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Exploring the Impacts of Substitution Position on Structural, Electronic, and Energetic Characteristics of Selected Chalcone Derivatives by DFT Method: A Quantum Computational Research

Year 2025, Volume: 46 Issue: 1, 79 - 90, 25.03.2025

Sümeyya Serin

https://doi.org/10.17776/csj.1548916

Abstract

Chalcone derivatives are frequently utilized as a versatile scaffold in molecular design studies due to their broad-spectrum activities. Structural modification studies applied to increase their biological activities to a remarkable level reveal the importance of substitution positions on aromatic rings. In this respect, the study aimed to explore the effects of changing substitution positions on molecular properties. Herein, the effects of distinct substitution positions on thermodynamic and physicochemical parameters, reactivity descriptors, absorption characteristics, and intramolecular interactions were investigated utilizing quantum chemical methods. To this end, (Density Functional Theory) DFT-based calculations were performed using the GAUSSIAN 16 software with B3LYP/6-311++G (d, p) level on ortho-OH, meta-OH, and para-OH substituted chalcone derivatives. While the calculated dipole moment and polarizability values differ, very similar results were obtained for the ∆E (total energy), ∆H (enthalpy), and ∆G (Gibbs free energy) parameters. The highest polarizability value, 296.193 a.u., was obtained for the para- isomer. The ∆Eg values in the gas phase were calculated as: 4.013 eV (m-) > 3.898 eV (p-) > 3.832 eV (o-). Also, the effects of different solvents on the absorption spectra of the studied isomers were investigated theoretically using (Time Dependent) TD-DFT calculations. Molecular orbitals contributing to electronic transitions were determined for each phase. It is further anticipated that the research findings will offer novel insights to inform future studies on the implications of the substitution position.

