Computational Analysis of Density Functional Theory (DFT method), Thermodynamic Investigations and Molecular Docking Studies on 1-(2'-Thiophen)-3- (2,3,5-trichlorophenyl)-2-propen-1-one

Hacer Gümüş^1* and Cengiz İpek^{2 *}Correspondence: Hacer Gümüş, Department of Marketing, Ali Rıza Veziroğlu Vocational School, Kocaeli University, Kocaeli, Turkey, Email:

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Introduction

Thiophene based materials, due to the richness of thiophene chemistry and the general stability of its compounds, have found applications in fields ranging from antistatic coatings to polymer electronics (Manjunath HR, et al., 2011; Huang W, et al., 1998). In medicinal chemistry, sulfur-containing heterocyclic is well known for its therapeutic applications. Thiophene-containing compounds are also widely used in electroluminescent polymer, electronic and optoelectronic devices, and modern drug design (Blumstengel S, et al., 1999; Batista RM, et al., 2009; Hosmane RS and Liebman JF, 1991). Compounds containing thiophene nucleus possess a broad range of biological activities such as anti-inflammatory, analgesic, antifungal, ocular hypertensive activities, and antimicrobial activities (Lin JW, Dudek LP, 1980; Jen KY, et al., 1986; Hu X and Xu L, 2000).

About the Study

Computational details

The molecular simulation of 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule was performed with Gaussian 09W program package (Frisch MJ, et al., 2009) and the output files were visualized by means of the GaussianView 5 software (Dennington R, et al., 2009). All theoretical data of 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule were calculated using B3LYP (Becke’s three parameter hybrid functional using the LYP correlation functional) (Becke AD, 1992; Lee C, et al., 1988) and HSEH1PBE (HeydScuseria-Ernzerh of functional) (Heyd J and Scuseria GE, 2004; Heyd J, Scuseria GE, 2004; Heyd J, et al., 2005; Heyd J, et al., 2003) levels with 6-311++G(d,p) basis set (Frisch MJ, et al., 1984).

Geometric structure

Optimized geometrical structure of 1-(2´-Thiophen)-3-(2,3,5- trichlorophenyl)-2-propen-1-one molecule was shown in Figure 1.

Figure 1: The optimized structure of 1-(2’-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one calculated at B3LYP/6-311++G(d,p)

Thermodynamic properties

The thermodynamic values of the 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule was calculated at DFT/B3LYP and DFT/HSEH1PBE methods. The calculated thermodynamic parameters were presented as shown in Table 1.

Table 1: Thermodynamic parameters of 1-(2’-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one

Mulliken, APT, NBO charge analysis

Mulliken, APT and NBO charges of 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule were calculated and results were given in Figure 2 and Table 2.

Table 2: The Mulliken, APT and NBO charges of 1-(2’-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one

Figure 2: Mulliken, APT and NBO charges plots of 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one

Electronic properties

The HOMO and LUMO are very important parameters in the electronic studies by quantum chemical calculations. The total energy, HOMO and LUMO energies, the energy gap (ΔE), the ionization potential (I), the electron affinity (A), the absolute electronegativity (c), the absolute hardness (h) and softness (S) for 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one were calculated at B3LYP and HSEH1PBE levels in the 6-311++G(d,p) basis set, and the results were presented in Table 3. The frontier orbital picture was depicted in Figure 3 with the 3D plots for the gas phase, and the positive and negative phases are represented in red and green color, respectively.

Table 3: Fragment Molecular Orbital (FMOs), energies and calculated physico-chemical properties

Figure 3: Molecular orbital pictures for 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one at HSEH1PBE/6-311++G(d,p)

Molecular docking

1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule docking has been examined in active sites of the selected protein. The 1Z8V protein exhibits the min binding energy of -4.95 kcal/mol, intermolecular energy of -5.4 kcal/mol, and inhibition constant of 234.9 micromolar (uM). The deviation between the ligand-protein has been analyzed, where the Root Mean Square Deviation (RMSD) value has been calculated as 2.63 for 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one. The molecular interaction diagrams of target protease Protein Data Bank (PDB) 1Z8V and ligand (1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one) were shown in Figure 4.

Figure 4: Detailed view of the interaction between protein and ligand

Conclusion

The geometry of 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one molecule was optimized in different levels with DFT/B3LYP and DFT/ HSEH1PBE method using 6-311++G(d,p) basis set. The correlations between the statistical thermo-dynamics and temperature are also obtained. It is seen that the heat capacities, entropies and enthalpies increase with the increasing temperature owing to the intensities of the molecular vibrations increase with increasing temperature. Frontier molecular orbitals, energies and energy gap between HOMO and LUMO were calculated. Additionally, interaction between 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-pro-pen-1-one and PDB 1Z8V protein has been docked.

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