6-membered Ring Research Articles

Insight into performance over IM-5, ZSM-5 and ZSM-11 zeolites for n-heptane cracking to light olefins in the absence & presence of steam

The three dimension (3D) 10-membered ring channels zeolite has a unique advantage in increasing light olefins for catalytic cracking reaction. Herein, zeolites IM-5, ZSM-5 and ZSM-11 were synthesized hydrothermally to achieve comparable texture properties and SiO2/Al2O3 ratios. The acid content and acid strength of the three zeolites were as follows: IM-5 > ZSM-5 > ZSM-11. Meanwhile, 1H DQ MAS NMR confirmed that there was a synergistic effect between Brønsted and Lewis acids in IM-5 zeolite. However, IM-5 zeolite with lots of strong BAS had an unexpected low TOF in n-heptane cracking. Furthermore, the light olefins selectivity was as follows: IM-5 > ZSM-11 > ZSM-5 at 550–650 ℃ in the absence of steam. IM-5 zeolite had the particular advantage in ethylene, and its selectivity was up to 44.9 %. After steam was introduced, the monomolecular cracking reaction, the aromatization of propylene and the deep cracking of C3 and C4 hydrocarbons were inhibited over the three zeolites. Steam could prolong the activity of IM-5 zeolite, but accelerate the deactivation of ZSM-5 and ZSM-11 zeolites. The primary cause for the rapid deactivation of ZSM-5 and ZSM-11 zeolites was dealuminization in steam, whereas for the IM-5 zeolite, it was the rapid formation of coke on its surface, thereby blocking its micropore channels.

Structure Formation in an Ionic Liquid Wetting Layer: A Combined STM, IRAS, DFT and MD Study of [C2C1Im][OTf] on Au(111).

In a solid catalyst with ionic liquid layer (SCILL), ionic liquid (IL) coatings are used to improve the selectivity of noble metal catalysts. To understand the origins of this selectivity control, we performed model studies by surface science methods in ultrahigh vacuum (UHV). We investigated the growth and thermal stability of ultrathin IL films by infrared reflection absorption spectroscopy (IRAS). We combined these experiments with scanning tunneling microscopy (STM) to obtain information on the orientation of the ions, the interactions with the surface, the intermolecular interactions, and the structure formation. Additionally, we performed density-functional theory (DFT) calculations and molecular dynamics (MD) simulations to interpret the experimental data. We studied the IL 1-ethyl-3-methylimidazolium trifluoromethanesulfonate [C2C1Im][OTf] on Au(111) surfaces. We observe a weakly bound multilayer of [C2C1Im][OTf], which is stable up to 390 K, while the monolayer desorbs at ~450 K. [C2C1Im][OTf] preferentially adsorbs at the step edges and elbows of the herringbone reconstruction of Au(111). The anion adsorbs via the SO3 group with the molecular axis perpendicular to the surface. At low coverage, the [C2C1Im][OTf] crystallizes in a glass-like 2D phase with short-range order. At higher coverage, we observe a phase transition to a 6-membered ring structure with long-range order.

Baeckea frutescens L.: A Review on Phytochemistry, Biosynthesis, Synthesis, and Pharmacology

Background In traditional medicine of Southeast Asian countries, Baeckea frutescens L. (family Myrtaceae) has a long history of use. Numerous research projects have shown that this plant contains metabolites with remarkable medicinal value. No review document, to date, has given an insight into the role of B frutescens constituents in pharmacological development. Objective The current review briefly offers crucial information on the phytochemistry, biosynthesis, synthesis, and pharmacology of B frutescens. Methods B frutescens is the most meaningful keyword to search for literature data. It was used either on its own or in combination with other keywords. References have been gathered from various resources such as Google Scholar, SciFinder, and PubMed. More than 50 electronic references were collected from the 1960s. Results Approximately 130 metabolites have been isolated and structurally determined from this medicinal plant. They included phloroglucinols, phloroglucinol-based meroterpenoids, sesquiterpenoids, triterpenoids, flavonoids, chromones, 5-membered ring compounds, and others. B frutescens fresh tissues were thought to be a rich resource of essential oils. Tasmanone is a precursor in the biosynthesis of various B frutescens compounds, while phloroglucinol derivatives can be seen as initial compounds in the synthetic procedures of various B frutescens molecules. B frutescens plant extracts and compounds isolated from them possess a variety of pharmacological properties, such as cytotoxic, antimicrobial, anti-inflammatory, antioxidant, antirheumatoid, skin protective, and mosquito larvicidal activities. Conclusion More experimental reports on phytochemistry and pharmacology are required. In vivo pharmacological studies on the mechanisms of action of the active compounds are urgently required since most of the results obtained so far have been from in vitro assays.

