A theoretical study of the separation of enantiomers of the drug modafinil by nanotubes: molecular docking simulations and density functional theory

Document Type : Review Paper

Authors

1 Faculty of Chemistry, Shahrood University of Technology, Shahrood, IRAN

2 Shahrood university of technology, Shahrood, Iran

Abstract

The separation of drug enantiomers is crucial in the pharmaceutical industry, as each enantiomer can exhibit different biological activities. Modafinil is a racemic drug, with the R enantiomer being primarily responsible for its pharmacological effects. The main objective of this study was to identify a suitable carbon nanotube (CNT) structure to effectively separate the enantiomers of Modafinil.
Molecular docking simulations were performed to investigate the binding of Modafinil enantiomers with various chiral CNTs (7,6), (8,7), (9,8), and (10,9) with lengths ranging from 11 to 15 Angstroms. Molecular docking simulations showed that the CNT (8,7) with a length of 15 Angstroms could effectively separate the S and R enantiomers of Modafinil. The R enantiomer was adsorbed on the surface of the CNT, with a binding energy of -3.49 kcal/mol, while the S enantiomer was located inside the nanotube, with a binding energy of -4.34 kcal/mol.
Density functional theory (DFT) calculations at the B3LYP/6-31G level were then employed to optimize the structures and investigate the interactions of the drug enantiomers with the selected CNT. Density functional theory (DFT) calculations revealed that the R enantiomer had a higher binding energy compared to the S enantiomer, indicating better stability upon adsorption on the CNT surface. Further analysis of electronic properties, including frontier orbital energies, reactivity descriptors, Mulliken atomic charges, dipole moments, and molecular electrostatic potentials, provided insights into the differences in the behavior and interactions of the two Modafinil enantiomers with the CNT.

Keywords

References

[1] Xie Z, Gao L, Li C, et al. Chiral separation of racemic drugs using functionalized carbon nanotubes. Nanoscale. 2020;12(21):11585-11593.

[2] Tanaka M, Watanabe K, Tsukahara T. Enantioselective adsorption of ibuprofen on chiral carbon nanotubes. ACS Appl Nano Mater. 2021;4(3):2644-2651.

[3] Bayat P, Shukla R, Barrow CJ, Loon A, Dunstan DE. Chiral carbon nanotubes for enantioselective separations and sensing. Small. 2020;16(22):1907359.

[4] Zhang X, Zhang Y, Ren X, et al. Chiral carbon nanotubes for enantioselective adsorption and separation of pharmaceutical drugs. ACS Appl Mater Interfaces. 2022;14(33):37762-37771.

[5] Qi Z, Xu J, Liu C, Hou J, Liu Y. Functionalized carbon nanotubes for chiral recognition and enantioseparation. New J Chem. 2020;44(23):9920-9937.

[6] Wang Y, Li Y, Wang Z, Tang Z. Chiral carbon nanotubes: synthesis, properties and applications. Nanoscale. 2022;14(3):790-810.

[7] Silvestri IP, Colbon PJ. The growing importance of chirality in 3D chemical space exploration and modern drug discovery approaches for Hit-ID: Topical Innovations. ACS Med Chem Lett. 2021;12(8):1220-1229.

[8] Banik SD, Nandi N. Chirality and protein biosynthesis. In: Queisser G, ed. Biochirality: Origins, Evolution and Molecular Recognition. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013:255-305.

[9] Nguyen LA, He H, Pham-Huy C. Chiral drugs: an overview. Int J Biomed Sci. 2006;2(2):85.

[10]Inaki M, Liu J, Matsuno K. Cell chirality: its origin and roles in left–right asymmetric development. Philos Trans R Soc B Biol Sci. 2016;371(1710):20150403.

[11]Williams K, Lee E. Importance of drug enantiomers in clinical pharmacology. Drugs. 1985;30(4):333-354.

[12]McConathy J, Owens MJ. Stereochemistry in drug action. Prim Care Companion J Clin Psychiatry. 2003;5(2):70.

[13]Kim D. Practical use and risk of modafinil, a novel waking drug. Environ Health Toxicol. 2012;27:e2012007.

[14]Murillo-Rodríguez E, Barciela Veras A, Barbosa Rocha N, Budde H, Machado S. An overview of the clinical uses, pharmacology, and safety of modafinil. ACS Chem Neurosci. 2018;9(2):151-158.

