DFT Studies on the Mechanisms of Carboamination/Diamination of Unactivated Alkenes Mediated by Pd(IV) Intermediates.

Density functional theory (DFT) calculations have been employed to investigate the mechanism of carboamination and diamination of unactivated alkenes mediated by Pd(IV) intermediates. Both reactions share a common Pd(IV) intermediate, serving as the starting point for either the carboamination or the diamination pathway. The formation of this Pd(IV) intermediate encompasses a transition state that substantially impacts the turnover frequency (TOF) of catalytic cycles, with an apparent activation free-energy barrier of 26.1 kcal mol-1. Carboamination of unactivated alkenes proceeds through the coordination of a toluene molecule, C-H activation, inner reductive elimination, and the separation of the carboamination product from this intermediate, while diamination of unactivated alkenes involves the formation of the ion nucleophile, SN2 attack, and the separation of the diamination product. A comparison of the free-energy profiles for carboamination and diamination of unactivated alkenes can elucidate the origin of the chemoselectivity, and Bader's atoms in molecules (AIM) wave function analyses have been performed to analyze the contributions of the outer C-N bonding in the diamination process.

The treatment of dispersion terms for solution systems.

DFT calculations of reaction mechanisms in solution have always been a hot topic, especially for transition-metal-catalyzed reactions, in which the traditional DFT-D3 method has been extensively employed. The overestimation of the dispersion from the traditional DFT-D3 method leads to a quite low activation free-energy barrier, so it is worth finding a proper way to deal with the dispersion for solution systems. The solvent-solute dispersion is also important for solution systems, and thus it should be calculated together with the solute dispersion. The newly generated solute-solute dispersion energy should be shared equally with the newly formed cavity between two interacting species; therefore, only half of the solute-solute and solvent-solute dispersion terms belong to the solute molecule. The detailed treatment of dispersion correction for solution systems has been fully addressed, and this method has been confirmed with the examples of ligand exchange reactions and catalytic reactions.

DFT calculations in solution systems: solvation energy, dispersion energy and entropy.

DFT calculations of reaction mechanisms in solution have always been a hot topic, especially for transition-metal-catalyzed reactions. The calculation of solvation energy is performed using either the polarizable continuum model (PCM) or the universal solvation model SMD. The PCM calculation is very sensitive to the choice of atomic radii to form a cavity, where the self-consistent isodensity PCM (SCI-PCM) has been recognized as the best choice and our IDSCRF radii can provide a similar cavity. Moving from a gas-phase case to a solution case, dispersion energy and entropy should be carefully treated. The solvent-solute dispersion is also important in solution systems, and it should be calculated together with the solute dispersion. Only half of the solvent-solute dispersion energy from the PCM calculation belongs to the solute molecules to maintain a thermal equilibrium between a solute molecule and its cavity, similar to the treatment of electrostatic energy. Relative solute dispersion energy should also be shared equally with the newly formed cavity. The entropy change from a gas phase to a liquid phase is quite large, but the modern quantum chemistry programs can only calculate the gas-phase translational entropy based on the idea-gas equation. In this review, we will provide an operable method to calculate the solution translational entropy, which has been coded in our THERMO program.

IL-17A mediates pyroptosis via the ERK pathway and contributes to steroid resistance in CRSwNP.

