A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase

Abstract The chemical resistance of drugs against any change in their composition and studying the rate of multiwell-multichannel reactions in the liquid phase, respectively, are the important challenges of pharmacology and chemistry. In this article, we investigate two challenges together through s...

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Autores principales:	Hamed Douroudgari, Morteza Vahedpour
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/462450179ebb44388114ac163ce3ba05
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spelling	oai:doaj.org-article:462450179ebb44388114ac163ce3ba052021-11-28T12:20:50ZA computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase10.1038/s41598-021-01751-z2045-2322https://doaj.org/article/462450179ebb44388114ac163ce3ba052021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01751-zhttps://doaj.org/toc/2045-2322Abstract The chemical resistance of drugs against any change in their composition and studying the rate of multiwell-multichannel reactions in the liquid phase, respectively, are the important challenges of pharmacology and chemistry. In this article, we investigate two challenges together through studying drug stability against its unimolecular reactions in the liquid phase. Accordingly, multiwell-multichannel reactions based on 1,4-H shifts are designed for simplified drugs such as 3-hydroxyl-1H-pyrrol-2(5H)-one, 3-hydroxyfuran-2(5H)-one, and 3-hydroxythiophen-2(5H)-one. After that, the reverse and forward rate constants are calculated by using the Rice Ramsperger Kassel Marcus theory (RRKM) and Eckart tunneling correction over the 298–360 K temperature range. Eventually, using the obtained rate constants, we can judge drug resistance versus structural changes. To attain the goals, the potential energy surfaces of all reactions are computed by the complete basis set-quadratic Becke3 composite method, CBS-QB3, and the high-performance meta hybrid density functional method, M06-2X, along with the universal Solvation Model based on solute electron Density, SMD, due to providing more precise and efficient results for the barrier heights and thermodynamic studies. To find the main reaction pathway of the intramolecular 1,4-H shifts in the target molecules, all possible reaction pathways are considered mechanistically in the liquid phase. Also, the direct dynamics calculations that carry out by RRKM theory on the modeled pathways are used to distinguish the main reaction pathway. As the main finding of this research, the results of quantum chemical calculations accompanied by the RRKM/Eckart rate constants are used to predict the stability of drugs. This study proposes a new way to examine drug stability by the computer-aided reaction design of target drugs. Our results show that 3-hydroxyfuran-2(5H)-one based drugs are the most stable and 3-hydroxythiophen-2(5H)-one based drugs are more stable than 3-hydroxy-1H-pyrrol-2 (5H)-one based drugs in water solution.Hamed DouroudgariMorteza VahedpourNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-25 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hamed Douroudgari Morteza Vahedpour A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
description	Abstract The chemical resistance of drugs against any change in their composition and studying the rate of multiwell-multichannel reactions in the liquid phase, respectively, are the important challenges of pharmacology and chemistry. In this article, we investigate two challenges together through studying drug stability against its unimolecular reactions in the liquid phase. Accordingly, multiwell-multichannel reactions based on 1,4-H shifts are designed for simplified drugs such as 3-hydroxyl-1H-pyrrol-2(5H)-one, 3-hydroxyfuran-2(5H)-one, and 3-hydroxythiophen-2(5H)-one. After that, the reverse and forward rate constants are calculated by using the Rice Ramsperger Kassel Marcus theory (RRKM) and Eckart tunneling correction over the 298–360 K temperature range. Eventually, using the obtained rate constants, we can judge drug resistance versus structural changes. To attain the goals, the potential energy surfaces of all reactions are computed by the complete basis set-quadratic Becke3 composite method, CBS-QB3, and the high-performance meta hybrid density functional method, M06-2X, along with the universal Solvation Model based on solute electron Density, SMD, due to providing more precise and efficient results for the barrier heights and thermodynamic studies. To find the main reaction pathway of the intramolecular 1,4-H shifts in the target molecules, all possible reaction pathways are considered mechanistically in the liquid phase. Also, the direct dynamics calculations that carry out by RRKM theory on the modeled pathways are used to distinguish the main reaction pathway. As the main finding of this research, the results of quantum chemical calculations accompanied by the RRKM/Eckart rate constants are used to predict the stability of drugs. This study proposes a new way to examine drug stability by the computer-aided reaction design of target drugs. Our results show that 3-hydroxyfuran-2(5H)-one based drugs are the most stable and 3-hydroxythiophen-2(5H)-one based drugs are more stable than 3-hydroxy-1H-pyrrol-2 (5H)-one based drugs in water solution.
format	article
author	Hamed Douroudgari Morteza Vahedpour
author_facet	Hamed Douroudgari Morteza Vahedpour
author_sort	Hamed Douroudgari
title	A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
title_short	A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
title_full	A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
title_fullStr	A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
title_full_unstemmed	A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
title_sort	computer-aided method for controlling chemical resistance of drugs using rrkm theory in the liquid phase
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/462450179ebb44388114ac163ce3ba05
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A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase

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