Search Results (66)

Density functional theory (DFT) calculations elucidate the mechanism of diastereoselective cyclization of 2-picoline with 1,5-hexadiene catalyzed by a cationic half-sandwich scandium complex. The catalytic cycle proceeds through four key stages: formation of active species, initial alkene insertion, cis-selective cyclization, and protonation. Central to the mechanism is the dual role of 2-picoline, which initially coordinates as a supporting ligand to facilitate C–H activation and regioselective 1,2-insertion but must dissociate to enable stereocontrol. The mono(2-picoline)-coordinated complex C3 is identified as the thermodynamically favored active species. C–H activation reactivity follows the trend: ortho-C(sp²)–H (2-picoline-free) > ortho-C(sp²)–H (2-picoline-coordinated) > benzylic C(sp³)–H (2-picoline-free) > benzylic C(sp³)–H (2-picoline-coordinated), a preference governed by a wider C_α–Sc–C_α′ angle and shorter Sc···X (X = C_α, C_α′, H) distances that enhance scandium–substrate interaction. Subsequent 1,5-hexadiene insertion proceeds with high 1,2-regioselectivity through a picoline-assisted pathway. The stereoselectivity-determining step reveals a mechanistic dichotomy: while picoline coordination is essential for initial activation, its dissociation is required for intramolecular cyclization. This ligand displacement avoids prohibitive steric repulsion in the transition state, directing the reaction exclusively toward the cis-cyclized product. The cycle concludes with a sterically accessible mono-coordinated protonation. This work establishes a “ligand-enabled then ligand-displaced” mechanism, highlighting dynamic substrate coordination as a critical design principle for achieving high selectivity in rare-earth-catalyzed C–H functionalization. Full article

HDAC8 is a histone deacetylase enzyme that plays a key role in the development of various diseases in humans, including cancers, neurodegenerative diseases, and alcohol use disorder. Although HDAC8 is classified as a Zn²⁺-dependent metalloenzyme, available data regarding the affinity of other biologically relevant ions, such as Fe²⁺, Ni²⁺, Co²⁺, and Mg²⁺, for the HDAC8 enzyme active site remain unclear and contradictory. The mechanism by which these ions compete with Zn²⁺ for the HDAC8 active site is not well understood. In this study, we performed density functional theory (DFT) calculations at the B3LYP/6-31+G(d) level of theory, combined with polarizable continuum model computations (PCM) in water (ε = 78) and methanol (ε = 32). The results show that Zn²⁺ remains the thermodynamically preferred cofactor across all modeled reactions. Although Fe²⁺ and Co²⁺ gain partial stabilization upon increasing coordination number, the associated entropic and desolvation penalties prevent them from outcompeting Zn²⁺ under physiologically relevant conditions. Only a limited number of substitution reactions for Fe²⁺ and Co²⁺ yield ∆G values near thermodynamic neutrality, and only in specific coordination states. In contrast, all modeled Ni²⁺ substitution reactions are unfavorable, and Mg²⁺ is strongly excluded from the HDAC8 active site in all reactions. The resulting metal preference hierarchy—Zn²⁺ > Co²⁺ ≈ Fe²⁺ > Ni²⁺ > Mg²⁺—supports experimental observations and clarifies the intrinsic selectivity of the HDAC8 enzyme towards Zn²⁺. These insights provide a molecular basis for understanding HDAC8 metallo-regulation and may guide the rational design of novel, isoform-specific HDACi with improved binding properties. Full article

3,4-dihydroquinolone and its derivatives are structural motifs found in diverse pharmacologically active compounds. Direct oxidation of tetrahydroquinolines represents the most efficient synthetic route to 3,4-dihydroquinolone. However, the reaction conditions reported in previous studies were either relatively harsh or complex. We also attempted previously reported photocatalytic oxidation methods for the α-carbonylation of amines, but these approaches failed to efficiently produce 3,4-dihydroquinolone. Herein, we present an efficient photocatalytic oxidation methodology facilitated by our in-house high-throughput microfluidic system, which can be carried out under mild conditions with a short reaction time. Moreover, a new reaction mechanism, in which the organic base DBU serves a dual role as both an electron donor and a hydrogen atom transfer (HAT) mediator, is proposed and supported by DFT calculations. Full article

