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

AbstractThe 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.

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Atmospheric reaction of hydrazine plus hydroxyl radical

Scientific Reports ◽

10.1038/s41598-021-92563-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hamed Douroudgari ◽

Morteza Vahedpour ◽

Fahime Khouini

Keyword(s):

Hydroxyl Radical ◽

Rate Constants ◽

Reaction Pathway ◽

Radical Reaction ◽

Basis Sets ◽

Rate Coefficients ◽

Stationary Points ◽

Main Reaction ◽

Partition Functions ◽

Oh Radicals

AbstractUnderstanding the mechanism of hydrazine oxidation reaction by OH radical along with the rate constants of all possible pathways leads to explain the fate of hydrazine in the atmosphere. In this article, the comprehensive mechanisms and kinetics of the hydrazine plus hydroxyl radical reaction have been investigated theoretically at different temperatures and pressures. To achieve the main goals, a series of high levels of quantum chemical calculations have been widely implemented in reliable channels of the H-abstraction, SN2, and addition/elimination reactions. The energy profile of all pathways accompanied by the molecular properties of the involved stationary points has been characterized at the MP2, M06-2X, and CCSD(T)/CBS levels. To estimate accurate barrier energies of the H-abstraction channels, large numbers of the CCSD (T) calculations in conjunction with various augmented basis sets have been implemented. The direct dynamic calculations have been carried out using the validated M06-2X/maug-cc-pVTZ level, and also by the CCSD(T) (energies) + MP2 (partition functions) level. The pressure-dependent rate constants of the barrierless pathways have been investigated by the strong collision approach. Therefore, the main behaviors of the N2H4 + OH reaction have been explored according to the influences of temperature and pressure on the computed rate coefficients within the well-behaved theoretical frameworks of the TST, VTST, and RRKM theories. It has been found that the H-abstraction mechanism (to form N2H3) is dominant relative to the SN2 reaction and OH-addition to the N center of N2H4 moiety (to form H2NOH + NH2). The computed high pressure limit rate constant of the main reaction pathway, k(298.15) = 7.31 × 10–11 cm3 molecule−1 s−1, has an excellent agreement with the experimental value (k (298.15) = (6.50 ± 1.3) × 10–11 cm3 molecule−1 s−1) recommended by Vaghjiani. Also, the atmospheric lifetime of hydrazine degradation by OH radicals has been demonstrated to be 32.80 to 1161.11 h at the altitudes of 0–50 km. Finally, the disagreement in the calculated rate constants between the previous theoretical study and experimental results has been rectified.

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Conversion of methane to benzene in CVI by density functional theory study

Scientific Reports ◽

10.1038/s41598-019-56136-0 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Kun Li ◽

Hejun Li ◽

Ningning Yan ◽

Tiyuan Wang ◽

Wei Li ◽

...

Keyword(s):

Density Functional Theory ◽

Rate Constants ◽

Density Functional ◽

Reaction Pathway ◽

Chemical Species ◽

State Theory ◽

Chemical Vapor Infiltration ◽

Basis Set ◽

Functional Theory ◽

Conversion Of Methane

AbstractA density functional theory (DFT) study was employed to explore the mechanism of the conversion of methane to benzene in chemical vapor infiltration (CVI) based on the concluded reaction pathways from C1-species to C6-species. The geometry optimization and vibrational frequency analysis of all the chemical species and transition states (TS) were performed with B3LYP along with a basis set of 6–311 +G(d, p), and Gaussian 09 software was used to perform the study. The rate constants were calculated by KiSThelP according to the conventional transition state theory (TST), and the Wigner method was applied to acquire the tunneling correction factors. Then the rate constants were fitted to the modified Arrhenius expression in the temperature range of 800–2000 K. As for the barrierless reactions calculated in this paper, the rate constants were selected from the relating references. Through the energetic and kinetic calculations, the most favorable reaction pathway for benzene formation from methane was determined, which were mainly made of the unimolecular dissociation. The conversion trend from C1-species to C4-species is mainly guided by a strong tendency to dehydrogenation and the pathways from C4-species to C6-species are all presumed to be able to produce C6H6 molecule.