Synthesis and Spectrophotometric Studies of Heterocyclic Bay-Substituted Naphthalenediimide Colorimetric pH Indicators

Four naphthalenediimide colorimetric pH indicators were synthesized with N,N-dimethylethyleneamine at the imide positions and with 5- to 7-membered heterocyclic rings at the bay positions, namely pyrrolidine, morpholine, piperidine and azepane. The pH indicators are constructed in a modular receptor–spacer–fluorophore–spacer–receptor format based on a photoinduced electron transfer (PET) design. The compounds were studied by UV–visible absorption and steady-state fluorescence spectroscopy in 1:1 (v/v) methanol/water. Brilliant colour changes are observed between pH 2 and 4 due to an internal charge transfer (ICT) mechanism. Fluorescence turn-on enhancements range from 10–37 fold; however, the maximum fluorescence quantum yield in the presence of acid is <0.004, which is below naked eye detection. Hence, from the viewpoint of a human observer, these chemosensors function as colorimetric YES logic gates, and fluorimetric PASS 0 logic gates.

Sulfur-Arylation of Sulfenamides via Ullmann-Type Coupling with (Hetero)aryl Iodides.

Sulfur-(hetero)arylation of sulfenamides with commercially abundant (hetero)aryl iodides by Ullmann-type coupling with inexpensive copper(I) iodide as the catalyst is reported. A broad scope of reaction inputs was demonstrated, including both aryl and alkyl sulfenamides and highly sterically hindered aryl and 5- and 6-membered ring heteroaryl iodides. Relevant to many bioactive high oxidation state sulfur compounds, the (hetero)arylation of S-methyl sulfenamides is reported, including for complex aryl iodides. Smiles rearrangement of electron-deficient S-heteroaryl sulfilimines is also disclosed.

Designing Site Specificity in the Mechanochemical Cargo Release of Small Molecules.

Mechanical force can trigger the predictable and precise release of small molecules from macromolecular carriers. In this article, based on mechanochemical simulations, we show that norborn-2-en-7-one (NEO), I, and its derivatives can selectively release CO, N2, and SO2 and produce two distinctly different products, A ((3E,5Z,7E)-dimethyl-5,6-diphenyldeca-3,5,7-triene-1,10-diyl bis(2-bromo-2-methylpropanoate)) and B (4',5'-dimethyl-4',5'-dihydro-[1,1':2',1''-terphenyl]-3',6'-diyl)bis(ethane-2,1-diyl) bis(2-bromo-2-methylpropanoate). Site-specific design in the pulling points (PP) ensures that by changing the regioselectivity, either A or B can be exclusively generated. Controlling the rigidity of the NEO scaffold by replacing a 6-membered ring with an 8-membered ring and concomitantly tuning the pulling groups makes it mechanolabile toward the selective formation of B. The diradical intermediate formed during I → A is predicted to be persistent for ∼150 fs. The structural design holds the key to the trade-off between mechanochemical rigidity and lability.

Persistent topological Laplacian analysis of SARS-CoV-2 variants.