BACKGROUND: Pyroptosis is closely related to inflammation. However, the molecular mechanisms and pathologic contributions of pyroptotic epithelial cell are not yet fully understood. OBJECTIVE: This study aimed to explore the function and molecular mechanisms of IL-17A on human nasal epithelial cell (hNEC) pyroptosis. METHODS: The expression of pyroptosis-related biomarkers and IL-17A was assessed in sinonasal mucosa from control individuals, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by using quantitative RT-PCR. Their localization was analyzed via immunohistochemistry and immunofluorescence. The ultrastructural characteristics of IL-17A-induced pyroptosis in hNECs were visualized by using electron microscopy. IL-17A functional assays were performed on hNECs and airway epithelial cell lines. Cytokine levels were quantified via ELISA. The signaling pathways involved in IL-17A-induced pyroptosis were studied via unbiased RNA sequencing and Western blotting. RESULTS: The expression of IL-17A and the pyroptotic biomarkers NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D, and IL-1ß was increased in nasal mucosa from patients with CRSwNP compared with in those with chronic rhinosinusitis without nasal polyps and the control subjects. IL-17A was positively correlated and colocalized with the pyroptotic biomarkers. IL-17A treatment induced pyroptosis in the hNECs and cell lines analyzed, primarily through the extracellular signal-regulated kinase (ERK)-NLRP3/caspase-1 signaling pathway, and increased IL-1ß and IL-18 secretion in hNECs. Moreover, IL-17A-induced pyroptosis contributed to steroid resistance by affecting glucocorticoid receptor-α and glucocorticoid receptor-ß expression, and the inhibition of pyroptotic proteins partially abolished IL-17A-induced steroid resistance in hNECs. CONCLUSION: Elevated IL-17A level promotes pyroptosis in hNECs through the ERK-NLRP3/caspase-1 signaling pathway and contributes to glucocorticoid resistance by affecting glucocorticoid receptor homeostasis in patients with CRSwNP.

[Mechanism of puerarin reversing SH-SY5Y cell injury induced by Aß_(1-42) based on proteomics].

Puerarin has the anti-Alzheimer's disease (AD) activity,which can reverse nerve injury induced by Aßand inhibit neuronal apoptosis.However,its potential pharmacodynamic mechanism still needs to be further researched.The occurrence and development of AD is due to the change of multiple metabolic links in the body,which leads to the destruction of balance.Puerarin may act on multiple targets and multiple metabolic processes to achieve therapeutic purposes.Quantitative proteomic analysis provides a new choice to understand the mechanism as completely as possible.This research adopted SH-SY5Y cells induced by Aß_(1-42)to establish AD cell model,and Aßimmunofluorescence detection showed that Aßdecreased significantly after puerarin intervention.The mechanism of puerarin reversing SH-SY5Y cell injured by Aß_(1-42)was further explored by using label-free non-labeled quantitative technology and Western blot detection based on bioinformatics analysis result.The results showed that most of the differential proteins were related to biological processes such as cellular component organization or biogenesis,cellular component organization and cellular component biogenesis,and they mainly participated in the top ten pathways of P value such as pathogenic Escherichia coli infection,m TOR signaling pathway,regulation of autophagy,regulation of actin cytoskeleton,spliceosome,hepatocellular carcinoma,tight junction,non-small cell lung cancer,apoptosis and gap junction.Annexin V/PI flow cytometry and TUNEL were used to detect apoptosis,and the results showed that Aßdecreased significantly and the rate of apoptosis decreased significantly after puerarin intervention.Western blot analysis found that the protein expression level of autophagy related protein LC3Ⅱwas up-regulated after Aßinduction,and the degree of this up-regulation was further enhanced in puerarin intervention group.The trend of the ratio of LC3Ⅱ/LC3Ⅰamong groups was the same as the protein expression level of LC3Ⅱ，the protein expression level of p62 in the control group,AD model group and puerarin intervention group decreased successively.Protein interaction network analysis showed that CAP1 was correlated with TUBA1B,HSP90AB2P,DNM1L,TUBA1A and ERK1/2,and the correlation between CAP1 and ERK1/2 was the highest among them.Western blot showed that the expressions of p-ERK1/2,Bax and CAP1 were significantly down-regulated and the protein expression level of Bcl-2 was significantly up-regulated after puerarin intervention.Therefore,puerarin might improve the SH-SY5Y cells injured by Aß_(1-42)through the interaction of multiple biological processes and pathways in cells multiple locations,and CAP1 might play an important role among them.

Dissociative electron transfer of copper(ii) complexes of glycyl(glycyl/alanyl)tryptophan in vacuo: IRMPD action spectroscopy provides evidence of transition from zwitterionic to non-zwitterionic peptide structures.