Keywords

Chalcone Substitution position DFT Reactivity Absorption characteristics

References

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  • [6] Parikh K., Joshi D., Antibacterial and Antifungal Screening of Newly Synthesized Benzimidazole-Clubbed Chalcone Derivatives, Med. Chem. Res., 22(8) (2013) 3688-3697.
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  • [10] Patil P., Zangade S., Synthesis and Comparative Study of Cytotoxicity and Anticancer Activity of Chalconoid-Co(II) Metal Complexes with 2-hydroxychalcones Analogue Containing Naphthalene Moiety, J. Indian Chem. Soc., 99 (2022) 100274.
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  • [13] Sahib M.A., Mahdi M.F., Molecular Docking, Synthesis, Characterization and Preliminary Evaluation of some New 3-Ethyl-1H-Indole Derivatives as Potential COX-2 Inhibitors, Adv. J. Chem. A, 8(5) (2025) 948-960.
  • [14] Sandeli A.E., Khiri-Meribout N., Benzerka S., Boulebd H., Gürbüz N., Özdemir N., Özdemir I., Synthesis, Structures, DFT Calculations, and Catalytic Application in the Direct Arylation of Five-Membered Heteroarenes with Aryl Bromides of Novel Palladium-N-Heterocyclic Carbene PEPPSI-Type Complexes, New J. Chem., 45 (2021) 17878-17892.
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  • [18] Becke A.D., Density‐Functional Thermochemistry. III. The Role of Exact Exchange, J. Chem. Phys., 98 (1993) 5648–5652.
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  • [21] Tomasi J., Mennucci B., Cammi R., Quantum Mechanical Continuum Solvation Models, Chem. Rev., 105 (2005) 2999–3093.
  • [22] Casida M.E., Jamorski C., Casida K.C., Salahub D.R., Molecular Excitation Energies to High-Lying Bound States from Time-Dependent Density-Functional Response Theory: Characterization and Correction of the Time-Dependent Local Density Approximation Ionization Threshold, J. Chem. Phys., 108 (1998) 4439–4449.
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  • [25] Serdaroğlu G., Durmaz S., DFT and statistical mechanics entropy calculations of diatomic and polyatomic molecules, Indian J. Chem., 49 (2010) 861-866.
  • [26] Koopmans T., Über die zuordnung von wellenfunktionen und eigenwerten zu den einzelnen elektronen eines atoms, Physica 1–6 (1934) 104–113.
  • [27] Parr R.G., Electrophilicity Index, J. Am. Chem. Soc., 121 (1999) 1922-1924.
  • [28] Parr R.G., Pearson R.G., Absolute Hardness: Companion Parameter to Absolute Electronegativity, J. Am. Chem. Soc., 105 (1983) 7512-7516.
  • [29] Pearson R.G., Absolute Electronegativity and Hardness Correlated with Molecular Orbital Theory, Proc. Natl. Acad. Sci. U.S.A, 83 (1986) 8440-8441.
  • [30] Perdew J.P. and Levy M., Physical Content of the Exact Kohn-Sham Orbital Energies: Band Gaps and Derivative Discontinuities, Phys. Rev. Let., 51 (1983) 1884-1887.
  • [31] Perdew J.P., Parr R.G., Levy M. and Balduz J.L, Density-Functional Theory for Fractional Particle Number: Derivative Discontinuities of the Energy, Phys. Rev. Let., 49 (1982) 1691.
  • [32] Gazquez J.L., Cedillo A. and Vela A., Electrodonating and Electroaccepting Powers, J. Phys. Chem. A., 111(10) (2007) 1966-1970.
  • [33] Gomez B., Likhanova N.V., Domínguez-Aguilar M.A., Martínez-Palou R., Vela A. and Gazquez J.L., Quantum Chemical Study of the Inhibitive Properties of 2-Pyridyl-azoles, J. Phys. Chem. B., 110(18) (2006) 8928-8934.
  • [34] Weinhold F., Landis C.R., Glendening E.D., What Is NBO Analysis and How Is It Useful? Int. Rev. Phys. Chem., 35 (2016) 399-440.
  • [35] Reed A.E., Curtiss L.A. and Weinhold F., Intermolecular Interactions from a Natural Bond Orbital, Donor-Acceptor Viewpoint, Chem. Rev. 88(6) (1988) 899-926.
  • [36] Sahib M.A., Mahdi M.F., Identification of Indole Derivatives as Selective Cyclooxygenase-2 Inhibitors by Virtual Screening and Molecular Dynamic Simulation, Turkish Comp. Theo. Chem. (TC&TC), 9(2) (2025) 19-32.
  • [37] Qiu X.Y., Yang S.L., Liu W.S. and Zhu H.L., (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one, Acta Cryst. E62 (2006) 3324-3325.
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  • [40] Shubhalaxmi, Hahne S., Zschille C., Jayarama A., Bhat K.S., Crystal Structure Studies and Thermal Characterization of Novel 4-hydroxychalcone Derivative, Chem. Sci. Trans., 2(3) (2013) 841-846.
  • [41] Prasad A.A., Muthu K., Meenatchi V., Rajasekar M., Agilandeshwari R., Meena K., Manonmoni J.V., Meenakshisundaram S.P., Spectrochim. Acta A Mol. Biomol. Spectrosc. 140 (2015) 311–327.
  • [42] Murray J.S., Sen K., Molecular Electrostatic Potentials: Concepts and Applications, first ed., Elsevier, (Amsterdam, 1996).
  • [43] Turowska-Tyrk I., Grzesniak K., Trzop E., Zych T., Monitoring Structural Transformations in Crystals. Part 4. Monitoring Structural Changes in Crystals of Pyridine Analogs of Chalcone During [2+2]-Photodimerization and Possibilities of the Reaction in Hydroxy Derivatives, J. Solid State Chem., 174 (2003) 459–465.
  • [44] Tomečková V., Guzy J., Kušnír J., Fodor K., Mareková M., Chavková Z., Perjési P., Comparison of the Effects of Selected Chalcones, Dihydrochalcones and Some Cyclic Flavonoids on Mitochondrial Outer Membrane Determined by Fluorescence Spectroscopy, J. Biochem. Biophys. Methods, 69 (2006) 143–150.