Due to high thermodynamic stability, the direct generation of formic acid by CO₂ hydrogenation is not easy to achieve experimentally. However, when Nakahara and coworkers studied the equilibrium of formic acid reversibly decomposing into CO₂ and H₂, they found that using imidazolium formate ionic liquid as an additive could shift the reaction equilibrium to the formic acid side. Subsequently, imidazolium acetate ionic liquid and imidazolium bicarbonate ionic liquid have also been experimentally proven to be able to be used for CO₂ hydrogenation to directly produce formic acid. In order to investigate the mechanism of action of ionic liquids in the process of CO₂ catalyzed hydrogenation to formic acid, we performed DFT calculations. The results showed that, after the hydrogenation of CO₂ to formic acid, the ionic liquids and formic acid molecules form adducts through hydrogen bonding, and then stabilize the product formic acid. The further use of methyl to replace H at the position of the cation R3 of the ionic liquids can improve the ability of the ionic liquids to stabilize formic acid, which also supports the experimental work of Nakahara and coworkers. In addition, among the three ionic liquids, the imidazolium acetate ionic liquid had the best stabilizing effect on formic acid, and the second best is the imidazolium formate ionic liquid, while the imidazolium bicarbonate ionic liquid has a relatively weak stabilizing ability. Full article

In this work, a novel approach for the catalytic reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride is proposed. It was shown that a continuous-flow microreactor system is an optimal tool for PdNP synthesis with dimensions of 3.0 ± 0.5 nm, as well as the performance of catalytic tests with high process efficiency, while keeping a high level of safety. The results obtained from the microreactor system allowed for 100% conversion to 4-aminophenol and were compared to processes carried out in a batch reactor, as well as to a hybrid system which was a combination of a microreactor (synthesis of PdNPs) and batch reactor (catalytic test). These investigations were enhanced by kinetic studies, for which a stopped-flow spectrophotometer was applied due to the extremely high rate of the reaction, i.e., formation of PdNPs (2.1 s), as well as to measure in situ the rate of the heterogeneous catalytic process. To visualize the progress of the heterogeneous reaction more precisely, color coding based on transmittance measurements was employed. Furthermore, to deepen the understanding of the process, a detailed mechanism supported by DFT calculations for the conversion of 4-nitrophenol to 4-aminophenol in the presence of PdNPs was proposed. Full article

The reverse water–gas shift (RWGS) reaction efficiently converts CO₂ to CO, with vital applications in carbon emission reduction and Fischer-Tropsch chemical production. This study used density functional theory (DFT) to investigate CO₂ adsorption and activation on CeO₂, oxygen-vacancy CeO₂ (CeO_2−x), and single-atom Ni-loaded CeO₂ (Ni/CeO₂). Adsorption energy analysis indicates that CO₂ preferentially adsorbs at the intermediate oxygen sites on CeO₂ and Ni/CeO₂, but on CeO_2−x, it preferentially adsorbs at the oxygen vacancies. Mulliken charge and band gap results indicate that CeO_2−x and Ni/CeO₂ exhibit higher activity than pure CeO₂. Density of states studies indicate that CeO₂, CeO_2−x, and Ni/CeO₂ can activate CO₂ to varying degrees; strong hybridization between Ni’s d-orbitals and CO₂’s O p-orbitals is key to Ni/CeO₂’s high activity. Mechanistically, CeO_2−x follows the RWGS redox mechanism, while Ni/CeO₂ follows the formate-associated mechanism. This work innovatively clarifies differential CO₂ adsorption-activation by vacancies and Ni in CeO₂-based catalysts, providing a theoretical basis for RWGS catalyst design and supporting low-energy carbon conversion development. Full article