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Kinetics of esterification of monoisopropylphenols with phosphoryl trichloride

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19891311 ◽

1989 ◽

Vol 54 (5) ◽

pp. 1311-1317

Author(s):

Miroslav Magura ◽

Ján Vojtko ◽

Ján Ilavský

Keyword(s):

Liquid Phase ◽

Rate Constants ◽

Reaction Rates ◽

Activation Energies ◽

The Individual ◽

Kinetics Of

The kinetics of liquid-phase isothermal esterification of POCl3 with 2-isopropylphenol and 4-isopropylphenol have been studied within the temperature intervals of 110 to 130 and 90 to 110 °C, respectively. The rate constants and activation energies of the individual steps of this three-step reaction have been calculated from the values measured. The reaction rates of the two isomers markedly differ: at 110 °C 4-isopropylphenol reacts faster by the factors of about 7 and 20 for k1 and k3, respectively. This finding can be utilized in preparation of mixed triaryl phosphates, since the alkylation mixture after reaction of phenol with propene contains an excess of 2-isopropylphenol over 4-isopropylphenol.

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The Effect of p-Toluidine on the Two-Step Electroreduction of Zn(II) in Water-Methanol and Water-Dimethylformamide

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19990585 ◽

1999 ◽

Vol 64 (4) ◽

pp. 585-594 ◽

Cited By ~ 2

Author(s):

Barbara Marczewska

Keyword(s):

Electron Transfer ◽

Binary Mixtures ◽

Rate Constant ◽

Rate Constants ◽

Electrode Surface ◽

Mercury Electrode ◽

Forward Rate ◽

Solvent Molecules ◽

Activated Complex

The acceleration effect of p-toluidine on the electroreduction of Zn(II) on the mercury electrode surface in binary mixtures water-methanol and water-dimethylformamide is discussed. The obtained apparent and true forward rate constants of Zn(II) reduction indicate that the rate constant of the first electron transfer increases in the presence of p-toluidine. The acceleration effect may probably be accounted for by the concept of the formation on the mercury electrode an activated complex, presumably composed of p-toluidine and solvent molecules.

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Photochemistry of 1-Phenyl-4-Allyl-Tetrazol-5-One: A Theoretical Study Contribution towards Mechanism Elucidation

Applied Sciences ◽

10.3390/app11094045 ◽

2021 ◽

Vol 11 (9) ◽

pp. 4045

Author(s):

Amilcar Duque-Prata ◽

Carlos Serpa ◽

Pedro J. S. B. Caridade

Keyword(s):

Density Functional ◽

Reaction Pathway ◽

Intramolecular Proton Transfer ◽

Polarizable Continuum Model ◽

Uv Spectra ◽

Point Of View ◽

Basis Set ◽

Pathway Evolution ◽

Photodegradation Mechanism ◽

Energetic Point

The photodegradation mechanism of 1-phenyl-4-allyl-tetrazol-5-one has been studied using (time-dependent) density functional theory with the M06-HF, B3LYP, and PBE0 functionals and the VDZ basis set. All calculations have been carried out using the polarizable continuum model to simulate the solvent effects of methanol. The reaction pathway evolution on the triplet state has been characterised to validate a previously postulated experimental-based mechanism. The transition states and minimums have been initially located by local scanning in partial constrained optimisation, followed by a fully relaxed search procedure. The UV spectra has shown to be better described with PBE0 functional when compared with the experimental results, having the M06-HF a shift of 40 nm. From the energetic point of view, the postulated mechanism has been validated in this work showing a concerted photoextrusion of the N2 molecule. The intramolecular proton transfer occurs at a later stage of the mechanism after cyclization of the allyl group on a triplet biradical intermediate. The photoproduct observed experimentally, a pyrimidinone, has been characterised. The infrared spectroscopic reaction profile has also been proposed.

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Absolute Rate Constants for Hydrocarbon Autoxidation. Part XX. Oxidation of Some Organic Sulfides

Canadian Journal of Chemistry ◽

10.1139/v71-356 ◽

1971 ◽

Vol 49 (12) ◽

pp. 2178-2182 ◽

Cited By ~ 11

Author(s):

J. A. Howard ◽

S. Korcek

Keyword(s):

Liquid Phase ◽

Hydrogen Atom ◽

Rate Constants ◽

Hydrogen Atom Abstraction ◽

Absolute Rate ◽

Organic Sulfides

Absolute rate constants for the liquid phase autoxidation of some organic sulfides at 30 °C have been measured. The reactivities of organic sulfides towards t-butylperoxy radicals are equal to or somewhat less than the reactivities of structurally analogous ethers. The α-alkylthiylalkylperoxy radicals appear to be about 3–5 times more reactive in hydrogen atom abstraction than the α-alkoxyalkylperoxy radicals.