We report herein the first detailed study of the mechanism of redox reactions occurring during the gas-phase dissociative electron transfer of prototypical ternary [CuII(dien)M]˙2+ complexes (M, peptide). The two final products are (i) the oxidized non-zwitterionic π-centered [M]˙+ species with both the charge and spin densities delocalized over the indole ring of the tryptophan residue and with a C-terminal COOH group intact, and (ii) the complementary ion [CuI(dien)]+. Infrared multiple photon dissociation (IRMPD) action spectroscopy and low-energy collision-induced dissociation (CID) experiments, in conjunction with density functional theory (DFT) calculations, revealed the structural details of the mass-isolated precursor and product cations. Our experimental and theoretical results indicate that the doubly positively charged precursor [CuII(dien)M]˙2+ features electrostatic coordination through the anionic carboxylate end of the zwitterionic M moiety. An additional interaction exists between the indole ring of the tryptophan residue and one of the primary amino groups of the dien ligand; the DFT calculations provided the structures of the precursor ion, intermediates, and products, and enabled us to keep track of the locations of the charge and unpaired electron. The dissociative one-electron transfer reaction is initiated by a gradual transition of the M tripeptide from the zwitterionic form in [CuII(dien)M]˙2+ to the non-zwitterionic M intermediate, through a cascade of conformational changes and proton transfers. In the next step, the highest energy intermediate is formed; here, the copper center is 5-coordinate with coordination from both the carboxylic acid group and the indole ring. A subsequent switch back to 4-coordination to an intermediate IM1, where attachment to GGW occurs through the indole ring only, creates the structure that ultimately undergoes dissociation.

Grinding-Triggered Single Crystal-to-Single Crystal Transformation of a Zinc(II) Complex: Mechanochromic Luminescence and Aggregation-Induced Emission Properties.

We first report single crystal X-ray analysis of ground crystals of mechanochromic luminescence (MCL) that shows single crystal-to-single crystal transformation (SCSCT). Single crystals of [ZnL2] (1-SG, HL = 2-[[[4-(2-benzoxazolyl)phenyl]imino]-methyl]-5-(diethylamino)-phenol) were obtained upon slight grinding of single crystals of [ZnL2]·0.5CH3OH (1), both of which were characterized by single crystal X-ray diffraction. Crystals of 1 showed emission centered at 647 nm (red color), while crystals of 1-SG showed emission band at 624 nm (orange-red color) under UV light, indicating MCL property of the Zn(II) complex. Reversible MCL property with emission color change between red and yellow for 1 was observed upon high grinding and recrystallization. Single crystal X-ray analysis suggested that it is due to the alteration of molecular conformation of ligands in ZnL2 instead of weak intermolecular interaction that 1 exhibits MCL. Investigation of the control Zn(II) complexes (2-4) indicated that flexible substituents and rotated aromatic rings are desirable to generate the MCL-active complexes. In addition, 1 was highly fluorescent in THF solution, but its fluorescence quenched upon addition of water. DFT calculations suggested that this is due to the formation of the excited hydrated ZnL2 species via Zn-O coordination bond, which results in electron-driven proton transfer (EDPT). Aggregates formed as water fraction ( fw) in THF/H2O (v/v) reached 70%, and fluorescence emission was enhanced. This phenomenon continued until fw was 90%, indicating aggregation-induced emission (AIE) property. The mechanism of AIE of ZnL2 in THF/H2O is the restriction of intramolecular rotation (RIR).

PdIV Species Mediation in PdII-Catalyzed Direct Alkylation of Arenes with Oxiranes: A DFT Study.

The reaction mechanisms of Pd(OAc)2-catalyzed dehydrogenative alkylation of 2-phenylpyridine with oxirane were investigated using DFT calculations. The most plausible reaction pathway was confirmed as a PdII/IV/II catalytic cycle consisting of four processes: C-H activation, ring-opening oxidative addition of oxirane, reductive elimination, and recovery of the catalyst. According to the B2PLYP/DGDZVP computational data, the oxidative addition of oxirane for converting PdII to PdIV was assigned to be the rate-determining step with a free-energy barrier of 28.1 kcal·mol-1. For comparison, we also studied the alternative PdII-only pathway without a change of oxidation state and found that it was hindered kinetically by a high free-energy barrier of 75.1 kcal·mol-1 occurring for the ring-opening migratory insertion of oxirane. In addition, the small-ring strain of oxirane should be responsible for the feasible C-O bond-cleavage and subsequent PdII → PdIV conversion, because the designed four-, five-, and six-membered-ring reagents did not display such an oxidative addition reactivity. Lastly, an extended reactivity order among oxirane, PhI, PhBr, and PhCl toward oxidative addition onto PdII to form PdIV was proposed in this article based on the computed kinetic parameters.