The reverse water gas shift reaction (RWGS) is a key step in the valorization of CO₂ to value-added products such as fuel. Metal carbides, particularly molybdenum carbide (Mo₂C), supported on transition metal oxide supports have been reported as promising materials to be used as catalysts for the low-temperature RWGS reaction. A deeper understanding of catalyst support interactions can be greatly beneficial for the development of better and more efficient catalysts in the future. To this end, this study computationally investigated the effect of the interaction between the Mo₂C(001) surface and the MgO(001) surface on the RWGS mechanism. The RWGS mechanisms were explored at the Mo₂C/MgO interface, as well as on the bare surface of Mo₂C. While the pathway at the interface went through an associative-type mechanism and a carboxylate intermediate, the Mo₂C surface was found to go through a redox-type mechanism. Interestingly, both the kinetics and thermodynamics of each pathway were similar, suggesting that the observed differences in the CO₂ hydrogenation pathways were primarily limited by the diffusion of CO₂ across the MgO surface rather than inhibitory energetics resulting from the interplay of the Mo₂C material and MgO support. Full article

Strategic scaffolds in molecules increase the possibility of obtaining derivatives with potential uses in scientific and industrial areas. The regio- and stereoselective reactions can be considered to gain these tactical motifs. Natural diterpenes are key molecules for reaching such aims. Among this class of compounds, neo-clerodanes are highlighted by the presence of a furan moiety in their chemical structure. This work describes a regio- and stereoselective strategy to gain beta-lactone and oxirane derivatives from kerlinic acid (1) when the β,γ-unsaturated carboxylic acid system is oxidized, preserving the furan moiety. Oxidation of 1 yielded salviaolide (2), suggesting regio- and stereoselective means. A reaction mechanism was proposed when oxidation of the acetate (1a), benzoate (1b), and methyl ester (1c) derivatives from 1 were gained. The obtention of the epoxide derivative 3, kernolide (4), and kernolide epoxide (5) also supported the reaction mechanism. X-ray diffraction analysis of 3, Karplus-type analyses, and DFT calculations from hypothetical intermediates revealed conformational preferences that guide the regioselectivity. The stereoselectivity was attributed to the natural origin of 1. All compounds were characterized by their physical and spectroscopical data. These results suggest the feasibility of promoting regioselective oxidation on neo-clerodane compounds, preserving the furan moiety. Full article

Carbon dioxide is naturally present in the Earth’s atmosphere and plays a role in regulating and balancing the planet’s temperature. However, due to various human activities, the amount of carbon dioxide is increasing beyond safe limits, disrupting the Earth’s natural temperature regulation system. Today, CO₂ is the most prevalent greenhouse gas; as its concentration rises, significant climate change occurs. Therefore, there is a need to utilize anthropogenically released carbon dioxide in valuable fuels, such as formic acid (HCOOH). Single-atom catalysts are widely used, where a single metal atom is anchored on a surface to catalyze chemical reactions. In this study, we investigated the potential of Cu@Phosphorene as a single-atom catalyst (SAC) for CO₂ reduction using quantum chemical calculations. All computations for Cu@Phosphorene were performed using density functional theory (DFT). Mechanistic studies were conducted for both bimolecular and termolecular pathways. The bimolecular mechanism involves one CO₂ and one H₂ molecule adsorbing on the surface, while the termolecular mechanism involves two CO₂ molecules adsorbing first, followed by H₂. Results indicate that the termolecular mechanism is preferred for formic acid formation due to its lower activation energy. Further analysis included charge transfer assessment via NBO, and interactions between the substrate, phosphorene, and the Cu atom were confirmed using quantum theory of atoms in molecules (QTAIM) and non-covalent interactions (NCI) analysis. Ab initio molecular dynamics (AIMD) calculations examined the temperature stability of the catalytic complex. Overall, Cu@Phosphorene appears to be an effective catalyst for converting CO₂ to formic acid and remains stable at higher temperatures, supporting efforts to mitigate climate change. Full article