Year 2025, Volume: 46 Issue: 1, 79 - 90, 25.03.2025

Sümeyya Serin

https://doi.org/10.17776/csj.1548916

Abstract

References

  • [1] Narwal S., Devi B., Dhanda T., Kumar S. and Tahlan S., Exploring Chalcone Derivatives: Synthesis and Their Therapeutic Potential, J. Mol. Struct., 1303 (2024) 137554.
  • [2] Yadav P., Lal K., Kumar A., Guru S.K., Jaglan S., Bhushan S., Green Synthesis and Anticancer Potential of Chalcone Linked-1,2,3-triazoles, Eur. J. Med. Chem., 126 (2017) 944-953.
  • [3] Wang G., Xue Y., An L., Zheng Y., Dou Y., Zhang L., Liu Y., Theoretical Study on the Structural and Antioxidant Properties of Some Recently Synthesized 2,4,5-trimethoxy Chalcones, Food Chem., 171 (2015) 89-97.
  • [4] Reddy M.V.B., Hung H.Y., Kuo P.C., Huang G.J., Chan Y.Y., Huang S.C., Wu S.J., Morris-Natschke S.L., Lee K.H. and Wu T.S., Synthesis and Biological Evaluation of Chalcone, Dihydrochalcone, and 1,3-diarylpropane Analogs as Anti-inflammatory Agents, Bioorg. Med. Chem. Lett., 27(7) (2017) 1547-1550.
  • [5] Sharma C.S., Shekhawat K.S., Chauhan C.S., Kumar N., Synthesis and Anticonvulsant Activity of Some Chalcone Derivatives, J. Chem. Pharm. Res., 5(10) (2013) 450-454.
  • [6] Parikh K., Joshi D., Antibacterial and Antifungal Screening of Newly Synthesized Benzimidazole-Clubbed Chalcone Derivatives, Med. Chem. Res., 22(8) (2013) 3688-3697.
  • [7] Abbo H.S., Lai C.H., Titinchi S.J.J., Substituent and Solvent Effects on UV-visible Absorption Spectra of Chalcones Derivatives: Experimental and Computational Studies, Spectrochim. Acta A Mol. Biomol. Spectrosc., 303 (2023) 123180.
  • [8] Ma L., Yang Z., Li C., Zhu Z., Shen X.,Hu L., Design, Synthesis and SAR Study of Hydroxychalcone Inhibitors of Human β-secretase (BACE1), J. Enzyme Inhib. Med. Chem., 26(5) (2011) 643–648.
  • [9] Cyboran-Mikołajczyk S., Matczak K., Olchowik-Grabarek E., Sękowski S., Nowicka P., Krawczyk-Łebek A., Kostrzewa-Susłow E., The Influence of the Chlorine Atom on the Biological Activity of 2′-hydroxychalcone in Relation to the Lipid Phase of Biological Membranes - Anticancer and Antimicrobial Activity, Chem. Biol. Interact., 398 (2024) 111082.
  • [10] Patil P., Zangade S., Synthesis and Comparative Study of Cytotoxicity and Anticancer Activity of Chalconoid-Co(II) Metal Complexes with 2-hydroxychalcones Analogue Containing Naphthalene Moiety, J. Indian Chem. Soc., 99 (2022) 100274.
  • [11] Bronikowska J., Kłosek M., Janeczko T., Kostrzewa-Susłow E., Czuba Z.P., The Modulating Effect of Methoxy-Derivatives of 2’-hydroxychalcones on the Release of IL-8, MIF, VCAM-1 and ICAM-1 by Colon Cancer Cells, Biomed. Pharmacother., 145 (2022) 112428.
  • [12] Wilhelm A., Bonnet S.L., Twigge L., Rarova L., Stenclova T., Visser H.G., Schutte-Smith M., Synthesis, Characterization and Cytotoxic Evaluation of Chalcone Derivatives, J. Mol. Struct., 1251 (2022) 132001.
  • [13] Sahib M.A., Mahdi M.F., Molecular Docking, Synthesis, Characterization and Preliminary Evaluation of some New 3-Ethyl-1H-Indole Derivatives as Potential COX-2 Inhibitors, Adv. J. Chem. A, 8(5) (2025) 948-960.
