Quantum Chemical Investigation of Structural, Spectroscopic, Electronic and Nonlinear Optical Properties of Gefitinib Using DFT

Document Type : Original Article

Authors

1 Department of Physics,University of Lucknow, Lucknow-226007, India

2 Department of Physics,Siddharth University, Siddharthnagar, Uttar Pradesh, India

3 Department of Chemistry,M. L. K. (PG) College, Balrampur, Uttar Pradesh, India

10.22075/ppam.2026.40899.1215

Abstract

Gefitinib, a well-known epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer, was investigated in this study using density   functional theory (DFT). The molecular structure was optimized at the B3LYP/6-311G(d,p) level of theory, and the absence of imaginary frequencies confirmed the stability of the optimized structure. Vibrational analysis provided detailed insight into the characteristic functional groups of the molecule. The electronic properties were analyzed using frontier molecular orbital analysis. The HOMO and LUMO energies were calculated to be −6.0734 eV and −1.8243 eV, respectively, with an energy gap of 4.2491 eV, indicating the good kinetic stability of the molecule. TD-DFT studies demonstrated a main absorption band at approximately 325 nm, which was mainly attributed to π → π* electronic transitions in the conjugated quinazoline framework. Solvent-phase analysis using the PCM model revealed a slight red shift in the absorption wavelength, confirming the effect of solvation on the electronic excitation characteristics of gefitinib. The calculated nonlinear optical parameters showed significant polarizability and first hyperpolarizability values, which can be attributed to effective intramolecular charge transfer and extended π-conjugation.

Keywords

Main Subjects

© 2026 The Author(s). Progress in Physics of Applied Materials published by Semnan University Press. This is an open access article under the CC-BY 4.0 license. (https://creativecommons.org/licenses/by/4.0/)