Topological data analysis (TDA) is an emerging field in mathematics and data science. Its central technique, persistent homology, has had tremendous success in many science and engineering disciplines. However, persistent homology has limitations, including its inability to handle heterogeneous information, such as multiple types of geometric objects; being qualitative rather than quantitative, e.g., counting a 5-member ring the same as a 6-member ring, and a failure to describe non-topological changes, such as homotopic changes in protein-protein binding. Persistent topological Laplacians (PTLs), such as persistent Laplacian and persistent sheaf Laplacian, were proposed to overcome the limitations of persistent homology. In this work, we examine the modeling and analysis power of PTLs in the study of the protein structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain (RBD). First, we employ PTLs to study how the RBD mutation-induced structural changes of RBD-angiotensin-converting enzyme 2 (ACE2) binding complexes are captured in the changes of spectra of the PTLs among SARS-CoV-2 variants. Additionally, we use PTLs to analyze the binding of RBD and ACE2-induced structural changes of various SARS-CoV-2 variants. Finally, we explore the impacts of computationally generated RBD structures on a topological deep learning paradigm and predictions of deep mutational scanning datasets for the SARS-CoV-2 Omicron BA.2 variant. Our results indicate that PTLs have advantages over persistent homology in analyzing protein structural changes and provide a powerful new TDA tool for data science.

The effect of vacancy size on the oxidation process of graphene by CO2: A ReaxFF molecular dynamics study

The gasification process of graphene has been studied extensively, but the kinetic behavior of its surface vacancies under CO2 atmosphere is not clear enough. Correctly understanding its behavior can help people to better understand the evolution of carbon structure during gasification from a microscopic perspective. In this study, ReaxFF-MD was used to investigate the entire gasification process of the defective graphene in the CO2 atmosphere, including the generation of some gases. When the vacancy existed, the stable structure of the surface would be destroyed, resulting in the formation of the 5-member ring and 7-member ring vacancies. Meanwhile, the carbon bond near these vacancies would extend or break, which was used to capture the O atom of CO2 molecule and generate CO gas molecule. With the increase of the aperture of the vacancy, the number of active sites on the defective surface increased, which not only improved the CO2 adsorption reaction rate but also promoted the expansion of the vacancy size. Our study will have important implications for clarifying the gasification process of CO2 gas molecules on the carbon structure of vacancies of different sizes, deepening the understanding of the gasification mechanism from the atomic scale. By revealing the interaction mechanism between the defective graphene and CO2, it provides a theoretical basis for the industrial graphene application process.

Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products.

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is 'external' to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the 'real' substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.

Total Syntheses of (+)-Waixenicin A, (+)-9-Deacetoxy-14,15-deepoxyxeniculin, and (-)-Xeniafaraunol A.

The first asymmetric total synthesis of the Xenia diterpenoid waixenicin A, a potent and highly selective TRPM7 inhibitor, is reported. The characteristic trans-fused oxabicyclo[7.4.0]tridecane ring system was constructed via a diastereoselective conjugate addition/trapping sequence, followed by an intramolecular alkylation to forge the 9-membered ring. While a β-keto sulfone motif enabled efficient ring-closure, the subsequent radical desulfonylation suffered from (E)/(Z)-isomerization of the C7/C8-alkene. Conducting the sequence with a trimethylsilylethyl ester allowed for a fluoride-mediated decarboxylation that proceeded without detectable isomerization. The acid-labile enol acetal of the delicate dihydropyran core was introduced at an early stage and temporarily deactivated by a triflate function. The latter was critical for the introduction of the side chain. Diverting from a common late-stage intermediate provided access to waixenicin A and 9-deacetoxy-14,15-deepoxyxeniculin. A high-yielding base-mediated dihydropyran-cyclohexene rearrangement of 9-deacetoxy-14,15-deepoxyxeniculin led to xeniafaraunol A in one step.

