A DFT Study of Cenobamate and Its New Isomers as an Effective Medical Treatment for Epilepsy Medications
DOI:
https://doi.org/10.15407/ujpe69.5.314Keywords:
DFT, B3LYP, cenobamate, isomers, activityAbstract
Many anti-epileptic drugs use cenobamate, a voltage-gated sodium channel blocker, to the fullest extent. This study investigates the electronic, quantum chemical, and photolytic properties of Cenobamate and its novel designed isomers. The results show that the LUMOs levels are higher than the HOMO energies. The HOMO levels are unpaired and of s-character locally around the chlorine atoms. The reactivity and stability are explained by the frontier molecular energy values and different biochemical descriptors. All isomers have smallest energy gap means with a higher reactivity for biological applications. The most frequent reaction sites are found to be the three acyl carbons in the cenobamate molecule, the chloride related to the phenyl ring, the heterocyclic ring, and the carbonyl oxygen and nitrogen in the ester amide group. The novel isomers have high ability to interact with species, and this takes place either in clinical use or under clinical trials. The isomers are soft compounds, and can easily interact with big soft molecules such as DNA.
References
R. Roberti, C. De Caro, L.F. Iannone et al. Pharmacology of cenobamate: Mechanism of action, pharmacokinetics, drug-drug interactions and tolerability. CNS Drugs 35, 609 (2021).
https://doi.org/10.1007/s40263-021-00819-8
N. Das, M. Dhanawat, S.K. Shrivastava. An overview on antiepileptic drugs. Drug Discov Ther. 6, 178-93 (2012).
https://doi.org/10.5582/ddt.2012.v6.4.178
S.S. Chung, J.A. French, J. Kowalski et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology 94, e2311 (2020).
https://doi.org/10.1212/WNL.0000000000009530
J.A. French. Cenobamate for focal seizures - a game changer? Nat. Rev. Neurol 16, 4 (2020).
https://doi.org/10.1038/s41582-019-0309-7
F.A. Mohammed, H.I. Abbood. Electronic structure of vanadium tetrachloride di-hydroxyl metal complex. J. Engin. Appl. Sci. 13, 9823 (2018).
K. Bamba, O.W. Patrice, N. Ziao. NBO Population analysis and electronic calculation of four azopyridine ruthenium complexes by DFT method. Comput. Chem. 5, 51 (2017).
https://doi.org/10.4236/cc.2017.51005
A.A. Muhmood, F.A. AL-Temimei. New ruthenium metal complexes for their activity with DNA and cells of cncer/DFT-B3LYP calculations. Indian J. Public Health 10, 1241 (2019).
https://doi.org/10.5958/0976-5506.2019.01463.3
A.F. LeRoy. Interactions of platinum metals and their complexes in biological systems. Environmental Health Perspectives 10, 73 (1975).
https://doi.org/10.2307/3428411
A.S. Abu-Surrah, M. Kettunen. Platinum group antitumor chemistry: Design and development of new anticancer drugs complementary to cisplatin. Current Med. Chem. 13, 1337 (2006).
https://doi.org/10.2174/092986706776872970
K. Zheng, J. Wang, Y. Shen et al. Studies on 4,7-di-substitution effects of one ligand in [Ru(Phen)3]2 with DFT method. J. Comput. Chem. 23, 436 (2002).
https://doi.org/10.1002/jcc.10038
J. Foresman, E. Frish. Exploring chemistry. (Gaussian Inc., 1996).
P. Hohenberg, W. Kohn. Inhomogeneous electron gas. Phys. Rev. 136, b864 (1964).
https://doi.org/10.1103/PhysRev.136.B864
M.J. Frisch, G.W. Trucks, H.B. Schlegel et al. GAUSSIAN 09, Revision A.02. (Gaussian, Inc., CT, 2009).
P.J. Hay, W.R. Wadt. Ab initio effective core potentials for molecular calculations - potentials for the transition-metal atoms Sc to Hg. J. Chem. Phys. 82, 270 (1985).
https://doi.org/10.1063/1.448799
F.A. AL-Temimei, H.A. Mraity. DFT/TD-DFT investigation of novel D- -A configuration dyes for improving solar cell efficiency. Struct Chem. 33, 859 (2022).
https://doi.org/10.1007/s11224-022-01901-7
J.B. Collins, P.V. Schleyer, J.S. Binkley et al. Selfconsistent molecular orbital methods. XVII. Geometries and binding energies of second-row molecules. A comparison of three basis sets. J. Chem. Phys. 64, 5142 (1976).
https://doi.org/10.1063/1.432189
F.A. AL-Temimei. Design high-efficiency organic dyes based on fluorescein toward dye-sensitized solar cells: A DFT/TD-DFT study. Opt Quant Electron 54, 600 (2022).
https://doi.org/10.1007/s11082-022-03997-x
A Kumar, V. Deval, P. Tandon, A. Gupta. Experimental and theoretical (FT-IR, FT-Raman, UV-Vis, NMR) spectroscopic analysis and first-order hyperpolarizability studies of non-linear optical material: (2E)-3-[4-(methylsulfanyl) phenyl]-1-(4-nitrophenyl) prop-2-en-1-one using density functional theory. Spectrochimica Acta Part A. 130, 41 (2014).
https://doi.org/10.1016/j.saa.2014.03.072
R.T. Morrison, R.N. Boyd. Organic Chemistry (New York University, 2007).
