In vitro biological evaluation and in silico studies of linear diarylheptanoids from Curcuma aromatica Salisb. as urease inhibitors.

Plants of the Zingiberaceae family, specifically those belonging to the Curcuma species, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromatica Salisb. (or so-called "Nghe trang" in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1-3) and six known 3,5-dihydroxyl diarylheptanoids (4-9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4 and 9 significantly inhibit urease, with an IC50 value of 9.6 and 21.4 µM, respectively, more substantial than the positive control, hydroxyurea (IC50 = 77.4 µM). The structure-activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds via our constructed in silico model, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.

Ab initio kinetics of the CH3NH + NO2 reaction: formation of nitramines and N-alkyl nitroxides.

This study provides a detailed understanding of how the reaction between CH3NH, one of the primary products of the CH3NH2 + OH/Cl reactions, and NOx occurs in the atmosphere since the reaction is expected to be a dominant sink for the tropospheric CH3NH radical. First, we focus on the reaction of the aminyl radical CH3NH with NO2, complementing the known reaction between CH3NH and NO, to provide the overall picture of the CH3NH + NOx system. The reaction was meticulously examined across the extended range of temperature (298-2000 K) and pressure (0.76-76 000 torr) using quantum chemistry calculations and kinetic modeling based on the framework of the Rice-Ramsperger-Kassel-Marcus (RRKM)-based master equation. Highly correlated electronic structure calculations unveil that the intricate reaction mechanism of the CH3NH + NO2 reaction, which can proceed through O-addition or N-addition to form NO2, encompasses numerous steps, channels, and various intermediates and products. The temperature-/pressure-dependent kinetic behaviors and product distribution of the CH3NH + NO2 reaction are revealed under atmospheric and combustion conditions. The main products under atmospheric conditions are found to be CH3NHO and NO, as well as CH3NHNO2, while under combustion conditions, the primary products are only CH3NHO and NO. Given its stability under ambient conditions, CH3NHNO2, a nitramine, is believed to have the potential to induce DNA damage, which can ultimately result in severe cancers. Secondly, by building upon prior research on the CH3NH + NO system, this study shows that the reaction of CH3NH with NOx holds greater importance in urban areas with elevated NOx emissions than other oxidants like O2. Furthermore, this reaction occurs swiftly and results in the creation of various compounds, such as the carcinogenic nitrosamine (CH3NHNO), carcinogenic nitramine (CH3NHNO2), CH3NNOH, (CH3NN + H2O) and (CH3NHO + NO).

Identification of potential anti-hyperglycemic compounds in Cordyceps militaris ethyl acetate extract: in vitro and in silico studies.

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (1-14) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α-amylase (IC50 = 6.443 ± 0.364 mg.mL-1) and α-glucosidase (IC50 = 2.580 ± 0.194 mg.mL-1). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; DS¯ -12.3 kcal.mol-1; polarizability 34.7 Å3; logP - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS¯ -12.6 kcal.mol-1; polarizability 24.9 Å3; logP - 3.39), and 12 (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; DS¯ -12.5 kcal.mol-1; polarizability 52.4 Å3; logP - 4.39). The results encourage further experimental tests on cordycepin (1), mannitol (10), and adenosylribose (12) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.

Mechanistic and Kinetic Insights into OH-Initiated Atmospheric Oxidation of Hymexazol: A Computational Study.

