Solvent Effects on Structural and Electronic Properties of Lomustine Combined With DFT Method

Abdul Hakim Sh. Mohammed

Authors

Abdul Hakim Sh. Mohammed Department of Physics, College of Education, University of Kirkuk, Kirkuk, Iraq

Keywords:

lomustine, solvents, UV-Vis spectra, frontier HOMO-LUMO, DFT

Abstract

The objective of this work is to examine the solute-solvent interactions by using optimised conformations of lomustine in various solvents and UV-Vis spectra by DFT calculations. The adjusted geometry of lomustine in the gas phase and in chloroform, acetone, ethanol, and water was estimated. A theoretical investigation of the potential stable formation of lomustine was conducted in various solvents using DFT/B3LYP with the 6-311G+(d) basis set. The findings indicate that the structural bonds vary with the solvent's polarity and solvation energy. The effects of solvents on lomustine were investigated using the conductor-like polarisable continuum model (CPCM) technique. The electronic absorption spectra of the molecule was assessed using the time-dependent density functional theory (TD/DFT) approach at the same level of analysis. In this work, the energy gap (HOMO–LUMO) was determined by quantum chemical calculations. The Frontier Molecular Orbital (FMO) investigation examined the highest occupied molecular orbital (HOMO) values of the molecule in several solvents, yielding -7.2530 eV for chloroform, -7.2533 eV for acetone, -7.2533 eV for ethanol, and -7.2533 eV for water. Their lowest unoccupied molecular orbital (LUMO) values were -2.4947 eV, -2.4882 eV, -2.4877 eV, and -2.4866 eV, resulting in corresponding band gaps of 4.7583 eV, 4.7651 eV, 4.7656 eV, and 4.7667 eV. Notably, water solvent had the largest energy gap (4.7667 eV) among the solvents used, indicating elevated kinetic energy and substantial chemical reactivity.

References

[1] S. Agarwal, D. K. Jangir, P. Singh, and R. Mehrotra, "Spectroscopic analysis of the interaction of lomustine with calf thymus DNA," J. Photochem. Photobiol. B: Biol., vol. 130, pp. 281–286, Jan. 2014.

[2] A. Mehrotra, R. C. Nagarwal, and J. K. Pandit, "Lomustine loaded chitosan nanoparticles: characterization and in vitro cytotoxicity on human lung cancer cell line L132," Chem. Pharm. Bull., vol. 59, no. 3, pp. 315–320, 2011.

[3] H. P. Lipp and J. T. Hartmann, "Cytostatic and cytotoxic drugs," in Side Effects of Drugs Annual, vol. 30, Elsevier, 2008, pp. 520–532.

[4] R. B. Weiss and B. F. Issell, "The nitrosoureas: carmustine (BCNU) and lomustine (CCNU)," Cancer Treat. Rev., vol. 9, pp. 313–330, 1982.

[5] B. Lebeau, C. Chouaïd, M. Baud, M. J. Masanès, and M. Febvre, "Oral second-and third-line lomustine–etoposide–cyclophosphamide chemotherapy for small cell lung cancer," Lung Cancer, vol. 67, no. 2, pp. 188–193, Feb. 2010.

[6] S. Bibi et al., "Investigation of the adsorption properties of gemcitabine anticancer drug with metal-doped boron nitride fullerenes as a drug-delivery carrier: a DFT study," RSC Adv., vol. 12, no. 5, pp. 2873–2887, 2022.

[7] C. T. Gnewuch and G. Sosnovsky, "Critical appraisals of approaches for predictive designs in anticancer drugs," Cell. Mol. Life Sci., vol. 59, pp. 959–1023, Jun. 2002.

[8] S. M. Ridha, Z. T. Ghaleb, and A. M. Ghaleb, "The computational investigation of IR and UV-Vis spectra of 2-isopropyl-5-methyl-1,4-benzoquinone using DFT and HF methods," East Eur. J. Phys., vol. 2, no. 1, pp. 197–204, Mar. 2023.

[9] S. M. Ridha, Z. T. Ghaleb, and A. Ghaleb, "Theoretical investigation of the effects of solvents and para-substituents," Rev. Mex. Fis., vol. 71, no. 1 Jan-Feb, pp. 010401-1, Jan. 2025.

[10] C. Møller and M. S. Plesset, "Note on an approximation treatment for many-electron systems," Phys. Rev., vol. 46, p. 618, 1934.

[11] M. J. Frisch et al., Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford, CT, 2009.

[12] R. Ditchfield, W. J. Hehre, and J. A. Pople, "Self‐consistent molecular orbital methods. IX. Extended Gaussian‐type basis for molecular orbital studies of organic molecules," J. Chem. Phys., vol. 54, pp. 724–730, 1971.

[13] V. Barone and M. Cossi, "Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model," J. Phys. Chem. A, vol. 102, no. 11, pp. 1995–2001, Mar. 1998.

[14] P. Hohenberg and W. Kohn, "Inhomogeneous electron gas," Phys. Rev., vol. 136, pp. B864–B871, 1964.

[15] R. Bauernschmitt and R. Ahlrichs, "Treatment of electronic excitations within the adiabatic approximation of time-dependent density functional theory," Chem. Phys. Lett., vol. 256, pp. 454–464, 1996.

[16] C. J. Cramer and F. M. Bickelhaupt, "Essentials of computational chemistry," Angew. Chem. Int. Ed. Engl., vol. 42, no. 4, pp. 381–384, 2003.

[17] S. Jafari, M. Cheki, and H. N. Moghadam, "Lomustine and 6 MV X-ray combination effect on U87-MG cancer cells," Pharmacophore, vol. 8, no. 5, pp. 40–46, 2017.

[18] W. Bououden and Y. Benguerba, "Computational quantum chemical study, drug-likeness and in silico cytotoxicity evaluation of some steroidal anti-inflammatory drugs," J. Drug Deliv. Ther., vol. 10, no. 3-s, pp. 68–74, Jun. 2020.