This paper presents the expected and unexpected, but typically substituent-dependent, ferrocene-catalyzed DDQ-mediated oxidative transformations of a series of 5,8-bis(methylthio)-1-aryl-1,2-dihydropyridazino[4,5-d]pyridazines and 8-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(methylthio)-1-aryl-1,2-dihydropyridazino[4,5-d]pyridazines. Under noncatalytic conditions the reactions were sluggish, mainly producing a substantial amount of undefined tarry materials; nevertheless, the ferrocene-catalyzed reactions of the 5,8-bis(methylthio)-substituted precursors gave the aromatic products the expected aromatic products in low yields. Their formation was accompanied by ring transformations proceeding via aryne-generating fragmentation/Diels–Alder (DA)/N₂-releasing retro Diels–Alder (rDA) sequence to construct arene-fused phthalazines. On the other hand, neither the noncatalytic nor the catalytic reactions of the 8-pyrazolyl-5-methylthio-substituted dihydroaromatics yielded the expected aromatic products. Instead, depending on their substitution pattern, the catalytic reactions of these pyrazolyl-substituted precursors also led to the formation of dearylated arene-fused phthalazines competing with an unprecedented multistep fragmentation sequence terminated by the hydrolysis of cationic intermediates to give 4-(methylthio)pyridazino[4,5-d]pyridazin-1(2H)-one and the corresponding 3,5-dimethyl-1-aryl-1H-pyrazole. When 0.6 equivalents of DDQ were applied in freshly absolutized THF, a representative pyrazolyl-substituted model underwent an oxidative coupling to give a dimer formed by the interaction of the cationic intermediate, and a part of the N-nucleophilic precursor remained intact. A systematic computational study was conducted on these intriguing reactions to support their complex mechanisms proposed on the basis of the structures of the isolated products. Full article

In a recent investigation the corrosion-fighting potential of five benzaldehyde derivatives were explored: 4-Formylbenzonitrile (BA1), 4-Nitrobenzaldehyde (BA2), 2-Hydroxy-5-methoxy-3-nitrobenzaldehyde (BA3), 3,5-Bis(trifluoromethyl)benzaldehyde (BA4), and 4-Fluorobenzaldehyde (BA5). Benzaldehyde derivative (BA-2) showed a maximum inhibition efficiency of 93.3% at 500 ppm. Several techniques were used to evaluate these compounds’ ability to protect mild steel from corrosion in a 1 M HCl solution, including potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), adsorption isotherms, and computational methods. Supporting techniques Fourier transform infrared spectroscopy (FTIR) and ultraviolet–visible (UV-Vis) spectroscopy were also employed to validate the results. Despite sharing a common benzene ring, the molecules differ in their substituents, allowing for a comprehensive examination of the substituents’ impact on corrosion inhibition. PDP analysis disclosed that the inhibitors exhibited mixed-type inhibition behavior, interacting with anodic as well as cathodic reactions, influencing the corrosion process. EIS analysis revealed that benzaldehyde derivatives formed a protective passive film on the metal, exhibiting high corrosion resistance by shielding the alloy from corrosive attacks. The benzaldehyde inhibitors followed the Langmuir adsorption isotherm, with high R² values near one, indicating a monolayer adsorption mechanism. DFT results indicate that BA 2 is the most effective inhibitor. FTIR and UV-vis spectroscopy revealed the molecular interactions between metal and benzaldehyde derivative molecules, providing insight into the binding mechanism. Experimental results support the outcomes obtained from the molecular dynamic (MD) simulations. Full article