Hypothermic preconditioning but not ketamine reduces oxygen and glucose deprivation induced neuronal injury correlated with downregulation of COX-2 expression in mouse hippocampal slices.

Hypothermic preconditioning is an effective treatment for limiting ischemic injury, but the mechanism is poorly understood. This study was aimed to explore the effect of hypothermic and ketamine preconditioning on oxygen and glucose deprivation (OGD) induced neuronal injury in mouse hippocampal slices, and to investigate its possible mechanism. The population spike (PS) was recorded in the CA1 region of mouse hippocampal slices using extracellular recordings, Na+/K+ ATPase activity in slices was determined by spectrophotometer and the expression of Cyclooxygenase-2 (COX-2) was measured by Western blot. Ten min of OGD induced a poor recovery of PS in slices after reoxygenation. Hypothermic (33 °C) preconditioning delayed the appearance of transient recovery (TR) of PS and improved the recovery amplitude of PS after reoxygenation. Hypothermic preconditioning also decreased the expression of COX-2 and increased Na+/K+ ATPase activity in slices. Pretreatment of ketamine, a non-competitive NMDA receptor antagonist at a subanesthetic dose has no effect on OGD induced neuronal injury. Moreover, the protection of hypothermic preconditioning was not added by ketamine. The downregulation of COX-2 expression and the increase of Na+/K+ ATPase activity may be associated with the effectiveness of hypothermic preconditioning in increasing tolerance to an OGD insult.

Involvement of N-Methyl-D-Aspartic Acid Receptor and DL-α-Amino-3-Hydroxy-5- Methyl-4-Isoxazole Propionic Acid Receptor in Ginsenosides Rb1 and Rb3 against Oxygen-Glucose Deprivation-Induced Injury in Hippocampal Slices from Rat.

OBJECTIVE: Ginsenosides, Rb1 and Rb3, are the major protopanaxadiol components of ginseng saponin. In the present study, the influences of ginsenosides Rb1 and Rb3 on N-methyl-D-aspartic acid (NMDA) receptor or DL-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic transmission after oxygen-glucose deprivation (OGD) were investigated. METHODS: NMDA receptor population spike (NMDA-PS) or AMPA receptor-mediated population spike (AMPA-PS) was recorded in the CA1 pyramidal cell layer of rat hippocampal slices by electrophysiological techniques. RESULTS: Under normal conditions, ginsenosides Rb3 and Rb1 depressed glutamate receptors-mediated synaptic transmission. Fourteen min of OGD resulted in a poor recovery amplitude of NMDA-PS or AMPA-PS after reoxygenation. Ginsenoside Rb3 significantly delayed the appearance of transient recovery of PS during OGD, and improved the recovery amplitudes of NMDA-PS and AMPA-PS after reoxygenation. However, the similar protective effects of ginsenoside Rb1 were observed only on NMDA-PS but not AMPA-PS. CONCLUSION: These results suggest that ginsenosides Rb1 and Rb3 have the different inhibitions on NMDA and AMPA receptors-mediated response, which may partially explain the different protective effects of these agents on ischemic neuronal death.

Coordination-Directed Stacking and Aggregation-Induced Emission Enhancement of the Zn(II) Schiff Base Complex.