Hymexazol is a volatile fungicide widely used in agriculture, causing its abundance in the atmosphere; thus, its atmospheric fate and conversion are of great importance when assessing its environmental impacts. Herein, we report a theoretical kinetic mechanism for the oxidation of hymexazol by OH radicals, as well as the subsequent reactions of its main products with O2 and then with NO by using the Rice-Ramsperger-Kassel-Marcus-based Master equation kinetic model on the potential energy surface explored at the ROCBS-QB3//M06-2X/aug-cc-pVTZ level. The predicted total rate constants ktotal(T, P) for the reaction between hymexazol and OH radicals show excellent agreement with scarcely available experimental values (e.g., 3.6 × 10-12 vs (4.4 ± 0.8) × 10-12 cm3/molecule/s at T = 300 K and P = 760 Torr); thus, the calculated kinetic parameters can be confidently used for modeling/simulation of N-heterocycle-related applications under atmospheric and even combustion conditions. The model shows that 3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl (IM2), 3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl (IM3), and (3-hydroxy-1,2-oxazol-5-yl)methyl (P8) are the main primary intermediates, which form the main secondary species of (3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl)dioxidanyl (IM4), (3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl)dioxidanyl (IM7), and ([(3-hydroxy-1,2-oxazol-5-yl)methyl]dioxidanyl (IM11), respectively, through the reactions with O2. The main secondary species then can react with NO to form the main tertiary species, namely, (3,4-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-5-yl)oxidanyl (P19), (3,5-dihydroxy-5-methyl-4,5-dihydro-1,2-oxazol-4-yl)oxidanyl (P21), and [(3-hydroxy-1,2-oxazol-5-yl)methyl]oxidanyl (P23), respectively, together with NO2. Besides, hymexazol could be a persistent organic pollutant in the troposphere due to its calculated half-life τ1/2 of 13.7-68.1 h, depending on the altitude.

The interplay of membrane fluidity, acyl chain order and area per lipid on the partitioning of two antidepressants paroxetine and sertraline.

Selective serotonin reuptake inhibitors (SSRIs) are among the popular drugs for treating depression and mental disorders. Membrane fluidity has previously been considered as the main factor in modulating the membrane partitioning of SSRIs, while other biophysical properties, such as the acyl chain order and area per lipid, were often neglected. Varying the lipid membrane composition and temperature can significantly modify the physical phase and, in turn, affect its fluidity, acyl chain order and area per lipid. Here, we investigate the role of membrane fluidity, acyl chain order and area per lipid in the partitioning of two SSRIs, paroxetine (PAX) and sertraline (SER). The model membranes were either POPC : SM (1 : 1 mol ratio) or POPC : SM : Chol (1 : 1 : 1 mol ratio) and studied in the temperature range of 25-45 °C. The order parameters and area per lipid in the two lipid mixtures were calculated using molecular dynamics simulations. The membrane partitioning of PAX and SER was determined via second derivative spectrophotometry. In a lower temperature range (25-32 °C), membrane fluidity favors the SSRI partitioning into Lo/Ld POPC:SM:Chol. In a higher temperature range (37-45 °C), the interplay between membrane fluidity, acyl chain order and area per lipid favors drug partitioning into Ld POPC:SM. The findings offer indication for the inconsistent distribution of SSRIs in tissues as well as the possible interaction of SSRIs with lipid domains and membrane-bound proteins.

OH-initiated oxidation of vinyl butyrate: ab initio insights.

The widespread use of vinyl butyrate (CH2CHOC(O)CH2CH2CH3 or VB) in the polymer industry and daily-life materials inevitably results in its emission into the atmosphere. Therefore, understanding the mechanism and kinetics of the VB conversion is critical for evaluating its fate and environmental impacts. Herein, we theoretically investigate the chemical transformation of VB initiated by OH radicals in the atmosphere using the stochastic Rice-Ramsperger-Kassel-Marcus (RRKM)-based master equation kinetic model on the potential energy surface explored at the M06-2X/aug-cc-pVTZ level of theory. Showing excellent agreement with limited experimental kinetic data, the VB + OH kinetic model reveals that H-abstraction from Cß (i.e., -CßH2CH3) prevails over the OH-addition to the double bond (CC), even at low temperatures. The detailed analyses, including those of the time-resolved species profiles, reaction rate, and reaction flux, reveal the reaction mechanism shift with temperature (causing the U-shaped temperature dependence of k(T, P)) and the noticeable pressure dependence of k(T, P) at low temperatures. The secondary chemistry under atmospheric conditions (namely, the reaction of the main product with O2 and its subsequent reactions with NO) was then characterized within the same framework to reveal the detailed kinetic mechanism (e.g., [4-(ethenyloxy)-4-oxobutan-2-yl]oxidanyl (IM12) + NO2 is the dominant channel under atmospheric conditions), suggesting VB is not a persistent organic pollutant and a new environmental concern regarding the formed NO2. Also, the kinetic behaviors of vinyl butyrate and its oxidation products were extended from atmospheric to combustion conditions for further applications. Moreover, through TD-DFT calculations, it is shown that several related important species (i.e., 1-(ethenyloxy)-1-oxobutan-2-yl (P4), [4-(ethenyloxy)-4-oxobutan-2-yl]dioxidanyl (IM7), and IM12) can potentially undergo photolysis in the atmosphere.