Corrosion poses a critical challenge to the durability and performance of metals and alloys, particularly steel, with significant economic, environmental, and safety implications. The corrosion susceptibility of steel is influenced by aggressive chemical species, intrinsic material defects, and environmental factors. Understanding the atomic-scale mechanisms governing corrosion is essential for developing advanced corrosion-resistant materials. Density functional theory (DFT) has become a powerful computational tool for investigating these mechanisms, providing insight into the adsorption, diffusion, and reaction of corrosive species on iron surfaces, the formation and stability of metal oxides, and the influence of defects such as vacancies and grain boundaries in localised corrosion. This review presents a comprehensive analysis of recent DFT-based studies on iron and steel surfaces, emphasising the role of solvation effects and van der Waals corrections in improving model accuracy. It also explores defect-driven corrosion mechanisms and the formation of protective and reactive oxide layers under varying oxygen coverages. By establishing accurate DFT modelling approaches, this review provides up-to-date literature insights that support future integration with machine learning and multiscale modelling techniques, enabling reliable atomic-scale predictions. Full article

The stereoselective synthesis of bicyclo[3.2.0]heptanes via an anion radical [2+2] photocycloaddition of aryl bis-enone derivatives was investigated. By employing chiral oxazolidinone auxiliaries bound to aryl bis-enone substrates, enantioenriched, highly substituted bicyclo[3.2.0]heptanes have been synthesized. The reaction, mediated by Eosin Y and promoted by LiBr under visible light irradiation, has been studied both experimentally and computationally to elucidate the mechanism and stereoselective outcomes. The process proceeds via a syn-closure pathway, leading to the formation of the corresponding cis-anti diastereoisomers as major products isolated and characterized by X-ray analysis; DFT calculations provided useful insights and computational support which allow a plausible reaction mechanism to be proposed that agrees with the collected experimental data. Full article

The electrochemical CO₂ reduction reaction (eCO₂RR), driven by renewable energy, represents a promising strategy for mitigating atmospheric CO₂ levels while generating valuable fuels and chemicals. Its practical implementation hinges on the development of highly efficient electrocatalysts. In this study, a novel dual-metal atomic catalyst (DAC), composed of niobium and palladium single atoms anchored on a ferroelectric α-In₂Se₃ monolayer (Nb-Pd@In₂Se₃), is proposed based on density functional theory (DFT) calculations. The investigation encompassed analyses of structural and electronic characteristics, CO₂ adsorption configurations, transition-state energetics, and Gibbs free energy changes during the eCO₂RR process, elucidating a synergistic catalytic mechanism. The Nb-Pd@In₂Se₃ DAC system demonstrates enhanced CO₂ activation compared to single-atom counterparts, which is attributed to the complementary roles of Nb and Pd sites. Specifically, Nb atoms primarily drive carbon reduction, while neighboring Pd atoms facilitate oxygen species removal through proton-coupled electron transfer. This dual-site interaction lowers the overall reaction barrier, promoting efficient CO₂ conversion. Notably, the polarization switching of the In₂Se₃ substrate dynamically modulates energy barriers and reaction pathways, thereby influencing product selectivity. Our work provides theoretical guidance for designing ferroelectric-supported DACs for the eCO₂RR. Full article

A facile strategy to increase the chemoselectivity of domino reactions was proposed and successfully applied in the α-functionalization of ketones. The strategy involved widening the activation energy of the main reaction and side reaction through intermolecular interactions, thereby increasing the chemoselectivity of the domino reaction. In the proposed α-functionalization reaction, TMSCF₃ acted as an excellent reagent which increased the nucleophilicity of DMF through the Van der Waals force and reduced the nucleophilicity of H₂O through a hydrogen bond. We found that TMSCF₃ can increase the activation energy difference between the main reaction and side reaction using DFT calculations, which greatly increased chemoselectivity and avoided the formation of by-products. TMSCF₃ was recycled by rectification, and the average recovery rate was 87.2%. DFT calculations, XRD experiments, and control experiments were performed to support this mechanism. We are confident that this strategy has the potential to deliver significant practical advancements while simultaneously fostering broader innovation in the field of domino synthesis. Full article