Experimental and kinetic modelling studies on the gas hydrate inhibition effect of PVP K-90 in drilling fluids

The hydrate inhibitors play a very important role in preventing hydrate growth inside the drilling fluid systems, which is desirable for smooth drilling operation. It has been demonstrated in several scenarios that the water-soluble polymer such as polyvinyl pyrrolidone (PVP K-90) efficiently reduces hydrate formation rates. In this study, the influence of on hydrate inhibition in predesigned drilling fluids in presence of a mixture gas of methane, ethane and propane has been investigated. As the concentration of the PVP K-90 increase, the induction time continues to increase. The rheological studies of drilling fluids conducted at different temperature and pressure condition with varying concentration of indicates their better performance. The chemical structure of polymer is a single 5-membered lactam ring attached to a carbon backbone which is responsible for the inhibition effect of the drilling fluid samples. The large concentration range tested allows unprecedented visualization of the shifting of formation rate in compare to pure water. Hydrate formation rate appears to reduce as concentration of increases from 0.1 wt% to 0.7 wt%. The results suggest that increasing the concentration of the inhibitor up to 0.7 wt% may reach to a level that saturates all the growth sites and there are enough PVP K-90 molecules available to block the hydrate crystal growth, which significantly reduces the formation rate. The experimental investigation offers new understanding of the operational mechanics of kinetic hydrate inhibitor (KHI) in drilling operations.

Mercaptoamine-assisted Post-encapsulation of Metal Nanoparticles within Preformed Zeolites and their Analogues for Hydroisomerization and Methane Decomposition.

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1-2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.

Ten-Membered Cyclodecatetraene Derivatives Including Two Gallium Atoms: Experimental and Theoretical Studies on Synthesis, Structures, and Their Transformations to Nine- and Five-Membered Gallacycles

The chemistry of medium-sized ring compounds, including group 13 elements, has scarcely been investigated. Herein, we report that 5,10-digallacyclodeca-1,3,6,8-tetraene derivatives Cl2Ga2C8R8 (R = Me (5a), Et (5b)) can be obtained by the reaction of GaCl3 and zirconacyclopentadiene Cp2ZrC4R4 (R = Me (2a), Et (2b), Cp: η5-C5H5) in toluene. X-ray crystal structure analysis revealed that compound 5b has a 10-membered cyclodecatetraene structure composed of two butadiene skeletons and two GaCl fragments. X-ray crystal structure analysis and IR measurement confirmed that compound 5b forms Ga2Cl2 four-membered rings via intermolecular Cl to Ga donor–acceptor interactions, which result in the formation of oligomeric chain structures in the solid state and toluene solution. The treatment of compound 5b with 2 equivalents of 4-(dimethylamino)pyridine (DMAP) proceeded via the coordination of DMAP to the Ga center and the ring contraction to give DMAP-coordinated five-membered gallole Cl(DMAP)GaC4Et4 (4bDMAP). The reaction of compound 5a with 2 equivalents of MesLi (Mes: 2,4,6-Me3C6H2) in toluene to form a 9,10-digallabicyclo[4.3.1]decatriene derivative (MesGaC8Me8)GaMes (6a) caused ring contraction. Theoretical investigation revealed that the 10-membered ring derivative, Cl2Ga2C8H8 (GaH-10), is formed by the dimerization of two gallole molecules, ClGaC4H4 (GaH-5), via the addition of two Ga–C bonds without an energy barrier. The immediate formation of GaH-10 was attributed to the transannular electronic interaction between the expanded empty p-orbital on the Ga atom and the electron-rich sp2 carbons of the C═C double bond in GaH-5. Moreover, GaH-10 and one of the isomer, nine-membered ring derivative (ClGaC8H8)GaCl, were found to be thermodynamically more stable, as compared to GaH-5.

Evaluation of Molecular Fragmentation in Polycyclic Aromatic Hydrocarbons by Time-of-Flight Secondary Ion Mass Spectrometry