Metal complexes of benzimidazole-derived as potential anti-cancer agents: synthesis, characterization, combined experimental and computational studies.

In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from 2-(1H-benzimidazole-2-yl)-phenol derivatives and corresponding metal salt solutions. The compound structures were identified by FT-IR, 1H-NMR, powder X-ray diffraction and ESI-MS analyses, and the presence of the metal in the complexes was confirmed by ultraviolet-visible spectroscopy and ICP optical emission spectrometry. Electronic structure calculations were also carried out to describe the detailed structures in addition to the electronic absorption spectra of the ligands. The cytotoxic activity of the complexes was evaluated against three human cancer cell lines: lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cells. All complexes inhibited anti-proliferative cancer cells better than free ligands, especially Zn (II) and Ag (I) complexes, which are most sensitive to MDA-MB-231 cells. In addition, showing the growth inhibition of three cancer cell lines with IC50 < 10.4 µM, complexes C1 , C3 and C14 could be considered potential multi-targeted anti-cancer agents.

Formation of lipid raft nanodomains in homogeneous ternary lipid mixture of POPC/DPSM/cholesterol: Theoretical insights.

Lipid rafts, in biological membranes, are cholesterol-rich nanodomains that regulate many protein activities and cellular processes. Understanding the formation of the lipid-raft nanodomains helps us elucidate many complex interactions in the cell. In this study, the formation of lipid-raft nanodomains in a ternary palmitoyl-oleoyl-phosphatidylcholine/stearoyl-sphingomyelin/cholesterol (POPC/DPSM/Chol) lipid mixture, the most realistic surrogate model for biological membranes, has been successfully observed for the first time in-silico using microsecond timescale molecular dynamics simulations. The model reveals the formation of cholesterol-induced nanodomains with raft-like characteristics and their underlying mechanism: the cholesterol molecules segregate themselves into cholesterol nanodomains and then enrich the cholesterol-rich domain with sphingomyelin molecules to form a lipid raft thanks to the weak bonding of cholesterol with sphingomyelin. Besides, it is found that the increase in cholesterol concentration enhances the biophysical properties (e.g., bilayer thickness, area per lipid headgroup, and order parameter) of the lipid raft nanodomains. Such findings suggest that the POPC/DPSM/Chol bilayer is a suitable model to fundamentally extend the nanodomain evolution to investigate their lifetime and kinetics as well as to study protein-lipid interaction, protein-protein interaction, and selection of therapeutic molecules in the presence of lipid rafts.

On The Radical Scavenging and DNA Repairing Activities by Natural Oxygenated Diterpenoids: Theoretical Insights.