References

[1] Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T., ... & Rosell, R. 2015. Non-small-cell lung cancer. Nature reviews Disease primers, 1(1), p.15009.
[2] Hendriks, L. E., Remon, J., Faivre-Finn, C., Garassino, M. C., Heymach, J. V., Kerr, K. M., ... & Reck, M. 2024. Non-small-cell lung cancer. Nature Reviews Disease Primers, 10(1), p.71.
[3] Ke, X., & Shen, L. 2017. Molecular targeted therapy of cancer: The progress and future prospect. Frontiers in Laboratory Medicine, 1(2), pp.69-75.
[4] Kris, M. G., Natale, R. B., Herbst, R. S., Lynch Jr, T. J., Prager, D., Belani, C. P., ... & Kay, A. C. 2003. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non–small cell lung cancer: a randomized trial. Jama, 290(16), pp.2149-2158.
[5] Penne, K., Bohlin, C., Schneider, S., & Allen, D. 2005. Gefitinib (IressaTM, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy. Cancer nursing, 28(6), pp.481-486.
[6] Srivastava, A. K., & Misra, N. 2021. DFT based studies on bioactive molecules. Bentham Science Publishers.
[7] Frisch, A. 2009. Gaussian 09W Reference. Wallingford, USA, 25p 470(4).
[8] Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., ... & Nakatsuji, H. 2009. Uranyl extraction by N, N-dialkylamide ligands studied by static and dynamic DFT simulations. Gaussian, 9(9), p.227.‏
[9] Becke, A. D. 1993. Density‐functional thermochemistry. III. The role of exact exchange. The Journal of chemical physics, 98(7), pp.5648-5652.
[10] Lee, C., Yang, W., & Parr, R. G. 1988. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical review B, 37(2), p.785.
[11] Almlof, J., Helgaker, T., & Taylor, P. R. 1988. Gaussian basis sets for high-quality ab initio calculations. The Journal of Physical Chemistry, 92(11), pp.3029-3033.
[12] Porezag, D., & Pederson, M. R. 1999. Optimization of Gaussian basis sets for density-functional calculations. Physical Review A, 60(4), p.2840.
[13] Tikaram, Kumar, R., Kumar, Y. and Kumar, N. 2026. Physical, Electro-Optical, and Spectroscopic Properties of I52 liquid crystal: A Computational Study. Progress in Physics of Applied Materials, 6(4), pp.315-330.
[14] Sucheta, M., Pramod, A. G., Zikriya, M., Salma, K. M., Venugopal, N., Chaithra, R., ... & Murthy, S. 2022. Frontier molecular orbital, molecular structure and Thermal properties of 2, 4, 6, 8-tetramethyl-2, 3, 6, 7-tetrahydro-s-indacene-1, 5-dione using DFT calculation. Materials Today: Proceedings, 62, pp.5241-5244.
[15] Bayrakdar, A., Kart, H. H., Elçin, S., Ashfaq, M., Mali, S. N., Yasin, H. K. A., & Smerat, A. 2025. Concise experimental and DFT study of newly synthesized 5, 17-di (2-antracenylazo)-25, 27-[1, 3-ethylene-bis (aminocarbonylmethoxy)]-26, 28-dihydroxycalix [4] arene. Chemical Physics Impact, 11, p.100965.
[16] Priya, M. K., Revathi, B. K., Renuka, V., Sathya, S., & Asirvatham, P. S. 2019. Molecular structure, spectroscopic (FT-IR, FT-Raman, 13C and 1H NMR) analysis, HOMO-LUMO energies, Mulliken, MEP and thermal properties of new chalcone derivative by DFT calculation. Materials Today: Proceedings, 8, pp.37-46.
[17] Ramirez-Balderrama, K., Orrantia-Borunda, E., & Flores-Holguin, N. 2017. Calculation of global and local reactivity descriptors of carbodiimides, a DFT study. Journal of Theoretical and Computational Chemistry, 16(03), p.1750019.
[18] Chattaraj, P. K., Nath, S., & Maiti, B. 2003. Reactivity descriptors. Computational medicinal chemistry for drug discovery, 11, p.295.
[19] Liyanage, P. S., de Silva, R. M., & de Silva, K. N. 2003. Nonlinear optical (NLO) properties of novel organometallic complexes: high accuracy density functional theory (DFT) calculations. Journal of Molecular Structure: THEOCHEM, 639(1-3), pp.195-201.
[20] Sarala, S., Geetha, S. K., Muthu, S., & Irfan, A. 2021. Computational investigation, comparative approaches, molecular structural, vibrational spectral, non-covalent interaction (NCI), and electron excitations analysis of benzodiazepine derivatives. Journal of Molecular Modeling, 27(9), p.266.
[21] Marković, J. M. D., Marković, Z. S., Krstić, J. B., Milenković, D., Lučić, B., & Amić, D. 2013. Interpretation of the IR and Raman spectra of morin by density functional theory and comparative analysis. Vibrational spectroscopy, 64, pp.1-9.