In time-of-flight secondary ion mass spectrometry (TOF-SIMS), ionized molecules and molecular fragments (secondary ions) are generated in collisions of high-energy ions (primary ions) with a solid sample surface. Mass spectra of the emitted secondary ions are typically used to identify molecular species and to determine their spatial distribution on the sample surface. Here, we extend this application in a TOF-SIMS study of a series of polycyclic aromatic hydrocarbons (PAHs) where we focus on the fragmentation of these molecules, with the purpose of better understanding the fragmentation patterns of heavy aromatic molecules in petroleum. For all PAHs, the collision process generated (i) a series of smaller cation fragments and (ii) cations close in size to the original PAH (molecular cations). Stark differences are measured for various PAHs regarding the abundance of smaller fragments versus molecular cations. Observation of hydrogen-deficient (H-deficient) cation fragments indicates the formation of polyynes and allenes. For PAHs producing higher fractions of small cation fragments, these ions are surprisingly hydrogen rich (H-rich). The H/C ratio of fragments does not scale with the fraction of Clar sextet carbon, nor with energies of low-lying electronic transitions. Free radical cation fragments tend to be suppressed. For sufficiently large fragments, aromatic cations appear to be formed and include some free radical aromatics. There is ample production of molecular ions with loss of a single carbon atom or a methine group, which corresponds to the reduction of a 6-membered aromatic ring to a 5-membered ring. There is some enhancement of free radical molecular cations due to the corresponding formation of neutral polyynes. Fragment anions are also produced with a strong preference for very H-deficient carbon clusters, in some cases being the same as carbon cluster anions observed in space. Comparisons of PAH TOF-SIMS spectra with those of asphaltenes are discussed in detail.

BAr2 -Bridged Azafulvene Dimers with Tunable Energy Levels for Photostable Near-Infrared Dyes.

Organic dyes with strong absorption in the near-infrared (NIR) region are potentially useful in medical applications, such as tumor imaging and photothermal therapy. In this work, new NIR dyes combining BAr2 -bridged azafulvene dimer acceptors with diarylaminothienyl donors in a donor-acceptor-donor configuration were synthesized. Surprisingly, it was found that in these molecules the BAr2 -bridged azafulvene acceptor adopts a 5-membered, rather than 6-membered ring structure. The influence of the aryl substituents on the HOMO and LUMO energy levels of the dye compounds was assessed from electrochemical and optical measurements. Strong electron-withdrawing fluorinated substituents (Ar=C6 F5 , 3,5-(CF3 )2 C6 H3 ) lowered the HOMO energy while preserving the small HOMO-LUMO energy gap, resulting in promising NIR dye molecules that combine strong absorption bands centered around 900 nm with good photostability.

Recognizing zeolite topologies for Cu2+ localizations with effective activities for selective catalytic reduction of nitrogen oxide

Cu-loaded zeolites are widely investigated in selective catalytic reduction of nitrogen oxide, but effects of zeolite topologies on formed active species and the changing tendency remain unexplored. In this work, catalytic turnover frequencies (TOF) of Cu loaded ZSM-5, Beta, MOR, and SSZ-13 were first determined. The topology-localized Cu species in these zeolites were analyzed by temperature-programmed reduction of H2. Then Multiple Linear Regression distinguished TOF contributions (kj, s−1·mol−1) of the Cu species. Density functional theory calculated NH3 dehydrogenation energy of the Cu species. As a result, topologies with more node atoms showed bigger kj and lower dehydrogenation energies simultaneously. The best topology in each zeolite was 10-membered ring (ZSM-5), 6-membered ring facing a 12-membered ring (Beta), 8-membered ring (MOR), and cha cage (SSZ-13). Moreover, cha cage-localized Cu2+ exhibited the largest kj and the lowest dehydrogenation energy among all the Cu species. This work reveals topology-catalysis relationships in the zeolite, which benefits zeolite design for enhanced catalytic performances.

Prediction of KRASG12C inhibitors using conjoint fingerprint and machine learning-based QSAR models