[15]Ikai T, Okamoto Y. Structure control of polysaccharide derivatives for efficient separation of enantiomers by chromatography. Chem Rev. 2009;109(11):6077-6101.

[16]Bereznitski Y, Thompson R, O'Neill E, Grinberg N. Thin-layer chromatography—a useful technique for the separation of enantiomers. J AOAC Int. 2001;84(4):1242-1251.

[17]Kim D. Practical use and risk of modafinil, a novel waking drug. Environ Health Toxicol. 2012;27:e2012007.

[18]Murillo-Rodríguez E, Barciela Veras A, Barbosa Rocha N, Budde H, Machado S. An overview of the clinical uses, pharmacology, and safety of modafinil. ACS Chem Neurosci. 2018;9(2):151-158.

[19]Darwish M, Kirby M, Hellriegel ET, Robertson P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29:613-623.

[20]Power TD, Skoulidas AI, Sholl DS. Can chiral single walled carbon nanotubes be used as enantiospecific adsorbents. J Am Chem Soc. 2002;124(9):1858-1859.

[21]Mark A. Argus Lab 4.0.1. Seattle, WA: Thompson, Planaria Software LLC; 2002.

[22]Melchor S, Dobado JA. An algorithm for connecting two arbitrary carbon nanotubes. J Chem Inf Comput Sci. 2004;44(5):1639-1646.

[23]Johnson JE, Speir JA. Quasi-equivalent viruses: a paradigm for protein assemblies. J Mol Biol. 1997;269(5):665-675.

[24]Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys. 1993;98(7):5648-5652.

[25]Frisch MJ, Trucks GW, Schlegel HB, et al. GAUSSIAN 03, Revision C.02. Wallingford, CT: Gaussian, Inc.; 2004.

[26]Pearson RG. Chemical hardness and the electronic chemical potential. Inorg Chim Acta. 1992;198-200:781-786.

[27]Demircioğlu Z, Kaştaş ÇA, Büyükgüngör O. Theoretical analysis (NBO, NPA, Mulliken Population Method) and molecular orbital studies (hardness, chemical potential, electrophilicity and Fukui function analysis) of (E)-2-((4-hydroxy-2- methylphenylimino)methyl)-3-methoxyphenol. J Mol Struct. 2015;1091:183-195.

[28]Kumar SA, Bhaskar BL. Preliminary investigation of drug impurities associated with the anti-influenza drug Favipiravir–An in silico approach. Comput Theor Chem. 2021;1204:113375.

[29]Saikia N, Deka RC. A comparison of the effect of nanotube chirality and electronic properties on the π–π interaction of single‐wall carbon nanotubes with pyrazinamide antitubercular drug. Int J Quantum Chem. 2013;113(9):1272-1284.

[30]Pandey AK, Dwivedi A, Mishra AK, Tiwari SN, Vuai SA, Singh V. Quantum chemical study of effect on adsorption properties of antituberculosis drug NCyclopentylidenepyridine-4-carbohydrazide interaction with CNT (C56H16). J Indian Chem Soc. 2023;100(1):100851.

[31]Ravikumar N, Rajendran A, Sivalingam A. Computational study on the adsorption mechanism of telmisartan drug on pristine and functionalized single-walled carbon nanotube as a drug delivery system. Struct Chem. 2022;33(1):293-303.

[32]Xu H, Li L, Fan G, Chu X. DFT study of nanotubes as the drug delivery vehicles of Efavirenz. Comput Theor Chem. 2018;1131:57-68.

[33]Choudhary V, Bhatt A, Dash D, Sharma N. DFT calculations on molecular structures, HOMO–LUMO study, reactivity descriptors and spectral analyses of newly synthesized diorganotin (IV) 2‐chloridophenylacetohydroxamate complexes. J Comput Chem. 2019;40(27):2354-2363.

[34]Karthick V, Kumari KV. Computational study on the adsorption behavior of atazanavir drug on pristine and functionalized single-walled carbon nanotubes as a drug delivery system. Struct Chem. 2022;33(2):1019-1030.

[35]Mathew B, Suresh J, Mathew GE. Novel benzothiazole derivatives as antioxidants and cholinesterase inhibitors: A computational study. J Mol Struct. 2020;1209:127891.
Challenges in Nano and Micro Scale Science and Technology
Volume 12, Issue 1
March 2024
Pages 27-39

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