Diterpenoids are abundant and important compounds in Euphorbia species owing to their structural diversity; therefore, in this study, we investigate the modern-concept antioxidant activities, including free-radical scavenging and oxidative DNA damage repairing, of highly oxygenated diterpenoids originating from the aerial part of Euphorbia helioscopia. Four compounds with structural types of ent-abietane, containing a fused furan ring in their structures, including euphelionolide A (1), euphelionolide D (2), euphelionolide I (3), and euphelionolide L (4) are selected. First, the radical-scavenging activity of these compounds was evaluated with two typical radicals HOO• and HO• in water and pentyl ethanoate (PEA, to mimic lipid environment) via three main mechanisms, namely, hydrogen atom transfer (HAT), radical adduct formation (RAF), and single electron transfer. It is found that the studied compounds are able to scavenge free radicals at multiple reactive sites favorably via HAT and RAF mechanisms, in which the former dominates in the case with HOO• while both mechanisms are competitive in the reaction with HO•. Second, chemical repairing of DNA damage is modeled with the H-atom and single electron being transferred from the studied molecules to damaged 2'-deoxyguanosine (2dG) (i.e., 2dG• radicals and 2dG•+ radical cation). Among the four compounds, euphelionolide A is shown as the most effective radical scavenger and also the highest potential species for chemical repairing of radical-damaged DNA in both water and PEA.

Reaction kinetics of 1,4-cyclohexadienes with OH radicals: an experimental and theoretical study.

This work presents the OH-initiated oxidation kinetics of 1,4-cyclochexadiene (1,4-CHD). The temperature dependence of the reaction was investigated by utilizing a laser flash photolysis flow reactor and laser-induced fluorescence (LPFR/LIF) technique over the temperature range of 295-438 K and a pressure of ∼50 torr. The kinetics of the reaction was followed by measuring the LIF signal of OH radicals near 308 nm. The reaction of OH radicals with 1,4-CHD exhibited a clear negative temperature dependence. To discern the role of various channels, ab initio and RRKM-based ME calculations (RRKM-ME) were performed over temperatures of 200-2000 K and pressures of 0.76-7600 torr. The computed energy profile revealed that the reaction proceeds via the formation of a pre-reaction van der Waals complex at the entrance channel. The complex was found to be more stable than that usually seen in other alkenes + OH reactions. Both the addition channel and the abstraction reaction of allylic hydrogen were found to have negative energy barriers. Interestingly, the abstraction reaction exhibited a negative temperature dependence at low temperatures and contributed significantly (∼37%) to the total rate coefficients even under atmospheric conditions. At T ≥ 900 K, the reaction was found to proceed exclusively (>95%) via the abstraction channel. Due to the competing channels, the reaction of OH radicals with 1,4-CHD displays complicated kinetic behaviours, reflecting the salient features of the energy profile. The role of competing channels was fully characterized by our kinetic model. The calculated rate coefficients showed excellent agreement with the available experimental data.

Ab Initio Kinetics of Initial Thermal Pyrolysis of Isopropyl Propionate: A Revisited Study.

This work reports a detailed mechanism of the initial thermal pyrolysis of isopropyl propionate, (C2H5C(=O)OCH(CH3)2), an important biodiesel additive/surrogate, for a wide range of T = 500-2000 K and P = 7.6-76 000 Torr. The detailed kinetic behaviors of the title reaction on the potential energy surface constructed at the CBS-QB3 level were investigated using the RRKM-based master equation (RRKM-ME) rate model, including hindered internal rotation (HIR) and tunneling corrections. It is revealed that the C3H6 elimination occurring via a six-centered retro-ene transition state is dominant at low temperatures, while the homolytic fission of the C-C bonds becomes more competitive at higher temperatures. The tunneling treatment is found to slightly increase the rate constant at low temperatures (e.g., ∼1.59 times at 563 K), while the HIR treatment, being important at high temperatures, decreases the rate (e.g., by 5.9 times at 2000 K). Showing a good agreement with experiments in low-temperature kinetics, the kinetic model reveals that the pressure effect should be taken into account at high temperatures. Finally, the temperature- and pressure-dependent kinetic mechanism, consisting of the calculated thermodynamic and kinetic data, is provided for further modeling and simulation of any related systems.

New Mechanistic Insights into Atmospheric Oxidation of Aniline Initiated by OH Radicals.