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Reaction mechanism of the magnesium ion-dependent adenosine triphosphatase of frog muscle myosin and subfragment 1

Biochemical Journal ◽

10.1042/bj1710165 ◽

1978 ◽

Vol 171 (1) ◽

pp. 165-175 ◽

Cited By ~ 41

Author(s):

M A Ferenczi ◽

E Homsher ◽

R M Simmons ◽

D R Trentham

Keyword(s):

Steady State ◽

Rate Constants ◽

Myosin Atpase ◽

Forward Rate ◽

Magnesium Ion ◽

Skeletal Muscle Myosin ◽

General Terms ◽

Predominant Component ◽

Main Components ◽

Muscle Myosin

The Mg2+-dependent ATPase (adenosine 5′-triphosphatase) mechanism of myosin and subfragment 1 prepared from frog leg muscle was investigated by transient kinetic technique. The results show that in general terms the mechanism is similar to that of the rabbit skeletal-muscle myosin ATPase. During subfragment-1 ATPase activity at 0-5 degrees C pH 7.0 and I0.15, the predominant component of the steady-state intermediate is a subfragment-1-products complex (E.ADP.Pi). Binary subfragment-1-ATP (E.ATP) and subfragment-1-ADP (E.ADP) complexes are the other main components of the steady-state intermediate, the relative concentrations of the three components E.ATP, E.ADP.Pi and E.ADP being 5.5:92.5:2.0 respectively. The frog myosin ATPase mechanism is distinguished from that of the rabbit at 0-5 degrees C by the low steady-state concentrations of E.ATP and E.ADP relative to that of E.ADP.Pi and can be described by: E + ATP k' + 1 in equilibrium k' − 1 E.ATP k' + 2 in equilibrium k' − 2 E.ADP.Pi k' + 3 in equilibrium k' − 3 E.ADP + Pi k' + 4 in equilibrium k' − 4 E + ADP. In the above conditions successive forward rate constants have values: k' + 1, 1.1 × 10(5)M-1.S-1; k' + 2 greater than 5s-1; k' + 3, 0.011 s-1; k' + 4, 0.5 s-1; k'-1 is probably less than 0.006s-1. The observed second-order rate constants of the association of actin to subfragment 1 and of ATP-induced dissociation of the actin-subfragment-1 complex are 5.5 × 10(4) M-1.S-1 and 7.4 × 10(5) M-1.S-1 respectively at 2-5 degrees C and pH 7.0. The physiological implications of these results are discussed.

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Kinetics of the successive chlorination of 1,2-dichloroethane in the liquid phase

Australian Journal of Chemistry ◽

10.1071/ch9691177 ◽

1969 ◽

Vol 22 (6) ◽

pp. 1177 ◽

Cited By ~ 6

Author(s):

DS Caines ◽

RB Paton ◽

DA Williams ◽

PR Wilkinson

Keyword(s):

Liquid Phase ◽

Rate Constants ◽

Relative Rate ◽

Stirred Tank ◽

Continuous Stirred Tank Reactor ◽

Alternative Pathways ◽

Tank Reactor ◽

Relative Rate Constants ◽

Continuous Stirred Tank ◽

Kinetics Of

Liquid 1,2-dichloroethane has been chlorinated by dissolved chlorine to a succession of chloroethanes up to the ultimate hexachloroethane. The results of both batch and continuous stirred tank reactor systems have been analysed by computer techniques to give a set of relative rate constants from which one can predict the product composition for a given chlorine uptake, the aim in this work being to optimize the production of tetrachloroethanes. An unusual feature of the kinetics is that 1,1,1,2- and 1,1,2,2-tetrachloroethanes provide alternative pathways between 1,1,2-trichloroethane and pentachloroethane.

