Theoretical Study of the Encapsulation of the Anticancer Drug of Letrozole: DFT/TD-DFT and Spectroscopic Studies

Document Type : Original Research Articles

Authors
Nasrin Masnabadi 1
Shiva Masoudi 2
Sjad Rahbari 2
1 1 Department of Chemistry, Ro. C., Islamic Azad University, Roudehen, Islamic Republic of Iran
2 2 Department of Chemistry, CT. C., Islamic Azad University, Tehran, Islamic Republic of Iran
10.22059/jsciences.2026.401653.1007951
Abstract
The DFT description and comparison of the loading of Letrozole (LTZ) on boron nitride (AlNNT) and aluminum nitride (BNNT) nanotubes were studied herein. The results of the thermochemical parameters indicate that LTZ with AlNNT nanotube would be a more spontaneous and exothermic process in comparison with that of BNNT. The study included electron delocalization effects, stereoelectronic interaction, steric repulsion effects, electronic properties, and reactivity of LTZ on the AlNNT nanotube using DFT B3LYP/6-31G* level of theory. The UV-Vis absorption analysis and the IR spectrum were used to ascertain the changes that take place on adsorption of LTZ onto AlNNT. The molecular orbital distribution was further assessed to monitor electronic structure changes, adsorption energies (Ead), and electrical conductivity during the adsorption process on both substrates. The NBO analysis of the LTZ-AlNNT complex shows that the highest resonance energy is provided due to the instability of electrons of LP (1)N73→ BD*(2)N75-C85 (51.96 kcal.mol-1), which in turn signifies that there is electron transfer from the LTZ drug in the LTZ-AlNNT complex. This in the UV-Vis spectrum corroborated by the drug adsorption-related wavelength change from 226.7 nm to 254.3 nm on the AlNNT demonstrates bathochromic shift.We hope that this study can aid in modeling and designing a suitable adsorbent for drug delivery based on its findings. Thus, electronic, thermochemical, and structural properties of LTZ drug complexes with the nanotubes AlNNT and BNNT were elucidated with a combination of DFT calculations and graphical analysis of the non-covalent interactions index (NCI) analysis.
Keywords
Adsorption energy
Aluminum nitride nanocarrier
Density functional theory (DFT)
Letrozole
Interaction
Subjects
1.  Ziani K, Fang Y, McClements DJ. Encapsulation of functional lipophilic components in surfactant-based colloidal delivery systems: Vitamin E, vitamin D, and lemon oil. Food chemistry. 2012 Sep 15;134(2):1106-12.
2.  Elhissi A, Ahmed W, Dhanak V, Subramani K. Carbon nanotubes in cancer therapy and drug delivery. InEmerging nanotechnologies in dentistry 2012 Jan 1 (pp. 347-363). William Andrew Publishing.
3.  Vashist SK, Zheng D, Pastorin G, Al-Rubeaan K, Luong JH, Sheu FS. Delivery of drugs and biomolecules using carbon nanotubes. Carbon. 2011 Nov 1;49(13):4077-97.
4.  Mendes RG, Bachmatiuk A, Büchner B, Cuniberti G, Rümmeli MH. Carbon nanostructures as multi-functional drug delivery platforms. Journal of Materials Chemistry B. 2013;1(4):401-28.
5.  Mendes RG, Bachmatiuk A, Büchner B, Cuniberti G, Rümmeli MH. Carbon nanostructures as multi-functional drug delivery platforms. Journal of Materials Chemistry B. 2013;1(4):401-28.
6.  Lin Y, Bunker CE, Fernando KS, Connell JW. Aqueously dispersed silver nanoparticle-decorated boron nitride nanosheets for reusable, thermal oxidation-resistant surface enhanced Raman spectroscopy (SERS) devices. ACS applied materials & interfaces. 2012 Feb 22;4(2):1110-7.
7.  Griebel M, Hamaekers J. Molecular dynamics simulations of boron-nitride nanotubes embedded in amorphous Si-BN. Computational materials science. 2007 May 1;39(3):502-17.
8.  Hughes GA. Nanostructure-mediated drug delivery. Nanomedicine: nanotechnology, biology and medicine. 2005 Mar 1;1(1):22-30.
9.  Yang L, Sheldon BW, Webster TJ. Nanophase ceramics for improved drug delivery. Am Ceram Soc Bull. 2010;89(2):24-32.
10. El Khalifi M, Duverger E, Gharbi T, Boulahdour H, Picaud F. Theoretical demonstration of the potentiality of boron nitride nanotubes to encapsulate anticancer molecule. Physical Chemistry Chemical Physics. 2015;17(44):30057-64.
11. Shakerzadeh E, Noorizadeh S. A first principles study of pristine and Al-doped boron nitride nanotubes interacting with platinum-based anticancer drugs. Physica E: Low-dimensional Systems and Nanostructures. 2014 Mar 1; 57:47-55.
12. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr JA, Vreven T, Kudin KN, Burant JC, Millam JM. Gaussian 03, Revision D. 01, 2004, Gaussian, Inc. Wallingford, CT.
13. Lewars E. Introduction to the theory and applications of molecular and quantum mechanics. J. Computational chemistry, Ontario Canada. 2003.
14. Jalali Sarvestani MR, Ahmadi R. Evaluating the Performance of 2, 3-dihydro-1H-phenothiazine-4 (5aH)-one as an Ionophore in Construction of a Cation Selective Electrode by Density Functional Theory. International Journal of New Chemistry. 2018 Jan 1;5(1):1-0.
15. Jalali Sarvestani MR, Ahmadi R. Investigating the Complexation of a recently synthesized phenothiazine with Different Metals by Density Functional Theory. International Journal of New Chemistry. 2017 Dec 1;4(4):101-10.
16. Masnabadi N. DFT Study and NBO analysis of conformation properties of 2, 5, 5-Trimethyl-1, 3, 2-Dioxaphosphinane 2-selenide and their dithia and diselena analogous. Journal of Sciences, Islamic Republic of Iran. 2020 Apr 1;31(2):137-46.
17. Danaie E, Masoudi S, Masnabadi N. A Computational Study of the Conformational Behavior of 2, 5-Dimethyl-1, 4-dithiane-2, 5-diol and Analogous S and Se: DFT and NBO Study. Letters in Organic Chemistry. 2020 Oct 1;17(10):749-59.
18. Masnabadi N. The study of Letrozole adsorption upon CCT nanotube: A DFT/TD-DFT and spectroscopic (excited states and UV/Vis). Main Group Chemistry. 2022 Dec 20;21(4): 1013-27.doi:10.3233/MGC-210098
19. Hosseinzadeh M, Masoudi S, Masnabadi N, Azarakhshi F. Adsorption of Diethylstilbestrol Drug into BNNT: DFT/TD-DFT and Spectroscopic (Excited States, UV/Vis and NMR) Studies. Letters in Organic Chemistry. 2023 Apr 1;20(4):347-61.
20. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Landis CR, Weinhold F. NBO 6.0. Theoretical Chemistry Institute, University of Wisconsin, Madison. 2013.
21. Politzer P, Seminario JM, editors. Modern density functional theory: a tool for chemistry. Elsevier; 1995 Jan 27.
22. Masnabadi N. DFT and NBO analysis on conformers of dioxaphosphinane derivatives. Int. J. Bio-Inorg. Hybr. Nanomater. 2022;11(3):127-35.
23. Masnabadi N. Conformational Stability, FMO, NMR, MEP and NBO Analysis of 2, 5-Dimethyl-2, 5-bis (methylthio)-1, 4-dithiane and Dimethoxy compounds by DFT Approach. Letters in Organic Chemistry. 2021 Aug 1;18(8):656-68.
24. Masnabadi N, Thalji MR, Alhasan HS, Mahmoodi Z, Soldatov AV, Ali GA. Structural, electronic, reactivity, and conformational features of 2, 5, 5-trimethyl-1, 3, 2-diheterophosphinane-2-sulfide, and its derivatives: DFT, MEP, and NBO calculations. Molecules. 2022 Jun 22;27(13):4011.
25. Mikołajczyk M, Ziemnicka B, Krzywański J, Cypryk M, Gostyński B. Nucleophilic substitution at tetracoordinate phosphorus. stereochemical course and mechanisms of nucleophilic displacement reactions at phosphorus in diastereomeric cis-and trans-2-halogeno-4-methyl-1, 3, 2-dioxaphosphorinan -2-thiones: Experimental and DFT studies. Molecules. 2021 Jun 15;26(12):3655.
26. Doust Mohammadi M, Abdullah HY. The adsorption of chlorofluoromethane on pristine, Al‐, Ga‐, P‐, and As‐doped boron nitride nanotubes: a PBC‐DFT, NBO, and QTAIM study. ChemistrySelect. 2020 Oct 22;5(39):12115-24.
27. Sakr MA, Sherbiny FF, El-Etrawy AA. Hydrazone-based materials; DFT, TD-DFT, NBO analysis, fukui function, MESP analysis, and solar cell applications. Journal of Fluorescence. 2022 Sep;32(5):1857-71.
28. Sindhuja S, Karnan M, Gayathri R, Kavimani M. Non-covalent interaction, topology, molecular properties, spectral and quantum chemical analysis of 2, 5-dinitrophenol. Journal of the Indian Chemical Society. 2024 Oct 1;101(10):101276.
29. Liu XM, Zhao DX, Yang ZZ. Transition from Noncovalent Interaction to Covalent Bond Based on One-Electron Potential, Quantum Chemical Topology, and Molecular Face Theory. The Journal of Physical Chemistry A. 2025 Jun 30.
