investigations.In the study of the organic reaction mechanisms the thermodynamic quantum chemical data are extensively used.
Thermodynamic parameters; thermal energy, specific heat capacity, rotational constants, entropy and sum of electronic and thermal enthalpy of the S1 and S2 forms were calculated by using the B3LYP/6-31++G(d,p) level in the gas phase.Thermodynamic parameters such as change in the free energy (G) in Cal.Mol -1 , and entropy (S) in Cal.Mol - 1 .K -1 were determined using the following equations [18]: Where o for the total electronic energy, Kd is the equilibrium constant, G is the internal energy, T is the temperature in Kelvin and R is the gas constant [19].The values of the thermodynamic parameters are depended on temperature of the compound were given in Table 4.

Conclusion
The aims of this study are to give a complete description of the physical and chemical properties of the methanol and simmondsin complex theoretically.This study will be helpful to systematically understanding of the structures of methanol and simmondsin for studying the structure-activity relationship.The electronic and thermodynamic properties of the compound were also investigated in the gas phase at B3LYP/6-31++G(d,p) level.The thermodynamic properties of the title compound were calculated in the gas phase and were interpreted in different temperatures.HOMO-LUMO energy gap is calculated as 5.14 eV at B3LYP/6-31++G(d,p) level.This high energy gap value show us the charge transfer in the molecule is very little or not exist.The high electron density is mostly localized on the OH group around the N atom as can be seen in Figure 3. On the other hand, this reaction has been found out that the formation of methanol and simmondsin complex compound is endothermic, and it is easy to obtain this complex as the temperature increases.

Figure 2 .
Figure 2. Optained the molecular orbitals of the title compound by using B3LYP/6-311G++(d,p) level in the gas phase.
If the reaction is endothermic, the value of E is positive.But, if the reaction is spontaneous, the value of G is negative.The high equilibrium constant (Kd) indicates that the spontaneity of the reaction increases at high temperature.The plotting 1/T against lnKd is shown in Fig4(y = 1.3759x -0.6114; R² = 0.9999).R² value which obtained by using the least squares method is very close to 1.It means that the data obtained the Kd equilibrium constant values are consistent with each other and have a linear relationship between the variable.

Figure 4 .
Figure 4.The thermodynamic behavior of the title compound is illustrated by plotting 1/T against lnKd graph.

Table 1 .
The electronic structure parameters calculated for the molecule.

Table 2 .
Second order perturbation theory analysis of Fock matrix in NBO for the molecule S1 in gas phase basis for6-31++G(d,p)

Table 4 .
The values of the thermodynamic parameters [the internal thermal energy (Etot), constant volume heat capacity (Ctot) and entropy (Stot)] depended on temperature of the compound (in the S1 and S2 forms).