[22] Gautam, V., Mishra, M., Thapa, K. B., Kumar, J., Singh, D., & Kumar, D. 2023. Electronic, optical and spectroscopic properties of N-dialkyl-imidazolium hexafluorophosphate (CN MIM. PF6) ionic liquid crystal molecules investigated by computational methods. Journal of Molecular Modeling, 29(9), p.274.
[23] Rahman, A. M., Korashy, H. M., & Kassem, M. G. 2014. Gefitinib. Profiles of drug substances, excipients and related methodology, 39, pp.239-264.‏
[24] Ganiev, B., Mardonov, U., & Kholikova, G. 2023. Molecular structure, HOMO-LUMO, MEP-Analysis of triazine compounds using DFT (B3LYP) calculations. Materials Today: Proceedings.
[25] Toriyama, M. Y., Ganose, A. M., Dylla, M., Anand, S., Park, J., Brod, M. K., ... & Snyder, G. J. 2022. How to analyse a density of states. Materials today electronics, 1, p.100002.
[26] Hussein, H. A. 2023. A DFT study of structural-stability, Mulliken charges, MEP, FMO, and NLO properties of trans alkenyl substituted chalcones conformers: theoretical study. Structural Chemistry, 34(6), pp.2201-2223.
[27] Rawat, P., Singh, R. N., Ranjan, A., Ahmad, S., & Saxena, R. 2017. Antimycobacterial, antimicrobial activity, experimental (FT-IR, FT-Raman, NMR, UV-Vis, DSC) and DFT (transition state, chemical reactivity, NBO, NLO) studies on pyrrole-isonicotinyl hydrazone. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 179, pp.1-10.
[28] Kurtz, L. A., Smith, R. E., Parks, C. L., & Boney, L. R. 1978. A comparison of the method of lines to finite difference techniques in solving time-dependent partial differential equations. Computers & Fluids, 6(2), pp.49-70.
[29] Buckingham, A. D., & Orr, B. J. 1967. Molecular hyperpolarisabilities. Quarterly Reviews, Chemical Society, 21(2), pp.195-212.
[30] Mveme, C. D. D., Nya, F. T., Ejuh, G. W., Kamsi, R. A. Y., & Ndjaka, J. M. B. 2020. Density functional theory study of optoelectronic, nonlinear optical, piezoelectric and thermodynamic properties of poly (3, 4-ethylenedioxythiophene), poly (3, 4-ethylenedioxyselenophene) and their derivatives. Optical and Quantum Electronics, 52, pp.1-16.
[31] Kamsi, R. A. Y., Ejuh, G. W., Mkounga, P., & Ndjaka, J. M. B. 2020. Study of the molecular structure, electronic and chemical properties of Rubescin D molecule. Chinese Journal of Physics, 63, pp.104-112.
[32] Yossa Kamsi, R. A., Ejuh, G. W., Tchoffo, F., Mkounga, P., & Ndjaka, J. M. B. 2019. Electronic Structure, Spectroscopic (IR, Raman, UV‐Vis, NMR), Optoelectronic, and NLO Properties Investigations of Rubescin E (C31H36O7) Molecule in Gas Phase and Chloroform Solution Using Ab Initio and DFT Methods. Advances in Condensed Matter Physics, 2019(1), p.4246810.
[33] Midoune, A., & Messaoudi, A. 2020. DFT/TD-DFT computational study of the tetrathiafulvalene-1, 3-benzothiazole molecule to highlight its structural, electronic, vibrational and non-linear optical properties. Comptes Rendus. Chimie, 23(2), pp.143-158.
[34] Kurtz, H. A., Stewart, J. J. P., & Dieter, K. M. 1990. Calculation of the nonlinear optical properties of molecules. Journal of Computational Chemistry, 11(1), pp.82–87.
[35] Johnson, E. R., Keinan, S., Mori-Sánchez, P., Contreras-García, J., Cohen, A. J., & Yang, W. 2010. Revealing noncovalent interactions. Journal of the American Chemical Society, 132(18), pp.6498-6506.
[36] Contreras-García, J., Johnson, E. R., Keinan, S., Chaudret, R., Piquemal, J. P., Beratan, D. N., & Yang, W. 2011. NCIPLOT: a program for plotting noncovalent interaction regions. Journal of chemical theory and computation, 7(3), pp.625-632.
[37] Tretiakov, S., Nigam, A., & Pollice, R. 2025. Studying noncovalent interactions in molecular systems with machine learning. Chemical reviews, 125(12), pp.5776-5829.
[38] Vengatesh, G., Vinushya, N., Jeyaprakash, G. M., Mohini, A., Mondal, P., Reddy, R., & Shriram, Z. O. 2025. Crystal structures, NCI-RDG, Hirshfeld surface and energy framework analysis of tetra aryl substitute bispidine and oxaquinuclidine core containing derivatives: A potential COVID-19 drug candidate. Journal of Molecular Structure, 1321, p.140202.

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History

  • Receive Date: 15 April 2026
  • Revise Date: 22 May 2026
  • Accept Date: 05 June 2026

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