2-(Trityliminomethyl)-quinolin-8-ol (HL) and its Zn(II) complex were synthesized and characterized by single-crystal X-ray diffraction. HL is an unsymmetrical molecule and coordinated with Zn(II) ion to form ZnL2 in the antiparallel-mode arrangement via Zn-O (hydroxyl group) and Zn-N (quinoline ring) of HL. A high degree of ZnL2 molecules ordering stacking is formed by the coordination bonds and intermolecular π-π interactions, in which head-to-tail arrangement (J-mode stacking) for L- is found. HL is nonfluorescent and ZnL2 is weakly fluorescent in THF. The fluorescence emission of ZnL2 enhances in THF/H2O as H2O% (volume %) is above 60% and aggregates particles with several hundred nanometers are formed, which is confirmed by DLS data and TEM images. The J-aggregates stacking for L- in ZnL2 results in aggregation-induced emission enhancement (AIEE) for ZnL2 in THF/H2O. Theoretical computations based on B3LYP/6-31G(d, p) and TD-B3LYP/6-31G(d, p) methods were carried out. ESIPT is the supposed mechanism for fluorescent silence of HL, and fluorescence emission of ZnL2 is attributed to the restriction of ESIPT process. The oscillator strength of ZnL2 increases from 0.017 for monomer to 0.032 for trimer. It indicates that a high degree of ZnL2 molecules ordering stacking in THF/H2O is of benefit to fluorescence enhancement. HL is an ESIPT-coupled AIEE chemosensor for Zn(II) with high selectivity and sensitivity in aqueous medium. HL can efficiently detect intracellular Zn(II) ions because of ESIPT-coupled AIEE property of ZnL2 in mixed solvent.

Excited Oxidized-Carbon Nanodots Induced by Ozone from Low-Temperature Plasma to Initiate Strong Chemiluminescence for Fast Discrimination of Metal Ions.

Carbon nanodots (C-dots) are recently well examined due to the emissions with color-tuning and nonblinking properties, while more studies are still needed for the appropriate understanding and application of distinct emissions. In this work, we found the emission of chemiluminescence (CL) by introducing low-temperature plasma (LTP) into C-dots solutions without any reagent added, whose intensity was affected by the presence of different metal ions. Based on both experimental data and theoretical calculations, we found with the ozonation by ozone from LTP, excited oxidized-C-dots would be generated with the addition of ozone onto the conjugated double bonds of C-dots, and these excited species could directly initiate strong CL combining with the deactivation of excited species to the ground state. Significantly, the cross-reactive CL signals were obtained from different kinds of C-dots with the presence of different metal ions. Therefore, a new sensor array (electronic tongue) composed of five different C-dots was designed for fast discrimination of metal ions, which achieved the accurate discrimination of 13 kinds of metal ions in pure water and real samples. It exhibited good reproducibility and sensitivity, which can be used for the quantitative analysis of metal ions such as showing a linear range from 4 × 10(-7) to 6 × 10(-5) mol·L(-1) (R(2) > 0.99) for Fe(3+) with a detection limit of 2.5 × 10(-7) mol·L(-1). This work not only provides a novel finding of CL from C-dots revealing explicit relationship between structures and CL properties, but also realizes the fast discrimination of metal ions, showing potentials in environmental monitoring and quality identifications.

Multi-Pathway Consequent Chemoselectivities of CpRuCl(PPh3 )2 /MeI-Catalysed Norbornadiene Alkyne Cycloadditions.

Chemoselectivities of five experimentally realised CpRuCl(PPh3 )2 /MeI-catalysed couplings of 7-azabenzo-norbornadienes with selected alkynes were successfully resolved from multiple reaction pathway models. Density functional theory calculations showed the following mechanistic succession to be energetically plausible: (1) CpRuI catalyst activation; (2) formation of crucial metallacyclopentene intermediate; (3) cyclobutene product (P2) elimination (ΔGRel(RDS) ≈11.9-17.6 kcal mol-1 ). Alternative formation of dihydrobenzoindole products (P1) by isomerisation to azametalla-cyclohexene followed by subsequent CpRuI release was much less favourable (ΔGRel(RDS) ≈26.5-29.8 kcal mol-1 ). Emergent stereoselectivities were in close agreement with experimental results for reactions a, b, e. Consequent investigations employing dispersion corrections similarly support the empirical findings of P1 dominating in reactions c and d through P2→P1 product transformations as being probable (ΔG≈25.3-30.1 kcal mol-1 ).

An Explicit Interpretation of the Directing Group Effect for the Pd(OAc)2-Catalyzed Aromatic C-H Activations.