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A Study on Pathway and QSPR Models for Debromination of PBDEs with Pseudopotential Method

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.997.25 ◽

2014 ◽

Vol 997 ◽

pp. 25-32 ◽

Cited By ~ 3

Author(s):

Ling Yun Li ◽

Yi Miao Lin ◽

Ji Wei Hu

Keyword(s):

Rate Constants ◽

Polybrominated Diphenyl Ethers ◽

Reaction Rate ◽

Linear Regression Analysis ◽

Basis Set ◽

Pseudopotential Method ◽

Computational Time ◽

Least Squares Regression ◽

Reaction Rate Constants ◽

Qspr Study

Neutral PBDEs congeners and their corresponding radical anions were studied with the pseudopotential method of stuttgart group (SDD) effective-core potentials basis set for the bromine atoms and the all-electron basis set for all other atoms. The pseudopotential method can be used for compounds containing heavy elements with relativistic effects and can reduce the computational time. The quantitative structure property relationship (QSPR) study was also performed in this work to develop models to predict the normolized reaction rate constants for the reductive debromination of polybrominated diphenyl ethers (PBDEs) by zero-valent iron (ZVI). The partial least squares regression (PLSR), principal component analysis-multiple linear regression analysis (PCA-MLR), and back propagation artificial neural network (BP-ANN) approaches were employed for the QSPR study between the molecular descriptors and the logarithm of normalized reaction rate constants of fourteen selected BDE congeners. The results show that the ANN models could be more satisfactorily to predict the rate constants than the PLSR and PCA-MLR models.

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Reaction kinetics of OH radicals with glutaric acid and adipic acid in the aqueous phase

10.5194/egusphere-egu21-15624 ◽

2021 ◽

Author(s):

Liang Wen ◽

Thomas Schaefer ◽

Hartmut Herrmann

Keyword(s):

Aqueous Phase ◽

Adipic Acid ◽

Rate Constants ◽

Density Functional ◽

Glutaric Acid ◽

Radical Reaction ◽

Basis Set ◽

Oh Radicals ◽

Oh Radical ◽

Energy Barriers

Dicarboxylic acids (DCAs) are widely distributed in atmospheric aerosols and cloud droplets and are mainly formed by the oxidation of volatile organic compounds (VOCs). For example, glutaric acid and adipic acid are two kinds of the DCAs that can be oxidized by hydroxyl radical (&#8231;OH) reactions in the aqueous phase of aerosols and droplets. In the present study, the temperature- and pH-dependent rate constants of the aqueous OH radical reactions of the two DCAs were investigated by a laser flash photolysis-long path absorption setup using the competition kinetics method. Based on speciation calculations, the OH radical reaction rate constants of the fully protonated (H2A), deprotonated (HA-) and fully deprotonated (A2-) forms of the two DCAs were determined. The following Arrhenius expressions for the T-dependency of the OH radical reaction of glutaric acid, k(T, H2A) = (3.9 &#177; 0.1) &#215; 1010 &#215; exp[(-1270 &#177; 200 K)/T], k(T, HA-) = (2.3 &#177; 0.1) &#215; 1011 &#215; exp[(-1660 &#177; 190 K)/T], k(T, A2-) = (1.4 &#177; 0.1) &#215; 1011 &#215; exp[(-1400 &#177; 170 K)/T] and adipic acid, k(T, H2A) = (7.5 &#177; 0.2) &#215; 1010 &#215; exp[(-1210 &#177; 170 K)/T], k(T, HA-) = (9.5 &#177; 0.3) &#215; 1010 &#215; exp[(-1200 &#177; 200 K)/T], k(T, A2-) = (8.7 &#177; 0.2) &#215; 1010 &#215; exp[(-1100 &#177; 170 K)/T] (in unit of L mol-1 s-1) were derived.The energy barriers of the H-atom abstractions were simulated by the Density Functional Theory calculations run with the GAUSSIAN package using the M06-2X method and the basis set m062x/6-311++g(3df,2p). The results showed that the energy barriers were lower at the C&#946;-atoms and are higher at the C&#945;-atoms of the two DCAs, clearly suggesting that the H-atom abstractions occurred predominately at the C&#946;-atoms. In addition, the ionizations can enhance the electrostatic effects of the carboxyl groups, significantly reducing the energy barriers, leading to the order of OH radical reactivity as &#160;< &#160;< . This study intends to better characterize the losing processes of glutaric acid and adipic acid in atmospheres.

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