  • [14] Sandeli A.E., Khiri-Meribout N., Benzerka S., Boulebd H., Gürbüz N., Özdemir N., Özdemir I., Synthesis, Structures, DFT Calculations, and Catalytic Application in the Direct Arylation of Five-Membered Heteroarenes with Aryl Bromides of Novel Palladium-N-Heterocyclic Carbene PEPPSI-Type Complexes, New J. Chem., 45 (2021) 17878-17892.
  • [15] Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E. et.al. (2016). Gaussian 16 Rev. B.01, Wallingford, CT.
  • [16] Lee C., Yang W. and Parr R.G., Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density, Phys. Rev. B., 37 (1988) 785–789.
  • [17] Becke A.D., A New Mixing of Hartree–Fock and Local Density‐Functional Theories, J. Chem. Phys., 98 (1993) 1372–1377.
  • [18] Becke A.D., Density‐Functional Thermochemistry. III. The Role of Exact Exchange, J. Chem. Phys., 98 (1993) 5648–5652.
  • [19] Dennington R., Keith T.A., Millam J.M., GaussView, Version 6 Semichem Inc., Shawnee Mission, KS 2016.
  • [20] O’Boyle N.M., Tenderholt A.L., Langer K.M.J., cclib: A Library for Package-Independent Computational Chemistry Algorithms, Comp. Chem., 29 (2008) 839.
  • [21] Tomasi J., Mennucci B., Cammi R., Quantum Mechanical Continuum Solvation Models, Chem. Rev., 105 (2005) 2999–3093.
  • [22] Casida M.E., Jamorski C., Casida K.C., Salahub D.R., Molecular Excitation Energies to High-Lying Bound States from Time-Dependent Density-Functional Response Theory: Characterization and Correction of the Time-Dependent Local Density Approximation Ionization Threshold, J. Chem. Phys., 108 (1998) 4439–4449.
  • [23] McQuarrie D.A., Statistical Thermodynamics, Harper & Row Publishers, New York, 1973.
  • [24] Herzberg G., Molecular Spectra and Molecular Structure III, 1. Edition, D. Van Nostrand Company, Inc., New York, 1964.
  • [25] Serdaroğlu G., Durmaz S., DFT and statistical mechanics entropy calculations of diatomic and polyatomic molecules, Indian J. Chem., 49 (2010) 861-866.
  • [26] Koopmans T., Über die zuordnung von wellenfunktionen und eigenwerten zu den einzelnen elektronen eines atoms, Physica 1–6 (1934) 104–113.
  • [27] Parr R.G., Electrophilicity Index, J. Am. Chem. Soc., 121 (1999) 1922-1924.
  • [28] Parr R.G., Pearson R.G., Absolute Hardness: Companion Parameter to Absolute Electronegativity, J. Am. Chem. Soc., 105 (1983) 7512-7516.
  • [29] Pearson R.G., Absolute Electronegativity and Hardness Correlated with Molecular Orbital Theory, Proc. Natl. Acad. Sci. U.S.A, 83 (1986) 8440-8441.
  • [30] Perdew J.P. and Levy M., Physical Content of the Exact Kohn-Sham Orbital Energies: Band Gaps and Derivative Discontinuities, Phys. Rev. Let., 51 (1983) 1884-1887.
  • [31] Perdew J.P., Parr R.G., Levy M. and Balduz J.L, Density-Functional Theory for Fractional Particle Number: Derivative Discontinuities of the Energy, Phys. Rev. Let., 49 (1982) 1691.
  • [32] Gazquez J.L., Cedillo A. and Vela A., Electrodonating and Electroaccepting Powers, J. Phys. Chem. A., 111(10) (2007) 1966-1970.