A comprehensive DFT investigation has been performed for a series of the Pd(OAc)2-catalyzed C-H activations, updating and extending the understanding of directing group effect. In the beginning, the directed and undirected C-H activation mechanisms, based on 10 model reactions, have been discussed comparatively, which disclosed that directing group can exert a thermodynamic driving force, not necessarily a kinetic promotion, on the C-H activation process. Formation of the open palladation species via the undirected pathway is thermodynamically unspontaneous (ΔG = 4-9 kcal/mol), in sharp contrast to that of the cyclopalladation species via the directed pathway (ΔG < 0). Further calculations revealed that the free-energy barriers of proton-transfer are in fact not so high on the undirected pathway (17-24 kcal/mol), while mediation of some O-center groups in the directed pathway would increase the free-energy barriers of proton-transfer. For pyridine N-oxide systems, the undirected mechanism was estimated to be more plausible than the 4-member-directed one both thermodynamically and kinetically. In addition, the uncommon 7-membered cyclopalladation has been tentatively explored using two current examples, predicting that electron-rich directing groups can help to stabilize the 7-membered palladacycles formed.

Theoretical studies on CuCl-catalyzed C-H activation/C-O coupling reactions: oxidant and catalyst effects.

Copper-complex catalyzed coupling reactions have been widely applied in the production of many important organic moieties from a synthetic perspective. In this work, a series of density functional theory (DFT) calculations, employing the B3LYP + IDSCRF/DZVP method, have been performed for a typical CuCl-catalyzed C-O cross-coupling reaction. The novel reaction mechanism was reported as four successive processes: oxidative radical generation (ORG) or oxidative addition (OA), hydrogen abstraction (HA), C-H activation/reductive elimination, and separation of product and recycling of catalyst (SP & RC). Our calculations provided a deep understanding on the dissimilar chemical activities associated with varying the oxidants used; detailed energy profile analyses suggested that the first oxidation process could proceed via either of the two competing channels (ORG and OA mechanisms) which is the basis to explain the different experimental yields. In addition, our molecular modelling gave theoretical evidence that Cu(ii) → Cu(i) reduction by solvent DMF (and a water molecule) might serve as a preliminary step to produce some more active Cu(i) species that could subsequently be oxidized into Cu(iii) favorably. In contrast, the Cu(ii) → Cu(iii) direct pathway was estimated to be prohibited from thermodynamics. All the calculation results in this work are parallel with the experimental observations.

A DFT kinetic study on 1,3-dipolar cycloaddition reactions in solution.

Several popular density functional theory (DFT) methods have been employed to characterize a series of 1,3-dipolar cycloaddition reactions, including the exploration of reaction mechanisms and the calculations of kinetic parameters. Both the gas- and solution-phase translational entropy models have been used to calculate the activation entropies, and the results obtained from the latter method are quite close to the experimental measurements. For some of the reactions studied, e.g., a1 + b9, a1 + b10, a5 + b9 and a12 + b5, the explicit + implicit solvation model, namely, a cluster-continuum type model, should be employed to account for the specific solvent-solute interactions. The quasi rigid-rotor-harmonic-oscillator (qRRHO) small frequency vibrational entropy correction, in conjunction with the conformational entropy correction, could further improve the calculated activation entropy data. The comparison between calculation data with experimental measurements, using 23 activation entropies and 160 reaction rate constants as test benchmark, demonstrated that our present strategy could calibrate the root-mean-square-deviation (RMSD) of activation entropies to be 1.8 cal mol-1 K-1 and that of Gibbs free energy barriers to be 1.8 kcal mol-1.

Theoretical estimation of kinetic parameters for nucleophilic substitution reactions in solution: an application of a solution translational entropy model.