This study theoretically reports the comprehensive kinetic mechanism of the aniline + OH reaction in the range of 200-2000 K and 0.76-7600 Torr. The temperature- and pressure-dependent behaviors, including time-resolved species profiles and rate coefficients, were studied within the stochastic RRKM-based master equation framework with the reaction energy profile, together with molecular properties of the species involved, characterized at the M06-2X/aug-cc-pVTZ level. Hindered internal rotation and Eckart tunneling treatments were included. The H-abstraction from the -NH2 moiety (to form C6H5NH (P1)) is found to prevail over the OH-addition on the C atom at the ortho site of aniline (to form 6-hydroxy-1-methylcyclohexa-2,4-dien-1-yl (I2)) with the atmospheric rate expressions (in cm3/molecule/s) as kabstraction(P1) = 3.41 × 101 × T-4.56 × exp (-255.2 K/T) for 200-2000 K and kaddition(I2) = 3.68 × 109 × T-7.39 × exp (-1163.9 K/T) for 200-800 K. The U-shaped temperature-dependent characteristics and weakly positive pressure dependence at low temperatures (e.g., T ≤ 800 K and P = 760 Torr) of ktotal(T) are also observed. The disagreement in ktotal(T) between the previous calculations and experimental studies is also resolved, and atmospheric aniline is found to be primarily removed by OH radicals (τOH ∼ 1.1 h) in the daytime. Also, via TD-DFT simulations, it is recommended to include P1 and I2 in any atmospheric photolysis-related model.

Multiple dehydrogenation of fluorene cation and neutral fluorene using the statistical molecular fragmentation model.

The statistical molecular fragmentation (SMF) model was used to analyze the 306 fragmentation channels (containing 611 different species) that result from the fluorene (C13H10+) cation losing up to three hydrogen atoms (neutral radicals and/or a proton). Breakdown curves from such analysis permit one to extract experimentally inaccessible information about the fragmentation of the fluorene cation, such as the locations of the lost hydrogen atoms (or proton), yields of the neutral fragments, electronic states of the residues, and quantification of very low probability channels that would be difficult to detect. Charge localization during the fragmentation pathways was studied to provide a qualitative understanding of the fragmentation process. Breakdown curves for both the fluorene cation and neutral fluorene were compared. The SMF results match the rise and fall of the one hydrogen loss yield experimentally measured by imaging photoelectron-photoion coincidence spectroscopy using a VUV synchrotron.

Newly synthesised oxime and lactone derivatives from Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction.

Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a-3m) and 7 lactones (4, 5, 6a-6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a-3m, 4, 5, and 6a-6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC50 of 2.73 ± 0.05 µM) > 6c (IC50 of 4.62 ± 0.12 µM) > 6e (IC50 of 7.31 ± 0.11 µM), and the computation-based analysis confirmed this, i.e., 5 (mass: 416.2 amu; polarisability: 52.4 Å3; DS: -14.9 kcal mol-1) > 6c (mass: 490.1 amu; polarisability: 48.8 Å3; DS: -13.7 kcal mol-1) > 6e (mass: 549.2 amu; polarisability: 51.6 Å3; DS: -15.2 kcal mol-1). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation.

Ab initio kinetic mechanism of OH-initiated atmospheric oxidation of pyrrole.

The comprehensive kinetic mechanism of the OH-initiated gas-phase oxidation of pyrrole is first theoretically reported in a broad range of conditions (T = 200-2000 K &P = 1-7600 Torr). On the potential energy surface constructed at the M06-2X/aug-cc-pVTZ level, the temperature- and pressure-dependent behaviors of the title reaction were characterized using the stochastic Rice-Ramsperger-Kassel-Marcus based Master Equation (RRKM-ME) rate model. The corrections of the hindered internal rotation and quantum tunneling treatments were included. The calculated results reveal the competition between the two distinct pathways: OH-addition and direct H-abstraction. The former channels are found favorable at low-temperature and high-pressure range (e.g., T < 900 K and P = 760 Torr) where non-Arrhenius and positive pressure-dependent behaviors of the rate constants are noticeably observed, while the latter predominate at temperatures higher than 900 K at atmospheric pressure and no pressure dependence on the rate constant is found. The predicted global rate constants are in excellent agreement with laboratory values; thus, the derived kinetic parameters are recommended for modeling/simulation of N-heterocycle-related applications in atmospheric and even in combustion conditions. Besides, pyrrole should not be considered as a persistent organic pollutant owing to its short atmospheric lifetime (∼1 h) towards OH radicals. The secondary mechanisms of the subsequent reactions of two OH-pyrrole adducts (namely, I1 and I2) with two abundant species, O2/NO, which are relevant to the atmospheric degradation process, were also investigated. It is also revealed by TD-DFT calculations that two OH-pyrrole adducts (I1 &I2), nine intermediates, Ii (i = 3-11) and four products (P1, P2, P3 and P6) can undergo photodissociation under the sunlight.

