Short Communication - (2024) Volume 15, Issue 1

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 Gümüş1* and Cengiz İpek2
 
*Correspondence: Hacer Gümüş, Department of Marketing, Ali Rıza Veziroğlu Vocational School, Kocaeli University, Kocaeli, Turkey, Email:

Author info »

Abstract

In this study, quantum chemical calculations of 1-(2’-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one have been performed using Gaussian 09 program. Theoretical computational analysis data of the molecule in the ground state have been calculated using HSEH1PBE (The exchange part of the screened Coulomb potential of Heyd, Scuseria, and Ernzerhof) and Becke’s 3-Parameter (B3LYP) hybrid functional using B exchange and, Lee-Yang-Par (LYP) correlation levels of Density Functional Method (DFT) with the 6-311++G(d,p) basis set. The effect of temperature on the 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one and its thermodynamic parameters entropy, enthalpy, and heat capacity have been analyzed. Mulliken, Natural Bond Orbital (NBO) charges and Atomic Polar Tensor (APT) charges of the investigated molecule have also been calculated. In addition, the molecular frontier orbital energies Highest Occupied Molecular Orbital (HOMO), HOMO-1, Lowest Unoccupied Molecular Orbital (LUMO) and LUMO+1) of the 1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one have been calculated. Finally, Molecular Docking (MD) study has been carried out with the help of AutoDock computational program.

Keywords

1-(2´-Thiophen)-3-(2,3,5-trichlorophenyl)-2-propen-1-one, DFT, APT charge, Molecular docking

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.

optimized

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.

Thermal energy, E (Kcal/mol) B3LYP/6-311++G (d,p) HSEH1PBE/6-311++G (d,p)
Rotational 0.889 0.889
Translational 0.889 0.889
Vibrational 109.807 110.72
Total 111.584 112.498
Heat capacity, Cv (cal/mol K)
Rotational 2.981 2.981
Translational 2.981 2.981
Vibrational 54.395 53.917
Total 60.356 59.879
Entropy, S (cal/mol K)
Rotational 35.331 35.299
Translational 43.147 43.147
Vibrational 59.322 58.899
Total 137.8 137.345
Rotational constants (GHz)
A 0.48472 0.49041
B 0.11713 0.11839
C 0.09612 0.0971
Rotational temperature (Kelvin)
A 0.02326 0.02354
B 0.00562 0.00568
C 0.00461 0.00466
Thermal properties (Hartree/particle)
Zero-point correction 0.161242 0.162813
Thermal correction to energy 0.177821 0.179276
Thermal correction to enthalpy 0.178765 0.18022
Thermal correction to Gibbs free energy 0.113292 0.114963
Sum of electronic and zero-point Energies -2353.67 -2352.47
Sum of electronic and thermal energies -2353.65 -2352.45
Sum of electronic and thermal free energies -2353.72 -2352.52
Zero point vibrational energy (kcal/mol) 101.1809 102.1668

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.

Atom Mulliken APT NBO
  B3LYP HSEH1PBE B3LYP HSEH1PBE B3LYP HSEH1PBE
C5 0.182877 0.242625 -0.0512 -0.06046 -0.35915 -0.37059
C4 -1.02756 -1.2941 -0.23192 -0.23498 -0.26104 -0.26769
C3 0.853826 1.084759 0.067185 0.060301 -0.19995 -0.2062
C2 0.078725 0.04221 -0.37674 -0.38242 -0.28708 -0.29755
S1 -0.30987 -0.44474 0.069065 0.074749 0.49527 0.50474
H5 0.253474 0.302216 0.088389 0.094965 0.22764 0.23554
H4 0.155224 0.195729 0.057511 0.063034 0.22129 0.22823
H3 0.168715 0.222099 0.071079 0.076065 0.21709 0.22409
C6 -0.61573 -0.69056 1.382795 1.390493 0.4781 0.47821
C8 0.113801 0.137899 -0.49717 -0.50789 -0.25304 -0.26317
H10 -0.07143 -0.07955 0.045291 0.050518 0.19546 0.20248
C9 -0.60694 -0.66571 0.206979 0.205659 -0.11967 -0.1259
H9 0.22852 0.271274 0.087625 0.09289 0.24091 0.24828
C10 0.049648 0.08434 0.013585 0.011463 -0.06042 -0.06498
C15 -0.98813 -1.104 -0.20286 -0.20434 -0.19811 -0.20342
C11 -0.18953 -0.31847 0.211441 0.205244 -0.05607 -0.0634
C14 0.598797 0.530977 0.455038 0.44591 -0.02654 -0.03697
H15 0.175482 0.214328 0.066657 0.069803 0.22553 0.2322
C12 0.321991 0.361641 0.402394 0.403663 -0.0519 -0.06075
C13 -1.00449 -1.04518 -0.24013 -0.23866 -0.225 -0.23029
H13 0.217082 0.259692 0.088641 0.092138 0.23997 0.24648
O7 -0.24489 -0.22566 -0.83519 -0.83888 -0.56578 -0.5613
Cl16 0.690923 0.785682 -0.23989 -0.23626 0.05408 0.06401
Cl18 0.490234 0.561975 -0.30383 -0.30188 0.04816 0.05759
Cl19 0.479251 0.570533 -0.33476 -0.33111 0.02024 0.03037

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

Mulliken

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

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.

Electronic properties B3LYP /6-311++G(d,p) HSEH1PBE/6-311++G(d,p)
EHOMO (eV) -7.10196 -6.91447
ELUMO (eV) -2.95382 -3.14593
ΔE=ELUMO-EHOMO (eV) 4.148136 3.768535
I (eV) 7.101955 6.914468
A (eV) 2.953819 3.145933
c (eV) 5.027887 -5.0302
h (eV) 2.074068 -1.88427
S (eV-1) 0.070403 -0.07231
ETotal (a.u) -2353.83 -2352.63

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

Thiophen

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.

protein

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.

References

Author Info

Hacer Gümüş1* and Cengiz İpek2
 
1Department of Marketing, Ali Rıza Veziroğlu Vocational School, Kocaeli University, Kocaeli, Turkey
2Department of Civil Engineering, Istanbul Medeniyet University, Istanbul, Turkey
 

Citation: Gümüş H: 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

Received: 11-Dec-2023 Accepted: 25-Dec-2023 Published: 01-Jan-2024, DOI: 10.31858/0975-8453.15.1.24-28

Copyright: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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