The kinetic parameters, such as activation entropy, activation enthalpy, activation free-energy, and reaction rate constant, for a series of nucleophilic substitution (SN) reactions in solution, are investigated using both a solution-phase translational entropy model and an ideal gas-phase translational entropy model. The results obtained from the solution translational entropy model are in excellent agreement with the experimental values, while the overestimation of activation free-energy from the ideal gas-phase translational entropy model is as large as 6.9 kcal mol(-1). For some of the reactions studied, such as and in methanol, and and in aqueous solution, the explicit + implicit model, namely, a cluster-continuum type model, should be employed to account for the strong solvent-solute interactions. In addition, the explicit + implicit models have also been applied to the DMSO-H2O mixtures, which would open up a door to investigate the reactions in a mixed solvent using density functional theory (DFT) methods.

A Theoretical Study of Ene Reactions in Solution: A Solution-Phase Translational Entropy Model.

Several density functional theory (DFT) methods, such as CAM-B3LYP, M06, ωB97x, and ωB97xD, are used to characterize a range of ene reactions. The Gibbs free energy, activation enthalpy, and entropy are calculated with both the gas- and solution-phase translational entropy; the results obtained from the solution-phase translational entropies are quite close to the experimental measurements, whereas the gas-phase translational entropies do not perform well. For ene reactions between the enophile propanedioic acid (2-oxo-1,3-dimethyl ester) and π donors, the two-solvent-involved explicit+implicit model can be employed to obtain accurate activation entropies and free-energy barriers, because the interaction between the carbonyl oxygen atom and the solvent in the transition state is strengthened with the formation of C-C and O-H bonds. In contrast, an implicit solvent model is adequate to calculate activation entropies and free-energy barriers for the corresponding reactions of the enophile 4-phenyl-1,2,4-triazoline-3,5-dione.

Competing Mechanisms, Substituent Effects, and Regioselectivities of Nickel-Catalyzed [2 + 2 + 2] Cycloaddition between Carboryne and Alkynes: A DFT Study.

Competing reaction mechanisms, substituent effects, and regioselectivities of Ni(PPh3)2-catalyzed [2 + 2 + 2] carboryne-alkyne cycloadditions were characterized by density functional theory using the real chemical systems and solvent effects considered. A putative mechanism involving the following steps was characterized: (1) exothermic carboryne-catalyst complexation and nucleophilic attack by the first alkyne; (2) insertion of the second alkyne, the rate-determining step (RDS) in all four reactions studied; (3) isomerization of reactant-bound complexes; and (4) product elimination and catalyst regeneration. The RDS in three reactions is mediated by free energy barriers of 27.2, 31.1, and 36.6 kcal·mol(-1), representative of the corresponding experimental yields of 67, 54, and 33%, respectively. A fourth reaction with 0% experimental yield showed representative RDS free energy barriers of 60.4 kcal·mol(-1), which are difficult to surmount even at 90 °C. Alternative pathways leading to differing isomers were similarly characterized and successfully reproduced experimentally determined product regioselectivities. Kinetic data derived from free energy barriers are in quantitative agreement (< ± 0.75-3.0 kcal·mol(-1)) of the experimental times, affirming the theoretical results as representative of the real chemical transformations. Complementary determinations show the use of truncated models (Ni(PMe3)2, Ni(PH3)2) causes the RDS to vary from step 2 (alkyne insertion) to step 1 (alkyne attack), highlighting the need to employ real chemical systems in modeling these reactions.

DFT studies on the directing group dependent arene-alkene cross-couplings: arene activation vs. alkene activation.

Due to its green-chemistry advantages, the dehydrogenative Heck reaction (DHR) has experienced enormous growth over the past few decades. In this work, two competing reaction channels were comparatively studied for the Pd(OAc)2-catalyzed DHRs of arenes with alkenes, referred to herein as the arene activation mechanism and the alkene activation mechanism, respectively, which mainly differ in the involvement of the reactants in the C-H activation step. Our calculations reveal that the commonly accepted arene activation mechanism is plausible for the desired arene-alkene cross-coupling; in contrast, the alternative alkene activation mechanism is kinetically inaccessible for the desired cross-coupling, but it is feasible for the homo-coupling of alkenes. The nature of directing groups on reactants could mainly determine the dominance of the two competing reaction routes, and therefore, influence the experimental yields. A wide range of directing groups experimentally used are examined by the density functional theory (DFT) method in this work, providing theoretical guidance for screening compatible reactants.