30. Goswami S, Ganguly A. Analysis of Non‐Covalent Interactions Present within a Series of Nucleobase Dimers from the Perspective of Quantum Topology and Aromaticity. Advanced Theory and Simulations. 2025 Apr 22:2500121.
31. Tretiakov S, Nigam A, Pollice R. Studying Noncovalent Interactions in Molecular Systems with Machine Learning. Chemical reviews. 2025 Jun 9.
32. Sharma SK, Chiang LY, Hamblin MR. Photodynamic therapy with fullerenes in vivo: reality or a dream? Nanomedicine. 2011 Dec 1;6(10):1813-25. https://doi.org/10.2217/nnm.11.144
33. Faver JC, Zheng Z, Merz KM. Model for the fast estimation of basis set superposition error in biomolecular systems. The Journal of chemical physics. 2011 Oct 14;135(14). https://doi.org/10.1063/1.3641894
 
34. Sahayarayan JJ, Rajan KS, Vidhyavathi R, Nachiappan M, Prabhu D, Alfarraj S, Arokiyaraj S, Daniel AN. In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches. Saudi Journal of Biological Sciences. 2021 Jan 1;28(1):400-7.
35. Luo J, Zhang R, Wang X, Hou Z, Guo S, Jiang B. Binding properties of marine bromophenols with human protein tyrosine phosphatase 1B: Molecular docking, surface plasmon resonance and cellular insulin resistance study. International Journal of Biological Macromolecules. 2020 Nov 15; 163:200-8.
36. Paneru TR, Chaudhary MK, Tandon P, Chaudhary T, Joshi BD. Theoretical study on molecular stability, reactivity, and drug potential of cirsilineol from DFT and molecular docking methods. Chemical Physics Impact. 2024 Jun 1; 8:100641.
37. Adindu EA, Godfrey OC, Agwupuye EI, Ekpong BO, Agurokpon DC, Ogbodo SE, Benjamin I, Louis H. Structural analysis, reactivity descriptors (HOMO-LUMO, ELF, NBO), effect of polar (DMSO, EtOH, H2O) solvation, and libido-enhancing potential of resveratrol by molecular docking. Chemical Physics Impact. 2023 Dec 1; 7:100296.
38. Zhang S, Zhao D, Cui Q. Gap-Δenergy, a New Metric of the Bond Energy State, Assisting to Predict Molecular Toxicity. ACS omega. 2024 Apr 12;9(16):17839-47.
39. Sarala S, Geetha SK, Muthu S, Irfan A. Computational investigation, comparative approaches, molecular structural, vibrational spectral, non-covalent interaction (NCI), and electron excitations analysis of benzodiazepine derivatives. Journal of Molecular Modeling. 2021 Sep;27(9):266.
40. Kříž K, Řezáč J. Non-covalent interactions atlas benchmark data sets 4: σ-hole interactions. Physical Chemistry Chemical Physics. 2022;24(24):14794-804.
41. Sunny SA, Thomas R. Exploring non-covalent interactions: A computational study of Methyl acetate in chloroform and Hexafluoroisopropanol. Chemical Physics Impact. 2024 Jun 1; 8:100514.
42. Kumar AR, Ilavarasan L, Mol GS, Selvaraj S, Azam M, Jayaprakash P, Kesavan M, Alam M, Dhanalakshmi J, Al-Resayes SI, Ravi A. Spectroscopic (FT-IR, FT-Raman, UV–Vis and NMR) and computational (DFT, MESP, NBO, NCI, LOL, ELF, RDG and QTAIM) profiling of 5 chloro-2 hydroxy-3-methoxybenzaldehyde: a promising antitumor agent. Journal of Molecular Structure. 2024 Feb 15; 1298:136974.
43. Neetha S, Santhosh C, Sheela K, Ravi Singh K, Sridhar M, Sadashiva M. A comprehensive analysis of the molecular packing in the crystal of (4-methoxyphenyl) methyl 4-(4-chlorophenyl)-1, 3-thiazole-2-carboxylate: insights of X-ray crystallography and DFT analysis. Journal of Molecular Structure. 2025 Jan 5; 1319:139584.
44. Jia Z, Pang H, Li H, Wang X. A density functional theory study on complexation processes and intermolecular interactions of triptycene-derived oxacalixarenes. Theoretical Chemistry Accounts. 2019 Sep;138(9):113.
45. Glendening ED, Landis CR, Weinhold F. NBO 7.0: New vistas in localized and delocalized chemical bonding theory. Journal of computational chemistry. 2019 Sep 30;40(25):2234-41.
 
Journal of Sciences, Islamic Republic of Iran
Volume 36, Issue 2
Spring 2025
Pages 127-142