  • [33] Gomez B., Likhanova N.V., Domínguez-Aguilar M.A., Martínez-Palou R., Vela A. and Gazquez J.L., Quantum Chemical Study of the Inhibitive Properties of 2-Pyridyl-azoles, J. Phys. Chem. B., 110(18) (2006) 8928-8934.
  • [34] Weinhold F., Landis C.R., Glendening E.D., What Is NBO Analysis and How Is It Useful? Int. Rev. Phys. Chem., 35 (2016) 399-440.
  • [35] Reed A.E., Curtiss L.A. and Weinhold F., Intermolecular Interactions from a Natural Bond Orbital, Donor-Acceptor Viewpoint, Chem. Rev. 88(6) (1988) 899-926.
  • [36] Sahib M.A., Mahdi M.F., Identification of Indole Derivatives as Selective Cyclooxygenase-2 Inhibitors by Virtual Screening and Molecular Dynamic Simulation, Turkish Comp. Theo. Chem. (TC&TC), 9(2) (2025) 19-32.
  • [37] Qiu X.Y., Yang S.L., Liu W.S. and Zhu H.L., (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one, Acta Cryst. E62 (2006) 3324-3325.
  • [38] Paixão J.A., Beja A.M., Silva M.R., Alte da Veiga L., Serra A.C., 3-Hydroxybenzaldehyde, Acta Cryst. C56 (2000) 1348-1350. [39] Jasinski J.P., Butcher R.J., Narayana B., Swamy M.T., Yathirajan H.S., Redetermination of 4-hydroxybenzaldehyde, Acta Cryst. E64 (2008) o187.
  • [40] Shubhalaxmi, Hahne S., Zschille C., Jayarama A., Bhat K.S., Crystal Structure Studies and Thermal Characterization of Novel 4-hydroxychalcone Derivative, Chem. Sci. Trans., 2(3) (2013) 841-846.
  • [41] Prasad A.A., Muthu K., Meenatchi V., Rajasekar M., Agilandeshwari R., Meena K., Manonmoni J.V., Meenakshisundaram S.P., Spectrochim. Acta A Mol. Biomol. Spectrosc. 140 (2015) 311–327.
  • [42] Murray J.S., Sen K., Molecular Electrostatic Potentials: Concepts and Applications, first ed., Elsevier, (Amsterdam, 1996).
  • [43] Turowska-Tyrk I., Grzesniak K., Trzop E., Zych T., Monitoring Structural Transformations in Crystals. Part 4. Monitoring Structural Changes in Crystals of Pyridine Analogs of Chalcone During [2+2]-Photodimerization and Possibilities of the Reaction in Hydroxy Derivatives, J. Solid State Chem., 174 (2003) 459–465.
  • [44] Tomečková V., Guzy J., Kušnír J., Fodor K., Mareková M., Chavková Z., Perjési P., Comparison of the Effects of Selected Chalcones, Dihydrochalcones and Some Cyclic Flavonoids on Mitochondrial Outer Membrane Determined by Fluorescence Spectroscopy, J. Biochem. Biophys. Methods, 69 (2006) 143–150.
There are 43 citations in total.

Details

Primary Language English
Subjects Computational Chemistry
Journal Section Natural Sciences
Authors

Sümeyya Serin 0000-0002-4637-1734

Publication Date March 25, 2025
Submission Date September 12, 2024
Acceptance Date February 12, 2025
Published in Issue Year 2025Volume: 46 Issue: 1

Cite

APA Serin, S. (2025). Exploring the Impacts of Substitution Position on Structural, Electronic, and Energetic Characteristics of Selected Chalcone Derivatives by DFT Method: A Quantum Computational Research. Cumhuriyet Science Journal, 46(1), 79-90. https://doi.org/10.17776/csj.1548916
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