W.B. De Almeida, H.F.D Santos, P.J. O'Malley. A molecular mechanics and semiempirical conformational analysis of the herbicide diuron inhibitor of photosystem II. Struct Chem. 6, 383 (1995).
https://doi.org/10.1007/BF02310180
T. Pooventhiran, U. Bhattacharyya, D.J. Rao et al. Detailed spectra, electronic properties, qualitative non-covalent interaction analysis, solvatochromism, docking and molecular dynamics simulations in different solvent atmosphere of cenobamate. Struct Chem. 31, 2475 (2020).
https://doi.org/10.1007/s11224-020-01607-8
P. Atkins, R. Friedman, Molecular Quantum Mechanics (Oxford University Press Inc, 2005).
M.E. Casida, C. Jamorski, K.C. Casida et al. Molecular excitation energies to high-lying bound states from timedependent density-functional response theory: Characterization and correction of the time-dependent local density approximation ionization threshold. J. Chem. Phys. 108, 4439 (1998).
https://doi.org/10.1063/1.475855
R. Bauernschmitt, R. Ahlrichs. Treatment of electronic excitations within the adiabatic approximation of time dependent density functional theory, Chem. Phys. Lett. 256, 454 (1996).
Downloads
Published
How to Cite
Issue
Section
License
Copyright Agreement
License to Publish the Paper
Kyiv, Ukraine
The corresponding author and the co-authors (hereon referred to as the Author(s)) of the paper being submitted to the Ukrainian Journal of Physics (hereon referred to as the Paper) from one side and the Bogolyubov Institute for Theoretical Physics, National Academy of Sciences of Ukraine, represented by its Director (hereon referred to as the Publisher) from the other side have come to the following Agreement:
1. Subject of the Agreement.
The Author(s) grant(s) the Publisher the free non-exclusive right to use the Paper (of scientific, technical, or any other content) according to the terms and conditions defined by this Agreement.
2. The ways of using the Paper.
2.1. The Author(s) grant(s) the Publisher the right to use the Paper as follows.
2.1.1. To publish the Paper in the Ukrainian Journal of Physics (hereon referred to as the Journal) in original language and translated into English (the copy of the Paper approved by the Author(s) and the Publisher and accepted for publication is a constitutive part of this License Agreement).
2.1.2. To edit, adapt, and correct the Paper by approval of the Author(s).
2.1.3. To translate the Paper in the case when the Paper is written in a language different from that adopted in the Journal.
2.2. If the Author(s) has(ve) an intent to use the Paper in any other way, e.g., to publish the translated version of the Paper (except for the case defined by Section 2.1.3 of this Agreement), to post the full Paper or any its part on the web, to publish the Paper in any other editions, to include the Paper or any its part in other collections, anthologies, encyclopaedias, etc., the Author(s) should get a written permission from the Publisher.
3. License territory.
The Author(s) grant(s) the Publisher the right to use the Paper as regulated by sections 2.1.1–2.1.3 of this Agreement on the territory of Ukraine and to distribute the Paper as indispensable part of the Journal on the territory of Ukraine and other countries by means of subscription, sales, and free transfer to a third party.
4. Duration.
4.1. This Agreement is valid starting from the date of signature and acts for the entire period of the existence of the Journal.
5. Loyalty.
5.1. The Author(s) warrant(s) the Publisher that:
– he/she is the true author (co-author) of the Paper;
– copyright on the Paper was not transferred to any other party;
– the Paper has never been published before and will not be published in any other media before it is published by the Publisher (see also section 2.2);
– the Author(s) do(es) not violate any intellectual property right of other parties. If the Paper includes some materials of other parties, except for citations whose length is regulated by the scientific, informational, or critical character of the Paper, the use of such materials is in compliance with the regulations of the international law and the law of Ukraine.
6. Requisites and signatures of the Parties.
Publisher: Bogolyubov Institute for Theoretical Physics, National Academy of Sciences of Ukraine.
Address: Ukraine, Kyiv, Metrolohichna Str. 14-b.
Author: Electronic signature on behalf and with endorsement of all co-authors.
.png){kind=small}