Kirsten rat sarcoma virus G12C (KRASG12C) is the major protein mutation associated with non-small cell lung cancer (NSCLC) severity. Inhibiting KRASG12C is therefore one of the key therapeutic strategies for NSCLC patients. In this paper, a cost-effective data driven drug design employing machine learning-based quantitative structure-activity relationship (QSAR) analysis was built for predicting ligand affinities against KRASG12C protein. A curated and non-redundant dataset of 1033 compounds with KRASG12C inhibitory activity (pIC50) was used to build and test the models. The PubChem fingerprint, Substructure fingerprint, Substructure fingerprint count, and the conjoint fingerprint—a combination of PubChem fingerprint and Substructure fingerprint count—were used to train the models. Using comprehensive validation methods and various machine learning algorithms, the results clearly showed that the XGBoost regression (XGBoost) achieved the highest performance in term of goodness of fit, predictivity, generalizability and model robustness (R2 = 0.81, Q2CV = 0.60, Q2Ext = 0.62, R2 – Q2Ext = 0.19, R2Y-Random = 0.31 ± 0.03, Q2Y-Random = −0.09 ± 0.04). The top 13 molecular fingerprints that correlated with the predicted pIC50 values were SubFPC274 (aromatic atoms), SubFPC307 (number of chiral-centers), PubChemFP37 (≥1 Chlorine), SubFPC18 (Number of alkylarylethers), SubFPC1 (number of primary carbons), SubFPC300 (number of 1,3-tautomerizables), PubChemFP621 (N–C:C:C:N structure), PubChemFP23 (≥1 Fluorine), SubFPC2 (number of secondary carbons), SubFPC295 (number of C-ONS bonds), PubChemFP199 (≥4 6-membered rings), PubChemFP180 (≥1 nitrogen-containing 6-membered ring), and SubFPC180 (number of tertiary amine). These molecular fingerprints were virtualized and validated using molecular docking experiments. In conclusion, this conjoint fingerprint and XGBoost-QSAR model demonstrated to be useful as a high-throughput screening tool for KRASG12C inhibitor identification and drug design.

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study.

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely 1H-14N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N-H···O, N-H···N, and C-H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O-H···O and very weak N-H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH2 group in the crystal participates in intermolecular hydrogen bonds N-H···N and N-H···O, in the precatalytic state only in N-H···O, while in the active state in N-H···N and N-H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.

Revisiting the coupling reaction between 4-aminoantipyrine and phenols: a potential one-pot reaction pathway to 4,11- and 5,12-naphthoxazepine isomers

A while ago, this journal ( Canadian Journal of Chemistry) published a set of seminal studies that revealed the underlying mechanism supporting the widely used 4-aminoantipyrine (4-AAP)-based analytical technique for detecting phenols at low levels in domestic water supplies. The current paper revisits these studies, but with a primary focus on an aspect of the mechanism that synthesizes a 6- and a 7-membered heterocyclic ring containing both N and O in a single step. Here we report a rather unusual outcome of this aspect in which, while the same naphthoquinonimide product is produced in the oxidative coupling of 4-AAP to 1-naphthol in aqueous solution and in the condensation of 4-AAP with 1,4-naphthoquinone in chloroform, a similar pair of reactions with 2-naphthol and 1,2-naphthoquinone produces two oxazepine isomers instead. In one isomer, the 4-AAP/naphthol C–N and C–O linkages are at positions 1 and 2 of the naphthyl ring, respectively; in the other isomer, these linkages are at positions 2 and 1, respectively. This unexpected difference in a one-pot reaction at ambient temperature is potentially the flexibility needed to synthesize families of pharmaceutically relevant oxazepines. Spectroscopic features useful for identifying 12 heterocyclic compounds synthesized here, nine of which are new, are also provided.

First-principles computational study on adsorption and inhibition mechanism of kinetic hydrate inhibitors

Kinetic hydrate inhibitors (KHIs) have been used in the oil and gas industry as a cost-effective hydrate mitigation strategy, but the intrinsic inhibition mechanisms are less conclusive and require further verification. In this study, we have focus on the adsorption of KHIs on the metal surfaces to understand the inhibition performance by performing the first-principles computational method. The results show that KHIs are preferentially adsorbed onto the Fe surface than the Fe3O4 surface, and they accept electrons from the Fe surface, but donate electrons to the Fe3O4 surface. The hydrophobic interaction plays a dominate role in the adsorption affinity, and the electron transfer between KHIs and the surface enhances the adsorption stability. In addition, the adsorption affinity of four poly(N-vinyl lactam)s with 5–8-membered rings is compared, and PVCap that has a 7-membered ring shows the strongest adsorption strength on the Fe surface.