Detailed kinetics of hydrogen abstraction from trans-decalin by OH radicals: the role of hindered internal rotation treatment.

In this study, the detailed kinetic mechanism of the trans-decalin + OH reaction is firstly investigated for a wide range of conditions (i.e., T = 200-2000 K & P = 0.76-76 000 Torr) using the M06-2X/aug-cc-pVTZ level and stochastic Rice-Ramsperger-Kassel-Marcus based master equation (RRKM-ME) rate model, which includes corrections of the hindered internal rotor (HIR) and tunneling effects. Our predicted global rate constant excellently matches with the scarce experimental measurement (R. Atkinson, et al. Int. J. Chem. Kinet., 1983, 15, 37-50). The H-abstraction channel from Cα of trans-decalin is found to be dominant at low temperatures. A U-shaped temperature-dependent behavior and slightly positive pressure-dependence at low temperatures (e.g., T ≤ 400 K & P = 760 Torr) of the total rate constants are also observed. Detailed analysis reveals that the HIR treatment is essential to capture the kinetic behavior while the tunneling correction only plays a minor role.

Correction to Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil.

[This corrects the article DOI: 10.1021/acsomega.0c00772.].

Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil.

Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC-MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body.

A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation.

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHEPh-AgCl and (NHEPh-AgCl)2 with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (NHE-Ag) and bis-silver-tetrylene complexes (NHE-Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC-Ag and NHC-Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)2, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order of NHC-Ag > NHSi-Ag > NHGe-Ag and NHSi-Ag-bis > NHGe-Ag-bis > NHC-Ag-bis. The natural bond orbital analysis implies that the [NHEPh→AgCl] and [(NHEPh)2→(AgCl)2] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbene NHC-Ag, bis-silver-carbene NHC-Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from -17.5 to -16.5 kcal mol-1 and -16.9 to -16.6 kcal mol-1, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver-carbene NHC-Ag and bis-silver-carbene NHC-Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.

Ab initio dynamics of hydrogen abstraction from N2H4 by OH radicals: an RRKM-based master equation study.

The detailed reaction mechanism of the N2H4 + OH reaction is comprehensively reported for a wide range of conditions (i.e., T = 200-3000 K & P = 1-7600 Torr) using the CCSD(T)/CBS//M06-2X/6-311++G(3df,2p) level and the master equation/Rice-Ramsperger-Kassel-Marcus (ME/RRKM) rate model, which includes corrections of the hindered internal rotor (HIR) and tunneling treatments. Our calculated rate constants are found in excellent agreement with the latest experimental data (G. L. Vaghjiani, Int. J. Chem. Kinet., 2001, 33, 354-362), which helps to resolve the discrepancy between the previous experimental and theoretical studies. The reaction mechanism is revealed as: (i) the H-abstraction channel is more thermodynamically favorable than the OH-substitution mechanism; (ii) non-Arrhenius behaviors and slightly positive pressure-dependence at low temperature (T≤ 500 K) of the rate coefficients are observed and (iii) the HIR treatment plays a substantial role in obtaining the reliable rate constants. Moreover, the performance of several molecular electronic structure methods (i.e., M06-2X, B3LYP, BH&HLYP and MP2) on the rate coefficient calculations is also discussed thoroughly in this work.